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PurposeChronic ankle instability (CAI) causes maladaptive neuroplastic changes in the central nervous system, which may lead to high injury potential under dual-task conditions. This study aims to explore the effects of dual-task paradigm on the injury potential during landing among individuals with CAI.MethodsTwenty participants with CAI (4 female and 16 male, 12 were affected with their right limbs and 8 were affected with their left limbs, 20.4 ± 1.7 years, 176.9 ± 5.0 cm, and 72.0 ± 11.1 kg) and eighteen without CAI (6 female and 12 male, 20.2 ± 1.5 years, 173.5 ± 7.0 cm, and 70.3 ± 10.8 kg) were recruited. They drop-landed on a trap-door device, with their affected or matched limbs on a flippable platform, under single- (drop-landing only) and dual-task (drop-landing while subtracting of serial threes) conditions. A twelve-camera motion capture system was used to capture the kinematic data. Two-way ANOVA with mixed design (CAI vs non-CAI groups by single-vs dual-task conditions) was used to analyze the data.ResultsSignificant group-by-condition interactions were detected in the ankle inversion angle (P = 0.040, η2p = 0.012) and ankle inversion angular velocity (P = 0.038, η2p = 0.114). Both indicators decreased among individuals without CAI from single-to dual-task conditions, while remained unchanged among those with CAI; and they were higher among individuals with CAI under both single- and dual-task conditions, compared to those without CAI.ConclusionIndividuals with CAI have a reduced ability to limit ankle inversion compared to those without CAI. Under dual-task conditions, individuals without CAI limited their ankle inversion, while those with CAI did not. Drop-landing, especially under dual-task conditions, poses a high risk of excessive ankle inversion for individuals with CAI.

PurposeTo investigate the effects of transcranial direct current stimulation (tDCS) combined with Bosu ball training on the injury potential during drop landing in people with chronic ankle instability (CAI).MethodsA total of 40 participants with CAI were recruited and randomly divided into the tDCS + Bosu and Bosu groups. The people in the tDCS + Bosu group received intervention of tDCS combined with Bosu ball training, and those in the Bosu group received intervention of sham tDCS and Bosu ball training, for 6 weeks with three 20-min sessions per week. Before (week0) and after (week7) the intervention, all participants drop-landed on a trap-door device, with their affected limbs on a moveable platform, which could be flipped 24° inward and 15° forward to mimic an ankle inversion condition. The kinematic data were captured using a twelve-camera motion capture system. Two-way ANOVA with repeated measures was used to analyze data.ResultsSignificant group-by-intervention interactions were detected in the peak ankle inversion angular velocity (p = 0.047, η2p = 0.118), the time to peak ankle inversion (p = 0.030, η2p = 0.139), and the plantarflexion angle at the moment of peak ankle inversion (p = 0.014, η2p = 0.173). Post hoc comparisons showed that compared with week0, the peak ankle inversion angular velocity and the plantarflexion angle at the moment of peak ankle inversion were reduced, the time to peak ankle inversion was advanced in both groups at week7, and the changes were greater in the tDCS + Bosu group compared to the Bosu group. And, a significant intervention main effect was detected in the peak ankle inversion angle in the two groups (p < 0.001, η2p = 0.337).ConclusionCompared with the Bosu ball training, the tDCS combined with Bosu ball training was more effective in reducing the injury potential during drop landing in people with CAI.

ObjectiveTo investigate parental knowledge, attitudes, and practices (KAP) toward adolescent depression.MethodsA cross-sectional survey was conducted between October 2022 and October 2023 at The First Affiliated Hospital of Ningbo University among parents of adolescents diagnosed with depression. A self-administered questionnaire was used to collect the parents’ demographic characteristics and KAP toward adolescent depression.ResultsA total of 522 questionnaires were collected from parents of depressed adolescents. Among the participants, 383 (73.37%) were female. In addition, 426 participants (81.61%) had children aged 14–18. The mean knowledge, attitude, and practice scores were 9.09 ± 2.37 (possible range: 0–12), 37.04 ± 4.11 (possible range: 11–55), and 31.53 ± 3.84 (possible range: 8–40), respectively. There were significant positive correlations between knowledge and attitude (r = 0.225, p

