Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, attenuates molecular pathological alterations in learning memory in AD mice.

OBJECTIVE: Previous studies have revealed that Propane-2-sulfonic acid octadec-9-enyl-amide(N15) exerts a protective role in the inflammatory response after ischemic stroke and in neuronal damage. However, little is known about N15 in Alzheimer's disease (AD). The aim of this study was to investigate the effects of N15 on AD and explore the underlying molecular mechanism. METHODS: AD mice model was established by lateral ventricular injection with Aß25-35. N15 was daily intraperitoneal administered for 28 days. Morris Water Maze was used to evaluate the neurocognitive function of the mice. The expression of PPARα/γ, brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT3), ADAM10, PS1 and BACE1 were measured by qPCR. Aß amyloid in the hippocampus was measured by Congo red assay. Toluidine blue staining was used to detect the neuronal apoptosis. Protein levels of ADAM10, PS1 and BACE1 were determined using immunoblotting. RESULTS: N15 treatment significantly reduced neurocognitive dysfunction, which also significantly activated the expression of PPARα/γ at an optimal dose of 200 mg/kg. Administration of N15 alleviated the formation of Aß amyloid in the hippocampus of AD mice, enhanced the BDNF mRNA expression, decreased the mRNA and protein levels of PS1 and BACE1, upregulated ADAM10 mRNA and protein levels. CONCLUSION: N15 exerts its neuroprotective effects through the activation of PPARα/γ and may be a potential drug for the treatment of AD.

Network Pharmacology Study on Herb Pair Bletilla striata-Galla chinensis in the Treatment of Chronic Skin Ulcers.

BACKGROUND: Herb-paired Bletilla striata-Galla chinensis (BS-GC) is a classic combination of topical traditional Chinese medicine formulae in the treatment of chronic skin ulcers (CSUs). OBJECTIVE: The aim of this study is to explore the effective active ingredients of BS-GC, as well as the core targets and signal transduction pathways of its action on CSUs. METHODS: The ingredients of BS-GC were obtained from TCMSP and HERB databases. The targets of all active ingredients were retrieved from the SwissTargetPrediction database. The targets of CSUs were obtained from OMIM, GeneCards, Drugbank, and DisGeNET databases. A drug-disease target protein-protein interaction (PPI) network was constructed to select the most core targets, and an herb-ingredient-target network was built by utilizing Cytoscape 3.7.2. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG) analysis and verified the results of network pharmacology through molecular docking. RESULTS: A total of 40 active ingredients from the herb pair BS-GC were initially screened, and a total of 528 targets were retrieved. Meanwhile, the total number of CSU targets was 1032. Then, the number of common targets between BS-GC and CSUs was 107. The 13 core targets of herb pair BS-GC with CSUs were filtered out according to the PPI network, including AKT1, TNF, EGFR, BCL2, HIF1A, MMP-9, etc. The 5 main core active ingredients were 1-(4-Hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene-4,7-diol, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol, physcion, dihydromyricetin, and myricetin. The main biological processes were inflammation, oxidative stress, and immune response, involving the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, NF-κB signaling pathway, and calcium signaling pathway. Molecular docking results showed good binding activity between the 5 main core active ingredients and 13 core targets. CONCLUSION: This study predicted the core targets and signal transduction pathways in the treatment of CSUs to provide a reference for further molecular mechanism research.

Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

Enhancing SN38 prodrug delivery using a self-immolative linker and endogenous albumin transport.

