Identification and functional characterization of laminin receptor in the mud crab, Scylla paramamosain, in response to MCDV-1 challenge.

Laminin receptor (LR), which mediating cell adhesion to the extracellular matrix, plays a crucial role in cell signaling and regulatory functions. In the present study, a laminin receptor gene (SpLR) was cloned and characterized from the mud crab (Scylla paramamosain). The full length of SpLR contained an open reading frame (ORF) of 960 bp encoding 319 amino acids, a 5' untranslated region (UTR) of 66 bp and a 3' UTR of 49 bp. The predicted protein comprised two Ribosomal-S2 domains and a 40S-SA-C domain. The mRNA of SpLR was highly expressed in the gill, followed by the hepatopancreas. The expression of SpLR was up-regulated after mud crab dicistrovirus-1(MCDV-1) infection. Knocking down SpLR in vivo by RNA interference significantly down-regulated the expression of the immune genes SpJAK, SpSTAT, SpToll1, SpALF1 and SpALF5. This study shown that the expression level of SpToll1 and SpCAM in SpLR-interfered group significantly increased after MCDV-1 infection. Moreover, silencing of SpLR in vivo decreased the MCDV-1 replication and increased the survival rate of mud crabs after MCDV-1 infection. These findings collectively suggest a pivotal role for SpLR in the mud crab's response to MCDV-1 infection. By influencing the expression of critical innate immune factors and impacting viral replication dynamics, SpLR emerges as a key player in the intricate host-pathogen interaction, providing valuable insights into the molecular mechanisms underlying MCDV-1 pathogenesis in mud crabs.

Impacts of the vegetable Urtica dioica on the intestinal T and B cell phenotype and macronutrient absorption in C57BL/6J mice with diet-induced obesity.

In two previous studies, we showed that supplementing a high-fat (HF) diet with 9% w/w U. dioica protects against fat accumulation, insulin resistance, and dysbiosis. This follow-up study in C57BL6/J mice aimed at testing: (i) the efficacy of the vegetable at lower doses: 9%, 4%, and 2%, (ii) the impact on intestinal T and B cell phenotype and secretions, (iii) impact on fat and glucose absorption during excess nutrient provision. At all doses, the vegetable attenuated HF diet induced fat accumulation in the mesenteric, perirenal, retroperitoneal fat pads, and liver but not the epididymal fat pad. The 2% dose protected against insulin resistance, prevented HF diet-induced decreases in intestinal T cells, and IgA+ B cells and activated T regulatory cells (Tregs) when included both in the LF and HF diets. Increased Tregs correlated with reduced inflammation; prevented increases in IL6, IFNγ, and TNFα in intestine but not expression of TNFα in epididymal fat pad. Testing of nutrient absorption was performed in enteroids. Enteroids derived from mice fed the HF diet supplemented with U. dioica had reduced absorption of free fatty acids and glucose compared to enteroids from mice fed the HF diet only. In enteroids, the ethanolic extract of U. dioica attenuated fat absorption and downregulated the expression of the receptor CD36 which facilitates uptake of fatty acids. In conclusion, including U. dioica in a HF diet, attenuates fat accumulation, insulin resistance, and inflammation. This is achieved by preventing dysregulation of immune homeostasis and in the presence of excess fat, reducing fat and glucose absorption.

Subcortical structure alteration in patients with drug-induced parkinsonism: Evidence from neuroimaging.

