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 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*

Objective:To analyze the epidemiological features of respiratory syncytial virus (RSV) infection in Beijing, and monitor the sequence variations in RSV glycoprotein (G) gene and clinical features of infected children.Methods:Respiratory tract specimens were collected from children with acute respiratory infection in the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 1, 2023 to December 31, 2023. RSV-positive specimens screened by multiple nucleic acid testing were subjected to PCR to amplify the full-length RSV G gene. A phylogenetic tree was constructed after gene sequencing to analyze RSV subtypes and trace G gene variants. Clinical data were retrieved from the medical record system to analyze the clinical features of children with RSV infection in Beijing.Results:A total of 5 489 respiratory specimens were collected from 3 046 male patients and 2 443 female patients. The average age of the patients was 4.36 years. A total of 589 RSV-positive specimens (10.7%, 589/5 489) were detected with 349 from male patients and 240 from female patients. The average age of children with RSV infection was (2.51±2.78) years and the median age was 0.48 years. RSV had been circulating among children in Beijing since March 2023 with two epidemic peaks in May (24.6%, 122/496) and December (18.2%, 126/693). The predominant subtype of RSV in the first half of 2023 was subtype A, but it was replaced by subtype B from November 2023. Phylogenetic analysis revealed a novel G gene of RSV subtype B (RSV-B-BA9-954bp) with a length of 954 bp, which belonged to a new cluster in the phylogenetic tree. The percentage of patients admitted to the Intensive Care Unit (ICU) was higher in children with new variant of RSV subtype B infection than in those with common RSV subtype B infection [44.1% (15/34) vs 25.2% (31/123), χ 2=4.600, P=0.032], while the counts of white blood cells and the levels of C-reactive protein were lower in the children with new variant infection ( P<0.05). Conclusions:RSV has been prevalent among children in Beijing since March 2023 with two epidemic peaks. The predominant A subtype is gradually replaced by to B subtype. A new variant of RSV B G gene (RSV-B-BA9-954bp) is detected among the children.

Diabetes mellitus is a complex metabolic disease involving multiple organ systems in the body.In recent years,its global incidence rate has increased year by year.In China,the blood glucose control of patients with diabetes mellitus who receive oral hypogly-cemic agents or insulin treatment remains poor.In the early disease stages,exercise is important to control blood glucose levels.Recently,many studies have found that the occurrence of type 2 diabetes mellitus was related to declining levels of irisin,an exercise-related muscle factor.Furthermore,studies have found that irisin improved insulin resistance,promoted the production of pancreatic isletβcells,and affected the body's glucose and lipid metabolism.In addition,its levels were also implicated in the occurrence of various complications,such as diabetic nephropathy and diabetes-related cardiovascular diseases.This article summarizes and analyzes the role of irisin in the occurrence and development of diabetes mellitus and further describes its impact and mechanism on various diabetic complications.

Humans ; Alzheimer Disease ; Cross-Sectional Studies ; Creatine Kinase ; Brain/metabolism*

