Single-cell signaling network profiling during redox stress reveals dynamic redox regulation in immune cells.

In eukaryotic cells, reactive oxygen species (ROS) serve as crucial signaling components. ROS are potentially toxic, so constant adjustments are needed to maintain cellular health. Here we describe a single-cell, mass cytometry-based method that we call signaling network under redox stress profiling (SN-ROP) to monitor dynamic changes in redox-related pathways during redox stress.

Multiplexed assays of human disease-relevant mutations reveal UTR dinucleotide composition as a major determinant of RNA stability.

Untranslated regions (UTRs) contain crucial regulatory elements for RNA stability, translation and localization, so their integrity is indispensable for gene expression. Approximately 3.7% of genetic variants associated with diseases occur in UTRs, yet a comprehensive understanding of UTR variant functions remains limited due to inefficient experimental and computational assessment methods.

SpliceAPP: an interactive web server to predict splicing errors arising from human mutations.

Background: Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants.

Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit.

Hypertension as a Novel Link for Shared Heritability in Age at Menarche and Cardiometabolic Traits.

Context: Extremely early age at menarche, also called precocious puberty, has been associated with various cardiometabolic traits, but their shared heritability remains unclear.

Objectives: This work aimed to identify new shared genetic variants and their pathways for age at menarche and cardiometabolic traits and to investigate the influence of central precocious puberty on childhood cardiometabolic traits.

Methods: Using the conjunction false discovery rate method, this study analyzed genome-wide association study data from the menarche-cardiometabolic traits among 59 655 females of Taiwanese ancestry and systemically investigated pleiotropy between age at menarche and cardiometabolic traits.

Continuous fixation of dissolved arsenite from flooded soil by cooperating ferrihydrite with Geobacter sulfurreducens.

The fixed arsenic in soil is easy to be released into the aquatic environment in the form of arsenite (As(III)) with high toxicity and mobility due to the eutrophication of environment under anaerobic conditions. However, As(III) is difficult to be fixed in situ continuously by traditional methods, especially for the most efficient fixation method by iron ores. Based on that Fe(II) could promote the fixation of As(III), this study investigated the possibility that Geobacter sulfurreducens (G.

Mechanism and modeling of human disease-associated near-exon intronic variants that perturb RNA splicing.

It is estimated that 10%-30% of disease-associated genetic variants affect splicing. Splicing variants may generate deleteriously altered gene product and are potential therapeutic targets. However, systematic diagnosis or prediction of splicing variants is yet to be established, especially for the near-exon intronic splice region.

Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an international cohort.

Introduction: Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear.

Methods: This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions.

Estimating the causal effect of embryo transfer day on clinical in vitro fertilization outcomes using propensity score matching.

Background: For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e.

Age effect on in vitro fertilization pregnancy mediated by anti-Mullerian hormone (AMH) and modified by follicle stimulating hormone (FSH).

Background: Both follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) are widely used to assess the ovarian reserve in women for in vitro fertilization (IVF). However, studies also showed that both AMH and FSH are significantly associated with age: as age increases, AMH decreases and FSH increases. This study aims to investigate the mechanism of age effect on IVF live birth rate, particularly through mediation and interaction by AMH and FSH.

Cigarette smoking increases the risk of nasopharyngeal carcinoma through the elevated level of IgA antibody against Epstein-Barr virus capsid antigen: A mediation analysis.

Background: The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein-Barr virus (EBV) infection for NPC risk.

Methods: 1235 male NPC cases and 1262 hospital-based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained.