In the Ukraine crisis since 2022, the Russian army has adopted a wide range of strategies for medical support as required by the battlefield, including adjusting the ways of medical evacuation, increasing the number of medical institutions and personnel, optimizing the mechanism for medical supplies, improving rehabilitation and sanatorium facilities, enhancing military medical education and training, developing new health care equipment and field rescue techniques. This paper analyzes the characteristics and effects of these new strategies implemented by the Russian army.

In the era of rational molecular design of fusion proteins, linker selection has garnered significant attention as a critical determinant of construct functionality. Suboptimal selection of linkers may result in such structural perturbations as protein misfolding, reduced expression yields, and compromised bioactivity. Consequently, the strategic selection of linkers tailored to specific objectives of molecular design by optimizing spatial orientation, maintaining domain autonomy or enabling post-translational modifications has emerged as a pivotal research frontier. Given these challenges, this review outlines the common properties of linkers, ways of classification, and the functional-structural interplay in current applications. Furthermore, we propose context-dependent selection frameworks for therapeutic proteins, biosensors, and enzyme cascades, which can serve as a systematic methodology to guide linker optimization in next-generation fusion protein engineering.

In 2024, the U.S. Defense Advanced Research Projects Agency （DARPA） intensified its deployment and management of biotechnological defense applications that involved four major domains： combat effectiveness enhancement, biosecurity defense, development of military materials, and intelligent biotechnology. This paper conducts an in-depth analysis of DARPA′s 2024 biotech advancements to provide a reference for related research and development in China.

Uncontrolled hemorrhage is the leading cause of potentially survivable combat casualty death,dominated by non-compressible hemorrhage in the torso and junctional areas. Rapid hemostasis using war trauma dressings is the mainstay of treatment for such casualties. The article reviews the research progress of novel hemostatic dressings for war trauma,including novel improved dressings,multifunctional dressings,electrospinning wound dressings,and smart dressings in order to provide references for the research on war trauma dressings.

Objective To explore the neuroprotective effects of nicotinamide riboside against microwave radiation-induced brain injury in mice. Methods Mice were subjected to whole-body uniform microwave radiation （at a central frequency of 2.856 GHz,and average power density of 20 mW/cm⊃2; for 30 min）. After radiation,the mice received intraperitoneal injections of nicotinamide riboside chloride at doses of 250,500,or 1000 mg/（kg·d）. Behavioral performance was assessed using the open field test （OFT） and elevated plus maze （EPM）. Histopathological changes in the cortex （CTX）,hippocampus （HPC）,and hypothalamus （HT） were detected via hematoxylin-eosin （HE） staining. Levels of such pro-inflammatory cytokines as tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the CTX,HPC,and HT were measured using enzyme-linked immunosorbent assay （ELISA）. Proteomic analysis was performed to assess changes in protein expressions in the CTX. Results After microwave exposure,the exploratory behavior of mice was reduced,and the entries into the central zone and open arms were decreased （P<0.05）. Neuronal injuries were increased,and the levels of TNF-α and IL-6 were elevated （P<0.05）. Proteomic analysis indicated that differentially expressed proteins were mostly enriched through oxidative phosphorylation related pathways. NR interventions significantly ameliorated these alterations,as evidenced by increased exploratory behavior,reduced neuronal injury,decreased inflammatory cytokine levels （P<0.05）,and the reversal of expressions of dysregulated proteins,including zinc finger AN1-type domain-containing protein 5 （Zfand5）. Conclusion NR can alleviate brain injury and associated behavioral and neuroinflammatory alterations in mice induced by microwave radiation,which might involve the zfands and other key molecules.

Objective To investigate the effects of intermittent microwave irradiation on pathological structure and cognitive function of Alzheimer’s disease （AD） mice. Methods Forty C57BL/6J mice and another forty 5×FAD mice were randomly divided into the sham irradiation （sham-WT）,irradiation （MW-WT）,AD sham irradiation （sham-AD）,and AD irradiation （MW-AD） groups,with 20 mice in each. Mice underwent daily 1-hour microwave irradiation （900 MHz,40 Hz repetition rate） on an intermittent schedule： 2 weeks on,2 weeks off,and 2 weeks on again. The cognitive function of mice was assessed via behavioral experiments conducted both immediately and six weeks after irradiation. The expressions of phosphorylated tau（p-Tau） and β amyloid protein （Aβ） plaques were detected via immunofluorescence. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of key enzymes involved in Aβ production and neuroinflammatory factors in the brain tissue. Results Compared with the sham-WT group,the novel object recognition index and the novel arm recognition index in the sham-AD group were significantly reduced（P<0.05）, but those were significantly increased in the MW-AD group compared to the sham-AD group （P<0.05）. In addition,the levels of p-Tau and Aβ proteins in the brain of the MW-AD group were significantly decreased （P<0.05） while the levels of β-secretase and γ-secretase in the cortex were significantly increased （P<0.05）. The levels of CD68,tumor necrosis factor-α （TNF-α）,and interleukin-10 （IL-10） were also increased to varying degrees （P<0.05）. Conclusion Intermittent microwave irradiation （900 MHz,40 Hz） can ameliorate cognitive deficits and attenuate Aβ and p-Tau pathology in AD mice rather than inhibit the key secretases involved in Aβ production or the occurrence of neuroinflammation.

In military operational environments, soldiers are frequently exposed to the combined effects of multiple stressors, whether natural, physical or psychological, which combine to impact their physiological and psychological health. This paper elaborates stress among soldiers in military operational environments in terms of manifestations, underlying mechanisms and interventions. It has been found that the primary physiological mechanisms involve the activation of the hypothalamic-pituitary-adrenal （HPA） axis while psychological ones are related to cognitive appraisal and emotional regulation. Coping strategies for stress include stress assessment in soldiers, virtual reality（VR） simulation training and psychological interventions, such as cognitive-behavioral therapy, exposure therapy and mindfulness meditation. Subsequent research should focus on the psychophysiological interactiond under specific military stressors and development of personalized intervention programs, such as adaptive VR training protocols. These advancements are crucial to enhancing psychological resilience and preserving the overall combat effectiveness of military forces.

