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    Original articles
  • Original articles
    CHEN Yi, GE Yingwei, ZHOU Lijie, WANG Siying, ZHANG Lingqiang
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    Objective To profile ubiquitination in cysteinyl aspartate-specific proteinase-2(CASP2) deficient cells under heat shock and investigate the role of CASP2 in stress response. Methods Ubiquitination levels in subcellular fractions of control and CASP2 knockout (KO) cells were detected via Western blotting. After 2 hours of heat shock treatment, Soluble Ⅱ and Pellet fractions were collected from both control and CASP2 KO cells for ubiquitinome analysis. Anti-di-glycine remnant (K-ε-GG) antibody-based proteomic analysis was performed to identify differentially ubiquitinated proteins and associated key signaling pathways. Proteins that displayed significantly upregulated ubiquitination in CASP2 KO cells under heat shock were subjected to His-tag pull-down assays to find out whether CASP2 regulated the ubiquitination of these proteins. Results Under heat shock, CASP2 KO cells displayed significantly higher accumulation of overloaded ubiquitinated conjugates in the Pellet fraction compared to controls. Ubiquitinomics analysis revealed substantial alterations in protein ubiquitination patterns following CASP2 KO. One hundred proteins exhibited significantly elevated ubiquitination levels while 36 proteins had their ubiquitination reduced relative to controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that hyper-ubiquitinated proteins were primarily associated with Huntington disease, Alzheimer disease, bile secretion, carbon metabolism and autophagy. His-tag pull-down assays combined with Western blotting revealed increased ubiquitination of nicotinamide adenine dinucleotide reduced - ubiquinone oxidoreductase 1 beta subcomplex subunit 3 (NDUFB3) and autophagy-related protein 9A (ATG9A) in CASP2 KO cells under heat shock. Conclusion Overloaded ubiquitinated conjugates are accumulated due to CASP2 deficiency during heat shock. CASP2 modulates ubiquitination levels through multiple signaling pathways.
  • Original articles
    CHEN Chen, XU Litao, YIN Xu, CI Weihao, XIANG Shensi, YANG Xiaoming, REN Guangming
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    Objective To construct nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) knockout mice in order to investigate the effects of NLRP3 knockout on radiation-induced acute pneumonitis and pulmonary fibrosis. Methods Nlrp3+/+ and Nlrp3-/- mice were randomly divided into the control group and irradiation group. To induce radiation-caused acute pneumonitis, the control group was exposed to sham irradiation while the irradiation group was exposed to 60Co γ-rays at a dose of 22 Gy at a dose rate of 184.30 R/min. At 14 days post-irradiation,the body weight of each mouse and the wet weight of its lung tissue were measured separately using an analytical balance to calculate the lung coefficient. Quantitative real-time PCR (qPCR) and cytometric bead array (CBA) were used to detect inflammatory responses in lung tissues and serum. Hematoxylin-eosin (HE) staining and F4/80 immunohistochemical staining were used to assess pathological changes and inflammatory cell infiltration in lung tissues. Cysteinyl aspartate specific proteinase-1(caspase-1) activation was analyzed by Western blotting. To establish a model of radiation-induced pulmonary fibrosis, mice were irradiated with 60Co γ-rays at a dose of 18 Gy at a dose rate of 174.67 R/min. At 24 weeks post-irradiation, HE staining and Masson staining were performed to evaluate pulmonary fibrosis. Results NLRP3 knockout inhibited caspase-1 activation, reduced inflammatory responses in lung tissues and serum, suppressed macrophage infiltration, alleviated pulmonary edema, and thereby protected against acute radiation-induced lung injury. Additionally, NLRP3 knockout significantly ameliorated late-stage radiation-induced pulmonary fibrosis. Conclusion NLRP3 knockout can mitigate both early radiation-induced pneumonia and lateradiation-induced pulmonary fibrosis.
