Small microscopic entities known as microbes, having a population of hundreds of billions or perhaps even in trillions, reside in our gastrointestinal tract. A healthy immune system, digestion, and creation of vitamins and enzymes are all thanks to these microbes. However, new research has shown a hitherto unrecognized connection between the microbiota of the intestines and the genesis of neurodegenerative diseases. Neurons in the CNS gradually deteriorate in neurodegenerative illnesses like multiple sclerosis and Parkinson's disease (PD). This deterioration impairs cognitive and physical function. Amyotrophic lateral sclerosis (ALS), PD, and Alzheimer's disease (AD) are just a few examples of neurodegenerative illnesses that pose a serious threat to world health and have few effective treatments. Recent research suggests that the gut microbiota, a diverse microbial population found in the gastrointestinal system, may substantially impact the cause and development of various diseases. The discovery of altered gut microbiota composition in people with these illnesses is one of the most critical lines of evidence connecting gut microbiota dysbiosis to neurodegenerative diseases. AD patients have a distinct characteristic of having a particular microbiota profile. In addition, an excess population of a specific microbe data profile is seen as compared to a healthy individual. Similar changes in the gut microbiota composition have been noted in people with multiple sclerosis and PD. The latest study indicates the potential that dysbiosis, a condition characterized by alteration in the intestinal microbiota's makeup and functioning, may have an effect on the onset and progression of neurodegenerative diseases, including PD and multiple sclerosis. In order to emphasize any potential underlying mechanisms and examine potential treatment repercussions, the review article's goal is to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders. The review article aims to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders, highlighting potential underlying mechanisms and examining potential treatment repercussions. The gut microbiome is a vast community composed of billions of microorganisms that play a significant role in the smooth operation of human life. Research has shown the influence of gut microbiome on disease influenced by gut microbes. Furthermore, experimental studies in animal models have further supported intestinal microbes' function in neurological conditions. For instance, studies indicate that compared to rodents bred traditionally, pathogen-free mice, which lack intestinal microbes, display reduced neuroinflammation and enhanced cognitive function. These data imply that dysbiotic gut microbiota may factor in several diseases like neuroinflammation and neuronal dysfunction observed in neurodegenerative diseases. The "gut-brain axis" theory emphasizes the network that links the gastrointestinal tract and the brain in both directions. This complex interaction comprises hormonal, immunological, immunological, and microbial pathways that collectively affect biological processes while affecting the health of the intestinal tract and the brain .Through the microbiota-gut-brain axis, gut dysbiosis, a significant root cause in numerous gastrointestinal illnesses, may also increase pro-inflammatory cytokines, monocytes, lipopolysaccharides, and T helper cells, promoting intestine and the permeability of the blood-brain barrier (BBB). As a result, the progression of neurodegenerative illnesses, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), is accelerated. These diseases encompass demyelination, axonal damage, and multiple sclerosis. According to studies, consuming probiotics may aid in the integrity of the intestine and BBB, ameliorating the aforementioned neurodegenerative illnesses . ThroughThe control of immune responses, the production of metabolites that may impact brain health, and the accumulation of proteins linked to the disease have also been associated with specific bacterial species. For example, compared to normal subjects, those with PD and AD have less diversity of microbes and different microbial makeup. Furthermore, it has been discovered that people with neurodegenerative diseases have drastically changed levels of particular bacteria, including Firmicutes and Bacteroidetes. With the inclusion of the complex world of gut microbiota, these discoveries have prompted a rethinking of the factors that contribute to neurodegenerative illnesses, going beyond just hereditary and environmental factors. Modern developments in metagenomic analysis and high-throughput sequencing technology have sparked research into the relationship between intestinal microbes and neurological disorders. These approaches have given researchers previously unheard-of insights into the richness and makeup of the gut microbiota, enabling them to pinpoint specific microbial taxa and functional pathways linked to neurodegenerative diseases. For instance, research has shown that people with PD and AD have altered gut microbiotas, showing variations in the abundance of particular bacterial taxa and the possibility of metabolic pathway dysregulation ,5. It isTo explain how gut microbiota can affect neurodegenerative illnesses, several hypotheses have been put forth. First off, dysbiosis can result in widespread inflammation, resulting in neuroinflammation. Gut bacteria play a critical role in regulating immune system activity. Second, different metabolites produced by gut bacteria, including short-chain fatty acids (SCFAs) and neurotransmitters, can have an impact on the health and function of the brain. The gut microbiota may additionally influence the BBB's integrity, which can lead dangerous neurotoxins to enter the CNS. These results highlight not only the intestinal microbiota's potential relevance but also the significance of unique microbial profiles that may influence illness vulnerability and development. The therapeutic possibilities of using the microbiota of the gastrointestinal tract to control or perhaps prevent neurodegenerative illnesses are gaining traction in light of these fascinating results. A new route for intervention has opened up with the idea of "psychobiotics," living microorganisms that may have psychological advantages. In order to reduce inflammation, strengthen the gut barrier, and possibly slow the advancement of neurodegenerative diseases, probiotics, prebiotics, and dietary interventions that modify the composition of the intestinal microbiota and encourage the growth of beneficial microbes have been investigated ,8.MethodologyA comprehensive literature search strategy was implemented to identify relevant studies investigating the role of gut microbiota in neurodegenerative diseases. Electronic databases, including PubMed/MEDLINE, Embase, and Google Scholar, were searched using keywords and Medical Subject Headings (MeSH) terms. The search was limited to articles published within the last 10 years without language restrictions. The reference lists of relevant articles and review papers were manually screened to identify additional studies. To ensure the inclusion of appropriate studies, specific inclusion criteria were applied. Eligible studies are needed to focus on the role of gut microbiota in neurodegenerative diseases. Studies unrelated to the research question, those focusing on non-human subjects or in vitro/experimental models, and articles lacking sufficient data or available only as conference abstracts, editorials, commentaries, or opinion articles were excluded. The selection process involved screening the titles and abstracts of identified articles, followed by a full-text assessment based on the inclusion and exclusion criteria. Any disagreements or uncertainties were resolved through discussions among the authors. By implementing these rigorous methodology steps, we aimed to ensure the inclusion of high-quality and relevant studies in this review article, thus providing a comprehensive and reliable overview of the role of gut microbiota in neurodegenerative diseases. Figure Introduction to gut microbiota and neurodegenerative diseasesThe human body, a highly orchestrated symphony of biological processes, is home to a diverse variety of microorganisms, the majority of which reside in the digestive system. The gut microbiota is an amalgam of bacteria, viruses, fungi, and other microscopic life forms that coexist peacefully with the host organism, humans, affecting a wide range of biological processes besides conventional digestion and metabolism . The graNeurodegenerative diseases: an overviewA category of chronic, progressive conditions known as neurodegenerative diseases is characterized by the slow degeneration of neurons in the CNS. These disorders frequently result in crippling cognitive, physical, and psychological problems and ultimately result in the loss of certain brain functions. PD, ALS, and AD are three of the most common neurodegenerative illnesses. Each has unique clinical characteristics, pathological signatures, and underlying mechanisms.Parkinson's DiseaseThe loss of dopamine-producing neurons in the substantia nigra region of the brain causes PD, a disorder that affects movement. Motor symptoms like stiffness, bradykinesia (slowed movement), tremors, and postural instability are brought on by this dopamine insufficiency. Non-motor symptoms like cognitive decline and emotional disorders are also linked to PD. Lewy bodies, clumps of the protein alpha-synuclein, are the distinguishing feature of PD. Although hereditary factors and exposure to environmental chemicals have been linked to PD, its specific origin is still unknown .Amyotrophic Lateral SclerosisThe motor neuron ailment ALS, often known as Lou Gehrig's disease, causes both upper and lower motor neurons to deteriorate progressively. This leads to eventual respiratory failure, muscular weakening, and paralysis. Most occurrences of ALS are random; however, a small percentage are inherited because of mutations in genes like SOD1 and C9orf72. Neurodegeneration in ALS is caused by incorrect protein folding, compromised axonal transport, and activated glial cells .Alzheimer's DiseaseAD accounts for 60-70% of all occurrences of dementia, making it the most prominent cause. The buildup of tau protein tangles and beta-amyloid plaques in the brain distinguishes it. Memory loss, cognitive deterioration, and behavioral changes are caused by these aberrant protein aggregates, which interfere with neural communication .The gut-brain axis: mechanism of communicationThe CNS and GI system interact with one another in an intricate network known as the gut-brain axis. It produces a dynamic connection between the microorganisms in the GI tract, the brain, and those microorganisms. This axis is composed of numerous complex pathways, including microbial, neurological, hormonal, and immunological ones. Together, these routes support constant information flow. In addition to digestion and nutritional absorption, this interplay has effects on a variety of physiological processes, such as mood regulation, cognition, immune response regulation, and even behavior ,14.Neural PathwaysThe gut-brain axis is built on the vagus nerve, a crucial component of the autonomic nervous system that establishes a direct neurological connection between the gut and the brain . The vagHormonal PathwaysAnother crucial pathway for communication between the gut and brain is hormonal signaling. Enteroendocrine cells, found throughout the digestive system, release hormones in response to various stimuli, such as the presence of nutrients or metabolites made by the gut microbiota. Ghrelin, glucagon-like peptide-1, and cholecystokinin are a few of the hormones that control hunger, satiety, and energy levels. In addition to affecting metabolic functions, gut hormones can also affect how we think and feel .Microbial PathwaysThe part the gut microbiota plays in the gut-brain axis is arguably the most intriguing. These microscopic creatures weigh between 1 and 2 kg and can produce a fantastic variety of bioactive