IntroductionStenotrophomonas maltophilia complex (Smc) comprises opportunistic Gram-negative bacilli responsible for various nosocomial infections. Limited data exists concerning its evolutionary lineage, global prevalence and pathogenicity.MethodsWe conducted an extensive genomic analysis on 734 Smc genomes, of which 90 were newly sequenced and isolated from different patients. The species composition and evolutionary relationships of Smc were examined using core protein sequence analysis. Pathogenicity evaluation was used by assays for swimming motility, biofilm formation and identification of virulence factors. The broth microdilution method was used to evaluate the drug resistance spectrum of clinical isolates.ResultsPhylogenetic analyses delineated 24 species-level clades, dominated by S. maltophilia (42.8%), S. sepilia (13.6%) and S. geniculata (9.9%). Geographically, strains were primarily distributed in Europe (34.2%), Asia (33.7%) and North America (24.0%), with intricate global distribution patterns. Meanwhile, 154 virulence-associated genes and 46 antimicrobial resistance genes within Smc were identified. These genes encoded span various functions, including motility, adherence, toxin, RND antibiotic efflux pumps, beta-lactamases and aminoglycoside-modifying enzymes. Moreover, significant variations were indicated in swimming motility and biofilm-forming capability across the different species, with S. sepilia exhibiting superior levels of both traits. Additionally, no statistically significant discrepancy was detected among Smc species to other antibiotics, despite the fact that all S. geniculata isolates were resistant to Ceftazidime and much higher than other species.ConclusionOur findings indicate the need to pay increased attention to other mainstream species of Smc besides S. maltophilia in order to better manage Smc-related infections and tailor effective treatment strategies.

To fairly use demand response to regulate customer load , support the economic and environmental protection, and assess the quantity and quality of the synergistic growth of the integrated energy system, a multi-objective optimum scheduling model and a solution method considering exergy efficiency and demand response are presented. To begin with, a mathematical model of each energy gadget is created. The electricity–gas load demand response model is then built using the price elasticity matrix, while the cooling load demand response model is built taking into account the user’s comfort temperature. On this basis, a multi-objective optimal dispatching model is developed with the optimization goals of minimizing system operation costs, reducing carbon emissions, and increasing exergy efficiency. Finally, the model is solved using NSGA-II to produce the Pareto optimal frontier solution set in various situations, and the VIKOR decision procedure is utilized to identify the complete best dispatching solution. The simulation results suggest that the proposed model can match the system’s scheduling needs in terms of numerous objectives such as economy, environmental protection, and exergy efficiency while also assuring user’s comfort.

Vibrio cholerae serogroup O1 (V. cholerae O1) is closely associated with cholera epidemics and has two main immunologically distinguishable serotypes, Ogawa and Inaba. Isolates serotype as Ogawa if the O-antigen polysaccharide (O-PS) is methylated or as Inaba if the O-PS is not methylated. This methylation is mediated by a methyltransferase encoded by the rfbT gene, and the mutation and low expression of rfbT results in serotype switch from Ogawa to Inaba. Previously, we have shown that cAMP receptor protein (CRP) activates rfbT. In this study, we demonstrated that histone-like nucleoid structuring protein (H-NS) is directly involved in the transcriptional repression of rfbT. This finding is supported by the analyses of rfbT mRNA level, rfbT-lux reporter fusions, electrophoretic mobility shift assay (EMSA), and DNase I footprinting assay. The rfbT mRNA abundances were significantly increased by deleting hns rather than fis which also preferentially associates with AT-rich sequences. A single-copy chromosomal complement of hns partly restored the down-regulation of rfbT. Analysis of rfbT-lux reporter fusions validated the transcriptional repression of hns. Subsequent EMSA and DNase I footprinting assay confirmed the direct binding of H-NS to rfbT promoter and mapped the exact binding site which was further verified by site-directed mutagenesis and promoter functional analysis. Furthermore, we found that in hns deletion mutant, CRP is no longer required for transcriptionally activating rfbT, suggesting that CRP functions as a dedicated transcription factor to relieve H-NS repression at rfbT. Together, this study expanded our understanding of the genetic regulatory mechanism of serotype conversion by global regulators in V. cholerae O1.

