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.Cox proportional hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between LDL-C categories(<70.0,70.0-99.9,100.0-129.9[reference group],130.0-159.9,160.0-189.9,and≥190.0 mg/dL)and all-cause and cause-specific mortality.Results:During a median follow-up of 3.7 years,57,391 and 23,241 deaths from all-cause and overall CVD were documented.We observed J-shaped associations between LDL-C and death from all-cause,overall CVD,coronary heart disease(CHD),and ischemic stroke,and an L-shaped association between LDL-C and hemorrhagic stroke(HS)mortality(P for non-linearity<0.001).Compared with the reference group(100.0-129.9 mg/dL),very low LDL-C levels(<70.0 mg/dL)were significantly associated with increased risk of overall CVD(hazard ratio[HR]:1.10,95%confidence interval[CI]:1.06-1.14)and HS mortality(HR:1.37,95%CI:1.29-1.45).Very high LDL-C levels(≥190.0 mg/dL)were associated with increased risk of overall CVD(HR:1.51,95%CI:1.40-1.62)and CHD mortality(HR:2.08,95%CI:1.92-2.24).The stronger associations of very low LDL-C with risk of CVD mortality were observed in individuals with older age,low or normal body mass index,low or moderate 10-year atherosclerotic CVD risk,and those without diagnosed CVD or taking statins.Stronger associations between very high LDL-C levels and all-cause and CVD mortality were observed in younger people.Conclusions:People with very low LDL-C had a higher risk of all-cause,CVD,and HS mortality;those with very high LDL-C had a higher risk of all-cause,CVD,and CHD mortality.On the basis of our findings,comprehensive health assessment is needed to evaluate cardiovascular risk and implement appropriate lipid-lowering therapy for people with very low LDL-C.

紫外光协同磁性离子交换树脂活化过硫酸盐去除水中腐殖酸的效能与机理

采用紫外光协同磁性离子交换树脂活化过硫酸盐去除水中腐殖酸,探究了紫外光/过硫酸盐/磁性离子交换树脂(UV/PMS/MIEX)体系对水中腐殖酸的去除效能、影响腐殖酸去除的环境因素、活性氧化物质产生机理及腐殖酸去除机理。UV/PMS/MIEX体系对水中腐殖酸具有显著的去除效能,反应120 min后去除率可达91.71%。树脂投加量和温度的提高可促进腐殖酸的去除,一定程度上增加PMS浓度可提升腐殖酸的去除效率,而溶液pH对腐殖酸去除的影响不明显。该体系以氧化过程为主,在树脂表面的铁氧化物,含氧官能团及外加紫外光等多种协同作用下,可有效活化过硫酸盐产生·OH, SO_(4)^(·-), O_(2)^(·-)和^(1)O_(2)等多种活性氧化物质,自由基与非自由基途径共同协作降解腐殖酸。MIEX树脂体现出良好的重复使用性能,同时对于体系中的各类副产物可有效吸附去除。本研究为去除水中腐殖酸提供了一种新方法,所构建的氧化体系表现出良好应用前景。

残余胆固醇与心血管、癌症死亡率的相关性:一项全国性队列研究

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 China HEART,an ongoing government-funded public health program throughout China,from November 2014 through December 2022.The study assessed mortality risk of all-cause mortality,cardiovascular disease(CVD)mortality(including mortality from ischemic heart diseases(IHD),ischemic stroke(IS),and hemorrhagic stroke(HS),separately),and cancer mortality(including lung cancer,stomach cancer,and liver cancer,separately).During the 4-year follow-up,23,646 individuals died from CVD(including 8807 from IHD,3067 from IS,and 5190 from HS),and 20,318 from cancer(including 6208 from lung cancer,3013 from liver cancer,and 2174 from stomach cancer).Compared with individuals with remnant cholesterol<17.9 mg/d L,multivariable-adjusted mortality hazard ratios(HRs)for individuals with remnant cholesterol≥27.7 mg/d L were 1.03(1.00–1.05)for all-cause mortality,1.17(1.12–1.21)for CVD(1.19(1.12–1.27)for IHD mortality,and 1.22(1.09–1.36)for IS mortality),and 0.90(0.87–0.94)for allcancer mortality(0.94(0.87–1.02)for lung cancer,0.59(0.53–0.66)for liver cancer,and 0.73(0.64–0.83)for stomach cancer).In summary,this study revealed a correlation between increased remnant cholesterol levels and an elevated risk of cardiovascular disease mortality,as well as a reduced risk of mortality for certain types of cancer.

Modification of the substrate specificity of leucine dehydrogenase by site‑directed mutagenesis based on biocomputing strategies

Synthesis of chiral amines by amine dehydrogenase has the advantages of environmental friendliness,high stereoselectivity,and mild reaction conditions.However,amine dehydrogenase has low catalytic activity,which greatly limits its application in the large-scale synthesis of chiral amines.In this study,a novel amine dehydrogenase was obtained by modifying the substrate specificity of leucine dehydrogenase via computer-aided protein engineering strategy.Furthermore,conservation analysis,homology modeling and molecular docking analysis were carried out via biocomputing strategy to select the mutation sites,and the mutants L52S and T143C were obtained.The enzyme activities of the two mutants to 2-pentanone were 1.55 U/mg and 2.06 U/mg,respectively.The enzyme activity of the latter was 188%and the Tm value was 2.55°Chigher than those of the original mutant,which laid a foundation for the efficient preparation of chiral amines by using this novel enzyme.