chemicals. Neurotransmitters, SCFAs, and other metabolites produced by gut bacteria can directly impact brain activity and behavior. For instance, certain gut bacteria can create neurotransmitters like dopamine and serotonin, which can influence mood and emotional reactions. Additionally, microbial metabolites can alter the BBB's integrity, affecting how molecules travel from the gut to the brain .Gut microbiota dysbiosis in neurodegenerative diseasesIt has received a lot of attention that gut microbiota dysbiosis, which is characterized by an imbalance in the makeup and function of the gut microbial population, may have a role in the pathogenesis and development of a number of neurodegenerative illnesses.Dysbiosis and InflammationChronic inflammation in the brain is frequently linked to neurodegenerative illnesses like AD, PD, and ALS. Through a number of methods, dysbiosis in the gut microbiota can foster an inflammatory milieu. Inflammation throughout the body can result from metabolites that dysbiotic microorganisms can generate. Additionally, a dysbiosis-related disruption in gut barrier function can cause microbial compounds to leak into the bloodstream, setting off an inflammatory cascade ,18.Metabolite ProductionNumerous metabolites, such as SCFAs and neuroactive substances, are abundant in the gut microbiota. It has been demonstrated that the SCFAs produced by gut bacteria during the fermentation of dietary fibers have neuroprotective qualities. They can control the generation of neurotransmitters, the regulation of immunological responses, and BBB integrity. Dysbiosis can change the equilibrium of SCFAs, which could affect their advantageous effects on brain health. Some gut bacteria can also create neuroactive substances like GABA and serotonin, which are vital for controlling mood and maintaining brain health. Dysbiosis-related dysregulated synthesis of these substances may be a factor in the development of neurodegenerative diseases ,20.Protein Misfolding and AggregationAccording to a growing body of studies, unfolded proteins linked to neurodegenerative illnesses may move from the gut to the brain via prion-like pathways. For instance, in PD, aggregates of misfolded alpha-synuclein have been discovered in the ENS before reaching the brain. Dysbiosis aids in this process by encouraging the accumulation of misfolded proteins and the sequent transport to the brain. The complex connections between gut health, protein aggregation, and neurodegeneration are highlighted by this phenomenon .Microbiota-brain signaling and neuroinflammationOne of the important mechanisms by which the gut microbiota influences neurodegenerative diseases is by orchestrating microbiota-brain signaling, which can contribute to neuroinflammation, a hallmark feature of these disorders. The complex communication network between the gut and the brain, known as the gut-brain axis, plays a pivotal role in the modulation of various physiological and pathological processes .Neuroinflammation and NeurodegenerationMicroglia are activated during neuroinflammation, a complicated immune response affecting the CNS. Inflammatory mediators such as cytokines and chemokines are also released. The pathogenesis of neurodegenerative illnesses, including AD, PD, and ALS, is thought to be influenced by chronic and severe neuroinflammation, although inflammation is a natural protective response. Microglia, the brain's native immune cells, can over-activate in conditions that cause neurodegenerative illnesses and release neurotoxic compounds that cause cell death and neuronal damage ,24.Microbiota-Induced NeuroinflammationSignals coming from the gut can affect brain function and vice versa through the gut-brain axis, which acts as a bidirectional communication channel. An imbalance in the gut microbial community known as dysbiosis can start signaling pathways that support neuroinflammation. Lipopolysaccharides and other compounds released by dysbiotic microorganisms can breach the gut barrier and activate immune cells in the gut-associated lymphoid tissue. Pro-inflammatory cytokines and other signaling molecules are released as a result of this activation, and they can go to the brain via a variety of paths, including neurological and circulatory pathways ,15.Immune Cell Migration and ActivationImmune cells move and get activated due to dysbiosis, causing neuroinflammation in the brain. Immune cells and chemicals can go through the damaged intestinal barrier and into the bloodstream and then travel to the brain. In response to inflammatory signals, peripheral immune cells such as monocytes and T cells can invade the brain. These immune cells then contribute to the neuroinflammatory response in the brain by releasing cytokines, chemokines, and other pro-inflammatory substances that keep the cycle of inflammation and neuronal injury going .Gut Microbial MetabolitesSCFAs, a type of metabolite generated by the gut microbiota, are crucial for the communication between the microbiota and the brain. SCFAs can affect the synthesis and release of neurotransmitters, BBB integrity, and immune cell activity. The production and availability of these metabolites can be altered by dysbiosis, interfering with their beneficial effects on the control of neuroinflammation and general brain health .Implications for disease progression and onsetBeyond simple connections, the complex relationship between the gut microbiota and neurodegenerative disorders has important ramifications for the beginning and development of these crippling ailments. The complicated interplay that can either increase disease pathogenesis or provide opportunities for therapeutic approaches is made possible by the bidirectional communication along the gut-brain axis.Disease Progression and AggregationThe gut microbiota's effects can strongly impact the course of the disease on protein misfolding and aggregation, two symptoms of neurodegenerative diseases. It is possible that misfolded proteins, such as beta-amyloid and tau in AD and alpha-synuclein in PD, start in the stomach before spreading to the brain. These proteins may aggregate in the ENS due to changes in the gut environment brought on by dysbiosis, making it easier for them to travel through neural pathways to the brain. This phenomenon indicates the possible function of the gut microbiota in triggering or amplifying neurodegenerative processes and potentially hastening the progression of the disease .Early Biomarkers and DiagnosticsThe impact of the gut microbiota on neurodegenerative illnesses may open up new possibilities for early identification and treatment. Recent research indicates that alterations in the mix of gut bacteria and metabolite profiles may be used as indicators for neurodegenerative disorders. Researchers could isolate different microbial fingerprints connected to illness states by examining the gut microbiota. These microbial indicators allow for the early detection of those at risk of neurodegenerative illnesses, allowing for prompt therapeutic interventions and individualized treatment plans .Therapeutic InterventionsThe gut microbiome significantly impacts neurodegenerative illnesses, which opens up novel therapy options. Slowing disease onset can be slowed by altering the gut microbiota through dietary changes, probiotics, prebiotics, and postbiotics. It might lessen neuroinflammation, enhance neurotransmitter balance, and impact protein misfolding by encouraging a gut environment rich in advantageous microorganisms. Additionally, methods to increase the production of neuroprotective metabolites, including SCFAs, may provide neuroprotection and postpone the start of the disease ,31.Therapeutic approaches and future directionsA paradigm change in therapy strategies and new avenues for future study have been made possible by the complex interactions between gut microbiota and neurodegenerative disorders. Utilizing the gut-brain axis's two-way connection offers new ways to slow disease progression, enhance patient outcomes, and even change how neurodegenerative diseases are managed.Microbiota Modulation for NeuroprotectionIncreasing data points to the potential for neuroprotection offered by targeted manipulation of the gut microbiota. The development of advantageous microbial species that generate neuroprotective compounds may be encouraged by methods for reestablishing a healthy gut microbial balance, such as dietary interventions high in fiber and prebiotics. These substances, which include SCFAs and other bioactive chemicals, may help to preserve cognitive function, keep the brain healthy, and prevent the beginning of neurodegenerative illnesses ,33.Development of Probiotics and PostbioticsLive microorganisms known as probiotics are being studied as treatment options for neurodegenerative illnesses because of their potential health advantages. Specific probiotic strains may influence the gut-brain axis, lessen inflammation, and improve the balance of neurotransmitters, according to research. Postbiotics, bioactive substances created by probiotics during fermentation, also show promise since they can deliver comparable advantages without requiring live microorganisms .Biomarker Discovery and Personalized MedicineThe identification of biomarkers that can forecast risk factors for illness, development, and therapy response is made possible by developments in microbiome research. Diagnostic tools and individualized treatment plans may be created by discovering microbial signatures linked to particular neurodegenerative disorders. These methods may improve early diagnosis and allow customized therapies based on each person's unique gut microbiota patterns .The complex interaction between gut microbiota and neurodegenerative disorders has revealed a fascinating new area of medical research. The complex interactions between the gut and the brain have shed light on the possibility of using the microbiota as a potent moderator of illness development and progression. The importance of gut microbiota in determining brain health is underscored by the research surrounding its effects on inflammation, protein misfolding, neurotransmitter abnormalities, and more. The prospects for this field in the future are both exciting and difficult. The therapeutic potential of microbiota-based approaches may transform the management of neurodegenerative diseases. Advanced treatments that focus on many elements of disease etiology are made possible by precise microbiota interventions, creative delivery techniques, personalized courses, and multi-omics integration. The discovery of biomarkers and the creation of ethical and legal frameworks become crucial as researchers attempt to understand the complex pathways connecting the gut and the brain. This trip has its challenges, though. For microbiota-based therapeutics to be shown to be safe and effective, rigorous clinical trials are essential. Careful maneuvering is needed to balance the ethical issues of patient autonomy, fair access, and potential hazards. Transforming scientific discoveries into practical applications that help patients will require interdisciplinary cooperation. Additionally, considering the complexity of neurodegenerative illnesses necessitates multiple strategies that consider patient groups' variation. The gut microbiota stands out as a remarkable participant in the larger picture of neurological health, with the ability to influence disease trajectories and rethink therapy approaches. Researchers and doctors are in a prime position to find ground-breaking treatments that provide hope for those suffering from neurodegenerative diseases by comprehending and utilizing the strength of this deep link. It is becoming increasingly obvious as science develops that the gut-brain axis holds the key to opening up fresh therapeutic possibilities and revolutionizing the field of study and treatment of neurodegenerative diseases. However, the study has certain limitations, such as the fact that most of the research was conducted on animal models, which may not directly translate to humans. Thus, more research and sampling must be done to confirm the findings in human bodies.