  • Original articles
    FENG Mingjie, ZHANG Xiaochang, LI Jiangbo, WANG Chenhui, HAN Wei, GENG Xiaoen, ZHOU Zhe
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    Objective To identify candidate compounds that activate thermogenesis during cold exposure by integrating the Library of Integrated Network-Based Cellular Signatures (LINCS) with RNA expression profiles specific to cold-induced thermogenesis. Methods Gene expression profiles of interscapular brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) were generated from 8-week-old C57BL/6J mice which were housed at 5 ℃ or room temperature (23 ℃) for 7 days. The gene expression signatures of the cold-induced BAT and iWAT were compared to the LINCS dataset to predict potential candidates for testing in a cold challenge model that was intended to assess thermogenesis activation. The pharmacological potential of the identified compounds was evaluated in a cold-exposed mouse model. The core body temperature and infrared thermal imaging were collected to monitor physiological responses during cold exposure. Additionally, hematoxylin and eosin (HE) staining was used to assess morphological changes of fat cells of BAT, iWAT, and epididymal white adipose tissue (eWAT). Results The transcriptomic signatures related to cold-induced thermogenesis were obtained and the top 20 candidate compounds were identified by comparison with the LINCS dataset. Mice treated with withaferin A (WA) during the cold challenge exhibited elevated rectal temperatures and smaller adipocyte sizes compared to controls. Conclusion Our drug repurposing strategy, which connects transcriptional profiles with LINCS data, identifies potential compounds. WA enhances thermogenesis and metabolic activity in adipose tissue, which helps maintain body temperature, and improves cold tolerance during exposure to low temperatures.
  • Original articles
    YANG Zhe, DUAN Min, YE Yumeng, WANG Yongyi, ZHANG Jiao, WANG Xuejia, WANG Jun, LI Yang
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    Objective To investigate the impact of myeloid cell-specific knockout of the granulocyte colony-stimulating factor receptor(G-CSFR) on the progression of acute radiation pneumonitis. Methods Myeloid cell-specific G-CSFR knockout(G-CSFR-/-,Lyz2-cre) mice were constructed. G-CSFR-/-,Lyz2-cre and C57BL/6N mice underwent a single whole-body irradiation with 6.5 Gy of 60Co γ-rays to establish a model of radiation injury. The lung function of mice was assessed using a mouse lung function test system at 3,7 and 14-days post γ-ray irradiation. Pathological changes in the lung tissue were analyzed via hematoxylin and eosin (HE) staining of paraffin sections. Tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels were measured via radioimmunoassay. IL-8 and its receptor CXCR2 were quantified using enzyme-linked immunosorbent assay (ELISA). The infiltration of neutrophils in lung tissue was evaluated by immunohistochemical detection of myeloperoxidase. Results At 3-,7- and 14-days post-irradiation with 6.5 Gy of 60Co γ-rays,there were no significant differences observed in lung function or interstitial inflammatory lesions between G-CSFR-/-,Lyz2-cre mice and C57BL/6N mice. However,the infiltration of neutrophils in lung tissue of G-CSFR-/-,Lyz2-cre mice was significantly reduced (P<0.01),and the levels of IL-8,CXCR2 and TNF-α in lung tissues were markedly lower than in C57BL/6N mice (P<0.05). Conclusion The myeloid cell-specific knockout of G-CSFR can effectively diminish neutrophil infiltration as well as inflammatory cytokine levels in lung tissues following radiation exposure.
  • Original articles
    ZHANG Yubing, LI Hongchang, WANG Siying, ZHANG Lingqiang
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    Objective To investigate how deubiquitinase OTU domain-containing protein 3 (OTUD3) suppresses the progression of hepatocellular carcinoma via gut-liver axis metabolic remodeling and microbiome dynamics. Methods A total of 24 male 2-week-old littermate C57BL/6J mice (12 wild-type and 12 Otud3-/-) were divided into two differential genotype groups before 6 mice from each group were randomly chosen to receive intraperitoneal injections of N-nitrosodiethylamine(DEN) for hepatocellular carcinoma (HCC)induction. The mice were divided into four groups (n=6/group): Otud3+/+ control (WT CON), Otud3-/- control (KO CON), Otud3+/+ DEN-induced HCC (WT DEN), and Otud3-/- DEN-induced HCC (KO DEN). At 40 weeks of age, liver tissues were collected for metabolomic profiling, and fecal samples were obtained for 16S rRNA sequencing. Results Multivariate analyses, including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), sparse partial least squares-discriminant analysis (sPLS-DA), and orthogonal partial least squares-discriminant analysis (OrthoPLS-DA), demonstrated complete intergroup separability. Fifty-four differential metabolites were identified between the WT DEN and KO DEN groups through metabolomic profiling, with gut-liver axis-associated pathways such as cholesterol metabolism and fatty acid biosynthesis revealed by KEGG pathway analysis. Microbiome analysis indicated an upregulation of Bacteroides at the genus level in the KO DEN group compared to WT DEN. Pearson correlation analysis highlighted amino acids and derivatives as predominant metabolite classes and revealed Bacteroidetes and Firmicutesas the dominant gut microbial phyla. Conclusion OTUD3 suppresses HCC progression by modulating gut-liver axis metabolism, potentially mediated by elevated betaine and increased abundance of Odoribacter, Alistipes, and Lachnoclostridium.
