Petroleum hydrocarbons pose a substantial threat to marine ecosystems. Their release into the ocean due to human activities, such as drilling, manufacturing, storage, and the transportation of crude oil and oil products, raises significant concerns. As climate change opens up new shipping routes in the Arctic, the risks of oil spills resulting from oil and gas exploration, as well as increased marine traffic in the region, have grown considerably .One challenge in studying the biodegradation of oil in cold marine environments is identifying and characterizing the oil-degrading microbial species and their potential interactions. Different oil components possess diverse chemical structures and properties, necessitating various microbial species with specific enzymes and pathways for degradation. Furthermore, the microbial consortia degrading oil in seawater and sediments are both dynamic and complex, with their composition and activity subject to fluctuations depending on environmental conditions and the availability of nutrients and oxygen. While it is confirmed that oil biodegradation can occur at low and sub-zero temperatures, knowledge about the extent of this process and the specific microorganisms involved in cold marine environments remain limited . As a reOne approach to mitigating the negative impact of oil pollution in the marine environment is bioremediation, which involves using microorganisms to degrade or detoxify pollutants. Bioremediation can be used to clean up oil spills and reduce the long-term effects of petroleum hydrocarbons on the marine ecosystem. However, to develop effective bioremediation strategies, it is crucial to understand the microbial communities involved in the process and their response to different environmental conditions .The objective of this Special Issue was to gather articles investigating microbial taxa and consortia with specific metabolic pathways involved in the biodegradation of oil compounds within various marine compartments in cold marine environments. The focus was on the abilities of marine microbes at taxonomic, functional, and genomic levels to react to and degrade hydrocarbons originating from oil spills at low and sub-zero temperatures. Furthermore, the Special Issue explored the development and application of oil bioremediation techniques to address marine oil spills in cold seawater and ice-affected areas.The research article by Peeb et al.  assessedTwo papers addressed oil bioremediation in the cold marine environment. The effect of biostimulation on microbial community abundance, structure, dynamics, and the metabolic potential for oil hydrocarbon degradation in oil-contaminated Arctic seawater were studied by Nõlvak et al. . The secThe study by Zakaria et al.  investigDietzia psychralcaliphila J1ID isolated from sediments near Deception Island [Another study from Antarctica characterized the phenanthrene-degrading bacterial strain of n Island . Based oIn summary, this Special Issue features a series of research papers showcasing how recent advancements in molecular and data analysis techniques, coupled with cultivation-based methodologies, have significantly enhanced our understanding of marine microbial communities and their relationship with oil exposure and biodegradation in cold marine environments. As microbial communities play a critical role in the biodegradation of oil compounds in cold marine environments, the information provided by these studies allows for better predictions of oil biodegradation capacities in seawater, sediments, and coastal areas. Additionally, the findings from these studies contribute to the development of targeted mitigation strategies to the minimize negative impacts on vital ecosystem functions, such as nutrient cycling and hypoxia, in cold marine ecosystems. As our knowledge of marine microbial communities and their relationship with oil exposure and biodegradation expands, future research should focus on the microbial ecology of oil biodegradation in the presence of co-contaminants, especially microplastics. This would involve understanding the synergistic or antagonistic effects of these co-contaminants on biodegradation processes. Moreover, assessing the impact of marine oil pollution on animal microbiomes will provide insights into the potential consequences of oil pollution for marine life and ecosystem health.Furthermore, there is a need to develop and optimize bioremediation approaches for responding to marine oil spills in cold climates and ice-affected regions. This could involve the identification and use of native psychrophilic or psychrotolerant microorganisms, as well as the implementation of novel strategies to improve the efficiency of bioremediation efforts. By addressing these research gaps, we can better protect fragile, cold marine environments and maintain the health of these vital ecosystems in the future.


With the in-depth understanding of bone regeneration mechanisms and the development of bone tissue engineering, a variety of scaffold carrier materials with desirable physicochemical properties and biological functions have recently emerged in the field of bone regeneration. Hydrogels are being increasingly used in the field of bone regeneration and tissue engineering because of their biocompatibility, unique swelling properties, and relative ease of fabrication. Hydrogel drug delivery systems comprise cells, cytokines, an extracellular matrix, and small molecule nucleotides, which have different properties depending on their chemical or physical cross-linking. Additionally, hydrogels can be designed for different types of drug delivery for specific applications. In this paper, we summarize recent research in the field of bone regeneration using hydrogels as delivery carriers, detail the application of hydrogels in bone defect diseases and their mechanisms, and discuss future research directions of hydrogel drug delivery systems in bone tissue engineering. Large bone defect is a common clinical disease that can occur at all ages. Bone loss often leads to irregular shapes and incomplete organ functions, and can have adverse psychological and social effects on patients . There aTrauma and various systemic diseases involving bone tissue, such as diabetes and congenital bone dysplasia, are the primary causes of bone defects ,13. TrauIn the past decade, research on nanotechnology-based drug delivery mechanisms and tissue engineering has made tremendous progress and has great potential to improve human health . NanomatThe main components of hydrogel drug delivery systems are nano- or micron-sized particle molecules. As an alternative treatment in the field of bone regeneration, hydrogel particles are designed in different diameters (1–1000 μm). Hydrogels can be designed as three physical states, hydrogel suspension, granular hydrogel, or hydrogel complex, depending on the experimental needs. In the field of bone regeneration, hydrogel suspensions and hydrogel complexes are widely used . The pro2 by ionic cross-linking, while methacrylate modified gelatin is cross-linked at elevated temperatures or UV irradiation [The key feature of hydrogel complexes is the way in which the molecules within the hydrogel are bound. Chemical cross-linking is the main form of internal bonding, and it mainly depends on the basic components inside the hydrogel. For example, alginate is mainly bound to CaCladiation . Hyaluroadiation . The hydThis paper summarizes the applications of hydrogel drug delivery systems for bone regeneration in recent years, and hydrogels with MSCs for osteochondral defect repair are discussed, focusing on the mechanism of bone immunomodulation. Finally, the future direction of bone repair and the urgent issues that need to be addressed are outlined.The repair of cranial defects is particularly important to isolate external stimuli and maintain normal brain function ,57. The Jawbone and alveolar bone defects are mainly caused by neoplastic diseases, inflammation, and trauma . BacteriArticular cartilage is a special structure with complex functions that covers the surface of the bone for a cushioning function and reduces the friction during the movement of the joint. The purpose of cartilage tissue engineering is to remove inflammatory factors around the joints, promote chondrocyte regeneration and proliferation, and avoid joint degeneration and necrosis caused by the progression of arthritis, in order to restore the original physiological structure and function of cartilage . Stem ceOsteochondral repair is a difficult area for bone regeneration because it is more difficult than simple bone regeneration and cartilage regeneration. Osteochondral defects are diseases that occur at the junction of bone and cartilage and are caused by bone and cartilage resorption because of inflammation and trauma . Bone anThe traditional approach for repairing osteochondral defects is to implant a hydrogel with the flavonoid epimedium, which has osteogenic and chondrogenic properties, conjugated with hyaluronic acid (HA) and gelatin, and co-culture it with BMSCs. A fully layered osteochondral defect in a rabbit patella was treated with this method, and bone defect repair after one month and three months was demonstrated ,113. TheMSCs are a class of stem cells with multidirectional differentiation and high proliferative capacity. They come from a wide range of sources and can be derived from bone marrow, fat, and dental pulp. Stem cells for clinical and engineering purposes fall into three groups: multipotent somatic stem cells, such as MSCs; pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs); and next generation