Enhancing the delivery and release efficiency of hydroxyl agents, constrained by high pKa values and issues of release rate or unstable linkage, is a critical challenge. To address this, a self-immolative linker, composed of a modifiable p-hydroxybenzyl ether and a fast cyclization adapter (N-(ortho-hydroxyphenyl)-N-methylcarbamate) was strategically designed, for the synthesis of prodrugs. The innovative linker not only provides a side chain modification but also facilitates the rapid release of the active payloads, thereby enabling precise drug delivery. Particularly, five prodrug model compounds (J1, J2, J3, J5 and J6) were synthesized to evaluate the release rates by using ß-glucuronic acid as trigger and five hydroxyl compounds as model payloads. Significantly, all prodrug model compounds could efficiently release the hydroxyl payloads under the action of ß-glucuronidase, validating the robustness of the linker. And then, to assess the drug delivery and release efficiency using endogenous albumin as a transport vehicle, J1148, a SN38 prodrug modified with maleimide side chain was synthesized. Results demonstrated that J1148 covalently bound to plasma albumin through in situ Michael addition, effectively targeting the tumor microenvironment. Activated by ß-glucuronidase, J1148 underwent a classical 1, 6-elimination, followed by rapid cyclization of the adapter, thereby releasing SN38. Impressively, J1148 showed excellent therapeutic efficacy against human colonic cancer xenograft model, leading to a significant reduction or even disappearance of tumors (3/6 of mice cured). These findings underscore the potential of the designed linker in the delivery system of hydroxyl agents, positioning it at the forefront of advancements in drug delivery technology.

Deliberate self-harm among pediatric psychiatric inpatients in China: A single-center retrospective study.

BACKGROUND: For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China. AIM: To understand the situation of DSH among hospitalized children and adolescents and its related factors. METHODS: In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH. RESULTS: A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting (n = 115, 48.12%) was the most common type of DSH. Females (n = 171, 71.55%) were more likely to engage in DSH than males (n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse. CONCLUSION: Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH.

HSG-MGAF Net: Heterogeneous subgraph-guided multiscale graph attention fusion network for interpretable prediction of whole-slide image.

BACKGROUND AND OBJECTIVE: Pathological whole slide image (WSI) prediction and region of interest (ROI) localization are important issues in computer-aided diagnosis and postoperative analysis in clinical applications. Existing computer-aided methods for predicting WSI are mainly based on multiple instance learning (MIL) and its variants. However, most of the methods are based on instance independence and identical distribution assumption and performed at a single scale, which not fully exploit the hierarchical multiscale heterogeneous information contained in WSI. METHODS: Heterogeneous Subgraph-Guided Multiscale Graph Attention Fusion Network (HSG-MGAF Net) is proposed to build the topology of critical image patches at two scales for adaptive WSI prediction and lesion localization. The HSG-MGAF Net simulates the hierarchical heterogeneous information of WSI through graph and hypergraph at two scales, respectively. This framework not only fully exploits the low-order and potential high-order correlations of image patches at each scale, but also leverages the heterogeneous information of the two scales for adaptive WSI prediction. RESULTS: We validate the superiority of the proposed method on the CAMELYON16 and the TCGA- NSCLC, and the results show that HSG-MGAF Net outperforms the state-of-the-art method on both datasets. The average ACC, AUC and F1 score of HSG-MGAF Net can reach 92.7 %/0.951/0.892 and 92.2 %/0.957/0.919, respectively. The obtained heatmaps can also localize the positive regions more accurately, which have great consistency with the pixel-level labels. CONCLUSIONS: The results demonstrate that HSG-MGAF Net outperforms existing weakly supervised learning methods by introducing critical heterogeneous information between the two scales. This approach paves the way for further research on light weighted heterogeneous graph-based WSI prediction and ROI localization.

Chemical Logic Gates on Active Colloids.

Recent studies have shown that active colloidal motors using enzymatic reactions for propulsion hold special promise for applications in fields ranging from biology to material science. It will be desirable to have active colloids with capability of computation so that they can act autonomously to sense their surroundings and alter their own dynamics. It is shown how small chemical networks that make use of enzymatic chemical reactions on the colloid surface can be used to construct motor-based chemical logic gates. The basic features of coupled enzymatic reactions that are responsible for propulsion and underlie the construction and function of chemical gates are described using continuum theory and molecular simulation. Examples are given that show how colloids with specific chemical logic gates, can perform simple sensing tasks. Due to the diverse functions of different enzyme gates, operating alone or in circuits, the work presented here supports the suggestion that synthetic motors using such gates could be designed to operate in an autonomous way in order to complete complicated tasks.

