Prevalence of Motoric Cognitive Risk Syndrome Among Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically review the prevalence of motoric cognitive risk syndrome (MCR) among community-dwelling older adults and provide evidence-based support for policymakers planning health and social care policies. METHOD: Web of Science, PubMed, and Cochrane Library databases were searched for cross-sectional, prospective cohort, or population-based longitudinal studies of community-dwelling older adults aged ≥60 years with MCR from inception of the database through December 18, 2021. RESULTS: Seventeen studies were included. Pooled prevalence of MCR was found to be 10% (95% confidence interval [8%, 12%], I2 = 98.4%). Results of a subgroup analysis revealed a combined prevalence of MCR of 8.2% in males and 9.2% in females. Pooled prevalence of MCR was 9.7% in Asia and 10.2% in other regions. CONCLUSION: Prevalence of MCR in community-dwelling older adults is high. Our research may improve the epidemiological understanding of MCR, draw attention to older adults with MCR, and thus promote research of MCR and the formulation of relevant public health policies. With early identification and intervention of MCR, cognitive function can be improved, and the onset of dementia can be delayed or prevented. [Journal of Gerontological Nursing, 50(4), 16-24.].

Clinical distribution of carbapenem genotypes and resistance to ceftazidime-avibactam in Enterobacteriaceae bacteria.

Introduction: Bacterial resistance is a major threat to public health worldwide. To gain an understanding of the clinical infection distribution, drug resistance information, and genotype of CRE in Dongguan, China, as well as the resistance of relevant genotypes to CAZ-AVI, this research aims to improve drug resistance monitoring information in Dongguan and provide a reliable basis for the clinical control and treatment of CRE infection. Methods: VITEK-2 Compact automatic analyzer was utilized to identify 516 strains of CRE collected from January 2017 to June 2023. To determine drug sensitivity, the K-B method, E-test, and MIC methods were used. From June 2022 to June 2023, 80 CRE strains were selected, and GeneXpert Carba-R was used to detect and identify the genotype of the carbapenemase present in the collected CRE strains. An in-depth analysis was conducted on the CAZ-AVI in vitro drug sensitivity activity of various genotypes of CRE, and the results were statistically evaluated using SPSS 23.0 and WHONET 5.6 software. Results: This study identified 516 CRE strains, with the majority (70.16%) being K.pneumoniae, followed by E.coli (18.99%). Respiratory specimens had highest detection rate with 53.77% identified, whereas urine specimens had the second highest detection rate with 17.99%. From June 2022 to June 2023, 95% of the strains tested using the CRE GeneXpert Carba-R assay possessed carbapenemase genes, of which 32.5% were blaNDM strains and 61.25% blaKPC strains. The results showed that CRE strains containing blaKPC had a significantly higher rate of resistance to amikacin, cefepime, and aztreonam than those harboring blaNDM. Conclusions: The CRE strains isolated from Dongguan region demonstrated a high resistance rate to various antibiotics used in clinical practice but a low resistance rate to tigecycline. These strains produce Class A serine carbapenemases and Class B metals ß-lactamases, with the majority of them carrying blaNDM and blaKPC. Notably, CRE strains with blaKPC and blaNDM had significantly lower resistance rates to tigecycline. CAZ-AVI showed a good sensitivity rate with no resistance to CRE strains carrying blaKPC. Therefore, CAZ-AVI and tigecycline should be used as a guide for rational use of antibiotics in clinical practice to effectively treat CRE.

Ferroptosis contributing to cardiomyocyte injury induced by silica nanoparticles via miR-125b-2-3p/HO-1 signaling.

BACKGROUND: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described. RESULTS: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation. CONCLUSIONS: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.

Can corporate ESG performance improve audit efficiency?: Empirical evidence based on audit latency perspective.

