Semi-rational engineering of leucine dehydrogenase for enhanced L-tert-leucine production.

Leucine dehydrogenase (LeuDH) is a promising enzyme for the industrial production of L-tert-leucine (L-Tle), but its catalytic activity toward trimethylpyruvate (TMP) requires enhancement. In this study, we employed a semi-rational design approach involving homology modeling of LeuDH from Exiguobacterium sibiricum (EsiLeuDH) and molecular docking with TMP to predict potential mutation sites. These sites were tested using an alanine scanning strategy to assess their impact on enzymatic activity, followed by site-saturation mutagenesis and iterative saturation mutagenesis.

Forecasting cardiovascular disease risk and burden in China from 2020 to 2030: a simulation study based on a nationwide cohort.

Background: Cardiovascular disease (CVD) remains a significant public health challenge in China. This study aimed to project the burden of CVD from 2020 to 2030 using a nationwide cohort and to simulate the potential impact of various control measures on morbidity and mortality.

Methods: An agent-based model was employed to simulate annual CVD incidence and mortality from 2021 to 2030.

Association of long-term exposure to ozone with cardiovascular mortality and its metabolic mediators: evidence from a nationwide, population-based, prospective cohort study.

Background: Previous studies about chronic effects of ozone (O) on cardiovascular mortality are scarce and inconclusive. We aimed to investigate the association between cardiovascular mortality and a broad range of long-term O exposure levels.

Methods: This analysis included 3,206,871 participants aged 35-75 years enrolled in the ChinaHEART study.

Predictive Value of Life's Crucial 9 for Cardiovascular and All-Cause Mortality: A Prospective Cohort Study From the NHANES 2007 to 2018.

Background: The predictive value of Life's Crucial 9 (LC9), a recently proposed cardiovascular health risk score combining psychological health and Life's Essential 8 (LE8), remains unclear.

Methods And Results: In this cohort study, we included 16 290 adults without cardiovascular disease from the 2007 to 2018 cycles of NHANES (National Health and Nutrition Examination Survey). The LC9 was the mean of the LE8 score and the depression score, which represented a dimension of psychological health.

Semi-rational engineering of ω-transaminase for enhanced enzymatic activity to 2-ketobutyrate.

Transaminases (EC 2.6.1.

Association and its population heterogeneities between low-density lipoprotein cholesterol and all-cause and cardiovascular mortality: A population-based cohort study.

Background: The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups.

Methods: A total of 2,968,462 participants aged 35-75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014-2019) were included.

Effects of genetically proxied statins on diabetic nephropathy and retinopathy: a Mendelian randomization study.

There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study.

Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial.

Background: Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke.

Methods: In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg.

Prognostic Value of a Multi-mRNA Signature for 1-Year All-Cause Death in Hospitalized Patients With Heart Failure With a Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction is a major global public health problem, while effective risk stratification tools are still lacking. We sought to construct a multi-mRNA signature to predict 1-year all-cause death.

Methods: We selected 30 patients with heart failure with preserved ejection fraction who died during 1-year follow-up and 30 who survived in the discovery set.

Iron Metabolic Biomarkers and the Mortality Risk in the General Population: A Nationwide Population-Based Cohort Study.

Context: Iron is an essential element in the human body and plays a critical role in many physiological and cellular processes. However, the association between iron status and the risk of all-cause or cause-specific mortality has not been well-investigated. And it is unclear whether the association between iron metabolic biomarkers and the risk of mortality differs between people with and without diabetes mellitus (DM).

Design and rationale of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study: A cluster randomized controlled trial for hypertension management in primary care.

Background: Hypertension management in China is suboptimal with high prevalence and low control rate due to various barriers, including lack of self-management awareness of patients and inadequate capacity of physicians. Digital therapeutic interventions including mobile health and computational device algorithms such as clinical decision support systems (CDSS) are scalable with the potential to improve blood pressure (BP) management and strengthen the healthcare system in resource-constrained areas, yet their effectiveness remains to be tested. The aim of this report is to describe the protocol of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study assessing the effect of a multifaceted hypertension management system for supporting patients and physicians on BP lowering in primary care settings.

Development of a machine learning-based model for predicting individual responses to antihypertensive treatments.

Background And Aims: Personalized antihypertensive drug selection is essential for optimizing hypertension management. The study aimed to develop a machine learning (ML) model to predict individual blood pressure (BP) responses to different antihypertensive medications.

Methods And Results: We used data from a pragmatic, cluster-randomized trial on hypertension management in China.

Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

Background: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice.

Methods: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours.

