The molecular mechanisms and therapeutic implications of PANoptosis in ischemic diseases.

The singular forms of programmed cell death (PCD), including pyroptosis, apoptosis, and necroptosis, are inadequate for comprehensively elucidating the complex pathological mechanisms underlying ischemic diseases. PANoptosis is a unique lytic, innate immune, and inflammatory cell death pathway, initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes. In diseases like cerebral ischemia, retinal ischemia, myocardial ischemia, renal ischemia, and spinal cord ischemia, targeting key regulatory factors of PANoptosis can help mitigate tissue damage.

Recent advances in oxygen reduction reaction catalysis under neutral conditions.

The oxygen reduction reaction (ORR) is central to energy devices and sustainable chemical production. While acidic and alkaline ORR systems are well studied, neutral media offer advantages such as biocompatibility, environmental safety, and material stability, yet remain less explored. This mini-review summarizes recent progress in ORR electrocatalysis under neutral conditions, covering both four-electron (4e) and two-electron (2e) pathways.

Clinical gene therapy restores hearing: a paradigm shift.

Recent breakthroughs in gene therapy for autosomal recessive deafness 9 (DFNB9) caused by OTOF mutations have transformed treatment paradigms for hereditary hearing loss (HHL). To date, eight clinical trials targeting DFNB9 have been registered in 51 centers across eight countries, demonstrating the rapid progress of gene therapy in auditory medicine. These pioneering studies establish the framework for the clinical translation of gene therapy targeting HHL.

Erratum: Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates.

[This corrects the article DOI: 10.1016/j.omtm.

SGLT2 inhibition, acylcarnitines and heart failure: a Mendelian randomization study.

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are guideline-recommended agents for treating heart failure (HF), but the role of metabolomic biomarkers in underlying mechanisms, particularly acylcarnitines, remains unclear. This study examined the associations of acylcarnitines with SGLT2 inhibition and incident HF.

Methods: This subcohort study included 2178 participants from the prospective China Kadoorie Biobank without cardiovascular disease, diabetes or cancer at baseline.

The mediating effect of blood pressure between healthy lifestyles and stroke: Results from the China Kadoorie Biobank study.

While a healthy lifestyle is known to reduce stroke risk, the extent to which blood pressure (BP) mediates this association remains unclear. The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence. Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline, we employed structural equation modeling to assess the mediating effects of systolic (SBP) and diastolic (DBP) blood pressure.

Physiological Response of to CO Controlled Atmosphere Stress Under Trehalose Feeding.

This study investigated the physiological regulatory mechanisms by which exogenous trehalose intake enhances the adaptation of the global stored-grain pest to high-concentration carbon dioxide (CO) stress. By supplementing exogenous trehalose under high-CO controlled atmosphere stress, we measured the activities of key detoxification enzymes (e.g.

Patterns and correlates of visual impairment and ocular hypertension among older adults in the general Chinese population: results from the CKB Biobank.

Background: While numerous ophthalmology-specific cohort studies have been conducted in China, there is a significant lack of comprehensive, population-based study on the potential determinants of visual impairment and ocular hypertension (OHT) in the general Chinese population.

Methods: In the 2020-2021 resurvey of the China Kadoorie Biobank study, ~25 000 randomly selected participants from 10 diverse localities (5 urban and 5 rural) were surveyed. Presenting visual acuity (PVA) was measured using the Random E eye chart and intraocular pressure (IOP) was measured using a handheld Icare (ic100) tonometer.

Physician turnover in China, 2011-2021: a nationwide longitudinal study.

Background: There have been a globally paucity of comprehensive quantitative studies on the physician turnover trends. This study aimed to investigate the trajectory and magnitude of Chinese physician turnover, as well as its influencing factors.

Methods: We established a retrospective cohort by combining annual physician surveillance data and annual medical institution report data between 2011 and 2021.

The ionic and protonation states of flavin control the activation and recovery of Drosophila cryptochrome.

Drosophila cryptochrome (dCry) is a flavin-containing photoreceptor. The release of C-terminal tail (CTT) upon illumination is a crucial step for the light sensing of dCry. Here, we demonstrated that both anionic semiquinone (asq) and anionic hydroquinone (hq) triggered CTT release, while neutral semiquinone (nsq) formation suppressed it.

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

Pregnancy-associated fulminant type 1 diabetes mellitus: Two case reports and literature review.

Pregnancy-associated fulminant type 1 diabetes mellitus (PFT1DM) occurs during pregnancy or within 2 weeks after delivery. Despite the low incidence of PFT1DM in obstetrics, it poses a great threat to the lives of mothers and infants. The present study reported the management of 2 cases with PFT1DM, emphasizing the importance of early diagnosis and appropriate treatments to improve pregnancy outcomes.

Effect of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: An Exploratory Metabolomics and Validation Study.

Background: Bariatric surgery presents a significant alleviation for non-alcoholic fatty liver disease (NAFLD), which relies in part on achieving substantial weight loss in post-surgical period. We aimed to understand the effect of bariatric surgery on NAFLD remission via metabolomics and to validate the results in a general population-based cohort.

Methods: In a pilot study, ten patients with NAFLD who underwent bariatric surgery were enrolled.

Finotonlimab (PD-1 inhibitor) plus bevacizumab (bevacizumab biosimilar) as first-tier therapy for late-stage hepatocellular carcinoma: a randomized phase 2/3 trial.

We aimed to assess the tolerability and efficacy of finotonlimab (an anti-programmed cell death protein-1 antibody) in combination with SCT510, a bevacizumab biosimilar, versus sorafenib in unresectable advanced HCC. This randomized phase 2 and 3 study (ClinicalTrials.gov, NCT04560894; Chinadrugtrials.