The increasing complexity of modern military operations has heightened research attention to the impacts of sleep restriction （SR） on soldiers’ combat effectiveness. This article analyzes SR-induced deficits in military performance, reviews global military countermeasures （spanning technical interventions to institutional safeguards）, and proposes actionable optimization frameworks for military sleep management.

Objective To find out about perceived stress, self-compassion, cognitive flexibility, and depression among young males at high altitudes, construct a relational model between perceived stress and depression, explore the relationship between perceived stress and depression, and examine the roles of self-compassion and cognitive flexibility. Methods Using the convenient sampling method, 733 young males from a high-altitude unit were surveyed via the general information questionnaire, the Chinese Perceived Stress Scale （CPSS）, the Cognitive Flexibility Inventory （CFI）, Self-Compassion Scale （SCS） and Center for Epidemiologic Studies Depression Scales （CES-D）. Results （1）The CES-D score was 13.92±; 3.38. （2）Perceived stress was positively correlated with depression （r=0.28,P< 0.01）. （3）Self-compassion partially mediated the relationship between perceived stress and depression, accounting for 59.05% of the total effect. （4）Cognitive flexibility moderated the relationship between self-compassion and depression （P< 0.05）. Conclusion Young males at high altitudes exhibit notable levels of depressive symptoms. Perceived stress was significantly positively correlated with depression.By enhancing self-compassion and cognitive flexibility, the incidence of depressive symptoms among young males in prolonged high-stress conditions can be reduced.

目的 军事无人机操作具有远程操控、轮班作业、长时间飞行等作业特点,操作人员容易产生疲劳、失眠、睡眠不足和睡眠质量降低等问题。对军事无人机操控员的睡眠质量和疲劳状况进行调查,为采取干预措施提供理论依据。方法 随机抽取无人机操控员107例,采用匹兹堡睡眠质量指数量表（PSQI）和疲劳量表（FS-14）对睡眠质量和疲劳状态进行评估。结果 无人机操控员睡眠障碍检出率为28%;PSQI总分为（6.21±2.67）分,显著高于国内普通成人群和歼击机飞行员（P<0.01）,但与运输机飞行员得分无统计学差异（P>0.05）;高原地区无人机操控员PSQI总分显著高于平原地区（P<0.05）。无人机操控员在体力疲劳、脑力疲劳和疲劳总分3个维度均低于歼击机飞行员,但无统计学差异（P>0.05）。相关分析结果显示,PSQI总分与体力疲劳、脑力疲劳和FS-14疲劳总分均呈显著正相关。结论 军事无人机操控员睡眠状况需重点关注,不同飞行作业类别对睡眠和疲劳的影响程度不同,有必要开展战训现地客观检测及相关保障措施研究。

Modern warfare poses a severe challenge to medical support so that portable, efficient, and real-time battlefield diagnostic technologies are needed desperately. This review focuses on wearable ultrasound devices by summarizing their applicability and developments in military medical support. This article analyzes the advantages unique to flexible transducers, portable acquisition of data, and wireless communication as well as ways in which such technologies revolutionize the immediate diagnosis of combat injuries （such as craniocerebral and thoracoabdominal trauma and fractures） and daily health monitoring （including musculoskeletal injuries and cardiovascular assessments）. The article also offers insights into the critical challenges facing imaging quality, data processing, and energy supply endurance in order to clarify the significant implications of this device for enhancing the timeliness of battlefield casualty care, optimizing the allocation of medical resources, and safeguarding soldiers’ health. Furthermore, this study points to the need for intensified research and development of hardware design and intelligent algorithms to accelerate the related applications in military medicine.

Objective To establish a rapid detection method for Clostridium botulinum in food. Methods A rapid detection method based on RPA-CRISPR/Cas12a was developed by integrating recombinase polymerase amplification （RPA） with the CRISPR-Cas12a system. After the reaction conditions were optimized,the method′s sensitivity,specificity,and usefulness were methodically confirmed. Results and Conclusion The optimized method achieved detection within 1 hour,with a limit of detection （LOD） of 1.91 copies/µL. No cross-reactivity was observed with non-target pathogens. The RPA-CRISPR/Cas12a-based detection method developed in this study exhibits high specificity,sensitivity,and operational simplicity and may provide a feasible solution for the rapid detection of foodborne pathogens.

Objective To investigate the direct stimulatory effects of calprotectin S100A8/A9 on hepatic stellate cells （HSCs） and underlying regulatory mechanisms. Methods Primary HSCs of mice were stimulated with S100A8/A9 heterodimer recombinant protein at 200 and 1000 ng/mL. Data on quantitative proteomics was obtained using the tandem mass tag （TMT）-labeled method before changes in the protein level of HSCs were analyzed. Differentially expressed proteins （DEPs） were screened using Significance B method and P< 0.05, followed by Reactome pathway enrichment analysis. Furthermore, protein-protein interactions between the DEPs enriched in the pathways were analyzed using the STRING database. Results The protein expression profile of HSCs was significantly altered after treatment with S100A8/A9 at 1000 ng/mL. Reactome pathway enrichment analysis revealed significant enrichment in such pathways as transforming growth factor-beta （TGF-β） signaling, nuclear factor kappa-B （NF-κB） signaling activation, cytokine-mediated immune regulation, and collagen biosynthesis. The analysis of protein-protein interactions identified NF-kappa-B transcription factor subunit （RELB）, chemokine （C-X-C motif） ligand 10 （CXCL10） and Notch receptor 1 （NOTCH1） as key hub proteins in the regulatory network. Conclusion S100A8/A9 can directly stimulate the activation of HSCs, through NF-κB signaling, TGF-β signaling, and Notch signaling pathways potentially. This study sheds light on the mechanisms underlying the activation of HSCs stimulated by S100A8/A9.