stem cells. The third category is an edited stem cell based on potent chimeric antigen receptor (CAR) technology and the advent and evolution of CRISPR. Next-generation stem cells are considered the most promising engineered stem cells for treatment; however, technical and regulatory improvements are still needed . Stem ceSemi-solid gels can be specifically adapted to the size of the bone defect, and the internal space can support the morphology of the cells . Additio+ and Thy+), osteoblasts (Thy+), and stromal cells (6C3+). The activity of skeletal stem cells is a factor affecting bone formation, in addition to bone, cartilage, stromal progenitor (BCSP). BCSPs have a complex function and their activity is regulated by estrogen. Directly combining estrogen with poly  (PLGA) in the fracture area promotes osteogenesis. However, the PLGA fabrication process is complex and lacks stability; thus, an efficient and simple drug delivery system is needed to further improve drug delivery [More recently, researchers have found that differences in the sex of the mouse affect the ability of bone stem cells to differentiate. Postmenopausal mice with osteoporosis showed a sharp drop in estrogen and had less osteogenic ability than the male mice at the same time. Studies have shown that mouse skeletal stem cell (mSSC) expression is positive for CD51 and CD200 and negative for CD105. When stimulated by growth differentiation factors such as estrogen, mSSCs can be CD105 positive and further differentiate into chondrocytes , to promote myocardial, bone, and cartilage regeneration in vivo ,151. TheBone immunomodulation has been one of the most important modalities in the field of bone regeneration in recent years. Aaron and Choi in 2000 first proposed bone immunomodulation in inflammatory bone diseases, explaining the interaction of the skeletal system with the immune system. The RANK signaling pathway is the main pathway through which osteoblasts associate with immune cells. Increased levels of RANKL induce the differentiation of the myeloid progenitor to osteoclasts. Within the bone tissue, osteoclasts and osteoblasts control the dynamic balance of bone mass .2+ and CO to promote macrophage M2 polarization and vascular endothelial factor release to repair the bone defect [Immune cells and bone-associated cells constitute the main body of immunomodulation, which regulates the interaction between them and bone-associated cells by guiding, activating, stimulating, and inhibiting them . At the e defect ,164.The stabilization of bone tissue is a dynamic balance between osteoblasts and osteoclasts. Osteoblasts secrete the bone matrix, which is mineralized and forms bone tissue. Osteoclasts are cells with bone resorbing activity which produce acids and proteases that digest and absorb the bone tissue that has been formed. Osteoblasts are mainly differentiated from MSCs in the bone marrow cavity and are mononuclear cells. Osteoblasts are polymorphic cells derived from the aggregation of myeloid progenitor cells or monocytes. Myeloid progenitor cells differentiate into osteoclasts and transform into macrophages via the macrophage colony stimulating factor (M-CSF) . In boneStaphylococcus aureus. Hydrogel combined with pravastatin sodium and manganese dioxide (MnO) is injected locally to promote MnO decomposition by reacting to ROS to release a drug [2+ is an important regulatory factor that can play a role in immune regulation and anti-inflammation. The Mn2+ recruits macrophages to the defect and induces them to polarize toward the M2 type, while also removing excess ROS and reducing the damage to tissues and cells in the defect area from oxidative stress. Mn2+ also interferes with the bacterial metabolism and inhibits the proliferation of Gram-positive and Gram-negative bacteria, reducing the risk of tissue infection [Hydroxypropylchitosan hydrogel combined with porous chitosan in an injectable drug delivery system on porous microspheres is the cornerstone of osteochondral defect repair. This new composite hydrogel promotes the proliferation and migration of BMSCs, while modulating the immune response and increasing M2 polarization. Dimethyloxyglycine (DMOG) plays a role in inhibiting the hypoxia-inducible factor (HIF) during hydrogel degradation and promotes macrophage polarization in a direction favorable to inflammation resolution and tissue repair . M2 macre a drug . Mn2+ isnfection ,175,176.nfection .The ECM is a network structure comprising extracellular macromolecules including proteins, proteoglycans, and polysaccharides ,178. TheBMSCs’ exosomes are extracellular vesicles that have multiple functions and are often used as carriers to deliver nucleic acid molecules and signaling proteins in the field of tissue engineering. The exosomes secreted by the cells contain mainly small molecules of RNA, and the types of RNA encapsulated in the exosomes produced by BMSCs in various states are different. Compared with the exosomes from normal BMSCs, the exosome from hypoxia-treated BMSCs had a significant promotional effect on the growth of articular chondrocytes. This may be related to miR-205-5p in the exosomes of hypoxia-treated BMSCs, which promote cartilage defect repair through activation of the PENT/AKT signaling pathway. Injectable cellulose hydrogels encapsulate exosomes, protecting them from physicochemical stimuli while also slowing their release through their own degradation for continuous drug delivery . The locThe DNA molecule benefits from its precise base complementary pairing principle and hydrophilicity ,188, whiThe nucleic acid molecules contained in exosomes are mainly small messenger RNAs with more limited sources and a smaller variety, and the use of larger DNA or RNA molecules in exosomes is often restricted. With the intensive study of RNA molecules in signal transduction and transcriptional regulation, drug delivery systems using biological scaffolds or materials as carriers to carry RNA families for the treatment of bone defect diseases show great potential . Single-The influence of the biological microenvironment on a hydrogel in the bone defect area is multifaceted. On the one hand, the specific components of the microenvironment activate the release or function of the hydrogel, which is mostly observed in the responsive hydrogel system carrying monomeric molecules. For example, in bone defects caused by chronic periodontitis, the ROS content in the local microenvironment is greater than that of the normal group, and through the activation of the hydrogel responsive release of doxycycline and metformin, local antibacterial and hypoglycemic effects are achieved and the surrounding inflammatory microenvironment is improved, thus promoting bone repair ,198. TheBone tissue engineering materials, with advantages of low immunogenicity and biocompatibility, have introduced new hope for the repair of large area bone defects. The 3D-printed biomaterials are important vehicles for bone tissue engineering; however, improvements are still needed in terms of applicability and personalization. For example, 3D-printed scaffold materials are very stiff, and some defects require soft tissue. High strength scaffolds often cause impaired local soft tissue functional recovery. Therefore, a material with controllable morphology and adjustable hardness is needed. Hydrogels are transparent gels with a three-dimensional internal structure that can store water and have a certain toughness. Their physical properties are reversible under certain conditions, which gives them a wide range of applications . HydrogeIn recent years, 3D-printed hydrogels have gradually become used for bone and cartilage repair . This 3DRepairing osteochondral defects has long been a major challenge in the field of bone regeneration. Trauma, osteoarthritis and infection can cause damage to bone and cartilage tissues. Because of their unique physical and biological properties, hydrogels are increasingly showing their advantages in the repair of osteochondral defects. Hydrogel drug delivery systems deliver cells, proteins, and nucleic acids into the body, facilitating the release and transformation of drugs. For the repair of osteochondral defects, layered design and biphasic repair are highlights of hydrogels, showing higher healing ability and functional recovery of the defect. Hydrogels promote bone regeneration and cartilage regeneration, restore the osteochondral interface, and reconstruct the biological function of both. Here, we summarized and proposed the concept of the “layered repair” of osteochondral defects, with the aim of providing a new way of thinking in the field of bone regeneration for repairing bone defects. We also clarified the important role of hydrogels in layered repair, in addition to their roles as cell carriers and drug carriers . RegardiIn conclusion, hydrogels have great potential for application in the field of bone regeneration because of their simple synthesis, high drug loading rate, low biosafety, and certain physical strength. However, the healing of bone tissue is not only dependent on external drugs alone, but also on the synergistic effect of various cells and tissues in the areas of bone defects. Bone regeneration still requires drugs that can both promote osteogenesis and coordinate the physiological function of the bone defect area, and even the immunity of the whole body. Hydrogels have been proven to be drug carriers in promoting local bone regeneration. In the future, it remains a great challenge to determine whether hydrogels can replace tissue-engineered scaffold materials and coordinate the dynamic balance of bone volume.


