Genetic and Cellular Architecture of Breast Cancer Risk in Multi-Ancestry Studies of 159,297 Cases and 212,102 Controls.

Breast cancer genome-wide association studies (GWAS) have identified over 200 independent genome-wide significant susceptibility markers. However, most studies have focused on one or two ancestral groups. We examined breast cancer genetic architecture using GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR) and Hispanic/Latina (H/L) samples, totaling 159,297 cases and 212,102 controls, comprising the largest multi-ancestry study of breast cancer to date.

Three-dimensional quantitative evaluation of hypertension-induced aortic fibre remodelling based on multiphoton microscopy: a cross-age perspective.

Hypertension is the primary cause of cardiovascular diseases, and its worldwide prevalence has continued to increase recently. Aortic fibre remodelling is critical in the development of hypertension and is strikingly age-related. However, the underlying microlevel variations remain unknown.

Multitasking and workplace wellbeing: the roles of job stress and job autonomy.

This cross-sectional study investigated how multitasking associates with workplace wellbeing, emphasizing the mediating role of job stress, and the moderating role of job autonomy. Grounded in the Job Demands-Resources (JD-R) and Conservation of Resources (COR) theories, this research proposed that multitasking negatively associates workplace wellbeing by increasing job stress, and that job autonomy buffers this relationship between multitasking and job stress. Data were collected from 354 employees in the information technology industry in China, with a response rate of 98.

Assessment of adipokine and inflammation biomarkers with cancer risk among Chinese men: A prospective cohort study.

Background: Obesity and chronic inflammation are associated with cancer risk. We investigated the association between adipokines, inflammation markers, and cancer risk among Chinese men.

Methods: Using pre-diagnosis fasting plasma samples from 4,051 (6.

The association between weight-adjusted-waist index and serum neurofilament light chain: Results from NHANES 2013 to 2014.

Neurofilament light chain (NfL) is an important biomarker for neuronal damage, widely used in the study of neurodegenerative diseases. The weight-adjusted-waist index (WWI), as a measure of abdominal obesity, is closely related to metabolic diseases. However, the association between WWI and NfL has not been systematically investigated.

Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits.

All cells in an animal collectively ensure, moment-to-moment, the survival of the whole organism in the face of environmental stressors . Physiology seeks to elucidate the intricate network of interactions that sustain life, which often span multiple organs, cell types, and timescales, but a major challenge lies in the inability to simultaneously record time-varying cellular activity throughout the entire body. We developed WHOLISTIC, a method to image second-timescale, time-varying intracellular dynamics across cell-types of the vertebrate body.

Lead (Pb) exposure results in cell type specific changes in the mouse retina and optic nerve.

Chronic exposure to lead (Pb) is known to cause deficits in neuronal function across the nervous system, including the visual nervous system. Visual deficits have been observed in both humans and rodent models following Pb exposure. However, how Pb exposure causes visual deficits is poorly understood.

Predictors of Quality of Life in Myasthenia Gravis Patients from Southwestern China: Validation of Clinical and Socioenvironmental Determinants.

Introduction: Myasthenia gravis (MG) presents a substantial clinical burden, characterized by increased incidence of myasthenic crises, heterogeneity in treatment response, significant functional impairment, and gradually increasing mortality rates with marked geographical heterogeneity across China. While improving quality of life (QOL) is the focus of MG management, multifactorial determinants of QOL impairment remain unclear, especially in socioeconomically underrepresented regions, particularly Southwestern China. This study aimed to explore myasthenia-specific risk factors for QOL and develop a parsimonious prediction model.

Rademikibart monotherapy for moderate-to-severe atopic dermatitis in a 1-year, randomized, phase II trial (SEASIDE CHINA): initial two-week dosing, followed by two-week or four-week dosing.

Background: Rademikibart (CBP-201) is a potent, next-generation, optimized IL-4Rα-targeting antibody.

Objectives: To evaluate rademikibart efficacy and safety, initially dosed every other week (Q2W), and Q2W or every fourth week (Q4W) from Week 16, in Chinese adults/adolescents with moderate-to-severe atopic dermatitis (AD).

Methods: SEASIDE CHINA (NCT05017480) was a phase II trial: Stage 1 (16-week treatment period), Stage 2 (36-week treatment and 8-week follow-up periods).

Decoding the AML1/ETO translocation cipher: In-depth exploration into the pathogenesis and cutting-edge therapeutic strategies of t(8;21) acute myeloid leukemia.