Environmental, Social and Governance (ESG) is closely related to the "dual carbon" objective and the concept of sustainable development. The impact of ESG performance on audit efficiency, especially on audit delays, is still an issue to be studied in depth. Drawing on stakeholder theory, sustainable development theory, shared value concept and corporate social responsibility theory, this study adopts regression analysis and structural equation modeling (SEM) to investigate the impact of ESG on audit efficiency based on the data of A-share listed companies in the period of 2015-2022, with a focus on audit delay. The results of regression analysis show that ESG performance has a significant effect on reducing audit delay, and audit delay is reduced by 0.007 on average for each unit increase in ESG performance. In structural equation modeling, the effect of ESG performance on audit delay is more significant, with an estimated value of -0.555 and a standard error of 0.097. In addition, the study shows that the corporate ESG performance on audit efficiency has a positive impact is more pronounced among firms with stronger ESG practices, especially among non-state-owned firms with lower institutional investor ownership and firms audited by "Big Four" firms. These results not only demonstrate the importance of ESG performance in improving audit efficiency, but also provide important guidance for corporate management and policy making. This study enriches the existing literature on corporate ESG performance and audit efficiency and provides new perspectives and directions for future research.

Proteomics revealed composition- and size-related regulators for hepatic impairments induced by silica nanoparticles.

Along with the growing production and application of silica nanoparticles (SiNPs), increased human exposure and ensuing safety evaluation have progressively attracted concern. Accumulative data evidenced the hepatic injuries upon SiNPs inhalation. Still, the understanding of the hepatic outcomes resulting from SiNPs exposure, and underlying mechanisms are incompletely elucidated. Here, SiNPs of two sizes (60 nm and 300 nm) were applied to investigate their composition- and size-related impacts on livers of ApoE-/- mice via intratracheal instillation. Histopathological and biochemical analysis indicated SiNPs promoted inflammation, lipid deposition and fibrosis in the hepatic tissue, accompanied by increased ALT, AST, TC and TG. Oxidative stress was activated upon SiNPs stimuli, as evidenced by the increased hepatic ROS, MDA and declined GSH/GSSG. Of note, these alterations were more dramatic in SiNPs with a smaller size (SiNPs-60) but the same dosage. LC-MS/MS-based quantitative proteomics unveiled changes in mice liver protein profiles, and filtered out particle composition- or size-related molecules. Interestingly, altered lipid metabolism and oxidative damage served as two critical biological processes. In accordance with correlation analysis and liver disease-targeting prediction, a final of 10 differentially expressed proteins (DEPs) were selected as key potential targets attributable to composition- (4 molecules) and size-related (6 molecules) liver impairments upon SiNPs stimuli. Overall, our study provided strong laboratory evidence for a comprehensive understanding of the harmful biological effects of SiNPs, which was crucial for toxicological evaluation to ensure nanosafety.

Predictive Value of NT-proBNP for New-onset Atrial Fibrillation in the Acute Phase of Myocardial Infarction.

Objective: The objective of this study was to assess the predictive value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels on admission and new-onset atrial fibrillation (AF) in patients with acute myocardial infarction (AMI). Methods: In this study, a retrospective cohort study design scheme was used to include a total of 291 consecutive patients who were hospitalized for AMI from July 2019 to May 2020, of whom 36 (12.4%) developed new-onset atrial fibrillation (AF) during their hospitalization, which was classified as the AF group, and the rest of the patients were in the non-AF group. The impact of NT-pro-BNP on new-onset atrial fibrillation was investigated using the general data, laboratory tests, cardiac ultrasonography, and coronary angiography results of the two groups. Logistic regression analysis was employed to investigate the effect of NT-pro-BNP on new-onset atrial fibrillation. Additionally, we analyzed the significance of NT-pro-BNP in predicting new-onset AF in AMI patients using the the area under the AUC. Results: Univariate analysis indicated that patients in the AF group had significantly higher (P < .05) age, leukocyte count on admission, high-sensitivity C-reactive protein (hs-CRP), blood creatinine, uric acid, NT-pro-BNP, and left ventricular end-diastolic internal diameter (LVED) than those in the non-AF group. Patients in the AF group had lower blood pressure and left ventricular ejection fraction compared with the non-AF group. Logistic multifactorial regression analysis indicated that NT-pro-BNP was an independent risk factor for new-onset AF in patients with AMI (OR=2.752, 95% CI 1.352-5.602, P = .005). The area under the AUC was 0.747 (95% CI 0.655-0.84; P = .001), with a sensitivity of 64%, a specificity of 78%, and a Jordon's index of 0.458. This corresponds to an optimal cutoff value of 5374 pg/ml, suggesting that NT-pro-BNP performs well in predicting new-onset atrial fibrillation. Conclusion: NT-pro-BNP on admission can be a useful predictor of whether new-onset atrial fibrillation occurs in patients with AMI, with good predictive value. This finding helps better to meet patients' diagnostic and therapeutic needs and provides useful clinical guidance to improve the management and prognosis of AMI patients.

