Deciphering the tumour microenvironment of clear cell renal cell carcinoma: Prognostic insights from programmed death genes using machine learning.

Clear cell renal cell carcinoma (ccRCC), a prevalent kidney cancer form characterised by its invasiveness and heterogeneity, presents challenges in late-stage prognosis and treatment outcomes. Programmed cell death mechanisms, crucial in eliminating cancer cells, offer substantial insights into malignant tumour diagnosis, treatment and prognosis. This study aims to provide a model based on 15 types of Programmed Cell Death-Related Genes (PCDRGs) for evaluating immune microenvironment and prognosis in ccRCC patients. ccRCC patients from the TCGA and arrayexpress cohorts were grouped based on PCDRGs. A combination model using Lasso and SuperPC was constructed to identify prognostic gene features. The arrayexpress cohort validated the model, confirming its robustness. Immune microenvironment analysis, facilitated by PCDRGs, employed various methods, including CIBERSORT. Drug sensitivity analysis guided clinical treatment decisions. Single-cell data enabled Programmed Cell Death-Related scoring, subsequent pseudo-temporal and cell-cell communication analyses. A PCDRGs signature was established using TCGA-KIRC data. External validation in the arrayexpress cohort underscored the model's superiority over traditional clinical features. Furthermore, our single-cell analysis unveiled the roles of PCDRG-based single-cell subgroups in ccRCC, both in pseudo-temporal progression and intercellular communication. Finally, we performed CCK-8 assay and other experiments to investigate csf2. In conclusion, these findings reveal that csf2 inhibit the growth, infiltration and movement of cells associated with renal clear cell carcinoma. This study introduces a PCDRGs prognostic model benefiting ccRCC patients while shedding light on the pivotal role of programmed cell death genes in shaping the immune microenvironment of ccRCC patients.

Unravelling infiltrating T-cell heterogeneity in kidney renal clear cell carcinoma: Integrative single-cell and spatial transcriptomic profiling.

Kidney renal clear cell carcinoma (KIRC) pathogenesis intricately involves immune system dynamics, particularly the role of T cells within the tumour microenvironment. Through a multifaceted approach encompassing single-cell RNA sequencing, spatial transcriptome analysis and bulk transcriptome profiling, we systematically explored the contribution of infiltrating T cells to KIRC heterogeneity. Employing high-density weighted gene co-expression network analysis (hdWGCNA), module scoring and machine learning, we identified a distinct signature of infiltrating T cell-associated genes (ITSGs). Spatial transcriptomic data were analysed using robust cell type decomposition (RCTD) to uncover spatial interactions. Further analyses included enrichment assessments, immune infiltration evaluations and drug susceptibility predictions. Experimental validation involved PCR experiments, CCK-8 assays, plate cloning assays, wound-healing assays and Transwell assays. Six subpopulations of infiltrating and proliferating T cells were identified in KIRC, with notable dynamics observed in mid- to late-stage disease progression. Spatial analysis revealed significant correlations between T cells and epithelial cells across varying distances within the tumour microenvironment. The ITSG-based prognostic model demonstrated robust predictive capabilities, implicating these genes in immune modulation and metabolic pathways and offering prognostic insights into drug sensitivity for 12 KIRC treatment agents. Experimental validation underscored the functional relevance of PPIB in KIRC cell proliferation, invasion and migration. Our study comprehensively characterizes infiltrating T-cell heterogeneity in KIRC using single-cell RNA sequencing and spatial transcriptome data. The stable prognostic model based on ITSGs unveils infiltrating T cells' prognostic potential, shedding light on the immune microenvironment and offering avenues for personalized treatment and immunotherapy.

Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: a systematic review and exposure-effect meta-analysis.

BACKGROUND: The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC). METHODS: We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship. RESULTS: Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55-2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51-1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35-1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36-2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21-2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29-1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001). CONCLUSION: An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.

Glycated albumin and risk of cardiovascular diseases and mortality in patients with and without dialysis: A meta-analysis.

