Objective:To compare the efficiency and characteristics of different carrier proteins and signal sequences in delivering antigens into Escherichia coli outer membrane vesicles (OMVs). Methods:The fusion protein F1V, which consisted of the main protective antigen of Yersinia pestis F1 and LcrV, was expressed using the carrier proteins such as cytolysin A (ClyA), outer membrane protein A (OmpA), or β-lactamases (Bla) signal sequence as a carrier protein. The expression, localization, and content of F1V protein in OMVs were compared and analyzed. Results:All three delivery methods successfully incorporated F1V protein into OMVs and localized it on the surface of OMVs. Notably, when OmpA was used as the carrier protein, the F1V fusion protein constituted up to 30% of the total protein in OMVs. The highest yield of OMVs, reaching 4.2 mg/L, was achieved when Bla signal sequence was used as the carrier.Conclusions:There is a significant difference in the efficiency of different carrier proteins in delivering the F1V antigen into OMVs of Escherichia coli. Considering both the yield of OMVs and the proportion of antigen in the total protein of OMVs, the carrier Bla signal sequence demonstrated the highest efficiency in delivering F1V into OMVs, showing a potential for the future development of OMVs-based plague vaccines.

Objective:To develop an air transfer stretcher for severely injured patients,so as to meet the requirements of severely injured patients for rapid transport of aviation medical treatment.Methods:The guide rails of hatch of mainstream civil airliner models were analyzed through investigation.Based on the principles of modularization,integration and intelligence,a highly universal and portable aviation stretcher with the functions of rapid transport and life support was designed and developed.The design of the stretcher was verified through simulation analysis and calculation,as well as tests in laboratory,which should meet the requirements of the standards from China Civil Aviation Regulations(CCAR)-25.Results:The results of simulation analysis and tests of laboratory showed that the aviation transport stretcher,and the strength and stiffness of its structure reached to requirement of CCAR-25 standard,which was suit to the portable aviation evacuation of severely injured patients on civil airliners,and the rapid transfer between air and ground.It has the function of supporting life,and the aviation transport stretcher with high universality and convenience can enhance the safety and rescue capability of aviation evacuation system of medical treatment of aviation.Conclusion:The portable aviation stretcher with high-versatility that was researched and developed by this study can effectively solve the problems of life support,injury monitoring,and emergently rescue and treatment during the transport for severely injured patients,which improve the support ability of air-ground transportation for severely injured patients.

Objective To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.

Objective:To compare the efficiency and characteristics of different carrier proteins and signal sequences in delivering antigens into Escherichia coli outer membrane vesicles (OMVs). Methods:The fusion protein F1V, which consisted of the main protective antigen of Yersinia pestis F1 and LcrV, was expressed using the carrier proteins such as cytolysin A (ClyA), outer membrane protein A (OmpA), or β-lactamases (Bla) signal sequence as a carrier protein. The expression, localization, and content of F1V protein in OMVs were compared and analyzed. Results:All three delivery methods successfully incorporated F1V protein into OMVs and localized it on the surface of OMVs. Notably, when OmpA was used as the carrier protein, the F1V fusion protein constituted up to 30% of the total protein in OMVs. The highest yield of OMVs, reaching 4.2 mg/L, was achieved when Bla signal sequence was used as the carrier.Conclusions:There is a significant difference in the efficiency of different carrier proteins in delivering the F1V antigen into OMVs of Escherichia coli. Considering both the yield of OMVs and the proportion of antigen in the total protein of OMVs, the carrier Bla signal sequence demonstrated the highest efficiency in delivering F1V into OMVs, showing a potential for the future development of OMVs-based plague vaccines.

Objective:To develop an air transfer stretcher for severely injured patients,so as to meet the requirements of severely injured patients for rapid transport of aviation medical treatment.Methods:The guide rails of hatch of mainstream civil airliner models were analyzed through investigation.Based on the principles of modularization,integration and intelligence,a highly universal and portable aviation stretcher with the functions of rapid transport and life support was designed and developed.The design of the stretcher was verified through simulation analysis and calculation,as well as tests in laboratory,which should meet the requirements of the standards from China Civil Aviation Regulations(CCAR)-25.Results:The results of simulation analysis and tests of laboratory showed that the aviation transport stretcher,and the strength and stiffness of its structure reached to requirement of CCAR-25 standard,which was suit to the portable aviation evacuation of severely injured patients on civil airliners,and the rapid transfer between air and ground.It has the function of supporting life,and the aviation transport stretcher with high universality and convenience can enhance the safety and rescue capability of aviation evacuation system of medical treatment of aviation.Conclusion:The portable aviation stretcher with high-versatility that was researched and developed by this study can effectively solve the problems of life support,injury monitoring,and emergently rescue and treatment during the transport for severely injured patients,which improve the support ability of air-ground transportation for severely injured patients.

Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.

Objective To This study aims to analyze the airworthiness compliance of transport stretchers for severely injured patients to ensure their safety and effectiveness in aeromedical rescue.Methods Through finite element modeling and analysis,using the analysis/calculation verification method(code MC2)in the Means of Compliance(MC),the structural static strength,stiffness,load and internal force of the transport stretcher were evaluated,and the damage tolerance assessment and vibration analysis of the connecting structure were carried out.Results The analysis results showed that the safety margins of the main structure and various components of the transport stretcher were all greater than zero,meeting the airworthiness design requirements.The damage tolerance analysis of the connecting structure showed that after the stretcher was installed,the aircraft body structure met the design requirements and did not change the inspection threshold value and interval.In addition,the performance analysis results of the transport stretcher in standard and enhanced vibration environments both indicated that the probability of failure was extremely low.Conclusion The transport stretcher meets the DO-160G standard in design and function and meets the requirements of relevant aviation regulations,providing scientific basis and practical guidance for the efficiency and safety of the aeromedical rescue system.

Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.

Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.