The petroleum sector is essential to supplying the world’s energy demand, but it also involves numerous environmental problems, such as soil pollution and oil spills. The review explores biosurfactants’ potential as a new tool for the petroleum sector. Comparing biosurfactants to their chemical equivalents reveals several advantages. They are ecologically sustainable solutions since they are renewable, nontoxic, and biodegradable. Biosurfactants are used in a variety of ways in the petroleum sector. They can improve the mobilization and extraction of trapped hydrocarbons during oil recovery procedures. By encouraging the dispersion and solubilization of hydrocarbons, biosurfactants also assist in the cleanup of oil spills and polluted locations by accelerating their breakdown by local microorganisms. The review gives insights into alternative methods for the petroleum industry that are more viable and cost-effective. Today, human life is extremely dependent on fossil fuels and related hydrocarbon products, viz., kerosene, gas, petrol, and diesel . Among tAround the world, the increasing universal energy demand required a strong energy supply response in addition to limited fossil fuel resources. To regulate the scarcity, researchers are developing techniques to improve the oil recovery from the existing reservoirs. In addition, recognizing alternative resources is paramount to easing the dependence on fossil fuels in the future . AccordiPetroleum biotechnology has the aim of introducing biological processes to produce and refine petroleum to generate value-added by-products with minimum pollution output . The adaVarious microbial species are capable of producing surface-active molecules to improve the bioavailability of hydrophobic, immiscible, and mostly inaccessible substrates, facilitating enhanced survival under low humidity conditions. The production of biosurfactants generally occurs in miscible hydrophilic and hydrocarbon carbon sources in the medium. The process of synthesis becomes attractive when the researcher develops it from waste substrates .The chemical composition of biosurfactants varies greatly depending on the type of microorganism and can be broadly categorized on the basis of their molecular weight and charge. The biosurfactants are classified into two classes: low molecular weight surfactants (which reduce surface tension between two immiscible liquids) and high molecular weight surfactants . The high molecular weight surfactants are more complex as they consist of heteropolysaccharides, lipopolysaccharides, lipoproteins, and proteins, whereas the low molecular weight biosurfactants are generally made up of exopolysaccharides that are capable of emulsifying immiscible liquids but are less efficient in reducing the surface tension . The lisex situ (synthesized outside the reservoir) and in situ processes (synthesized by indigenous microbes within the reservoir conditions).The laboratory synthesized biosurfactants are directly injected into the reservoir, whereas the in situ process identifies the proper microorganisms found in the reservoir that proliferate and synthesize the metabolites such as polymers and surfactants under harsh reservoir conditions  that facilitate the breaking of the emulsion before use  were employed to reduce the viscosity and break the semi-solid clogging, which increased production expenses and produced toxic waste but the process is not economical [29]. Recently, promising technologies have been developed for preparing stable oil-in-water emulsions through biosurfactants to promote oil mobility. fore use . A repore tubing .Enormous quantities of oil are stored in refinery oil tanks and transported for long periods by oil tankers or trucks. Most of these storage tanks are regularly cleaned or maintained, which often increases the problem of hazardous practices or the production of harmful waste material. Also, the sludge deposited on the walls or bottom of the tanks is viscous or semi-solid and cannot be removed with conventional pumps. Removal of this sludge is often done manually or may involve steam or hot water or solvents, these practices is time-consuming, labor intensive, costly and results in a large amount of waste disposal .A field trial conducted by Kuwait Oil Company has shown that biosurfactants can efficiently derive from storage tank cleaning activities. It was done by adding 2 tonnes of rhamnolipid biosurfactant-containing media through energy input to generate a vortex in the tank for 5 days at an ambient temperature of 40–50°C. Promising results were obtained, which showed the effective lifting and mobilization of oil sludge from the base of the tank and its dissolution in the form of emulsions. The process recovered approximately 91% of the hydrocarbons in the sludge, and the value of the crude oil should cover the cost of the cleaning process .The petroleum industry produces large amounts of petroleum sludge during the processes of oil exploration, storage, transportation, and refining. The disposal of such sludge has always been a major concern for the oil industry. For instance, the annual production of oil sludge in China is estimated to be approximately 1 million metric tonnes, primarily from the oil storage tank cleaning process . In IndiDietzia maris sp. LBBMA 191, Arthrobacter oxydans LBBMA 201, Pseudomonas aeruginosa LBBMA 88A, Bacillus sp. LBBMA 111A and Bacillus subtilis LBBMA 155) from oil-contaminated sites. Biosurfactants reduce the viscosity and promote the formation of oil–water emulsions, which facilitate mud pumping and emulsion destruction and improve crude oil recovery  as a final electron acceptor instead of oxygen are known to cause souring of the oil reservoir and microbial-induced corrosion, making them considered harmful for the oil field  requires proper maintenance as per the U.S. Clean Water Act and Oil Pollution Act to identify the specific products that control oil spills . ProductMenidia beryllina and Mysidopsis bahia. These CTDs recommend that dispersants alone are generally less toxic than oil when compared with dispersant-oil mixtures , may be useful as the first step to prioritize environmental risks from the use of dispersants. The CTD approach to two acute toxicity records (after NCP-Deep-sided flat lines) includes a median lethal concentration (LD 50) of dispersant alone and dispersants: oil mixture in two standard marine test species, mixtures .Furthermore, numerous tests have been used on various microbial species to assess the toxicity of synthetic and biological surfactants. Lethal concentration (LC50) is a process to estimate the population mortality of a species, indicating that the higher the concentration, the lower the toxicity of surfactant . The gerAdvances in petroleum biotechnology have become more apparent in recent years, and it has been concluded that many types of biosurfactants are becoming more recognized and valued due to the diversity and efficiency demonstrated in petroleum industry processes. Not only do these compounds play a supporting role, but they are also beginning to play an important role, making them a necessary compound for petroleum biotechnology. The only major advantage of biosurfactants is their biodegradability and non-toxic behavior, which significantly reduce the environmental impact of these compounds compared to chemical surfactants. However, other successful applications are gaining recognition and will lead to increased use in the oil industry.NS: data curation, formal analysis, methodology, writing – original draft, writing – review and editing. ML: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation. BL: project administration, resources, writing – review and editing.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.


A considerable amount of literature is available on the abnormal expression of ANXA proteins in various malignant diseases, including cancer, atherosclerosis and diabetes. As critical regulatory molecules in cancer, ANXA proteins play an essential role in cancer progression, proliferation, invasion and metastasis. Recent studies about their structure, biological properties and functions in different types of cancers are briefly summarised in this review. We further discuss the use of ANXA as new class of targets in the clinical diagnosis and treatment of cancer.The annexin A (ANXA) protein family is a well-known tissue-specific multigene family that encodes Ca The ANXA protein family in humans contains 12 species, ANXA1– ANXA11 and ANXA13  causes resistance to sunitinib in renal cancer cells because it stabilises ANXA1 and activates the AKT pathway independently of its nucleotide reductase activity . Spijkervia the degradation of ANXA3 as its target, thereby promoting the apoptosis of cancer cells , are able to inhibit the repair function of ANXA proteins at the cell membrane. TFP delays the accumulation of ANXA2-GFP at the damaged plasma membrane, inhibits ANXA-mediated membrane curvature, affects the membrane-forming ability of ANXA and, to some extent, impairs ANXA proteins from binding to membrane patches  Heitman. Not onlMost of the numerous members of the ANXA protein family have been found to be associated with cancer, which is characterised by abnormal changes in the normal cellular pathway through the up- or downregulation of expression. Due to the individual characteristics of tumour cells and the various post-translational patterns of the ANXA protein family, members of the ANXA protein family trigger different tumorigenesis and metastasis, thus leading to variable outcomes. A more in-depth study of the ANXA protein family in the tumour microenvironment, with careful consideration of the timing and approach to target selection, may suggest more biologically meaningful clinical treatment strategies. In the early stages of cancer, high expression of ANXA proteins may promote metastasis. It is therefore important to consider the timing of the use of ANXA proteins as clinical prognostic biomarkers. The expression of ANXA proteins is significantly altered during cancer progression, so they can be used as diagnostic and prognostic biomarkers for certain cancers. Furthermore, targeting ANXA proteins has emerged as a promising new strategy for cancer therapy. ANXA proteins are also closely associated with multidrug resistance in many cancers, including cisplatin, paclitaxel and sorafenib resistance. If this could be a research direction and the sensitivity of cancer cells to drugs could be improved, it would undoubtedly be of significant help in cancer treatment. Currently, most of the drug studies involving ANXA proteins are still in the laboratory stage with only a few clinical applications. How to apply these findings to clinical treatment is thus one of the future challenges in cancer research. Basic research on the ANXA protein family is currently relatively shallow, and many members of this protein family have not been studied in an integrated manner with the aim of enhancing tumour prevention and treatment. Future research should focus on the role of the ANXA protein family in the tumour microenvironment and consider tumour-related macrophages, tumour-related fibroblasts and lymphatic metastasis to achieve the combination of cancer prevention and treatment. Moreover, such research should focus on drug screening, as well as drug resistance and its role in immune suppression mechanisms, and aim to achieve precise treatments.


