A Salmonella bacteriophage,PJN025,was isolated from wastewater and characterized for its biological properties,including whole-genome sequencing and assessment of therapeutic poten-tial in animal infection models.Transmission electron microscopy classified it within the Caudovi-ricetes family.PJN025 selectively lysed S.typhimurium and S.enteritidis with an incubation period of approximately 10 min,a burst time of 80 min,and an average burst size of approximately 132 PFU/cell,demonstrating effective bactericidal activity.The phage showed robust stability at temperatures ranging from 30 to 70 ℃ and pH levels from 3 to 12.Whole-genome sequencing re-vealed a complete genome length of 46 478 bp with a G+C content of 45.9％,consisting of 82 open reading frames and one tRNA.No known virulence or resistance genes were found.In Galleria mellonella infection model,a survival rate of 70％was achieved with a preventative dose of 1 × 108 PFU/mL PJN025,compared to a 5％survival rate in the positive control group after 48 h of bacterial challenge.In SPF mice infected with S.typhimurium via intraperitoneal injection,all mices in the positive control group died within five days.However,in the co-infection group treated with 1×108 PFU/mL PJN025,a promising survival rate of 60％was observed.This study showed that the bacteriophage PJN025 had strong specificity,high lytic efficiency,good acid and alkali tol-erance,strong heat resistance,and good safety and prevention effects,providing materials and ex-perimental basis for the development of subsequent phage products.

Objective:To investigate the genomic characteristics of a clinical strain of respiratory syncytial virus (RSV) causing a severe pneumonia outbreak in a maternity center in a city in northern China in 2021.Methods:The whole genome sequence of RSV from a clinical sample obtained from a child with respiratory failure and heart failure was determined and analyzed using Sanger sequencing method. Sequence splicing and alignment were performed using bioinformatics software such as Sequencher 5.0, MEGA 7.0, and BioEdit 7.0. Besides, its phylogenetic relationship with the representative strains of RSV-B genotype, amino acid variations, and glycosylation sites were analyzed.Results:The genome of the clinical strain (named RSV/SY/2021) was 15 242 bp in length, consisting of 10 genes encoding 11 proteins, and possessed all the structural features of RSV. Phylogenetic analysis showed that the RSV/SY/2021 strain belonged to BA9 genotype and had the closest genetic relationship with the 2018 Netherlands epidemic strain MZ515558/Netherlands/2018. The termination codon mutation at the end of its attachment glycoprotein (G) gene resulted in the elongation of seven amino acids "Q-R-L-Q-S-Y-A" and the introduction of two additional O-glycosylation sites.Conclusions:This study suggests that RSV BA9 genotype may cause severe clinical symptoms, and clarifies the genome-wide characteristics and nucleotide/amino acid variation patterns of the RSV/SY/2021 strain. These findings enrich both national and global genome databases of RSV, and provide crucial etiological data for tracking RSV transmission, nucleic acid testing, and the development and evaluation of vaccines, antibodies and drugs against RSV.

Objective:To investigate the genomic characteristics of a clinical strain of respiratory syncytial virus (RSV) causing a severe pneumonia outbreak in a maternity center in a city in northern China in 2021.Methods:The whole genome sequence of RSV from a clinical sample obtained from a child with respiratory failure and heart failure was determined and analyzed using Sanger sequencing method. Sequence splicing and alignment were performed using bioinformatics software such as Sequencher 5.0, MEGA 7.0, and BioEdit 7.0. Besides, its phylogenetic relationship with the representative strains of RSV-B genotype, amino acid variations, and glycosylation sites were analyzed.Results:The genome of the clinical strain (named RSV/SY/2021) was 15 242 bp in length, consisting of 10 genes encoding 11 proteins, and possessed all the structural features of RSV. Phylogenetic analysis showed that the RSV/SY/2021 strain belonged to BA9 genotype and had the closest genetic relationship with the 2018 Netherlands epidemic strain MZ515558/Netherlands/2018. The termination codon mutation at the end of its attachment glycoprotein (G) gene resulted in the elongation of seven amino acids "Q-R-L-Q-S-Y-A" and the introduction of two additional O-glycosylation sites.Conclusions:This study suggests that RSV BA9 genotype may cause severe clinical symptoms, and clarifies the genome-wide characteristics and nucleotide/amino acid variation patterns of the RSV/SY/2021 strain. These findings enrich both national and global genome databases of RSV, and provide crucial etiological data for tracking RSV transmission, nucleic acid testing, and the development and evaluation of vaccines, antibodies and drugs against RSV.

Objective:To analyze the clinical characteristics of frailty in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:COPD patients aged ≥65 years registered in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of exacerbations in the past year, exposure to risk factors (smoking, biomass fuel exposure, occupational exposure), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, pulmonary tuberculosis, cardiovascular disease, diabetes mellitus) were collected. According to Fried′s frailty phenotype, patients meeting any 3 of the 5 criteria were defined as frail and divided into a frailty group and a non-frailty group. Multivariate regression analysis was used to screen the related factors of frailty in elderly COPD patients, and the receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of related factors for frailty assessment. Results:A total of 496 elderly COPD patients were included, of which 144(29.0%) had comorbid frailty. The frailty group had lower mass body index (BMI), FEV 1%pred, and FEV 1/FVC, higher mMRC and CAT scores, more exacerbations and hospitalizations in the past year (all P<0.001), and higher proportions of patients with junior high school education or below, Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E, and GOLD grades 3 and 4 (all P<0.05). Multivariate regression analysis showed that low education level ( OR=2.117, 95% CI: 1.119-4.003), low BMI ( OR=0.927, 95% CI: 0.867-0.991), GOLD grade 4 ( OR=4.251, 95% CI: 1.477-12.235), high CAT score ( OR=1.174, 95% CI: 1.127-1.224), and high mMRC score ( OR=4.578, 95% CI: 3.364-6.231) were independent risk factors for frailty in elderly COPD patients (all P<0.05). The ROC curve showed that CAT score (AUC=0.78) and mMRC score (AUC=0.81) had the highest AUC for assessing frailty in elderly COPD patients. Conclusions:Elderly COPD patients with frailty have lower BMI, worse lung function, and more severe symptom burden. The results provide clinical reference for the management of frail elderly COPD patients.

