Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.

Objective To explore the effects of the same dose of fractionated radiation and single radiation on radiation-induced heart damage in mice.Methods Twenty-one wild-type C57BL/6J mice were randomly divided into the normal group,fractionated radiation group and single radiation group.18 Gy X-ray,via fractionated(3 Gy/time,6 times)radiation or single radiation,was used to establish a radiation-induced heart damage model.The concentrations of myocardial enzyme damage markers(creatinekinase(CK),creatinekinase-MB(CK-MB),lactate dehydrogenase(LDH)and LDH1)and peripheral serum ions(K+,Ca2+,Fe2+and Cl-)were detected by an automatic biochemical analyzer at day 7 and 28 after radiation.Ultrasound was used to detect and analyze the cardiac function of mice at day 28 after radiation,including the left ventricular ejection fraction(EF),left ventricular fractional shortening(FS),left ventricular end-diastolic volume(LVEDV),left ventricular mass(LV mass)and left ventricular end-systolic volume(LVESV).The opening of the mitochondrial permeability transition pore(mPTP)and changes of mitochondrial membrane potential of myocardial cells were observed using a laser confocal microscope.The ultrastructure of myocardia was observed under a transmission electron microscope(TEM)and cardiac fibrosis was checked by Masson staining.The atherosclerosis of the aorta was examined by gross oil red staining.Real-time quantitative PCR(RT-qPCR)and Western blotting were performed to detect the expressions ofapoptosis-related genes and proteins,B cell lymphoma-2-associated X protein(BAX)and casepase-3.Results Seven days after 18Gy X-ray irradiation,the expression levels of CK,CK-MB,LDH and LDH1 in the single radiation group increased significantly or trended up,while only CK and LDH1 in the fractionated irradiation group continued to increase.Twenty-eight days after radiation,the expression levels of 4 enzymes in myocardial zymogram were increased by both radiation methods.Seven and twenty-eight days after radiation,the concentrations of serum ions K+,Fe2+,Ca2+and Cl-were significantly decreased by both radiation methods that could lead to the decrease of EF and FS,and the increase of LV mass,LVEDV and LVESV.Single radiation made more difference to EF and FS,and the difference between the two groups was statistically significant.Both methods could decrease the mPTP and mitochondrial membrane potential,especially single radiation,and there was significant difference between the two groups.The results of TEM showed that the mitochondrial cristae of myocardial cells decreased and vacuolated,and the myocardial fiber bundles became thicker after X-ray radiation.Masson staining showed that collagen fibers were deposited in the heart tissue ofmice after X-ray irradiation,particularly in the single radiation group.Gross oil red staining ofthe aorta showed that both methods could damage the aorta of mice,and the area of atherosclerotic plaques in the single radiation group was larger,which was statistically different from that of the fractionated radiation group.The results of RT-qPCR and Western blotting showed that X-ray radiation could increase the expression levels of apoptosis-related BAX and caspase-3 in cardiac tissue,especially in the single radiation group.The mRNAexpressions of BAX and caspase-3 increased more significantly in the single radiation group.Conclusion Both fractionated radiation and single radiation at the same dose can cause heart damage,so they can be used to establish a radiation-induced heart damage model of mice.Single radiation can cause more significant damage to the heart.Different modeling methods can be selected as required.

Objective To construct a mouse model with conditional knockout of deubiquitinase Otulin gene in the endocardium and to analyze the phenotype ofthe model.Methods A model ofmice with endocardium-specific conditional Otulin gene knockout was constructed with the Cre-loxP technique.The genotypes of Otulin gene knockout mice were determined by using polymerase chain reaction(PCR).Data on the reproduction of the knockout mice was statistically analyzed and the growth and development of the offspring were observed.The Cardiac function of mice was monitored by ultrasound and the changes of cellular components in blood were measured by a fully automatic hematology analyzer.Hematoxylin-eosin(HE)staining was used to analyze the pathological changes in all the tissues and organs ofthe offspring.Results An endocardium-specific Otulin gene knockout mouse model was established.The conditional knockout mice could grow and reproduce normally and the percentage of genotypes of their offspring conformed to Mende's law.Compared with littermate control mice,the conditional knockout mice had smaller body size,lighter weight,significantly enlarged spleens and spiking inflammatory cells in blood.In addition,the tricuspid valve defect and cardiac function were attenuated.Conclusion A mouse model of endocardium-specific Otulin gene knockout has been constructed.These mice show impaired cardiac function and obvious inflammatory response.