Parkinson's Disease (PD) and Drug-induced parkinsonism (DIP) are the most common subtypes of parkinsonism, yet no studies have reported that the subcortical volume alterations in DIP patients. This study aimed to identify specific alterations of subcortical structures volume in DIP patients, and investigate association between the subcortical structure modifications and clinical symptoms. We recruited 27 PD patients, 25 DIP patients and 30 healthy controls (HCs). The clinical symptom-related parameters (Unified Parkinson's Disease Rating Scale, UPDRS) were evaluated. Structural imaging was performed on a 3.0 T scanner, and volumes of subcortical structures were obtained using FreeSurfer software. Analysis of covariance (ANCOVA) and partial correlation analysis were performed. DIP group had significantly smaller volume of the thalamus, pallidum, hippocampus and amygdala compared to HCs. ROC curve analysis demonstrated that the highest area under curve (AUC) value was in the right pallidum (AUC = 0.831) for evaluating the diagnostic efficacy in DIP from HCs. Moreover, the volumes of the putamen, hippocampus and amygdala were negatively correlated with UPDRSII in the DIP patients. The volume of the amygdala was negatively correlated with UPDRSIII. The present study provides novel information regarding neuroanatomical alteration of subcortical nuclei in DIP patients, suggesting that these methods might provide the basis for early diagnosis and differential diagnosis of DIP.

UPLC-Q-TOF/MS analysis of chemical components of single decoction and combined decoction of Qige decoction reveals the differences between various preparation processes.

The aim of this work was to explore the differences between various pharmaceutical processes in combined solutions of a single decoction (QGHBY) and a combined decoction (QGHJY) of Qi-Ge decoction from the perspective of chemical composition changes, so as to further guide the clinical application of drugs. A combined solution of a single decoction and a combined decoction of Astragali Radix, Puerariae Lobatae Radix and Citri Reticulatae Chachiensis Pericarpium was prepared with the same technological parameters. The chemical components of the two were detected and identified based on UPLC-Q-TOF/MS, and the different components were determined by principal component analysis. Eighty-eight compounds were identified in the pharmaceutical solution of Qi-Ge decoction. Principal component analysis revealed 11 different components of QGHBY and QGHJY with the conditions of Variable Importance in Projection (VIP) ≥ 1, fold change ≥ 2 and p < 0.05, among which hesperidin, hesperitin, isosinensetin, sinensetin and 5-demethylnobiletin were the components of Citri Reticulatae Chachiensis Pericarpium. The levels of these 11 different components in QGHJY were higher than those of QGHBY. The combined decoction is beneficial for the dissolution of flavonoids and other chemical components, and there is a significant difference in the content of chemical components between modern herbal concentrate granules and traditional decoctions.

Prevalence and clinical significance of late gadolinium enhancement in children and adolescents with hypertrophic cardiomyopathy: a systematic review and meta-analysis.

OBJECTIVES: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death among the paediatric population. The aim of this study is to investigate the prevalence and clinical significance of late gadolinium enhancement, as assessed by cardiac MRI, in paediatric hypertrophic cardiomyopathy. METHODS: A systematic literature search was conducted in PubMed, SCOPUS, and Ovid SP to identify relevant studies. Pooled estimates with a 95% confidence interval were calculated using the random-effects generic inverse variance model. Statistical analysis was performed using Review Manager v5.4 and R programming. RESULTS: Seventeen studies were included in this meta-analysis, encompassing a total of 778 patients. Late gadolinium enhancement was highly prevalent in paediatric hypertrophic cardiomyopathy, with a pooled prevalence of 51% (95% confidence interval, 40-62%). The estimated extent of focal fibrosis expressed as a percentage of left ventricular mass was 4.70% (95% confidence interval, 2.11-7.30%). The presence of late gadolinium enhancement was associated with an increased risk of adverse cardiac events (pooled odds ratio 3.49, 95% confidence interval 1.10-11.09). The left ventricular mass index of late gadolinium enhancement-positive group was higher than the negative group, with a standardised mean difference of 0.91 (95% confidence interval, 0.42-1.41). CONCLUSION: This meta-analysis demonstrates that prevalence of late gadolinium enhancement in paediatric hypertrophic cardiomyopathy is similar to that in the adult population. The presence and extent of late gadolinium enhancement are independent predictors of adverse cardiac events, underscoring their prognostic significance among the paediatric population.