Establishment and validation of a prediction model for nonrecovery of left ventricular ejection fraction in acute myocardial infarction patients combined with decreased left ventricular ejection fraction.

BACKGROUND: This study aimed to investigate the risk factors for nonrecovery of left ventricular ejection fraction (LVEF) during follow-up in patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) combined with reduced LVEF, and establish and verify a risk prediction model based on these factors. METHODS: In this study, patients with AMI who underwent PCI in a high-volume PCI center between December 2018 and December 2021 were consecutively enrolled, screened, and randomly assigned to the model establishment and validation cohorts. A predictive model method based on least absolute shrinkage and selection operator regression was used for establishment and validation. RESULTS: Cardiac troponin I, myoglobin, left ventricular end-diastolic dimension, multivessel disease, and no-reflow were identified as potential predictors of LVEF recovery failure. The areas under the curve were 0.703 and 0.665 in the model establishment and validation cohorts, respectively, proving that the prediction model had some predictive ability. The calibration curves of the two cohorts showed good agreement with those of the nomogram model. In addition, the decision curve analysis showed that the model had a net clinical benefit. CONCLUSION: This prediction model can assess the risk of nonrecovery of LVEF in patients with AMI undergoing PCI combined with LVEF reduction during follow-up, and conveniently screen high-risk patients with nonrecoverable LVEF early.

Mechanic study based on untargeted metabolomics of Pi-pa-run-fei-tang on pepper combined with ammonia induced chronic cough model mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pi-pa-run-fei-tang (PPRFT), a traditional Chinese medicine formula with long-standing history, demonstrated beneficial effect on chronic cough. However, the mechanism underlying efficacy unclear. In current research, we explored the impact and molecular mechanism of chronic cough mouse stimulating with capsaicin combined with ammonia. AIM OF THE STUDY: To investigate the metabolic modulating effects, and potential mechanisms underlying the therapeutic effect of PPRFT in chronic cough. MATERIALS AND METHODS: Chronic cough mouse models were created by stimulating mice by capsaicin combined with ammonia. Number of coughs and cough latency within 2 min were recorded. With lung tissue and serum samples collected for histopathology, metabolomics, RT-qPCR, immunohistochemistry, and WB analysis. Lymphocytes were isolated and flow cytometric assays were conducted to evaluate the differentiation between Th17 and Treg cell among CD4+ cells. RESULTS: Results indicated that PPRFT obviously reduced the number of coughs, prolonged cough latency, reduced inflammatory cell infiltration and lung tissues damage, and decreased the serum level of IL-6, IL-1ß, TNF-α, and IL-17 while increasing IL-10 levels. Notably, PPRFT suppressed Th17 cell divergence and promoted Treg cell divergence. Furthermore, serum metabolomic assays showed that 46 metabolites differed significantly between group, with 35 pathways involved. Moreover, mRNA levels of IL-6, NF-κB, IL-17, RORγT, JAK2, STAT3, PI3K and AKT in lung tissues remarkably reduced and mRNA levels of IL-10 and FOXP3 were elevated after PPRFT pretreatment. Additionally, PPRFT treatments decreased the protein levels of IL-6, NF-κB, IL-17, RORγT, p-JAK2, p-STAT3, p-PI3K, and p-AKT and increased the protein levels of IL-10 and FOXP3, but no significantly effects to the levels on JAK2, STAT3, PI3K, and AKT in the lungs. CONCLUSION: Conclusively, our result suggested the effect with PPRFT on chronic cough may be mediated through IL-6/JAK2/STAT3 and PI3K/AKT/NF-κB pathway, which regulate the differentiation between Th17 and Treg cell. This beneficial effect of PPRFT in capsaicin and ammonia-stimulated chronic cough mice indicates its potential application in treating chronic cough.