BACKGROUND: Several studies have shown that glycated albumin (GA) is a more accurate measure of short-term blood sugar control in patients with dialysis. We aim to investigate the relationship between GA and the risk of cardiovascular diseases (CVDs) and mortality in patients both with and without dialysis. MATERIALS AND METHODS: We searched cohort studies of associations between GA level and CVD and mortality in PubMed, Cochrane Library and Embase databases. The effect size was summarized by the random effects model, and the dose-response association was determined by robust error meta-regression method. RESULTS: This meta-analysis included data from 80 024 participants in 17 cohort studies, 12 of which were prospective and five were retrospective. The results showed that higher levels of GA were associated with increased risk of CV mortality [hazard ratio = 1.90; 95% confidence interval (CI) 1.22-2.98], all-cause mortality (hazard ratio = 1.64; 95% CI 1.41-1.90), major adverse cardio-cerebral events (risk ratio = 1.41; 95% CI 1.17-1.71), coronary artery disease (odds ratio = 2.24; 95% CI 1.75-2.86) and stroke (risk ratio = 1.72; 95% CI 1.24-2.38). The dose-response analysis showed that GA levels were positively and linearly associated with the risk of CV mortality (p = .38), all-cause mortality (p = .57) and coronary artery disease (p = .18). Subgroup analysis showed that high levels of GA were associated with the risk of CV and all-cause mortality, regardless of dialysis status, with significant differences between subgroups of dialysis (CV mortality: p = .02; all-cause mortality: p = .03). CONCLUSION: High GA levels are associated with an increased risk of CVDs and mortality, regardless of dialysis status.

Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study.

BACKGROUND: Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated. OBJECTIVE: This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality. METHODS: This study included participants from the National Health and Nutrition Examination Survey 2011-2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied. RESULTS: This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p < 0.05). Compared with the participant in tertile 1 of serum Cu (< 16.31 mol/L), those in tertile 3 (≥ 19.84 mol/L) were significantly associated with CVD mortality (HR: 7.06, 95%CI: 1.85,26.96), and all-cause mortality (HR: 2.84, 95% CI: 1.66,4.87). The dose-response curve indicated a linear relationship between serum Cu and CVD mortality (p -nonlinear = 0.48) and all-cause (p -nonlinear = 0.62). A meta-analysis included additional three prospective cohorts with 13,189 patients confirmed the association between higher serum Cu and CVD (HR: 2.08, 95% CI: 1.63,2.65) and all-cause mortality (HR: 1.89, 95%CI: 1.58,2.25). CONCLUSION: The present study suggests excessive serum Cu concentrations are associated with the risk of CVD and all-cause mortality in American adults. Our findings and the causal relationships require further investigation.

Long Non-coding RNA ANRIL Downregulation Alleviates Neuroinflammation in an Ischemia Stroke Model via Modulation of the miR-671-5p/NF-κB Pathway.

The aim of this study was to investigate the role and underlying mechanism of the long non-coding RNA ANRIL (antisense noncoding RNA in the INK4 locus, ANRIL) in ischemia stroke (IS) injury. Downregulation of ANRIL by right intracerebroventricular injected si-ANRIL in middle cerebral artery occlusion-reperfusion (MCAO/R) C57/BL6 mice and by transferring si-ANRIL in oxygen glucose deprivation/reperfusion (OGD/R) HT22 cells. The results showed that ANRIL levels increased in IS model, downregulation of ANRIL reduced infract area, neurological deficit scores and injured cells, and prolong fall latency time in MCAO/R mice, improved cell viability and reduced cell cytotoxicity in OGD/R cells. Fluorescence in Situ Hybridization detected that there were both ANRIL and miR-671-5p in neurons; miranda v3.3a and dual luciferase reporter assay demonstrated that miR-671-5p was one of direct target of ANRIL; and our previously published research demonstrated that NF-κB was one of direct target of miR-671-5p. Downregulation of ANRIL alleviated neuroinflammation and reduced p-NF-κB, NF-κB, pro-inflammatory cytokines (IL-1ß, IL-6, TNF-a), and iNOS, which diminished by miR-671-5p antagomir both in in vivo and in vitro IS models. Downregulation of ANRIL alleviated disruption of blood brain barrier, and protected against tight junction (ZO-1, occludin and claudin 5) disorder in MCAO/R mice. This work clarified that downregulation of ANRIL reduced neuroinflammation by negatively regulating miR-671-5p to inhibit NF-κB in IS models, which provided a theoretical foundation for the protective effect of downregulating ANRIL for IS patients.

miR-671-5p Attenuates Neuroinflammation via Suppressing NF-κB Expression in an Acute Ischemic Stroke Model.