Objective To explore the role of dapansutrile （OLT1177） in radiation-induced intestinal injury and the mechanism. Methods C57BL/6J mice were locally irradiated in the abdomen with ⁶⁰Co to induce a model of radiation-induced intestinal injury. OLT1177 was intraperitoneally injected at a dose of 100 mg/kg 2 hours before irradiation and 6 hours after irradiation before the drug was administered once a day. At 12 hours after irradiation, intestinal tissues were taken for terminal deoxynucleotidyl transferase mediated nick end labeling（TUNEL） staining to detect apoptosis in intestinal tissues. At 4 days after irradiation, mouse serum was collected to detect the levels of inflammatory factors in the serum. Hematoxylin-eosin （HE） stainingwas used for the evaluation of the damage to the intestinal villus structure. Immunohistochemical staining was adopted to detect the changes in crypt proliferation in intestinal tissues. Finally, proteins were isolated from intestinal tissues, and Western blotting was employed to evaluate the activation of nucleotide-binding oligomerization domain-like receptor protein 3（NLRP3） inflammasome. Results After irradiation, the intestinal villi in mice were shortened. Meanwhile, there was a notable declinein the number of cells that were proliferating in the crypts, a surge in the number of apoptotic cells, and a significant spike in the overall inflammatory level. However, administration of OLT1177 inhibited the activation of the NLRP3 inflammasome, reduced apoptosis and pyroptosis, decreased the inflammatory level, and thus improved radiation-induced intestinal injury. Conclusion Administration of OLT1177 can significantly mitigate radiation-induced intestinal injury.

Objective To analyze the incidence of acute radiation dermatitis （ARD） induced by postoperative adjuvant radiotherapy in breast cancer patients during and after radiotherapy,and to explore the contributors to ARD so as to provide data for formulating phased and individualized prevention and management strategies. Methods A convenient sampling method was used to select 98 patients as subjects who had undergone postoperative intensity-modulated radiation therapy （IMRT） for breast cancer between June 2022 and June 2023. According to the grading criteria for Radiation Therapy Oncology Group （RTOG）,the occurrence and severity of ARD in patients during radiotherapy （once a week） and within 6 weeks of radiotherapy （once a week） were dynamically evaluated. The clinical data of the patients was collected. Chi-square test was used for univariate analysis,and Logistic regression analysis was conducted to screen independent contributors. Results Among the 98 patients,96 developed ARD above grade 0,with an overall incidence rate of 97.96%. The incidence rate was 74.5% （73/98） during radiotherapy and 23.5% （23/98） after radiotherapy. ARD was likely 3 to 5 weeks into radiotherapy and 2 weeks after radiotherapy. Univariate analysis showed that age and menopause were significantly correlated with the occurrence of ARD （P<0.05）. Multivariate Logistic regression analysis suggested that age <60 years old during radiotherapy was an independent risk factor for ARD （OR=0.272,95%CI 0.091-0.816,P=0.020）,so was menopause after radiotherapy （OR=3.057,95%CI 1.120-8.344,P=0.029）. Conclusion The overall incidence of ARD is high among breast cancer patients after postoperative radiotherapy,and varies by age. Young patients have a higher risk of ARD during radiotherapy while menopausal ones have an increased risk of ARD after radiotherapy. Clinically,phased prevention and control strategies should be implemented for high-risk groups in different periods to reduce the harm of ARD and improve the radiotherapy prognosis of patients.

Objective To establish a model that integrates ultrasound features and immunological characteristics for predicting the efficacy of neoadjuvant chemotherapy （NAC） in breast cancer patients. Methods A total of 203 breast cancer patients undergoing preoperative NAC at the Fifth Medical Center of the PLA General Hospital between July 2021 and July 2024 were screened. In line with the inclusion/exclusion criteria, 177 patients were included. Data on ultrasound and immunohistochemistry was collected. These patients were divided into pathological complete response （pCR） and non-pathological complete response（non-pCR） groups based on postoperative pathology. Factors with P<0.01 in univariate analysis were evaluated using multivariate Logistic regression. Independent predictive factors were used to construct and validate the ultrasound-immunohistochemical model via Bootstrap. Results The reduction rateof the maximum diameter of lesions, posterior echo attenuation, PR status and HER-2 status were identified as independent predictors of pCR （all P<0.05）. The model proved to be highly accurate and stable. Conclusion The model that combines ultrasound and immunohistochemical features can effectively evaluatep CR after NAC in breast cancer patients.

Osteoporosis is a globally prevalent metabolic bone disease, with bone homeostasis imbalance being its key pathogenic mechanism. Over the years, studies on the relationship between ambient temperature and bone health have shown heterogeneous results due to different conditions. Epidemiological studies indicate that the incidence of osteoporotic fractures varies geographically and climatically. People in cold regions experience earlier bone loss, and high-latitude cold areas are high-risk zones for hip fractures. Osteoporosis is more prevalent in North China that in South China. Additionally, the early stage of the disease is insidious, highlighting the need for early prevention and treatment across the entire population. Mechanistically, low temperatures affect acral bone development, reduce bone blood circulation, cause degradation of bone microstructure, and increase osteocyte apoptosis, thereby promoting bone resorption and reducing bone mass. This review aims to provide data and new lines of thought for the early precise prevention and effective clinical treatment of osteoporosis in cold regions.

