The collective behaviors of animals, from schooling fish to packing wolves and flocking birds, display plenty of fascinating phenomena that result from simple interaction rules among individuals. The emergent intelligent properties of the animal collective behaviors, such as self-organization, robustness, adaptability and expansibility, have inspired the design of autonomous unmanned swarm systems. This article reviews several typical natural collective behaviors, introduces the origin and connotation of swarm intelligence, and gives the application case of animal collective behaviors. On this basis, the article focuses on the forefront of progress and bionic achievements of aerial, ground and marine robotics swarms, illustrating the mapping relationship from biological cooperative mechanisms to cooperative unmanned cluster systems. Finally, considering the significance of the coexisting-cooperative-cognitive human-machine system, the key technologies to be solved are given as the reference directions for the subsequent exploration. Inspired by the fascinating collective behaviors of animals, swarm robotics could be designed to emerge intelligent properties via robotic cooperation for the unmanned swarm system and human-machine system. With the rapid technological development of the smart robot, varieties of robots are widely used in modern production and life. Many types of robots have emerged in the swarm, ranging in overall size from macro to micro, even nanometers . The intRobots are autonomous.Robots can interact with the surroundings and give feedback to modify the environment.Robots possess local perceiving and communicating capabilities.Robots do not exploit centralized swarm control or global knowledge.Robots cooperate with each other to accomplish the given task.On the basis of these attributes, properties of a swarm-robot system mainly include distribution of the organization, simplicity of the individual, flexibility of the action mode and intelligence on the swarm level, explained as follows ,11.There is no central node in the swarm and each individual follows simple behavioral rules with local perception, planning and communication abilities. Through local information interaction with the environment and neighbors, individuals adjust their behavior modes to adapt to the dynamic environment. A swarm can gain the stigmergy globally. Meanwhile, a distributed framework promotes the self-healing capability and scalability of the system . The intThe abilities or behavior rules adopted by individuals in a group are quite simple. Each individual performs only one or a limited number of actions and makes a few simple responses to external situations. This seemingly clumsy individual behavior makes the group extremely efficient, reflecting the emergence of intelligence. Thus, the swarm system is not a simple sum of individuals, but through the self-organization, coordination and cooperation between individuals, the system realizes multiplication and even exponential growth of the capacity.Flexibility mainly describes the swarm’s adaptability to the environment. The swarm individuals adapt to environment changes by adjusting their behaviors. In social animals, flexibility is promoted by the redundancy of the swarm size, simplicity of behaviors and other cooperated mechanisms. The flexibility is usually inconsistent with the stability of swarm systems, while the communities in nature tend to be both stable and flexible. From a physical point of view, the swarm could possibly maintain the balance between stability and flexibility during the system phase transition while moving near the critical point .Individuals exchange and share information by perceiving the environment situation, respond to external stimuli based on certain behavioral rules and enhance the swarm adaptability by adjusting the state, which is a process of learning and evolution. Individuals adaptively change their own behaviors according to feedback information from the environment to achieve strategies and experience learning, thereby obtaining the best adaptability to the external environment. The learning and evolution processes take place both in time and space manifested in the interactive learning of self-historical and external experiences, respectively.The natural collective behaviors of animals, from schooling fish to packing wolves and flocking birds, have long intrigued observers of nature and scientists. The emergent properties have risen in collective motion via simple interactions among individuals, like self-organization, distribution, robustness, adaptivity, etc. Thus, much attention has been placed on revealing delicate local interaction rules, which lead to emergent collective behaviors.Birds often fly in aggregations to display a variety of fascinating phenomena that reflect an obvious degree of swarm coordination and collective response. As a typical example of a small group, pigeon flocks possess a group size from several to dozens of individuals. A well-defined hierarchical structure has been found among pigeon flocks and the birds in the higher rank are more influential in the decision-making process of the flock . From thFish schools also exhibit complex and coordinated collective behaviors that link individual behavior to the properties of the dynamic swarm . Fish scAttraction: fish have the ability to copy another individual’s heading to some extent .Repulsion: speed regulation is a major component of repulsion, and speed changing is transmitted to the surrounding individuals.Interactions: the single nearest neighbor dominates social interactions to a large extent .These rules help account for the group cohesion and social information amplification responding to rapid variations in speed and direction.Wolf packs regularly engage in cooperative hunting through coordinative actions, which is an important aspect of cooperation . There eThere are many similarities between the biological swarm and the unmanned system swarm, as listed in Table et al. presented a more biologically realistic model to simulate the swarm’s collective behaviors arising from local repulsion, alignment and attractive trending on the basis of the location and direction of the individuals relative to their neighbors [Couzin eighbors . Couzin’Numerous variants of the above models considering the realistic situations have been designed. On this basis, the swarm models have been tested on the real hardware of swarm robotics .Swarm intelligence (SI) is defined as the emergence of consistent global collective motion from swarm cooperative behaviors through local interaction with the environment in [nment in . The swanment in ,33.The establishment of SI models is based on the use of natural mechanisms to attain comprehension of the patterns and rules resulting in flock behaviors. It has already been observed in animal systems comprising birds, fish or insects, but, though the aim of the swarm is sometimes rather complicated, each individual utilizes relatively simple rules, and interacts with their surrounding environment and individuals. Typically, one single flock individual has insufficient ability to find one superior solution, while the swarm is able to under appropriate conditions . More spWang and Beni first introduced the term ‘swarm intelligence’ in 1989 to describe the dynamics of swarm robots that can be framed as a form of intelligent collective behavior . This siExploration: swarm individuals independently explore the space for the current problem and obtain a series of information.Integration: all information explored by individuals is merged in some way.Feedback: the individual is stimulated to continue exploring by the feedback of merged group information.After extensive exploration by researchers, swarm intelligence progressively evolved into two main branches: the swarm intelligence algorithm and the distributed swarm system. As Dorigo defined, swarm intelligence includes the trial design of algorithms and devices for solving distributed problems under the inspiration of collective behaviors in social animal colonies . Swarm iThe design of a swarm-robot system with SI has faced many challenges with respect to the employment of the biological inspiration tool. From the perspective of an engineering application, it is indispensable to design the self-organization structure, local communication mechanism and feedback control method.The significance of a self-organization design needs to be emphasized since the system could achieve the complex task via simple rules of the individual. It is therefore highly desirable to seek self-organization behaviors in a swarm robotic system, as they can be obtained with minimal cost. Therefore, self-organization behaviors are supposed to be obtained in the swarm robotic system. Nevertheless, the definition of simple local rules for each individual is particularly challenging since it has an indirect relationship with complex global properties. To design the control system of the self-organized robotic swarm, definitions of the individual rules need to be given to promote the system’s desired pattern. The robotic swarms possess superiorities over a single robot in redundancy and the ability to handle multiple tasks simultaneously. The definition of individual self-organized behavior should adapt to the dynamic situation to promote the robustness of the swarm system. Through the self-organized rule, if a robot stops functioning, one in the swarm can replace it with no significant influence upon the system.In fact, global behaviors emerge from local interactions that have not been coded directly in the individual’s behavior rules. Thus, it is necessary to discover the interaction relationship among individuals and the environment resulting in self-organization. Then, the desired global behavior should be decomposed into simple individual behaviors and their interactions with neighbors. The stigmergy mentioned above is a core concept of the biological community in nature inspired by the nesting behavior of termites, defining the information coordination mechanism of the self-organized individual . StigmerFrom the perspective of control theory, feedback is one of the basic intrinsic elements of autonomous swarm behaviors, including both positive and negative feedback. Positive feedback strengthens the weak response of the swarm initially and urges this swarm to cope with change in the external environment. Negative feedback acts as damping to suppress the disturbance input. Positive and negative feedback respectively promote rapidity and stability. The balance between the two elements enables the group to respond quickly to the dynamic environment and remain stable in the face of uncertain disturbances.The structure of the self-organized swarm system is illustrated in Fig. A swarm of UAVs is a group of aerial robots working cooperatively to accomplish the given aim . Each UAIn Unmanned Aircraft Systems Roadmap 2005–2030 issued by the Office of the Secretary of Defense, an onion-like layered series of capabilities has been adopted to define ten levels of autonomy. The definitions handle remote operation and preprogrammed flight by a single aircraft to autonomous swarm flight . Small UTo satisfy the needs of long-range, low-cost, multi-wavelength, hierarchical mission execution capabilities of large-scale UAV swarms, aerial launch and recovery technology have rapidly developed. The ‘launch-work-recovery-relaunch’ mission execution mode can significantly improve the efficiency ratio and the sortie efficiency of autonomous UAV swarms. Aerial launch usually considers two methods: ejection and distribution. The current aerial launch projects are mostly conducted with a large transport plane or bomber that flies to the predefined location carrying a large number of small UAVs, drops them to perform reconnaissance, attack or interference tasks, and then recovers them after the tasks are completed or battery power is low. In the tests carried out on October 25, 2016, three US Navy F/A-18 Hornet two-seat variants successfully released a ‘swarm’ of 103 Perdix semi-autonomous drones during flight. On March 19, 2019, NASA tested a swarm of 100 US Navy Cicada drones released by four large drones . The Cicadas are mounted on the underside of a Hive drone and then released on demand with a mechanical switch . As annoFacing the challenges of complex battlefield