Abnormal function of EPHA2/p.R957P mutant in congenital cataract

AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

Multienzyme co-immobilization-based bioelectrode:Design of principles and bioelectrochemical applications

Enzyme cascade reactions play significant roles in bioelectrochemical processes because they permit more complex reactions. Co-immobilization of multienzyme on the electrode could help to facilitate substrate/intermediate transfer among different enzymes and electron transfer from enzyme active sites to the electrode with high stability and retrievability. Different co-immobilization strategies to construct multienzyme bioelectrodes have been widely reported, however, up to now, they have barely been reviewed. In this review, we focus on recent state-of-the-art techniques for constructing co-immobilized multienzyme electrodes including random and positional co-immobilization. Particular attention is given to strategies such as multienzyme complex and surface display. Cofactor co-immobilization on the electrode is also crucial for the enhancement of catalytic reaction and electron transfer, yet, few studies have been reported. The up-to-date advances in bioelectrochemical applications of multienzyme bioelectrodes are also presented. Finally, key challenges and future perspectives are discussed.

Maternal Preconception Serum Alanine Aminotransferase Levels and Risk of Preterm Birth among Reproductive-Aged Women—China,2013-2017

Summary What is already known about this topic?The significance of maternal liver health concerning preterm birth(PTB)is well recognized;however,there is a gap in understanding the precise influence of preconception serum alanine aminotransferase(ALT)levels on the risk of PTB.What is added by this report?

Association of psychological stress with wives’hypertension across over 10 million Chinese married female population aged 20-49 years

Background:Psychological stress has been reported to be a potential risk factor for hypertension among females,but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women.We examined the associations between stress within the family and hypertension among married women.Methods:Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects(NFPCP)across 31 provinces in China in 2016 and 2017.Perceived stress of wives or husbands was measured with a 5-point Likert-type scale,and assessed from three domains:work/life-related stress,economic stress,and overall stress.Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.Results:Of 10,027,644 couples,261,098(2.60%)women had hypertension.The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women(P_(for trend)<0.001).Compared with non-stressed participants,female participants with the highest stress themselves were at a greater risk of hypertension,with adjusted odds ratio(OR)of 1.31(95%confidence interval[CI]:1.25-1.37);and compared with participants whose husbands had no stress,those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24(95%CI:1.20-1.29).Moreover,compared with non-stressed status for both couples,only-wife-stressed,only-husband-stressed,and both-stressed couples were found to be significantly associated with increased risks of wives’hypertension,with adjusted ORs of 1.28(95%CI:1.25-1.31),1.19(95%CI:1.17-1.21),and 1.28(95%CI:1.26-1.31),respectively.Conclusion:Moderate to severe stress in both spouses might be associated with female hypertension prevalence,which highlights the importance of paying attention to the psychological stresses of couples within the family.

Effects of greenness on preterm birth: A national longitudinal study of 3.7 million singleton births

Exposure to greenness may lead to a wide range of beneficial health outcomes.However,the effects of greenness on preterm birth(PTB)are inconsistent,and limited studies have focused on the subcategories of PTB.A total of 3,751,672 singleton births from a national birth cohort in China's Mainland were included in this study.Greenness was estimated using the satellitebased Normalized Difference Vegetation Index(NDVI)and Enhanced Vegetation Index with 500-m and 1,000-m buffers around participants’addresses.The subcategories of PTB(20-36 weeks)included extremely PTB(EPTB,20-27 weeks).

Hematological Parameters in the First Trimester and the Risk of Gestational Diabetes Mellitus—Beijing,China,2017–2020

Summary What is already known about this topic?Hematological parameters may indicate the presence of chronic low-grade inflammation and increasing viscosity,which are involved in the pathological processes of gestational diabetes mellitus(GDM).However,the association between several hematological parameters in early pregnancy and GDM has yet to be elucidated.What is added by this report?Hematological parameters in the first trimester,particularly red blood cell(RBC)count and systematic immune index,have a significant impact on GDM incidence.The neutrophils(NEU)count in the first trimester was particularly pronounced for GDM.The upward trend of RBC,white blood cell(WBC),and NEU counts was consistent across all GDM subtypes.What are the implications for public health practice?Early pregnancy hematological parameters are associated with the risk of GDM.

2013~2017年中国空气质量改善与早产疾病负担改变

Preterm birth(PTB)is a leading cause of perinatal mortality and morbidity worldwide[1].Since maternal and fetal health protection has been included in the United Nations Sustainable Development Goals,identification of modifiable risk factors for PTB is particularly crucial.The Global Burden of Disease(GBD)Study 2019 recognized fine particulate matter(PM2.5)pollution as a risk factor for decreased gestational age and low birth weight.

Comparative metagenomic analysis of the vaginal microbiome in healthy women

The composition of these vaginal microbiome has a significant impact on women’s health.However,few studies have characterized the vaginal microbiome of healthy Chinese women using metagenomic sequencing.Here,we carried out a comparative metagenomic analysis to survey taxonomic,functional levels,and microbial communities’genome content in healthy women’s vaginal microbiome.Overall,we observed a total of 111 species,including all dominant vaginal Lactobacillus species,such as L.iners,L.crispatus,L.gasseri,and L.jensenii.Unlike microbial taxa,several pathways were ubiquitous and prevalent across individuals,including adenosine ribonucleotides de novo biosynthesis and pyruvate fermentation to acetate and lactate Ⅱ.Notably,our diversity analysis confirmed a significant difference in healthy women from different ethnic groups.Moreover,we binned vaginal assemblies into 62 high-quality genomes,including 9 L.iners,7 A.vaginae,5 L.jensenii,and 5 L.crispatus.We identified the pan and core genomes of L.iners and A.vaginae and revealed the genetic diversity.Primary differences between strains were the hypothetical genes and mobile element-like genes.Our results provide a framework for understanding the implications of the female reproductive tract’s composition and functional potential and highlight the importance of genome-resolved metagenomic analysis to further understand the human vaginal microbiome.

PENG ZU Study on Healthy Aging in China(PENG ZU Cohort):Design and Goals

Life expectancy is increasing,leading to the continuous aging of the population in China.Enhancing the health status of the older population is crucial to achieving healthy aging.The primary objective of the PENG ZU Study on Healthy Aging in China(PENG ZU Cohort)is to understand the natural progression of health status among the aging Chinese population.Specifically,the PENG ZU cohort aims to identify and validate multidimensional aging markers,uncover the underlying mechanisms of systemic aging and functional decline,and develop novel strategies and measures to delay functional decline and adverse health outcomes,while maintaining overall good health.The PENG ZU cohort consists of 26,000 individuals aged 25 to 89 years from seven major geographical regions in China.Diversified data and biospecimens are collected according to standardized procedures at baseline and follow-up visits.Baseline recruitment for the PENG ZU cohort was completed in October 2021.The extensive analysis of multidimensional health-related data and bioresources collected from the cohort is anticipated to develop methods for evaluating functional status and elucidating multilevel,cross-scale interactions and regulatory mechanisms of healthy aging.The findings from this study will enhance the understanding of health changes due to aging,facilitate efficient and effective interventions to maintain functional ability,and reduce the incidence and severity of age-related diseases,thereby further promoting healthy aging.