Shh regulates M2 microglial polarization and fibrotic scar formation after ischemic stroke.

BACKGROUND: Fibrotic scar formation is a critical pathological change impacting tissue reconstruction and functional recovery after ischemic stroke. The regulatory mechanisms behind fibrotic scarring in the central nervous system (CNS) remain largely unknown. While macrophages are known to play a role in fibrotic scar formation in peripheral tissues, the involvement of microglia, the resident immune cells of the CNS, in CNS fibrosis requires further exploration. The Sonic Hedgehog (Shh) signaling pathway, pivotal in embryonic development and tissue regeneration, is also crucial in modulating fibrosis in peripheral tissues. However, the impact and regulatory mechanisms of Shh on fibrotic scar formation post-ischemic stroke have not been thoroughly investigated. METHODS: This study explores whether Shh can regulate fibrotic scar formation post-ischemic stroke and its underlying mechanisms through in vivo and in vitro manipulation of Shh expression. RESULTS: Our results showed that Shh expression was upregulated in the serum of acute ischemic stroke patients, as well as in the serum, CSF, and ischemic regions of MCAO/R mice. Moreover, the upregulation of Shh expression was positively correlated with fibrotic scar formation and M2 microglial polarization. Shh knockdown inhibited fibrotic scar formation and M2 microglial polarization while aggravating neurological deficits in MCAO/R mice. In vitro, adenoviral knockdown or Smoothened Agonist (SAG) activation of Shh expression in BV2 cells following OGD/R regulated their polarization and influenced the expression of TGFß1 and PDGFA, subsequently affecting fibroblast activation. CONCLUSION: These results suggest that Shh regulates M2 microglial polarization and fibrotic scar formation after cerebral ischemia.

Risk level and removal performance of antibiotic resistance genes and bacterial pathogens in static composting with different temperatures.

The effect of different levels of temperature on resistance genes is not clear in mesophilic static composting (<50 °C). This study conducted livestock manure composting with different temperature gradients from 20 to 50 °C, it was found that the reduction rates of risk rank-I antibiotic resistance genes (from 3 % to 66 %), metal resistance genes (from -50 % to 76 %) and bacterial pathogens (from 72 % to 91 %) all increased significantly with increasing temperature from 20 to 50°C. The vulnerability of bacterial communities increased significantly, and the assembly process of bacterial communities changed from deterministic to stochastic with the increase of composting temperature. Higher temperature could accelerate the removal of thermolabile resistance genes hosts or pathogenic hosts carrying mobile genetic elements by directly or indirectly affecting organic acids content. Therefore, for soil safety, the temperature of the manure recycling process should be increased as much as possible.

Clinical benefit and safety profile of cross-line therapy with CDK4/6 inhibitors: a retrospective study of HR+/HER2- advanced breast cancer.

OBJECTIVE: CDK4/6 inhibitors (CDK4/6is) in combination with endocrine therapy have secured a central role in the treatment of hormone receptor (HR)-positive advanced breast cancer (ABC) and have transformed the therapeutic landscape. Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects. Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2 (HER2)- ABC. METHODS: This retrospective study enrolled 82 patients with HR+/HER2- ABC who were treated with cross-line CDK4/6is (abemaciclib, palbociclib, ribociclib, and dalpiciclib) after progression with another CDK4/6i. The primary endpoint was progression-free survival (PFS) according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included toxicity, objective response rate, disease control rate, and overall survival. Adverse events (AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events, as promulgated by the U.S. Department of Health and Human Services. RESULTS: Eighty-two HR+/HER2- ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled. The median age of the patients was 60 years. The median PFS of all patients was 7.6 months (95% CI, 5.9-9.2). Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS. Notably, patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months. The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i, then to a subsequent CDK4/6i merits further investigation. Hematologic toxicity was the most common grade ≥ 3 AEs. No instances of fatal safety events were observed. CONCLUSIONS: Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2- ABC, which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.

Disruption of network hierarchy pattern in bulimia nervosa reveals brain information integration disorder.