environments, such as land, sea, air, space, electromagnetic and network, establishing reliable communication networks among the UAV swarm is the key to carrying out cooperative tasks. Generally, the reliability of the communication network has many challenging parameters, such as time delay , switchiBased on the interaction topology network, the UAV swarm could carry out information aggregation and fusion, make decisions on the next mission and move on to complete the current action . First, The maturity of cooperative algorithms and technologies requires multiple iterations of technical application and validation experiments. The research group in Hungary proposed a flocking model that ensured seamless navigation in confined spaces, verified with 30 real drones in 2018 . ResearcGround robots in a swarm have always intrigued researchers and engineers due to their wide application in military operations, social activities, intelligent manufacturing, etc. Besides the advantages shared by aerial robots, ground robots play a key role in restricted space and environments with portability, concealment and flexibility. There are three frontier research topics in three different operation spaces.Micro- and nanorobotics is an emerging field of the research arising from the cross-fusion of micro-/nanotechnologies and robotics . CompareThe cooperation among multiple industrial robots will bring cooperative motion planning and synchronous motion control problems of multiple manipulators under constraints . In multThe cooperation of unmanned ground vehicles (UGVs) in a swarm puts forward requirements of precise positioning and navigation technology in both indoor and outdoor environments. The outdoor environment supports positioning and navigation devices, such as GPS, IMU, electronic compass and other sensors. However, the lack of prior information and GPS signal greatly increase the difficulty of navigation and positioning technology in indoor or GPS-denied environments. Thus, it is suitable to utilize vision-based systems as an alternative for indoor environments . ThereinUnmanned marine vehicles (UMVs) refer to marine robots moving above and below the water with no operation from the human on board. UMVs are usually equipped with the necessary sensors and payloads to accomplish neither civilian or military missions, such as environmental monitoring, target surveillance and region reconnaissance.A UMV consists of unmanned surface vehicles (USVs) and unmanned underwater vehicles (UUVs). USVs are a type of unmanned surface vessel that can be fully autonomous, semi-autonomous or switched to manual control. They are able to navigate autonomously and avoid obstacles intelligently by following the current parameters and waypoints obtained from programs. This makes them ideal for data collection, autonomous hydrographic surveys and military applications. UUVs are supposed to carry out tasks without real-time supervision and intervention from the operator. They are capable of cruising on a predetermined course, publishing and receiving the information and making decisions according to the posture change driven by the embedded program. UUVs mainly incorporate remotely operated vehicles (ROVs) and autonomous underwater vehicles (AUVs). The development of ROVs could overcome the limitations of the operators and manned marine vehicles. Therefore, they are remotely operated by crew on nearby vehicles and connected to their operating bases through an umbilical cord link. This link can provide lines and power supply, communication and data links. ROVs are usually placed in four categories according to their size: work-class ROVs, observation- or inspection-class ROVs, mini- or micro-ROVs. They can be employed in military and civilian scenarios, such as pipeline and offshore platform inspection tasks. AUVs can perform a task lasting several months without direct real-time control. They can execute the preprogrammed, predefined waypoints normally and make decisions on the emergent circumstances via intelligent algorithms. Most AUVs are powered by battery and propelled by thrusters. Therein, the underwater gliders use buoyancy changes to adjust the depth and work on sampling or monitoring tasks. AUVs with no link to the ground possess high operability and can travel to remote positions and through narrow complicated pathways . Other ACompared with land and air environments, the ocean water environment has more disturbances, such as ocean currents, faults and complex submarine topography. Underwater acoustic communication is an effective form of underwater communication, but the propagation speed of the acoustic wave is 5 orders of magnitude lower than that of electromagnetic waves, leading to problems such as low information transmission speed, serious delay, packet loss and fast attenuation. Meanwhile, it is difficult for one single UMV to conduct complicated tasks. However, the AUV swarm could implement tasks cooperatively to achieve greater efficiency in the complex marine environment . Thus, mConnected communication is the basis of reasonable and efficient cooperation between UMVs. Because the underwater environment has a strong attenuation effect on electromagnetic waves and light waves, long-distance communication relies heavily on underwater acoustic communication at present. Underwater acoustic communication is realized by the underwater acoustic communication machine carried by UMVs, and the communication content can be request, response, task, target, state information, control instruction and so on. However, the acoustic wave will generate a large transmission delay, so real-time communication between UMVs is difficult to achieve. Moreover, the transmission distance of acoustic waves is limited by the carrier frequency and transmitting power. The scattering, transmission loss and echo interference of acoustic waves in water have effects on the distance and quality of underwater acoustic communication. Thus, experts in related fields have done a lot of research to explore communication methods, such as IR sensors , blue liNavigation and location technology is the prerequisite and key technology of cooperation in the multi-UMV swarm. However, due to the complex underwater environment and the limitations of UMV itself in size, the methods to achieve multi-UMV locations are limited. They mainly include the following.Acoustic navigation location: although this method has high accuracy, the cost of the baseline layout is high and the location accuracy is limited by the coverage of the baseline.UMV navigation presumption: this method is characterized by simple operation and low cost, but the location error accumulates over time.Inertial navigation: this method possesses high precision with the expensive cost of high precision inertial equipment, especially in a large-scale group.Geophysical guidance : this method needs to provide a corresponding matching database, which is not suitable for unknown regions.Multiple-UMV cooperative location: a small number of UMVs are equipped with high-precision navigation equipment to provide accurate relative positioning information for other UMVs. Other UMVs utilize relative positioning information to correct their location errors. Multiple-UMV cooperative navigation has the characteristics of moderate cost and simple implementation, which can meet the needs of the rapid location. However, cooperative navigation usually relies on underwater acoustic communication for location information transmission, resulting in a large transmission delay.Many scholars have made significant contributions to theory research and hardware implementation of multi-UMV cooperation. For cooperation control, multiple UMVs are supposed to meet task requirements and environmental constraints. Because of environmental disturbance, discussions on this topic have been conducted in view of weak communication topology , communiIn biology, the experiments of bird flocks under human intervention provide an innovative way to further study the mechanisms of flock movement and communication interaction. The free flight experiments for long distances have accomplished human control of the robo-pigeon by neural stimulation . Then, cU.S. Army Unmanned Aircraft Systems Roadmap 2010–2035 issued in 2010 covered a 25-year period, divided into three distinct periods: near term, mid term and far term. The far term emphasized drastic commonality and capability improvements of both manned and unmanned systems to lay the foundation for man-machine cooperation. SUAS Flight Plan 2016–2036 proposed the concept of a loyal wingman, highlighting the man-to-machine means. Unmanned Systems Integrated Roadmap 2017–2042 addressed the critical need of interoperability to promote the capability synergy of manned and unmanned systems in 2018. The artificial intelligence strategic development plan announced by the Chinese State Council in 2017 covered man-machine cooperation eight times and considered it one of the key technologies for establishing the key generic technology system in the area of artificial intelligence. Professor Tianran Wang pointed out that the next generation of robots will cooperate with the human in the Opening Ceremony of the 2018 National Robot Development Forum and RoboCup China competition. In the 2018 IEEE/CSAA Guidance, Navigation and Control Conference, Professor Bangkui Fan pointed out that the high degree of cooperation between manned and unmanned systems is the key to realizing the practical application of a UAV swarm. Besides, the National Natural Science Foundation of China launched the first major research program in the field of robotics in China on the advice of experts, including Han Ding, Xuejun Yang and Nanning Zheng, to promote basic research on Tri-Co robots. Thus, it has become an important development trend to adopt the cooperation of manned and unmanned systems to realize the multiplication and even exponential increase of the task capability in cross-domain platform systems.Aiming at achieving the autonomous cooperation of the manned-unmanned system, Professor Jie Chen proposed research challenges containing four levels .System level: organizational structure and collaboration mode.Decision-making level: task allocation and behavior planning.Control level: cooperative motion control.Security level: security of command control.et al. proposed a vision of human-centric networked unmanned systems: the unmanned intelligent cluster. Cooperation can be achieved by knowledge sharing and social awareness between distributed unmanned systems and humans [Zheng d humans . Generald humans . The cond humans ; (2) thed humans ; (3) thed humans ; (4) thed humans .The level of swarm autonomy (LOA) can be roughly divided into three ranks: manual, mixed-initiative and fully autonomous LOA . Three bLevel 1: indirect transmission/receipt of UAV-related metadata and data.Level 2: direct transmission/receipt of UAV-related metadata and data.Level 3: control and monitoring of UAV payload, rather than the unit.Level 4: control and monitoring of the UAV, with no launch and recovery.Level 5: control and monitoring of the UAV, containing launch and recovery.It can be seen that level 5 requires the installation of a fully remote pilot station in the manned aircraft and offers the crew maximum control.In the manned and unmanned air systems, providing pilots or operators the ability to control UAS enables them to take full advantage of ISR  capabilities to enhance decision-making and improve safety during dull, dirty and dangerous tasks. As for manned and unmanned marine systems, divers may cooperate with UMVs to complement each other to accomplish the tasks of underwater salvage, rescue, maintenance and scientific research together. A variety of devices equipped by the UMVs could reduce divers’ loads, and enhance the flexibility and automation level, such as communication modules, multi-beam and side-scan sonar, and the ultrashort baseline location system. Meanwhile, UMVs are supposed to assess the physical condition of the divers via the connection with life detection and support systems. Thus, divers have the opportunity to escape dangers or accidents under the alarm and assistance of UMVs. The design of the human-UMV cooperation system should take the role of operators in complex tasks into account to be flexible and applicable, and, more importantly, adopt compliant control