The t(8;21) acute myeloid leukemia (AML) is driven by the AML1-ETO (AE) fusion protein formed through the translocation of chromosomes 8 and 21, which mediates AML malignant transformation via epigenetic reprogramming and cooperative genetic events. This review comprehensively delineates the molecular pathogenesis of the disease, emphasizing that splice isoforms such as AE9a acquire enhanced leukemogenic potential due to the loss of critical structural domains. Emerging evidence demonstrates that epigenetic dysregulation-including aberrant DNA methylation, dysregulated histone modifications, and non-coding RNA-mediated regulatory networks-synergizes with AE to orchestrate leukemogenesis.

The impact of paternal body mass index on semen parameters and assisted reproductive outcomes in couples undergoing IVF/ICSI-ET treatment.

Purpose: To investigate the impact of paternal body mass index (BMI) on semen parameters and assisted reproductive outcomes in couples undergoing their first IVF/ICSI-ET cycle.

Materials And Methods: This retrospective study included 7618 couples undergoing IVF/ICSI-ET for maternal tubal/pelvic factors from 2017 to 2023. Paternal BMI was classified according to WHO criteria: normal weight (n = 3433), overweight (n = 3248), and obese (n = 937).

Homozygous variant in JARID2 causes female infertility characterized by compromised blastulation efficiency.

Background: Impaired embryonic developmental competence is a critical determinant of assisted reproductive technology (ART) failure, yet current genetic diagnostics primarily address complete early embryonic arrest, leaving partial developmental defects unexplained, such as compromised blastulation efficiency (CBE). Jumonji and AT-rich interaction domain containing 2 (JARID2), encoding a chromatin-modifying factor essential for histone methylation regulation, emerges as a novel candidate in this context.

Results: We identified a homozygous JARID2 missense variant (c.

Cancer Incidence and Mortality Risk: Associations with Diet Quality Scores in a Predominantly Low-Income and Black Cohort Study.

Background: Diet quality is a modifiable risk factor for cancer incidence and mortality. However, a substantial research gap exists regarding diet quality metrics' relationships with cancer risk among Black individuals or those with low socioeconomic status (SES).

Objective: This study aimed to investigate the associations of Dietary Approaches to Stop Hypertension (DASH), Empirical Dietary Inflammatory Pattern (EDIP), and Empirical Dietary Index for Hyperinsulinemia (EDIH) scores with total, colorectal, prostate, and breast cancer incidence and mortality within the prospective Southern Community Cohort Study (SCCS).

Longitudinal retinal functional evaluation using full-field electroretinography in New Zealand white and Dutch Belted rabbits with aging.

Electroretinography (ERG) is pivotal in elucidating retinal function, yet investigations into the temporal dynamics of ERG signals in New Zealand White (NZW) and Dutch-belted (DB) rabbits remain scarce. This study presents a longitudinal assessment of retinal function in both NZW and DB strains. ERG recordings were conducted on four NZW and four DB rabbits at 2, 7, 15, and 24 months of age, encompassing both dark-adapted and light-adapted protocols at each time point.

Associations of Pre-diagnostic Serum Liver Enzyme Levels with Lung Cancer Risk in Predominantly Low-income African and European Americans.

Previous studies have linked liver diseases to lung cancer (LC) risk; however, few studies evaluated the associations of circulating liver enzyme levels with LC risk. We conducted a study of 353 incident LC cases and 646 matched controls with baseline serum alanine aminotransferase (ALT) and of 552 cases and 1039 matched controls with baseline serum alkaline phosphatase (ALP) nested within the Southern Community Cohort Study. Conditional logistic regression and generalized linear models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) among all study participants and by stratification of potential effect modifiers.

Effects of Glycopyrronium Bromide as an Adjuvant Treatment in the Prevention of Nausea and Vomiting After Abdominal, Thyroid, and Breast Surgery: A Multicenter Randomized Controlled Trial.

Background: Effective methods for the prevention of postoperative nausea and vomiting remain to be found. Building upon previous evidence, we examined whether glycopyrrolate bromide had a preventive effect on nausea and vomiting when used as an adjuvant treatment.

Methods: In 11 participating hospitals, patients who were scheduled to receive gynecological (n=123), gastrointestinal (n=201), thyroid (n=93), and breast surgery (n=51) under general anesthesia and received postoperative opioids were randomly allocated to receive 4 mg dexamethasone and 4 mg tropisetron (Group C) or 4 mg dexamethasone and 4 mg tropisetron combined with 0.

Mutational landscape of triple-negative breast cancer in African American women.