The development of green synthesized polymeric nanoparticles with anticancer studies has been an emerging field in academia and the pharmaceutical and chemical industries. Vegetable oils are potential substitutes for petroleum derivatives, as they present a clean and environmentally friendly alternative and are available in abundance at relatively low prices. Biomass-derived chemicals can be converted into monomers with a unique structure, generating materials with new properties for the synthesis of sustainable monomers and polymers. The production of bio-based polymeric nanoparticles is a promising application of green chemistry for biomedical uses. There is an increasing demand for biocompatible and biodegradable materials for specific applications in the biomedical area, such as cancer therapy. This is encouraging scientists to work on research toward designing polymers with enhanced properties and clean processes, containing oncology active pharmaceutical ingredients (APIs). The nanoencapsulation of these APIs in bio-based polymeric nanoparticles can control the release of the substances, increase bioavailability, reduce problems of volatility and degradation, reduce side effects, and increase treatment efficiency. This review discusses the use of green chemistry for bio-based nanoparticle production and its application in anticancer medicine. The use of castor oil for the production of renewable monomers and polymers is proposed as an ideal candidate for such applications, as well as more suitable methods for the production of bio-based nanoparticles and some oncology APIs available for anticancer application. The polymer industry plays a significant role in our society as polymers have become essential materials nowadays. However, concerns over the extensive use of fossil-based raw materials, large amounts of reagents, and the accumulation of polymeric materials in the environment have increased. The need to release the polymer industry from its dependence on depleting resources is pushing the search for industrially applicable renewable alternatives .Materials in the environment provide scientists and engineers with the possibility to change the polymerization process to develop a more sustainable society. Research has focused mainly on replacing fossil raw materials with renewable alternatives and developing end-of-life options that generate materials that are suitable for recycling or biodegradation .One sustainable technology is the application of the principles of green chemistry to various processes. The design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances is essential to living without having a negative impact on the environment. The sustainability evaluation of a product’s creation starts from the analysis of the feedstock used and its extraction. This highlights the importance of the seventh principle of green chemistry: “a raw material or feedstock should be renewable rather than depleting, wherever technically and economically practicable” .A collaborative effort by industry, academia, and the government is needed to promote the adoption of the green chemistry technologies necessary to achieve a sustainable civilization. The progress of chemistry research, associated with the industrial revolution, has created a new scope for the preparation of novel polymeric materials based on renewable resources.Biomass-derived chemicals can be converted into monomers with a unique structure, producing materials with novel properties, or modified in order to substitute commercial petroleum-based ones. Vegetable oils exhibit numerous reactive sites suitable for functionalization, including ester groups and double bonds present in unsaturated fatty acids, which can undergo chemical modifications through acrylation, transesterification, metathesis, and epoxidation reactions. These transformations enable the conversion of triglycerides into monomers capable of polymerization .The most commonly encountered polymerization techniques for bio-based monomers are radical polymerization, condensation polymerization, and cationic polymerization. These techniques have been employed for the synthesis of diverse vegetable oil-based polymer types, including polyesters, polyamides, epoxies, and polyurethanes . The fabrication of polymeric nanoparticles based on vegetable oils for biomedical applications can be achieved through various techniques. Among these, miniemulsion polymerization and solvent evaporation techniques are widely recognized and cited due to their inherent advantages, including process simplicity and stability.Miniemulsion polymerization is a heterogeneous polymerization process used for the production of polymers in the form of nanoparticles for different applications of polymeric material. The thiol-ene reactions can be used in polymer and monomer synthesis and modification, side-chain/end-group modification, and preparation of various types of branched macromolecules. In the solvent evaporation technique, polymer solutions are prepared in a volatile solvent, and emulsions are formulated. These kinds of polymeric nanoparticles can be used in biomedical and pharmaceutical applications, such as antitumor therapy ,6,7,8.Nanoparticles have been of significant interest over the last decade as they offer great benefits for drug delivery to overcome limitations in conventional chemotherapy for anticancer treatments, for example. Nanoparticles for use as antitumor drug carriers have been in development due to their many advantages such as prolonging the biological circulation time, minimizing non-specific uptake, preventing undesirable side effects, improving cellular penetration, and allowing for specific cancer targeting .A considerable amount of work has been conducted in search of novel cancer therapies using nanoparticle technology. Combined treatments employ either naturally active ingredients or drugs already intended for other uses so as to increase cell sensitivity to therapy and reduce drug toxicity, using a particular pharmaceutical combination and nanotechnology to develop drug delivery systems for targeting drugs to specific tumors . This study aims to elucidate the application of green chemistry principles in the development of bio-based polymeric nanoparticles for anticancer therapy. Furthermore, it compiles the use of vegetable oils as sources of renewable monomers and polymers, highlighting castor oil as a promising candidate for such purposes. Additionally, it explores more suitable methodologies for the production of bio-based nanoparticles and discusses various oncology active pharmaceutical ingredients (APIs) with potential for anticancer applications.The term green chemistry, as adopted by the IUPAC, is defined as the invention, design, and application of chemical products and processes to reduce or eliminate the use and generation of hazardous substances. Since their initial appearance in the scientific literature, the terms “green” and “sustainable” have been increasingly used and are nowadays present in several research areas. Green chemistry may be considered in the scientific and economical context in which academia, industry, and government are attempting to converge their efforts for the development of a sustainable civilization . Green chemistry, also called sustainable chemistry, dates from 1991 when the U.S. Environmental Protection Agency (EPA) launched the Alternative Synthetic Pathways for Pollution Prevention research program under the auspices of the Pollution Prevention Act of 1990. However, the name green chemistry was officially adopted in 1996. American chemist Paul Anastas, one of the principal founders of green chemistry, claimed that by improving how chemicals are synthesized, it might be possible to prevent the production of pollutants. Together with John Warner in 1998, they created green chemistry’s 12 principles, including preventing waste wherever possible, designing chemicals that break down into harmless products after they are used, or using renewable feedstocks . . 8]. The emulsification solvent evaporation technique was first reported in 1981 . HydrophSolvent evaporation is the most commonly used technique for the preparation of the nanoparticles of polymers in the current literature on techniques using a dispersion of preformed polymers ,44,45. IMiniemulsion is part of the emulsified polymerization systems, and its main characteristic is the size of the drops and the stability of the final emulsion. A nanoemulsion can be considered a conventional emulsion containing very small particles (size ranging from 50 to 500 nm) ,47.Ref.  were pioAsua (2002) defined miniemulsions as dispersions of small monomer drops in water, stabilized by a surfactant against the coalescence of the drops by the action of the Brownian motion (a union of two or more drops occurring the rupture of the interface and resulting in a larger drop) and a co-stabilizer to minimize diffusional degradation  . A typical formulation includes water, a monomer, co-stabilizing (when used), a surfactant, and an initiator (which can be soluble in the aqueous or organic phase). The surfactant is dissolved in water, the active to be encapsulated is dissolved in the monomer, and both are mixed under agitation. A shear mechanism (homogenization) is required to ensure the submicrometric size of the drops .The mechanical homogenization of miniemulsions can be obtained by different methods. Initially, simple agitation was used as the main means of homogenization. Subsequently, the use of omni-mixers and ultra-turrax was cataloged. However, the energy transferred by these techniques is not enough to obtain small drops distributed homogeneously. Much higher energy for the fragmentation of large drops into small ones is required. Currently, ultrasonication is used, especially for the homogenization of small quantities, while micro-corrugators or high-pressure homogenizers are favorable for large quantities of emulsion .In the first stage of the miniemulsion polymerization process, small drops are formed by a system containing the dispersed phase  and continuous phase (aqueous phase with a surfactant). The initiator can be added in the dispersed phase or continuous phase, depending on whether it is hydro- or organic-soluble. The surface area of the droplets in these systems is very large, and most surfactant is adsorbed on