Association of high-density lipoprotein cholesterol with all-cause and cause-specific mortality in a Chinese population of 3.3 million adults: a prospective cohort study.

Background: High-density lipoprotein cholesterol (HDL-C) has been inversely associated with cardiovascular disease (CVD) risk, but recent evidence suggests that extremely high levels of HDL-C are paradoxically related to increased CVD incidence and mortality. This study aimed to comprehensively examine the associations of HDL-C with all-cause and cause-specific mortality in a Chinese population.

Methods: The China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) project included 3,397,547 participants aged 35-75 years with a median follow-up of 3.

Healthy lifestyle, statin, and mortality in people with high CVD risk: A nationwide population-based cohort study.

Objective: To examine the joint association of healthy lifestyles and statin use with all-cause and cardiovascular mortality in high-risk individuals, and evaluate the survival benefits by life expectancy.

Methods: During 2015-2021, participants aged 35-75 years were recruited by the China Health Evaluation And risk Reduction through nationwide Teamwork. Based on number of healthy lifestyles related to smoking, alcohol drinking, physical activity, and diet, we categorized them into: very healthy (3-4), healthy (2), and unhealthy (0-1).

Associations of remnant cholesterol with cardiovascular and cancer mortality in a nationwide cohort.

The health significance of triglyceride-rich lipoproteins, also known as remnant cholesterol, has been increasingly recognized. However, evidence of their associations with cause-specific mortality in the general population was previously insufficient. To explore these associations and their heterogeneities across subgroups, a prospective cohort study was conducted including 3,403,414 community-based participants from ChinaHEART, an ongoing government-funded public health program throughout China, from November 2014 through December 2022.

Sociodemographic Factors, Leisure-Time Physical Activity and Mortality.

Introduction: Exploring sociodemographic effect modification is important to provide evidence for developing targeted recommendations and reducing health inequalities. This study evaluated how sociodemographic factors including age, sex, race/ethnicity and socioeconomic status (SES) modify the association between leisure-time physical activity (LTPA) and all-cause and major cause-specific mortality.

Methods: The study sample included 471,992 people from the 1997-2018 National Health Interview Survey (NHIS) and 41,830 people from the 1999-2018 National Health and Nutrition Examination Survey (NHANES).

Influence of Socioeconomic Gender Inequality on Sex Disparities in Prevention and Outcome of Cardiovascular Disease: Data From a Nationwide Population Cohort in China.

Background Knowledge gaps remain in how gender-related socioeconomic inequality affects sex disparities in cardiovascular diseases (CVD) prevention and outcome. Methods and Results Based on a nationwide population cohort, we enrolled 3 737 036 residents aged 35 to 75 years (2014-2021). Age-standardized sex differences and the effect of gender-related socioeconomic inequality (Gender Inequality Index) on sex disparities were explored in 9 CVD prevention indicators.

Educational inequalities in mortality and their mediators among generations across four decades: nationwide, population based, prospective cohort study based on the ChinaHEART project.

Objectives: To assess the different educational inequalities in mortality among generations born between 1940 and 1979 in China, and to investigate the role of socioeconomic, behavioural, and metabolic factors as potential contributors to the reduction of educational inequalities.

Design: Nationwide, population based, prospective cohort study.

Setting: The ChinaHEART (China Health Evaluation And risk Reduction through nationwide Teamwork) project in all 31 provinces in the mainland of China.

Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study.

Background The age-related trends in the predictive ability of carotid intima-media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age-related trends in the predictive value of CIMT for cardiovascular death. Methods and Results In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death.

A novel polygenic risk score improves prognostic prediction of heart failure with preserved ejection fraction in the Chinese Han population.

Aims: Mortality risk assessment in patients with heart failure (HF) with preserved ejection fraction (HFpEF) presents a major challenge. We sought to construct a polygenic risk score (PRS) to accurately predict the mortality risk of HFpEF.

Methods And Results: We first carried out a microarray analysis of 50 HFpEF patients who died and 50 matched controls who survived during 1-year follow-up for candidate gene selection.

Primary care institutional characteristics associated with hypertension awareness, treatment, and control in the China PEACE-Million Persons Project and primary health-care survey: a cross-sectional study.

Background: Since 2010, China has made vast financial investments and policy changes to the primary care system. We aimed to assess how hypertension awareness, treatment, and control might be used to assess quality of primary care systems, which reflect the outcomes of public health services and medical care.

Methods: We used The China Patient-centred Evaluative Assessment of Cardiac Events Million Persons Project, a government-funded public health project that focuses on cardiovascular disease risk in China.