An inducible CRISPRi circuit for tunable dynamic regulation of gene expression in Saccharopolyspora erythraea.

Actinomyces are gram-positive bacteria known for their valuable secondary metabolites. Redirecting metabolic flux towards desired products in actinomycetes requires precise and dynamic regulation of gene expression. In this study, we integrated the CRISPR interference (CRISPRi) system with a cumate-inducible promoter to develop an inducible gene downregulation method in Saccharopolyspora erythraea, a prominent erythromycin-producing actinobacterium. The functionality of the cumate-inducible promoter was validated using the gusA gene as a reporter, and the successful inducible expression of the dCas9 gene was confirmed. The developed inducible CRISPRi strategy was then employed to downregulate the expression of target genes rppA in the wild-type strain NRRL2338 and sucC in the high erythromycin-producing strain E3. Through dynamic control of sucC expression, a significant enhancement in erythromycin production was achieved in strain E3. This study demonstrated the effectiveness of an inducible gene downregulation approach using CRISPRi and a cumate-inducible promoter, providing valuable insights for optimizing natural product production in actinomyces.

Fatigue, Physical Activity, and Quality of Life in Patients with Inflammatory Bowel Disease: A Cross-Sectional Study.

Purpose: The benefits of physical activity (PA) are widely recognized, but the intensity of PA in inflammatory bowel disease (IBD) patients with varying disease activity levels remains controversial. We aimed to investigate the relationship between PA levels, fatigue, and other health-related quality of life (QoL) in Chinese IBD patients. Patients and Methods: The study is a cross-sectional investigation conducted at a comprehensive IBD diagnosis and treatment facility in East China, spanning from August 2022 to February 2023. A total of 245 participants were initially enrolled, and after excluding individuals with incomplete data about crucial exposure and outcome variables, the final sample size amounted to 237. Participants were provided with a questionnaire encompassing sociodemographic factors, clinical information, the International Physical Activity Questionnaire (IPAQ), the Multidimensional Fatigue Inventory (MFI-20), and the Inflammatory Bowel Disease Questionnaire (IBDQ). Correlation analysis was employed to assess the relationship between variables. Results: A majority of participants (144) exhibited low levels of PA. Furthermore, 40.5% of all participants reported experiencing fatigue. Individuals with low levels of PA had an average MIF-20 score of 62.9±16.0. Correlation analysis showed that PA was significantly and negatively associated with fatigue (r = -0.224, p < 0.001). Additionally, PA was also negatively correlated with anxiety (r = -0.150, p < 0.05) and depression (r = -0.242, p < 0.001). On the other hand, PA was positively correlated with quality of life (QoL) (r = 0.171, p < 0.01). Furthermore, our analysis indicated that sleep disorders were positively associated with both anxiety (r = 0.349, p < 0.01) and depression (r = 0.354, p < 0.001). Conclusion: The levels of PA are significantly low, and there is a high prevalence of fatigue among individuals with IBD. PA in IBD showed a strong negative correlation with fatigue and a strong positive correlation with quality of life.

Cancer cases attributable to modifiable lifestyle risk factors in Switzerland between 2015 and 2019.

Several modifiable lifestyle risk factors have been linked to higher cancer risk in the literature. Determining the proportion and number of cancer cases attributable to these risk factors is pivotal in informing effective cancer prevention and control plans that have the greatest effect on reducing cancer incidence. We aimed to estimate the proportion and number of incident cancer cases that were attributable to modifiable lifestyle risk factors (ie, tobacco smoking, high alcohol consumption, excess body weight, physical inactivity and unhealthy diet) in Switzerland between 2015 and 2019. The exposure prevalence of selected risk factors was estimated based on the representative national nutrition survey menuCH, the associated relative risks were obtained from systematic literature reviews and the numbers of incident cancer cases were provided by the National Institute for Cancer Epidemiology and Registration. The fractions and numbers of attributable cases were calculated overall, by sex and by the three major language regions of Switzerland. The investigated modifiable risk factors combined were linked to 25.2% of potentially preventable incident cancer cases in Switzerland between 2015 and 2019. The proportion and numbers were slightly larger in males (28.4%, 6945 cases per year) than in females (21.9%, 4493 cases per year), and variations were observed between language regions. Tobacco smoking, excess body weight and high alcohol consumption were the leading contributors to lifestyle-attributable cancer cases. The observed differences in the leading risk factors both within Switzerland and compared to other countries underline the need for regionally and nationally tailored cancer prevention and education strategies.