the surface of the droplets . In the Thiol chemistry, a versatile tool, was first described in 1905 by Posner. The author reports the thiol coupling to different types of mono- and bi-unsaturated compounds such as aliphatics, aromatics, terpenes, and hydroaromatics. The thiol-ene free radical addition is of special interest due to its application range and simplicity. Early work in this field appeared in the late-1930s to early-1950s .A patent concerning the polymerization of dithiols and dialkenes via radical additions dates back to 1941. The reaction is well-known to proceed via a free-radical mechanism. Generally, radical reactions are known to be quite fast reactions, and thiol-ene additions offer some additional features, such as robustness and efficiency, which has meant that this reaction is considered one of the click reactions, and it has become very popular in recent years .Like a traditional free-radical polymerization, thiol-ene polymerization reaction proceeds in three stages: initiation, propagation, and termination, plus a chain transfer step. At initiation, the formation of thiol groups occurs by removing hydrogen. During propagation, the thiol radical is added to the unsaturated moiety (ene) group of the olefin, which generates an unpaired electron in the central carbon of the chain. Chain transfer occurs when the central carbon donates the electron to the thiol group, producing another thiol group, thereby restoring the mechanism . TerminaThe efficiency of this reaction, therefore, requires unsaturation in the terminal position and strongly depends on the thiol compound used. As mentioned above, the propagation step of this reaction is the addition of a thiyl radical to a C=C double bond and the subsequent abstraction of a hydrogen atom by the formed carbon radical from another thiol compound, forming a new thiyl radical. The formation of the carbon radical is reversible and a rate-determining step, which explains the low reactivity of internal alkenes . There has been impressive growth in the use of the thiol-ene reaction in polymer synthesis and modification. Examples include use in monomer synthesis and side-chain/end-group modification, the preparation of various types of branched macromolecules, the preparation of inorganic–organic composites, nanoparticle modification, surface modification, bio-related applications, and cross-linked polymers .Cases of reactions between vegetable oils or derivatives and thiols found in the scientific literature  describeRef.  developeIn , cationiIn virtue of some of the aforementioned advantages of thiol-ene reactions, such as that they can be carried out under mild conditions, the possibility of producing cross-linked and functionalized structures and improving degradability, these kinds of reactions are considered environmentally friendly candidates for synthesizing biocompatible and biodegradable polymers for biomedical application, such as cancer therapy ,59,60,61The use of in situ miniemulsion polymerization (polymerization of a monomer and encapsulation of activity at the same time) by thiol-ene has been investigated. Nanoparticles have several applications: pharmaceutical, biomedical, and cosmetic. The development of polymeric nanoparticle formulations containing anticancer-like actives, for example, is relevant here. This type of system has the potential to enhance the bioavailability of encapsulated substances and mitigate issues associated with premature degradation. Furthermore, the surface functionalization of nanoparticles, such as protein conjugation, can be employed to promote prolonged circulation in the biological milieu and facilitate targeted delivery to specific sites.Nanoparticles have been of significant interest over the last decade, as they offer opportunities for new drug delivery systems. Recently, nanoparticles have been extensively employed as biomaterials because of their favorable characteristics in terms of simple elaboration and design, good biocompatibility, and a broad structure variety . NanoparChemotherapy is a predominant cancer treatment strategy in which anticancer drugs are used to induce cell death in cancer cells. However, it has several limitations, such as requiring a high drug dose, causing adverse effects, and multidrug resistance, which can reduce the efficacy of the therapy. To overcome the limitations associated with chemotherapy, nanomedicine strategies employing the formulations of anticancer drugs in various nanocarrier forms have been reported .The first clinical trial of nanoparticles for anticancer drug delivery took place in the mid-1980s, and the first nanoparticles  entered the pharmaceutical market in 1995. Since then, numerous new nanoparticles for cancer drug delivery have been under development given their many advantages, such as enhancing the solubility of hydrophobic drugs, prolonging circulation time, preventing side effects, improving intracellular penetration, and allowing for specific cancer targeting [In The use of nanoparticles in conventional chemotherapy is recognized and has been accepted by the FDA (Food and Drug Administration) for broader usage. Anticancer drug entrapment within nanoparticles guards them against efflux transporters, and the nano-sized range accelerates their entrance through biological membranes. Additionally, the polymer shell protects the drug against the body’s enzymes. Current developments in nanotechnology have revealed many types of targeting strategies for augmenting drug accumulation in the tumor while restricting the undesirable toxicity to normal cells. As the nanoparticles are designed for targeted drug delivery systems, they increase the anticancer active ingredients delivered to tumors without affecting non-cancerous regions .Some of the applications of nanoparticles in cancer therapy can be seen in the work of , who devRef.  evaluateRef.  synthesiFor these reasons, nanoparticles can be used in many applications in cancer remediation. There are a multitude of possibilities for nanoparticle technology that need to be explored to harness their remarkable use in applications as a new class of targeted remediation for cancer therapy ,130,131.Nanoparticles containing oncology APIs offer a different alternative to conventional treatments, mostly due to their targeted delivery and action. They can also be used as biosensors, enabling cancer detection or carriers in targeted drug delivery to specific locations .Oncology or anticancer APIs, also called antineoplastic drugs, refer to the biologically active components present in anticancer drugs. They are effective in the treatment of malignant or cancerous diseases. There are several major classes of oncology APIs. These include alkylating agents, antimetabolites, natural products, and hormones, which demonstrate anticancer activity and are used in the treatment of malignant diseases.The nanoencapsulation of oncology APIs exhibits other advantages over conventional medical methodologies. For example, they enter selective tissue at the molecular level, provide a large surface area and high absorption rate, increase cellular uptake and drug localization, provide accurate and targeted drug delivery to cancerous cells without interactions with healthy cells, use a lower dosage due to the encapsulation of drugs or small molecules, improve the uptake of poorly soluble drugs, decrease medicinal toxicity, and minimize or suppress the resistance arising from the physiological barriers in the body ,133.For these and other reasons already mentioned, new oncology APIs have been studied in cancer treatment strategies. The need to release the polymer industry from its dependence on non-renewable resources is a significant concern. Vegetable oils represent one of the most interesting classes of renewables for the synthesis of sustainable monomers and polymers that can be applied for biomedical use as nanoparticles containing active pharmaceutical ingredients for anticancer therapy. Nanoparticles are rapidly changing the direction of cancer treatment; they can deliver oncology APIs to a specific target, such as a tumor region and control the delivery release, increasing the effectiveness of treatments and reducing possible side effects. Incorporating the enhanced properties of green synthesized nanoparticles loaded into oncology APIs in cancer treatment and diagnosis has opened new possibilities for biomedical applications.


This scoping review aimed to assess the current state of knowledge regarding the relationship between bruxism and changes in density or volume of mandibular bone, based on medical imaging.Literature review was conducted following the PRISMA-ScR protocol. PubMed, Web of Science and Cochrane library databases were searched for peer-reviewed articles by two blinded reviewers. Studies based on the evaluation of mandibular bone density and/or bone volume with imaging examination in adult patients were examined. The selected articles were summarized in PICOS tables and assessed for methodological quality.Nine articles were included, according to the inclusion criteria. They showed that bruxer patients had more bony exostoses of the mandibular angle, smaller condyles, and morphological changes for cancellous and cortical mandibular bone compared to non-bruxer patients.Bruxism seems to induce morphological and anatomical changes in the different regions of the mandibular bone . Given the heterogeneity of the included studies, these results should be interpreted with caution. Further studies are needed to support these results, in particular via the analysis of three-dimensional imaging to overcome the limitations of panoramic radiograph. The manducatory apparatus, because of the great diversity of its anatomical components, can be the site of several types of symptomatology affecting the patient's quality of life: sequelae of facial trauma , temporoBruxism is defined as “a repetitive masticatory muscle activity characterized as forcefully maintaining a certain mandibular position and thrusting as forcefully moving the mandible in a forward or lateral direction—both activities without the necessary presence of tooth contact” . It is aA function in the context of habitual, "commonplace" bruxism,A parafunction, in the context of active, "frequent" bruxism,A pathogenic function in individuals with a fragile dental structure associated with