This study was designed to investigate the role of miR-671-5p in in vitro and in vivo models of ischemic stroke (IS). Middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 mice as well as oxygen-glucose deprivation and reoxygenation (OGD/R) in a mouse hippocampal HT22 neuron line were used as in vivo and in vitro models of IS injury, respectively. miR-671-5p agomir, miR-671-5p antagomir, pcDNA3.1-NF-κB, and negative controls were transfected into cells using riboFECT CP reagent. miR-671-5p agomir, pcDNA3.1-NF-κB, and negative vectors were administered into MCAO/R mice via intracerebroventricular injection. The results showed that miR-671-5p was significantly downregulated and that miR-671-5p agomir alleviated injury and neuroinflammation induced by ischemic reperfusion. A dual-luciferase reporter assay confirmed that NF-κB is a direct target of miR-671-5p. Reverse experiments showed that miR-671-5p agomir reduced neuroinflammation via suppression of NF-κB expression in both in vitro and in vivo models of IS. Our data suggest that miR-671-5p may be a viable therapeutic target for diminishing neuroinflammation in patients with IS.

Characterization of a neutral recombinant xylanase from Thermoactinospora rubra YIM 77501T.

A xylanase gene (TrXyn10) from Thermoactinospora rubra YIM 77501T was cloned and expressed in Escherichia coli. The amino acid sequence displayed 78% homology with Microbispora mesophila xylanase (WP_062413927.1). The recombinant xylanase (TrXyn10), with MW 46.1 kDa, could hydrolyse beechwood, birchwood and oatspelt xylan. Based on the sequence, enzymatic properties and tertiary structure of the protein, TrXyn10 belongs to glycoside hydrolase family 10 (GH10). The optimal pH and temperature for the recombinant enzyme were determined to be 7.0 and 55 °C, respectively. TrXyn10 was stable over a wide pH range, and it retained more than 45% of the total activity at pH 6.0-12.0 for 12 h. In addition, the activity was greatly promoted, by approximately 200% of the initial activity, after incubation at pH 6.0 and 7.0 for 12 h. Based on enzymatic properties and product analysis, we showed that TrXyn10 is a neutral endoxylanase.

Arthrobacter deserti sp. nov., isolated from a desert soil sample.

A Gram-stain-positive, non-motile, rod-shaped, catalase-positive and oxidase-negative bacterium, designated YIM CS25T, was isolated from a soil sample collected from Turpan desert in Xinjiang Uyghur Autonomous Region, north-western China. The isolate grew at 15-40 °C, at pH 6.0-8.0 and with 0-6 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain YIM CS25T belonged to the genus Arthrobacter and was closely related to Arthrobacter halodurans JSM 078085T (95.89 % similarity). The peptidoglycan type contained lysine, alanine and glutamic acid. The major whole-cell sugars were galactose, glucose and ribose. The isolate contained diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as the major polar lipids and MK-9 (H2) as the predominant menaquinone. The major cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0 and anteiso-C17 : 1ω9c. The genomic DNA G+C content was 68.3 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic analysis, strain YIM CS25T is considered to represent a novel species of the genus Arthrobacter, for which the name Arthrobacter deserti sp. nov. is proposed. The type strain is YIM CS25T ( = KCTC 39544T = CGMCC 1.15091T).

Synthesis of riccardin D derivatives as potent antimicrobial agents.

We describe the synthesis and biological evaluation of riccardin D derivatives, a novel class of antimicrobial molecules. Structural diversification of these derivatives was achieved by introducing hydroxy, methoxy, and bromine into the aromatic rings of riccardin D. The antimicrobial evaluation of these compounds was performed as in vitro assays against clinically isolated bacteria and fungi. The introduction of bromine atom into the arene B of riccardin D led to several strongly active antibacterial compounds with a MIC value ranging from 0.5 to 4µg/mL for Staphylococcus aureus, both methicillin-sensitive and -resistant strains. Antifungal tests found compound 34 was the most potent molecule with a MIC value of 2µg/mL against Candida albicans. This initial biological evaluation suggests that these novel molecules merit further investigation as potential antimicrobial agents.

Heterologous expression and characterization of a novel halotolerant, thermostable, and alkali-stable GH6 endoglucanase from Thermobifida halotolerans.

