Bacillus velezensis DJ1 exhibits broad-spectrum antagonistic activity against diverse phytopathogenic fungi, while its biocontrol mechanisms against Fusarium graminearum, the causal agent of maize stalk rot, remain poorly characterized. In this study, we integrated genomics and transcriptomics to elucidate the antifungal mechanisms of strain DJ1. The results demonstrated that DJ1 inhibited F. graminearum with the efficacy of 64.4%, while its polyketide crude extract achieved the control efficacy of 55% in pot experiments against this disease. Whole-genome sequencing revealed a single circular chromosome (3 929 792 bp, GC content of 47%) harboring 12 biosynthetic gene clusters for secondary metabolites, six of which encoded known antimicrobial compounds (macrolactin H, bacillaene, difficidin, surfactin, fengycin, and bacilysin). Transcriptomic analysis identified 243 differentially expressed genes (152 upregulated and 91 downregulated, P < 0.05), which were potentially associated with the antagonistic activity against F. graminearum. KEGG enrichment analysis highlighted activation (P < 0.05) of cysteine/methionine metabolism, pentose phosphate pathway, and polyketide biosynthesis pathways, indicating that DJ1 employed synergistic strategies involving antimicrobial compound synthesis, energy metabolism enhancement, and nutrient competition to suppress pathogens. This study provides a theoretical foundation for developing novel microbial resources and application technologies to combat phytopathogenic fungi.
Fusarium/drug effects* ; Bacillus/metabolism* ; Plant Diseases/prevention & control* ; Antifungal Agents/pharmacology* ; Genomics ; Zea mays/microbiology* ; Transcriptome ; Gene Expression Profiling ; Antibiosis ; Multigene Family ; Multiomics

Objective:To discuss the effect of asiatic acid(AA)on the inflammation and oxidative stress damage induced by lipopolysaccharide(LPS)in the primary cultured hippocampus neurons,and to clarify its mechanism.Methods:The primary cultured rat hippocampus neurons(cell purity identified by immunofluorescence staining)were divided into control group,LPS(10 mg·L-1)group,and LPS+AA group(10 mg·L-1 LPS+10,20,and 40 μmol·L-1 AA),AA group(20 μmol·L-1 AA),ML385 group[10 μmol·L-1 nuclear factor erythroid 2-related factor(Nrf2)inhibitor],and LPS+ML385+AA group(10mg·L-1 LPS+10 μmol·L-1 ML385+20 μmol·L-1 AA).After drug treatment,methylthiazolyldiphenyl-tetrazolium bromide(MTT)method was used to detect the survival rates of the hippocampus neurons in various groups;lactate dehydrogenase(LDH)kit was used to detect the LDH leakage rates of the hippocampus neurons in various groups;enzyme linked immunosorbent assay(ELISA)kit was used to detect the expression levels of inflammatory factors[interleukin(IL)-1β and tumor necrosis factor(TNF)-α]and the activities of superoxide dismutase(SOD)and malondialdehyde(MDA)levels in the hippocampus neurons in various groups;Griess method was used to detect the nitric oxide(NO)levels in supernatant of the hippocampus neurons in various groups;immunofluorescence staining was used to detect the expressions of Nrf2 and heme oxygenase-1(HO-1)proteins in the hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,HO-1,nuclear factor-kappa B(NF-κB),and B-cell lymphoma 2(Bcl-2)proteins in the hippocampus neurons in various groups.Results:Compared with control group,the survival rate of the hippocampus neurons,SOD activity,and Bcl-2 expression level in the cells in LPS group were significantly decreased(P＜0.01),while the LDH leakage rate,expression levels of IL-1β and TNF-α,MDA level,and NO level,as well as the expression level of NF-κB protein,were significantly increased(P＜0.01);the fluorescence intensities and expression levels of Nrf2 and HO-1 proteins in hippocampus neurons were significantly decreased(P＜0.01).Compared with LPS group,the survival rates of hippocampus neurons,SOD activities,and expression levels of Bcl-2 in the cells in LPS+10 μmol·L-1 AA group and 20 μmol·L-1 AA group were significantly increased(P＜0.01),while the LDH leakage rates,expression levels of IL-1β and TNF-α,MDA levels,and NO levels,as well as expression levels of NF-κB protein,were significantly decreased(P＜0.05 or P＜0.01),and the fluorescence intensities and protein expression levels of Nrf2 and HO-1 in the cells were significantly increased(P＜0.01).Compared with LPS+20 μmol·L-1 AA group,the fluorescence intensities of Nrf2 and HO-1 in the cells in LPS+ML385+AA group were significantly decreased(P＜0.01),and the expression levels of Nrf2 protein in the nucleus and cytoplasm,the expression levels of HO-1 and Bcl-2 proteins in the cells were significantly decreased(P＜0.01),while the expression level of NF-κB protein was significantly increased(P＜0.01).Conclusion:AA can improve LPS-induced inflammation and oxidative stress damage in the primary cultured rat hippocampus neurons,and its mechanism may be related to the activation of the Nrf2/HO-1 signaling pathway.