severe, "excessive" bruxism.In spite of the negative image conveyed by its first scientific descriptions at the beginning of the XXth century , then cWhen the mandibular movements produced during bruxism episodes by contraction of the mandibular elevator muscles generate inter-arch dental contacts, the force developed by the bruxer can be up to three times higher than during the functional activity of the manducatory apparatus –13. ThesMoreover, several methods exist for the diagnosis of bruxism, with varying degrees of reliability  : all reqThe objective of this scoping review was to assess the current state of knowledge regarding the relationship between bruxism and changes in density or volume of mandibular bone, based on medical imaging.This review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) protocol , 19.The PICOS tool, which stands for Population, Intervention, Comparison, Outcome, and Study type, is detailed in Table Adult patients,Patients diagnosed as bruxers or non-bruxers, without regard to the method used to diagnose bruxism,Patients who had undergone medical imaging of the mandible,Articles written in English,Studies approved by an ethics committee.The inclusion criteria were:Studies including patients with progressive or degenerative pathologies of the mandibular bone , fractures of the mandible or a history of oral radiotherapy,Single clinical case study, case report, literature review,In vitro or animal model study,Documents other than a scientific article .The exclusion criteria were:There were no restrictions on the year of publication.The search of scientific articles was conducted in three online databases, PubMed, Web of Science Cochrane library, up to February 05, 2023 by two blinded operators. Studies were excluded on the basis of titles and abstracts, and upon reading the full article. All phases were independently assessed by two evaluators (EC and BS), and in case of doubt or disagreement, a consensus between the two evaluators was sought.The search procedure used the keywords "bruxism" and "bruxer" together with keywords related to medical imaging examinations and others related to changes in the characteristics of the mandibular bone.Search equation for PubMed:("bruxism"[TIAB] OR "bruxer*"[TIAB]).AND .AND ) OR "radiomorphometric indice*" OR "morphological characteristic*" OR "craniomorphological characteristic*").Search equation for Web of Science:TS = ("bruxism" OR "bruxer*").AND ALL = ("radio*" OR "panoramic*" OR "scanner*" OR "CBCT" OR "cone beam").AND ALL = ) OR "radiomorphometric indice*" OR "morphological characteristic*" OR "craniomorphological characteristic*").Search equation for Cochrane library: ("bruxism" OR "bruxer*") in Title Abstract Keyword AND ("radio*" OR "panoramic*" OR "scanner*" OR "CBCT" or "cone beam") in All Text AND ) OR "radiomorphometric indice*" OR "morphological characteristic*" OR "craniomorphological characteristic*") in All Text.A qualitative analysis of protocols is offered in this scoping review, using the PICOS tool , associated with an assessment of the risk of bias and an evaluation of the results of the articles selected .Only the first affiliation of the first author was considered in the geographical analysis of publications.Thus, out of a total of 50 articles retained initially from the 3 databases, 15 duplicates were eliminated. 26 articles were excluded on the basis of their titles and abstracts. Nine articles were retained after reading the full texts and a total of nine articles corresponding to the inclusion criteria were selected and studied in this work , South America , Asia , and Europe . All studies were approved by the ethics committee of their respective institutions or hospitals. The strategies adopted to study bone characteristics were different, with different types of radiological examinations, so a direct comparison of bone density and bone volume could not be performed. The details of these different results are recorded in Tables The papers included in the final step of the review covered a wide geographical area, including the Middle East  used for the diagnosis of bruxism differed between studies . Interpretation of results is limited by the dearth of current studies on this subject. However, several avenues of research seem promising, for example, the greater number of bony exostoses at the mandibular angle, condylar morphology , and the quality of cortical and cancellous bone, and these avenues deserve to be explored more fully. Such research would allow the integration of medical imaging, as an additional element to be considered, into the rationales established by the practitioner or researcher for the diagnosis of bruxism. Particular attention should be paid to three-dimensional medical imaging, such as CBCT (Cone Beam Computed Tomography) in order to avoid certain biases common to all the studies included in this literature review, in which only 2D radiological analysis (panoramic X-ray) was used. However, since CBCT is not a reference radiological procedure for the diagnosis of bruxism, its possible justification can only be established following the analysis of CBCT initially indicated for other pathologies or oral therapeutic procedures. Given the high prevalence of bruxism in the general population, a better knowledge of the variations in bone density in these patients would be of real value for their management in certain fields of dentistry such as dentofacial orthopaedics, periodontology or implantology. Prospective clinical study analysing CBCT has just been initiated and may provide results about bone density. Consequently, if the hypothesis is verified, CBCT could become a complementary radiological examination to aid in the diagnosis of bruxism.


Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy. Taking into account the increasing role of the protein corona of EVs and protein-protein interactions on the surface of EVs in the pathogenesis of various diseases, we focused our attention in this review on the role of intravesicular proteins and the protein corona of EVs in the development of chemotherapy-induced polyneuropathy (CIPN). It has been shown that EVs are effectively internalized by the mechanisms of endocytosis and macropinocytosis by neurocytes and glial cells, carry markers of insulin resistance, functionally active proteins , and may be involved in the pathogenesis of CIPN. The mechanisms of CIPN associated with the EVs protein corona can be related with the accumulation of heavy chains of circulating IgG in it. G-class immunoglobulins in EVs are likely to have myelin hydrolyzing, superoxide dismutase, and oxidoreductase enzymatic activities. Moreover, circulating IgG-loaded EVs are a place for complement activation that can lead to membrane attack complex deposition in neuroglia and neurons. The mechanisms of CIPN development that are not associated with IgG in the EVs protein corona are somehow related to the fact that many anticancer drugs induce apoptosis of tumor cells, neurons, and neuroglial cells by various mechanisms. This process may be accompanied by the secretion of EVs with modified cargo . Polyneuropathy is a diffuse disorder of the peripheral nerves that is not limited to a single nerve or a single limb but is usually relatively symmetrical on both sides. Usually infections, toxins, drug, cancers, diabetes mellitus, autoimmune disorders can cause many peripheral nerves to malfunction. Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy.It has been shown that EVs are effectively internalized by the endocytosis and macropinocytosis by neurocytes and glial cells, carry markers of insulin resistance, functionally active proteins , and may be involved, for example, in the pathogenesis of diabetic polyneuropathy ,2. It isIt was found that a number of miRNAs secreted as part of EVs are involved in the pathogenesis of diabetic retinopathy and neuropathy, and in the future, they can also be useful as early and reliable markers of these complications ,12,13.Mesenchymal stem cell-derived EVs are also discussed as promising products for regenerative medicine, and in particular for the treatment of diabetic polyneuropathy ,15,16.Chemotherapy (CT) is one of the most common treatment options for cancer. However, severe side effects of CT often lead to the need for dosage adjustment, delay insubsequent cycles of CT and sometimes to complete cessation of treatment. Neurotoxicity is one of the specific complications of CT . PeripheWidely used in the treatment of gastric and colorectal cancer, oxaliplatin is included in modern chemotherapy regimens FOLFOX, XELOX, FLOX, FLOT. Taxanes have been successfully used in second-line chemotherapy in patients with gastric cancer after tumor progression on first-line chemotherapy.Clinically, CIPN is manifested by a complex of motor, sensory and autonomic disorders, which can be negative (symptoms of prolapse) or positive (symptoms of irritation) depending on the depth of the corresponding fiber type. Symptoms may be isolated, but more often they are in combination and have varying degrees of severity. Positive sensory symptoms (burning sensation and other paresthesias) usually appear first in the feet, most commonly in the fingertips. Negative sensory symptoms (numbness and decreased sensitivity) then appear and gradually spread in the proximal direction, as shorter fibers are affected ,23. Supe-disruption of microtubule dynamics and axon transport;-oxidative stress;-induction of apoptosis by mechanisms associated with microtubule dynamics;-effect on the endothelium;-mitochondrial dysfunction;-proteolytic stress;-changes in the functioning of the glutamatergic system in the central nervous system (CNS).Unlike the central nervous system, peripheral axons are not protected by the blood-brain barrier, which allows metabolites of cytostatics to penetrate into the nerve fibers from the surrounding interstitial fluid by direct diffusion and accumulate in them, causing their damage. Most likely, most of the manifestations of polyneuropathy are the result of a violation of the microtubular architectonics of axons along with direct damage to the distal axons (axonopathy), diffuse or segmental demyelination of neurons (myelinopathy) or degeneration of their bodies (neuronopathy) . SeveralThe disruption of axon transport under chemotherapeutic agents is caused by a change in the