Objective:To analyze the clinical characteristics of frailty in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:COPD patients aged ≥65 years registered in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of exacerbations in the past year, exposure to risk factors (smoking, biomass fuel exposure, occupational exposure), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, pulmonary tuberculosis, cardiovascular disease, diabetes mellitus) were collected. According to Fried′s frailty phenotype, patients meeting any 3 of the 5 criteria were defined as frail and divided into a frailty group and a non-frailty group. Multivariate regression analysis was used to screen the related factors of frailty in elderly COPD patients, and the receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of related factors for frailty assessment. Results:A total of 496 elderly COPD patients were included, of which 144(29.0%) had comorbid frailty. The frailty group had lower mass body index (BMI), FEV 1%pred, and FEV 1/FVC, higher mMRC and CAT scores, more exacerbations and hospitalizations in the past year (all P<0.001), and higher proportions of patients with junior high school education or below, Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E, and GOLD grades 3 and 4 (all P<0.05). Multivariate regression analysis showed that low education level ( OR=2.117, 95% CI: 1.119-4.003), low BMI ( OR=0.927, 95% CI: 0.867-0.991), GOLD grade 4 ( OR=4.251, 95% CI: 1.477-12.235), high CAT score ( OR=1.174, 95% CI: 1.127-1.224), and high mMRC score ( OR=4.578, 95% CI: 3.364-6.231) were independent risk factors for frailty in elderly COPD patients (all P<0.05). The ROC curve showed that CAT score (AUC=0.78) and mMRC score (AUC=0.81) had the highest AUC for assessing frailty in elderly COPD patients. Conclusions:Elderly COPD patients with frailty have lower BMI, worse lung function, and more severe symptom burden. The results provide clinical reference for the management of frail elderly COPD patients.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

Insufficient future liver remnant volume remains a critical limitation for single-stage resection in patients with hepatic malignancies. The techniques for promoting future liver remnant hypertrophy to realize two-stage hepatectomy include portal vein embolization， associating liver partition and portal vein ligation for staged hepatectomy， and portal vein ligation. In recent years， the application of auxiliary liver transplantation has further facilitated two-stage total hepatectomy. This article systematically reviews the clinical applications of these techniques and analyzes their advantages and limitations， so as to provide a reference for optimizing clinical decision-making.

Objective To investigate the features of resting-state electroencephalography(EEG)in stroke patients with limited upper limb movement,and assess its potential utility in evaluating upper limb motor function.Methods From March to August,2024,a total of 71 stroke patients with limited upper limb movement were enrolled as stroke group at the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine;while 63 healthy participants matched for age and sex were recruited as control group.They were tested with 19-chan-nel resting-state EEG(rsEEG),calculating of the pairwise derived brain symmetry index(pdBSI)and Delta/Al-pha ratio(DAR).The motor function was assessed with Fugl-Meyer Assessment-Upper Extremities(FMA-UE),the upper limb recovery was evaluated with Brunnstrom Stages and the activities of daily living was assessed with modified Barthel index(MBI)in stroke patients,Results Compared with the control group,the pdBSI of Global lead,Frontal region,Central region and Posterior region across Delta,Alpha and Beta1 frequency bands were significantly higher in the stroke group than in the control group(|Z|>2.289,P<0.05);as well as the pdBSI of Global lead,Central region and Posterior region across The-ta bands(|Z|>3.016,P<0.01),the pdBSI of Global lead,Frontal region,Central region and Posterior region across Beta2 bands(|Z|>3.222,P<0.01),DAR of Global lead,Frontal region,Central region and Posterior re-gion(|Z|>6.565,P<0.001).In the stroke group,the pdBSI of Global lead(r=-0.280,P=0.018)and Central region(r=-0.304,P=0.010)across the Delta band were significantly negatively correlated with FMA-UE,as well as the pdBSI of Global leads(r=-0.289,P=0.014),Central region(r=-0.244,P=0.040)and Posterior region(r=-0.356,P=0.002)across the Beta1 band,and the DAR of Global lead(r=-0.431,P<0.001),Fron-tal region(r=-0.429,P<0.001),Central region(r=-0.491,P<0.001)and Posterior region(r=-0.482,P<0.001).Conclusion Asymmetry in spectral power between hemispheres in the Delta(0.5 to 4 Hz)and Beta(13 to 20 Hz)bands is found in stroke patients,especially in the central region,which correlates with upper limb function limitations.pdBSI Delta,pdBSI Beta1 and DAR are potential neuroelectrophysiological markers for assessing upper limb motor function in stroke patients.