The human brain works as a hierarchical organization that is a continuous axis spanning sensorimotor cortex to transmodal cortex (referring to cortex that integrates multimodal sensory information and participates in complex cognitive functions). Previous studies have demonstrated abnormalities in several specific networks that may account for their multiple behavioral deficits in patients with bulimia nervosa (BN), but whether and how the network hierarchical organization changes in BN remain unknown. This study aimed to investigate alterations of the hierarchy organization in BN network and their clinical relevance. Connectome gradient analyses were applied to depict the network hierarchy patterns of fifty-nine patients with BN and thirty-nine healthy controls (HCs). Then, we evaluated the network- and voxel-level gradient alterations of BN by comparing gradient values in each network and each voxel between patients with BN and HCs. Finally, the association between altered gradient values and clinical variables was explored. In the principal gradient, patients with BN exhibited reduced gradient values in dorsal attention network and increased gradient values in subcortical regions compared to HCs. In the secondary gradient, patients with BN showed decreased gradient values in ventral attention network and increased gradient values in limbic network. Regionally, the areas with altered principal or secondary gradient values in BN group were mainly located in transmodal networks, i.e., the default-mode and frontoparietal network. In BN group, the principal gradient values of right inferior frontal gyrus were negatively associated with external eating behavior. This study revealed the disordered network hierarchy patterns in patients with BN, which suggested a disturbance of brain information integration from attention network and subcortical regions to transmodal networks in these patients. These findings may provide insight into the neurobiological underpinnings of BN.

Parasitic plants regulate C and N distribution among common mycorrhizal networks linking host and neighboring plants.

Common mycorrhizal networks (CMNs) can link multiple plants and distribute nutrients among them. However, how parasitic plants regulate the carbon and nutrient exchange between CMNs and the linked plants is unknown. Thus, we conducted a container experiment with two Trifolium pratense grown in two plastic cores and connected only by CMNs using a 25-µm nylon fabric in each container. Host T. pratense was parasitized or not parasitized by Cuscuta gronovii. CMNs were left intact or broken by rotating the cores with the host or neighboring T. pratense. The dual 15N and 13C labeling method was used to evaluate the N distributed by CMNs to the host and neighboring T. pratense and the recently fixed C from the host and neighboring T. pratense to CMNs. The results showed that CMNs distributed more 15N to unparasitized neighboring T. pratense than the parasitized host T. pratense. Moreover, the unparasitized neighboring T. pratense provides more recently fixed C to CMNs than the parasitized host T. pratense. These results revealed that the parasite regulated C and nutrient exchange between CMNs and the linked plants following the reciprocal rewards rule. Moreover, this study highlights the importance of parasitic plants in the regulation of mutualistic interactions in ecological webs.

Phase 1a study of ESG401, a Trop2 antibody-drug conjugate, in patients with locally advanced/metastatic solid tumors.

This phase 1a study assesses ESG401 in patients with heavily pretreated locally advanced or metastatic solid tumors, focusing on metastatic breast cancer. Forty patients are enrolled: three experience dose-limiting toxicities, establishing the maximum tolerated dose at 16 mg/kg on days 1, 8, and 15 of a 28-day cycle. The most common grade ≥3 treatment-related adverse events are neutropenia and leukopenia. Among 38 efficacy-evaluable patients, the objective response rate (ORR) is 34.2%, the disease control rate (DCR) is 65.8%, and the clinical benefit rate (CBR) is 50.0% (including stable disease for at least 6 months). The median progression-free survival is 5.1 months, and the median duration of response is 6.3 months. In patients receiving therapeutically relevant doses, the ORR, DCR, and CBR are 40.6%, 75.0%, and 56.3%, respectively. ESG401 demonstrates a favorable safety profile and promising antitumor activity in this heavily treated population. The trial is registered at ClinicalTrials.gov (NCT04892342).

Development of a Predictive Nomogram for Intra-Hospital Mortality in Acute Ischemic Stroke Patients Using LASSO Regression.

Background and Purpose: Ischemic stroke is a leading cause of mortality and disability globally, necessitating accurate prediction of intra-hospital mortality (IHM) for improved patient care. This study aimed to develop a practical nomogram for personalized IHM risk prediction in ischemic stroke patients. Methods: A retrospective study of 422 ischemic stroke patients (April 2020 - December 2021) from Chongqing Medical University's First Affiliated Hospital was conducted, with patients divided into training (n=295) and validation (n=127) groups. Data on demographics, comorbidities, stroke risk factors, and lab results were collected. Stroke severity was assessed using NIHSS, and stroke types were classified by TOAST criteria. Least absolute shrinkage and selection operator (LASSO) regression was employed for predictor selection and nomogram construction, with evaluation through ROC curves, calibration curves, and decision curve analysis. Results: LASSO regression and multivariate logistic regression identified four independent IHM predictors: age, admission NIHSS score, chronic obstructive pulmonary disease (COPD) diagnosis, and white blood cell count (WBC). A highly accurate nomogram based on these variables exhibited excellent predictive performance, with AUCs of 0.958 (training) and 0.962 (validation), sensitivities of 93.2% and 95.7%, and specificities of 93.1% and 90.9%, respectively. Calibration curves and decision curve analysis validated its clinical applicability. Conclusion: Age, admission NIHSS score, COPD history, and WBC were identified as independent IHM predictors in ischemic stroke patients. The developed nomogram demonstrated high predictive accuracy and practical utility for mortality risk estimation. External validation and prospective studies are warranted for further confirmation of its clinical efficacy.