microtubular architectonics of axons through inhibition  or a sharp increase in the polymerization processes (proteasome inhibitors) of tubulin, the main microtubule protein that is involved in maintaining the cytoskeleton and intracellular transport of substances ,28,29,30Microtubules are intracellular proteins that make up the cytoskeleton of eukaryotic cells, along with microfilaments and intermediate filaments. They are composed of two fundamental subunits, called α-tubulin and β-tubulin, bonded to each other to form polarized cylindrical structures in which α-tubulin is the negative terminal (−) and β-tubulin is the positive terminal (+). The third member of the tubulin family, γ-tubulin, plays a role in microtubule nucleation and assembly . MicrotuThe pathogenesis of vinca alkaloid-induced CIPN is related to the mechanisms by which vincristine performs its antitumor function. Vincristine acts primarily by altering the normal function of microtubule assembly and disassembly, followed by blockage of mitosis and cell death. In addition to this, all other microtubule-related activities are inevitably compromised. Microtubules are found in abundance in neurons as they make up the skeleton of axons and dendrites, giving them their specialized morphology. By binding to microtubules, vincristine causes changes in the shape and stability of neurons, preventing retrograde and anterograde axonal transport with subsequent degeneration, which consists in the reabsorption of the distal nerve segment after its injury, and also causes a change in the transmission of nerve impulses and neuronal death . MicrotuSome anticancer agents  enhance the production of reactive oxygen species (ROS) in cells. If the amount of ROS exceeds the capabilities of the antioxidant system and ROS accumulate in cells, then damage is initiated in it. This process is called oxidative stress . This coNeurotransmitter imbalance may also underlie oxidative stress. For example, as a catecholamine, dopamine is capable of autooxidation, which results in the formation of ROS as byproducts.It is based on lipid peroxidation, which primarily damages the membrane of neurons and their intracellular organelles . Oxidative stress plays an essential role in the development of the deficiency of nerve cell growth factors (neurotrophins) ,37,38.Apoptosis is the genetically programmed death of neurons. Apoptosis induction is a pathogenetic mechanism of neurotoxicity characteristic of platinum preparations, taxanes, vinca alkaloids, and proteasome inhibitors. There are two pathways to trigger apoptosis: the receptor and mitochondrial pathway. The first receptor-mediated pathway is induced by physiological factors that induce apoptosis  and begins with cell receptors specifically designed to turn on its program . These receptors in the extracellular region interact with inducers, specific ligands. It leads to the binding of their intracellular regions with adapters (cytoplasmic proteins) that facilitate the connection of receptors with inactive protease precursors from the caspase family, which are then activated as a result of proteolytic cleavage. The active caspases, in turn, affect mitochondria, which leads to the release of cytochrome C from them into the cytoplasm. The mitochondrial pathway of apoptosis activation is induced by DNA damage. It is associated with the activation of the p53 protein and the expression of genes encoding proteins of the Bcl-2, Bax, and Bid families. Causing a change in the permeability of the mitochondrial membrane, these proteins promote the release of cytochrome C . The use2+ across the mitochondrial membrane, decreasing both the amount and rate of Ca2+ uptake and decreasing its efflux. Modification of mitochondrial absorption and Ca2+ concentration alters mitochondrial function [Damage to mitochondria is one of the mechanisms of CIPN. Mitochondria are involved in the regulation of neurogenesis—neuronal differentiation, neuroplasticity formation, axon and dendrite formation . Mitochofunction , which lfunction  and ROS function . These cfunction ,42,43,44The occurrence of intracellular reactions reflecting proteolytic stress is typical of bortezomib and is primarily manifested by the induction of heat shock proteins (HSPs) expression in cells . AutophaIn addition to the peripheral nervous system, bortezomib can lead to dysregulation in the CNS. Since bortezomib cannot cross the blood-brain barrier, it probably causes CNS damage indirectly . ElevateUnderstanding of the pathogenesis of axonal degeneration of peripheral nerve fibers is based on the fact that peripheral axons and dorsal ganglia do not have a blood-brain barrier. This allows autoantibodies, immune complexes, toxic metabolites of cytostatics, and targeted drugs to directly contact nerve cells and nerve fibers and cause damage to myelin, tubulin, actin, and actin-binding proteins in them ,25. HoweIn terms of both the study of CIPN pathogenesis and feasibility of CIPN treatment, the study of the protein corona of the EVs, as well as intravesicular proteins, is very promising. In CIPN, the process of demyelination and damage to intraaxonal and neural proteins occurs in parallel with the regeneration of myelin via branching of dendrocytes and axons with the formation of new synapses that replace non-functioning ones . In someThe components of interstitial fluid and blood plasma are deposited on the surface EVs and form a protein corona, due to which EVs acquire a greater functional. Plasma-coated EVs had a higher density than nascent EVs and carried blood plasma proteins. Using confocal microscopy, capillary Western immunoassay, immune electron microscopy, and flow cytometry, E.A. Toth et al. (2021) identified nine common EVs corona proteins  that appear to be common corona proteins among EVs, viruses and artificial nanoparticles incubated with blood plasma .Most patients with multiple myeloma are characterized by monoclonal gammopathy with overproduction of IgG antibodies. The association of monoclonal gammopathy with B-cell non-Hodgkin’s lymphomas (NHL) is a well known phenomenon. Monoclonal gammopathy (MG) was detected in 17.2% of cases with B-cell NHL. IgG-MG was more frequent in cases with aggressive NHL, while IgM in cases with low risk NHL. MG was mostly associated with advanced stage and had not any prognostic significance on survival ,58.A high prevalence of autoimmune diseases was found in some types of cancer , and according to different authors, it ranges from 5 to 12%, it increases significantly with age, a history of polychemotherapy, radiation therapy, and targeted therapy ,60. In cIn addition to cancer cells, target antigens for therapeutic monoclonal antibodies and antibody-drug complexes (ADC) are also expressed on EVs. The antigen-presenting function of EVs is especially pronounced on salivary EVs, EVs derived from dendritic and immune cells. The list of antigens widely represented on circulating EVs includes HER2, CD20, CD30, CD33, BCMA, CD79b, PD-L1 ,65. CaseIn addition, the EVs protein crown is currently considered as a platform for complement activation. In the synovial fluid of patients with rheumatoid arthritis, significantly elevated level of leukocyte- derived EVs with complement components bound on their surface, including C1q, C4 and C3, were found. Red blood cell-derived EVs fix C1q followed by complement activation with binding of C3 fragments . SeveralThe mechanisms of CIPN development that are not associated with IgG in the protein corona of exosomes are somehow related to the fact that many anticancer drugs induce apoptosis by different mechanisms. The expression of HSPs in cells is increased in response to the administration of drugs. HSPs in cells function as chaperones. They can be secreted into the blood and expressed in the exosome membrane. It is known that HSP27, being in the cell, effectively prevents polyneuropathy ,73. MoreThe internalization of EVs by neurons and neuroglia is the most critical moment for the therapeutic effect of EVs. It is known that the mechanisms of internalization of EVs can be determined both by protein-protein interactions on the cell surface and EVs, and by specific mechanisms of endocytosis and macropinocytosis ,77. In aExtracellular vesicles derived from normal cells have previously been used to treat cancer and diabetic peripheral neuropathy in experimental models. For example, small extracellular vesicles or exosomes (sEVs) derived from fibroblasts carrying anti-Kras siRNAs have a therapeutic effect on a tumor in a mouse model of pancreatic cancer . ExosomeAlthough agents targeting neuroprotection with anti-inflammatory and antioxidant properties have shown promising effects on the prevention and treatment of CIPN in patients and animal models, challenges remain in developing treatments for CIPN in which the therapy effectively inhibits CIPN without compromising the antitumor efficacy of chemotherapy drugs. Zhang et al. (2017) demonstrated that sEVs derived from mesenchymal stromal cells (MSC-sEVs) contain miRNAs and proteins that mediate neuronal function. MSC-sEVs can be locally internalized by the distal axons of cortical neurons and subsequently promote axonal growth even when their growth is inhibited . The samCurrently, the role of intravesicular proteins and the EVs protein corona in the development of CIPN is under research. It has been shown that EVs are effectively internalized by the mechanisms of endocytosis and macropinocytosis by neurocytes and glial cells, carry markers of insulin resistance, functionally active proteins , and may be involved in the pathogenesis of drug-induced neuropathy. The mechanisms of CIPN associated with the EVs protein corona can be related with the accumulation of heavy chains of circulating IgG in it. G-class immunoglobulins in EVs are likely to have myelin hydrolyzing, superoxide dismutase, and oxidoreductase enzymatic activities. Moreover, circulating IgG-loaded EVs are a place for complement activation that can lead to membrane attack complex deposition in neuroglia and neurons. The mechanisms of CIPN development that are not associated with IgG in the EVs protein corona are somehow related to the fact that many anticancer drugs induce apoptosis of tumor cells, neurons, and neuroglial cells by various mechanisms. This process may be accompanied by the secretion of EVs with modified cargo .