Pulmonary Complications of Cytomegalovirus Infection in Neonates and Infants: A Systematic Review of Case Reports and Pooled Analysis.

BACKGROUND: Cytomegalovirus (CMV) causes intrauterine infections in 0.67% of neonates, with 12.7% displaying symptoms at birth. CMV can lead to severe multiorgan involvement, and mortality in symptomatic cases is around 30%. Pulmonary complications are rare in infants with CMV. This review assesses pulmonary complications and outcomes in infants with CMV infection. METHODS: A systematic literature search was conducted using PubMed, SCOPUS and Ovid SP to retrieve case reports on pulmonary complications in infants with congenital or perinatal CMV infection. Descriptive analysis and pooled analysis were conducted for the case reports. RESULTS: A total of 28 articles with 38 patients were included in this systematic review. The reported pulmonary complications in the case reports were CMV pneumonitis (34.2%), persistent pulmonary hypertension of the newborn (18.4%), emphysema and chronic lung disease (15.8%), diaphragmatic dysfunction (13.2%), lung cysts and calcifications (10.5%), Pneumocystis jirovecii infection (7.9%), pulmonary hypoplasia (5.3%) and bronchial atresia (2.6%). Seven (18.4%) of 38 patients passed away because of the pulmonary complications of CMV infection. Congenital transmission ( P = 0.0108), maternal CMV ( P = 0.0396) and presence of neonatal comorbidities ( P = 0.0398) were independent risk factors for mortality. CONCLUSIONS: This systematic review demonstrated infrequent occurrence of severe pulmonary involvement in CMV infection but should be considered in infants with persistent or severe respiratory symptoms.

Research on the Interaction Mechanism and Structural Changes in Human Serum Albumin with Hispidin Using Spectroscopy and Molecular Docking.

The interaction between human serum albumin (HSA) and hispidin, a polyketide abundantly present in both edible and therapeutic mushrooms, was explored through multispectral methods, hydrophobic probe assays, location competition trials, and molecular docking simulations. The results of fluorescence quenching analysis showed that hispidin quenched the fluorescence of HSA by binding to it via a static mechanism. The binding of hispidin and HSA was validated further by synchronous fluorescence, three-dimensional fluorescence, and UV/vis spectroscopy analysis. The apparent binding constant (Ka) at different temperatures, the binding site number (n), the quenching constants (Ksv), the dimolecular quenching rate constants (Kq), and the thermodynamic parameters (∆G, ∆H, and ∆S) were calculated. Among these parameters, ∆H and ∆S were determined to be 98.75 kJ/mol and 426.29 J/(mol·K), respectively, both exhibiting positive values. This observation suggested a predominant contribution of hydrophobic forces in the interaction between hispidin and HSA. By employing detergents (SDS and urea) and hydrophobic probes (ANS), it became feasible to quantify alterations in Ka and surface hydrophobicity, respectively. These measurements confirmed the pivotal role of hydrophobic forces in steering the interaction between hispidin and HSA. Site competition experiments showed that there was an interaction between hispidin and HSA molecules at site I, which situates the IIA domains of HSA, which was further confirmed by the molecular docking simulation.

Associations between self-leadership and self-reported execution of infection prevention and control among physicians and nurses.

BACKGROUND: There is poor self-reported (SR) execution of infection prevention and control (IPC) among physicians and nurses. Self-leadership is considered an important factor to enhance IPC SR-execution. This study aims to explore the associations between self-leadership and IPC SR-execution among physicians and nurses. METHODS: A cross-sectional study of 26,252 physicians and nurses was conducted in all secondary and tertiary hospitals in Hubei province, China. A questionnaire was designed to measure physicians' and nurses' self-leadership, which includes positive traits and negative traits, and IPC SR-execution, which includes motivation, process, and outcome. RESULTS: Positive traits and negative traits of self-leadership had significant positive associations with SR-execution motivation (ß = .582, P < .001) (ß = .026, P < .001), SR-execution process (ß = .642, P < .001) (ß = .017, P < .001), and SR-execution outcome (ß = .675, P < .001) (ß = .013, P < .001). CONCLUSIONS: This study recommends that health care institutions should focus on cultivating positive traits of self-leadership among physicians and nurses. Although negative traits of self-leadership can also promote IPC SR-execution, the association is limited and may lead to risks.