Power load forecasting has gained considerable research interest in recent years. The power load is vulnerable to randomness and uncertainty during power grid operations. Therefore, it is crucial to effectively predict the electric load and improve the accuracy of the prediction. This study proposes a novel power load forecasting method based on an improved long short-term memory (LSTM) neural network. Thus, an long short-term memory neural network model is established for power load forecasting, which supports variable-length inputs and outputs. The conventional convolutional neural network (CNN) and recurrent neural network (RNN) cannot reflect the sequence dependence between the output labels. Therefore, the LSTM-Seq2Seq prediction model was established by combining the sequence-to-sequence (Seq2Seq) structure with that of the long short-term memory model to improve the prediction accuracy. Four prediction models, i.e., long short-term memory, deep belief network (DBN), support vector machine (SVM), and LSTM-Seq2Seq, were simulated and tested on two different datasets. The results demonstrated the effectiveness of the proposed LSTM-Seq2Seq method. In the future, this model can be extended to more prediction application scenarios.

Rapid urbanization leads to changes in ecosystem services and may exacerbate ecological risks. Clarifying the relationship between these two factors in a specific context is essential to explore the integrated management model and achieve sustainable regional development. However, previous studies mainly lack an integrated analysis, fail to clearly explain the mechanism of ecosystem change, and can neither support landscape ecological security construction nor spatial planning and management. This study, using the urban agglomeration on the northern slope of the Tianshan Mountains (UANSTM) as an example, applied multi-source data from 2010 to 2020, investigated the changes and relationships between ecological risks and ecosystem services, and proposes an assessment framework. The total ecosystem services (TES) of the studied agglomeration showed a decreasing trend, with an overall loss of 0.43%. Corresponding to the decrease of ecosystem services, the ecological risk was higher in the south and north of the UANSTM and lower in the northwestern, central, and eastern regions. The proportion of ecological high-risk areas was expanding. The key to the relationship between ecological risks and ecosystem services is the change in hydrological conditions. Therefore, we suggest that the UANSTM actively transforms the development and use mode of water resources and coordinates their allocation, aiming to reduce regional ecological risks and optimize the pattern of ecosystem services.

This study aimed to investigate anemia treatment and other potential effects of two food-derived bioactive oligopeptide iron complexes on pregnant rats with iron deficiency anemia (IDA) and their offspring. Rats with IDA were established with a low iron diet and then mated. There were one control group and seven randomly assigned groups of pregnant rats with IDA: Control group [Control, 40 ppm ferrous sulfate (FeSO4)]; IDA model group (ID, 4 ppm FeSO4), three high-iron groups (H-FeSO4, 400 ppm FeSO4; MCOP-Fe, 400 ppm marine fish oligopeptide iron complex; WCOP-Fe, 400 ppm whey protein oligopeptide iron complex) and three low-iron groups (L-FeSO4, 40 ppm FeSO4; MOP-Fe, 40 ppm marine fish oligopeptide iron complex; WOP-Fe, 40 ppm whey protein oligopeptide iron complex). Rats in each group were fed the corresponding special diet during pregnancy until the day of delivery. After different doses of iron supplement, serum hemoglobin, iron, and ferritin levels in rats with IDA were significantly increased to normal levels (P < 0.05). Serum iron levels were significantly lower in two food-derived bioactive oligopeptide low-iron complex groups than in the low FeSO4 group (P