Objective To develop an ultra high performance liquid chromatography-mass spectrometry （UPLC-MS） method for quantifying serum levels of norepinephrine （NE） and 5-hydroxytryptamine （5-HT）,and to monitor the dynamic changes in these neurotransmitters during the process of establishing a model of acute reserpine-induced depression-like mice. Methods By evaluating matrix effect,recovery,precision,and accuracy efficiency,an UPLC-MS method for determining the concentrations of NE and 5-HT in serum was established. Forty-eight C57 mice were randomly divided into normal control and model groups,which were intraperitoneally injected with physiological saline （10 mL/kg） and reserpine （2.5 mg/kg）,respectively. At various time points after intraperitoneal injection,the degree of ptosis and decreases in body temperature of the mice were observed before orbital blood was sample for the determination of NE and 5-HT levels. Results The concentrations of NE and 5-HT showed good linearity within the range of 15.63 to 2000.00 ng/mL,with R⊃2; values greater than 0.999. The results of methodological validation met the requirements for the analysis of biological samples,with a lower limit of quantification of 15.63 ng/mg. After intraperitoneal injection of reserpine,the model mice exhibited varying body temperature decreases and ptosis. At 1 and 2 h post-administration,the depression-like symptoms in the model group were significantly different from those of the normal control group （P<0.01）. The body temperature of mice in the model group was significantly lower than that of mice in the normal control group （P<0.01）,while the score of the eyelid ptosis was significantly higher （P<0.001）. The levels of NE and 5-HT in the serum of model mice were also significantly depleted,and were significantly different from those of the normal control group at 0.5,1 and 2 h （P<0.05）. Conclusion The study process of established a rapid and accurate method for dynamically observing the changes in NE and 5-HT levels during the process of establishing a model of acute reserpine-induced depression-like mice,which might contribute to the study of the pathogenesis of depression and the development of new antidepressant drugs.

Amid increasing globalization, the risk of vector-borne diseases has risen significantly, posing a huge threat to public health in China. This situation is particularly pronounced in the military. Military personnel, who are highly concentrated and engaged in cross-regional operations, are exceedingly vulnerable to an epidemiconce exposed to vector organisms, thus impacting their combat effectiveness and health. Effective vaccines or preventive medications for vector-borne diseases are lacking, so vector control has become critical to curbing the spread. This paper not only analyzes the epidemiology of vector-borne diseases in China amid globalization and urbanization, but also summarizes the advancements in novel vector-control strategies that are compared and contrasted with traditional approaches. The prevention and control of vector organisms requires long-term, systematic, and collaborated efforts. China should comply with the basic principles concerning sustainable vector management （SVM）. By strengthening the monitoring system, fostering inter-regional collaboration, and promoting new technologies and equipment, we can safeguard public health and the safety of military personnel and civilians.

Objective To find out whether photobiomodulation （PBM） can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate （ATP） and adenosine receptors. Methods Twenty-four C57BL/6J mice were randomly divided into a control group, a stress group, and a treatment group. Chronic unpredictable mild stress was used to establish a mouse model of stress. Six weeks into modeling, the treatment group was subjected to one week of PBM interventions. Behavioral tests were conducted to observe behavioral changes in the mice. Western blotting （WB） was used to detect the expressions of A1, A2B, and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups. Twelve C57BL/6J mice were randomly divided into a control group and an intervention group. The intervention group received a week of PBM interventions and underwent behavioral testing. WB was used to detect the expression changes of A1, A2B, and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups. Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups. The ATP assay kit made by Beyotime Biotechnology Co., Ltd. was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice. Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents. Results Mice in the stress group covered a similar distance to the control group, but finished far fewer platform crossings. There was no significant difference between the treatment group and the control group in the number of times of platform crossings, but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower, but were increased by PBM. After PBM interventions in normal mice, platform crossings were increased significantly compared to the control group. PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex, and increased hippocampal c-Fos expressions. In vitro, PBM elevated intracellular ATP levels. Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions, thereby modulating neuronal responsiveness in the hippocampus.

Battalion aid stations usually serve as the critical bridge between medical rescue and early treatment, whose treatment efficiency will make a huge difference in the survival rate of casualties on battlefields in the future. This paper reviews the evolution of the functions of U.S. military battalion aid stations. By taking the U.S. Marine Corps and the 75th Ranger Regiment, this article elaborates on the practices by the U.S. military in the construction of battalion aid stations, and unveils the takeaways from the construction of the army battalion aid stations and their limitations. It is recommended that future battalion aid stations should set support tasks based on the need of medical services, optimize the make-up of battalion aid stations, improve their support capabilities and informatization, and provide better en-route treatment in order to ensure battalion aid stations can play a more important role.

Objective To evaluate the detection rates of sleep disorders among Chinese soldiers stationed in plateau regions，providing evidence-based support to inform future research and preventive interventions. Methods A comprehensive search was conducted across CNKI，WanFang Data，VIP Chinese Journal Database，Web of Science，and PubMed. The search encompassed studies from the inception of these databases up to August 1st，2024. The quality of the literature was assessed using the Agency for Healthcare Research and Quality（AHRQ） methodological checklist recommended by the Agency for Healthcare Research and Quality. Data extracted from the included studies were analyzed using R software （version 4.3.2） for Meta-analysis. A random-effects model was used to calculate the overall detection rate of sleep disorders and generate a forest plot，while subgroup analysis was performed based on the duration of high-altitude deployment in Chinese soldiers. Results A total of 1498 publications were retrieved，with 20 studies meeting the inclusion criteria. These studies comprised 11 991 soldiers stationed in plateau regions，among whom 3586 cases of sleep disorders were identified. The detection rate of sleep disorders among Chinese soldiers stationed in plateau regions was 36.8% ［95%CI（32.0%，41.5%）］. Subgroup analysis revealed that the detection rate was higher among soldiers stationed for less than one year，at 40.3% ［95%CI（33.5%，47.0%）］，compared to those stationed for more than one year，who had a detection rate of 30.0% ［95%CI（16.1%，43.9%）］. Conclusion The detection rate of sleep disorders in the soldiers stationed in the plateau regions is notably high. Soldiers who have been stationed for less than one year are more likely to susceptible sleep disorders. These findings underscore the need for effective preventive measures to address this issue.

