Phosphine-Catalyzed Stereospecific and Enantioselective Desymmetrizative [3+2] Cycloaddition of MBH Carbonates and N-(2-tert-Butylphenyl)maleimides.

Herein, we report an l-valine-derived amide phosphine-catalyzed [3+2] cyclization of MBH carbonates and N-(2-tert-butylphenyl)maleimides via asymmetric desymmetrization. Bicyclic N-aryl succinimide derivatives bearing three continuous chiral centers with a remote C-N atropisomeric chirality were constructed stereospecifically and enantioselectively. A wide variety of MBH carbonates could be employed in this process to deliver highly optically pure succinimide derivatives in moderate to excellent yields.

Removal and assessment of cadmium contamination based on the toxic responds of a soil ciliate Colpoda sp.

Bioremediation of cadmium (Cd) pollution, a recognized low-carbon green environmental protection technology, is significantly enhanced by the discovery of Cd-tolerant microorganisms and their underlying tolerance mechanisms. This study presents Colpoda sp., a soil ciliate with widespread distribution, as a novel bioindicator and bioremediator for Cd contamination. With a 24 h-LC50 of 5.39 mg l-1 and an IC50 of 24.85 µg l-1 in Cd-contaminated water, Colpoda sp. achieves a maximum bioaccumulation factor (BAF) of 3.58 and a Cd removal rate of 32.98 ± 0.74 % within 96 h. The toxic responses of Colpoda sp. to Cd stress were assessed through cytological observation with transmission electron microscopy (TEM), oxidative stress kinase activity, and analysis of Cd-metallothionein (Cd-MTs) and the cd-mt gene via qRT-PCR. The integrated biomarker response index version 2 (IBRv2) and structural equation models (SEM) were utilized to analyze key factors and mechanisms, revealing that the up-regulation of Cd-MTs and cd-mt expression, rather than the oxidative stress system, is the primary determinant of Cd accumulation and tolerance in Colpoda sp. The ciliate's ability to maintain growth under 24.85 µg l-1 Cd stress and its capacity to absorb and accumulate Cd particles from water into cells are pivotal for bioremediation. A new mathematical formula and regression equations based on Colpoda sp.'s response parameters have been established to evaluate environmental Cd removal levels and design remediation schemes for contaminated sites. These findings provide a novel bioremediation and monitoring pathway for Cd remobilization and accumulation in soil and water, potentially revolutionizing the governance of Cd pollution.

Urinary haloacetic acid concentrations in relation to sex and thyroid hormones among reproductive-aged men.

Sex and thyroid hormones are critical for male reproductive health. However, the associations between haloacetic acid (HAA) exposure - a known endocrine disruptor - and sex and thyroid hormones in humans remains unclear. We thus recruited 502 male participants seeking fertility evaluation from a reproductive center. We measured concentrations of sex and thyroid hormones in a single blood sample and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in repeated urine samples. Multivariable linear regression models were constructed to evaluate the associations between HAA concentrations and hormone measurements. After adjusting for potential confounders and urinary creatinine concentrations, urinary concentrations of TCAA were inversely associated with serum levels of sex hormone-binding globulin (SHBG), testosterone (T), T/luteinizing hormone ratio (T/LH), and thyroid stimulating hormone (TSH) (all P for trend < 0.10). Compared with participants in the lowest quartile of TCAA concentrations, those in the highest quartile had reduced serum levels of SHGB by 14.2 % (95% CI: -26.7, -3.0 %), T by 11.1 % (95% CI: -21.7, -1.3 %), T/LH by 21.0 % (95% CI: -36.7, -7.1 %), and TSH by 19.1 % (95% CI: -39.7, -1.5 %). Additionally, we observed inverse associations between continuous measurements of urinary HAAs and serum levels of free T, bioactive T, and estradiol. Our findings suggest that male HAA exposure may be associated with disrupted sex and thyroid function.