The emergence and spread of antibiotic resistance genes (ARGs) have imposed a serious threat on global public health. Horizontal gene transfer (HGT) via plasmids is mainly responsible for the spread of ARGs, and conjugation plays an important role in HGT. The conjugation process is very active in vivo and its effect on the spreading of ARGs may be underestimated. In this review, factors affecting conjugation in vivo, especially in the intestinal environment, are summarized. In addition, the potential mechanisms affecting conjugation in vivo are summarized from the perspectives of bacterial colonization and the conjugation process. En. En36]. increase . Firmicutes, resulting in an increase in the population of Proteobacteria, mainly Enterobacteriales . Co. Co32]. .5 times . It is iThough a number of reports about conjugation in vivo have been published, the compounds that affect this conjugation still need to be revealed. However, the establishment of an in vivo conjugation model is limited by many factors. To accelerate in vivo research, there is an urgent need for an in vivo model that is widely recognized and easily generalized.The density of donor and recipient bacteria, both intergeneric or intrageneric, is a key variable in the CF in vivo, especially in the gastrointestinal tract . TherefoThe colonization of plasmid-carrying pathogens in vivo, especially in the gastrointestinal tract, is the fundamental factor affecting the density of donor and recipient bacteria. The main mechanism is related to the colonization resistance (CR) of intestinal symbiotic flora and the invasion of pathogenic bacteria. In addition, intestinal inflammation can also alter bacterial colonization. The gut has an extremely dense and complex microbial community, which maintains gut homeostasis. Some intestinal bacteria can resist the colonization and invasion of pathogens, which is known as colonization resistance ,66. ConjSalmonella typhimurium strains can colonize the intestinal lumen and survive for a long period in host tissues, which depends on the type-3 secretion system-2 (TTSS-2) encoded by Salmonella pathogenicity islands (SPIs) ,7329,73]Overall, healthy and stable intestinal symbiotic microbiota is conducive to producing better CRs, thereby inhibiting the colonization of pathogens, significantly reducing their population density. In addition, it is necessary to explore the molecular mechanisms that affect in vivo conjugation and fundamentally control the transmission of resistance genes in vivo.tra gene follows a specific regulatory cascade ) ) ,89. ROS 2O2]) . Metal isetC and setD expression and eventually increasing the CF of SXT [Studies have shown that oxidative stress plays an important role in the development of antibiotic resistance and the conjugative transfer of resistance plasmids ,92. DNA F of SXT . In vivoF of SXT .In addition, conjugation can in turn induce SOS responses because SOS response-regulated DNA damage repair is triggered when ssDNA enters recipient cells during conjugation . TherefoAdenosine triphosphate (ATP) plays an important role in conjugation by providing energy for the assembly of conjugation-related components, plasmid replication and transportation . IntraceNicotinamide adenine dinucleotide (NADH) is an important electron donor in the bacterium’s electron transport chain . Under tThe bacterial cell membrane is semipermeable and composed of a phospholipid bilayer and membrane proteins. It plays an important role in nutrient absorption, the excretion of metabolic waste and protein, and material transport . The celecnB, exbB and exbD can regulate cell membrane stability and activate outer membrane transport [ompA, ompC and ompF, can increase CF [ompF plays an important role in cell membrane permeability. When ompF expression is inhibited, the pore protein channel is narrowed and blocked, leading to the obstruction of material transport and a significant reduction in CF [The underlying mechanisms change in the bacterial cell membrane may be related to the expression of membrane-related genes. For example, ransport , and therease CF ,107. Theon in CF ,109. AltIn vivo, especially in the gastrointestinal tract, high bacterial density, suitable temperature and nutritional conditions create a “melting pot” of plasmid conjugation for the spread of antibiotic resistance. However, the diversity of bacterial species, the dynamics of bacteria in different spaces and the diversity of drug-resistant plasmids pose great challenges to studying the conjugation-mediated ARGs transmission in vivo. Thus, few studies have systematically investigated the factors and mechanisms that influence conjugation in vivo. Understanding the factors affecting the conjugation of drug-resistant plasmids in vivo and the dynamic process of the conjugation of donor and recipient bacteria in vivo is critical to reduce the spread and prevalence of ARGs. Thus, we call for more attention to be paid to in vivo conjugation, including the establishment of scientific and reliable in vivo research methods, the early warning of factors contributing to conjugation, the development of conjugation inhibitors, and in-depth exploration of the in vivo mechanisms affecting conjugation.


Student engagement is a complex multidimensional construct that has attained great interest in health professions education (HPE). Definition and conceptualization of student engagement is an important step that should drive the development of the instruments for its measurement. We have recently proposed a comprehensive framework for student engagement in HPE with a definition of engagement as student investment of time and energy in academic and non-academic experiences that include learning, teaching, research, governance, and community activities. The dimensions of student engagement in this framework included the cognitive, affective, behavioral, agentic, and socio-cultural. Guided by the student engagement framework, this non-systematic review aims to identify, critically appraise, and summarize the existing methods for measuring student engagement in HPE. Extrapolating from higher education literature, we attempted to link the theoretical perspectives of student engagement with the published methods of its measurement in HPE context. In addition, we have described the different methods of measuring student engagement including self-report surveys, real time measures, direct observation, interviews/focus groups, and the use of multiple instruments. The span of engagement dimensions measured by self-report surveys ranges from one to five dimensions. However, measurement of agentic and sociocultural dimensions of engagement in HPE is still limited and further research is required. We have also reflected on the existing methods of measuring engagement of students as active partners in HPE. The review also describes the advantages, limitations, and psychometric properties of each method for measuring student engagement. We ended the review with a guiding conclusion on how to develop and select an instrument for measuring student engagement in HPE. Finally, we addressed the gaps in the literature about measuring engagement of HPE students and future research plans. The research agenda on student engagement in education has witnessed a progressive rise during the past three decades. The main drive for this rise is the significance of student engagement as a predictor of academic success, well-being, satisfaction, increased retention, decreased burnout, and enhanced self-directed learning . FurtherPrevious literature in higher education has included several definitions of student engagement according to the underlying theoretical perspectives. The prevailing three theoretical underpinnings that explain student engagement include the psychological, behavioral, and psychosocial perspectives , 6. The The multidimensional nature of student engagement as a construct poses a practical difficulty to its measurement. Student engagement is conceptualized into behavioral, cognitive, emotional, agentic, and sociocultural dimensions that are measured by relevant indicators. Behavioral engagement can be measured by indicators such as student attendance, participation in curricular or extracurricular activities, effort, and ability to persevere in academic pursuits despite challenges. Indicators of emotional engagement include the emotions students experience towards their learning, peers, faculty, and school. These emotions include happiness, enthusiasm, pride, enjoyment, and feeling of bonding. Cognitive engagement includes absorption in learning, metacognition, perceived value of academic tasks and use of high-order cognitive skills. Agentic engagement indicates the student power to influence to their education, their future lives, and their social environment . IndicatStudent engagement can be molded according to the changes in the surrounding environment. These changes will have direct implications on the methods used for its measurement. For example, student engagement varies according to the type of learning activity . Similarly, engagement of students differs according to the time scale, which can range from an engagement in a short learning activity to engagement along the duration of a course or a program.The spheres of students’ engagement include either engagement in their own learning or engagement as partners in education. The areas of engagement as partners include provision of education, scholarly research, governance, and community activities . AccordiTechnology-enhanced learning (TEL) environments are essentially conducted online and offer both opportunities and challenges for student engagement. These environments offer more flexibility and autonomy for students to customize their learning experience according to the most suitable time, method, and place. However, TEL requires students to possess the technology literacy that allows them to navigate online platforms, manage multimedia resources, and manage digital information. Furthermore, students require adaptation to different methods of communication and social skills compared with face-to-face settings to get engaged in online learning activities. Therefore, methods of measuring student engagement in face-to-face learning environments may not be suitable for use in online environments. For example, direct observation is suitable for measuring behavioral engagement of students through direct interactions in face-to-face classrooms. However, measuring behavioral engagement of students in an online environment may need to rely on other measures such as self-report surveys, data analytics and log files.This review aims to provide an overview of the methods of measuring student engagement in HPE. We linked each method with the underpinning theoretical perspectives, and described the measured engagement dimensions, advantages and limitations, and the psychometric properties of each method. In addition, we addressed the current gaps in the literature about measuring student engagement in HPE and directions for future research.n = 19) related to non-HPE contexts. Articles that used self-reports with only one statement for measuring student engagement were excluded from the review. We used EndNote  as the reference manager software for the bibliography of the identified articles.This manuscript represents a non-systematic literature review employing an explicit search strategy to reduce the biases in selection of included articles. The review included articles published in English with the focus of research on conceptualization and measurement of student engagement, and the main subjects are HPE students. We conducted literature search using the