Lipidomics Investigation Reveals the Reversibility of Hepatic Injury by Silica Nanoparticles in Rats After a 6-Week Recovery Duration.

Given the inevitable human exposure owing to its increasing production and utilization, the comprehensive safety evaluation of silica nanoparticles (SiNPs) has sparked concerns. Substantial evidence indicated liver damage by inhaled SiNPs. Notwithstanding, few reports focused on the persistence or reversibility of hepatic injuries, and the intricate molecular mechanisms involved remain limited. Here, rats are intratracheally instilled with SiNPs in two regimens (a 3-month exposure and a subsequent 6-week recovery after terminating SiNPs administration) to assess the hepatic effects. Nontargeted lipidomics revealed alterations in lipid metabolites as a contributor to the hepatic response and recovery effects of SiNPs. In line with the functional analysis of differential lipid metabolites, SiNPs activated oxidative stress, and induced lipid peroxidation and lipid deposition in the liver, as evidenced by the elevated hepatic levels of ROS, MDA, TC, and TG. Of note, these indicators showed great improvements after a 6-week recovery, even returning to the control levels. According to the correlation, ROC curve, and SEM analysis, 11 lipids identified as potential regulatory molecules for ameliorating liver injury by SiNPs. Collectively, the work first revealed the reversibility of SiNP-elicited hepatotoxicity from the perspective of lipidomics and offered valuable laboratory evidence and therapeutic strategy to facilitate nanosafety.

The potential toxicity of microplastics on human health.

Microplastics are plastic particles, films, and fibers with a diameter of < 5 mm. Given their long-standing existence in the environment and terrible increase in annual emissions, concerns were raised about the potential health risk of microplastics on human beings. In particular, the increased consumption of masks during the COVID-19 pandemic has dramatically increased human contact with microplastics. To date, the emergence of microplastics in the human body, such as feces, blood, placenta, lower airway, and lungs, has been reported. Related toxicological investigations of microplastics were gradually increased. To comprehensively illuminate the interplay of microplastic exposure and human health, we systematically reviewed the updated toxicological data of microplastics and summarized their mode of action, adverse effects, and toxic mechanisms. The emerging critical issues in the current toxicological investigations were proposed and discussed. Our work would facilitate a better understanding of MPs-induced health hazards for toxicological evaluation and provide helpful information for regulatory decisions.

RETINAL MICROVASCULAR CHANGES AND RISK OF CORONARY HEART DISEASE: A Systematic Review and Meta-Analysis.

PURPOSE: To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. RESULTS: The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. CONCLUSION: A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

Current progress of ferroptosis in cardiovascular diseases.

Ferroptosis, a newly recognized form of nonapoptotic regulated cell death, is characterized by iron-dependent lipid peroxidation. Biological processes, such as iron metabolism, lipid peroxidation, and amino acid metabolism, are involved in the process of ferroptosis. However, the related molecular mechanism of ferroptosis has not yet been completely clarified, and specific and sensitive biomarkers for ferroptosis need to be explored. Recently, studies have revealed that ferroptosis probably causes or exacerbates the progress of cardiovascular diseases, and could be the potential therapeutic target for cardiovascular diseases. In this review, we summarize the molecular mechanisms regulating ferroptosis, inducers or inhibitors of ferroptosis, and the current progresses of ferroptosis in cardiovascular diseases. Furthermore, we discuss the emerging challenges and future perspectives, which may provide novel insights into the treatment of cardiovascular diseases.

Nrf2 for a key member of redox regulation: A novel insight against myocardial ischemia and reperfusion injuries.

Nuclear factor erythroid-2 related factor 2 (Nrf2), a nuclear transcription factor, modulates genes responsible for antioxidant responses against toxic and oxidative stress to maintain redox homeostasis and participates in varieties of cellular processes such as metabolism and inflammation during myocardial ischemia and reperfusion injuries (MIRI). The accumulation of reactive oxygen species (ROS) from damaged mitochondria, xanthine oxidase, NADPH oxidases, and inflammation contributes to depraved myocardial ischemia and reperfusion injuries. Considering that Nrf2 played crucial roles in antagonizing oxidative stress, it is reasonable to delve into the up or down-regulated molecular mechanisms of Nrf2 in the progression of MIRI to provide the possibility of new therapeutic medicine targeting Nrf2 in cardiovascular diseases. This review systematically describes the generation of ROS, the regulatory metabolisms of Nrf2 as well as several natural or synthetic compounds activating Nrf2 during MIRI, which might provide novel insights for the anti-oxidative stress and original ideas targeting Nrf2 for the prevention and treatment in cardiovascular diseases.