Yangonin, one of the kavalactones isolated from Piper methysticum G. Forst, acts through cannabinoid 1 (CB1) receptors to induce an intrathecal anti-hyperalgesia.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst (Piperaceae) is traditionally consumed in Polynesian culture. The roots are used to produce an entheogenic drink and traditional medicine with sedative and anxiolytic properties. There is also evidence that it functions as a pain reliever. Kavalactones, its main active ingredients, exhibit psychoactive effects on the central nervous system. However, the active ingredients and pharmacological mechanisms underlying the analgesic effect of kavalactones are unclear. AIM OF THE STUDY: This study investigated the effects of kavain and yangonin on nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at the spinal level. MATERIALS AND METHODS: Male Sprague-Dawley rats were administered kavain and yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests were performed to evaluate the anti-nociceptive properties. The efficacy of kavain and yangonin on inflammatory hyperalgesia was examined using a plantar test in rats with carrageenan-induced paw inflammation. The von Frey test was used to assess mechanical allodynia induced by partial sciatic nerve ligation. RESULTS: Intrathecal injection of yangonin demonstrated a relatively potent anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These effects were completely reversed by the co-administration of PF 514273, a cannabinoid 1 (CB1) receptor antagonist. However, yangonin did not affect mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal level. CONCLUSIONS: Overall, our study demonstrated that yangonin exerts anti-nociception and anti-inflammatory hyperalgesia effects via CB1 receptors at the spinal level. We identified a single kavalactone, yangonin, extracted from kava as a promising treatment for pain.

Benign splenic lesions in BAP1-tumor predisposition syndrome: a case series.

BAP1-Tumor Predisposition Syndrome (TPDS) is caused by germline variants in BAP1 and predisposes to solid tumors. After observation of a radiologically malignant-appearing splenic mass with benign pathology in a patient with BAP1-TPDS, we sought to retrospectively characterize splenic lesions in individuals with BAP1-TPDS seen at a comprehensive cancer center. A dedicated radiology review for splenic abnormalities was performed. We identified 37 individuals with BAP1-TPDS, 81% with a history of cancer. Of 33 individuals with abdominal imaging, 10 (30%) had splenic lesions, and none were shown to be malignant on follow-up. Splenectomy in an individual with suspected splenic angiosarcoma showed a benign vascular neoplasm with loss of nuclear staining for BAP1 in a subset of cells. Benign splenic lesions appear to be common and potentially BAP1-driven in individuals with BAP1-TPDS; confirmation of these findings could lead to more conservative management and avoidance of splenectomy.

Deciphering the environmental chemical basis of muscle quality decline by interpretable machine learning models.

BACKGROUND: Sarcopenia is known as a decline in skeletal muscle quality and function that is associated with age. Sarcopenia is linked to diverse health problems, including endocrine-related diseases. Environmental chemicals (ECs), a broad class of chemicals released from industry, may influence muscle quality decline. OBJECTIVE: In our work, we aim to simultaneously elucidate the associations between muscle quality decline and diverse EC exposures based on the data from the 2011-2012 and 2013-2014 survey cycles in the National Health and Nutrition Examination Survey (NHANES) project using machine learning models. METHODS: Six machine learning models were trained based on the EC and non-EC exposures from NHANES to distinguish low from normal muscle quality index status. Different machine learning metrics were evaluated for these models. The SHAP (SHapley Additive exPlanations) approach was used to provide explainability for machine learning models. RESULTS: Random Forest (RF) performed best on the independent testing dataset. Based on the testing dataset, ECs can independently predict the binary muscle quality status with good performance by RF (Area Under the Receiver Operating Characteristic Curve (AUROC) = 0.793, Area Under the Precision-Recall Curve (AUPRC) = 0.808). The SHAP ranked the importance of ECs for the RF model. As a result, several metals and chemicals in urine, including 3-phenoxybenzoic acid and cobalt, were more associated with the muscle quality decline. CONCLUSIONS: Altogether, our analyses suggest that ECs can independently predict muscle quality decline with a good performance by RF, and the SHAP-identified ECs can be closely related to muscle quality decline and sarcopenia. Our analyses may provide valuable insights into environmental chemicals that may be the important basis of sarcopenia and endocrine-related diseases in U.S.