following databases: MEDLINE, PubMed, ProQuest, SCOPUS, Education Resources Information Centre (ERIC), Science Direct, and EBESCO. We searched for peer-reviewed research articles in the databases by title and abstract using key terms such as student engagement, engagement, learner engagement, students as partners, and partnership. We combined the previous terms with other words such as health professions, medical, dentistry, pharmacy, nursing, allied health professions, clinical psychology, physical therapy, nutrition, and occupational therapy. In addition, we selected relevant articles from the references list of identified key publications in student engagement. The literature search was limited to articles between 1990 and November 2022. Searching the databases yielded 3019 articles, while an additional 617 articles were identified through searching the listed references and hand-searching of HPE journals. Following deduplication and excluding irrelevant articles through screening of titles and abstracts, 144 articles were selected. Individual screening of full text articles by the two authors (SK and WE) led to the selection of 71 articles to be included in the review with a date of publication ranging from 2003 to 2022. Although the main emphasis of the review is on studies relevant to HPE context, authors agreed to include additional relevant articles , emotional (3 items), and cognitive (2 items) dimensions [The CES was initially designed in general education settings and imported for use in nursing education . The CESmensions , 35. Howmensions  to 0.88 mensions , 35.O videos in Anatomy education [The long version of the UEQ (68 items) has been developed and validated for measuring the experience in immersive virtual environments using participants mainly from information and communication technology or computer sciences . The shoducation . This ve3.Self-reports measuring three engagement dimensionsThe UES-20 has been developed for measuring engagement of commercial users with the learning resources to which they are exposed in online environments . The scaThis scale is one of the most used self-reports in HPE and has an established theoretical basis on the psychological perspective of engagement and the schoolwork engagement model. According to this model, engagement is conceptualized as a positive state of study-related fulfillment characterized by vigor , dedication (cognitive), and absorption  . DiffereThe earlier version of the USEI was originally developed in Portuguese to measure student engagement . This ve4.Self-reports measuring four engagement dimensionsThis scale intends to measure the engagement of students in TEL resources, with an example of its application in Anatomy education . The insThis scale attempts to measure the behavior, thoughts, and feelings of students in online learning. The initial version of the scale has been adapted from the Student Course Engagement Questionnaire (SCEQ) for use in online communication engineering courses . The que5.Self-reports measuring student engagement as partnersThis scale has been used for measuring learning engagement in online courses for Chinese nursing students . Authors6.Measures of institutional level of student engagementThis questionnaire measures the engagement of medical students as active partners in the provision of education . The queth century as a tool for measuring student engagement at the institutional level to improve the undergraduate experiences of students, document effective institutional practices, and benchmark between higher education institutions [The NSSE originated in the early 20itutions . This seitutions , 43. Theitutions  and useditutions –47. The b)Direct observationCLASSE is an adapted version of NSSE to measure engagement of students at the classroom level . The purSTROBEDirect observation can measure the engagement of individual students or the whole classroom during a learning activity. The observable indicators for student engagement are mainly focused on the behavioral dimension such as attention, asking questions, and participating in classroom activities. Observation measures can provide real-time changes in student engagement and describe rich information about the contextual factors affecting engagement. However, they are time-consuming, require training of observers, and limited to measuring the behavioral dimension of engagement. In addition, direct observation mostly includes a small number of students, which limits the generalizability of these measures. In the HPE literature, there are two reported direct observation methods, which are STROBE and In-class engagement measure (IEM).2)In-class engagement measure (IEM)The name of the STROBE instrument refers to the strobe light that intermittently captures events at regular intervals. The instrument consists of 5-minute observational cycles repeated during the classroom activities. During each cycle, the trained observer records the behavior of the teacher and four students, and the process is repeated. Categories of student behaviors on the STROBE include: 1) Learner-to-learner engagement, such as speaking, listening, or both, 2) Learner-to-instructor engagement, such as speaking, listening, or both, and 3) Self-engagement: Learner reading, writing, or otherwise not visibly interacting with other learners or instructor. The observers also write free comments at the end of each 5-minute observation cycle. The reliability of the instrument measured by inter-observer agreement of observers who simultaneously scored the engagement of students was good to excellent . In addic)Real-time measuresThe instrument is a revised form of STROBE to determine the level of engagement of students and teachers in the classroom settings on direct observation. Each observation cycle includes recording the behaviors of an instructor and four randomly selected students as snapshots for 5-min cycles , 60. EacStudent engagement is a dynamic construct that responds to changes in the educational context. Therefore, several real-time measures have been developed to measure moment-to-moment changes in student engagement as it unfolds especially at the level of an educational activity. Examples of real-time measures applied for measuring student engagement in HPE are log files, physiological measures, and eye tracking. Log files are computer-generated data files that record system-related information including the internet usage patterns and activities. Log files can capture several indicators of behavioral engagement of students in technology-enhanced learning environments –69. For d)Interviews and focus groupsFor example, heart rate changes are used for measuring cognitive engagement of medical students in different types of class activities . Eye-trae) Multiple methodsInterviews and focus groups have the advantage of collecting in-depth information about student engagement. The collected information is usually deep and rich as students have the chance to explain how their engagement unfolds in a learning environment. By discussing with HPE students, they can explain the contextual factors that trigger or inhibit their engagement –80. StudThe comprehensive nature of the engagement construct made it almost impossible to measure all its components using a single instrument. To address this problem, several studies have used mixed quantitative and qualitative methods to triangulate the evidence about student engagement , 82–87. The measurement of student engagement in HPE has been a challenge despite the progressive interest of studying the construct for more than two decades. We conclude this review by highlighting important points to consider before developing and selecting instruments for measuring student engagement in HPE as shown in Table First, conceptualizing and defining student engagement is an important step in its operationalization and developing the appropriate methods of measurement. Furthermore, aligning the methods of measuring engagement with the underlying theoretical perspectives would streamline the comparison of findings across student engagement studies. Most of the available methods focus on measuring the psychological perspective of student engagement, while the behavioral perspective is limited to measuring student engagement at the institutional level. However, methods of measuring engagement from the socio-cultural theoretical perspective in the HPE literature are still in infancy. This is particularly relevant to the sphere of student engagement as partners in HPE education where theories such as Community of Practice (CoP) and Positioning theory are applicable [plicable .Second, an important consideration during the design or selection of an instrument for measuring student engagement is identifying the dimensions of engagement that can be measured. Several instruments are available in the HPE literature for measuring behavioral, cognitive, and emotional engagement of students. However, the instruments designed to measure the agentic and socio-cultural dimensions of student engagement in HPE are limited and should be the target for future research.Third, a plethora of publications in HPE address the measurement of student engagement in the sphere of own learning while measuring engagement of students as partners has been limited. Furthermore, most of the existing instruments in HPE literature about measuring student engagement as partners are not focusing on the engagement construct. Instead, the instruments used in these studies are measuring the drivers [ drivers , 80, 89  drivers , 90 of sFourth, student engagement has been conceptualized as a multi-level construct with variable time scales. Therefore, the granularity of measured engagement  should be clearly identified at the outset of the study [he study . This isFinally, it is important to note that disengagement is not at the opposite end of the engagement spectrum. Engagement and disengagement are conceptually considered as distinct constructs with different outcomes. Accordingly, engagement and disengagement dimensions are distinct and require different structures of the instruments used for their measurement. Specifically, there is a lack of research on the measurement of student disengagement in HPE, highlighting the need for more studies to explore the different aspects related to this construct.


Frontotemporal dementia behavioral variant (bvFTD) is the most common subtype of frontotemporal dementia, characterized by early and often severely disabling alterations in personality and social conduct that carry a huge impact on the patient, family, and society.The aim of the study was to correlate the clinical data collected from our patient with relevant literature and discuss the diagnosis of bvFTD in the context of the COVID-19 pandemic.Case report and a systematic review of the literature.The middle-aged female patient we examined presented an array of psychiatric symptoms, including cognitive, behavioral, and personality changes that emerged in two months after a mild form of SARS-CoV-2 infection. Objectively, a cranial CT scan displayed frontal and anterior temporal lobe atrophy. The rapid and severe decline of the patient’s mental faculties throughout the last year, along with the circumstances in which the pathology developed, raised a question about the etiological factors that contributed to this early-onset dementia.Although diagnostic criteria are useful, frontotemporal dementia may be difficult to differentiate from other conditions because there are no disease-specific biomarkers. Correlations between the COVID-19 infection and the fulminant bvFTD symptoms remain unclear and require further investigations.None Declared