Sex-specific differences in the association between triglyceride glucose index and carotid plaque in a cardiovascular high-risk population: a cross-sectional study based on a Chinese community-dwelling population.

Background: To date, numerous studies have investigated the relationship between the triglyceride glucose (TyG) index and carotid plaques, but the impact of gender on this relationship has not been explored. Therefore, this study aims to investigate gender-specific differences in the relationship between the TyG index and carotid plaques in a high cardiovascular risk population in China.

Methods: This cross-sectional study's data were derived from a longitudinal pilot study involving 1,085 high-risk cardiovascular subjects.

Most Pleiotropic Effects of Gene Knockouts Are Evolutionarily Transient in Yeasts.

Pleiotropy, the phenomenon in which a single gene influences multiple traits, is a fundamental concept in genetics. However, the evolutionary mechanisms underlying pleiotropy require further investigation. In this study, we conducted parallel gene knockouts targeting 100 transcription factors in 2 strains of Saccharomyces cerevisiae.

Assessment of the reversibility of resistance in the absence of antibiotics and its relationship with the resistance gene's fitness cost: a genetic study with mcr-1.

Background: The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants.

Methods: In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model.

Inhibiting ferroptosis in brain microvascular endothelial cells: A potential strategy to mitigate polystyrene nanoplastics‒induced blood‒brain barrier dysfunction.

Polystyrene nanoplastics (PS-NPs), a group of ubiquitous pollutants, may injure the central nervous system through the blood‒brain barrier (BBB). However, whether exposure to PS-NPs contributes to BBB disruption and the underlying mechanisms are still unclear. In vivo, we found that PS-NPs (25 mg/kg BW) could significantly increase BBB permeability in mice and downregulate the distribution of the tight junction-associated protein zona occludens 1 (ZO-1) in brain microvascular endothelial cells (BMECs).

Isotopic characteristics and source analysis of atmospheric ammonia during agricultural periods in the Xichuan area of the Danjiangkou Reservoir.

Nitrogen deposition is an important means of exogenous nitrogen input in reservoir water. Agricultural activities around the reservoir lead to a sharp increase in the concentration of ammonia in the atmosphere, which poses a threat to the reservoir water body. Clarifying the contribution of agricultural ammonia release to atmospheric NH (gaseous NH and particulate NH), in the reservoir area can provide a theoretical foundation for local reactive nitrogen control.

Genome-wide probing of eukaryotic nascent RNA structure elucidates cotranscriptional folding and its antimutagenic effect.

The transcriptional intermediates of RNAs fold into secondary structures with multiple regulatory roles, yet the details of such cotranscriptional RNA folding are largely unresolved in eukaryotes. Here, we present eSPET-seq (Structural Probing of Elongating Transcripts in eukaryotes), a method to assess the cotranscriptional RNA folding in Saccharomyces cerevisiae. Our study reveals pervasive structural transitions during cotranscriptional folding and overall structural similarities between nascent and mature RNAs.

Comprehensive Transcriptome and Metabolome Analyses Reveal Primary Molecular Regulation Pathways Involved in Peanut under Water and Nitrogen Co-Limitation.

The yield and quality of peanut ( L.), an oil crop planted worldwide, are often limited by drought stress (DS) and nitrogen (N) deficiency. To investigate the molecular mechanism by which peanut counteracts DS and N deficiency, we conducted comprehensive transcriptomic and metabolomic analyses of peanut leaves.

Tafolecimab in Chinese Patients With Hypercholesterolemia (CREDIT-4): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial.

Background: Tafolecimab is a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, developed for the treatment of hypercholesterolemia.

Objectives: The purpose of this study was to assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia.

Methods: Patients with diagnoses of heterozygous familial hypercholesterolemia (HeFH) by the Simon Broome criteria or at high or very high cardiovascular risk with nonfamilial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.

Single-cell transcriptomics reveals heterogeneity and intercellular crosstalk in human intervertebral disc degeneration.