methods to guarantee the safety of divers while UMVs approach divers. To solve the complicated and uncertain situations with the human-UMV cooperation system, one of the foremost considerations must be the group role assignment problem. Through role-based collaboration methods, researchers could establish an efficient and flexible system . In mannThe development directions of the swarm-robot system are preliminarily discussed in this section, as shown in Fig. Research on the mechanisms of large-scale swarm movement of biological groups, such as birds and fish, has attracted extensive attention from researchers in different fields. Through simple rules and local interactions, biological groups show collective behaviors with strong robustness, high self-adaptiveness and good scalability, which are the desired characteristics of a swarm-robot system. Although we have a primary understanding of the collective mechanisms in biological swarms through theoretical modeling and empirical analysis, the self-organizing emergence mechanism of swarm intelligence still requires further research. Currently, swarm-robot systems pay more attention to the scale effect, hoping to suppress the enemy with the number advantage through cooperation. However, this line of research is only similar to animal communities in form and intuitionistic. Employing the intelligent mechanisms emerging from the biological swarm behaviors can improve the system efficiency to a greater extent and achieve exponential growth of task effectiveness. In this sense, research on the theory and method of biological swarm intelligence is becoming more and more important related to the heterogeneous group, individual learning, etc. Thus, data analysis from biological swarm experiments will help to reveal the internal mechanism of self-organizing intelligent swarm behaviors. The biological experiments under human intervention could be helpful for the exploration of the intelligent mechanisms in animal swarms. Also, the mapping mechanisms from animal collective behaviors to swarm robotic cooperation are supposed to be modeled with the task requirements.To adapt to the requirements of platform performance, battlefield environment and tactical tasks, the incentive and convergence mechanisms of swarm intelligence in nature are explored to change the bottleneck situation of the intelligent unmanned system with intelligence but no wisdom, sensing but no cognition, specialty but no generality, cooperation but no convergence. On the one hand, the coordinated mechanisms’ inner biological swarms are supposed to be utilized in the processes of flight management and control, collaborative decision-making and information sharing. On the other hand, swarm-robot systems are supposed to be endowed with the ability of self-learning and evolution by biological swarm intelligence to gain full autonomy. The autonomous control technology of swarm-robot systems based on bionics is expected to be broken through via the cutting-edge technology research of biology, control, artificial intelligence, robotics and other interdisciplinary fields. Thus, exploring the phenomenon of swarm intelligence incentive and convergence in the natural community and applying it to the subversive technology of autonomous swarm control of robots are very compatible both in terms of the theoretical framework and application requirements.In the complex multi-task environment, the intelligent swarm-robot system is required to comprehensively perceive and understand the environment. At the same time, information sharing and interaction within the swarm for individual decision-making are the basis for a swarm-robot system to achieve high-level autonomous control. The task of environment sensing is required to collect information data on the robot using the load equipment, such as photoelectric and radar, discover the rules and mine the targets from the data, and then identify the targets to improve the global recognition of the complex environment situation and enhance the reliability of the system. The eagle has the sharpest visual acuity among all animals, whose powerful vision perception mechanisms bring abundant inspiration for traditional visual applications. Biological eagle eye vision technology provides a creative way to solve visual perception issues . ThereinDrawing on experiences from the technology development model of military powers, the scenarized competition of the swarm-robot system needs to be vigorously promoted . FirstlyThe coordinated and ordered movements emerging from the aggregation of a large number of individuals in nature provide plenty of examples and abundant inspirations for swarm intelligence research. The kinetic model and behavior mechanism of swarm intelligence promote the development of cooperative control theory and methods of unmanned swarm systems. This article starts with an introduction of natural collective behaviors in schools, packs and flocks. Then, the connotation and mechanism of swarm intelligence are given on the basis of biological behaviors. Furthermore, the SI concept is applied in the cooperative control of three types of unmanned swarms, i.e. an aerial robotics swarm, a ground robotics swarm and a marine robotics swarm. Moreover, the intervention of human operators has led to multiple and even exponential growth of the mission capability of cross-domain platform systems. The advancement trending of swarm intelligence and the swarm system is discussed preliminarily as reference directions for subsequent exploration.


Acute ischemic stroke (AIS) is one of the leading diseases causing death and disability worldwide, and treatment options remain very limited. Traditional Chinese Medicine (TCM) has been used for thousands of years to treat ischemic stroke and has been proven to have significant efficacy, but its mechanism of action is still unclear. As research related to the brain-gut-microbe axis progresses, there is increasing evidence that the gut microbiota plays an important role during AIS. The interaction between TCM and the gut microbiota has been suggested as a possible key link to the therapeutic effects of TCM. We have compiled and reviewed recent studies on the relationship between AIS, TCM, and gut microbiota, with the expectation of providing more ideas to elucidate the mechanism of action of TCM in the treatment of AIS. Stroke is an acute focal injury to the central nervous system (CNS) caused by vascular causes and is the leading cause of disability and death worldwide , with acRecently, as the concept of the gut-brain-microbe axis (GBMAx) has become clearer , the impTraditional Chinese herbs have the advantages of being multicentric, multitargeted, holistically regulated, and having few side effects in the treatment of AIS  Several Many herbs have been found to promote neuroprotection and reduce excitotoxicity, oxidative stress, apoptosis, inflammation and autophagy of neurons in ischemic conditions . GastrodPromoting capillary angiogenesis is considered to be an effective way to combat ischemic diseases, and many herbal formulations, with monomeric compounds that have a pro-angiogenic effect, have an ameliorative effect on improving persistent ischemia in brain tissue in acute cerebral infarction . For exaImproved intracellular energy metabolism can effectively protect ischemic semidark zone nerve cells. Dan Hong injection (DHI) is a compound Chinese medicine used for the treatment of acute ischemic stroke. Dan Hong injection can improve energy metabolism in ischemic brain cells and reduce nerve damage in the semidark zone by restoring mitochondrial activity and cytoplasmic glycolytic activity . Herba lIt has been found that the gut microbiota plays an important role in facilitating food conversion and absorption, regulating body metabolism, maintaining homeostasis of the immune system, protecting the integrity of the intestinal mucosal barrier, and preventing pathogenic invasion . The gutParabacteroides, Oscillospira, Enterobacteriaceae, Megasphaera, Oscillibacter and Desulfovibrio present in the gut of stroke patients compared to healthy individuals whose gut is rich in Prevotella, Roseburia, fecalibacterium, etc.,  are organic fatty acids produced by the breakdown of leftover nutrients in the gut microbiota and are considered to be key signaling molecules in the communication between the gut and the brain . Lower lammation . TherefoIn recent years, there has been increasing evidence that the gut microbiota may play a key role in the treatment of AIS with TCM  Feng et. AIS canTraditional Chinese herbs regulate the diversity of the flora through direct contact with the gut microbiota. Oral administration of herbal tonics is the traditional method of administration in TCM. Interestingly, this creates enough time and space for the herbal ingredients to interact with the gut microbiota . It has By regulating the gut microbiota, Chinese herbs have been found to influence the metabolic levels of intestinal flora metabolites, improve the inflammatory environment in the gut, reduce neuronal apoptosis, and protect the integrity of the intestinal barrier.Blautia, Coprococcus, Streptococcus, Dorea, Streptococcus, Bifidobacterium, and Lactobacillus more accessible to healthy people (Verrucomicrobia and Akkermansia abundance to increase the levels of enteric butyric acid (Oscillospira, Lachnospiraceae, and Akkermansia to increase butyrate release (Reduced metabolic levels of SCFAs, particularly acetate and butyric acid, showed a positive correlation with the severity of AIS . Severaly people . XCD canric acid . The PLR release . In a st release . On the  release . BBR was release . Enema w release . Ginkgol release . Based o release .Mycobacterium avium, in the gut, thereby reducing the level of LPS biosynthesis (The intestinal immune environment has an important role in regulating inflammatory damage to brain tissue after AIS. Increasingly, studies have shown that by regulating gut microbiota, Chinese herbs can effectively improve the intestinal immune environment and reduce brain and intestinal inflammatory responses. At the cellular level, the HQ-HH combination reduces the number of TH17 cells in the gut, increases the number of Treg cells, and reduces inflammation in the gut and brain tissue . Tongqiaynthesis . It was ynthesis .A. muciniphila and Lactobacillus (Lactobacillus (A. muciniphila reproduction by stimulating intestinal mucus protein secretion, which forms a dense protective intestinal layer (An intact gut barrier is essential to reduce peripheral organ infections caused by the spread of enteric pathogens after AIS . Studiesbacillus . Oral adbacillus . BBR wasal layer , and pueal layer . In addial layer . It was al layer . Bile acal layer . It was al layer .Bifidobacterium breve, which may contribute to the enrichment of certain microorganisms with anti-inflammatory properties, such as Lactococcus and Ruminococcus (It has been found that the gut microbiota interacts with Chinese herbs and that many herbal compounds need to be transformed into more active and bioavailable molecular structures with the cooperation of gut microbiota . The ricnococcus . In the nococcus .The gut microbiota has an important impact on AIS prognosis, while the microbiota’s significance to gut health should not be overlooked. One study found that depletion of gut microbes by antibiotics alleviated brain injury in MCAO mice; however, the mice that lost their gut microbes invariably developed severe acute colitis after discontinuation of antibiotics . TraditiMost notably, the study of the regulatory effects of Chinese herbal medicine on the gut microbiota could shed more light on the principles of TCM theory. For example, the same treatment for different diseases is a very important and classical theory in TCM. In short, when different kinds of diseases have the same pattern, they can be grouped together as the same Chinese medicine syndrome and treated with the same therapeutic methods . LookingIn summary, TCM has the advantages of multipathway, multitarget, and synergistic treatment for AIS. Exploring the interaction between Traditional Chinese herbs and gut microbiota is a novel idea that is important for elucidating the mechanism of Traditional Chinese herbs in treating AIS. Meanwhile, this study can help bring the clinical value of TCM into play to a greater extent and has broad research potential.