Treatment outcomes of regenerative endodontic procedures in nonvital mature permanent teeth: a retrospective study.

OBJECTIVES: This retrospective study was undertaken to clinically and radiographically evaluate the long-term outcomes of regenerative endodontic procedures (REPs) for nonvital mature permanent teeth, to analyze predictors influencing treatment outcomes. METHODS: Nonvital mature permanent teeth treated by REPs with a minimum follow-up period of 6 months were included from 2015 to 2017. Treatment outcomes were categorized as success and failure. The periapical status and lesion healing were assessed in terms of the periapical index (PAI) and the percentage changes in periapical radiolucency (PARL) area. The clinical and radiographic outcomes of REPs were assessed by Mann-Whitney test at different follow-up period. Kaplan-Meier curves and Univariate Cox regression analysis were conducted to assess the success and identify potential predictors affecting outcomes, respectively. RESULTS: A total of 37 mature teeth with an average follow-up of 4.3 years satisfied the criteria, and 89.2% of the teeth had a successful outcome. Significant differences in PAI scores were found between each period with respect to the baseline (p < .05). Among different periods, there was a significant difference between intervals of 3-6 months and 7-12 months (p = .039) and no significant difference between each interval of more than 12 months (p > .05). Eighty-seven percent of teeth with preoperative PARL presented completely healed. REPs significantly decreased the PARL area at the interval of 7-12 months compared to 3-6 months (p = .025), with no significant difference between each interval of more than 12 months (p > .05). No significant predictor was found for the success of outcome (p > .05). Thirteen teeth (35.1%) regained pulp sensibility, and 40.5% of the teeth exhibited intracanal calcification. CONCLUSIONS: Within the limitations of this study, REPs provided a high long-term success rate and promoted the resolution of PARL as a biologically-based alternative treatment option for nonvital mature teeth. CLINICAL RELEVANCE: REPs provide a high long-term success rate and promoted healing of apical periodontitis comparable with reported outcomes for root canal therapy of mature teeth.

Evaluating the psychometric properties of the Chinese Depression Anxiety Stress Scale for Youth (DASS-Y) and DASS-21.

BACKGROUND: In recognizing the need for a reliable and valid instrument to assess psychological distress among children and adolescents, the present study translated the newly developed Depression Anxiety Stress Scale for Youth (DASS-Y) into Chinese, while also comparing its psychometric properties with those of the well-established DASS-21 within a primary and middle school demographic. METHODS: Utilizing a combination of convenience sampling and purposive sampling, a cohort comprising 1,507 primary and 1,131 middle school students was recruited. Rasch analysis, confirmatory factor analysis (CFA), and structural equation modeling (SEM) were used in the data analysis. RESULTS: Significant differences were observed between the DASS-Y and the DASS-21, notably within the anxiety subscale. The proportions of individuals with clinical mood disorders identified by the two scales demonstrated a significant disparity. Both scales, following an adjustment of responses, exhibited satisfactory internal consistency and convergent validity, with the acceptance of a three-factor structure. Furthermore, the DASS-Y showed superior discriminant validity relative to the DASS-21, providing more compelling evidence regarding concurrent validity. CONCLUSION: Overall, the Chinese version of the DASS-Y demonstrated superior robustness to the DASS-21 in terms of psychometric properties. The findings provide initial evidence for the psychometric properties of the DASS-Y from another culture.