The complexity of the human intervertebral disc (IVD) has hindered the elucidation of the microenvironment and mechanisms underlying IVD degeneration (IVDD). Here we determined the landscapes of nucleus pulposus (NP), annulus fibrosus (AF), and immunocytes in human IVD by scRNA-seq. Six NP subclusters and seven AF subclusters were identified, whose functional differences and distribution during different stages of degeneration (Pfirrmann I-V) were investigated.

Phylogenetic Comparative Analysis of Single-Cell Transcriptomes Reveals Constrained Accumulation of Gene Expression Heterogeneity during Clonal Expansion.

In the same way that a phylogeny summarizes the evolutionary history of species, a cell lineage tree describes the process of clonal expansion, in which gene expression differences between cells naturally accrue as a result of stochastic partitioning and imperfect expression control. How is functional homeostasis, a key factor in the biological function of any population of cells, maintained in the face of such continuous accumulation of transcriptomic heterogeneity remains largely unresolved. To answer this question, we experimentally determined the single-cell transcriptomes and lineage relationships of up to 50% cells in single-HEK293-seeded colonies.

Broadening horizons: The role of ferroptosis in myocardial ischemia-reperfusion injury.

Ferroptosis is a novel type of regulated cell death (RCD) discovered in recent years, where abnormal intracellular iron accumulation leads to the onset of lipid peroxidation, which further leads to the disruption of intracellular redox homeostasis and triggers cell death. Iron accumulation with lipid peroxidation is considered a hallmark of ferroptosis that distinguishes it from other RCDs. Myocardial ischemia-reperfusion injury (MIRI) is a process of increased myocardial cell injury that occurs during coronary reperfusion after myocardial ischemia and is associated with high post-infarction mortality.

Extremely dangerous hypopituitarism related long QT syndrome and transient ST-segment elevation: A case report.

Acquired long QT syndrome caused by hypopituitarism and transient ST-segment elevation has not been reported in cardiac arrest patients. We report a case of extremely dangerous acquired long QT syndrome and transient ST-segment elevation. A 44-year-old Chinese woman with renal failure experienced sudden cardiac arrest in the haemodialysis room.

A missed case of hereditary hemorrhagic telangiectasia: A case report.

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant disorder characterized by abnormal blood vessel formation. When an abnormal vascular architecture affects the lungs and central nervous system, serious complications can occur. We report a missed case of hereditary hemorrhagic telangiectasia with pulmonary arteriovenous malformations and cerebral arteriovenous malformations.

Postoperative anion gap associates with short- and long-term mortality after cardiac surgery: A large-scale cohort study.

Objective: To investigate whether postoperative anion gap (AG) is associated with short- and long-term mortality in patients following cardiac surgery.

Materials And Methods: We conducted a retrospective cohort study of adults who underwent cardiac surgery from the Medical Information Mart for Intensive Care - III database. The generalized additive model (GAM), logistic regression, and Cox regression were performed to assess the correlations between AG levels and in-hospital, 90-day, and 4-year mortality.

Two-minute walk distance reference equations for middle-aged and elderly Chinese individuals with obesity.

Background And Objective: While the six-minute walk test (6MWT) is often used to assess exercise capacity, the less well-known two-minute walk test (2MWT) is more feasible for some patients. In previous studies, we developed reference equations for the two-minute walk distance (2MWD) for healthy Chinese adults. However, our study did not recruit people with obesity, and the reference equations did not apply to participants with a body mass index (BMI) > 30 kg/m2.

The Molecular Mechanisms of Ferroptosis and Its Role in Blood-Brain Barrier Dysfunction.

The blood-brain barrier (BBB) is a selective, semi-permeable layer of endothelial cells that protects the central nervous system from harmful substances circulating in blood. It is one of the important barriers of the nervous system. BBB dysfunction is an early pathophysiological change observed in nervous system diseases.

miRNA-34c-5p targets Fra-1 to inhibit pulmonary fibrosis induced by silica through p53 and PTEN/PI3K/Akt signaling pathway.