IntroductionThe genetically determined progressive process that causes a gradual conversion of terminal hair into vellus hair is known as androgenetic alopecia (AGA). AGA male pattern baldness is very common among male medical students whose self-image is severely deteriorated by AGA and this affects the quality of their professional career. Hence, the assessment of the association of depression, loneliness, and internet addiction levels of male Bachelor of Medicine, Bachelor of Surgery (MBBS) students with AGA male pattern baldness is essential to improving academic and professional performance.Aims and objectivesThe aim of this study is to evaluate the effects of AGA male pattern baldness and its severity on depression, loneliness, and internet addiction levels of male medical students in Kolar.Materials and methodsThis questionnaire-based cross-sectional study was conducted among 100 male MBBS students from Sri Devaraj Urs Medical College in Kolar with AGA male pattern baldness of varying grades. The participants were selected through simple random sampling from July 2022 to November 2022 with their prior informed consent. Students' AGA severity was evaluated clinically using the Norwood-Hamilton Classification. Their levels of depression, loneliness, and internet addiction were assessed using the standardized Beck Depression Inventory (BDI) scale, University of Carolina Los Angeles - Loneliness Scale (UCLA-LS), and Young Internet Addiction Test - Short Form (YIAT-SF), respectively, and one-way analysis of variance (ANOVA) was used to ascertain the statistical significance between the means of BDI, UCLA-LS, and YIAT-SF with the severity of AGA. Chi-square/Fisher Exact test was used to find the significance of study parameters on a categorical scale between two or more groups. Significance was assessed at a 5% level of significance.ResultsThe mean of BDI , UCLA-LS , and YIAT-SF  scores in each of the AGA grades from Grade I to Grade V in our study showed that these scores increase along with an increase in the severity of AGA and are statistically significant. The frequency distribution of male medical students with varied degrees of AGA and the level of depression, loneliness, and internet addiction levels assessed by the BDI, UCLA-LS, and YIAT-SF showed a robust and statistically significant association between the severity of AGA and the severity of depression, loneliness, and internet addiction levels.ConclusionThe current study showed that there is a statistically significant association of depression, loneliness, and internet addiction levels in male MBBS students with AGA male pattern baldness. One of the distinguishing features of mammals is hair. It has always had a significant psychological and sociological role in shaping a person's appearance and personality. Different hairstyles and shaving techniques reflect the cultural origins of people. Additionally, it conveys the individual's standing and unique personality. Due to media and public hype surrounding hair, having too little hair, as in alopecia, is socially and cosmetically unacceptable . In bothAndrogenetic alopecia (AGA), the most prevalent kind of hair loss affecting approximately 70% of adult males and 50% of adult females, is a genetically set progressive process that gradually transforms terminal hair into vellus hair ,2. InvolPast research indicates that AGA may also have psychosocial side effects, such as depression, low self-esteem, altered self-image, and fewer frequent pleasurable social interactions. People with AGA frequently believe that their alopecia is a serious condition that will undoubtedly have negative effects on their lives .College students who are adolescents and young adults are in a crucial stage of psychological development, and their psychological state is unstable. College students with AGA might have to deal with the extra stress of hair loss, which could put a significant strain on their capacity for coping . The sigNumerous studies have demonstrated that during their time in medical school, students endure heightened levels of stress. They are under a lot of stress because of the sacrifices they must make on a personal and social level to maintain good academic outcomes in a setting of intense competition. Researchers discovered that medical students' stress levels were ostensibly higher than those of non-medical professional students. Stress can cause problems with one's physical and mental health. Drugs, painkillers, alcohol, the internet, smoking, and eating may be used to cope, but these are unproductive and may make the stress worse. It may also cause depression and anxiety . InterneMethodologyThis questionnaire-based cross-sectional study was conducted among 100 male Bachelor of Medicine, Bachelor of Surgery (MBBS) students from Sri Devaraj Urs Medical College in Kolar, Karnataka, India, with AGA male pattern baldness of varying grades, who were selected through simple random sampling from July 2022 to November 2022 with their prior informed consent. Students' AGA severity was evaluated clinically using the Norwood-Hamilton classification. The questionnaires that all participants in this study completed included questions about their socioeconomic status as well as assessments of their levels of depression, loneliness, and internet addiction using the standardized Beck Depression Inventory (BDI) scale, University of Carolina Los Angeles - Loneliness Scale (UCLA-LS), and Young Internet Addiction Test - Short Form (YIAT-SF), respectively.Statistical analysisData from the study was recorded into an Excel datasheet . The data analysis was done using IBM SPSS Statistics for Windows, Version 22.0  and R 3.2.2 . Results on continuous measurements were presented as mean ± SD (min-max) and results on categorical measurements were presented as number (%). To ascertain whether there were any statistically significant differences between the means of three or more independent (unrelated) groups, the one-way analysis of variance (ANOVA) was used. Chi-square/Fisher Exact test was used to find the significance of study parameters on a categorical scale between two or more groups. Significance was assessed at a 5% level of significance.One hundred MBBS students with varied degrees of male pattern AGA participated in the current study. Table The students in our study ranged in age from 18 to 24 years and had a mean age of 20.41. The MBBS students in our study had AGA male pattern baldness grades ranging from Grade I to Grade V using the Norwood-Hamilton scale. Table The current study's data indicate that the incidence of AGA severity increases with the year of MBBS; 94% of the students in our study had stress in their day-to-day activities. The mean of BDI, UCLA-LS, and YIAT-SF scores in each of the AGA male pattern baldness grades from Grade I to Grade V in our study shows that these scores increase along with an increase in the severity of AGA and are statistically significant. The severity of the AGA graded from Grade I to Grade V in our study, was compared to the mean of the BDI, UCLA-LS, and YIAT-SF scores in Table The frequency distribution of students with varied degrees of AGA male pattern baldness and the level of depression assessed by BDI showed a robust and statistically significant association between the severity of AGA and the severity of depression. Table There was a strong and statistically significant association between the severity of AGA and the severity of loneliness, as evidenced by the frequency distribution of students with various degrees of AGA male pattern baldness and the level of loneliness measured by the UCLA-LS. The frequency distribution of students with varying levels of AGA and the UCLA-LS scores of their level of loneliness are shown in Table The frequency distribution of students who displayed various levels of the AGA male pattern baldness and the degree of internet addiction determined by the YIAT-SF revealed a strong and statistically significant association between the severity of AGA and the severity of internet addiction. The frequency distribution of students with varying degrees of AGA and the degree of internet addiction as indicated by the YIAT-SF are shown in Table As the guardians of the future generation, medical students' health must be given the utmost priority. Due to their heavy academic load, personal issues, and the need to learn to save patients' lives, students in medical school experience a great deal of stress. Additionally, there is a very high prevalence of AGA male pattern baldness among medical students. In terms of interpersonal sensitivity, the psychological circumstances of medical students with AGA male pattern baldness are much worse than those of students in other professions ,5. MedicIn the current study, 94% of the students with AGA male pattern baldness reported experiencing stress from their daily activities. This result is in line with the elevated stress levels observed in the medical students as a whole in the study carried out by Jafri et al. in which they recorded 75.6% of medical students as having stress [The severity of AGA grading increased along with the degrees of depression in our study population. Mirza et al. recorded the rising prevalence of depression among medical students in general . Wang etCollege students who are sad have a propensity for isolation and a life devoted to various addictions ,8. Due tAccording to Perera et al., AGA male pattern baldness is the most typical cause of hair loss in medical students. They revealed that AGA male pattern baldness in medical students indicates a serious negative impact on their lives in terms of their general self-esteem and frame of mind, which seriously affects their psychic nature and results in depression, loneliness, and internet addiction . This reThe results of this study show that there is a statistically significant association of depression, loneliness, and internet addiction levels with AGA male pattern baldness in male MBBS students. Medical students are under constant stress during their medical school life. Male medical students have a relatively higher incidence of AGA male pattern baldness than the general population. AGA is aesthetically unappealing and has major psychological morbidity in male medical students. Because they are the doctors of tomorrow, medical students' health is of the utmost significance. Therefore, early detection and timely intervention have to be done to combat depression, loneliness, and internet addiction in male medical students with AGA.