Meroterpenoids with divers' rings systems from Phyllosticta capitalensis and their anti-inflammatory activity.

Four undescribed sesquiterpene-shikimates (1-4), eight undescribed monoterpene-shikimates (5-12), together with two known ones were isolated and identified from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Capitalensis A (1) was identified as the first sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid degradation product, while capitalensis B (2) is a sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid with a unique D-ring formed by a C-2-O-C-9' connection. The structures of these previously undescribed compounds were elucidated by multiple techniques, including IR, HR-ESI-MS, and NMR analysis. Furthermore, their absolute configurations were established through the comprehensive approach that involved the calculations of ECD spectra, optical rotation values, and single-crystal X-ray analysis. Moreover, the anti-inflammatory activity of all isolated compounds was evaluated using a lipopolysaccharide (LPS)-induced inflammation model in BV2 microglial cells. Meanwhile, these compounds exhibited activity in inhibiting NO production. Four compounds, capitalensis C (3), capitalensis D (4), 15-hydroxyl tricycloalternarene 5b (13) and guignarenone A (14) showed strong inhibitory effects with IC50 values of 21.6 ± 1.33, 12.2 ± 1.08, 18.6 ± 1.27, and 15.8 ± 1.20 µM, respectively. In addition, the structure-activity relationship of the anti-inflammatory activity of the compounds was discussed.

HIF-1-mediated regulation of LDH gene unravels key insights into MCDV-1 pathogenesis in mud crabs Scylla paramamosain.

Hypoxia-inducible factors -1 (HIF-1) is a crucial transcription factor that regulates the expression of glycolytic genes. Our previous study proved that the Mud crab dicistrovirus-1 (MCDV-1) can induce aerobic glycolysis that favors viral replication in mud crab Scylla paramamosain. However, the role of HIF-1 on key glycolytic genes during the MCDV-1 infection has not been examined. In this study, the intricate interplay between HIF-1 and the key glycolysis enzyme, lactate dehydrogenase (LDH), was investigated after MCDV-1 infection. The expression of LDH was significant increased after MCDV-1 infection. Additionally, the expression of HIF-1α was upregulated following MCDV-1 infection, potentially attributed to the downregulation of prolyl hydroxylase domains 2 expression. Subsequent examination of the SpLDH promoter identified the presence of hypoxia response elements (HREs), serving as binding sites for HIF-1α. Intriguingly, experimental evidence demonstrated that SpHIF-1α actively promotes SpLDH transcription through these HREs. To further elucidate the functional significance of SpHIF-1α, targeted silencing was employed, resulting in a substantial reduction in SpLDH expression, activity, and lactate concentrations in MCDV-1-infected mud crabs. Notably, SpHIF-1α-silenced mud crabs exhibited higher survival rates and lower viral loads in hepatopancreas tissues following MCDV-1 infection. These results highlight the critical role of SpHIF-1α in MCDV-1 pathogenesis by regulating LDH gene dynamics, providing valuable insights into the molecular mechanisms underlying the virus-host interaction.

Overexpression of TMEM150A in glioblastoma multiforme patients correlated with dismal prognoses and compromised immune statuses.

