Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

Objective: To understand the infection status, characteristics and drug resistance of non-O157 Shiga toxin-producing E. coli (STEC) in animal feces in Shandong Province. Methods: From 2015 to 2016, convient sampling method was used to collect 1 022 fresh feces of animals in Weishan county and Laizhou city, and 24 non-O157 STEC were isolated. The serotypes of non-O157 STEC strains were confirmed through serum agglutination test. The susceptibility was explored through the antimicrobial sensitivity experiments. ESBLs activity was confirmed by double-disc diffusion. PCR method was used to detect the resistance genes. PFGE typing was operated to assess the relatedness and variability of the strains. The multi-locus sequence typing (MLST) was adopted to get the allelic profile and ST sequence of strains. Analysis was made on the evolutionary relationship between different ST groups was made through CLC Sequence Viewer and Counting Express. Results: A total of 24 non-O157 STEC were isolated from animal feces. 23 strains were from pig feces, and 1 strain was from cow feces, and the serotypes were more dispersed. All of the 24 strains carried stx2 genes. The highest resistance rate was sulfamethoxazole(22 strains), the mount of cotrimoxazole and nalidixic acid was 18 strains, chloramphenicol was 13 strains, tetracycline was 19, and there was a phenomenon of multiple drug resistance. The drug resistance spectrum was sulfamethoxazole tetracycline-compound novammin-naphthidine-chloramphenicol. All strains were sensitive to cefepime and imipenem. The ESBLs confirmatory test showed that 4 strains of non O157 STEC produced beta lactamase. PCR detected 7 resistance genes, and 4 tetracycline resistance genes (Tet A, Tet B, tetC and tetD) were detected. The beta lactamase resistance genes (blaSHV-1, bla CTX-M, bla TEM) were all negative. 24 strains were divided into 15 PFGE types, and their clustering results were more dispersed and no dominant PFGE type. There were 11 kinds of MLST types, most of them are ST540 and ST5133 types, each of which was 4 strains, and clustered into 1 MLST genomes. Conclusion The serotypes of non-O157 STEC in animal feces O157 STEC were dispersed, and the resistant rate to common antibiotic was high. MLST typing results presents obvious polymorphism. Surveillance and manage ment of these strains should be strengthened.

Intracerebral hemorrhage (ICH) refers to bleeding within the brain parenchyma due to the rupture of blood vessels ,and is a highly lethal stroke subtype ,accounting for nearly 10%-15% of all strokes .The morbidity and mortality of ICH are very high and its pathophysiological mechanisms are currently not fully understood .Therefore ,based on current clini-cal evidence-based medicine ,there is no definite and effective medical treatment that can improve the prognosis and survival of patients available yet .As an important tool for basic research ,the development and application of the ICH animal model pro-moted the understanding of the pathophysiological mechanisms and molecular mechanisms leading to brain injury by ICH .Re-cently ,the ICH animal model studies contributed to a number of proposed potential therapeutic strategies ,such as the inhibi-tion of thrombin and the reduction of pro-inflammatory pathways .In addition ,recent research of stem cells suggested that cell transplantation therapy for the treatment of ICH may also have good prospects .In this review ,we discuss the development and application of animal models for studies on ICH and the advances regarding the potential therapeutic strategies for ICH .

Objective To explore the risk factors of urolithiasis incidence of migrant workers in Zhongshan,in order to provide the scientific evidence for preventing urolithiasis.Methods 1 630 workshop migrant workers and 1630 office white collar workers were selected as the subjects of this study.The questionnaire was conducted according to the age,gender,genetic factors,occupation,past illness factors,living environment,work environment factors,diet habit,the habit of drinking water survey,B ultrasound examination,the detection of blood uric acid.Results The incidence rate of urolithiasis was 6.53％,the incidence rate of workshop migrant workers was 8.28％,which was significantly higher than that of white collar 4.72％ (x2 =16.972,P ＜0.01).Conclusion Work environment,eating habits,drinking habits,smoking and sweating are related risk factors of urolithiasis.