In this review, we will describe the most updated bioengineering approaches to recapitulate the native cell microenvironment and reproduce functional tissues and organs in vitro. We have highlighted the limitations of the use of exogenous scaffolds in recapitulating the regulatory/instructive and signal repository role of the native cell microenvironment. By contrast, strategies to reproduce human tissues and organs by inducing cells to synthetize their own ECM acting as a provisional scaffold to control and guide further tissue development and maturation hold the potential to allow the engineering of fully functional histologically competent three-dimensional (3D) tissues.The extracellular microenvironment regulates cell decisions through the accurate presentation at the cell surface of a complex array of biochemical and biophysical signals that are mediated by the structure and composition of the extracellular matrix (ECM). On the one hand, the cells actively remodel the ECM, which on the other hand affects cell functions. This cell–ECM dynamic reciprocity is central in regulating and controlling morphogenetic and histogenetic processes. Misregulation within the extracellular space can cause aberrant bidirectional interactions between cells and ECM, resulting in dysfunctional tissues and pathological states. Therefore, tissue engineering approaches, aiming at reproducing organs and tissues  Tissue-engineered products are generally intended to regenerate, repair, or replace human tissue. However, these products have recently also been used as functional human tissue models in laboratory settings for the purpose of drug discovery, toxicity testing, and disease modeling. In this perspective, the goal is to replicate the complex microarchitecture and physiological functions of human tissues and create models that more accurately reflect human biology when compared to the traditional human experimental assay such as cell cultures or animal models . The majin vitro, which include the use of natural and synthetic ECM mimetic , the specific organization and amount of structural units of the ECM vary from organ to organ. Furthermore, in the same organ, spatial differences in the ECM can be observed. The dermis, for instance, presents two regions, the papillary and reticular dermis. They are produced by the same cells, the fibroblasts, and contain the same macromolecules that are differently organized, resulting in different final functions and properties . The der mimetic  and the  mimetic . In addi mimetic , showingeraction .The ECM is a macromolecular network that provides structural support, defines tissue architecture, and elicits signals relying on the status of the mechanical environment to adherent cells .From the discovery of integrins (and other ECM receptors) in the mid-1980s, the past concept of the ECM being a “passive” scaffold holding cells and tissue in place has been overcome, and the ECM’s regulatory role on cell functional states in normal physiology and homeostasis, disease progression, and development has been widely recognized . IntegriElastin and fibrillin are the main components of elastic fibers and are both critically important in the development and homeostasis of elastic tissues . In partIn the following section, we provide a sampling of ECM functions in pathophysiological events occurring in the human body and highlight the diversity of mechanisms that depend upon the actions of matrix molecules and their cellular receptors .The development of branched organs is an interesting example of the multiple roles played by the ECM in morphogenesis. The branching involves the invasion of epithelial buds and tubes into the surrounding embryonic mesenchyme rich in ECM. Several matrix molecules such as glycosaminoglycans (GAGs), collagens, and many other glycoproteins are involved as regulators of hair follicle, mammary gland, salivary gland, kidney, gut, and lung development. The branching units are surrounded by microenvironments of the ECM that change in composition and spatial distribution over time . This coThe mammary glands are a unique branched organ in which most of the branching morphogenesis are required to develop the ductal tree, which occurs postnatally during puberty. Therefore, they represent a deeply investigated model to understand how the ECM remodeling contributes to tissue morphogenesis and functional differentiation . The mamin vitro in 3D laminin-rich ECM can establish apical–basal polarity and express milk proteins in response to lactogenic hormones even in the absence of myoepithelial cells. On the contrary, if cultured in collagen gels lacking laminin, the cells display reversed polarity and lose mammary-specific gene expression  bulk processing  , (ii) fiBesides pore size, shape, interconnectivity, and spatial arrangement, many other important cues have to be implemented and opportunely modulated in the 3D scaffolds if one wishes to mimic the dynamic and instructive role of native extracellular space as close as possible. Therefore, cell instructive materials hosting molecular, topographical, mechanical, and morphogenetic cues have emerged as a new class of advanced biomaterials for tissue engineering applications .Molecular cues that are provided to cells arranged in 3D contexts can be divided into ECM-binding proteins , ECM-remodeling proteins, and GFs. The importance of ECM-binding proteins in in vitro cell cultures to promote their adhesion is widely recognized. Adsorption of such proteins on biomaterial surfaces to support cell adhesion is a common practice in tissue engineering applications. In addition, different biomaterial scaffolds are produced in the form of hydrogels or sponges made up of ECM proteins  sequence is the most important modifier of biomaterials as it has been recognized to be a pro-adhesive motif, via integrin binding, found mainly in collagen, gelatin, fibronectin, and laminins . Other tNanopatterns and mechanical cues represent other important sets of signals useful for bioengineering the cell microenvironment and to control cell fate. The advent of even more sophisticated microfabrication techniques such as photolithography, electron beam lithography, microcontact printing, microfluidics, and two photons has provided the possibility to fabricate biomaterials with specific nanometric features. Nanopatterning in the form of grooves and channels, pillars, wells and pits, and molecular motifs can be used to modulate adhesion, alignment, migration, and differentiation of the cells. Gradients of such signals can be obtained by spatially varying the pattern density. Patterning can be used to induce cell alignment or to orchestrate precise spatial distribution to mimic specific tissue architectures. Patterned collagen gel has been used to induce alignment of corneal keratinocytes  , their bioactivation degree and spatial arrangement as ECM surrogates still represent an “exogenous” environment, and although representing complex “bio-logic” systems, they are still far from the native context in terms of composition, architecture, functions, signal sequestration, and spatiotemporal presentation. The ECM is a biomaterial designed by nature that underwent over 600 million years of material optimization . Regarditissues) . Unlike in vitro applications, both recellularization and in vitro culture steps are still challenging, and specific bioreactors for cell seeding and tissue cultivation have to be designed. In addition, tdECMs do not allow the full preservation of both tissue and stem cell niches. Indeed, during the decellularization process and the following fixation steps, severe modification of the ECM macromolecules can occur. tdECMs are also produced in the form of bio-inks (Tissue-derived ECMs (tdECMs) are isolated from native organs after the removal of resident cell populations by means of physical, chemical, or enzymatic methods followed by a fixation step with the final aim to preserve the original ECM architecture and composition and to prevent host reactions after implantations  Swineha. The firbio-inks . The posbio-inks  C3 have bio-inks , liver . in vitro extracellular architectures that are close to the native organs, and for each organ, it is possible to replicate the specific physiological and pathophysiological features. cdECM can be engineered to recreate stem cell and tissue niches. Genetically modified cells have been used to produce recombinant human laminin sheets that, in turn, have been used to trigger the differentiation of either embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) toward pancreatic lineage  related to the decellularized ECMs is quite similar to the native counterpart and the presence of important key regulators of cell functions can be retained such as collagen, glycoproteins, proteoglycans, ECM-affiliated molecules, and secreted factors , lactadherin (MFGE8), biglycan (BGN), fibromodulin (FMOD), hyaluronan, and proteoglycan link protein 1 (HAPLN1). Interestingly, after seeding such decellularized ECM with dermal fibroblasts, it was observed that the specific microenvironment could control the fate of dermal fibroblasts. The latter primarily produce collagen type I but not collagen type II. However, when these cells were cultured in such decellularized ECM, the expression of collagen type I decreased and the expression of collagen type II increased according to the in vivo situation. Furthermore, by using different cell types, the cdECM possesses a different matrisome (Cell-derived ECMs (cdECMs), also called re-engineered ECMs, are obtained crowding , by inducrowding . Macromo lineage . Other s lineage ,  with the final aim to obtain more complex biological entities that in their final configuration are characterized by a connective compartment composed of fibroblasts embedded in their own ECM. These in vitro–formed ECMs can be defined as endogenous ECMs since the cells and their own ECM are not decoupled and evolve together during the entire in vitro tissue genesis process. The tissue engineering strategies that fall in this category comprise self-assembly of cell sheets  in 2D culture plates for up to 28 days of culture. Stromal cell sheets can be stacked to obtain thicker tissues and are further covered by epithelial cells to form full-thickness barrier tissues. In parallel, stromal cell sheets can be populated by organoids, cancer cell spheroids, and either vascular or lymphatic endothelial cells  and the importance to replicate an adequate supportive ECM. The relevance of the former has been widely demonstrated in several articles  during cancer progression, modifications of the ECM due to external stimuli , intrinsic stimuli , wound healing, or inflammations. With the term modification and/or alteration, we refer to the variations in compositions, architecture, biophysical properties, and spatial re-organization of signals occurring at the ECM level. To the best of our knowledge, by using exogenous matrices, the recreation of specific dynamics involving the TME has been only partially recapitulated. Often, the most relevant phenomenon that exogenous matrices have displayed is related to the stiffening and alignment of preexisting exogenous fibers due to traction force exerted by fibroblasts or cancer-activated fibroblasts (CAFs)  . By conts (CAFs)  have proll lines . It was ll lines . In a dill lines . Malignaobserved . Interesobserved , increasituation . FinallyReplication of dermis damage and repairing process. The human dermis displays relevant modifications after exposure to UV light and during the repairing process of deep wounds. The inflammation occurring after UV exposure leads to modifications of ECM composition and architecture. Such modifications play a crucial role in skin functions: the departure of ECM composition, architecture, and mechanical properties from the physiological status is responsible for skin aging, which is ultimately related to a wide range of pathological events  and by the short experimental time that hinders the possibility to follow the synthesis and assembly of other ECM components such as collagen and hyaluronic acid .in vitro. This has been analyzed in the light of relevant biological phenomena where the ECM matters: in vitro replication of spontaneous morphogenetic process as well as time and space evolution of the ECMs after damages. Endogenous-based approaches can potentially lead to the fabrication of living tissues possessing functionalities closer to their native counterparts. This will improve the outcome of treatments such as wound healing and organ regeneration. Moreover, fully endogenous tissues possess a superior biological relevance with tremendous advantage for the organ-on-chip applications. Although the production of endogenous tissue is longer than in other approaches, the preservation of the cell–ECM interaction allows the in vitro replication of the ECM-related phenomena that plays a crucial role in pathologic events such as fibrosis, TME transformation, and ECM remodeling. The use of endogenous engineered tissues for in vitro screening provides a more physiologically relevant environment by better mimicking the complexity of living systems and leading to more accurate predictions of drug efficacy and toxicity. Additionally, the use of patient-specific engineered tissues has the potential to offer personalized and more effective treatments. Despite some challenges, the benefits of this approach make it a promising area of research and development.We have reported that cells decoupled by their native context and reseeded in an exogenous scaffold are not able to restore the physiological cell–ECM interaction, which is crucial for replicating all biological processes occurring in the native tissues. In addition, decellularization of cell-derived ECMs should be considered an exogenous approach since the cells are not embedded in their own 3D context and cannot recognize the surrounding environment as native. The use of an endogenous-based approach seems to be more promising if one wishes to fully replicate the functions of native tissues