Transmembrane proteins have exhibited a significant correlation with glioblastoma multiforme (GBM). The current study elucidates the roles of transmembrane protein 150A (TMEM150A) in GBM. Data on patients with GBM were collected from The Cancer Genome Atlas and Xena databases. The objective was to identify the expression levels of TMEM150A in patients with GBM, and evaluate its diagnostic and prognostic values, accomplished using the receiver operating characteristic and survival analyses. On a cellular level, Cell Counting Kit-8, Wound healing, and Transwell experiments were performed to gauge the impact of TMEM150A on cell growth and migration. The study further investigated the correlation between TMEM150A expression and immune status, along with ribonucleic acid (RNA) modifications in GBM. The findings demonstrated TMEM150A overexpression in the cancerous tissues of patients with GBM, with an area under the curve value of 0.95. TMEM150A overexpression was significantly correlated with poor prognostic indicators. TMEM150A overexpression and isocitrate dehydrogenase (IDH) mutation status were predictive of poor survival time among patients with GBM. In vitro experiments indicated that suppressing TMEM150A expression could inhibit GBM cell proliferation, migration, and invasion. Moreover, TMEM150A overexpression was associated with stromal, immune, and estimate scores, immune cells (such as the T helper (Th) 17 cells, Th2 cells, and regulatory T cells), cell markers, and RNA modifications. Therefore, TMEM150A overexpression might serve as a promising biomarker for predicting poor prognosis in patients with GBM. Inhibiting TMEM150A expression holds the potential for improving the survival time of patients with GBM.

Effects of the Implementation of Transport-Driven Poverty Alleviation Policy on Health Care-Seeking Behavior and Medical Expenditure Among Older People in Rural Areas: Quasi-Experimental Study.

BACKGROUND: Improving the rural residents' accessibility to and affordability of health care is recognized as a common target globally. The Health in All Policies approach, from the Declaration of Helsinki to the United Nations' Decade Of Healthy Ageing, strengthened the far-reaching effect of large-scale public policies on health care-seeking behavior; however, the effects of national transport policy on health care-seeking behavior is unclear. OBJECTIVE: This quasi-experimental study aimed to examine the effects of the implementation of transport-driven poverty alleviation (TPA) policy on health care-seeking behavior and medical expenditure among older adults in rural areas and the mechanism underlying these effects. METHODS: We designed a quasi-experiment to estimate the effects of TPA policy implementation on health care-seeking behavior and medical expenditure among older adults in rural areas through a difference-in-differences (DID) analysis based on data from the China Health and Retirement Longitudinal Study in 2011, 2013, 2015, and 2018. The underlying mechanism was analyzed and effect modification patterns were further investigated by poor households, health status, and age. RESULTS: Our findings validated a positive contribution of TPA policy on health care-seeking behavior among older adults in rural areas. After the implementation of TPA policy, the number of inpatient visits increased by annually 0.35 times per person, outpatient medical expenditure increased by 192% per month, and inpatient medical expenditure increased by 57% annually compared with those of older adults in rural areas without the implementation of TPA policy. Further, there was a significant modification effect, with a positive effect among poor households, healthier older adults, and those aged 60-80 years. Additionally, the policy improved the patients' capabilities to seek long-distance care (ß=23.16, 95% CI -0.99 to 45.31) and high-level hospitals (ß=.08, 95% CI -0.02 to 0.13), and increased individual income to acquire more medical services (ß=4.57, 95% CI -4.46 to 4.68). CONCLUSIONS: These findings validate the positive contribution of TPA policy on health care-seeking behavior among older adults in rural areas; however, the medical expenditure incurred was also high. Concerted efforts are needed to address health care-seeking dilemmas in rural areas, and attention must be paid to curbing medical expenditure growth for older adults in rural areas during TPA policy implementation.

Identification and functional characterization of activating transcription factor 6 (ATF6) from the mud crab (Scylla paramamosain) in response to hydrogen peroxide and bacterial challenge.

Activating transcription factor 6 (ATF6) is critical for regulation of unfolded protein response (UPR), which is involved in the endoplasmic reticulum (ER) proteostasis maintenance and cellular redox regulation. In the present study, a ATF6 gene from the mud crab (designated as Sp-ATF6) has been cloned and identified. The open reading frame of Sp-ATF6 was 1917 bp, encoding a protein of 638 amino acids. The deduced amino acid sequences of Sp-ATF6 contained a typical basic leucine zipper (BZIP domain). Sp-ATF6 was widely expressed in all tested tissues, with the highest expression levels in the hemocytes and the lowest in the muscle. Subcellular localization showed that Sp-ATF6 was expressed in both nucleus and cytoplasm of S2 cells. The expression level of Sp-ATF6 was induced by hydrogen peroxide and V. parahaemolyticus challenge, indicating that the ATF6 pathway was activated in response to ER stress. In order to know more about the regulation mechanism of the Sp-ATF6, RNA interference experiment was investigated. Knocking down Sp-ATF6 in vivo can decrease the expression of antioxidant-related genes (CAT and SOD) and heat shock proteins (HSP90 and HSP70) after V. parahaemolyticus infection. All these results suggested that Sp-ATF6 played a crucial role in the defense against environmental stress and pathogen infection in crustaceans.

Essential role of the HSC70 in the mud crab Scylla paramamosain in response to Vibrio parahaemolyticus infection.

Heat shock proteins play an important role in host defense, and modulate immune responses against pathogen infection. In this study, a novel HSC70 from the mud crab (designated as SpHSC70) was cloned and characterized. The full length of SpHSC70 contained a 58 bp 5'untranslated region (UTR), an open reading frame (ORF) of 2,046 bp and a 3'UTR of 341 bp. The SpHSC70 protein included the conserved DnaK motif. The mRNA of SpHSC70 was highly expressed in the hemocytes, heart and hepatopancreas, and lowly expressed in the intestine. The subcellular localization results indicated that SpHSC70 was localized in both the cytoplasm and the nucleus. Moreover, SpHSC70 was significantly responsive to bacterial challenge. RNA interference experiment was designed to investigate the roles of SpHSC70 in response to bacterial challenge. V. parahaemolyticus infection induced the expression levels of SpPO, SpHSP70, SpSOD and SpCAT. Knocking down SpHSC70 in vivo can decrease the expression of these genes after V. parahaemolyticus infection. These results suggested that SpHSC70 could play a vital role in defense against V. parahaemolyticus infection via activating the immune response and antioxidant defense signaling pathways in the mud crab.

Multi-integrated approach for unraveling small open reading frames potentially associated with secondary metabolism in Streptomyces.

IMPORTANCE: Due to their small size and special chemical features, small open reading frame (smORF)-encoding peptides (SEPs) are often neglected. However, they may play critical roles in regulating gene expression, enzyme activity, and metabolite production. Studies on bacterial microproteins have mainly focused on pathogenic bacteria, which are importance to systematically investigate SEPs in streptomycetes and are rich sources of bioactive secondary metabolites. Our study is the first to perform a global identification of smORFs in streptomycetes. We established a peptidogenomic workflow for non-model microbial strains and identified multiple novel smORFs that are potentially linked to secondary metabolism in streptomycetes. Our multi-integrated approach in this study is meaningful to improve the quality and quantity of the detected smORFs. Ultimately, the workflow we established could be extended to other organisms and would benefit the genome mining of microproteins with critical functions for regulation and engineering useful microorganisms.

Resistance to Diet Induced Visceral Fat Accumulation in C57BL/6NTac Mice Is Associated with an Enriched Lactococcus in the Gut Microbiota and the Phenotype of Immune B Cells in Intestine and Adipose Tissue.

Humans and rodents exhibit a divergent obesity phenotype where not all individuals exposed to a high calorie diet become obese. We hypothesized that in C57BL/6NTac mice, despite a shared genetic background and diet, variations in individual gut microbiota function, immune cell phenotype in the intestine and adipose determine predisposition to obesity. From a larger colony fed a high-fat (HF) diet (60% fat), we obtained twenty-four 18-22-week-old C57BL/6NTac mice. Twelve had responded to the diet, had higher body weight and were termed obese prone (OP). The other 12 had retained a lean frame and were termed obese resistant (OR). We singly housed them for three weeks, monitored food intake and determined insulin resistance, fat accumulation, and small intestinal and fecal gut microbial community membership and structure. From the lamina propria and adipose tissue, we determined the population of total and specific subsets of T and B cells. The OP mice with higher fat accumulation and insulin resistance harbored microbial communities with enhanced capacity for processing dietary sugars, lower alpha diversity, greater abundance of Lactobacilli and low abundance of Clostridia and Desulfobacterota. The OR with less fat accumulation retained insulin sensitivity and harbored microbial communities with enhanced capacity for processing and synthesizing amino acids and higher diversity and greater abundance of Lactococcus, Desulfobacterota and class Clostridia. The B cell phenotype in the lamina propria and mesenteric adipose tissue of OR mice was characterized by a higher population of IgA+ cells and B1b IgM+ cells, respectively, compared to the OP. We conclude that variable responses to the HF diet are associated with the function of individuals' gut microbiota and immune responses in the lamina propria and adipose tissue.

The impacts of knowledge and attitude on behavior of antibiotic use for the common cold among the public and identifying the critical behavioral stage: based on an expanding KAP model.

BACKGROUND: This study aims to explore the impacts of knowledge and attitude on the behavior of antibiotic use during the treatment of the common cold based on the expanding KAP model, and then identify the critical behavioral stage. METHODS: A cross-sectional study was conducted on 815 public from 21 community health centers (CHCs) in Chongqing, China. Based on the expanding KAP model, a self-administered questionnaire was designed to measure knowledge, attitude, multi-stage behavior, and perceived threat, in which multi-stage behavior was divided into pre-use antibiotic behavior, during-use antibiotic behavior, and post-use antibiotic behavior. A structural equation model was used to examine the model fit and the direct, indirect, mediating effects, and moderating effect of the variables. RESULTS: The expanding KAP showed good model fit indices with χ²/df = 0.537, RMSEA = 0.033, CFI = 0.973, GFI = 0.971, NFI = 0.934, TLI = 0.979. Knowledge had a positive effect on attitude (ß = 0.503, p < 0.05), pre-use antibiotic behavior (ß = 0.348, p < 0.05), during-use antibiotic behavior (ß = 0.461, p < 0.001), and post-use antibiotic behavior (ß = 0.547, p < 0.001). Attitude had a positive effect on during-use antibiotic behavior (ß = 0.296, p < 0.001), and post-use antibiotic behavior (ß = 0.747, p < 0.001). The mediating effect of attitude was positive among knowledge, during-use antibiotic behavior (ß = 0.149, p < 0.05), and post-use antibiotic behavior (ß = 0.376, p < 0.001). Perceived threat also had a positive moderating effect between knowledge and post-use antibiotic behavior (ß = 0.021, p < 0.001). CONCLUSIONS: Knowledge, attitude and perceived threat had different effects on different stages of antibiotic behavior. The critical behavioral stage prioritized the post-use antibiotic behavior and during-use antibiotic behavior over pre-use antibiotic behavior.

TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.

BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression. METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC. RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications. CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.

The Vegetable 'Kale' Protects against Dextran-Sulfate-Sodium-Induced Acute Inflammation through Moderating the Ratio of Proinflammatory and Anti-Inflammatory LPS-Producing Bacterial Taxa and Augmenting the Gut Barrier in C57BL6 Mice.