Objective To investigate the role and mechanism of exosomes derived from mesenchymal stem cells in hyperbaric oxygen caused pulmonary oxygen toxicity.Methods Mice were divided into the control group that was exposed to normal air,and hyperbaric oxygen exposure groups treated with phosphate buffer saline(PBS)or exosomes,respectively.PBS and exosome treatment were given one day prior to exposure.Mice were subjected to 0.23 MPa pure oxygen for 8 hours.The lung wet-dry ratio,inflammation,exudation and pathological injury were analyzed,while cell death and antioxidant related molecules were detected.Results Pretreatment with exosome significantly attenuated lung injury caused by hyperbaric oxygen exposure by decreasing the lung wet-dry ratio,inflammation,and cell apoptosis.Conclusion Prophylactic administration of exosomes derived from mesenchymal stem cells can alleviate hyperbaric oxygen induced pulmonary oxygen poisoning by attenuating cell death and inflammation.

Objective To investigate the inhibitory effect of anlotinib combined with anti-PD1 antibody on a colon cancer mouse model,and to explore its possible mechanismfor remodeling the immune system and tumor microenvironment.Methods A BALB/c mouse model was established with colon cancer cells CT26,and the mice were divided randomly into four groups:the control group,the anlotinib group,anti-PD1 antibody group and anlotinib combined with anti-PD1 antibody group,with 6 mice in each.During the experiment,tumor volumes were measured every 2 days using a vernier caliper.After the experiment(on day 14),the weight of the tumors of mice in each group was measured.Flow cytometry was used to detect changes in the number of immune infiltrating cells in tumor tissues,including CD4+T cells,CD8+T cells,monocytic myeloid-derived suppressor cells(M-MDSCs),granulocytic myeloid-derived suppressor cells(G-MDSCs),and M2-type tumor-associated macrophages(M2-TAM).Furthermore,ELISA was employed to detect the levels of vascular endothelial growth factor(VEGF),interferon-γ(IFN-γ),interleukin-17(IL-17),and IL-10 in the serum of mice.Results Compared with the control group,the other three groups showed a decrease in the volume and weight of transplanted tumors in mice(P＜0.05),as well as decreased levels of cytokines VEGF,IL-10(P＜0.05),and IL-17(P＜0.01).Additionally,there was an increase in the level of IFN-γ(P＜0.05).In terms of the number of immune infiltrating cells,the number of M-MDSCs decreased in each treatment group compared to the control group,but without statistically significant difference(P＞0.05).In the combined group,the number of M2-type TAMs decreased compared to the control group and the anti-PD-1 antibody group(P＜0.05).Furthermore,flow cytometry results indicated that compared to the control group,the other three groups showed an increase in the number of CD8+T cells in mice(P＜0.05).The number of CD4+T cells decreased slightly compared to the other groups,but the statistically significant difference was only observed when compared to the anlotinib group(P＜0.05).Conclusion The combination ofanlotinib and anti-PD1 antibody may regulate the levels of cytokines VEGF,IFN-γ,IL-10,and IL-17,thereby influencing the number of immunosuppressive cells in the tumor microenvironment.The tumor microenvironment and immunity can also be improved,thus significantly inhibiting the growth ofmouse colonic transplant tumors.