  • Original articles
    LIU Zhuang, ZHAI Yanan, WANG Shunye, MA Ming, WANG Ziyang, LIU Yanqin, GAO Xiang, GAO Jing
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    Objective To heterologously express and purify the small ubiquitin-like modifier (SUMO) tag fused organophosphorus hydrolase mutant H257Y/L303T (YT),namely SUMO-YT,and evaluate its hydrolytic capacity against ethyl paraoxon and soman. Methods The SUMO tag encoding gene was constructed at the N-terminus of the YT encoding gene with a linker sequence via enzyme digestion and ligation before SUMO-YT was expressed in Escherichia coli. SUMO-YT and YT were purified through ammonium sulfate precipitation and affinity chromatography to obtain high-purity target proteins. The activity and kinetic parameters of the recombinant enzymes were examined using ethyl paraoxon and soman as substrates. Results The system for expression and purification of recombinant enzymes was established,yielding SUMO-YT and YT,and the former exhibited more significantly enhanced hydrolytic efficiency than the latter,with catalytic rates 11-fold higher for paraoxon and 4.4-fold higher for soman. At 37 ℃ and pH 7.2,SUMO-YT reduced the inhibition rate of acetylcholinesterase (AChE) by soman from 100% to 45.7% within 3 minutes,whereas YT reduced it to no more than 80%. Conclusion The high-activity recombinant SUMO-YT is prepared. SUMO tag fusion can significantly enhance the hydrolytic capacity of YT against ethyl paraoxon and soman.
  • Original articles
    CAI Juxing, ZHU Baorang, LI Jing, YANG Wuwei
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    Objective To assess potential associations between sarcoma and gut microbiota using Mendelian randomization (MR) analysis. Methods Instrumental variables (IV) for gut microbiota were identified from summary data of a genome-wide association studies (GWAS) involving 18 340 participants from 24 cohorts published by the MiBioGen Consortium. The GWAS on sarcoma from Europe served as an outcome,involving 456 276 sarcoma patients. The inverse-variance weighted (IVW) method was used for primary analysis while sensitivity analysis was made to test the reliability of results of MR analysis. Results IVW results showed that PeptostreptococcaceaeOR=0.353,95%CI 0.127 to 0.979,P=0.045) and FaecalibacteriumOR=0.408,95%CI 0.173 to 0.961,P=0.040) had a negative causal correlation with sarcoma,but the Eubacterium fissicatena groupOR=2.216,95%CI 1.101 to 4.462,P=0.026) and Lachnospiraceae UCG008 (OR=1.822,95%CI 1.005 to 3.305,P=0.048) exhibited a positive causal correlation with sarcoma. Sensitivity analysis showed no evidence of pleiotropy and heterogeneity. Conclusion Through two-sample MR, this study identifies a potential causal relationship between four gut microbiota and sarcoma. Peptostreptococcaceae and Faecalibacterium can reduce the risk of sarcoma while the Eubacterium fissicatena group and Lachnospiraceae UCG008 are linked to an increased risk of sarcoma. More research is required to find out more about the way gut microbiota influences the development of sarcoma.