Objective:To explore the molecular epidemiological characteristics of human metapneumovirus (HMPV) in children with acute respiratory infection (ARI) in Beijing from 2023 to 2024.Methods:In the longitudinal study, 9 834 children with ARI were enrolled from August 2023 to December 2024, including the influenza-like illness (ILI) group from emergency and outpatient department receiving influenza virus (Flu) and HMPV test and the ARI inpatient group for 13 common respiratory pathogen screening test including HMPV, Flu, respiratory syncytial virus, and so on. All respiratory samples positive with HMPV were genotyped by amplifying and sequencing of G gene and further phylogenetic analysis. The χ2 test and Wilcoxon rank-sum test were used to compare the positive rate and basic clinical data of the 2 groups. Results:Among 9 834 enrolled patient, there were 5 276 male and 4 558 female children, with age 5.4 (1.9, 8.2) years. In ILI group of 1 460 patients, there were 83 cases (5.7%) positive for HMPV, with the age 4.9 (3.6, 6.6) years and children under 6.0 years old 59 cases (71.1%). Among 8 374 ARI inpatients, there were 256 cases (3.1%) positive for HMPV, with age 3.5 (1.3, 6.4) years and children under 6.0 years old 188 cases (73.4%). The HMPV positive rate and the age of children positive for HMPV in ARI inpatient group were significantly lower than that in ILI group (both P<0.001). In December, 2024, the HMPV positive rates of ILI and ARI inpatient group (21.3% (17/80), 15.0% (47/314)) were significantly higher than the total positive rates of each group (both P<0.001). Among 279 subtyped specimens, there were 155 cases (55.6%) belonging to genotype A and 124 cases (44.4%) belonging to genotype B. Sub-lineage A2.2.2 containing 111nt-insertions was predominate one in 2023 with positive ratio 89.2% (91/102), and B2 was predominate in 2024 with positive ratio 64.4% (114/177). Conclusions:From 2023 to 2024, the positive rate of HMPV in the ILI group was higher than that in the ARI inpatient group, suggesting a common epidemic of HMPV infection. Children positive for HMPV in the ARI inpatient group were younger than that in the ILI group. A severe epidemic of HMPV was observed in the winter of 2024, which requires attention. Sub-lineage A2.2.2 with 111nt-duplicate insertions and B2 were the predominant epidemic strains in 2023 and 2024, respectively.