Objective To explore the mechanism by which hyperglycemia and hyperlipidemia promote apoptosis of placental trophoblasts in obese puerperae with gestational diabetes mellitus.Methods The placentas of 20 healthy(NC)puerperae,20 gestational diabetes mellitus(GDM)puerperae,20 obese(OB)puerperae and 20 obese puerperae combined with gestational diabetes mellitus(OB+GDM)were collected at the Second Hospital of Tianjin Medical University between January 2020 and January 2023.Placental pathology was detected via HE staining and the expressions of apoptosis-related proteins by immunohistochemistry.The expressions of mammalian sterile 20-like kinase 1(MST1),c-Jun N-terminal kinase(JNK),Bcl-2 associated X protein(BAX),B-cell lymphoma-2(Bcl-2),cysteinyl aspartate specific proteinase(caspase 3)and other apoptosis-related proteins were detected by Western blotting.Results HE staining revealed that hyperglycemia and hyperlipidemia could lead to a relative decrease and varying sizes of syncytial trophoblasts and cytotrophoblasts in placentas.The TUNEL method found that hyperglycemia and hyperlipidemia led to increased apoptosis in trophoblasts,particularly in syncytial trophoblasts,with the most pronounced apoptosis in the obese combined with GDM group.Immunohistochemical detection of placentas revealed that hyperglycemia and hyperlipidemia could increase the expressions of apoptosis-related proteins MST1 and JNK.The regulatory pathway of MST1-JNK-BAX-CASP3 apoptosis was found to be involved in the apoptotic process of placental trophoblasts by Western blotting.Conclusion The placental trophoblasts of obese women with gestational diabetes mellitus may overproduce reactive oxygen species in the internal environment formed by hyperglycemia and hyperlipidemia,which mediates the apoptosis of placental trophoblasts through the regulatory pathway of MST1-JNK-BAX-CASP3 apoptosis,thus affecting the placental function.

Preventing bioweapons is an important component of biosecurity,and the Biosecurity Law of the People's Republic of China has a chapter devoted to"Preventing Biological Terrorism and the Threat of Bioweapons".A good knowledge of the history plays a positive role in effective protection against bioweapons.This article analyzes history of bioweapons based on books and literature that have been published in order to provide reference for professionals in the sphere of biosecurity.

Abrin,the most lethal plant-derived toxin known today,has attracted widespread attention from both the International Chemical Weapon Convention and the Biological and Toxin Weapons Convention.There is an urgent demand for the development of efficient detection and detoxification countermeasures against Abrin to adress its potential threats to human health and public safety.This review,based on clustering analysis of literature and on knowledge of the structures of various subtypes of Abrin,provides an overview of the analysis and detection techniques,the mechanism of toxicity,and detoxification countermeasures against Abrin.It concludes with an examination of the challenges and emerging trends in this field.The main analysis and detection techniques of Abrin include affinity-based analysis,physico-chemical-based analysis,and activity-based detection techniques.The challenges and developments in this field are also outlined.There is a pressing need to establish sensitive,specific,and accurate methods of measurement that are tailored to the structure and activity of Abrin in order to precisely assess and mitigate the toxin threat.Unfortunately,no effective antidotes have been deployed so far,with medical treatments confined to symptomatic care.Research and development of neutralizing antibodies remain stands as the most promising strategy for counteracting Abrin intoxication.

Cognitive function enhancement refers to the process of enhancing one or more core component of human brain cognition.Transcranial direct current stimulation(tDCS),as a non-invasive neuromodulation technique,can regulate brain cortical excitability,synaptic plasticity and brain networks functional connection.tDCS can be used to modulate cognitive function components,such as perception,working memory,attention,motor learning and decision-making.This article reviews the neural and physiological mechanism of tDCS over cerebral cortex modulating neural activity and the research progress in human cognitive performance ofsingle tDCS on perception,working memory,attention,motor learning,decision-making and language of healthy individuals in order to provide reference for researchers.

The active denial system(ADS)is a millimeter wave electromagnetic directional energy non-lethal technology and the only microwave device against humans.Microwave radiation can cause damage to multiple systems in the human body,including the nervous,circulatory,immune,and reproductive systems.This article outlines the development,basic structure,and equipment of ADS,characteristics and mechanisms of medical injuries due to ADS,medical injury efficacy of ADS in terms of effects on the human body,determinants and skin depth.The precautions against and medical treatment of ADS-caused symptoms are briefly described.