The COVID-19 pandemic has had profound and wide-ranging effects beyond its medical implications, causing significant sociological, psychological, and economic consequences on a global scale. This pandemic posed a significant social challenge, and it has also provided us with invaluable lessons learned from facing this unprecedented situation. Specifically, recognizing the significance of self-care as a psychological resource in managing the pandemic mental health consequences, which has become increasingly crucial, and will continue to be critical in future public health crises.The WHO defines self-care as: “the ability of individuals, families and communities to promote health, prevent disease and maintain health, and to cope with illness and disability with or without the support of a healthcare provider” . The study highlighted the pandemic's influence on the ways people engage with the arts and culture, which were seen as helpful in rebuilding personal resilience and confidence. These findings underscore the importance of providing support for individuals and communities to cope with the emotional and social impacts of the pandemic.Ecker et al. found that parents were not necessarily at risk due to additional burdens, but instead they had better prospects for coping than those without children. In a longitudinal study carried out on Chilean parents, Pérez et al. reported an increase in depression and home chaos with respect pre-pandemic levels, which was moderated by factors such as financial stability, personality, and recent major stressful events. Additionally, research conducted among parents in Texas (USA) by Morgan et al. found that economic pressure led to worsened mental health, with stress mediating this pathway. Moreover, approach coping strategies were found to be more effective in moderating the association between stress and later anxiety symptoms compared to avoidant coping strategies. Sánchez-Hernández et al. suggested the implementation of interventions aiming at the promotion of resilience and emotional self-care to mitigate the impact of pandemics on families and healthcare professionals.This pandemic has also changed the organization of families at home. A study conducted in Germany during the early phase of the pandemic by Zou et al. explored the role of perceived stress and social support in explaining the relationship between three negative symptoms  among the frontline medical staff at the beginning of the pandemic in Wenzhou (China). They reported that occupational stressors were related to all negative symptoms, with perceived stress mediating, and social support moderating these associations. Perilli et al. evaluated perceived anxiety and stress by general practitioners and by hospital ward nurses in the district of ASL1 Avezzano-Sulmona-L'Aquila  during acute phase of the pandemic. They found higher levels of anxiety in general practitioners than among nurses, which were associated with increases in emotional distress. In addition, anxiety increases were coped with by enlarging the demand for social support in general practitioners. This coping strategy correlated with emotional distress and when enhanced, it corresponded to avoidance of the problem.Regarding the healthcare sector, the outbreak increased work demands for healthcare professionals, which had a particular impact on their mental health. Alqassim et al. examined the prevalence and the associated factors of burnout among schoolteachers in the Jazan Region (Saudi Arabia) in April 2021. Authors indicate that most teachers showed burnout symptoms, which were related to taking psychotropic medications, absenteeism, lack of job satisfaction, and school change. On the other hand, being an expert and having the ability to adapt to technology proved to reduce burnout symptoms effectively. Loebach et al. explored whether education staff from the state of New York (USA) spent more time outdoors during the pandemic as compared to pre-pandemic times. The majority of participants reported spending more time in natural outdoor environments since the pandemic had emerged, particularly in its early stages. The relative accessibility of those environments impacted the behavior of the participants, In terms of the number of occasions being outdoors and the number of natural outdoor environments visited. Liu et al. investigated the dynamic changes in the mental health status of Chinese university students in Xuzhou (province of Jiangsu) since the outbreak of the pandemic and after 1 year. They reported that the degree of recognition of the pandemic was an important factor that significantly affected the psychological state of college students, and that effective control of the environment slightly improved the behavior and mental state of the students. Similarly, Barankevich and Loebach explored the social interaction patterns of university students in northeastern USA during the outbreak of COVID-19. They suggested that students had spent significantly less time interacting with non-roommates in person during the pandemic, and more time in voice and video calls, and that meaningfulness had been higher for interactions with family or friends.The pandemic also interrupted education-learning processes, which added more stressors to students, teachers, and education staff since they had to change their working styles. In summary, the aforementioned studies provide robust evidence about the importance of considering the social determinants of mental health to promote mental wellbeing, and the central role self-care plays. It has been highlighted that self-care can positively influence health attitudes and behaviors in the population. Promoting mental health with a central focus on self-care enhances the quality of life, alleviates clinical symptoms, and increases awareness and use of available individual and collective health resources. Additionally, evidence supports the effectiveness of collective and individual actions on self-care, as they can favor healthy environments and lifestyles, and facilitate citizen reflection on self-management practices from a context-based perspective. Likewise, self-management practices can guide the implementation of targeted actions aimed at reducing the most prevalent health risks in the community. Thus, future public health recommendations should carefully consider the role of community-based decision-making actions that involve actively citizens to empower them to adopt and influence self-care behaviors, emphasizing problem-solving and collaborative development with health, social and political sectors.EL, MM, and EB-M were responsible for the manuscript design. All authors contributed to this work and approved the final manuscript.


Gastrointestinal cancers have become an important cause of cancer-related death in humans. Improving the early diagnosis rate of gastrointestinal tumors and improving the effect of surgical treatment can significantly improve the survival rate of patients. The conventional diagnostic method is high-definition white-light endoscopy, which often leads to missed diagnosis. For surgical treatment, intraoperative tumor localization and post-operative anastomotic state evaluation play important roles in the effect of surgical treatment. As a new imaging method, near-infrared fluorescence imaging (NIRFI) has its unique advantages in the diagnosis and auxiliary surgical treatment of gastrointestinal tumors due to its high sensitivity and the ability to image deep tissues. In this review, we focus on the latest advances of NIRFI technology applied in early diagnosis of gastrointestinal tumors, identification of tumor margins, identification of lymph nodes, and assessment of anastomotic leakage. In addition, we summarize the advances of NIRFI systems such as macro imaging and micro imaging systems, and also clearly describe the application process of NIRFI from system to clinical application, and look into the prospect of NIRFI applied in the theranostics of gastrointestinal tumors. Gastrointestinal cancers, including esophageal cancer, gastric cancer, and colorectal cancer (CRC), have the characteristics of high morbidity and high mortality. According to the latest research statistics in 2022, esophageal cancer, gastric cancer, and CRC rank second, third, and sixth, respectively, in the incidence of cancer in China, and rank fourth, third, and fifth, respectively, in the mortality of cancer in China .Under the current routine diagnostic methods, gastrointestinal cancer is often diagnosed at an advanced stage and the prognosis of advanced cancer is poor , 3. EarlThe principle of near-infrared fluorescence imaging (NIRFI) is that some dye molecules can be excited by light within the ultraviolet to the infrared spectrum to produce near-infrared fluorescence, which can be received by special optical sensors . CompareIn addition to gastrointestinal tumor diagnosis, NIRFI also has many applications in gastrointestinal surgery. Surgical resection is one of the important treatment methods for gastrointestinal tumors. The recognition of tumor location and lymph node (LN) metastasis, as well as the confirmation of anastomotic conditions, has a great impact on the therapeutic effect of surgery. At present, the treatment of these surgical conditions mainly depends on the subjective judgment of doctors, which might result in post-operative recurrence and metastasis. In addition to the molecular targeted fluorescent tracers mentioned above, near-infrared fluorescent molecules can also be imaged in tumors according to an enhanced permanency and retention (EPR) effect . With thTo date, some reviews have discussed the application of molecular imaging in the gastrointestinal tract  and someHerein, we review the latest progress in near-infrared fluorescence endoscopic imaging systems for the diagnosis and surgical treatment of gastrointestinal tumors; review the main advances in the application of NIRFI in the early diagnosis and surgical navigation of esophageal cancer, gastric cancer, and CRC; and discuss the application prospects, the concepts, issues, approaches, and challenges, with the aim of improving to develop NIRFI technology for precise diagnosis and therapy of gastrointestinal tumors.At present, endoscope systems used for NIRFI are mainly divided into two categories: macro and micro NIRFI systems , 31. WitTo overcome the contrast defects of the white-light endoscope and the autofluorescence endoscope, Waterhouse and colleagues  developeIn the NIRFI system, the selection of fluorescence probes has a great impact on the imaging effect. In order to determine the efficiency of various near-infrared fluorescence probes in the same lesion, Shrivastav and colleagues  developeIn addition to being used for cancer detection, the macro NIRFI system also has a strong application prospect in clinical surgery guidance. In order to solve the coexistence of normal surgical lighting and NIRFI, Liu and colleagues  proposedin vivo history [The commonly used microscopic NIRFI system is confocal laser endomicroscopy (CLE) . CLE use history .For example, to break through the limitation of imaging depth and realize deep-tissue imaging at the cellular level for gastrointestinal tissue, Wang and colleagues combined the near-infrared probe with CLE and developed a set of NIRFI system . The sysEsophageal adenocarcinoma (EAC) is one of the most common malignant tumors of the digestive tract, with a 5-year survival rate of <15% . Early dIn order to overcome the shortcomings of WLE and random biopsy in early EAC detection, Marcazzan and colleagues  conducteConventional high-definition white-light endoscopy (HD-WLE) can only recognize the visualization of surface morphological changes, whereas current fluorescent molecular endoscopy (FME) can realize cancer-specific pathological subsurface examination. Based on this, Nagengast and colleagues  proposedThere are great differences in the expression level of a single target between different patients, even between the same patient. Simultaneous imaging of multiple targets shows potential in improving diagnostic performance. Chen and colleagues  proposedGastric cancer was the sixth most common cancer and the third leading cause of cancer death worldwide in 2022 . Althoug+/– mice were injected using a Prosense680 probe and an MMP Sense 750 probe, respectively, and then in vivo and in vitro NIRFI were performed, respectively  is also a strategy for intraoperative tumor localization. For example, in order to solve the deficiency of intraoperative endoscopy in gastric tumor localization, Narihiro and colleagues  used NIRThe sentinel lymph node (SLN) is the first drainage station for primary