Objective To assess the potential causal association between baseline red blood cell （RBC） indices and high-altitude adaptation （HAA） among low-altitude residents by using the two-sample bidirectional Mendelian randomization （MR） analysis. Methods A total of 82 healthy volunteers from the plains were enrolled to find out whether baseline RBC indices measured under normoxia were correlated with the percent change in hemoglobin （HGB） after 4 hours of simulated hypobaric hypoxia exposure. Summary-level data from genome-wide association studies （GWAS） were collected for RBC indices among 162,255 residents on the plains of East Asia,and for HAA among a combined cohort of 10,295 Tibetans and non-Tibetan individuals of Eastern Asian ancestry. A two-sample bidirectional MR analysis was conducted to assess the potential causal association between baseline RBC indices and HAA. Results Significant negative correlations were observed between baseline RBC,HGB,and hematocrit （HCT） under normoxia on one hand and the percent change in HGB on the other hand after 4 hours of simulated hypobaric hypoxia exposure. Furthermore,when the subjects were dichotomized based on the percent change in HGB,baseline RBC indices could accurately predict the percent change in HGB post-hypoxia exposure （AUC=0.8491,95%CI=0.8178-0.8804）. Forward MR analysis suggested that an inverse-variance weighted random-effects model supported a significant positive correlation of genetically predicted higher baseline HCT （odds ratio [OR]=1.023;95%CI=1.009-1.036;P=8.94×10^-4） and HGB levels （OR=1.027; 95%CI=1.011-1.043; P=7.02×10^-4） with HAA. Reverse MR analysis indicated no significant reverse causation between HAA and baseline RBC indices. Conclusion Genetically predicted higher baseline levels of HCT and HGB may be helpful in the initial stage of HAA.

Heart failure （HF） is a cardiovascular disease with a high prevalence and mortality rate worldwide, and despite the widespread use of existing drugs, device intervetions and surgical procedures, the clinical outcomes are still unsatisfactory.The exploration of new methods to treat HF is still an urgent problem. Gene therapy provides a new therapeutic strategy for HF by targeting the regulation of pathogenic genes. This article systematically reviewed the delivery system optimization, key targets and clinical translational challenges of gene therapy for HF, aiming to provide a theoretical basis for the optimization of treatment strategies.

Ricin is a plant protein toxin and is a type Ⅱ ribosome inactivating protein. Ricin contains two peptide chains, A and B. Chain B has a lectin function and is responsible for identifying cell surface sites while chain A has N-glycosidase activity, which can inactivate ribosomes and produce cytotoxicity. Ricin is simple to prepare and strongly toxic,so it can be used as a biological warfare agent to threaten human safety. So far, no specific antidote has been officially approved for marketing. In this paper, the in vivo transport process, mechanism of ricin and the research progress in antidotes are reviewed, which is expected to provide a reference for subsequent development of ricin-specific antidotes.

Objective To establish a rapid immunological detection method for MPT64 protein based on red microspheres and select highly-sensitive and highly-specific antibody pairs. Methods A His-tagged prokaryotic expression vector was constructed for expression of MPT64 protein that was used to immunize New Zealand white rabbits after purification and validation. Peripheral blood mononuclear cells （PBMCs） were isolated from the rabbits, and antigen-specific B cells expressing antibodies were sorted using single B-cell flow cytometry. mRNA in B cells was reverse-transcribed into cDNA, and paired antibody heavy- and light-chain sequences were amplified via nested PCR. Expression vectors were constructed, and recombinant antibodies were produced in Expi293F cells. Fluorescent immunochromatography was employed to screen for matched antibody pairs. The selected antibodies were used to establish a rapid detection method based on red microsphere immunochromatography. Results Ten high-affinity monoclonal antibodies against MPT64 were generated. Two antibody pairs were selected for MPT64 immunodetection that reached a sensitivity of 0.0125 ng/mL. Conclusion High-affinity rabbit monoclonal antibodies against MPT64 are obtained via single B-cell technology, and a rapid red microspheres-based immunodetection method is established, enabling highly sensitive detection of Mycobacterium tuberculosis MPT64 protein.

Hemorrhagic shock （HS） is a state of acute circulatory failure caused by massive hemorrhage that results in a sharp decrease in effective circulating blood volume and tissue hypoperfusion. HS easily triggers a series of complex pathophysiological changes, among which mitochondrial dysfunction is regarded as a key link. Mitochondria are the center of cellular energy production, which are involved in the regulation of apoptosis, oxidative stress response and immune regulation. With in-depth studies on the pathophysiological mechanism of HS, the role of mitochondria in HS has received more attention, but the mechanism of action remains elusive. This article reviews the pathophysiological characteristics, molecular regulatory mechanisms and research progress related to therapeutic drugs for mitochondrial injury after HS in order to contribute to subsequent research in this area.