African American (AA) women have the highest incidence of triple-negative breast cancer (TNBC) among all racial groups, but are underrepresented in cancer genomic studies. In 462 AA women with TNBC, we characterized the tumor mutational landscape by whole-exome sequencing and RNA sequencing. We unveiled a high-resolution mutational portrait of TNBC in AA women reminiscent of that in Asian and non-Hispanic white women, with no evidence of associations of mutational features with African ancestry.

Ericoid mycorrhizal fungal metacommunity facilitates closely related Rhododendron species coexistence.

The structural and ecological significance of ericoid mycorrhizal (ErM) fungi is well recognized. Yet, it remains unknown whether the coexistence of ericaceous plants is facilitated by their symbioses with ErM fungi. Here, we use Rhododendron (Ericaceae) as a model to investigate how phylogenetic and functional limiting similarity, or facilitation through ErM fungal metacommunity, influences their co-occurrence in mountain ecosystems.

CHIP protects lysosomes from CLN4 mutant-induced membrane damage.

Understanding how cells mitigate lysosomal damage is critical for unravelling pathogenic mechanisms of lysosome-related diseases. Here we generate and characterize induced pluripotent stem cell (iPSC)-derived neurons (iNeuron) bearing ceroid lipofuscinosis neuronal 4 (CLN4)-linked DNAJC5 mutations, which revealed extensive lysosomal abnormality in mutant neurons. In vitro membrane-damaging experiments establish lysosomal damages caused by lysosome-associated CLN4 mutant aggregates, as a critical pathogenic linchpin in CLN4-associated neurodegeneration.

Nature-Inspired Meta-Heuristic Algorithms for Detecting Protein Complexes in Protein-Protein Interaction Networks: A Survey.

In cells, various proteins interact to form protein-protein interaction networks. Protein complexes serve as the fundamental units that enable essential functions in biological organisms. Directly detecting protein complexes in protein-protein interaction networks using biology-based methods is costly and time-consuming.

2 × 2 Charge Density Wave in FeNbSe Stabilized by Disordered Intercalation.

The complex interplay between electronic and lattice degrees of freedom underlies a rich variety of emergent phenomena in quantum materials, particularly charge density waves (CDWs). Understanding the distinct roles of electron carriers and structural order in CDW formation is crucial for elucidating the underlying mechanisms and enabling control over material properties. The intertwined effects of charge doping and structural periodicity make it challenging to isolate the individual contributions to lattice modulations.

Design of Security Control for Dual-Rate CPSs Under Two-Channel DoS Attacks: SAH-Based and ASP-Based Estimation Techniques.

This article investigates the state estimation and security control problem for discrete-time dual-rate cyber-physical systems (CPSs) under denial-of-service (DoS) attacks. The asynchrony predicament between different signals of dual-rate CPSs, exacerbated by the impact of cyber attacks on the sensor-to-controller channel, substantially increases the complexity of state estimation and control processes. Based on the signal-to-interference-plus-noise ratio and two-channel probability descriptions, an improved sample-and-hold (SAH) estimator is applied to dual-rate CPSs, ensuring favorable state estimates while enduring low-frequency sampling and DoS attacks.

Identification and functional analysis of novel precursor genes in cyclic peptide biosynthesis in Pseudostellaria heterophylla.

Background: , a member of the Caryophyllaceae family, is widely used in traditional Chinese medicine due to its bioactive cyclic peptides (CPs) with immunomodulatory functions. Caryophyllaceae- like CPs, one of the largest types plant-derived CPs, typically consist of 5–12 amino acids and are derived from ribosomally synthesized peptide precursors. The diversity of CPs arises from variations in their core peptide sequences.

Multi-Ancestry Transcriptome-wide Association Studies Uncover New Insights into Breast Cancer Genetics and Biology.

Genome-wide association studies (GWAS) have identified over 200 genetic risk loci for breast cancer, yet the target genes in these loci remain largely unknown. To address this knowledge gap, we conducted a series of multi-ancestry transcriptome-wide association studies (TWAS) to discover potential breast cancer susceptibility genes. We developed and validated ancestry-specific genetic models to predict levels of gene expression, alternative splicing, and 3' UTR alternative polyadenylation, using genomic and transcriptomic data from normal breast tissue samples of 652 females of African, Asian, or European ancestry.

A novel PADI6 splice-site variant induces non-canonical GC-AG splicing and embryonic arrest in humans.

Early embryonic arrest (EEA) represents the predominant cause of assisted reproductive technology (ART) failure. PADI6 was a disease-associated gene identified for EEA. To date, 42 likely causal PADI6 variants have been documented, predominantly located in exonic regions with clustering outside the N-terminal domain.