Fosfenopril Attenuates Inflammatory Response in Diabetic Dry Eye Models by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

Purpose: The purpose of this study was to investigate the involvement of the TLR4/NF-κB/NLRP3 signaling pathway and its underlying mechanism in diabetic dry eye. Methods: Two models of diabetic dry eye were established in high glucose-induced human corneal epithelial (HCE-T) cells and streptozotocin (STZ)-induced C57BL/6 mice, and the TLR4 inhibitor fosfenopril (FOS) was utilized to suppress the TLR4/NF-κB/NLRP3 signaling pathway. The expression changes in TLR4, NF-κB, NLRP3, and IL-1ß, and other factors were detected by Western blot and RT‒qPCR, the wound healing rate was evaluated by cell scratch assay, and the symptoms of diabetic mice were evaluated by corneal sodium fluorescein staining and tear secretion assay. Results: In the diabetic dry eye model, the transcript levels of TLR4, NF-κB, NLRP3, and IL-1ß were raised, and further application of FOS, a TLR4 inhibitor, downregulated the levels of these pathway factors. In addition, FOS was found to be effective in increasing the wound healing rate of high glucose-induced HCE-T cells, increasing tear production, and decreasing corneal fluorescence staining scores in diabetic mice, as measured by cell scratch assay, corneal sodium fluorescein staining assay, and tear production. Conclusions: The current study found that the TLR4/NF-κB/NLRP3 signaling pathway regulates diabetic dry eye in an in vitro and in vivo model, and that FOS reduces the signs of dry eye in diabetic mice, providing a new treatment option for diabetic dry eye.

The association between uric acid and erectile dysfunction in US adults: NHANES 2001-2004.

BACKGROUND: -Recent evidence suggests that hyperuricemia may act as independent risk factors for erectile dysfunction (ED), in addition to the already established factors. The current evidence supporting this relationship remains insufficient. METHODS AND RESULTS: -A total of 3,810 participants from the NHANES pool between 2001 and 2004 were included in our study, comprising 1,093 individuals with ED and 2,717 individuals without ED. Univariable and multivariable logistic regression analyses were conducted to examine the relationship between uric acid (UA) and the prevalence of ED. In the fully adjusted model, no significant association was observed between UA and ED (OR = 1.02, 95% CI: 0.84-1.24), and no significant differences were noted among the various UA levels (p = 0.5). In our sensitivity analyses, employing a stricter definition for ED, no significant results were found in the fully adjusted model (OR = 0.85, 95% CI: 0.60-1.19). Furthermore, no significant differences were observed among the various UA levels (p = 0.083). CONCLUSIONS: -Our study did not establish a correlation between UA levels and ED. Nonetheless, further research with larger sample cohorts is required to verify these findings.

A pharmacovigilance study of drug-reduced male semen quality based on the Food and Drug Administration adverse event reporting system database.