Objective To establish a quantum dot immunochromatographic test strip for simultaneous detection of central nervous system-specific protein （S100β） and neuron-specific enolase （NSE）, thereby achieving combined detection of both biomarkers. Methods A double-antibody sandwich immunochromatographic assay was developed using S100β and NSE capture antibodies as the test line and species-specific secondary antibodies as the control line coated on the nitrocellulose membrane. Quantum dot bead-conjugated antibodies targeting S100β and NSE served as fluorescent probes. The preparation parameters of the strip were optimized, and its performance was systematically evaluated to develop a rapid diagnostic strip for mild traumatic brain injury （mTBI）. The diagnostic efficacy of the strip was further validated using clinical samples. Results The total assay time for combined detection of S100β and NSE was 17 min, with a limit of detection （LOD） of 0.1 ng/mL for S100β and 2.67 ng/mL for NSE. The inter-batch reproducibility of the strips was excellent （coefficient of variation, CV<15%）. In clinical validation using 24 mTBI samples, the combined detection strip demonstrated a specificity of 90% and a sensitivity of 92.86%, outperforming single-marker detection. These results prove that the simultaneous quantification of S100β and NSE enhances diagnostic efficacy for mTBI patients. Conclusion A combined detection method for the biomarkers S100β and NSE in mTBI, based on quantum dot immunochromatography, has been preliminarily established. This method demonstrates promising clinical application prospects in the auxiliary diagnosis of mTBI.

The U.S. Department of Defense （DoD） has made tremendous efforts to build up its biological defense capability in recent years, so that the annual biological defense budget accounts for 14% to 15% of the total of the U.S. government, which is closely related to the rapid development of biotechnology and its strategic significance during the rival between world powers. A second contributor is that the United States has been seeking hegemony in the biological field. In fiscal year 2019-2024, the expenditure/budget of the US DoD′s biological defense spikedwith the layout focused on early warning of threats, pathogen detection and response, and capability enhancement. This initiative is characterized by simultaneous implementation of multiple projects in a wide range of fields, strong synergy between different agencies, integration of military and civil resources, systematic planning of support systems for biological defense technologies.

Objective To design and synthesize dual-target antidepressant compounds possessing high-affinity binding to the serotonin 1A receptor （5-HT_1A） and dual-site synergistic inhibition of the serotonin transporter （SERT）. Methods Based on a dual-target synergistic mechanism, benzodioxolane derivatives were designed via scaffold hopping strategy before being synthesized. Their binding affinities to both targets were determined via competitive radioligand binding assays, and their binding modes were investigated using molecular docking. Results Eleven structurally novel target compounds were synthesized and structurally characterized by electrospray ionization mass spectrometry （ESI-MS） and nuclear magnetic resonance （NMR）spectroscopy. Compound 18b demonstrated dual nanomolar affinity for both the 5-HT_1A receptor （K_i=2.72 nmol/L） and SERT （K_i=8.85 nmol/L）. Molecular docking revealed that its inhibitory effect on SERT resulted from simultaneous occupation of the orthosteric site S1 （Asp98 salt bridge） and the allosteric site S2 （Arg104 π-cation interaction）, while its high affinity for 5-HT_1A depended on the Asp116^3.32 salt bridge anchor and π-π stacking with Phe362^6.52. Conclusion The benzodioxolane-scaffold compounds designed and synthesized in this study exhibited functional synergy between simultaneous occupation of both the S1 and S2 sites of SERT and high-affinity binding to the 5-HT_1A receptor. Among them, compound 18b demonstrates superior activity and promises to be a lead compound for more investigation.

Objective To elucidate the spatiotemporal dynamics of Kupffer cells （KCs） in acetaminophen （APAP）-induced acute drug-induced liver injury and their regulatory mechanisms governing regional hepatocyte regeneration. Methods A Clec4f-iCre & Rosa26-tdTomato lineage-tracing mouse model was established to specifically label KCs. Acute liver injury was induced via intraperitoneal injection of acetaminophen （APAP, 400 mg/kg）. Liver tissues and blood samples were collected at 0,1,2,3 and 7 days post-APAP administration. Histopathological examinations （H&E staining, TUNEL assay for apoptosis detection）, serum biochemical analyses （ALT and AST）, and immunofluorescence staining were employed to find out about the spatiotemporal migration patterns of KCs, their phenotypic transition, and spatiotemporal correlations between KC dynamics and hepatocyte regeneration. Results On day 1 （D1） post-APAP injury, extensive hepatocyte necrosis and apoptosis were observed in the pericentral （PC） zone, accompanied by a reduction in KCs count and their migration from the periphery toward the necrotic core. From D2 onward, repair started, with the necrotic area progressively decreasing. By D3, inflammatory cell infiltration was pronounced in the PC zone, concurrent with a peak in hepatocyte proliferation （Ki67⁺ cells： approximately 22%, P<0.05）. During repair, monocytes （CD11b⁺ IBA-1^-） differentiated into monocyte-derived macrophages （CD11b⁺ IBA-1⁺）, which synergistically promoted the regeneration of cytochrome P450 2E1（CYP2E1⁺） hepatocytes in the pericentral zone. By D7, the hepatic lobular architecture was largely restored, indicating the completion of reconstruction of metabolic zonation. Conclusion KCs can regulate hepatocyte regeneration through spatiotemporal dynamics and phenotypic transitions of monocyte-derived macrophages. These findings underscore the pivotal role of macrophage spatiotemporal reprogramming in liver injury repair and may provide data for developing macrophage-targeted therapeutic interventions in hepatic injury.

With the rapid development and widespread application of microwave technology, people's lives and work have been made more convenient. However, the health of those who are constantly exposed to complex microwave environments is also threatened. In recent years, many studies have found that long-term exposure to microwaves can cause damage to cognitive function. However, the damage mechanism has not been fully understood. This article reviews the research progress of microwave radiation on cognitive function in recent years, the damage mechanism, and the related drugs for protection and treatment, in order to provide references for research in this field.