ICU nurses' practice and intention to implement early mobilization: A multi-centre cross-sectional survey.

BACKGROUND: Early mobilization (EM) is acknowledged for its safety and benefits in the recovery of critically ill patients, yet its implementation in intensive care units (ICU) remains inconsistently aligned with established guidelines. This discrepancy highlights a gap between theoretical endorsement and practical application. While barriers to EM have been extensively studied, the intentions and perceived practices of ICU nurses towards EM, especially in certain geographical regions, have not been adequately understood. AIM: The objective of this study is to assess the perceptions, actual practices and intentions of ICU nurses regarding the implementation of EM for patients in the ICU setting. STUDY DESIGN: A cross-sectional, multi-centre, survey-based study. RESULTS: The study collected data through an electronic questionnaire from 227 ICU nurses across eight hospitals in Beijing, China, concerning their experiences, practices and intentions related to EM. The survey response rate was 50% (114 of 227), indicating a moderate level of engagement by the target population. Among the surveyed participants, 68.7% (n = 156) reported having experience with EM for critically ill patients. Of these experienced nurses, 49.3% (n = 77) indicated they carried out EM less frequently than once per week, while only 29.5% (n = 46) reported dedicating more than 20 min to EM activities per patient. Only 24.2% (n = 55) of participants confirmed the presence of specific EM guidelines in their workplace. Notably, guideline adherence could be influenced by the patient's condition severity, which may affect how these protocols are applied. Notably, the approach and frequency of EM practices showed significant variation across different ICUs. A substantial majority (75%, n = 170) of participants expressed a strong intention towards implementing EM, correlating significantly with factors such as having a higher education level (bachelor's degree or higher), receiving departmental support, encountering fewer perceived barriers, and belonging to specific departments like respiratory (SICU) and surgery (RICU). The EM guidelines mentioned by participants were primarily focused on specific protocols and guidance, highlighting the emphasis on structured approaches to EM in their clinical settings. CONCLUSIONS: Despite the recognized experience with EM among ICU nurses, there is a notable divergence between their practices and the recommendations outlined in EM guidelines. This study underscores the need for the establishment of clear, actionable guidelines, alongside the provision of targeted educational programmes and robust support systems, to foster the consistent and effective implementation of EM in ICU settings. RELEVANCE TO CLINICAL PRACTICE: This study underscores the clinical relevance of EM in ICU settings, advocating for the development of precise EM guidelines to improve patient outcomes.

Low concentration of serum vitamin B12 may be a strong predictor of large-artery atherosclerosis stroke: A case-control study.

INTRODUCTION: Identifying controllable risk factors for large-artery atherosclerosis (LAA) stroke is crucial due to its significant role as a leading cause of ischemic stroke. We aimed to validate the correlation of serum vitamin B12 with LAA stroke. METHODS: Inpatients with LAA stroke and healthy controls were retrospectively collected for a case-control study from January 2020 to May 2022. Serum vitamin B12 concentration and other blood indicators, demographic, lifestyle factors and comorbidities were investigated. Logistic regression analysis was used to identify the correlation of serum vitamin B12 concentrations with LAA stroke, meanwhile adjusted for confounding factors. RESULTS: Patients with LAA stroke had significantly lower serum vitamin B12 concentrations in comparison to those of controls. In the fully adjusted model, vitamin B12 (per 1 interquartile range increase, odds ratio [OR] = 0.84, 95 % confidence interval [CI]: 0.77-0.91), vitamin B12 < 200 pg/mL (OR=7.70, 95 %CI: 2.19-27.03) and vitamin B12 < 300 pg/mL (OR=4.19, 95 %CI: 1.82-9.66) were independently factors for LAA stroke. Furthermore, the optimal cut-off values for vitamin B12 to predict LAA stroke were 305.25 pg/mL (area under the curve [AUC] = 0.71) when unadjusted and 308.25 pg/mL when adjusted for age and sex (AUC=0.68). Lower vitamin B12 concentrations were significantly associated with male sex, smoking, older age, higher neutrophil count, higher creatinine, lower folate and higher total homocysteine. CONCLUSION: Results indicate that low concentration of serum vitamin B12 may be a strong predictor for the risk of LAA stroke.