Silica dust particles are representative of air pollution and long-term inhalation of silicon-containing dust through the respiratory tract can cause pulmonary fibrosis. Epithelial-mesenchymal transformation (EMT) plays an important role in the development of fibrosis. This process can relax cell-cell adhesion complexes and enhance cell migration and invasion properties of these cells.

Prediction of Antibiotic Resistance Evolution by Growth Measurement of All Proximal Mutants of Beta-Lactamase.

The antibiotic resistance crisis continues to threaten human health. Better predictions of the evolution of antibiotic resistance genes could contribute to the design of more sustainable treatment strategies. However, comprehensive prediction of antibiotic resistance gene evolution via laboratory approaches remains challenging.

Reference equations for the six-minute walking distance in obese Chinese subjects more than 40 years old.

Background: Studies have shown that the reference equations for the six-minute walking distance (6MWD), which were mainly derived from healthy, normal-weight people, are not suitable for individuals with obesity. The main purpose of this study was to establish reference equations for the 6MWD in obese Chinese subjects.

Methods: In our study, a total of 214 individuals with obesity performed the six-minute walking tests (6MWTs) according to the American thoracic society (ATS) guidelines, and the longer 6MWD was used for further analysis.

Efficacy and safety of sacubitril valsartan in treating heart failure with midrange ejection fraction after acute myocardial infarction in diabetic patients.

Objective to evaluate the clinical efficacy and safety of sacubitril valsartan in the treatment of heart failure (HF) with midrange ejection fraction after acute myocardial infarction (AMI) in diabetic patients. From January 2015 to July 2020, HF patients with diabetes mellitus complicated with AMI were retrospectively analyzed. According to the medication, they were divided into 2 groups, that is, sacubitril valsartan group (84 cases) and valsartan group (86 cases).

Expression level is a major modifier of the fitness landscape of a protein coding gene.

The phenotypic consequence of a genetic mutation depends on many factors including the expression level of a gene. However, a comprehensive quantification of this expression effect is still lacking, as is a further general mechanistic understanding of the effect. Here, we measured the fitness effect of almost all (>97.

Transcriptome Analysis in Yeast Reveals the Externality of Position Effects.

The activity of a gene newly integrated into a chromosome depends on the genomic context of the integration site. This "position effect" has been widely reported, although the other side of the coin, that is, how integration affects the local chromosomal environment, has remained largely unexplored, as have the mechanism and phenotypic consequences of this "externality" of the position effect. Here, we examined the transcriptome profiles of approximately 250 Saccharomyces cerevisiae strains, each with GFP integrated into a different locus of the wild-type strain.

Specificity of mRNA Folding and Its Association with Evolutionarily Adaptive mRNA Secondary Structures.

The secondary structure is a fundamental feature of both non-coding RNAs (ncRNAs) and messenger RNAs (mRNAs). However, our understanding of the secondary structures of mRNAs, especially those of the coding regions, remains elusive, likely due to translation and the lack of RNA-binding proteins that sustain the consensus structure like those binding to ncRNAs. Indeed, mRNAs have recently been found to adopt diverse alternative structures, but the overall functional significance remains untested.

The evolution of sex chromosome dosage compensation in animals.

The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems, as in at least one of the sexes, the sex-linked gene dose has been reduced by half. It has been proposed that the transcriptional output of the whole X or Z chromosome should be doubled for complete dosage compensation in heterogametic sex. However, owing to the variability of the existing methods to determine the transcriptional differences between sex chromosomes and autosomes (S:A ratios) in different studies, we collected more than 500 public RNA-Seq data set from multiple tissues and species in major clades and proposed a unified computational framework for unbiased and comparable measurement of the S:A ratios of multiple species.

Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats.

Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)).