Facile Synthesis of Polymer-Reinforced Silica Aerogel Microspheres as Robust, Hydrophobic and Recyclable Sorbents for Oil Removal from Water.

With the rapid development of industry and the acceleration of urbanization, oil pollution has caused serious damage to water, and its treatment has always been a research hotspot. Compared with traditional adsorption materials, aerogel has the advantages of light weight, large adsorption capacity and high selective adsorption, features that render it ideal as a high-performance sorbent for water treatment. The objective of this research was to develop novel hydrophobic polymer-reinforced silica aerogel microspheres (RSAMs) with water glass as the precursor, aminopropyltriethoxysilane as the modifier, and styrene as the crosslinker for oil removal from water. The effects of drying method and polymerization time on the structure and oil adsorption capacity were investigated. The drying method influenced the microstructure and pore structure in a noteworthy manner, and it also significantly depended on the polymerization time. More crosslinking time led to more volume shrinkage, thus resulting in a larger apparent density, lower pore volume, narrower pore size distribution and more compact network. Notably, the hydrophobicity increased with the increase in crosslinking time. After polymerization for 24 h, the RSAMs possessed the highest water contact angle of 126°. Owing to their excellent hydrophobicity, the RSAMs via supercritical CO2 drying exhibited significant oil and organic liquid adsorption capabilities ranging from 6.3 to 18.6 g/g, higher than their state-of-the-art counterparts. Moreover, their robust mechanical properties ensured excellent reusability and recyclability, allowing for multiple adsorption-desorption cycles without significant degradation in performance. The novel sorbent preparation method is facile and inspiring, and the resulting RSAMs are exceptional in capacity, efficiency, stability and regenerability.

Analysis of Prognostic Risk Factors of Sepsis Patients With Myocardial Injury: Six-month Survival Outcome.

Context: Sepsis is a systemic, comprehensive inflammatory response that can induce serious complications for patients. No uniform definition and diagnostic criteria exist internationally for sepsis related to myocardial injury. Studying factors affecting prognosis for sepsis patients with myocardial injury can be helpful in providing a theoretical basis for clinical diagnosis and treatment. Objective: The study intended to explore the predictors of the short-term prognosis for septic patients with myocardial injury and to provide a theoretical basis for improving that prognosis. Design: The research team performed a retrospective study. Setting: The study took place at the Renmin Hospital at Hubei University of Medicine in Shiyan, Hubei, China. Participants: Participants were 138 patients with sepsis and myocardial injury at the hospital between January 2018 and February 2021. Groups: The research team divided participants into a survival group with 114 patients and a mortality group with 24 patients, based on their survival status at six months after being in the hospital. Outcome Measures: The research team collected and analyzed the following data: (1) demographic and clinical characteristics, such as age, gender, underlying disease, and disease severity; (2) echocardiographic indicators, including left ventricular ejection fraction (LVEF), stroke volume (SV), left ventricular end systolic dimension (LVESD), and left ventricular end diastolic dimension (LVEDD); and (3) myocardial injury markers and inflammatory factors, including white blood cell (WBC) count and levels of cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase (CK), C-reactive protein (CRP), and procalcitonin (PCT). Results: The six-month mortality rate for patients with sepsis with myocardial injury was 17.39%. Compared to the survival group at participants' initial visits to the hospital, the mortality group had a significantly greater age (P = .046), sepsis severity (P < .001), heart rate (P < .001), APACHE II score (P < .001), SOFA score (P < .001), and use of vasoactive drugs (P = .002), and its length of hospital stay was significantly shorter (P < .001). The mortality group's LVEF was significantly lower than that of the survival group (P < .001). The mortality group's levels of WBC, cTnI, NT-proBNP, CK, CRP, and PCT were significantly higher than those in survival group (all P < .001). The univariate analysis found that an age>64 years (P < .001), a high APACHE II score (P < .001), an elevated cTnI (P = .017), an elevated NT-proBNP (P = .029), an elevated CK (P < .001), an elevated CRP (P = .031), and an elevated PCT (P < .001) were risk factors for a poor prognosis for patients. Multifactor logistic regression analysis showed that the risk factors for death were an age > 64 years (P < .001), a high APACHE II score (P < .001), and elevated levels of cTnI (P = .013), NT-proBNP (P < .001), CK (P < .001), CRP (P < .001), and PCT (P = .009). Conclusion: In summary, risk factors for poor prognosis in septic patients with myocardial injury included age>64 years, high APACHE II, elevated cTnI, elevated NT-proBNP, elevated CK, elevated CRP, and elevated PCT.