Cancers is a collection of 13 impactful papers, comprising 7 original articles and 6 reviews. These contributions delve into emerging engineering approaches for immunotherapies, the characterization and modification of the TIME, and comprehensive reviews addressing diverse aspects of these topics. We will highlight several of these works below, and encourage the reader to refer to the Special Issue for additional details. Cancer immunotherapies, while promising and occasionally even curative, encounter numerous hurdles within the tumor microenvironment that hinder their efficacy. The presence of an immunosuppressive tumor immune microenvironment (TIME) significantly limits the effectiveness of targeted immunotherapies. To maximize the potential of cancer immunotherapies across different malignancies, it is crucial to expand our understanding of the TIME and develop innovative techniques to overcome the obstacles contained therein. Interdisciplinary approaches are particularly appealing as known barriers include both biological as well as physical hallmarks of tumors. This Special Issue of Salmonella typhimurium (ST) secreting a bacterial hyaluronidase (YS-HAse) in order to overcome the excessive stromal matrix components typically found within breast tumors. ST has an innate ability to preferentially colonize solid tumors, while carrying a highly controllable plasmid, allowing for targeted delivery of bacterial hyaluronidase with minimal systemic toxicity. In an orthotopic breast tumor mouse model, this team’s work demonstrates that administration of YS-HAse resulted in the colonization of the tumor and enabled the control of tumor growth through the degradation of intratumoral hyaluronic acid. Some of the most impressive immunotherapy outcomes have been observed in the treatment of leukemias; however, major challenges and unpredictable variations in response remain. It is well established that dysregulation of epigenetic activation and silencing is a hallmark of acute myeloid leukemia (AML). Hypermethylating agents are the standard of care for the treatment of AML, although resistance can develop, resulting in disease relapse. Using immune-deficient and immune-proficient AML mouse models, Ebelt and Manuel  highlighMyeloid-derived suppressor cells (MDSCs) play a pivotal role in the reorganization of the extracellular matrix (ECM) and the establishment of an immunosuppressive TIME, thereby promoting a pro-metastatic state. In their article, Roberts et al.  investigIn another contribution, Dunn et al.  report aThe remaining original studies included in this issue focus on other means of targeting therapy resistance to enhance treatment efficacy. For instance, Park et al.  demonstrIn addition to these new experimental studies, several insightful review papers are also presented. In their comprehensive review, Vitorino et al.  examine In their systematic review, Pal and Sheth  highlighAdditional review topics include an investigation of the barriers faced by adoptive T-cell therapies in solid tumors, which is presented by Fuchsl and Krackhardt , as wellThe TIME presents a critical barrier for existing therapies, but it also provides a potential target opportunity for more effective next-generation immunotherapies. To tackle both the biological as well as physical hurdles of the TIME head-on, we believe this field is poised to make great strides by embracing a fully interdisciplinary approach. We hope the articles amassed in this Special Issue may suggest that, with a better understanding and control of the TIME, researchers and clinicians can ultimately develop a new paradigm for effective antitumor management that can be of benefit to the majority of patients.


Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins but play important roles in regulating cellular processes. Multiple studies over the past decade have demonstrated the role of microRNAs (miRNAs) in cancer, in which some miRNAs can act as biomarkers or provide therapy target. Accumulating evidence also points to the importance of long non-coding RNAs (lncRNAs) in regulating miRNA-mRNA networks. An increasing number of ncRNAs have been shown to be involved in the regulation of cellular processes, and dysregulation of ncRNAs often heralds disease. As the population ages, the incidence of neurodegenerative diseases is increasing, placing enormous pressure on global health systems. Given the excellent performance of ncRNAs in early cancer screening and treatment, here we attempted to aggregate and analyze the regulatory functions of ncRNAs in neuronal development and disease. In this review, we summarize current knowledge on ncRNA taxonomy, biogenesis, and function, and discuss current research progress on ncRNAs in relation to neuronal development, differentiation, and neurodegenerative diseases. In 2019, about 50 million people had dementia due to neurodegenerative diseases, and this number is predicted to increase to 1.25 million by 2060 . Non-codOnly 1.5% of the human genome encodes protein, and the remaining genes are called “dark matter”, which are widely transcribed to generate a massive amount of ncRNAs . With moWith the discovery of lncRNA, more and more researchers focus on exploiting the functions of lncRNAs and the relationship between miRNAs and lncRNAs . The funBecause both lncRNA and miRNA are closely related to diseases, more and more research is devoted to developing their potential as biomarkers of diseases. However, experiments often require a lot of time and money, which can be solved through computer models. Although computational models have become an essential method for screening the most promising miRNA-disease pairs, their accuracy and universality still need to be improved . TherefoHowever, the research on ncRNA function and developing computer models related to ncRNA diseases are focused on cancer. Evidence shows that ncRNAs are closely associated with neurons’ development, differentiation, and dysfunction. The human central nervous system has roughly equal numbers of neurons and glial cells, and almost all 86 billion neurons are located in the brain . The conGiven the abundant functions of lncRNA and miRNA related to neuronal development and disease, few similar reviews on this topic have simultaneously discussed the relationship between lncRNA and miRNA and neuronal development, differentiation, and disease. We summarized the significance of miRNA and lncRNA in neurodevelopment and disease and their potential role in the future. We want to draw more attention to the potential roles of lncRNA and miRNA in neurons. We believe lncRNA and miRNA can be used as biomarkers and therapeutic targets for some neurological diseases. At the same time, the network basis of lncRNA-miRNA-mRNA can further expand the relevant research direction. However, because there are few research results on ncRNA as a therapeutic target for neurodegenerative diseases or we have yet to be able to retrieve relevant literature, the content of this part needs to be improved, which is the limitation of this review.After identifying the topic, we searched NCBI for multiple review articles with the keyword “neurons,” most of which came from authoritative journals in neurology. In the process of comprehensively reading these review articles, we focused on documenting and listing the outline framework of the articles. We searched the experimental articles according to the content of the framework. When reading experimental articles, we categorize them according to the topics and methods of the study. In the case of controversy in the process of collecting and organizing, we selected articles with a higher impact factor or listed controversial cases. After that, we collected and sorted out the relevant contents and completed the literature review of this article. The parts with similar content are arranged in tables, and pictures supplement the problematic parts to describe them in words.Usually, neuron cells can choose to differentiate or proliferate, which means that when a neuronal cell differentiates, its ability to proliferate is inhibited . The NotIn addition to controlling neuronal differentiation through the Notch signaling pathway, lncRNAs and microRNAs can also affect other mRNAs, thereby controlling neuronal differentiation. PTBP1 (polypyrimidine tract-binding protein 1) interacts with Pkny, and the knockdown of Pnky or PTBP1 enhances neurogenesis . LncKdm2Synaptic scale-related protein dysfunction is associated with neurological diseases, and abnormal ncRNA expression is usually associated with protein dysfunction . MiRNA bNeuronal death caused by progressive neuronal structure or function loss is considered neurodegeneration. Aging, oxidative damage and inflammation are all important factors causing neurodegeneration. Neuronal degeneration caused by environmental toxicants accelerates with aging . miR-29 Much work has demonstrated the relationship between ncRNAs and neuronal function. Dicer deletion reduced the number of mature miRNAs, enhancing learning and memory . MiR-132Major neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), frontotemporal lobar dementia (FTLD), and amyotrophic lateral sclerosis (ALS). Discrete populations of neurons are lost or damaged in nearly every neurodegenerative disease . Here, wAlzheimer’s disease (AD) is the prevalent CNS degenerative disease, which can lead to mood disturbances, cognitive decline and even death . The mosParkinson’s disease (PD) primarily affects the motor system of the CNS. With the deterioration of PD, there will also be autonomic dysfunction and other non-motor symptoms . HereditHuntington’s disease (HD) is a fatal dominant neurodegenerative disorder induced by repeat expansions of cytosine-adenine-guanine trinucleotides in the Huntington gene. Its symptoms include chorea, mental problems and dementia . OverexpIn a mouse model of Amyotrophic Lateral Sclerosis (ALS), an antisense oligonucleotide (ASO) inhibitor of miR-129-5p significantly increases survival and improves the neuromuscular phenotype of treated mice . MiR-155Research shows that early diagnosis can reduce the risk of Alzheimer’s disease by one-third . Howeverin vivo due to circulating RNase or cell endocytosis chamber, and its half-life is very short  Conduct statistical analysis with the help of bioinformatics to accurately guide the research direction. (ii) Combining with endogenous competitive RNA (ceRNA) mechanism, further improve the linkage map between miRNA and neurodegenerative diseases to seek more accurate targets. (iii) Further modify delivery materials (such as nanoparticles) and oligonucleotides to improve penetration and reduce toxicity.Here, we introduced ncRNAs and the nervous system separately and discussed the roles of ncRNAs in neuronal differentiation, function, and diseases. Although the mechanisms by which ncRNAs affect neuronal function and dysfunction are not fully understood, this review summarizes the current relevant research results. Because the differentiation of the nervous system happens mainly in a specific period, ncRNAs often delay or advance differentiation by acting on specific signaling pathways, thereby affecting the differentiation process. The current findings suggest that neurodegenerative diseases are often the result of disturbances at the protein level. LncRNAs and microRNAs often compete and alter protein stability, thereby changing the ratio of protein concentrations. Due to individual differences and the complexity of the nervous system, there are sometimes two independent studies with opposing results. In the end, our exploration of neuronal remains the tip of the iceberg. It cannot be excluded that with further research on ncRNAs and neurons in the future, more targets will be unlocked for therapeutic purposes.