Objective To investigate the relationship of TyG index and IC.Methods A cross-sectional study was conducted with 1000 older adults living in Wanshou Road Community from May to December 2023.Finally 820 participants were enrolled,and based on the TyG index,they were divided into lower TyG index group(≤7.349,404 cases)and higher TyG index group(＞7.349,416 cases).After PSM,there were only 522 participants subjected,including 261 individuals in the lower TyG index group 1 (≤7.349)and 416 ones in the higher TyG index group 2(＞7.349).Univariate and multivariate logistic regression analyses were used to assess the correlation between IC and the TyG index as both continuous and categorical variables.PSM was employed to eliminate the confounding effects of covariates to identify the relationship between TyG index and IC in different categories.Results Before PSM,the neutrophil count,WBC count,and Hcy,FPG,TC,TG and HbA1c levels were significantly lower,and lymphocyte count,monocyte count,and AST level were obviously higher in the low TyG index group than the high TyG index group(P＜0.05,P＜0.01).After PSM,the low TyG index group still had notably lower FPG,TG and HbA1c than the high TyG index group(P＜0.05,P＜0.01).ROC curve analysis revealed that the cutoff value of TyG index was 7.349.Taking 7.349 as the cutoff value and TyG index as the cate-gorical variable,multivariate logistic regression analysis displayed that TyG index was correlated with IC[OR=3.921,95％CI:2.800-5.491,P=0.001(Model 1);OR=2.744,95％CI:1.739-4.329,P=0.001(Model 2);OR=2.744,95％CI:1.805-4.171,P=0.001(Model 3);OR=2.722,95％CI:1.530-4.843,P=0.001(after PSM)],indicating that TyG index remains an independent risk factor for IC.Conclusion IC is still correlated with TyG index in community-dwelling elderly individuals under different baseline conditions after adjusting for relevant laboratory indicators.As an indicator generated from routine blood test,TyG index has advantages in terms of cost and time.With further validation,TyG may provide a direction for studying IC prediction.

Objective To investigate the regulatory effects of liraglutide(Lira)on adipocyte brown-ing and its underlying molecular mechanisms.Methods Adipose-derived mesenchymal stem cells were induced to differentiate with palmitic acid(PA)simulating a high-fat environment and lenti-viral transfection to silence the expression of PGC1α.The cell groups included control,Lira(100 nmol/L),PA(200 nmol/L),PA+Lira,scrambled siRNA,scrambled siRNA+Lira,siRNA PGC1α,and siRNA PGC1α+Lira groups(n=3).After corresponding treatments were given,quantitative PCR and Western blotting were employed to detect the mRNA and protein expres-sion levels of UCP-1,Prdm16,Agt,and adiponectin,as well as AMPK and p-AMPK.Results Compared to the control group,the PA group had significantly increased expression of Agt and adiponectin but decreased UCP-1 and Prdm16 at protein and mRNA levels,and the Lira group showed obviously increased protein and mRNA levels of UCP-1 and Prdm16 but decreased Agt and adiponectin levels(P＜0.05).Addition of Lira treatment resulted in increments in UCP-1 and Prdm16 while declines Agt and adiponectin at both mRNA and protein levels when compared with the levels in the PA group(P＜0.05).In comparison to the scrambled siRNA group,the siRNA PGC1α group showed decreases in UCP-1 and Prdm16 expression,accompanied by increa-ses in Agt and adiponectin levels(P＜0.05),similar results were observed in the scrambled siRNA+Lira group(P＜0.05).The p-AMPK/AMPK ratio was significantly increased in the scrambled siRNA+Lira group(1.415±0.176 vs 0.837±0.049,P＜0.05),but decreased in the siRNA PGC1α group(0.534±0.035 vs 0.837±0.049,P＜0.01)when compared with the scram-bled siRNA group.Conclusion Lira promotes adipocyte browning and improves lipid metabolism disorders in a high-fat environment by activating the AMPK/PGC1α signaling pathway.