Bioinformatics analysis of copper death gene in diabetic immune infiltration.

BACKGROUND: Copper plays an important role in the human body and is potentially related to the development of diabetes. The mechanism of copper death gene regulating immune infiltration in diabetes has not been studied. METHODS: Download microarray data from healthy normal and diabetic patients from the GEO database. The identification of differentially expressed genes (DEGs) was analyzed by gene enrichment. Using String online database and Cytoscape software to interact with the protein interaction network and make visual analysis. Using Wilcox analyze the correlation between the copoer death gene and diabetic mellitus. Analysis of the correlation between immune penetration cells and functions, and the difference between the diabetes group and the control group, screening the copper death gene associated with diabetes, and predicting the upper top of microRNA (miRNA) through the Funrich software. RESULTS: According to the identification of differential genes in 25 samples of GSE25724 and GSE95849 data sets, 328 differential genes were identified by consensus, including 190 up-regulated genes and 138 down-regulated genes (log2FC = 2, P < .01). KEGG results showed that neurodegeneration-multiple disease pathways were most significantly upregulated, followed by Huntington disease. According to Cytohubba, the TOP10 genes HCK, FPR1, MNDA, AQP9, TLR8, CXCR1, CSF3R, VNN2, TLR4, and CCR5 are down-regulated genes, which are mostly enriched in neutrophils. Immunoinfiltration-related heat maps show that Macrophage was strongly positively correlated with Activated dendritic cell, Mast cell, Neutrophil, and Regulatory T cell showed a strong positive correlation. Neutrophil was strongly positively correlated with Activated dendritic cell, Mast cell, and Regulatory T cell. Differential analysis of immune infiltration showed that Neutroph, Mast cell, Activated B cell, Macrophage and Eosinophil were significantly increased in the diabetic group. Central memory CD4 T cell (P < .001), Plasmacytoid dendritic cell, Immature dendritic cell, and Central memory CD8 T cell, etal were significantly decreased. DBT, SLC31A1, ATP7A, LIAS, ATP7B, PDHA1, DLST, PDHB, GCSH, LIPT1, DLD, FDX1, and DLAT genes were significantly associated with one or more cells and their functions in immune invasion. Forty-one miRNA. CONCLUSIONS: Copper death is closely related to the occurrence of diabetes. Copper death genes may play an important role in the immune infiltration of diabetes.

DNA intercalation makes possible superior-gain organic photoelectrochemical transistor detection.

DNA intercalation has increasingly been studied for various scenario implementations due to the diverse functions of DNA/intercalators. Nascent organic photoelectrochemical transistor (OPECT) biosensing taking place in organic electronics and photoelectrochemical bioanalysis represents a promising technological frontier in the arena. In this work, we first devise DNA intercalation-enabled OPECT for miRNA detection with a superior gain up to 17100. Intercalation of [Ru(bpy)2dppz]2+ within the miRNA-initiated hybrid chain reaction (HCR)-derived duplex DNA is realized for producing anodic photocurrent upon light stimulation, causing the corresponding target-dependent alternation in gate voltage (VG) and hence the modulated channel current (IDS) of poly (3,4-ethylenedioxythiophene) doped with poly (styrene sulfonate) (PEDOT:PSS) under specific drain voltage (VDS) for quantitative miRNA-21 analysis, which shows a wide linear relationship and a low detection limit of 5.5 × 10-15 mol L-1. This study features the DNA intercalation-enabled organic electronics with superior gain and is envisaged to attract more attention to explore DNA adducts for innovative bioelectronics and biosensing, given the diverse DNA binders with multiple functions.