BACKGROUND: Real-world big data studies on drug-reduced male semen quality are few and far between, with most studies based on animal trials, small scale retrospective studies, or a limited number of pre-market clinical trials. METHODS: This study aimed to identify culprit drugs that reduced male semen quality based on the United States Food and Drug Administration adverse event reporting system. The Medical Dictionary for Regulatory Activities preferred terms and standardized Medical Dictionary for Regulatory Activities queries were used to define reduced male semen quality. Adverse events related to drug-reduced male semen quality were then analyzed by disproportionality analysis using the United States Food and Drug Administration adverse event reporting system data between 2004 and 2023. RESULTS: At the preferred term level, 59 drugs with risk signals were detected to be associated with drug-reduced male semen quality, with the three most frequently reported second-level Anatomical Therapeutic Chemical groups being antineoplastic agents (n = 16, 27.12%), psychoanaleptics (n = 9, 15.25%), and psycholeptics (n = 6, 10.17%). At the standardized Medical Dictionary for Regulatory Activities queries level, the five drugs with the greatest number of cases were finasteride (845 cases, IC025 = 7.72), dutasteride (163 cases, IC025 = 7.22), tamsulosin (148 cases, IC025 = 5.99), testosterone (101 cases, IC025 = 4.08), and valproic acid (54 cases, IC025 = 2.44). Additionally, clinical information about drug-reduced male semen quality is absent from the Summary of Product Characteristics of 41 drugs in our study. CONCLUSIONS: Using the United States Food and Drug Administration adverse event reporting system database, we offer a list of drugs with risk signals for reducing male semen quality. In the future, there is still a need for more studies on drugs whose effects on male semen quality are not fully understood.

Molybdenum single-atoms decorated multi-channel carbon nanofibers for advanced lithium-selenium batteries.

The cathode in lithium-selenium (Li-Se) batteries has garnered extensive attention owing to its superior specific capacity and enhanced conductivity compared to sulfur. Nonetheless, the adoption and advancement of Li-Se batteries face significant challenges due to selenium's low reactivity, substantial volume fluctuations, and the shuttle effect associated with polyselenides. Single-atom catalysts (SACs) are under the spotlight for their outstanding catalytic efficiency and optimal atomic utilization. To address the challenges of selenium's low chemical activity and volume expansion in Li-Se batteries, through electrospun, we have developed a lotus root-inspired carbon nanofiber (CNF) material, featured internal multi-channels and anchored with molybdenum (Mo) single atoms (Mo@CNFs). Mo single atoms significantly enhance the conversion kinetics of selenium (Se), facilitating rapid formation of Li2Se. The internally structured multi-channel CNF serves as an effective host matrix for Se, mitigating its volume expansion during the electrochemical process. The resulting cathode, Se/Mo@CNF composite, exhibits a high discharge specific capacity, superior rate performance, and impressive cycle stability in Li-Se batteries. After 500 cycles at a current density of 1 C, it maintains a capacity retention rate of 82% and nearly 100% coulombic efficiency (CE). This research offers a new avenue for the application of single-atom materials in enhancing advanced Li-Se battery performance.

Computer-aided molecular design and optimization of potent inhibitors disrupting APC‒Asef interaction.

Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. At initial diagnosis, approximately 20% of patients are diagnosed with metastatic CRC (mCRC). Although the APC‒Asef interaction is a well-established target for mCRC therapy, the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging endeavor. In this study, we identified a novel structural scaffold based on MAI inhibitors, the first-in-class APC‒Asef inhibitors we reported previously. ONIOM model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed, and 24-fold greater potency was obtained with the best inhibitor compared to the parental compound. In addition, the cocrystal structure validated that the two-layer π‒π stacking interactions were essential for inhibitor stabilization in the bound state. Furthermore, in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC‒Asef interaction. These results provide an intrinsic structural basis to further explore drug-like molecules for APC‒Asef-mediated CRC therapy.

Liver Epigenomic Signature Associated with Chronic Oxidative Stress in a Mouse Model of Glutathione Deficiency.