  • Original articles
    XIA Tiantian, ZHOU Wei, TONG Li, SHEN Pan, WANG Ningning, ZHANG Nan, NI Zhexin, GAO Yue
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    Objective To investigate the clinical manifestations of traditional Chinese medicine (TCM) and their associations with TCM constitutions in individuals who have migrated to plateau areas,and to provide a scientific basis for plateau health management. Methods Migrants living in areas above 3000 m were selected as research subjects. Data were collected by using TCM symptom assessment scales and constitution assessment scales. Descriptive statistical analysis was conducted to determine the incidence and severity of symptoms among individuals with different migration durations,and core symptoms were identified. Factor analysis was performed by using SPSS software to extract symptom clusters and explore the correlation between core symptoms and TCM constitutions. Results Among individuals who migrated to plateau areas,the incidence of discomfort symptoms was 83.44%. The five most common symptoms were dry skin (67.94%),forgetfulness (56.03%),dry mouth (52.06%),yellow urine (48.73%),and insomnia (47.14%). In the top 10 symptoms with the highest increase in incidence,yellow urine (33.51%) and forgetfulness (26.33%) were both present in the top 10 symptoms across different migration durations. Factor analysis extracted 5,2,4,and 6 symptom clusters from the overall population,individuals who migrated within 1 year,those who migrated for 1-2 years,and those who migrated over 2 years,respectively. Qi-deficiency constitution (QDC),blood stasis constitution (BSC),qi stagnation constitution (QSC),phlegm-dampness constitution (PDC),and dampness-heat constitution (DHC) were significantly positively correlated with forgetfulness. Conclusion Migrating to plateau areas can induce discomfort symptoms,and both the number and incidence of symptoms increase with longer migration durations. The number and incidence of high-frequency symptoms (incidence≥30%) increase with prolonged migration time. There are differences in the composition and severity of symptom clusters across different migration durations. QDC,BSC,QSC,PDC,and DHC are closely related to forgetfulness and can be considered risk constitutions for forgetfulness. Timely attention to changes in symptom clusters and constitutions can help prevent and mitigate the occurrence and development of symptoms.
  • Reviews
  • Reviews
    TIAN Hao, BA Qi, GONG Wei, WANG Yuli, YANG Yang, GAO Chunsheng, YANG Meiyan
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    Infectious pneumonia caused by bacteria,viruses,or other pathogenic microorganisms remains a huge threat to human health. Immunocyte-derived biomimetic nano-drug delivery systems can be used for drug delivery by taking advantage of the natural anti-inflammatory effect of immune cells and thus show great potential in lung-targeted therapy. This review begins by introducing different types of immune cells in the lung. The preparation methods of immunocyte-derived biomimetic nano-drug delivery systems and their applications in bacterial pneumonia,viral pneumonia,acute respiratory distress syndrome and cytokine storms are also reviewed. The review is expected to provide data for the targeted therapy of infectious pneumonia.
  • Reviews
    SONG Dengcen, LIU Zijing, CAO Cheng, WANG Haoyong
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    Transient receptor potential vanilloid 1 (TRPV1) ion channel, a non-selective cation channel, not only plays a key role in pain transmission but also serves as a bridge between the nervous system and immune system by regulating neuropeptide release, immune cell activation, and inflammatory signaling pathways. This article summarized its crucial role in inflammatory signal transduction, discussed the interaction mechanism between TRPV1 and the neuro-immune regulatory axis, and explored its potential as a therapeutic target for inflammatory diseases.
  • Reviews
    XU Xi, OU Haifeng, SITU Wenfeng, PENG Junjie
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    With the growing complexity and higher risk of modern warfare, artificial intelligence (AI) technologies have been increasingly used in the field of military medicine. This study investigates the innovative applications of AI in military medicine, focusing on practices in such countries as the United States, Israel and the United Kingdom. The research reveals that AI technologies have been extensively applied in battlefield medical training, casualty status monitoring, medical decision support and unmanned rescue operations. Through virtual reality simulation, intelligent decision support and vital sign monitoring technologies, AI has significantly improved the efficiency and precision of battlefield medical care. Despite challenges related to technological implementation, environmental adaptability and ethical controversies, future battlefield medical care will increasingly rely on unmanned systems and intelligent equipment to deliver efficient medical treatment through human-machine collaboration.
  • Short report
  • Short report
    YAO Lei, ZHAO Yuqiong, CAO Yuquan, YANG Yan, WU Chunhai, CHEN Liusheng
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  • Short report
    GUO Jianlian, XIE Zhixiong
    Abstract ( ) Download PDF ( )   Knowledge map   Save
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