Objective: To evaluate the efficacy and safety of Jiawei Simiao powder (JWSMP) combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials (RCTs). Methods: The Chinese National Knowledge Infrastructure Databases, Chinese Scientific Journal Database, Wanfang, Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched from inception until December 2023. Continuous variables were analyzed using the mean difference (MD) for analysis, and dichotomous variables were used as risk ratios. Data with similar characteristics were pooled for meta-analysis, and heterogeneity was assessed using I2. The Cochrane Handbook was used to assess the risk of bias and quality. RevMan 5.3 software was used to perform the meta-analysis. Results: Thirteen RCTs involving 1007 patients were included in the study. The quality of the included studies was low (unclear randomization processes and insufficient blinding reporting). The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid (SUA, MD = −66.32, 95% confidence interval (CI): −80.97 to −51.67, P < .001), erythrocyte sedimentation rate (ESR, MD = −6.05, 95% CI: −8.29 to −3.82, P < .001), C-reactive protein (CRP, MD = −7.39, 95% CI: −11.15, −3.63, P < .001), and joint pain score (VAS score, MD = −2.14, 95% CI: −2.4 to −1.88, P < .001) compared to celecoxib alone. Additionally, the JWSMP combined group had a higher total effective rate (risk ratio = 1.22, 95% CI: 1.14 to 1.29, P < .001) and fewer adverse compared to celecoxib alone. Conclusions JWSMP combined with celecoxib is more effective than celecoxib alone in improving the total efficacy rate, alleviating joint pain, and improving SUA, ESR, and CRP levels. JWSMP also reduced the occurrence of adverse events caused by celecoxib. However, the quality of the included studies was low, highlighting the need for further high-quality research with larger sample sizes and robust methodologies, such as double-blind randomization, to confirm these findings.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To discuss the protective effect of carnosine(CAR)against oxygen-glucose deprivation/reoxygenation(OGD/R)-induced astrocyte(AS)injury,and to clarify its possible mechanism.Methods:The AS were divided into control group,model group(OGD/R group),OGD/R+CAR group(CAR group),and OGD/R+CAR+AMP-activated protein kinase(AMPK)activator AICAR group(CAR+AICAR group).MTT assay and green cyanine staining method were used to detect the survival rates and green cyanine staining positive rates of the AS in various groups;Annexin V-FITC/PI method and flow cytometry were used to detect the apoptotic rates of the AS in various groups;Western blotting method was used to detect the expression levels of AMPK,phosphorylated AMPK(p-AMPK),mammalian target of rapamycin(mTOR),phosphorylated mTOR(p-mTOR),microtubule-associated protein light chain 3B(LC3B),Beclin-1,and P62 proteins in the AS in various groups;immunofluorescence staining was used to observe the LC3B positive fluorescence intensities in the AS in various groups.Results:Compared with control group,the survival rate and green cyanine staining positive rate of the AS in OGD/R group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).Compared with OGD/R group,the survival rate and green cyanine staining positive rate of the AS in CAR group were increased(P＜0.01),the apoptotic rate of the AS was decreased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were decreased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were increased(P＜0.01).Compared with CAR group,the survival rate and green cyanine staining positive rate of the AS in CAR+AICAR group were decreased(P＜0.01),the apoptotic rate of the AS was increased(P＜0.01),the ratios of p-AMPK/AMPK and LC3B Ⅱ/LC3B Ⅰ and the expression level of Beclin-1 protein were increased(P＜0.01),and the ratio of p-mTOR/mTOR and the expression level of P62 protein were decreased(P＜0.01).The LC3B immunofluorescence staining results were consistent with the Western blotting results.Conclusion:CAR has the protective effect on injury of the AS induced by OGD/R,and its molecular mechanism may be related to the inhibition of the AMPK/mTOR signaling pathway,thereby inhibiting autophagy.

Objective:To summarize the best evidence for the management of lower urinary tract dysfunction (LUTD) in total hysterectomy patients, so as to provide evidence-based basis for clinical practice.Methods:According to the "6S" pyramid model, literature related to the management of LUTD in total hysterectomy patients was successively searched from guide websites, evidence-based websites, professional websites and comprehensive databases. The search deadline was from the establishment of the databases to March 31, 2023. Two researchers evaluated the quality of the included literature, extracted evidence and recommended the level of evidence.Results:A total of 14 articles were included, including one clinical decision, two evidence summaries, three guidelines, one expert consensus and seven systematic evaluations. A total of 25 pieces of evidence were summarized from four aspects, such as symptom assessment, urinary tract management, symptom intervention and health education.Conclusions:Medical staff should manage lower urinary tract dysfunction in patients undergoing total hysterectomy based on evidence-based evidence to prevent or reduce the occurrence of lower urinary tract dysfunction in patients.

Objective:To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases.Methods:Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated.Results:Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg -1·d -1 and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status ( OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication ( OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion:L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.