The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics and glucose-lowering drugs (thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) in patients with type 2 diabetes from randomized con-trolled trials (RCTs). The PubMed, Web of science, Embase, and Cochrane Library databases were searched on the treatment effects of probiotics and glucose-lowering drugs on glycemia, lipids, and blood pressure metabolism published between Jan 2015 and April 2021. We performed meta-analyses using the random-effects model. We included 25 RCTs (2,843 participants). Overall, GLP-1RA, SGLT-2i, and TZD significantly reduce fasting blood sugar (FBS) and glycated hemoglobin (HbA1c), whereas GLP-1 RA increased the risk of hypoglycaemia. Multispecies probiotics decrease FBS, total cholesterol (TC), and systolic and diastolic blood pressure (SBP, DBP). Moreover, subgroup analyses indicated that participants aged >55 years, BMI ≥30 kg/m2, longer duration of intervention, and subjects from Eastern countries, showed significantly higher reduction in FBS and HbA1c, TC, TG and SBP. This meta-analysis revealed that including multiple probiotic rather than glucose-lowering drugs might be more beneficial regarding T2D prevention who suffering from simultaneously hyperglycemia, hypercholesterolemia, and hypertension.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment.Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls.Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively.Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment.Clinical Trial Registration:ClinicalTrials.gov, identifier: ChiCTR2100046954.

ObjectivesThis study aimed to analyze the periodontal conditions of patients with obstructive sleep apnea (OSA) in relation to the salivary microbiome.Materials and MethodsIn total, 54 male adults (27 with OSA, 27 controls) completed this cross-sectional study. All participants were monitored by overnight polysomnography (PSG) and underwent full-mouth periodontal examination. Saliva samples were then collected, and the microbial 16S ribosomal RNA gene was sequenced. The data were analyzed to determine the microbial distribution and the community structure of the two groups.ResultsDemonstrated by alpha and beta diversity, the OSA group had a lower microbial richness and a lower observed species than the controls. There was no significant difference in the microbial species diversity or evenness between the OSA and the non-OSA groups. The OSA group had fewer operational taxonomic units (OTUs), and the distribution of microbiome showed that several gram-positive bacteria had higher abundance in the OSA group. As for periodontal pathogens, the relative abundance of Prevotella was significantly increased in the OSA group. No significant difference was observed in the relative abundance of other pathogens at either the genus or species level.ConclusionsThe salivary microbial community structure was altered in patients with OSA in terms of species richness and trans-habitat diversity, along with an increase in Prevotella, a specific periodontal pathogen. These findings might explain the high prevalence of periodontitis in OSA patients.

Objective: To observe the changes in sleep characteristics and BDI scores in patients with short-term insomnia disorder (SID) using a longitudinal observational study.Methods: Fifty-four patients who met the criteria for SID of the International Classification of Sleep Disorders, third edition, were recruited. Depression levels were assessed using the Beck depression inventory (BDI) at enrollment and after 3 months of follow-up, respectively. Sleep characteristics were assessed by polysomnography.Results: After 3 months of follow-up, the group was divided into SID with increased BDI score (BDI >15) and SID with normal BDI score (BDI ≤ 15) according to the total BDI score of the second assessment. The differences in rapid eye movement (REM) sleep latency, REM sleep arousal index, and NREM sleep arousal index between the two groups were statistically significant. The total BDI score was positively correlated with REM and NREM sleep arousal index and negatively correlated with REM sleep latency, which were analyzed by Pearson correlation coefficient. Multiple linear regression was used to construct a regression model to predict the risk of depression in which the prediction accuracy reached 83.7%.Conclusion: REM sleep fragmentation is closely associated with future depressive status in patients with SID and is expected to become an index of estimating depression risk.

Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis worldwide, has a strong ability to form biofilms on surfaces. Quorum sensing (QS) is a process widely used by bacteria to communicate with each other and control gene expression via the secretion and detection of autoinducers. OpaR is the master QS regulator of V. parahaemolyticus operating under high cell density (HCD). OpaR regulation of V. parahaemolyticus biofilm formation has been reported, but the regulatory mechanisms are still not fully understood. bis-(3′-5′)-cyclic di-GMP (c-di-GMP) is an omnipresent intracellular second messenger that regulates diverse behaviors of bacteria including activation of biofilm formation. In this work, we showed that OpaR repressed biofilm formation and decreased the intracellular concentration of c-di-GMP in V. parahaemolyticus RIMD2210633. The OpaR box-like sequences were detected within the regulatory DNA regions of scrA, scrG, VP0117, VPA0198, VPA1176, VP0699, and VP2979, encoding a group of GGDEF and/or EAL-type proteins. The results of qPCR, LacZ fusion, EMSA, and DNase I footprinting assays demonstrated that OpaR bound to the upstream DNA regions of scrA, VP0117, VPA0198, VPA1176, and VP0699 to repress their transcription, whereas it positively and directly regulated the transcription of scrG and VP2979. Thus, transcriptional regulation of these genes by OpaR led directly to changes in the intracellular concentration of c-di-GMP. The direct association between QS and c-di-GMP metabolism in V. parahaemolyticus RIMD2210633 would be conducive to precise control of gene transcription and bacterial behaviors such as biofilm formation.

Vibrio cholerae and Vibrio parahaemolyticus are common diarrheal pathogens of great public health concern. A multiplex TaqMan-based real-time PCR assay was developed on the BD MAX platform; this assay can simultaneously detect and differentiate V. cholerae and V. parahaemolyticus directly from human fecal specimens. The assay includes two reactions. One reaction, BDM-VC, targets the gene ompW, the cholera toxin (CT) coding gene ctxA, the O1 serogroup specific gene rfbN, and the O139 serogroup specific gene wbfR of V. cholerae. The other, BDM-VP, targets the gene toxR and the toxin coding genes tdh and trh of V. parahaemolyticus. In addition, each reaction contains a sample process control. When evaluated with spiked stool samples, the detection limit of the BD MAX assay was 195–780 CFU/ml for V. cholerae and 46–184 CFU/ml for V. parahaemolyticus, and the amplification efficiency of all genes was between 95 and 115%. The assay showed 100% analytical specificity, using 63 isolates. The BD MAX assay was evaluated for its performance compared with conventional real-time PCR after automated DNA extraction steps, using 164 retrospective stool samples. The overall percent agreement between the BD MAX assay and real-time PCR was ≥ 98.8%; the positive percent agreement was 85.7% for ompW, 100% for toxR/tdh, and lower (66.7%) for trh because of a false negative. This is the first report to evaluate the usage of the BD MAX open system in detection and differentiation of V. cholerae and V. parahaemolyticus directly from human samples.

Attached Vibrio cholerae biofilms are essential for environmental persistence and infectivity. The vps loci (vpsU, vpsA-K, and vpsL-Q) are required for mature biofilm formation and are responsible for the synthesis of exopolysaccharide. Transcription of vps genes is activated by the signaling molecule bis-(3′–5′)-cyclic di-GMP (c-di-GMP), whose metabolism is controlled by the proteins containing the GGDEF and/or EAL domains. The ferric uptake regulator (Fur) plays key roles in the transcription of many genes involved in iron metabolism and non-iron functions. However, roles for Fur in Vibrio biofilm production have not been documented. In this study, phenotypic assays demonstrated that Fur, independent of iron, decreases in vivo c-di-GMP levels and inhibits in vitro biofilm formation by Vibrio cholerae. The Fur box-like sequences were detected within the promoter-proximal DNA regions of vpsU, vpsA-K, vieSAB, and cdgD, suggesting that transcription of these genes may be under the direct control of Fur. Indeed, the results of luminescence, quantitative PCR (qPCR), electrophoretic mobility shift assay (EMSA), and DNase I footprinting assays demonstrated Fur to bind to the promoter-proximal DNA regions of vpsU, vpsA-K, and cdgD to repress their transcription. In contrast, Fur activates the transcription of vieSAB in a direct manner. The cdgD and vieSAB encode proteins with GGDEF and EAL domains, respectively. Thus, data presented here highlight a new physiological role for Fur wherein it acts as a repressor of V. cholerae biofilm formation mediated by decreasing the production of exopolysaccharide and the intracellular levels of c-di-GMP.

