This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.

Aim To investigate the effect of ACSL4 on the malignant biological behavior of esophageal cancer cells and gefitinib resistance by regulating FASN,and to explore the related mechanism.Methods Thirty-five fresh esophageal cancer tissues and adjacent nor-mal tissues,and 30 esophageal cancer tissues with ge-fitinib resistance were collected.The expressions of ACSL4 and FASN were detected by qRT-PCR and im-munohistochemistry.The expression levels of ACSL4 and FASN in human normal esophageal cells HET-1 A,esophageal cancer cell lines ECA109,EC9706,TE-1 and TE-1/GR were detected by qRT-PCR.Cells in each group were constructed by liposome transfection technique,and the drug resistance and proliferation a-bility of cells were detected by cloning and CCK-8 as-say,cell apoptosis was detected by flow cytometry,cell invasion ability was detected by Transwell,and EMT pathway protein expression was detected by Western blot.Results Compared with adjacent normal tis-sues,the expression of ACSL4 and FASN genes in cancer tissues increased,and there was a positive corre-lation.The expression of ACSL4 significantly increased in ECA109,EC9706 and TE-1 cells compared with HET-1 A cells.With the increase of gefitinib concen-tration,the expression of ACSL4 in TE-1 cells gradually increased,and the expression of ACSL4 in TE-1/GR cells was higher than that of TE-1.Compared with the control group and the si-NC group,the cell proliferation and invasion ability of si-ACSL4 group decreased,the number of apoptosis increased,the expression of E-Cadherin increased,and the expression of N-Cadherin,Vimentin and β-catenin decreased.The response ex-periment showed that compared with the si-ACSL4 group and the si-ACSL4+oe-NC group,the cells in the si-ACSL4+oe-FASN group increased drug resistance,increased proliferation and invasion ability,decreased apoptosis number and decreased expression of E-Cad-herin.The expressions of N-Cadherin,Vimentin and β-catenin increased.Conclusions By down-regulating the expression of FASN,ACSL4 reverses the resistance of esophageal cancer TE-1/GR cells to gefitinib and in-hibits the proliferation,invasion and accelerates apopto-sis of TE-1/GR cells,which may be related to the regu-lation of EMT signaling pathway.

Objective:To observe the effect of Guilu Taohong Formula on semen quality in varicocele(VC)models of rats,and to explore its possible mechanism.Methods:Forty-eight male SD rats were randomly divided into four groups(sham group,model group,Guilu Taohong Formula group and L-carnitine group).After the establishment of models,the rats were treated with intra-gastric administration for eight consecutive weeks.The general condition of the rats was observed.After the gavage,the testicular and epididymal indices were calculated.Semen quality was assessed using an automatic semen analyzer.Apoptosis of testicular cells was assessed by TUNEL staining.And the expression levels of B-cell lymphocytoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and cys-teine aspartate protease-3(caspase-3)in testicular tissue were detected by Western blot.Results:Compared with the sham group,testicular index,epididymal index,sperm concentration,the percentage of progressive motility of sperm(PR％)and the expression level of Bcl-2 decreased in model group(P＜0.01).An increased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were observed in model group as well(P＜0.01).Compared with the model group,the testicular index,epidid-ymal index,sperm concentration,PR％and the expression level of Bcl-2 in Guilu Taohong Formula group increased significantly(P＜0.05,P＜0.01).A decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were de-tected in Guilu Taohong Formula group as well(P＜0.01).Similarly,the L-carnitine group showed increased testicular index,epidid-ymal index,sperm concentration,PR％and the expression level of Bcl-2 protein(P＜0.05,P＜0.01),where showed decreased ap-optosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins compared with model group(P＜0.01,P＜0.05).Conclusion:Guilu Taohong Formula improves semen quality in VC model rats and reduces the apoptosis rate of spermato-genic cells in testicular tissue,which may be related to the promotion of Bcl-2 protein expression and the inhibition of Bax and caspase-3 protein expression levels.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Objective To investigate the status quo,driving factors and clinical intervention measures of intrinsic capacity(IC)in elderly patients with cerebrovascular disease.Methods Clinical data of 206 elderly patients with cerebrovascular disease admitted to our hospital from January to December 2024 were retrospectively collected.According to the IC score,they were divided into a low IC group(123 cases,IC score＜4)and a good IC group(83 cases,IC score≥4).The IC scores were compared between the two groups,and the driving factors affecting the IC were analyzed.Results The low IC group exhibited significantly lower IC score than the good IC group(1.94±0.49 vs 4.52±0.15,P＜0.01).The age ≥80 years,dysfunctions,three or more chronic diseases,frailty,albumin ≤ 35 g/L,pre-albumin ≤280 mg/L,rehabilitation guidance and regular exercises were the influencing factors of IC in elderly patients with cerebrovascular disease(P＜0.05,P＜0.01).Conclusion The IC of elderly patients with cerebrovascular disease is associated with many factors,and corresponding clinical intervention measures should be implemented to promote the improvement of patient's IC.