The rising demand for medicinal oxygen due to the COVID-19 pandemic exacerbated an underlying chronic shortage of the commodity in Africa. This situation is particularly dire in protracted crises where insecurity, dysfunctional health facilities, poor infrastructure and prohibitive costs hinder equitable access to the commodity. Against this backdrop, the Ministry of Health of South Sudan, with the guidance of its partners, procured and installed a pressure swing adsorption central oxygen supply plant to address the shortfall. The plant aimed to ensure a more sustainable and technologically appropriate medicinal oxygen supply system for the country and to bridge the humanitarian and development divide, which had always been challenging. This article discusses the key issues, challenges and lessons associated with the procurement and installation of this plant. The major challenges encountered during the procurement and installation of the plant were the time it took to procure and install in the face of urgent needs for medicinal oxygen and its short and long-term sustainability. Lessons learnt include the need for exhaustive and evidence-based considerations in deciding on which source of medicinal oxygen to deploy in protracted crisis settings. The successful installation and operationalization of the plant demonstrated that it is possible to bridge the humanitarian-development divide amidst the complexities of a protracted crisis and an ongoing pandemic. The Ministries of Health, with the support of its partners, should assess and document the impact of this and other similar central oxygen production plants in protracted crisis settings regarding their sustainability, cost, and effectiveness on medicinal oxygen supply. The Ministry of Health of South Sudan should expedite the finalization and operationalization of the longer-term public-private partnership and continue to monitor the quality of oxygen produced by this plant. COVID-19, a disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), primarily affects the upper and lower respiratory system of humans. Most people infected by the virus will manifest mild to moderate respiratory symptoms, but a small percentage of patients develop a severe illness that requires isolation, hospitalization, and medical care . It has Oxygen plays a critical role in the survival of humans, animals, and plants. In the healthcare sector, it is an indispensable life-saving medicine utilized at all healthcare system levels. It is administered to treat pneumonia and COVID-19, used in the management and during the transportation of critically ill patients, and to aid asphyxiated mothers and newborns. Additionally, the commodity is used in end-of-life care within hospices and home settings . CryogenNaturally occurring oxygen is produced through photosynthesis by green algae and cyanobacteria in marine ecosystems and by terrestrial plants . ArtificProtracted crisis settings are characterized by peculiar challenges that pose significant obstacles to achieving sustainable production and supply of medicinal oxygen, particularly in Africa. These include disrupted health systems, particularly inadequate and unsustainable financing of healthcare services and inadequate human resources for health, poor infrastructure and lack of the appropriate technology to manage oxygen production. In addition to the aforementioned factors, which generally limit oxygen production and distribution capacities in Africa, insecurity stemming from armed conflicts that disrupt supply chain systems and dysfunctional health facilities that mostly lack access to electricity are features of protracted crises that limit equitable access to medicinal oxygen and other COVID-19 medical commodities. This was the situation when the COVID-19 pandemic struck South Sudan, the world’s youngest country in April 2020 . In thisper capita was only US$2.63, which is grossly inadequate to provide good quality health services  of 1.1%  and a cuThe country procured cylinders of medicinal oxygen from neighboring countries to address the shortage. In addition, some health partners procured and deployed several oxygen concentrators to address the immediate oxygen needs of COVID-19 patients . The lacThe plant was manufactured by NOVAIR France and installed at the Teaching Hospital Complex in the capital city of Juba. The NOVAIR plant was selected based on the presence of the manufacturer in the sub-region (Kenya and Uganda), which guaranteed ready access to spare parts and after-sales services. Furthermore, the same type of plant had been installed in Ghana with good outcomes. It has a continuous flow rate of 29 cubic meters of above 95% pure oxygen per hour and can refill 48 oxygen cylinders, each with a capacity of 50 liters at a pressure of 200 Bar, daily. The plant was procured with essential components such as 240 spare oxygen cylinders of 50 liters each, a comprehensive four-year spare part kit, and detailed installation and user training manuals. To ensure an uninterrupted power supply, it was connected to the Juba power grid and a 150-kilovolt-ampere standby electricity power generator was installed as a backup power source. Ten South Sudanese biomedical engineers and technicians were trained on-site by NOVAIR engineers to operate, manage, and perform periodic plant maintenance .The procurement, transportation, storage, and installation of the oxygen production plant presented several challenges, potential benefits and lessons learned, which we discuss in this article.The lead time for procuring the oxygen plant was long primarily due to the lengthy administrative procedures within WHO and extensive negotiations between WHO and NOVAIR to finalize the plant’s specifications.The local biomedical engineers and technicians who were trained had other responsibilities within the MoH, thus limiting their availability to operate the plant daily. This challenge is associated with the broader fragmentation of the health system in South Sudan, where the chronic shortage of healthcare workers often means multitasking, constraining the delivery of adequate healthcare services.The MoH faced difficulties in immediately assuming full ownership and management of the plant due to its lack of funding to cover the operational, staffing, and running costs.Technical challenges arose from damage to some plant components and spare parts during transportation and storage. Furthermore, the specification of some spare parts was incorrect, and some electrical installations in the purposely constructed building that housed the plant were inappropriate.Creative and locally available solutions were used to address these challenges. With the support of WHO, the MoH negotiated an agreement with the African Medical and Research Foundation (AMREF), an international non-governmental organization, to support the plant’s operational, staffing, and maintenance costs while a longer-term public-private partnership model was being developed. Innovative measures were employed to locally fabricate and replace the damaged components and inadequate spare parts while waiting for replacements from NOVAIR. To overcome the challenges of transporting the oxygen cylinders, special arrangements were made with the United Nations Humanitarian Air Service to airlift the filled cylinders to the state capitals and bring back the empty ones. These collaborative efforts and creative solutions played a crucial role in ensuring the successful implementation of the project despite the challenges encountered. This aligns with the recommendations of Ross et al. who posited that expedited approaches for improving access to supplemental medicinal oxygen therapy should be implemented using locally led, context-specific and sustainable solutions .Despite the associated challenges, the oxygen plant brought some potential benefits. Its installation in the premises of Juba Teaching Hospital, the biggest hospital in the country, which also housed the largest COVID-19 treatment center and is a short distance from the largest pediatric hospital in the country, improved access to medicinal oxygen for the treatment of COVID-19 and other diseases in the capital city and its environs. However, the plant did not have enough capacity to supply the whole country. The training of local biomedical engineers and technicians, which included didactic classroom and practical sessions , resulteBased on the experiences in procuring and installing this central oxygen plant, we highlight six key lessons that we believe would be useful in planning, procuring, and installing oxygen plants in similar and other settings. First, deciding which source of medicinal oxygen to deploy in protracted crisis settings requires exhaustive and evidence-based considerations. While oxygen concentrators may seem to be the most appropriate for immediate deployment for emergency use in protracted crisis settings, the requirement of an uninterrupted electricity supply and maintenance facility, which is often not available in such settings, is a major constraint for the mass deployment of these devices . On the This case study highlights the key issues, challenges and lessons associated with achieving equitable access to medicinal oxygen for managing COVID-19 and other diseases in a protracted crisis setting. It has demonstrated that exhaustive and evidence-based analyses of various sources of medicinal oxygen are required to identify the most cost-effective option in protracted crisis settings. Furthermore, it demonstrated the possibility of successfully installing and operating a central oxygen supply plant amidst the complexities of a protracted crisis like in South Sudan and the challenges of an ongoing pandemic. This is a testament to the possibility of bridging the divide between humanitarian aid and long-term development in the healthcare sector of countries in protracted crises. We believe that the lessons learnt from this, and other similar situations will stimulate the scale-up of similar initiatives to bridge the humanitarian-development divide in South Sudan and other protracted crises.Moving forward, we propose some recommendations based on the lessons learned from this case study. First, Ministries of Health of countries in protracted crises, with the support of its partners, should assess the impact of this and other similar central oxygen plants, regarding their sustainability, cost, and effectiveness in improving medicinal oxygen supply. The lessons learnt from such an assessment should be compiled into a comprehensive compendium outlining standardized specifications, planning considerations, procurement processes, transportation and storage guidelines, installation procedures, and sustainability strategies for such plants. Second, MoH South Sudan, with the support of its partners, should expedite the finalization and operationalization of the longer-term public-private partnership. Third, MoH South Sudan should continue to monitor and document the quality of oxygen produced by this plant and consider procuring and installing additional plants in other parts of the country to supplement this plant. Fourth, WHO should conduct research studies to gain a deeper insight into how to effectively bridge the humanitarian and development divide within the health sector of countries in protracted crises. Such studies should evaluate ongoing health interventions to bridge the humanitarian and development nexus in crisis situations to identify the key issues and challenges. Such information should be used to develop comprehensive frameworks addressing the complex health system challenges these settings face.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.OO: Conceptualization, Project administration, Supervision, Writing – original draft. AF: Conceptualization, Project administration, Supervision, Writing – review & editing. JW: Project administration, Supervision, Writing – review & editing. AG: Project administration, Supervision, Writing – review & editing. BK: Project administration, Writing – review & editing. MT: Project administration, Supervision, Writing – review & editing. SM: Conceptualization, Project administration, Supervision, Writing – review & editing.