Oxidative stress is intimately involved in the pathogenesis of fatty liver disease (FLD). A major factor contributing to oxidative stress is the depletion of the ubiquitous antioxidant glutathione (GSH). Unexpectedly, chronic GSH deficiency renders glutamate-cysteine ligase modifier subunit (Gclm)-null mice protected from fatty liver injuries. Epigenetic regulation serves as an important cellular mechanism in modulating gene expression and disease outcome in FLD, although it is not well understood how systemic redox imbalance modifies the liver epigenome. In the current study, utilizing the Gclm-null mouse model, we aimed to elucidate redox-associated epigenomic changes and their implications in liver stress response. We performed high-throughput array-based DNA methylation profiling (MeDIP array) in 22,327 gene promoter regions (from -1300 bp to +500 bp of the Transcription Start Sites) in the liver and peripheral blood cells. Results from the MeDIP array demonstrate that, although global methylation enrichment in gene promoters did not change, low GSH resulted in prevalent demethylation at the individual promoter level. Such an effect likely attributed to a declined availability of the methyl donor S-adenosyl methionine (SAM) in Gclm-null liver. Functional enrichment analysis of liver target genes is suggestive of a potential role of epigenetic mechanisms in promoting cellular survival and lipid homeostasis in Gclm-null liver. In comparison with the liver tissue, MeDIP array in peripheral blood cells revealed a panel of 19 gene promoters that are candidate circulating biomarkers for hepatic epigenomic changes associated with chronic GSH deficiency. Collectively, our results provided new insights into the in vivo interplay between liver redox state and DNA methylation status. The current study laid the groundwork for future epigenetic/epigenomic investigations in experimental settings or human populations under conditions of liver oxidative stress induced by environmental or dietary challenges.

Perspective on Agricultural Industrialization: Modification Strategies for Enhancing the Catalytic Capacity of Keratinase.

Keratinases is a special hydrolytic enzyme produced by microorganisms, which has the ability to catalyze the degradation of keratin. Currently, keratinases show great potential for application in many agricultural and industrial fields, such as biofermented feed, leather tanning, hair removal, and fertilizer production. However, these potentials have not yet been fully unleashed on an industrial scale. This paper reviews the sources, properties, and catalytic mechanisms of keratinases. Strategies for the molecular modification of keratinases are summarized and discussed in terms of improving the substrate specificity, thermostability, and pH tolerance of keratinases. The modification strategies are also enriched by the introduction of immobilized enzymes and directed evolution. In addition, the selection of modification strategies when facing specific industrial applications is discussed and prospects are provided. We believe that this review serves as a reference for the future quest to extend the application of keratinases from the laboratory to industry.

Preoperative CECT-Based Multitask Model Predicts Peritoneal Recurrence and Disease-Free Survival in Advanced Ovarian Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: Peritoneal recurrence is the predominant pattern of recurrence in advanced ovarian cancer (AOC) and portends a dismal prognosis. Accurate prediction of peritoneal recurrence and disease-free survival (DFS) is crucial to identify patients who might benefit from intensive treatment. We aimed to develop a predictive model for peritoneal recurrence and prognosis in AOC. METHODS: In this retrospective multi-institution study of 515 patients, an end-to-end multi-task convolutional neural network (MCNN) comprising a segmentation convolutional neural network (CNN) and a classification CNN was developed and tested using preoperative CT images, and MCNN-score was generated to indicate the peritoneal recurrence and DFS status in patients with AOC. We evaluated the accuracy of the model for automatic segmentation and predict prognosis. RESULTS: The MCNN achieved promising segmentation performances with a mean Dice coefficient of 84.3% (range: 78.8%-87.0%). The MCNN was able to predict peritoneal recurrence in the training (AUC 0.87; 95% CI 0.82-0.90), internal test (0.88; 0.85-0.92), and external test set (0.82; 0.78-0.86). Similarly, MCNN demonstrated consistently high accuracy in predicting recurrence, with an AUC of 0.85; 95% CI 0.82-0.88, 0.83; 95% CI 0.80-0.86, and 0.85; 95% CI 0.83-0.88. For patients with a high MCNN-score of recurrence, it was associated with poorer DFS with P < 0.0001 and hazard ratios of 0.1964 (95% CI: 0.1439-0.2680), 0.3249 (95% CI: 0.1896-0.5565), and 0.3458 (95% CI: 0.2582-0.4632). CONCLUSION: The MCNN approach demonstrated high performance in predicting peritoneal recurrence and DFS in patients with AOC.

Highly Curved Defect Sites: How Curvature Effect Influences Metal-Free Defective Carbon Electrocatalysts.