Vitamin D Deficiency in the Acute Phase of Stroke May Predict Post-stroke Depression: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct the association between vitamin D levels in the acute phase of stroke and post-stroke depression (PSD) in stroke patients. METHODS: Five international databases (PubMed, Web of Science, Embase, Ovid MEDLINE(R), Cochrane Library) and one Chinese database (Wanfang Data) were searched for observational studies in any language reporting on PSD and vitamin D levels tested in the acute phase of stroke in stroke patients from inception to May 2024. Data extraction and study quality assessment were conducted by two authors independently. Qualitative and quantitative analyses of data were performed. The meta-analysis was registered in the PROSPERO database (CRD42023398581). RESULTS: We included 7 studies containing 3537 participants in the systematic review and meta-analysis. All studies that met the inclusion and exclusion criteria were conducted in China. Vitamin D levels in the acute phase of stroke were lower in PSD patients compared with non-PSD patients (weighted mean difference = -14.97 nmol/L; 95% confidence interval = -19.54, -10.40). Stroke patients with vitamin D deficiency (<50 nmol/L) had an increased risk of PSD compared with stroke patients with vitamin D sufficiency (≥75 nmol/L) (odds ratio = 3.59; 95% confidence interval = 2.05, 6.27). However, the association between vitamin D insufficiency (50-75 nmol/L) and PSD were not statistically significant (odds ratio = 4.15; 95% confidence interval = 0.87, 19.78). CONCLUSION: Vitamin D deficiency in the acute phase of stroke may be a risk factor for PSD.

Factors affecting the readiness for hospital discharge of initially treated pulmonary tuberculosis patients in China: a phenomenological study.

BACKGROUND: Despite readiness for hospital discharge widespread popularity since readiness for hospital discharge introduction in 1979 and extensive study, readiness for hospital discharge among pulmonary tuberculosis (PTB) patients has not yet been investigated. Moreover, the factors influencing this process remain unclear. OBJECTIVE: The objective of this study was to investigate the factors influencing readiness for hospital discharge in initially treated PTB patients using the capability, opportunity, motivation-behavior (COM-B) model. METHODS: This phenomenological study was conducted from December 2023 to March 2024. Face-to-face individual interviews were conducted with 18 initially treated patients with PTB according to a semistructured interview guide developed on the basis of the COM-B model. The interview data were subjected to analysis using NVivo 14 software and Colaizzi's method. RESULTS: As a result, 6 themes and 14 subthemes were identified. Physical capability for readiness for hospital discharge (subthemes included poor health status, early acquisition of adequate knowledge about PTB, inadequate knowledge about readiness for hospital discharge), psychological capability for readiness for hospital discharge(subthemes included false perceptions about readiness for hospital discharge, high treatment adherence), physical opportunity for readiness for hospital discharge (subthemes included high continuity of transition healthcare, insufficient financial support, insufficient informational support), social opportunity for readiness for hospital discharge (subthemes included stigmatization, inadequate emotional support), reflective motivation for readiness for hospital discharge (subthemes included lack of reflection on coping with difficulties, intention to develop a readiness for hospital discharge plan), and automatic motivation for readiness for hospital discharge (subthemes included strong desire to be cured, negative emotions). CONCLUSION: We established factors related to readiness for hospital discharge in initially treated PTB patients in terms of capability, opportunity and motivation, which can inform the future development of readiness for hospital discharge plans. To improve patients' readiness for hospital discharge, patients need to be motivated to plan and desire readiness for hospital discharge, patients' knowledge and treatment adherence should be improved, and patients' transition healthcare continuity and emotional support should be focused on. Moreover, the quality of readiness for hospital discharge and discharge education should be assessed in a timely manner to identify impeding factors and provide interventions.

Association of visceral adiposity index with phenotypic age acceleration: insight from NHANES 1999-2010.