The field of biophoton is expanding at an accelerated rate. Biophoton is one of the most prominent characteristics of biological organisms. Decades have been devoted to the exhaustive study of biophoton, with researchers focusing on elucidating the mechanisms underlying its generation and investigating its diverse properties. Biophoton, as a promising non-invasive diagnostic instrument, possesses substantial potential and utility for the examination of complex biological systems. Biophoton has been linked to electron transfer processes and the production of reactive oxygen species within the metabolic framework for many years. Its initial application, entrenched in the evaluation of the quality and safety of Chinese herbs, marked a significant turning point. Currently, biophoton encompasses diverse fields, including biology, clinical medicine, chemistry, and traditional Chinese medicine. However, the scope of diseases currently under investigation remains limited, and exhaustive data are urgently needed to strengthen the foundation of biophoton research. Researchers are simultaneously weaving a tapestry of omics techniques and biophoton to decipher the complex theories and mechanisms governing the physiology and pathology of organisms. This convergence gives disciplines including traditional Chinese medicine and clinical medicine new vitality.Bioluminescence Imaging (BLI) has been developed by expanding upon the foundation of biophoton research and its practical applications. BLI is a cutting-edge technique used to visualize physiological processes in animals, bridging a significant void in the non-invasive monitoring of experimental animals. It enables the observation of multiple physiological processes in real time without necessitating euthanasia, including the non-invasive surveillance of the regulation of islet beta cell function. BLI has the potential to considerably advance pharmacological and physiological research. In recent years, the limitations of single-modal imaging have been addressed by the development of multimodal imaging technology. As an optical imaging technique, BLI provides non-invasive, real-time imaging that precisely identifies the locations and physiological processes of specific cells as well as their interactions with adjacent cells. BLI has predominantly been a preclinical technology, but it has the potential to become a clinical tool for diagnosing and treating human diseases, despite substantial obstacles.In order to maintain a clinical focus and enhance our involvement in basic science, metabolism, and other clinically relevant areas, the compilation of new research findings in this field will undoubtedly contribute to its future development. We look forward to collaborating with you in the sphere of biophoton in the future years.


Wiig et al.). The research reported in this Research Topic features the critical role of professional engagement, the challenges and solutions surrounding workplace violence, and the need for continuous training in fields like nursing . Moreover, these studies emphasize the importance of adaptability and resilience in healthcare systems and teams .The ever-changing healthcare demands and the challenges posed by global health crises have prompted the healthcare sector to give increased importance to occupational health. Stemming from the realization that a productive and sustainable workforce is rooted in the health and wellbeing of workers, there is growing interest in formulating and implementing strategies that help identify, prevent, and manage occupational health risks . This trBabaie et al. in neonatal intensive care units explores the multifaceted nature of safety culture from the perspective of frontline medical staff in Iran. Ellis, Tran et al. showed the adaptability and resilience of healthcare systems during challenging organizational changes, emphasizing the role of a supportive workplace culture in their empirical study of an Australian hospital undergoing significant transformation. The poignant commentary from Montgomery and Lainidi, highlights the urgent need for systemic shifts in healthcare organizational cultures, a sentiment further amplified by the global challenges presented by the COVID-19 pandemic. In a different cultural setting, Wang, Zhang et al. developed a scale for the hospital organizational environment in China, reflecting its vital role for understanding the values and behaviors of both clinicians and nursing staff. As the world continues to grapple with the COVID-19 crisis, the case study by Paquay et al. recounts the benefits of post-shift clinical debriefings, signifying the integral role of organizational strategy in ensuring patient safety and bolstering clinician wellbeing. Lastly, the salient perspective article by Ellis, Falkland et al. critically reflects the intricacies and challenges tied to defining, measuring, and improving safety culture in healthcare. Understanding organizational culture is crucial, as it directly influences the mental wellbeing of its workers, shaping workforce burnout and staff retention. In the aftermath of the COVID-19 pandemic, burnout is one of the most prevalent staff wellbeing problems, with the ability to being able to retain and attract healthcare workers being fundamental to the ability to provide healthcare services in the future.The wellbeing of healthcare professionals, encompassing their physical, mental, and emotional health, is deeply intertwined with the quality of care delivered to patients . OrganizSeaward et al. highlight the occupational health and safety issues within residential aged care, suggesting potential neglect of worker wellbeing. Arad et al. investigated the interplay between teamwork and the psychological safety of surgical staff in Israel. Similarly, a study conducted in Germany by Treusch et al. examined the association between job satisfaction and the mental health of physician assistants, which encompassed facets such as general job satisfaction, work-related factors, and mental health indicators. This study paints a comprehensive picture of the challenges experienced. Yang et al. explored job burnout among primary health workers in China, illuminating the protective role of work-family support. The demanding nature of anesthesia work and its implications for staff wellbeing is captured in the study from Khalafi et al. The detrimental effects of incivility in hospitals, as discussed by Pavithra et al., emphasize the significance of a respectful and nurturing workplace culture for maintaining staff wellbeing. Together, these papers demonstrate the profound impact of workplace environments on the psychological health of healthcare professionals and, consequently, the care and care quality they deliver to patients.An integral aspect of occupational health, especially in sectors like healthcare, is understanding and addressing professionals' mental and emotional wellbeing. The psychological state of health care workers can significantly affect their cognitive capacity, influencing their performance, decision-making, and interactions with others . The psyIn the complex and dynamic landscape of healthcare, the importance of the wellbeing of healthcare workers stands out more than ever. Occupational health plays a significant role in determining the quality and efficiency of patient care. As global health challenges continue to emerge, healthcare professionals' resilience, adaptability, and mental fortitude are tested, underscoring the need for supportive and nurturing workplace cultures. The research presented in this Research Topic serves as a testament to the impacts on safety and wellbeing of the intricate relationship between organizational culture, workplace environment, and the health of healthcare professionals. It reinforces the idea that a positive organizational culture uplifts the spirits of those working within its confines, directly translating to better patient outcomes. As we reflect on these findings, several questions arise: How can healthcare institutions uphold and enhance positive organizational cultures amidst resource constraints and mounting external pressures? What measures can be taken to bridge the gap between recognizing the importance of occupational health and implementing effective solutions? How can interventions be tailored to address the unique challenges diverse healthcare settings face worldwide? And given the ongoing impact of the COVID-19 pandemic, how can healthcare systems better equip themselves-both in terms of infrastructure and the wellbeing of their healthcare workers-to respond to future global health crises? The insights gleaned from this Research Topic show a pressing need to prioritize and invest in the wellbeing of healthcare professionals. As the backbone of the healthcare industry, their physical and psychological health inevitably determines the quality of care patients receive. Moving forward, it is imperative for stakeholders at all levels, from policymakers to hospital administrators, to commit to fostering environments that champion the holistic wellbeing of healthcare professionals, thereby ensuring a brighter and healthier future for all.YT: Writing – original draft. LE: Writing – review & editing. RC-W: Writing – review & editing. KC: Writing – review & editing. SW: Writing – review & editing.