Cholera toxin (CT) and toxin coregulated pilus (TCP, TcpA is the major subunit) are two major virulence factors of Vibrio cholerae, both of which play critical roles in developing severe diarrhea in human. Expression of CT and TCP is under the tight control of the regulatory cascade known as the ToxR virulence regulon, which is composed of three regulators ToxR, TcpP, and ToxT. Besides, their expression is also regulated by the quorum sensing (QS) master regulator HapR and the regulatory protein Fur. Though transcription of tcpP, toxT, and/or tcpA are reported to be regulated by HapR and Fur, to date there are no studies to verify their direct regulations. In the present study, we showed that HapR directly repress the transcription of tcpP and tcpA by binding to their promoter regions, and possibly repress toxT transcription in an indirect manner. Fur directly activated the transcription of tcpP, toxT, and tcpA by binding to their promoters. Taking account of the sequential expression of hapR, fur, tcpP, toxT, and tcpA in the different growth phases of V. cholerae, we deduce that at the early mid-logarithmic growth phase, Fur binds to the promoters of tcpP, toxT, and tcpA to activate their transcription; while at the later mid-logarithmic growth phase, HapR can bind to the promoters of tcpP and tcpA to repress their transcription. Our study reveals the new recognition in the virulence regulatory pathways in V. cholerae and suggests the complicated and subtle regulation network with the growth density dependence.

The biotype El Tor of serogroup O1 and most of the non-O1/non-O139 strains of Vibrio cholerae can produce an extracellular pore-forming toxin known as cholera hemolysin (HlyA). Expression of HlyA has been previously reported to be regulated by the quorum sensing (QS) and the regulatory proteins HlyU and Fur, but lacks the direct evidence for their binding to the promoter of hlyA. In the present work, we showed that the QS regulator HapR, along with Fur and HlyU, regulates the transcription of hlyA in V. cholerae El Tor biotype. At the late mid-logarithmic growth phase, HapR binds to the three promoters of fur, hlyU, and hlyA to repress their transcription. At the early mid-logarithmic growth phase, Fur binds to the promoters of hlyU and hlyA to repress their transcription; meanwhile, HlyU binds to the promoter of hlyA to activate its transcription, but it manifests direct inhibition of its own gene. The highest transcriptional level of hlyA occurs at an OD600 value of around 0.6–0.7, which may be due to the subtle regulation of HapR, Fur, and HlyU. The complex regulation of HapR, Fur, and HlyU on hlyA would be beneficial to the invasion and pathogenesis of V. cholerae during the different infection stages.

Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis, harbors two separate T6SSs on chromosomes 1 and 2, i.e., T6SS1 (VP1386-1420) and T6SS2 (VPA1025-1046). T6SS1 contains at least 7 putative operons: VP1386-1387, VP1388-1390, VP1392-1391, VP1393-1406, VP1400-1406, VP1409-1407, and VP1410-1420. V. parahaemolyticus AphA and OpaR are the two master regulators of quorum sensing (QS) system that are highly expressed at low cell density and high cell density, respectively. ToxR is a membrane-bound virulence regulatory protein conserved across the Vibrio family. In the present work, we show that ToxR coordinates with AphA and OpaR to repress T6SS1 expression in V. parahaemolyticus. OpaR binds to the promoters of VP1388-1390, VP1400-1406, and VP1409-1407 to repress their transcription, but it appears to negatively regulate VP1393-1406 transcription in an indirect manner. By contrast, AphA negatively regulated the above four T6SS1 operons in an indirect manner. In addition, ToxR binds to the promoters of VP1400-1406 and VP1409-1407 to inhibit their transcription, but it presents an indirect interaction with VP1388-1390 and VP1393-1406 promoters. Notably, the expression of ToxR also manifested in a QS-dependent manner and the highest expression occurred at LCD. Meanwhile, the highest expression of T6SS1 occurred at an OD600 value of 0.6 to 0.8 due to the tight regulation of ToxR and QS, suggesting T6SS1 functions only during the mid-logarithmic growth phase. These observations provide significant insight into the molecular mechanism of T6SS1 gene regulation by QS and ToxR in V. parahaemolyticus.