tumor metastasis . An expe+ LN was detected in 20 of them, confirming the efficacy of NIR in lymphatic mapping  is one of the most worrisome complications of gastrointestinal surgery; because of its high morbidity and mortality characteristics, AL places enormous pressure on both patients and physicians . In esopP < 0.001). These results suggest that NIR imaging may be used to predict AL after esophagectomy.The incidence of AL in esophagectomy ranges from 5% to 20%  and NIR-NIR angiography is more widely used in reducing the incidence of AL after colorectal surgery . To reduP = 0.001), and TD had excellent performance in both univariate and multivariate analysis and could be used to predict AL in gastric cancer surgery. The experimental results demonstrate the feasibility of TD in predicting AL in gastric cancer surgery [Recently, have also been some studies on NIR angiography for the evaluation of AL in gastric cancer surgery . For exa surgery .ICG is currently the most common fluorescent agent in NIRFI, but its specificity needs to be improved . NIRFI wIn order to achieve clinical translation, the following work needs to be done well. The toxicological profile is required for any first-in-human investigation in order to establish a safe starting dose for humans. Most preclinical investigations recognize the maximum tolerated dose, particularly for new drugs. The maximal tolerable dose is not always necessary for fluorescent agents to produce the best results, which is a significant distinction between fluorescent agents and therapeutic research medications. For the medicine to have the desired effect, the proper dosage must be determined. The clinical transformation of innovative selective fluorescence probes depends on achieving a high target-to-surrounding-tissue ratio with modest dosages of fluorescent chemicals.Additionally, contemporary imaging systems are needed for the clinical translational procedure. Even though NIRFI imaging system development has made significant strides, the software and hardware of the system still need to be tuned to make it more portable. To maximize tumor detection during surgical procedures, laparoscopic or endoscopic equipment must incorporate imaging technologies that adhere to the trend toward minimally invasive surgery.Although NIRFI allows precise tumor imaging, doctors' attention spans may greatly affect detection rates due to endoscopists' limitations as individuals . TherefoThe utilization of nanoparticles offers a novel tool for the imaging of malignancies for diagnostic purposes since materials acquire special characteristics at the nanoscale. Particles of any substance with a diameter of between 1 and 100 nm are considered nanoparticles because of their remarkable physical and chemical characteristics. Due to their tiny size, adaptable surface features, and retention effects, nanoparticles such as quantum dots, iron oxide nanoparticles, and gold nanoparticles have recently been very useful in gastrointestinal cancer imaging. Studies using nanoparticles in conjunction with conventional imaging techniques for gastrointestinal cancers have greatly increased the rate of early diagnosis and staging accuracy .Especially as nanotechnology develops very fast, some nanoprobes combined with NIRFI and photothermal therapy or photodynamic therapy have been designed and developed for imaging directed therapy of gastrointestinal tumors and have clinical translation prospects . TherefoAs shown in In this review, we evaluated the most recent NIRFI developments in gastrointestinal cancer, including a near-infrared endoscopic imaging system, early tumor detection, and gastrointestinal tumor surgery. These techniques have great application prospects in improving the diagnostic rate and the effect of surgical treatment of gastrointestinal tumors. The near-infrared endoscope imaging system can recognize small lesions that the traditional white-light endoscope cannot detect and can conduct real-time navigation in surgery. Combining NIRFI with more other modes is a new tendency for the near-infrared endoscopic imaging system. By integrating the advantages of multiple imaging modes, better imaging effect can be achieved. For cancer detection, NIRFI-assisted diagnosis has been actively applied for various gastrointestinal tumors, but the development of targeted fluorescent molecular probes has limited the development of imaging technology. Future research should concentrate on developing novel probes that can be paired with tumor targets. For the application of ICG in gastrointestinal surgery, there are many cases of using ICG in the surgical guidance of esophageal cancer, gastric cancer, and CRC, which has very good application prospects. However, the research on the quantitative standard of surgical guidance is still insufficient.In summary, NIRFI has been actively explored to apply in theranostics of gastrointestinal tumors and has made great advances; it will have better application prospects in precise theranostics of gastrointestinal tumors in the near future. We believe that NIRFI can reduce the threat of gastrointestinal tumors to human health and provide opportunities to improve the quality of human life as the rapid development of NIRFI technology is integrated with new targeted nanoprobes.N.Q.S., C.Z., and N.T. were involved in the initial drafting of the manuscript; X.C. selected the figures; and D.X.C. suggested writing this review and revised the manuscript. All authors were involved in the final approval of the manuscript.


Drosophila and mammalian systems, and is recognized for its pivotal role in regulating cellular proliferation, control of organ size, and embryonic development. During the process of follicle development, the components of the Hippo pathway show temporal and spatial variations. Recent clinical studies have shown that ovarian fragmentation can activate follicles. The mechanism is that the mechanical signal of cutting triggers actin polymerization. This process leads to the disruption of the Hippo pathway and subsequently induces the upregulation of downstream CCN and apoptosis inhibitors, thereby promoting follicle development. Thus, the Hippo pathway plays a crucial role in both the activation and development of follicles. In this article, we focused on the development and atresia of follicles and the function of Hippo pathway in these processes. Additionally, the physiological effects of Hippo pathway in follicle activation are also explored.The follicle is the functional unit of the ovary, whereby ovarian development is largely dependent on the development of the follicles themselves. The activation, growth, and progression of follicles are modulated by a diverse range of factors, including reproductive endocrine system and multiple signaling pathways. The Hippo pathway exhibits a high degree of evolutionary conservation between both  The ovary is a complex, dynamic structure that undergoes extensive tissue remodeling throughout each reproductive cycle. This periodic remodeling includes follicular formation and atresia, ovulation, formation and regression of the corpus luteum (CL), and accompanying changes in the vascular system and microenvironment, which are essential factors for maintaining normal reproductive function . The ovaOvarian reserve refers to the quantity and quality of remaining oocytes in the ovary, which is the basic indicator of female fertility . Human fAlthough the endocrine system  exerts a critical influence over follicular development and atresia, more and more pathways are also found to be involved in this regulation . The intMammalian oocytes mature in the follicles, which serve as the fundamental units of the ovary. Consequently, ovarian development is fundamentally dependent on follicular development . OvarianFirst, proliferating PGCs migrate to the nascent genital ridge, differentiate into oogonia, which are encapsulated by a single layer of follicular epithelium or granular cells (GCs), and subsequently enter meiosis to become primary oocytes . The priDuring follicular growth, the volume of oocytes can increase by 100–300 times and stop at the preantral stage. Furthermore, it has been observed that the quantity of granulosa cells surrounding oocytes exhibits a gradual increase , and at The maturation of oocytes includes cytoplasmic and nuclear maturation, which must be completed to enable gametes to obtain developmental ability . The nucIt is well known that oocytes not only provide genetic information to developing embryos, but also provide them with energy, nutrients, and mtDNA sets . The difDuring follicular development, most follicles undergo a degenerative process of atresia, which makes the primordial follicles continuously depleted . FollicuDrosophila melanogaster  are expressed in follicles at different stages . CorrelaSav1 gene by small interfering RNA (siRNA) can disrupt the Hippo pathway, leading to elevated YAP activity and subsequently promote proliferation of granulosa cells , steroidogenic acute regulatory protein (STAR), estrogen receptor (ESR), etc. , etc. . At the  and ESR .in vitro, the low expression of yap inhibited follicle growth, whereas overexpression of Yap resulted in follicle activation as indicated by decreased primordial follicle number and increased secondary follicle number  to form AP axis polarity of oocyte compartment. Several signaling pathways in the polar follicle cells (PFCs) are essential for the establishment of dorsal-ventral polarity during mid-oogenesis. These pathways include JAK/STAT, EGFR, Notch, and Hippo  and dorsal-ventral axes, and follicular cell differentiation along the AP axis is a critical step in the normal development of the egg chamber and the establishment of oocyte polarity . Yu et and Hippo . One of nd Hippo . In non-nd Hippo . In contnd Hippo .Yap1 gene in bovine granulosa cells in vitro has demonstrated a marked decrease in FSH-induced E2 production, with an 80% reduction observed in comparison to the control group  and FSHβ (Fshb)]. The transcription of Fshb is mainly regulated by TGFβ superfamily ligands, the most prominent of which is activin . ActivinIn vitro treatment of bovine granulosa cells with vetiporfin, a YAP1/TEAD inhibitor, the downregulation of CTGF downstream of YAP1 and a decrease in epidermal growth factor receptor mRNA abundance were observed  in mice promotes the expression of Akt and/or mTOR  of follicles, ovarian fragmentation  followed by IVA drug treatment (AKT stimulation). Successful pregnancies have been reported after transplantation of small ovarian fragments exposed to PI3K/Akt activators into patients diagnosed with POF  increases the activity of Yki. Both Hh signaling and Yki positively regulate the rate of FSC proliferation  inhibits Hippo activity, which impairs the formation of the Hpo-Wts signaling complex, thus increasing the expression of Yki in nucleus.There are few studies investigating the mechanism of Hippo and Hh interaction in the human ovary, and there is evidence for an association between the Hippo and Hh pathways in medulloblastoma . Activatferation . Li et aYap1 overexpression, and Notch2, identified as the targeted gene of YAP1-TEAD complex, was expressed at high levels in the cell membrane and GCs of ovarian follicles (Drosophila ovaries and that the SWH signal is involved in Notch-dependent maturation of the PFC.Regarding the association of Hippo and Notch pathway, related studies have found that in the intestinal canal, activated YAP1 transcription upregulates Notch receptor expression, leading to an increase of Notch signaling activity . Severalollicles . MeigninThe mechanism of Hippo pathway and the crosstalk of several pathways to regulate ovarian development is complex and diverse, so a large number of experimental studies are still needed to confirm.Hippo pathway and its downstream transcription effector YAP/TAZ have emerged as key regulatory players in ovarian development and function, regulating the proliferation and migration of ovarian germ cells and somatic cells, follicular activation and development, and cell apoptosis. This article elucidates the process of ovarian development and the function and molecular mechanism of Hippo pathway in it. However, ovarian development and regulatory mechanisms are complex, and Hippo pathway intersects with other pathways that regulate follicular development, and is affected by ovarian endocrine and metabolic regulation. Therefore, further experimental research is still needed to clarify the localization and regulatory mechanism of Hippo pathway molecules at various stages of follicular development, which is of great significance for clinical treatment of various ovarian diseases.


