Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Soybean meal (SBM) prepared by soybean crushing is the most popular protein source in the poultry and livestock industries (Cai et al., 2015) due to its economic manufacture, high protein content, and good nutritional value. Despite these benefits, SBM contains various antigen proteins such as glycinin and β-conglycinin, which account for approximately 70% of the total proteins of the SBM and reduce digestibility and damage intestinal function (Peng et al., 2018). Treating SBM with proteases (neutrase, alcalase, and trypsin) or fermentation can eliminate these antigen proteins (Contesini et al., 2018). Because of its safety and rapid growth cycle, Bacillus strains are considered ideal for the fermentation industry (Yao et al., 2021). SBM fermented by Bacillus yields products with high nutritional value and low levels of antinutritional factors (ANFs), stimulating research in this area (Yuan et al., 2017). Kumari et al. (2023) demonstrated that fermentation with Bacillus species effectively degrades antigen proteins and increases crude protein content. The degradation of antigen proteins relies on protease hydrolysis. Low protease production is the major obstacle hindering the widespread use of microbial fermentation techniques.
Bacillus amyloliquefaciens/metabolism* ; Fermentation ; Glycine max/metabolism* ; Soybean Proteins/metabolism* ; Peptide Hydrolases/metabolism* ; Ribosomes/metabolism* ; Globulins ; Antigens, Plant ; Seed Storage Proteins

Objective With the intensification of population aging,the incidence of aging-related neurodegenerative diseases continues to rise,however,their pathogenesis remains elusive and therapeutic options are limited.This study used bioinformatics approaches to explore brain cell-type-specific changes in gene expression during brain aging and their impacts,to provide further insights into the biological mechanisms of brain aging.Methods We analyzed single-cell sequencing datasets(GSE169606)from young and old mouse brains,including integration,quality control,normalization,conduct cell-type annotation and differential gene expression analysis to identify differentially expressed genes(DEGs)across various cell types,using the Seurat package in R software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation and enrichment analyses,and interactions between DEGs were analyzed by protein-protein interaction(PPI)networks.The hub genes in each cell type were identified using the MCC,MNC,DMNC,and Dgree algorithms in the cyto Hubba plugin.Results A total of 13 cell types were identified through cell annotation.After comparing the aged and young groups,we focused on in-depth analyses of the DEGs screened from four major cell types:neurons,microglia,astrocytes,and endothelia.GO analysis revealed that DEGs in neurons,astrocytes,and endothelial cells were significantly enriched in biological pathways related to circadian rhythm,and KEGG analysis indicated that DEGs in microglia and endothelial cells were enriched in circadian rhythm-related signaling pathways.PPI analysis also demonstrated that the biological networks of DEGs in neurons,microglia,and endothelial cells were significantly enriched in circadian rhythm functional clustering modules.Furthermore,based on the intersection of the four algorithms,we identified core genes within these cell types and also identified specific variations in circadian rhythm genes in microglia,astrocytes,and endothelial cells.Conclusions This study employed single-cell transcriptomics technology to reveal the differential expression of genes in neurons,microglia,astrocytes,and endothelial cells during aging.The identification of hub genes in microglia,astrocytes,and endothelial cells indicated specific changes in circadian rhythm genes across these three cell types.These findings provide a foundation for further studies of the molecular mechanisms involved in brain aging and for the development of related intervention strategies.

Objective To analyze the efficacy of vascularized lymph node transplantation(VLNT)combined with lymphatic venous anastomosis(LVA)in the treatment of secondary lower extremity lymphedema assisted by super microsurgical techniques.Methods A retrospective analysis was performed for 15 patients with secondary lower limb lymphedema who underwent VLNT+LVA surgery in the Department of Reconstructive and Reconstructive Microsurgery of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2021 to July 2023,and compared the circumference and volume of each segment of the lower limb between the preoperative and postoperative 90 days.LVA according to the results of ICG examination,3-5 parts of the lower limb were selected for"Z"shaped surgery,and the lymphatic vessels and venules were anastomosed under the microscope in the subcutaneous fat layer.VLNT confirmed and labeled the saphenous branch of the descending knee artery and its accompanying veins in the popliteal fossa,and the latissimus dorsi lymph node flap was incised,and the flap vessels were anastomosed with the saphenous branch of the descending knee artery and its accompanying veins.Postoperative observation of flap vascularization.The circumference and volume of the affected limb were measured before surgery and 90 days after surgery.Results A total of 15 patients with lower extremity lymphedema were included without serious complications.Statistical analysis showed that the circumference of all levels of the affected limb and the volume of the affected limb were improved 90 days after operation compared with those before surgery.Among them,the limb circumference and volume at each level from the highest point of the dorsum of the foot to 52 cm above the ankle improved 90 days after the operation compared with those before the operation.Conclusion LNT+LVA treatment for secondary lower extremity lymphedema can effectively control edema and improve the function of the affected limb.