Topological defects are widely recognized as effective active sites toward a variety of electrochemical reactions. However, the role of defect curvature is still not fully understood. Herein, carbon nanomaterials with rich topological defect sites of tunable curvature is reported. The curved defective surface is realized by controlling the high-temperature pyrolytic shrinkage process of precursors. Theoretical calculations demonstrate bending the defect sites can change the local electronic structure, promote the charge transfer to key intermediates, and lower the energy barrier for oxygen reduction reaction (ORR). Experimental results convince structural superiority of highly-curved defective sites, with a high kinetic current density of 22.5 mA cm-2 at 0.8 V versus RHE for high-curvature defective carbon (HCDC), ≈18 times that of low-curvature defective carbon (LCDC). Further raising the defect densities in HCDC leads to the dual-regulated products (HCHDC), which exhibit exceptionally outstanding ORR activity in both alkaline and acidic media (half-wave potentials: 0.88 and 0.74 V), outperforming most of the reported metal-free carbon catalysts. This work uncovers the curvature-activity relationship in carbon defect for ORR and provides new guidance to design advanced catalysts via curvature-engineering.

SlNAC3 suppresses cold tolerance in tomatoes by enhancing ethylene biosynthesis.

Low temperature stress poses a significant challenge to the productivity of horticultural crops. The dynamic expression of cold-responsive genes plays a crucial role in plant cold tolerance. While NAC transcription factors have been extensively studied in plant growth and development, their involvement in regulating plant cold tolerance remains poorly understood. In this study, we focused on the identification and characterisation of SlNAC3 as the most rapid and robust responsive gene in tomato under low temperature conditions. Manipulating SlNAC3 through overexpression or silencing resulted in reduced or enhanced cold tolerance, respectively. Surprisingly, we discovered a negative correlation between the expression of CBF and cold tolerance in the SlNAC3 transgenic lines. These findings suggest that SlNAC3 regulates tomato cold tolerance likely through a CBF-independent pathway. Furthermore, we conducted additional investigations to identify the molecular mechanisms underlying SINAC3-mediated cold tolerance in tomatoes. Our results revealed that SlNAC3 controls the transcription of ethylene biosynthetic genes, thereby bursting ethylene release in response to cold stress. Indeed, the silencing of these genes led to an augmentation in cold tolerance. This discovery provides valuable insights into the regulatory pathways involved in ethylene-mediated cold tolerance in tomatoes, offering potential strategies for developing innovative approaches to enhance cold stress resilience in this economically important crop species.

Reliability and validity tests of the Chinese version of the Geriatric Locomotive Function Scale (GLFS-25) in tumor survivors.

Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P < 0.001). Subsequent confirmatory factor analysis (CFA) extracted four distinct factors: Social Activity Engagement, Daily Living Ability, Pain Experience and Physical Mobility. These factors accounted for 72.668 % of the variance, indicating substantial construct validity for measuring LS among this population. CFA supported the model's fit with the following indices: χ2/df = 1.559, RMSEA = 0.077, GFI = 0.924, CFI = 0.941, NFI = 0.919, and TLI = 0.933. The factor loadings for the four factors ranged from 0.771 to 0.931, indicating the items corresponding to the four factors effectively represented the constructs they were designed to measure. The correlation coefficients among the four factors were between 0.306 and 0.469, all lower than the square roots of the respective AVEs (0.838-0.867). This suggests a moderate correlation among the four factors and a distinct differentiation between them, indicating the Chinese version of the GLFS-25 exhibits strong discriminant validity in Chinese tumor survivors. Reliability testing revealed a high Cronbach's α coefficient for the overall scale at 0.961, with the subscales yielding coefficients of 0.751, 0.836, 0.930, and 0.952. The overall ICC was determined to be 0.935, with subscale ICCs ranging from 0.857 to 0.941, reinforcing the scale's reliability in this context. Conclusions: The Chinese version of the GLFS-25 exhibits strong reliability and validity for the assessment of LS in tumor survivors. It may serve as a diagnostic tool for LS, contributing to the prevention and management of musculoskeletal disorders and enhancing the prognosis for this patient population.