Objective To investigate the short-term efficacy of arthroscopic total internal suture combined with platelet-rich plasma(PRP)in the treatment of lateral meniscal popliteal hiatus area injuries.Methods Forty-eight patients diagnosed with lateral meniscal popliteal hiatus area injuries in our hospital from January 2020 to December 2022 were selected and divided into Fast-Fix total internal suture group(FF group,n=23)and Fast-Fix total internal suture combined with PRP group(PRP group,n=25)according to treatment methods.The positive rate of McMurray test at 6 and 12 months after surgery,the preoperative and postoperative visual analogue scale(VAS)of pain,the International Knee Documentation Committee(IKDC)scores,the Lysholm Knee Function Scores,and the Knee Society Scores(KSS)were compared between the two groups.Results No adverse events such as vascular and nerve injury,fever and infection occurred in both groups.There was no significant difference between the two groups in the positive rates of McMurray test at 6 and 12 months(χ2=0.880,P=0.348;Fisher's exact test,P=0.479).In the PRP group,25 cases were followed up for11-14 months,with an average of(12.2±0.8)months;in the FF group,23 cases were followed up for11-14 months,with an average of(12.8±0.8)months.The VAS scores at 6 months and 12 months after surgery were significantly lower than those before surgery in both groups(all P=0.000).The VAS scores of the PRP group at 6 and 12 months after surgery were significantly lower than those of the FF group(P<0.05).Both groups showed significant improvements in IKDC,Lysholm,and KSS scores at 6 and 12 months after surgery compared to preoperative levels(all P=0.000).The IKDC,Lysholm,and KSS scores of the PRP group at 6 and 12 months after surgery were significantly higher than those of the FF group(P<0.05).Conclusion Compared to Fast-Fix total internal suture alone,PRP joint cavity adjuvant therapy based on Fast-Fix total internal suture surgery could reduce the postoperative pain of patients,and promote the functional recovery of the knee joint,which is more recommended in clinical practice.

Objective:To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation.Methods:A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlations were analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children′s Medical Center (Ethics No.: 2022-406B00).Results:The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c. 2668C>T; p. Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case reports has associated it with this phenotypic spectrum. It was not observed in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. Conclusion:This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c. 2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies in prenatal diagnostics. Above findings have advanced our understanding of pleiotropic effects in type Ⅱ collagen disorders and lay the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities in high-risk families.

Objective:To develop a nomogram model utilizing serological indicators for predicting in-hospital major adverse cardiovascular events(MACE)in elderly patients diagnosed with acute coronary syndrome(ACS).Methods:This study involved a retrospective analysis of clinical data from 1, 818 elderly patients with ACS who were treated at the First Medical Center of the General Hospital of the People's Liberation Army from January 2022 to May 2024.The patients were randomly assigned to a training set(1, 272 cases)and a validation set(546 cases)in a 7: 3 ratio.Following a comparison of the two groups, the training set was further categorized into non-MACE and MACE groups based on the occurrence of endpoint events.Univariate analysis, Lasso regression, and multivariate logistic regression analyses were sequentially employed to identify factors influencing in-hospital MACE and to construct the nomogram model.The performance of the model was assessed using receiver operating characteristic(ROC)curves, calibration curves, and decision curves.Results:Among the 1, 818 ACS patients, the mean age was 67 years(interquartile range: 61.0 to 73.0), with 70.4% being male.Almost all indicators(except platelet count)exhibited no statistically significant differences between the training and validation sets(all P>0.05).However, statistically significant differences(all P<0.05)were observed in age, body mass index, neutrophil count, lymphocyte count, monocyte count, white blood cell count, hemoglobin, red blood cell distribution width, mean platelet volume, C-reactive protein(CRP), fibrinogen, D-dimer, albumin, direct bilirubin, troponin T(TnT), fasting blood glucose(FBG), estimated glomerular filtration rate(eGFR), uric acid, N-terminal pro-B-type natriuretic peptide(NT-proBNP), glycated hemoglobin(HbA1c), and high-density lipoprotein cholesterol(HDL-C)between the non-MACE and MACE groups in the training set.Ultimately, seven variables—neutrophil count, hemoglobin, red blood cell distribution width, CRP, TnT, FBG, and NT-proBNP—were selected to construct the nomogram model.The model demonstrated high discrimination in both the training and validation sets, with an area under the curve of 0.86(95% CI: 0.82-0.90)for the training set and 0.85(95% CI: 0.81-0.90)for the validation set.Furthermore, the calibration curves for both cohorts indicated a close agreement between predicted and actual risk estimates, suggesting improved model calibration.Decision curve analysis indicated that the predictive model has notable clinical utility. Conclusions:The constructed nomogram enhances the accuracy of predicting in-hospital MACE in elderly patients with ACS, thereby offering a valuable reference for clinical practice.

Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.

OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*