Objective To investigate the functional changes of oligodendrocytes in a mouse model of cognitive impairment induced by microwave radiation and the mechanism. Methods C57BL/6N male mice were exposed to S-band microwave at 2.856 GHz and 8 mW/cm2 for 15 min. The rectal temperature of mice was monitored by an optical fiber thermometer during microwave radiation. The changes of autonomous exploration behavior and learning and memory ability of mice on the 1st and 7th days after microwave radiation were detected via the open field test and novel object recognition test. Immunofluorescence was used to detect the expression and distribution of neuroglia-2 proteoglycan （NG2） and myelin basic protein （MBP） in the hippocampus of mice on the 1st and 7th days after radiation. Clemastine fumarate,a drug that promoted the maturation of oligodendrocyte precursor cells was administered by gavage,and the expression levels of brain-derived neurotrophic factor （BDNF） and fibroblast growth factor 2 （FGF2） in hippocampal tissues were detected by radioimmunoassay at 1 and 7 days after radiation. The changes of myelin sheath structure an 1 and 7 days after radiation were observed by transmission electron microscopy. The effects of clemastine fumarate on learning and memory impairment induced by microwave exposure in mice were assessed via open field and new object recognition experiments. Results Under the experimental conditions,the rectal temperature in mice caused by microwave radiation increased by less than 1 ℃,which was within the thermal safety range of the body. The open field test showed that compared with the control group,the microwave radiation group didn′t change significant in terms of movement speedon the 1st and 7th days,but the time spent exploring in the central area was significantly reducedon the 1st day after radiation （P< 0.05）. In the novel object recognition test,the indexes of the mice on the 1st day were significantly reduced （P< 0.05）,indicating that the anxiety like behavior and cognitive function of the mice were impaired after microwave radiation. Compared with the control group,the proportion of NG2+ area in the hippocampus was significantly decreased （P< 0.05） in the microwave radiation group,while that of MBP+ area hardly changed on the 1st day after microwave radiation （P>; 0.05）. The expression level of oligodendrocyte related BDNF in the hippocampus was significantly decreased （P< 0.05）. The myelin of the corpus callosum was broken,and the myelin g ratio was significantly increased （P< 0.05）,suggesting that microwave radiation could reduce the number of oligodendrocyte precursors and damage the secretion and myelin function of oligodendrocyte. Compared with the radiation group,the expression levels of BNDF and FGF2 in the radiation combined with clemastine fumarate group were up-regulated,the myelin g ratio was significantly decreased on the 1st day after radiation（P< 0.05）,and the novel object recognition index was significantly increased （P< 0.05）. Conclusion Pulsed microwave radiation below the body's fever threshold can cause cognitive dysfunction and other brain damage in mice. The impaired secretion and myelin function of oligodendrocytes and the decreased self-repair ability are the important mechanisms of cognitive dysfunction induced by microwave radiation.

Objective To develop a new hemostatic material that is both highly efficient and cost-effective using mica and agarose as raw materials. Methods A porous mica-agarose composite gel sponge was prepared via direct cross-linking, followed by freeze-drying. The microstructure was characterized by scanning electron microscopy （SEM）. The influence of the mica content on pore size, water absorption, and volumetric swelling ratio was investigated. Hemostatic performance was assessed by measuring the hemolysis rate and blood clotting index, along with a mouse tail-amputation model. Results The prepared sponge exhibited a uniformly porous structure. Both water absorption and the volumetric swelling ratio increased with the mica content. However, excessive mica led to reduced stability of the pore structure. Biological evaluations revealed a hemolysis rate below 5% and a coagulation index of approximately 30%, suggesting favorable biocompatibility and effective hemostatic performance. Conclusion A composite hemostatic gel sponge based on mica and agarose has been developed, which promises wide applications in clinical hemostasis.

Objective To investigate the effects of insulin-like growth factor binding protein 7 （IGFBP7） on the sensitivity of glioma cells to temozolomide （TMZ） and the related mechanism. Methods IGFBP7 mRNA expression levels in TMZ-sensitive （U87 TMZ-S, U251 TMZ-S） and TMZ-resistant （U87 TMZ-R, U251 TMZ-R） glioma cells were analyzed using RNA sequencing data from the gene expression omnibus （GEO） dataset GSE151680. TMZ-resistant U87 and U251 cell lines were established via stepwise dose escalation. IGFBP7 expressions in TMZ-R cells were detected by quantitative real-time PCR （qPCR） and Western blotting. IGFBP7 was stably knock-downed in TMZ-R cells while IGFBP7 was stably overexpressed in TMZ-S cells using lentiviral infection. Cell viability, migration, invasion and TMZ sensitivity were assessed using CCK-8 assay, apoptosis assay,wound healing assay, Transwell invasion assay and colony formation assay respectively. Cellular senescence was detected by β-galactosidase （SA-β-Gal） staining. The expression levels of senescence molecular markers cyclin-dependent kinase inhibitor 1 （p21） and tumor protein p53 （p53）, as well as DNA damage marker γ-H2A histone family member X （γ-H2AX） were determined by Western blotting. The differences in mRNA expressions of IGFBP7 between glioma tissues and normal tissues as well as the correlations with the overall survival of glioma patients were analyzed using the cancer genome atlas （TCGA）,Chinese Glioma Genome Atlas（CGGA） ,genotype-tissue expression （GTEx） database. Results Compared to normal glioma cells,IGFBP7 expressions were significantly elevated in TMZ-R glioma cells. Overexpression of IGFBP7 in TMZ-S glioma cells enhanced cell viability but suppressed apoptosis following TMZ treatment. The expressions of senescence-associated marker （p21, p53） and DNA damage marker （γ-H2AX） were upregulated in these cells. Notably, IGFBP7 expressions were significantly higher in glioma tissues than in normal tissues, and high IGFBP7 expressions were associated with poor prognosis in glioma patients. Conclusion Knockdown of IGFBP7 promotes TMZ-induced cell senescence and DNA damage, thereby enhancing the sensitivity of gliomas cells to TMZ.