Factors influencing civil servants' willingness to implement cardiopulmonary resuscitation in Chongqing, China: Based on the theory of planned behavior.

Background: Timely bystander cardiopulmonary resuscitation is the key to improving the survival rate of out-of-hospital cardiac arrest. Civil servants are potential bystander CPR providers. This study aimed to explore civil servants' willingness to implement CPR in Chongqing, identify the influencing factors and mechanisms affecting civil servants' willingness to perform CPR, and then seek countermeasures to improve civil servants' willingness to implement CPR. Methods: We introduced the theory of perceived risk into the theory of planned behavior, developed a 7-point Likert scale based on the extended theory of planned behavior, and conducted a questionnaire survey on civil servants in Chongqing, China. Descriptive statistical analysis and one-way ANOVA were employed to explore respondents' willingness and differences. Structural equation modeling was used to analyze the relationship between attitude, subjective norm, perceived behavioral control and perceived risk and respondents' willingness to implement CPR. Results: A total of 1235 valid questionnaires were included for analysis. 50.1 % of respondents were willing to implement CPR. Male, over 40 years old, living with the elderly, having previous experience performing CPR on another person, and having higher CPR knowledge scores were associated with a more positive willingness to perform CPR. Attitude, subjective norm and perceived behavioral control had significant positive effects on willingness, and the standardized regression coefficients were 0.164, 0.326 and 0.313, respectively. The perceived risk has a significant negative effect on willingness, and the standardized regression coefficient was -0.109. The four latent variables accounted for 44.2 % of the variance in the willingness of civil servants to implement CPR. Conclusions: The willingness of civil servants in Chongqing to implement CPR needs to be improved, and the countermeasures to enhance the subjective norm and perceived behavioral control of civil servants should be emphasized, such as developing a social support network for rescuing conduct, establishing regular training mechanisms and improving the practical applicability and popularization of the Chinese-style "Good Samaritan Law" etc., to improve the willingness of civil servants in Chongqing to implement CPR.

Age at menopause and risk of ischemic stroke: a systematic review and meta-analysis.

AIMS: Despite ischemic stroke having much importance as one of the top 10 causes of death in older women, there is limited data on age at menopause and ischemic stroke. We performed a systematic review and meta-analysis to estimate the effect of age at menopause on ischemic stroke. METHODS: We screened four databases (PubMed, Cochrane, Web of Science, and EMBASE databases) up to July 17, 2023. This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42023444245). Data extraction and quality assessment were independently undertaken by two reviewers. A random-effects model was used for meta-analysis using Revman5.4 to calculate the risk ratio of the incidence of ischemic stroke. Heterogeneity was assessed using I2. Meta-regression and assessment for bias were performed. RESULTS: Out of 725 records identified, 10 studies were included in the qualitative synthesis and the quantitative meta-analysis. The pooled incidence rate for ischemic strokes which age at menopause before 43 years old was 1.22 (95% confidence interval (CI): 1.02-1.46). The pooled incidence rate of early menopause was 1.26 (95% CI: 1.07-1.48) for ischemic stroke. The incidence rate of ischemic stroke for women with early menopause may be in an environment with a high incidence for a long time. CONCLUSION: This meta-analysis suggests that early menopause is associated with an increased risk of ischemic stroke. Age at onset of menopause before 43 years old may be the cut-off value of increased risk of ischemic stroke.

Ischemic stroke has much importance as one of the top 10 causes of death in older women. We performed a systematic review and meta-analysis to estimate the effect of age at onset of menopause on ischemic stroke. Our findings suggest that early menopause is associated with an increased risk of ischemic stroke. Age at onset of menopause before 43 years old may be the cut-off value of increased risk of ischemic stroke, which provides some nexus between the relationship of early menopause and ischemic stroke risk.