Non-coding RNAs (ncRNAs) are involved in the occurrence and development of PCa and the response to PCa treatment. ncRNAs are known to execute diverse regulatory roles in cellular processes, despite their inability to encode proteins. Among them, microRNAs, long non-coding RNAs, and circular RNAs play key roles in the regulation of the Wnt signaling pathway in PCa. Aberrant expression of these ncRNAs and dysregulation of the Wnt signaling pathway are one of the causes of cell proliferation, apoptosis, invasion, migration, and angiogenesis in PCa. Moreover, these ncRNAs affect the characteristics of PCa cells and hold promise as diagnostic and prognostic biomarkers. Herein, we summarize the role of ncRNAs in the regulation of the Wnt signaling pathway during the development of PCa. Additionally, we present an overview of the current progress in research on the correlation between these molecules and clinical features of the disease to provide novel insights and strategies for the treatment of PCa.Prostate cancer (PCa) is one of the most common cancers in males, exhibiting a wide spectrum of clinical manifestations that pose challenges in its diagnosis and treatment. The Wnt signaling pathway, a conserved and complex pathway, is crucial for embryonic development, tissue homeostasis, and various physiological processes. Apart from the classical Wnt/β-catenin signaling pathway, there exist multiple non-classical Wnt signaling pathways, including the Wnt/PCP and Wnt/Ca In males, prostate cancer (PCa) is one of the most common cancers and the fifth leading cause of cancer-related deaths . Accordi2+ signal transduction  have been recognized as critical regulatory factors in gene expression and signal transduction in both normal physiology and disease pathogenesis, particularly in PCa . ncRNAs In conclusion, our review presents a comprehensive elucidation of the intricate interplay between ncRNAs and the Wnt signaling pathway in the context of PCa occurrence, progression, and therapeutic approaches. Significantly, we underscore the profound implications of ncRNAs as promising diagnostic and prognostic biomarkers, accentuating their pivotal role in modulating PCa aggressiveness and therapeutic response. Moreover, we delve deep into the immense potential of targeting ncRNAs as therapeutic interventions for PCa, exploring a plethora of strategic avenues. Finally, we address the contemporary challenges encountered in this ever-evolving field.2+ signaling pathways  signaling pathway, is gaining recognition as a key factor in the pathogenesis of PCa . This prThe dysregulation of ncRNAs has been associated with the occurrence and progression of PCa . Recent Despite the aforementioned findings, the molecular mechanism of the regulation of the Wnt signaling pathway by ncRNAs in PCa is not entirely understood, and additional investigations are required to elucidate the complex interplay between various types of ncRNAs and other regulatory factors that activate or inhibit the Wnt signaling pathway in PCa. Furthermore, the investigation of ncRNAs poses technical challenges, owing to their low abundance and high sequence variability . AdvanceThe Wnt signaling pathway plays a key role in the progression of PCa, with ncRNAs as crucial regulatory factors of this pathway . Recent miRNAs are RNA molecules that are 22 nucleotides in length and regulate gene expression by binding to complementary target messenger RNAs (mRNAs) . The tisLncRNAs are RNA molecules that are 200 nucleotides in length and do not encode proteins . AlthougCircRNAs were first discovered in plant viruses and the Sendai virus through electron microscopy in 1976 . HoweverMetastasis is the primary cause of most cancer-related deaths . InvasioLi et al. demonstrated that miR-1297 directly targets the 3′-untranslated region of AEG-1 and regulates its mRNA and protein expression levels . In addi+ cells during IL-6-induced PCa cell progression, thereby suppressing cell proliferation, cell cycle progression, and invasion  in diameter and originate from endosomes . Many stEarly detection of PCa is crucial for effective treatment and improved survival rates . For exaEarly screening and diagnosis of cancer are crucial for patient survival . The idePatient prognostic information is essential in the process of making informed treatment decisions . MountinCancer treatment has long been regarded as one of the most formidable challenges worldwide, despite the progress made in treatment modalities . TargeteTargeting ncRNAs has been considered an attractive strategy for cancer treatment . In addiChemoresistance is a notable concern in cancer treatment, and enhancing chemosensitivity in PCa through ncRNA intervention has become a strategy that is increasingly being recognized and investigated . Targetiin vivo has hindered their potential clinical application, necessitating the exploration of more reliable strategies to target ncRNAs.This review provided a comprehensive overview of the role of the Wnt signaling pathway and related ncRNAs  in PCa. MiRNAs affect the expression of target genes associated with the Wnt signaling pathway. Additionally, the Wnt signaling pathway establishes feedback mechanisms and functions as an upstream mediator of miRNAs. In most cases, lncRNAs regulate the expression of proteins in the Wnt signaling pathway by serving as sponges for miRNAs. CircRNAs also regulate the expression of the Wnt signaling pathway; however, similar to lncRNAs, they primarily regulate the expression of the Wnt signaling pathway by targeting miRNAs. We also discussed the novel avenues for the development of siRNAs and shRNAs that target the Wnt signaling pathway and their potential clinical applications. However, the limited efficacy of siRNAs and shRNAs Although the regulation of the Wnt signaling pathway through ncRNA intervention is a promising avenue for the treatment of PCa, certain issues need to be addressed. First, the Wnt signaling pathway is highly intricate, consisting of 19 distinct types of Wnt-secreted glycoproteins and over 15 types of Wnt receptors in humans, which activate various downstream pathways. Second, the differences and balance between the classical and non-classical Wnt signals are difficult to capture, making targeting the Wnt signaling pathway even more challenging. Third, the Wnt signaling pathway plays a fundamental role in the dynamic balance of systems, such as the digestive and hematopoietic systems; therefore, blocking the Wnt signaling pathway may lead to systemic toxicity. Hence, modulation of the Wnt signaling pathway as a therapeutic strategy for PCa is both an opportunity and a challenge, warranting further research. In the future, it will be necessary to conduct additional investigations of the interplay between the Wnt signaling pathway and ncRNAs and develop more reliable methods for targeting ncRNAs for their clinical application. Simultaneously, alternative therapeutic strategies for PCa should also be explored to improve the efficacy of treatment and the quality of life of patients.