Introduction: Cuproptosis seems to promote the progression of diverse diseases. Hence, we explored the cuproptosis regulators in human spermatogenic dysfunction (SD), analyzed the condition of immune cell infiltration, and constructed a predictive model. Methods: Two microarray datasets (GSE4797 and GSE45885) related to male infertility (MI) patients with SD were downloaded from the Gene Expression Omnibus (GEO) database. We utilized the GSE4797 dataset to obtain differentially expressed cuproptosis-related genes (deCRGs) between SD and normal controls. The correlation between deCRGs and immune cell infiltration status was analyzed. We also explored the molecular clusters of CRGs and the status of immune cell infiltration. Notably, weighted gene co-expression network analysis (WGCNA) was used to identify the cluster-specific differentially expressed genes (DEGs). Moreso, gene set variation analysis (GSVA) was performed to annotate the enriched genes. Subsequently, we selected an optimal machinelearning model from four models. Finally, nomograms, calibration curves, decision curve analysis (DCA), and the GSE45885 dataset were utilized to verify the predictions' accuracy. Results: Among SD and normal controls, we confirmed that there are deCRGs and activated immune responses. Through the GSE4797 dataset, we obtained 11 deCRGs. ATP7A, ATP7B, SLC31A1, FDX1, PDHA1, PDHB, GLS, CDKN2A, DBT, and GCSH were highly expressed in testicular tissues with SD, whereas LIAS was lowly expressed. Additionally, two clusters were identified in SD. Immuneinfiltration analysis showed the existing heterogeneity of immunity at these two clusters. Cuproptosis-related molecular Cluster2 was marked by enhanced expressions of ATP7A, SLC31A1, PDHA1, PDHB, CDKN2A, DBT, and higher proportions of resting memory CD4+ T cells. Furthermore, an eXtreme Gradient Boosting (XGB) model based on 5-gene was built, which showed superior performance on the external validation dataset GSE45885 (AUC = 0.812). Therefore, the combined nomogram, calibration curve, and DCA results demonstrated the accuracy of predicting SD. Conclusion: Our study preliminarily illustrates the relationship between SD and cuproptosis. Moreover, a bright predictive model was developed. [ABSTRACT FROM AUTHOR]

The largest solid organ of the male genitalia, the prostate gland, is comprised of a variety of cells such as prostate epithelial cells, smooth muscle cells, fibroblasts, and endothelial cells. Prostate diseases, especially prostate cancer and prostatitis, are often accompanied by acute/chronic inflammatory responses or even cell death. Pyroptosis, a cell death distinct from necrosis and apoptosis, which mediate inflammation may be closely associated with the development of prostate disease. Pyroptosis is characterized by inflammasome activation via pattern recognition receptors (PRR) upon recognition of external stimuli, which is manifested downstream by translocation of gasdermin (GSDM) protein to the membrane to form pores and release of inflammatory factors interleukin (IL)-1β and IL-18, a process that is Caspase-dependent. Over the past number of years, many studies have investigated the role of inflammation in prostate disease and have suggested that pyroptosis may be an important driver. Understanding the precise mechanism is of major consequence for the development of targeted therapeutic strategies. This review summarizes the molecular mechanisms, regulation, and cellular effects of pyroptosis briefly and then discuss the current pyroptosis studies in prostate disease research and the inspiration for us.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in diabetic cardiomyopathy (DCM) remain largely unknown. In this study, we sought to determine whether GDF11 could prevent DCM. After establishing a mouse model of diabetes by administering a high-fat diet and streptozotocin, intramyocardial injection of an adeno-associated virus was used to achieve myocardium-specific GDF11 overexpression. GDF11 remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression and activity were observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were eliminated by SIRT1 depletion. Our results demonstrate for the first time that GDF11 protects against DCM by regulating SIRT1 signaling pathway.