BACKGROUND: Obesity correlates with accelerated aging. This study aims to investigate the association between the visceral adiposity index (VAI) and accelerated aging. METHODS: Biological aging was evaluated by phenotypic age acceleration (PhenoAgeAccel). Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2010, we employed weighted multivariable logistic regression models, along with subgroup analysis, to examine the association between VAI and PhenoAgeAccel. Moreover, smooth curve fitting was utilized to identify potential nonlinear association, complemented by a two-piece linear regression model to investigate threshold effects. RESULTS: Of the included 11,340 participants aged 20 years and older, the mean (95% CI) age was 46.569 (45.946, 47.191) years, and 49.189% were male. The mean (95% CI) VAI for all participants was 2.176 (2.114, 2.238), and the mean (95% CI) PhenoAgeAccel was -6.306 (-6.618, -5.994) years. In the fully adjusted model, each incremental unit increase of VAI was associated with a 0.312-year increase in PhenoAgeAccel (ß = 0.312, 95% CI: 0.217, 0.408). This positive association was more statistically significant among individuals with cancer. Furthermore, a segmented association was observed between VAI and PhenoAgeAccel, with a turning point identified at 10.543. Below this threshold, VAI exhibited a positive correlation with PhenoAgeAccel (ß = 0.617, 95% CI: 0.499, 0.735), while beyond it, the association became nonsignificant. CONCLUSION: This study demonstrated a positive association between VAI and accelerated aging within a nationally representative population. The findings suggest that controlling adiposity may exert anti-aging effects and help prevent aging-related diseases.

Serum levels of vitamin B12 combined with folate and plasma total homocysteine predict ischemic stroke disease: a retrospective case-control study.

PURPOSE: This study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke. MATERIALS AND METHODS: This retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke. RESULTS: Serum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098-4.770), SVD (aOR = 4.471, 95% CI = 1.110-4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733-5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954-6.449), CEI (aOR = 2.809, 95% CI = 1.073-4.991), SVD (aOR = 5.376, 95% CI = 1.708-6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535-7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008-5.148), CEI (aOR = 2.212, 95% CI = 1.247-5.946), SVD (aOR = 2.957, 95% CI = 1.324-6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586-4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR. CONCLUSIONS: Vitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD.

Bulimia nervosa selectively reshapes the structure and intrinsic function of anterior insula subregions associated with cognition-emotion integration.

BACKGROUND: Existing evidence suggests that anterior insula plays a crucial role in cognitive control and emotional regulation and is implicated in the onset and maintenance of bulimia nervosa (BN). However, it remains unclear how structural and functional abnormalities in specific subregions of anterior insula contribute to BN. METHODS: In this study, we analyzed structural MRI and resting-state functional MRI data from 54 BN patients and 56 healthy controls (HCs). We conducted voxel-based morphometry, amplitude of low frequency fluctuation (conventional band: 0.01-0.08 Hz, slow-5: 0.01-0.027 Hz) and seed-based whole-brain functional connectivity (FC) analysis of the anterior insula subregions for both groups. Additionally, we investigated the correlation between neuroimaging findings and clinical characteristics in the BN group. RESULTS: Our findings revealed that BN patients exhibited reduced gray matter volume in the right dorsal anterior insula (dAI) and bilateral ventral anterior insula (vAI) and demonstrated decreased ALFF in slow-5 band of bilateral dAI. The BN group also showed increased FC between bilateral dAI and precuneus or right superior frontal gyri which significantly correlated with the severity of BN or its key symptom. In addition, the decreased FC between bilateral vAI and anterior cingulate and paracingulate gyri and/or median cingulate and paracingulate gyri were both significantly correlated with the severity and its restrained eating behavior. CONCLUSIONS: Our findings further indicate that the functional separation of anterior insula subregions may underlie the pathophysiology of BN. Notably, the vAI associated with emotional processing may serve as a promising neuroimaging biomarker which could inform therapeutic strategy.

Developing and Validating a Nomogram Model for Predicting Ischemic Stroke Risk.

Background and purpose: Clinically, the ability to identify individuals at risk of ischemic stroke remains limited. This study aimed to develop a nomogram model for predicting the risk of acute ischemic stroke. Methods: In this study, we conducted a retrospective analysis on patients who visited the Department of Neurology, collecting important information including clinical records, demographic characteristics, and complete hematological tests. Participants were randomly divided into training and internal validation sets in a 7:3 ratio. Based on their diagnosis, patients were categorized as having or not having ischemic stroke (ischemic and non-ischemic stroke groups). Subsequently, in the training set, key predictive variables were identified through multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods, and a nomogram model was constructed accordingly. The model was then evaluated on the internal validation set and an independent external validation set through area under the receiver operating characteristic curve (AUC-ROC) analysis, a Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) to verify its predictive efficacy and clinical applicability. Results: Eight predictors were identified: age, smoking status, hypertension, diabetes, atrial fibrillation, stroke history, white blood cell count, and vitamin B12 levels. Based on these factors, a nomogram with high predictive accuracy was constructed. The model demonstrated good predictive performance, with an AUC-ROC of 0.760 (95% confidence interval [CI]: 0.736-0.784). The AUC-ROC values for internal and external validation were 0.768 (95% CI: 0.732-0.804) and 0.732 (95% CI: 0.688-0.777), respectively, proving the model's capability to predict the risk of ischemic stroke effectively. Calibration and DCA confirmed its clinical value. Conclusions: We constructed a nomogram based on eight variables, effectively quantifying the risk of ischemic stroke.

AND Logic-Gate-Based Dual-Locking Probe System for the Sensitive Detection of microRNA and APE1.

MicroRNA (miRNA) and apurinic/apyrimidinic endonuclease 1 (APE1) have been reported to be closely associated with cancers, making them potential crucial biomarkers and therapeutic targets. However, focusing on the detection of a single target is not conducive to the diagnosis and prognosis assessment of diseases. In this study, an AND logic-gate-based dual-locking hairpin-mediated catalytic hairpin assembly (DL-CHA) was developed for sensitive and specific detection of microRNA and APE1. By addition of a lock to each of the hairpins, with APE1 and microRNA serving as keys, fluorescence signals could only be detected in the presence of simultaneous stimulation by APE1 and miRNA-224. This indicated that the biosensor could operate as an AND logic gate. DL-CHA exhibited advantages such as a low background, rapid response, and high logic capability. Therefore, the biosensor serves as a novel approach to cancer diagnosis with significant potential applications.

Mendelian randomization as a cornerstone of causal inference for gut microbiota and related diseases from the perspective of bibliometrics.

Gut microbiota, a special group of microbiotas in the human body, contributes to health in a way that can't be ignored. In recent years, Mendelian randomization, which is a widely used and successful method of analyzing causality, has been investigated for the relationship between the gut microbiota and related diseases. Unfortunately, there seems to be a shortage of systematic bibliometric analysis in this field. Therefore, this study aims to investigate the research progress of Mendelian randomization for gut microbiota through comprehensive bibliometric analysis. In this study, publications about Mendelian randomization for gut microbiota were gathered from 2013 to 2023, utilizing the Web of Science Core Collection as our literature source database. The search strategies were as follows: TS = (intestinal flora OR gut flora OR intestinal microflora OR gut microflora OR intestinal microbiota OR gut microbiota OR bowel microbiota OR bowel flora OR gut bacteria OR intestinal tract bacteria OR bowel bacteria OR gut metabolites OR gut microbiota) and TS = (Mendelian randomization). VOSviewer (version 1.6.18), CiteSpace (version 6.1.R1), Microsoft Excel 2021, and Scimago Graphica were employed for bibliometric and visualization analysis. According to research, from January 2013 to August 2023, 154 publications on Mendelian randomization for gut microbiota were written by 1053 authors hailing from 332 institutions across 31 countries and published in 86 journals. China had the highest number of publications, with 109. Frontiers in Microbiology is the most prolific journal, and Lei Zhang has published the highest number of significant articles. The most popular keywords were "Mendelian randomization," "gut microbiota," "instruments," "association," "causality," "gut microbiome," "risk," "bias," "genome-wide association," and "causal relationship." Moreover, the current research hotspots in this field focus on utilizing a 2-sample Mendelian randomization to investigate the relationship between gut microbiota and associated disorders. This research systematically reveals a comprehensive overview of the literature that has been published over the last 10 years about Mendelian randomization for gut microbiota. Moreover, the knowledge of key information in the field from a bibliometric perspective may greatly facilitate future research in the field.

Ir Nanoparticles Supported on Oxygen-Deficient Vanadium Oxides Prepared by a Polyoxovanadate Precursor for Enhanced Electrocatalytic Hydrogen Evolution.