Objective To optimize an oxygen dissociation analysis （ODA） technology in order to evaluate the oxygen release capacity of hemoglobin-based oxygen carriers （HBOCs） rapidly and accurately. Methods The ODA procedures and statistical approach were optimized. In the course of preparation,HBOCs samples were oxygenated with air for 10 cycles （5 min/cycle ） to reach oxygen saturation. During the testing,N₂ was used at a rate of 20 L/min with a duration of 50 cycles to ensure utter deoxygenation. For statistical analysis,the oxygen release ratio and oxygen release capacity of HBOCs were calculated by using natural hemoglobin （Hb） as the benchmark. After method optimization,the coefficient of variation （CV） decreased from 0.10 to 0.03. The calculation of the oxygen release rate was introduced,and results were positively correlated with P₅₀,which was often used to represent the oxygen-carrying/release ability. Additionally,a semi-quantitative method was adopted to evaluate the Bohr effect to distinguish between acid- and base-Bohr effects. Results After method optimization,the high-throughput ODA could quantify HBOCs’ oxygen release capacity more rapidly and more accurately by measuring the oxygen release ratio,oxygen release rate and semiquantitative Bohr effect.Conclusion The high-throughput ODA is optimized and is applicable to evaluating HBOC’s oxygen release capacity in vitro,which can facilitate HBOCs development.

Objective To investigate the effects and possible mechanisms of YL-0919 （a novel class 1.1 antidepressant drug with an original chemical structure, independently developed by our research institute）in the treatment of post-traumatic stress disorder （PTSD） and cognitive impairment in a mouse model of inescapable footshock （IFS）. Methods Highly selective sigma-1 receptor antagonist BD-1047 was intraperitoneally injected to verify the target of YL-0919： （1） Mice were randomly divided into the control group, IFS⁺vehiclegroup, IFS⁺YL-0919 （2.5 mg/kg）⁺vehicle group, and IFS⁺YL-0919⁺BD-1047 （2.0 or 4.0 mg/kg） groups. The plantar surface of the mice was subjected to two consecutive days of electric shockto establish an IFS model. Mice in the IFS⁺YL-0919⁺vehicle group and the IFS⁺YL-0919⁺BD-1047 group were orally administeredwith YL-0919 （2.5 mg/kg） twice daily while those in theBD-1047 group （2.0 or 4.0 mg/kg）were administered intraperitoneally once daily, starting two days before YL-0919 administration. One hour after drug administration on the seventh day, the rapid anti-PTSD effect of YL-0919 was evaluated via behavioral experiments. （2）Fluoxetine （Flx） was used as a positive control drug. Mice were randomly divided into the control group, IFS⁺vehicle group, IFS⁺YL-0919 （2.5 mg/kg）⁺vehicle group, IFS⁺YL-0919⁺BD-1047 （2.0 mg/kg） group, and IFS⁺Flx （10.0 mg/kg）⁺vehicle group. Twenty-four hours after drug administration on the fifth day, the rapid anti-PTSD effect of YL-0919 was assessed via behavioral experiments. （3） Western blot was used to detect the expression levels of synaptic plasticity protein PSD95, AMPA-type glutamate receptor subunit-1 （GluA1）, and brain-derived neurotrophic factor （BDNF） in the prefrontal cortex of mice. Results （1） Compared with the control group, there was an increase in freezing time and asignificant decrease in recognition indexes in the IFS model group （P<0.05）. Compared with the IFS group, these changes were significantly reversed by YL-0919 （2.5 mg/kg） （P<0.05）. In contrast, Flx （10.0 mg/kg） did not mitigate the behavior after 5 days of continuous administration, but14 days of administration of Flx （10.0 mg/kg） showed a significant anti-PTSD effect but failed to significantly improve cognitive deficits in the IFS model mice, suggesting that YL-0919 could exert rapid anti-PTSD effect and improve cognitive function compared to Flx. Compared with the IFS⁺YL-0919⁺vehicle group, the anti-PTSD and pro-cognitive effects of YL-0919 were blocked by BD-1047 （2.0 or 4.0 mg/kg）. （2） Compared with the control group, the expression levels of PSD95, BDNF, and GluA1 proteins in the prefrontal cortex of mice were significantly reduced in the IFS model group （P<0.05）, but were significantly increased in the IFS⁺YL-0919 （2.5 mg/kg, administration for 5 days） group compared with the IFS model group （P<0.05）. Compared with the IFS⁺YL-0919 ⁺vehicle group, the increased expression levels of PSD95, BDNF, and GluA1 proteins induced by YL-0919 were blocked after BD-1047 （2.0 mg/kg） administration. Compared with the IFS model group, the expression levels of PSD95, BDNF, and GluA1 proteins in the prefrontal cortex of mice in the IFS⁺Flx （10 mg/kg, administration for 5 days） group did not change significantly. Conclusion YL-0919 can exert rapid anti-PTSD effects and relieve cognitive impairment in the IFS model, and the mechanism of the action may be related to the activation of sigma-1 receptors to regulate synaptic plasticity and BDNF expression in the prefrontal cortex.

Organoids are three-dimensional tissue structures derived from stem cells. In recent years, significant progress has been made in the culture technology of human lung organoids. This technology can create three-dimensional tissue structures that can recapitulate the architecture and function of the human lung via stage-specific induction of directed differentiation among stem cells or specialized progenitor cells. As a powerful tool for research, this technology allows in-depth investigation into lung development, provides mechanistic insights into pulmonary diseases, and accelerates the discovery of drugs. This review summarizes the latest progress in the generation of human lung organoids from adult stem cells, embryonic stem cells, and induced pluripotent stem cells in general and what needs to be optimized in current culture systems in particular, such as the development of organoid models that can accurately reproduce the distal lung architecture. In addition, the article outlines the applications of human lung organoids in pulmonary disease research, cancer drug screening, and regenerative medicine while opportunities and future applications of this promising technology are also predicted.