Objective To analyze the efficacy of vascularized lymph node transplantation(VLNT)combined with lymphatic venous anastomosis(LVA)in the treatment of secondary lower extremity lymphedema assisted by super microsurgical techniques.Methods A retrospective analysis was performed for 15 patients with secondary lower limb lymphedema who underwent VLNT+LVA surgery in the Department of Reconstructive and Reconstructive Microsurgery of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2021 to July 2023,and compared the circumference and volume of each segment of the lower limb between the preoperative and postoperative 90 days.LVA according to the results of ICG examination,3-5 parts of the lower limb were selected for"Z"shaped surgery,and the lymphatic vessels and venules were anastomosed under the microscope in the subcutaneous fat layer.VLNT confirmed and labeled the saphenous branch of the descending knee artery and its accompanying veins in the popliteal fossa,and the latissimus dorsi lymph node flap was incised,and the flap vessels were anastomosed with the saphenous branch of the descending knee artery and its accompanying veins.Postoperative observation of flap vascularization.The circumference and volume of the affected limb were measured before surgery and 90 days after surgery.Results A total of 15 patients with lower extremity lymphedema were included without serious complications.Statistical analysis showed that the circumference of all levels of the affected limb and the volume of the affected limb were improved 90 days after operation compared with those before surgery.Among them,the limb circumference and volume at each level from the highest point of the dorsum of the foot to 52 cm above the ankle improved 90 days after the operation compared with those before the operation.Conclusion LNT+LVA treatment for secondary lower extremity lymphedema can effectively control edema and improve the function of the affected limb.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective With the intensification of population aging,the incidence of aging-related neurodegenerative diseases continues to rise,however,their pathogenesis remains elusive and therapeutic options are limited.This study used bioinformatics approaches to explore brain cell-type-specific changes in gene expression during brain aging and their impacts,to provide further insights into the biological mechanisms of brain aging.Methods We analyzed single-cell sequencing datasets(GSE169606)from young and old mouse brains,including integration,quality control,normalization,conduct cell-type annotation and differential gene expression analysis to identify differentially expressed genes(DEGs)across various cell types,using the Seurat package in R software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation and enrichment analyses,and interactions between DEGs were analyzed by protein-protein interaction(PPI)networks.The hub genes in each cell type were identified using the MCC,MNC,DMNC,and Dgree algorithms in the cyto Hubba plugin.Results A total of 13 cell types were identified through cell annotation.After comparing the aged and young groups,we focused on in-depth analyses of the DEGs screened from four major cell types:neurons,microglia,astrocytes,and endothelia.GO analysis revealed that DEGs in neurons,astrocytes,and endothelial cells were significantly enriched in biological pathways related to circadian rhythm,and KEGG analysis indicated that DEGs in microglia and endothelial cells were enriched in circadian rhythm-related signaling pathways.PPI analysis also demonstrated that the biological networks of DEGs in neurons,microglia,and endothelial cells were significantly enriched in circadian rhythm functional clustering modules.Furthermore,based on the intersection of the four algorithms,we identified core genes within these cell types and also identified specific variations in circadian rhythm genes in microglia,astrocytes,and endothelial cells.Conclusions This study employed single-cell transcriptomics technology to reveal the differential expression of genes in neurons,microglia,astrocytes,and endothelial cells during aging.The identification of hub genes in microglia,astrocytes,and endothelial cells indicated specific changes in circadian rhythm genes across these three cell types.These findings provide a foundation for further studies of the molecular mechanisms involved in brain aging and for the development of related intervention strategies.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.