Psychometric evaluation of the depression, anxiety, and stress scale-21 (DASS-21) among Chinese primary and middle school teachers.

BACKGROUND: Teachers in high-stress roles face increasing psychological distress such as anxiety and depression, underscoring the need for validated assessment instruments. Given the current absence of a comprehensive, designated, and time-efficient scale capable of evaluating depression, anxiety, and stress among the teacher population, the Depression, Anxiety, and Stress Scale-21 (DASS-21) presents itself as a promising alternative. Despite the widespread application of the DASS-21 for assessing psychological distress across various populations, its validity among teachers, along with questions about its factor structure and its potential property of time equivalence, remain unverified. This study endeavors to address these considerations by investigating the psychometric properties of the DASS-21 specifically within the population of Chinese primary and middle school teachers. METHODS: Cross-sectional (n = 9,030) and longitudinal surveys (n = 1,642) were conducted using a non-probability sampling method. In addition to the DASS-21, the Chinese version of Chinese Teachers' Job Burnout Questionnaire (CTJBO) was utilized to evaluate the criterion validity of this scale. Three different approaches, namely confirmatory factor analysis, Rasch analysis, and network analysis, were employed to evaluate internal reliability, construct validity, as well as time invariance of the DASS-21. RESULTS: The DASS-21 demonstrated a high degree of internal consistency (Cronbach's α > 0.85) as well as excellent convergent validity, despite poor discriminant validity as determined by average variance extracted. Confirmatory factor analysis and network analysis further supported convergent validity. The three-factor structure outperformed one- and two-factor alternatives, establishing time invariance. Rasch analysis at the item level identified six inappropriate items within the anxiety and stress subscales, which were subsequently removed. Network analysis presented a better revised network. Regression analysis with emotional exhaustion as the criterion provided logical and accurate results. CONCLUSION: The DASS-21 was found to be a reliable and valid tool for measuring the mental health of teachers over time. To assess the instrument's psychometric properties, a combination of confirmatory factor analysis, Rasch analysis, and network analysis was utilized, which proved effective and is recommended for evaluating contentious instruments. Based on the results of the study, researchers and healthcare professionals are recommended to use the DASS-21 for assessing teachers' psychological distress. However, certain items identified in the study may need to be removed to enhance the instrument's appropriateness for this specific population.

Molecular subtypes and tumor microenvironment infiltration signatures based on cuproptosis-related genes in colon cancer.

Background: Colon cancer is one of the common cancers, and its prognosis remains to be improved. The role of cuproptosis as a newly discovered form of cell death in the development of colon cancer has not been determined. Methods: Based on 983 colon cancer samples in the TCGA database and the GEO database, we performed a comprehensive genomic analysis to explore the molecular subtypes mediated by cuproptosis-related genes. Single-sample gene set enrichment analysis (ssGSEA) was utilized to quantify the relative abundance of each cell infiltrate in the TME. A risk score was established using least absolute shrinkage and selection operator regression (LASSO), and its predictive ability for colon cancer patients was verified to explore its guiding value for treatment. Results: We identified two distinct cuproptosis-related molecular subtypes in colon cancer. These two distinct molecular subtypes can predict clinicopathological features, prognosis, TME activity, and immune-infiltrating cells. A risk model was developed and its predictive ability was verified. Compared with patients in the high-risk score group, patients in the low-risk score group were characterized by lower tumor microenvironment score, higher stem cell activity, lower tumor mutational burden, lower microsatellite instability, higher sensitivity to chemotherapeutics, and better immunotherapy efficacy. Conclusion: This study contributes to understanding the molecular characteristics of cuproptosis-related subtypes. We demonstrate a critical role for cuproptosis genes in colon cancer s in the TME. Our study contributes to the development of individualized treatment regimens for colon cancer.