The impact of bilateral brachial-ankle pulse wave velocity difference on cardiovascular disease and all-cause mortality.

Background: This study aims to investigate the association between an elevated bilateral pulse wave velocity difference (BPWVD) and cardiovascular diseases (CVDs) and all-cause mortality. Methods: This study included a total of 38,356 participants. A multivariable Cox proportional hazards regression was used to assess the association between high BPWVD and the increased risk of CVDs and all-cause mortality by calculating hazard ratios (HRs) with 95% confidence intervals. Results: A total of 1,213 cases of CVDs were identified over a mean duration of 6.19 years, including 886 cases of cerebral infarction (CI), 105 cases of intracerebral hemorrhage (ICH), and 222 cases of myocardial infarction (MI), along with 1,182 cases of all-cause mortality. The median BPWVD was 42 cm/s (19-80 cm/s). After adjusting for all confounders and baseline brachial-ankle PWV (baPWV), our analysis revealed a significant correlation between a higher risk of CVDs, MI, and all-cause mortality with an increase in BPWVD per standard deviation. HRs (95% confidence interval) were found to be 1.06 (1.01-1.11), 1.11 (1.02-1.21), and 1.07 (1.04-1.10), respectively. Among the participants with higher baPWV on the left side, the HRs (95% confidence interval) were 1.08 (1.02-1.14) for CVDs, 1.27 (1.10-1.46) for incident ICH, 1.16 (1.00-1.24) for incident MI, and 1.10 (1.07-1.15) for all-cause mortality, for per standard deviation increase in BPWVD. Conclusions: Our findings reveal a significant correlation between elevated BPWVD and the risks of developing CVDs and all-cause mortality. This highlights the importance of thoroughly evaluating BPWVD as a means of detecting individuals at risk for CVDs and mortality.

ER Ca2+ overload activates the IRE1α signaling and promotes cell survival.

BACKGROUND: Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. Although Ca2+ depletion has been known to cause ER stress which in turn activates the unfolded protein response (UPR), how UPR sensors/transducers respond to excess Ca2+ when ER stores are overloaded remain largely unclear. RESULTS: Here, we report for the first time that overloading of ER Ca2+ can directly sensitize the IRE1α-XBP1 axis. The overloaded ER Ca2+ in TMCO1-deficient cells can cause BiP dissociation from IRE1α, promote the dimerization and stability of the IRE1α protein, and boost IRE1α activation. Intriguingly, attenuation of the over-activated IRE1α-XBP1s signaling by a IRE1α inhibitor can cause a significant cell death in TMCO1-deficient cells. CONCLUSIONS: Our data establish a causal link between excess Ca2+ in ER stores and the selective activation of IRE1α-XBP1 axis, underscoring an unexpected role of overload of ER Ca2+ in IRE1α activation and in preventing cell death.

Association between polymorphisms in connexin 40 gene (Cx40) and risk of atrial fibrillation: a meta-analysis based on 3,452 subjects.

INTRODUCTION: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with heart failure and stroke, leading sometimes to death. But the pathogenesis of AF remains unclear. Numerous studies have investigated whether the connexin 40 (Cx40) polymorphisms influences the risk of AF, but the results are controversial. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine the existence of genetic associations between the Cx40 polymorphisms and the risk of AF. All relevant studies were screened and meta-analyzed using Review Manager 5.0. RESULTS: A total of 12 studies, including 10 studies for -44 polymorphism (rs35594137) and 4 studies for -26 polymorphism (rs10465885), were identified for the meta-analysis. For -44 polymorphism, the results showed a significantly increased risk of AF in the five genetic models in the overall analysis. Furthermore, in subgroup analysis, increased AF risks were also observed in Asian and non-Asian populations. For -26 polymorphism, the overall OR revealed an increased risk of AF in dominant model. In subgroup analysis, increased AF risk was only found in recessive genetic model of the Asian population. CONCLUSIONS: The Cx40 polymorphisms were positively associated with AF in both populations, especially on -44 polymorphism.