A novel endoglucanase gene was cloned from Thermobifida halotolerans YIM 90462(T), designated as thcel6A for being a member of glycoside hydrolase family 6. The gene was 1332 bp long and encoded a 443-amino-acid protein with a molecular mass of 45.9 kDa. The purified recombinant endoglucanase had optimal activity at 55 °C and pH 8.5. Thcel6A showed high hydrolytic activities at 25-55 °C and retained 58% of initial activity after incubation at 90 °C for 1 h. It retained more than 80% of activity after incubation for 12 h at pH values from 4 to 12. Thcel6A displayed higher hydrolytic activities in 5-15% NaCl (w/v) than at 0% NaCl. Activity increased 2.5-fold after incubation with 20% (w/v) NaCl at 37 °C for 10 min. These properties suggest that this novel endoglucanase has potential for specific industrial application.

A maximal element theorem in FWC-spaces and its applications.

A maximal element theorem is proved in finite weakly convex spaces (FWC-spaces, in short) which have no linear, convex, and topological structure. Using the maximal element theorem, we develop new existence theorems of solutions to variational relation problem, generalized equilibrium problem, equilibrium problem with lower and upper bounds, and minimax problem in FWC-spaces. The results represented in this paper unify and extend some known results in the literature.

Pharmacokinetics of Nitazoxanide Dry Suspensions After Single Oral Doses in Healthy Subjects: Food Effects Evaluation and Bioequivalence Study.

Nitazoxanide (NTZ) is an effective antiparasitic drug with potent antiviral and antimicrobial activity. This randomized, open-label, 2-sequence, 2-period crossover trial was designed to evaluate the bioequivalence (BE) of the NTZ dry suspension in healthy subjects and investigated the effect of food intake on the pharmacokinetic (PK) properties of tizoxanide (an active metabolite of NTZ, TIZ). Sixty healthy Chinese subjects were enrolled and received a single dose of 500 mg/25 mL of preparations on days 1 and 4 under overnight fasting or fed conditions, respectively. The plasma concentration of TIZ was determined using high-performance liquid chromatography/tandem mass spectrometry. PK parameters were calculated using WinNonlin 8.2 and BE was evaluated using SAS 9.4. The 90% confidence intervals for the geometric mean ratio (test/reference) of maximum concentration (Cmax), the area under the curve from time 0 to the time of the last quantifiable concentration (AUC0-t), and the area under the curve from time 0 to extrapolation to infinity (AUC0-∞) were all within the equivalent interval of 80%-125%, compliant with BE requirements. In comparison with fasting, on taking the reference and test preparations of the NTZ dry suspension after a meal, the AUC0-t increased by 48.9% and 47.3%, respectively, the AUC0-∞ increased by 48.4% and 48.3%, respectively, and the post-meal Tmax was prolonged by 1.8-2 hours. Our results demonstrate that the test and reference preparations were bioequivalent. High-fat meals significantly improve the degree of drug absorption and delay the rate of drug absorption.

hdWGCNA and Cellular Communication Identify Active NK Cell Subtypes in Alzheimer's Disease and Screen for Diagnostic Markers through Machine Learning.

BACKGROUND: Alzheimer's disease (AD) is a recognized complex and severe neurodegenerative disorder, presenting a significant challenge to global health. Its hallmark pathological features include the deposition of ß-amyloid plaques and the formation of neurofibrillary tangles. Given this context, it becomes imperative to develop an early and accurate biomarker model for AD diagnosis, employing machine learning and bioinformatics analysis. METHODS: In this study, single-cell data analysis was employed to identify cellular subtypes that exhibited significant differences between the diseased and control groups. Following the identification of NK cells, hdWGCNA analysis and cellular communication analysis were conducted to pinpoint NK cell subset with the most robust communication effects. Subsequently, three machine learning algorithms-LASSO, Random Forest, and SVM-RFE-were employed to jointly screen for NK cell subset modular genes highly associated with AD. A logistic regression diagnostic model was then designed based on these characterized genes. Additionally, a protein-protein interaction (PPI) networks of model genes was established. Furthermore, unsupervised cluster analysis was conducted to classify AD subtypes based on the model genes, followed by the analysis of immune infiltration in the different subtypes. Finally, Spearman correlation coefficient analysis was utilized to explore the correlation between model genes and immune cells, as well as inflammatory factors. RESULTS: We have successfully identified three genes (RPLP2, RPSA, and RPL18A) that exhibit a high association with AD. The nomogram based on these genes provides practical assistance in diagnosing and predicting patients' outcomes. The interconnected genes screened through PPI are intricately linked to ribosome metabolism and the COVID-19 pathway. Utilizing the expression of modular genes, unsupervised cluster analysis unveiled three distinct AD subtypes. Particularly noteworthy is subtype C3, characterized by high expression, which correlates with immune cell infiltration and elevated levels of inflammatory factors. Hence, it can be inferred that the establishment of an immune environment in AD patients is closely intertwined with the heightened expression of model genes. CONCLUSION: This study has not only established a valuable diagnostic model for AD patients but has also delved deeply into the pivotal role of model genes in shaping the immune environment of individuals with AD. These findings offer crucial insights into early AD diagnosis and patient management strategies.

Atrial fibrillation and breast cancer-Vicious twins? A systematic review and meta-analysis.

Background: Epidemiological studies suggest a bidirectional association between atrial fibrillation and breast cancer. This study aimed to conduct a meta-analysis to elucidate the prevalence of atrial fibrillation among breast cancer patients, and the bidirectional association between atrial fibrillation and breast cancer. Methods: PubMed, the Cochrane Library, and Embase were searched to identify studies reporting the prevalence, incidence, and bidirectional association between atrial fibrillation and breast cancer. The study was registered with PROSPERO (CRD42022313251). Levels of evidence and recommendations were assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Twenty-three studies (17 retrospective cohort studies, 5 case-control studies and 1 cross-sectional study) involving 8,537,551 participants were included. Among patients with breast cancer, the prevalence of atrial fibrillation was 3% (11 studies; 95% CI: 0.6 to 7.1%) and the incidence was 2.7% (6 studies; 95% CI: 1.1 to 4.9%). Breast cancer was associated with increased risk of atrial fibrillation (5 studies; hazard ratio [HR]: 1.43, 95% CI: 1.12 to 1.82, I2 = 98%). Atrial fibrillation was also significantly associated elevated risk of breast cancer (5 studies HR: 1.18, 95% CI: 1.14 to 1.22, I2 = 0%). Grade assessment shown low certainty of the evidence for the risk of atrial fibrillation and moderate certainty of the evidence for the risk of breast cancer. Conclusion: Atrial fibrillation is not uncommon in patients with breast cancer and vice versa. There is a bidirectional association between atrial fibrillation (low certainty) and breast cancer (moderate certainty).

miR-671-5p Upregulation Attenuates Blood-Brain Barrier Disruption in the Ischemia Stroke Model Via the NF-кB/MMP-9 Signaling Pathway.

Blood-brain barrier (BBB) disruption can induce further hemorrhagic transformation in ischemic stroke (IS). miR-671-5p, a micro-RNA, is abundant in the cortex of mammalian brains. Herein, we investigated the roles and potential mechanisms for the effects of miR-671-5p on BBB permeability in IS. Results showed that miR-671-5p levels were significantly downregulated in the cerebral cortex of middle cerebral artery occlusion/reperfusion (MCAO/R) C57/BL6 mice in vivo. miR-671-5p agomir administration via right intracerebroventricular injection significantly reduced infarct volume, improved neurological deficits, the axon of neurons and nerve fiber, attenuated cell injury and apoptosis, as well as reduced BBB permeability in MCAO/R mice. Treatment with miR-671-5p agomir alleviated tight junction proteins degradation, including claudin, occludin, and ZO-1 in MCAO/R mice, and these effects were reversed following NF-κB overexpression. Bend.3 brain endothelial cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) treatment in vivo, and then miR-671-5p agomir was transfected into the cells. This resulted in reduction of cytotoxicity, improved cell viability, trans-endothelial electrical resistance, reduced fluorescein sodium permeability, and inhibited tight junction degradation in Bend.3 OGD/R cells. However, these effects were reversed following NF-κB overexpression. These results demonstrated that upregulation of miR-671-5p in IS models in vivo and in vitro alleviated BBB permeability by targeting NF-κB/MMP-9. In summary, miR-671-5p is a potential therapeutic target for protecting BBB permeability in IS to minimize cerebral hemorrhage transformation.

Sex differences in mortality and hospitalization in heart failure with preserved and mid-range ejection fraction: a systematic review and meta-analysis of cohort studies.

Introduction: The influence of sex on the prognosis of heart failure with preserved or intermediate ejection fraction (HFpEF and HFmrEF) remains uncertain. This study aimed to investigate whether sex differences impact the prognosis of patients diagnosed with HFpEF and HFmrEF. Methods: A comprehensive search across three databases (PubMed, the Cochrane Library, and Embase) was conducted to identify sex-related prognostic cohort studies focusing on HFpEF and HFmrEF. Risk estimates were synthesized using the random effects model. The analysis included 14 cohorts comprising 41,508 HFpEF patients (44.65% males) and 10,692 HFmrEF patients (61.79% males). Results: Among HFpEF patients, men exhibited significantly higher rates of all-cause mortality (13 studies; hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.15 to 1.33)) and cardiovascular disease mortality (5 studies; HR: 1.22, 95% CI: 1.14 to 1.31) compared to women. However, no significant difference was observed in HF admissions. For HFmrEF patients, men displayed notably higher all-cause mortality (HR: 1.21, 95% CI: 1.12 to 1.31) but no significant differences in cardiovascular mortality or HF admissions. Discussion: These findings suggest that male patients diagnosed with HFpEF and HFmrEF may face a more unfavorable prognosis in terms of all-cause mortality. Variations were noted in cardiovascular mortality and HF admissions, indicating potential complexities in sex-related prognostic factors within these heart failure categories. In summary, male patients with HFpEF and HFmrEF may have a more unfavorable prognosis.

The regulation of circRNA and lncRNAprotein binding in cardiovascular diseases: Emerging therapeutic targets.

Noncoding ribonucleic acids (ncRNAs) are a class of ribonucleic acids (RNAs) that carry cellular information and perform essential functions. This class encompasses various RNAs, such as small nuclear ribonucleic acids (snRNA), small interfering ribonucleic acids (siRNA) and many other kinds of RNA. Of these, circular ribonucleic acids (circRNAs) and long noncoding ribonucleic acids (lncRNAs) are two types of ncRNAs that regulate crucial physiological and pathological processes, including binding, in several organs through interactions with other RNAs or proteins. Recent studies indicate that these RNAs interact with various proteins, including protein 53, nuclear factor-kappa B, vascular endothelial growth factor, and fused in sarcoma/translocated in liposarcoma, to regulate both the histological and electrophysiological aspects of cardiac development as well as cardiovascular pathogenesis, ultimately leading to a variety of genetic heart diseases, coronary heart disease, myocardial infarction, rheumatic heart disease and cardiomyopathies. This paper presents a thorough review of recent studies on circRNA and lncRNAprotein binding within cardiac and vascular cells. It offers insight into the molecular mechanisms involved and emphasizes potential implications for treating cardiovascular diseases.

Body mass index and atrial fibrillation recurrence post ablation: A systematic review and dose-response meta-analysis.

Objectives: The aim of this study was to evaluate the shape of the dose-response relationship between body mass index (BMI) and atrial fibrillation (AF) recurrence in patients who have undergone radiofrequency ablation. Methods: Studies investigating BMI and AF recurrence in patients with AF after ablation were identified through electronic searches in the PubMed, EMBASE, and Cochrane Library databases. The potential non-linear relationship was fitted using robust error meta-regression. Our study was registered with PROSPERO (CRD42019121373). Results: Twenty-six cohort studies with 7,878 cases/26,450 individuals were included, and a linear dose-response relationship between BMI and AF recurrence (P non-linearity = 0.12) was found. The risk of AF recurrence in patients with a BMI over 28 was significantly increased. Specifically, for each 5 kg/m2 increase in BMI, the risk of AF recurrence increased by 15% (95% CI: 1.08-1.22) with moderate heterogeneity (I 2 = 53%). Subgroup analyses showed that the pooled risk ratio was not significantly changed in subgroup analysis adjustment for the following important potential intermediate factors: left atrial diameter and obstructive sleep apnea. Conclusion: This study showed that there is a borderline positive linear association between BMI and AF recurrence post ablation. Overweight and obesity are significantly associated with AF recurrence. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42019128770.