Emerging Infectious Diseases (EIDs) and Re-Emerging Infectious Diseases (REIDs) constitute significant health problems and are becoming of major importance. Up to 75% of EIDs and REIDs have zoonotic origin. Several factors such as the destruction of natural habitats leading humans and animals to live in close proximity, ecological changes due to natural disasters, population migration resulting from war or conflict, interruption or decrease in disease prevention programs, and insufficient vector control applications and sanitation are involved in disease emergence and distribution. War and natural disasters have a great impact on the emergence/re-emergence of diseases in the population. According to a World Bank estimation, two billion people are living in poverty and fragility situations. Wars destroy health systems and infrastructure, curtail existing disease control programs, and cause population movement leading to an increase in exposure to health risks and favor the emergence of infectious diseases. A total of 432 catastrophic cases associated with natural disasters were recorded globally in 2021. Natural disasters increase the risk of EID and REID outbreaks by damaging infrastructure and leading to displacement of populations. A Generic National Action Plan covering risk assessment, mechanism for action, determination of roles and responsibilities of each sector, the establishment of a coordination mechanism, etc. should be developed. ConversMany factors such as the destruction of natural habitats, which leads humans and animals to live in close proximity, changing climate and ecosystems, replacing reservoir hosts or intermediate insect vectors, and microbial genetic mutations are involved in the emergence of new diseases . Ecologith century has begun in recent years , it was found that an increase in the number of cases had been observed over and over due to conflict conditions. Violence against healthcare workers and Ebola treatment centers inhibited the rapidity of case isolation, treatment, following up the contacts of cases, and vaccination programs due to continuous conflict events . War in Destruction of healthcare infrastructure during wars resulting in weakened prevention and treatment programs can cause new strains of infectious diseases to emerge . EradicaAs of 20 March 2023, around 8.1 million Ukrainians have moved to other European countries since 24 February 2022 after the attack by Russia on Ukraine, 5 million of whom were recruited into protection programs . Owing tThere have been numerous reported outbreaks of conflict/war-associated EIDs/REIDs from a wide range of countries. Selected outbreak reports are presented in 3.Natural disasters increase the risk of infectious disease outbreaks, including EIDs and REIDs, by damaging infrastructure and leading to displacement of populations . The popA total of 432 catastrophic cases associated with natural disasters were recorded globally in 2021 though the average was 357 between 2001 and 2020 . The annNatural disasters are stratified into several categories by experts. Even though one classification divides natural disasters broadly into three general types , any disaster in one category can have elements of another, for example earthquakes can cause avalanches and tsunamis, which can, in turn, cause flooding .Hydrometeorological disasters such as floods from rains, hurricanes, cyclones, typhoons, and tsunamis are the most common natural disasters followed by geophysical disasters  while geo-meteorological ones are rarer than the others . SometimThere have been numerous reported outbreaks of natural disaster associated EIDs/REIDs from a wide range of countries. Selected outbreak reports are presented in 4.There are several causal factors in emerging and re-emerging infectious disease outbreaks in wars and natural disasters. Population movement and migration, environmental health disruption and ecological changes, displacement of domestic and wild animals, the collapse of health systems and disruption of disease control programs, inadequate surveillance and early warning and response systems, impaired laboratory services and diagnosis, and breakdown in infection control and treatment in effectiveness and development of drug resistance are the most accepted drivers of emerging and re-emerging infectious disease outbreaks in wars and natural disasters.The impact of wars and natural disasters on emerging and re-emerging infectious disease outbreaks can be direct or indirect.5.Campylobacter, Cryptosporidium, Escherichia coli, Giardia, Hepatitis A virus, Norovirus, Shigella, and Salmonella are generally reported from the affected areas  enhancing vector population densities , 85. ExiMosquito-borne diseases were also reported during drought conditions. Drought causes reduce in the size of water bodies making them stagnant which leads to additional breeding places for mosquitoes . Also, tThe risk of diseases transmitted by rodents such as leptospirosis and Hantavirus Pulmonary Syndrome increases as the probability of contact with bacteria and their animal hosts rise during heavy rainfall and flooding , 95. FloRarely, unusual disease outbreaks such as coccidioidomycosis and scrub typhus have been observed following earthquakes. For example, an outbreak of acute pulmonary coccidioidomycosis related to exposure to high-level airborne dust following landslides after the 1994 earthquake occurred in southern California , 98. ThiAlso, the destruction of infrastructure such as electricity, water supply, sewage disposal, and gas supply increases the risk of food poisoning and water-borne diseases after natural disasters , 101.Outbreaks of leptospirosis and malaria were reported in Guatemala and Nicaragua after Hurricane Mitch in 1998. The number of diagnosed malaria cases was considerably higher than the number of cases diagnosed before the hurricane .Melioidosis cases were reported in survivors of the tsunami which occurred in coastal areas of the Indian Ocean in December 2004 , 81. TheBunyaviridae), emerged in the Southwest USA in 1993 after El Nino Southern Oscillation events the year before, which had allowed excess precipitation, warmer seasons, and plenty of food for rodents , Lebanon , and Jordan  .The displaced population is generally housed in temporary settlements or camps with overcrowded shelters, which increases infectious disease transmission and the number of endemic and epidemic-prone disease cases , 85. TheBeing the largest refugee crisis since World War II, the Syrian crisis is one of the examples of how conflict and refugees change epidemiological patterns of diseases not only in the source country but also in neighboring countries , 110. CuSalmonella enterica, and chickenpox resulting from post-disaster living conditions increases after earthquakes  warns the countries accepting Ukrainians about rabies risk as it is still endemic in sylvatic animals and dogs and cats in Ukraine due to the reports describing displaced Ukrainians as fleeing with their pets .7.7.1.The deterioration of the public health systems leads to an interruption in health measures such as immunization, surveillance, prevention and control programs, sanitation, and hygiene services and results in an increase in communicable diseases , 133. DiThe incidence of vector-borne diseases such as malaria can increase due to the disruption of control activities . Re-emerP. falciparum malaria was re-established after 35 years in Tajikistan due to mass population movement to and from Afghanistan  of outbreaks which is especially important in effective disease/outbreak control and the management of conditions that occur secondary to the prime cause of the outbreak/disaster , 156. ThDisplaced persons or refugees are generally at great distance from access to laboratory facilities  which maThe debilitating earthquake in 2005 in Pakistan posed a unique problem with the supplies for the maintenance of laboratory services. The health management in affected areas was almost paralyzed and the existing healthcare system was completely demolished leading to total disruption of the primary and secondary healthcare system. Additionally, health staff became vulnerable due to landslides and weather conditions. The establishment of diagnostic laboratory services was a unique and special challenge. Unavailable appropriate shelters specified for laboratory equipment caused to work in uncontrolled conditions. The efficiency of sensitive equipment was affected due to drastic changes in temperature and electricity supply as the generators were limited. There was a great problem with effective logistic and technical support, and the supply of reagents and diagnostic kits . The wea7.4.Breakdown in infection control in natural disasters and wars is generally observed. The principles of infection prevention and control (IPC) remain especially important given the disrupted health services, insufficient trained staff and personal protective equipment, and the unhygienic circumstances after disasters, which can enable the amplification of infectious diseases. Infection control is especially important in areas where there is a transmission risk of infectious diseases such as Ebola, Middle East Respiratory Syndrome (MERS) , 138.Staff of healthcare centers are at high risk of contracting and transmitting the diseases to their family and the community , 162. PrA Marburg hemorrhagic fever outbreak was recorded in long-term war affected Angola in 2004–2005. The outbreak was amplified by multiple usage of injectors and multi-dose ampoules in health facilities , 32, 1657.5.The collapse of health facilities, impeded access of the population to surviving health facilities, and insufficient quantities of treatment drugs can cause the cessation of continuing treatment regimens and usage of un-prescribed drugs or inappropriate drug regimens and outdated drugs resulting in pathogens’ increase in infectious diseases transmission and resistance to drugs in conflict situations and natural disasters , 85, 166The emergence of Antimicrobial Resistance (AMR) in microorganisms is a major health problem. It is linked to insufficient health facilities, inappropriate sanitation measures, weak health care, overuse of antimicrobials, and lack of or outdated treatment guidelines , 168. EvStaphylococcus aureus (MRSA) and multidrug-resistant Enterobacteriaceae (MDRE) than the host country population  is one of the major causes of hospital-acquired infections in recent years , housing, and vector/animal after disasters . In anotThe extent  of the disaster is also important in the context of the coping capacity of the country. For example, the devastating earthquake on 6 February 2023 with a 7.8 magnitude followed by 5,700 aftershocks directly affected 11 provinces living 15 million people in Türkiye and 11 million families in the Syrian Arab Republic , 205.A Generic National Action Plan covering risk assessment, a mechanism for action, determination of roles and responsibilities of each sector, establishment of a coordination mechanism, etc. should be developed. Each province/region should prepare its own plan of action considering local conditions such as epidemiology of EIDs/REIDs, vector and reservoir species and their distribution, response capacity and additional needs, etc.Even though there have been common risks and drivers for EIDs/REIDs in wars and natural disasters, they have idiosyncratic risks. For example, security is a great problem in wars while the continuity of a natural disaster itself, such as in an earthquake poses, additional risks in implementing control measures.In order to increase response capacity, planning and investments including awareness raising additional to finance are needed for disaster preparedness and early warning. The establishment or adaptation of the current EIDs/REIDs Surveillance and Early Warning System covering the probable effects of wars and natural disasters on EIDs/REIDs is a prerequisite for recognizing disease clusters/outbreaks, and monitoring and evaluating control interventions. Being an important part of a strong surveillance system, enhanced laboratory services should be planned to include mobile even field laboratories which are capable of sustaining their work under inappropriate conditions in order to provide rapid diagnosis of diseases. Maintenance of surveillance and control activities, waste management services, and food security are of great importance during and after wars and natural disasters in order to reduce their impact on EIDs/REIDs. Given the risk of EIDs/REIDs is much higher in overcrowding and unsanitary conditions, priority should be given to the displaced population and refugees living in temporary shelters and regular screenings can be performed especially for vector-borne diseases such as malaria and leishmaniasis.Free roaming animals, whether domestic/wild or stray/owned, should definitely be considered, and special control interventions should be implemented as most of the EIDs/REIDs have zoonotic origin. Planning of vector and rodent control is of great importance too. The risk of occurrence of natural disasters and, EIDs/REIDs following natural disasters and during conflict conditions are increasing due to climate change which contributes to creating environmental changes especially favorable for vector-borne diseases.Therefore, the impact of wars and natural disasters on EIDs/REIDs should be taken seriously. Recommended actions in order to prevent and control EIDs/REIDs in wars and natural disasters are summarized in ST, AT-O, and EA: conceptualization, writing—review and editing, and visualization. ST and AT-O: methodology. AT-O and EA: validation. ST: resources and writing—original draft preparation. EA: supervision. All authors contributed to the manuscript development and approved the final version to be published.This study was supported by TOBB-ETU.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.