Analysis of the prognostic and immune role of MCM6 in pan-cancer and experimental validation in lung adenocarcinoma cells.

Mini-chromosome maintenance protein 6 (MCM6), a member of the DNA replication initiation complex, is considered a potential prognostic marker for multiple tumors. However, the biological role of MCM6 has not been reported in pan-cancer. In present study, a pan-cancer analysis of MCM6 was performed using multiple databases and online websites.

FN14 promotes ventilator-induced lung injury by regulating pyroptosis via the ANXA2/ERK1/2 axis.

Background: Uncontrollable inflammatory cascade is a key factor in the development of Ventilator-induced lung injury (VILI). Studies have shown that FN14 is involved in the pathophysiological processes of various acute inflammatory diseases. However, its mechanism of action in VILI has not been elucidated.

Osteocytes function as biomechanical signaling hubs bridging mechanical stress sensing and systemic adaptation.

Osteocytes, the most abundant bone cells embedded within mineralized matrix, are pivotal regulators of skeletal and systemic homeostasis. Recent advances highlight their mechanotransductive roles via mechanosensors, enabling detection of mechanical stimuli and conversion into biochemical signals to orchestrate bone remodeling. Beyond bone, osteokines derived from osteocytes engage themselves in bidirectional crosstalk with distant organs or tissues-modulating brain, liver, kidney, muscle, adipose tissue, nerve, blood vessel, and cancer.

Genetic influences on the association between DNA methylation and obesity measures: insights from a twin study design.

Background: Both obesity and DNA methylation (DNAm) are influenced by genetic factors. Despite more than a thousand of obesity-related DNAm sites (CpGs) being identified, studies that account for genetic influences in these associations are limited.

Results: Using data from 1,074 twins in the Chinese National Twin Registry and bivariate structural equation models (SEMs), we investigated the phenotypic (Rph), genetic (Ra), and environmental (Re) correlations between genome-wide DNAm and three obesity indices: BMI, waist circumference (WC), and waist-to-hip ratio (WHR).

Phenome-wide association of physical activity with morbidity and mortality risk in China: A prospective cohort study.

Research in high-income countries has established the health benefits of physical activity (PA), but evidence from low- and middle-income countries, including China, where PA patterns vary from those in high-income countries, remains limited. Moreover, previous research, mainly focused on specific diseases, failing to fully capture the health impacts of PA. We investigated the associations of PA with 425 distinct diseases and 53 causes of death using data from 511,088 participants aged 30-79 years in the China Kadoorie Biobank.

Impact of genetic risk and lifestyles on cardiovascular disease-free and total life expectancy: a cohort study.

Background: Understanding the role of genetic risk and lifestyles on life expectancy (LE) without cardiovascular disease (CVD) and total LE may help optimize healthy aging strategies after taking genetic background into account.

Methods: The China Kadoorie Biobank recruited participants from five urban and five rural areas across China during 2004-2008 and followed them up till December 31, 2018. A polygenic risk score (PRS) comprising 3.

Gene Therapy vs Cochlear Implantation in Restoring Hearing Function and Speech Perception for Individuals With Congenital Deafness.

Importance: OTOF gene therapy (GT) has been shown to improve hearing and speech. The efficacy of GT remains to be compared against cochlear implantation (CI), the current gold standard for congenital deafness.

Objective: To evaluate treatment outcomes in auditory and speech perception between patients with congenital deafness treated with GT, CI, or both.

Prospective associations of diabetes with 15 cancers in 2.2 million UK and Chinese adults.

Background: Diabetes has been associated with the risk of numerous cancers but the causal relevance of many of these associations remains unclear.

Methods: We investigated associations between diabetes and risks of 15 cancers using Cox-regression and individual-level data from 2.2 million adults (334,978 incident cancer cases) in three prospective cohorts, UK Biobank (UKB), Million Women Study (MWS), and China Kadoorie Biobank (CKB).

Risk thresholds for soft versus hard cardiovascular disease outcome models for initiating statin therapy among Chinese adults: a cost-utility analysis.

Background: Current guidelines for atherosclerotic cardiovascular disease (ASCVD) primary prevention mostly recommend risk scores that predict risk of non-fatal myocardial infarction, fatal ischemic heart disease (IHD), and fatal or non-fatal ischemic stroke (hard outcomes), ignoring the burden from other non-fatal IHD outcomes. We explored the optimal risk thresholds for statin initiation using non-laboratory-based soft and hard ASCVD outcome models and compared the cost-utility of such models in the Chinese population.

Methods: We constructed Markov cohort models to estimate the incidence of ASCVD events, costs, and quality-adjusted life years (QALYs) over a lifetime from a social perspective.

Genetic Risk and Prognosis of the First Incident Stroke Survivors: Findings from China Kadoorie Biobank and UK Biobank.

Background And Objectives: Stroke is known for its poor prognosis. Although genetic instruments have shown promise in stratifying first stroke risk in the general population, it is unknown whether they are associated with stroke prognosis. Our study aims to explore the role of genetic risk of stroke in the progression from stroke-free to first stroke and then to recurrent stroke, subsequent coronary heart disease (CHD), and death in China and the United Kingdom.

GDF15 and its receptors as pathways mediating smoking related weight change.

Background: Smokers have lower body weight than non-smokers, while smoking cessation results in weight gain. Understanding the mechanisms involved can help identify potential therapeutic targets to enhance smoking cessation.

Methods: We measured plasma levels of growth/differentiation factor 15 (GDF15), a stress-responsive protein, and its two receptors (proto-oncogene tyrosine-protein kinase receptor Ret [RET], GDNF family receptor alpha-like [GFRAL]) among 3936 Chinese adults (mean BMI 24.