Natriuretic peptides as predictors for atrial fibrillation recurrence after catheter ablation: A meta-analysis.

BACKGROUND: Catheter ablation (CA) has become the first-line treatment strategy for atrial fibrillation (AF) but remains with a substantial recurrence rate. The aim of this meta-analysis was to determine the association between baseline natriuretic peptide levels and AF recurrence after CA. METHODS: We systematically searched PubMed, EMBASE, Web of Science, and Wiley-Cochrane Library for relevant studies published up until May 2022. Overall effect analysis and subgroup analysis were performed with Review Manager software. RESULTS: Finally, 61 studies that met the inclusion criteria were included in our meta-analysis. Compared with the nonrecurrence group, the recurrence group had increased baseline level of atrial natriuretic peptide (ANP) (standardized mean difference [SMD] = 0.39, 95% confidence interval [CI]: 0.21-0.56), brain natriuretic peptide (BNP) (SMD = 0.51, 95% CI: 0.31-0.71), N-terminal pro-BNP (SMD = 0.71, 95% CI: 0.49-0.92), and midregional N-terminal pro-ANP (SMD = 0.91, 95% CI: 0.27-1.56). CONCLUSIONS: Increased baseline natriuretic peptide levels, including ANP, BNP, N-terminal pro-BNP, and midregional N-terminal pro-ANP, are associated with a higher risk of AF recurrence after CA. Nonetheless, further studies are needed to elucidate the predictive value of baseline natriuretic peptides in AF patients undergoing CA.

Identification of immune-related genes in acute myocardial infarction based on integrated bioinformatical methods and experimental verification.

Background: Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. The etiology of AMI is complex and has not been fully defined. In recent years, the role of immune response in the development, progression and prognosis of AMI has received increasing attention. The aim of this study was to identify key genes associated with the immune response in AMI and to analyze their immune infiltration. Methods: The study included a total of two GEO databases, containing 83 patients with AMI and 54 healthy individuals. We used the linear model of microarray data (limma) package to find the differentially expressed genes associated with AMI, performing weighted gene co-expression analysis (WGCNA) to further identify the genes associated with inflammatory response to AMI. We found the final hub genes through the protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) regression model. To verify the above conclusions, we constructed mice AMI model, extracting myocardial tissue to perform qRT-PCR. Furthermore, the CIBERSORT tool for immune cells infiltration analysis was also carried out. Results: A total of 5,425 significant up-regulated and 2,126 down-regulated genes were found in GSE66360 and GSE24519. A total of 116 immune-related genes in close association with AMI were screened by WGCNA analysis. These genes were mostly clustered in the immune response on the basis of GO and KEGG enrichment. With construction of PPI network and LASSO regression analysis, this research found three hub genes (SOCS2, FFAR2, MYO10) among these differentially expressed genes. The immune cell infiltration results revealed that significant differences could be found on T cells CD4 memory activated, Tregs (regulatory T cells), macrophages M2, neutrophils, T cells CD8, T cells CD4 naive, eosinophils between controls and AMI patients.

Silica nanoparticles promoted pro-inflammatory macrophage and foam cell transformation via ROS/PPARγ/NF-κB signaling.

Experimental evidence has pointed out silica nanoparticles (SiNPs) possessing a proatherogenic capability. However, the interplay between SiNPs and macrophages in the pathogenesis of atherosclerosis was poorly understood. Here, we demonstrated SiNPs could promote macrophage adhesion to endothelial cells, accompanied by elevated Vcam1 and Mcp1. Upon SiNPs stimuli, macrophages manifested enhanced phagocytic activity and a pro-inflammatory phenotype, as reflected by the transcriptional determination of M1/M2-related biomarkers. In particular, our data certified the increased macrophage M1 subset facilitated more lipid accumulation and resultant foam cell transformation in comparison to the M2 phenotype. More importantly, the mechanistic investigations revealed ROS-mediated PPARγ/NF-κB signaling was a key contributor to the above phenomena. That was, SiNPs caused ROS accumulation in macrophages, resulting in the deactivation of PPARγ, nuclear translocation of NF-κB, ultimately contributing to macrophage phenotype shift toward M1 and foam cell transformation. Collectively, we first revealed SiNPs facilitated pro-inflammatory macrophage and foam cell transformation via ROS/PPARγ/NF-κB signaling. These data would provide new insight into the atherogenic property of SiNPs in a macrophage model.