Developing highly active electrocatalysts is crucial for the application of electrocatalytic water splitting. In this study, we prepared vanadium oxide-graphene carbon nanocomposites (VxOy/C) with abundant defects using a carbon- and oxygen-rich hexavanadate derivative Na2[V6O7{(OCH2)3CCH3}4] as a precursor without the addition of an extra carbon source. Subsequently, the VxOy/C was used as a catalyst support to load a small amount of Ir, forming the Ir/VxOy/C nanoelectrocatalyst. This catalyst exhibited low hydrogen evolution overpotentials of only 18.90 and 13.46 mV at a working current density of 10 mA cm-2 in 1.0 M KOH and 0.5 M H2SO4 electrolyte systems, outperforming the commercial Pt/C catalysts. Additionally, the catalyst showed excellent chemical stability and long-term durability. This work provides a new strategy for the design and synthesis of highly active electrocatalysts for water splitting.

The correlation between the need for continuing care services, influencing factors, and social support and discharge readiness among discharged patients with pulmonary tuberculosis in China: A cross-sectional study.

OBJECTIVE: To understand the relationship between the need for continuing care services and influencing factors, social support, readiness for discharge among discharged pulmonary tuberculosis (PTB) patients. METHODS: A cross-sectional study was conducted among 170 patients from a database of discharged patients with PTB from September 2023 to January 2024. A demographic and disease characteristics questionnaire, continuing care services basic modality questionnaire, continuing care services need questionnaire, the Social Support Rating Scale (SSRS), and the Readiness for Hospital Discharge Scale (RHDS) were used for this investigation. Univariate analysis and multiple linear regression analysis were used to analyze the associated factors. RESULTS: The mean total score for the need for continuing care services among patients with PTB discharged from the hospital was (121.61 ± 22.98). The dimension with the highest score was health education guidance need. Compared to the the original hospital medical personnel, the primary source of care information after discharge was the local medical institutions was statistically significant and negatively correlated with continuing care service need (P = 0.005). Social support was positively associated with need for continuing care services (P = 0.042). CONCLUSION: Discharged PTB patients had a high degree of continuing care service need. Factors influencing the need for continuing care services are the primary source of care information after discharge was the local medical institutions, the social support. Medical staff need to provide targeted continuing care services based on relevant influencing factors to meet the discharge needs of patients.

Intervention of exogenous VEGF protect brain microvascular endothelial cells from hypoxia-induced injury by regulating PLCγ/RAS/ERK and PI3K/AKT pathways.

Ischemic stroke rapidly increases the expression level of vascular endothelial growth factor (VEGF), which promotes neovascularization during hypoxia. However, the effect and mechanism of VEGF intervention on cerebrovascular formation remain unclear. Therefore, our research discussed the protective effect of exogenous VEGF on cells in hypoxia environment in cerebral microvascular endothelial cells, simulating ischemic stroke in hypoxic environment. Firstly, we detected the proliferation and apoptosis of cerebral microvascular endothelial cells under hypoxia environment, as well the expression levels of VEGF-E, vascular endothelial growth factor re-ceptor-2 (VEGFR-2), BCL2, PRKCE and PINK1. Moreover, immunofluorescence and western blotting were used to verify the regulation of exogenous VEGF-E on VEGFR-2 expression in hypoxic or normal oxygen environment. Lastly, we manipulated the concentration of VEGF-E in the culture medium to investigate its impact on phospholipase Cγ1 (PLCγ1)/extracellular signaling regulatory protein kinase (ERK) -1/2 and protein kinase B (AKT) pathways. Additionally, we employed a PLCγ1 inhibitor (U73122) to investigate its impact on proliferation and PLCγ1/ERK pathways. The results show that hypoxia inhibited the proliferation of cerebral microvascular endothelial cells, promoted cell apoptosis, significantly up-regulated the expression of VEGF-E, VEGFR-2, PRKCE and PINK1, but down-regulated the expression of BCL2. Interference from exogenous VEGF-E activated PLCγ1/ERK-1/2 and AKT pathways, promoting cell proliferation and inhibiting apoptosis of hypoxic brain microvascular endothelial cells. In summary, exogenous VEGF-E prevents hypoxia-induced damage to cerebral microvascular endothelial cells by activating the PLCγ1/ERK and AKT pathways. This action inhibits the apoptosis pathway in hypoxic cerebral microvascular endothelial cells, thereby safeguarding the blood-brain barrier and the nervous system.