Kale (Brassica oleracea var. acephala), a food rich in bioactive phytochemicals, prevents diet-induced inflammation and gut dysbiosis. We hypothesized that the phytochemicals protect against the lipopolysaccharide (LPS)-induced acute inflammation which results from gut dysbiosis and loss of gut barrier integrity. We designed this study to test the protective effects of the whole vegetable by feeding C57BL/6J mice a rodent high-fat diet supplemented with or without 4.5% kale (0.12 g per 30 g mouse) for 2 weeks before administering 3% dextran sulfate sodium (DSS) via drinking water. After one week, DSS increased the representation of proinflammatory LPS (P-LPS)-producing genera Enterobacter and Klebsiella in colon contents, reduced the representation of anti-inflammatory LPS (A-LPS)-producing taxa from Bacteroidales, reduced the expression of tight junction proteins, increased serum LPS binding protein, upregulated molecular and histopathological markers of inflammation in the colon and shortened the colons. Mice fed kale for 2 weeks before the DSS regime had a significantly reduced representation of Enterobacter and Klebsiella and instead had increased Bacteroidales and Gram-positive taxa and enhanced expression of tight junction proteins. Downstream positive effects of dietary kale were lack of granuloma in colon samples, no shortening of the colon and prevention of inflammation; the expression of F4/80, TLR4 and cytokines 1L-1b, IL-6, TNF-a and iNOS was not different from that of the control group. We conclude that through reducing the proliferation of P-LPS-producing bacteria and augmenting the integrity of the gut barrier, kale protects against DSS-induced inflammation.

Depression as a Mediator and Social Participation as a Moderator in the Bidirectional Relationship Between Sleep Disorders and Pain: Dynamic Cohort Study.

BACKGROUND: Chronic pain, sleep disorders, and depression are major global health concerns. Recent studies have revealed a strong link between sleep disorders and pain, and each of them is bidirectionally correlated with depressive symptoms, suggesting a complex relationship between these conditions. Social participation has been identified as a potential moderator in this complex relationship, with implications for treatment. However, the complex interplay among sleep disorders, pain, depressive symptoms, and social participation in middle- and old-aged Asians remains unclear. OBJECTIVE: This study aimed to examine the bidirectional relationship between sleep disorders and pain in middle- and old-aged Chinese and measure the role of depression as a mediator and social participation as a moderator in this bidirectional relationship through a dynamic cohort study. METHODS: We used data from the China Health and Retirement Longitudinal Study across 5 years and included a total of 7998 middle- and old-aged people (≥45 years old) with complete data in 2011 (T1), 2015 (T2), and 2018 (T3). The cross-lag model was used to assess the interplay among sleep disorders, pain, depressive symptoms, and social participation. Depressive symptoms were assessed by the 10-item Centre for Epidemiological Studies Depression scale. Sleep disorders were assessed by a single-item sleep quality scale and nighttime sleep duration. The pain score was the sum of all pain locations reported. Social participation was measured using self-reported activity. RESULTS: Our results showed significant cross-lagged effects of previous sleep disorders on subsequent pain at T2 (ß=.141; P<.001) and T3 (ß=.117; P<.001) and previous pain on subsequent poor sleep at T2 (ß=.080; P<.001) and T3 (ß=.093; P<.001). The indirect effects of previous sleep disorders on pain through depressive symptoms (ß=.020; SE 0.004; P<.001; effect size 21.98%), as well as previous pain on sleep disorders through depressive symptoms (ß=.012; SE 0.002; P<.001; effect size 20.69%), were significant across the 3 time intervals. Among participants with high levels of social participation, there were no statistically significant effects of previous sleep disorders on subsequent pain at T2 (ß=.048; P=.15) and T3 (ß=.085; P=.02), nor were there statistically significant effects of previous pain on subsequent sleep disorders at T2 (ß=.037; P=.15) and T3 (ß=.039; P=.24). Additionally, the mediating effects of depressive symptoms on the sleep disorders-to-pain pathway (P=.14) and the pain-to-sleep disorders pathway (P=.02) were no longer statistically significant. CONCLUSIONS: There is a bidirectional relationship between sleep disorders and pain in middle- and old-aged Asians; depression plays a longitudinal mediating role in the bidirectional relationship between them; and social participation moderates the bidirectional relationship between them directly and indirectly by affecting depression. Future interventions may consider the complex relationship between these conditions and adopt a comprehensive treatment regime.