This study uses experimental methods, theoretical research, and numerical prediction to study the dynamic mechanical properties and damage evolution of CFRP laminates at ultra-low temperatures. Based on the Split Hopkinson Pressure Bar (SHPB) device, we set up an ultra-low temperature dynamic experimental platform with a synchronous observation function; the dynamic mechanical properties of laminates were tested, and the damage evolution process was observed. The experimental results are as follows: The compression strength and modulus increase linearly with the increase in strain rate and show a quadratic function trend of increasing and then decreasing with the decrease in temperature. The damage degree of the dynamic bending sample increases obviously with the impact velocity and decreases first and then increases with the decrease in temperature. Based on the low-temperature dynamic damage constitutive, failure criterion, and interlayer interface damage constitutive of the laminates, a numerical model was established to predict the dynamic mechanical properties and damage evolution process of CFRP laminates at ultra-low temperatures, and the finite element analysis (FEA) results are consistent with the experimental results. The results of this paper strongly support the application and safety evaluation of CFRP composites in extreme environments, such as deep space exploration. Due to their remarkable advantages, such as high specific strength, elevated impact resistance, light weight, and low-cost manufacturing, CFRP composites have been widely used in critical fields, including aerospace, the automotive industry, and rail transit in recent years ,2,3. WitUnder ultra-low temperatures, researchers conducted static mechanical experiments on the CFRP laminates, such as tensile, compression, and three-point bending ,7,8,9. Tearchers ,16 used The prediction of mechanical properties and the damage evolution of composites using constitutive models and FEA is an essential direction for future research. Wysmulski et al. ,18,19 esIn this paper, the dynamic mechanical properties and the damage evolution of CFRP laminates at ultra-low temperatures are studied using experimental methods, theoretical research, and numerical prediction. Firstly, based on the SHPB device, we set up an ultra-low temperature dynamic experimental platform with a synchronous observation function; the dynamic mechanical properties of CFRP laminates were tested, and the damage evolution process was observed. Secondly, the low-temperature dynamic constitutive model of CFRP laminates was established by introducing the strain rate and temperature effect into the classical constitutive model of laminates. Then, we also considered the 3D Hashin criterion and the interlayer interface damage constitutive based on the bilinear cohesive zone model. Finally, according to the theoretical model mentioned above, the numerical prediction model was established to predict the dynamic mechanical properties and damage evolution process of CFRP laminates at ultra-low temperatures, and the FEA results are consistent with the experimental results.Based on the SHPB device, we independently set up an ultra-low temperature dynamic experimental platform with a synchronous observation function. The schematic diagram of some critical equipment of the platform is shown in 2s. Then, vacuum package the mold containing prepreg. Finally, push the mold into the autoclave and cure it according to the specific curing curve 〈σn〉employed :(15)GC=GFEA is widely used to evaluate the mechanical properties and failure behavior of fiber-reinforced composites because it can provide full-field stress and strain distribution at a low cost. According to the actual size of the dynamic compression and bending samples, the commercial analysis software ABAQUS 2017 was used to establish the finite element model of laminates. As shown in According to the static mechanical experimental results of the single-layer plate at different temperatures , the temBased on the proposed dynamic constitutive model introducing temperature and strain rate effects, user subroutine VUMAT was developed and implemented in FEA models containing the failure criterion, damage evolution, and interlayer interface damage constitutive. The classical step-by-step iterative method in strain incremental forms was used. After each incremental step, the stress states of the elements were updated and examined under the failure criterion. When the failure criterion was met, the damage variable was called, and the element stiffness degenerated to describe the occurrence of damage. The calculation flowchart of ABAQUS calling user subroutine VUMAT is shown in According to the original data of the dynamic compression experiment, the equations provided by Ref.  can calcAs shown in In the dynamic bending experiment, only the samples with an impact velocity of  in Ref. , as show.In this study, the dynamic mechanical properties of CFRP laminates at ultra-low temperatures are systematically studied through experimental testing, a theoretical model, and simulation analysis, and the damage evolution process is discussed. There are the following important conclusions:We independently designed the observable cryogenic box and improved the Hopkinson bending bar. Based on the SHPB device, we set up an ultra-low temperature dynamic experimental platform with a synchronous observation function; the dynamic mechanical properties of CFRP laminates at ultra-low temperatures were tested, and the damage evolution process was observed simultaneously. The experimental results are as follows: CFRP laminates exhibit a noticeable strain rate effect during dynamic compression; the compression strength and modulus increase linearly with the increase in strain rate and show a quadratic function variation trend of first increasing and then decreasing with the increase in temperature. The damage degree of the dynamic bending sample increases obviously with the increase in impact velocity and decreases first and then increases with the decrease in temperature, and the damage degree is minimum at Based on the ultra-low temperature dynamic constitutive, failure criterion, and interlayer interface damage constitutive of CFRP laminates, a numerical prediction model was established to predict the mechanical properties and damage evolution process of the dynamic compression and bending of CFRP laminates at ultra-low temperatures. The predicted results of the relationship between the dynamic mechanical properties and strain rate and temperature agree with the experimental results. The FEA results of the damage evolution process of CFRP laminates are basically consistent with the experimental observations.


Climate change accelerates or enhances the incidence of a variety of abiotic and biotic stresses on agricultural and forest productivity. By changing different aspects of agriculture management, we can lower the risk of climate change over plant-derived productivity, including food, fiber, and bioenergy.Legumes (Fabaceae) is the third largest family of flowering plants, with more than 20000 species. They play central roles in  food and plant-based protein production. Legume crops emit fewer greenhouse gases , allow more sequestration of carbon in soils, and save fossil energy inputs in the system by reducing N fertilizer needs. In intercropping systems, legumes may facilitate circulation of soil nutrients , water retention and availability, and breaking pest and disease cycles, depending on the climate, soil, and management of agro-ecosystems in which they are included .Mutualistic relationships of legumes with either bacteria or fungi have been investigated intensively, usually as bi-partite interactions. Their collective contribution to plant growth and performance appears to be affected by crop genotype, microbial interactions, and environmental variables. However, diverse symbiotic and mutualistic interactions take place simultaneously or sequentially under field conditions . The intOverall, the legume holobiome (legume and its microbiome as a unit) is a promising tool to mitigate the climate change impact while addressing the need for healthy and nutritious food for a rapidly growing population. The challenge is to understand the dynamics of the legume-intercrop-microbiome-soil system and use those insights as a solid basis for developing new integrated technologies and practices. In addition, with the rapid development of the bioinput market, a comprehensive evaluation of the impact of the exogenously introduced microbes on the native microbiota is urgently needed.on Legumes and their Microbiome in Climate Change Mitigation consists of 4 publications: 2 original research articles and 2 reviews, on three main topics: breeding, intercropping, and microbiome. One of the articles reviews the relevance of studying and improving underutilized legumes, such as Bambara groundnut, considering them as an holobiome. Another article reports how soil water availability affects the competitiveness of a co-dominant legume Lespedeza davurica in an intercropping system, and the last two articles focus on the effect of beneficial bacteria, studying how the beneficial bacteria Pseudomonas monteilii could protect the forest plantation of Dalbergia sissoo from mortality caused by fungi, and the effect of rhizobia inoculation and P fertilizer increasing yield of three grain-legumes in a meta-analysis.This Frontiers in Plant Science virtual Research Topic As summarized below, each paper ties legume crops and their microbiome with some climate change-derived challenges.Ajilogba et al. highlight the agronomic and nutritional advantages of Bambara groundnut (Vigna subterranea) which is the third most-eaten legume in sub-Sahara Africa. It has wild and cultivated varieties with a high ability to tolerate drought, grown in marginal soils, and large genetic variability to improve the crop. The authors emphasized the need to improve this type of underutilized legumes preserving the interaction with their microbiomes, which must complement the use of the major crops shortly in the context of climate change.Breeding programs have been largely developed in plants’ optimal growing conditions, losing some relevant genes for the interaction of the crops with beneficial microorganisms . AjilogbXu et al. studied the effect of soil water availability in the intercropping system formed by the two native forage species from China: the legume Lespedeza davurica and the grass Bothriochloa ischaemum. The higher water availability produced a higher increase in the herbaceous grass biomass when in mixtures, indicating that the legume presence improved the yield of the grass. The more stable ratio of both species in a mixture was obtained at 10:2 (B. ischaemun: L davurica) when their intra- and interspecific competitiveness tended to be equal, providing the highest water use efficiency and total relative yield.Intercropping is a good management tool to improve yields by combining mutual benefits for different species (such as grasses and legumes). Buernor et al. carried out an interesting meta-analysis over 33 publications conducted in Ghana, to review what is known about the effect of biological nitrogen fixers (BNF) and P fertilization on the yield of 3 legumes  in four agroecological zones of the region. The combined treatment with BNF and P fertilizer was the major yield driver in soybean, while genotype was the first factor for cowpea and peanut. Although in the three crops, the combined fertilization treatment was the most effective to increase yield, the highest average yield change was observed in cowpea. Results suggest that breeding programs and BNF inoculation technologies for groundnut and cowpea could largely benefit low-income farmers in Ghana, in comparison to soybean which present already good elite genotypes and effective inoculants.Considering the microbiome of legumes in further research is critical to improving the yield and quality of legume production, as much as crop protection. Srivastava et al. characterized the native bacteria, Pseudomonas monteilii MN759447, previously isolated from Shisham  forest ecosystem in the Western Himalayas. They aim to study a biocontrol agent for the dieback and wilt of the forest. The causal agent of the high mortality rates is unknow, but the pathogenic fungi Aspergillus calidoustus, Talaromyces verruculosus, Fusarium oxysporum, and Talaromyces pinophilus are present in the forest and P. monteilii showed antifungal effect against them. The strain was positive for siderophore production, and two pseudomonine derivatives were identified by LC-MS, supporting a potential use of the bacterial strain as a commercial product to improve the health and nutrition of the forest.On the other hand, MI, RA, and FL draft revised and approved the editorial text. All authors contributed to the article and approved the submitted version.