Depression, a prevalent mental disorder with significant socioeconomic burdens, underscores the urgent need for safe and effective non-pharmacological interventions. Recent advances in microbiome research have revealed the pivotal role of gut microbiota dysbiosis in the pathogenesis of depression. Concurrently, exercise, as a cost-effective and accessible intervention, has demonstrated remarkable efficacy in alleviating depressive symptoms. This comprehensive review synthesizes current evidence on the interplay among exercise, gut microbiota modulation, and depression, elucidating the mechanistic pathways through which exercise ameliorates depressive symptoms via the microbiota-gut-brain (MGB) axis. Depression is characterized by gut microbiota alterations, including reduced alpha and beta diversity, depletion of beneficial taxa (e.g., Bifidobacterium, Lactobacillus, and Coprococcus), and overgrowth of pro-inflammatory and pathogenic bacteria (e.g., Morganella, Klebsiella, and Enterobacteriaceae). Metagenomic analyses reveal disrupted metabolic functions in depressive patients, such as diminished synthesis of short-chain fatty acids (SCFAs), impaired tryptophan metabolism, and dysregulated bile acid conversion. For instance, Bifidobacterium longum deficiency correlates with reduced synthesis of neuroactive metabolites like homovanillic acid, while decreased Coprococcus abundance limits butyrate production, exacerbating neuroinflammation. Furthermore, elevated levels of indole derivatives from Clostridium species inhibit serotonin (5-HT) synthesis, contributing to depressive phenotypes. These dysbiotic profiles disrupt the MGB axis, triggering systemic inflammation, neurotransmitter imbalances, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Exercise exerts profound effects on gut microbiota composition, diversity, and metabolic activity. Longitudinal studies demonstrate that sustained aerobic exercise increases alpha diversity, enriches SCFA-producing genera (e.g., Faecalibacterium prausnitzii, Roseburia, and Akkermansia), and suppresses pathobionts (e.g., Desulfovibrio and Streptococcus). For example, a meta-analysis of 25 trials involving 1 044 participants confirmed that exercise enhances microbial richness and restores the Firmicutes/Bacteroidetes ratio, a biomarker of metabolic health. Notably, endurance training promotes Veillonella proliferation, which converts lactate into propionate, enhancing energy metabolism and delaying fatigue. Exercise also strengthens intestinal barrier integrity by upregulating tight junction proteins (e.g., ZO-1, occludin), thereby reducing lipopolysaccharide (LPS) translocation and systemic inflammation. However, excessive exercise may paradoxically diminish microbial diversity and exacerbate intestinal permeability, highlighting the importance of moderate intensity and duration. Exercise ameliorates depressive symptoms through multifaceted interactions with the gut microbiota, primarily via 4 interconnected pathways. First, exercise mitigates neuroinflammation by elevating anti-inflammatory SCFAs such as butyrate, which suppresses NF-κB signaling to attenuate microglial activation and oxidative stress in the hippocampus. Animal studies demonstrate that voluntary wheel running reduces hippocampal TNF‑α and IL-17 levels in stress-induced depression models, while fecal microbiota transplantation (FMT) from exercised mice reverses depressive behaviors by modulating the TLR4/NF‑κB pathway. Second, exercise regulates neurotransmitter dynamics by enriching GABA-producing Lactobacillus and Bifidobacterium, thereby counteracting neuronal hyperexcitability. Aerobic exercise also enhances the abundance of Lactobacillus plantarum and Streptococcus thermophilus, which facilitate 5-HT and dopamine synthesis. Clinical trials reveal that 12 weeks of moderate exercise increases fecal Coprococcus and Blautia abundance, correlating with improved 5-HT bioavailability and reduced depression scores. Third, exercise normalizes HPA axis hyperactivity by reducing cortisol levels and restoring glucocorticoid receptor sensitivity. In rodent models, chronic stress-induced corticosterone elevation is reversed by probiotic supplementation (e.g., Lactobacillus), which enhances endocannabinoid signaling and hippocampal neurogenesis. Furthermore, exercise upregulates brain-derived neurotrophic factor (BDNF) via microbial metabolites like butyrate, promoting histone acetylation and synaptic plasticity. FMT experiments confirm that exercise-induced microbiota elevates prefrontal BDNF expression, reversing stress-induced neuronal atrophy. Fourth, exercise reshapes microbial metabolic crosstalk, diverting tryptophan metabolism toward 5-HT synthesis instead of neurotoxic kynurenine derivatives. Butyrate inhibits indoleamine 2,3-dioxygenase (IDO), a key enzyme in the kynurenine pathway linked to depression. Concurrently, exercise-induced Akkermansia enrichment enhances mucin production, fortifies the gut barrier, and reduces LPS-driven neuroinflammation. Collectively, these mechanisms underscore exercise as a potent modulator of the microbiota-gut-brain axis, offering a holistic approach to alleviating depression through microbial and neurophysiological synergy. Current evidence supports exercise as a potent adjunct therapy for depression, with personalized regimens (e.g., aerobic, resistance, or yoga) tailored to individual microbiota profiles. However, challenges remain in optimizing exercise prescriptions (intensity, duration, and type) and integrating them with probiotics, prebiotics, or FMT for synergistic effects. Future research should prioritize large-scale randomized controlled trials to validate causality, multi-omics approaches to decipher MGB axis dynamics, and mechanistic studies exploring microbial metabolites as therapeutic targets. The authors advocate for a paradigm shift toward microbiota-centric interventions, emphasizing the bidirectional relationship between physical activity and gut ecosystem resilience in mental health management. In conclusion, this review underscores exercise as a multifaceted modulator of the gut-brain axis, offering novel insights into non-pharmacological strategies for depression. By bridging microbial ecology, neuroimmunology, and exercise physiology, this work lays a foundation for precision medicine approaches targeting the gut microbiota to alleviate depressive disorders.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child