Data-independent acquisition mass spectrometry quantitative proteomic analysis reveals that skin aging-related proteins differ between men and women

The skin is the largest organ of the human body,and its aging is visible to the naked eye.The aging rate of men and women is slightly different.This study compared the protein expression of skin samples on the curved forearms of 11 healthy women and 9 healthy men.Quantitative proteomics analysis found that the expression of epidermal proteins in men and women of the same age group was different.Compared with female skin,in male skin,20 proteins were upregulated,and 7 proteins were downregulated.These data suggest that men and women have differences in the speed of skin aging.For the first time in this experiment,a non-invasive mass spectrometer was used to detect 27 different-related epidermal proteins between men and women.Compared with women,among the 20 epidermal proteins upregulated in men,their functions can be classified into antioxidants,epidermal lipid metabolism,signal transduction,membrane transport,and cell biological processes;the 7 downregulated proteins are involved in a variety of biological processes and inflammatory reactions.Our experiments have discovered epidermal proteins related to the differences between men and women,enriching the library of epidermal differential proteins between men and women and enriching the mechanism of skin aging between men and women from the perspective of epidermal differential proteins.

长期PM_(1)暴露与高血压住院风险增加之间的潜在因果关联

大气污染在全球范围内导致了严重的健康问题,使全球平均预期寿命缩短了近3年,超过了艾滋病和吸烟的影响^([1]).大气细颗粒物(PM_(2.5))作为其中最重要的污染之一,受到了广泛的关注.据估计,2019年PM_(2.5)造成全球约1.18亿伤残调整生命年,其中心血管疾病约占51.5%^([2]).高血压是主要的心血管疾病之一,同时也是其他心脑血管疾病(如中风)最重要的危险因素之一.

PM_(1)颗粒物长期暴露与高血压住院:一项基于中国南方大型社区队列的因果推断研究

Limited evidence exists on the effect of submicronic particulate matter(PM_(1)) on hypertension hospitalization. Evidence based on causal inference and large cohorts is even more scarce. In 2015, 36,271 participants were enrolled in South China and followed up through 2020. Each participant was assigned single-year, lag0–1, and lag0–2 moving average concentration of PM_(1)and fine inhalable particulate matter(PM2.5) simulated based on satellite data at a 1-km resolution. We used an inverse probability weighting approach to balance confounders and utilized a marginal structural Cox model to evaluate the underlying causal links between PM_(1)exposure and hypertension hospitalization, with PM2.5-hypertension association for comparison. Several sensitivity studies and the analyses of effect modification were also conducted. We found that a higher hospitalization risk from both overall(HR: 1.13, 95% CI:1.05–1.22) and essential hypertension(HR: 1.15, 95% CI: 1.06–1.25) was linked to each 1 μg/m3increase in the yearly average PM_(1)concentration. At lag0–1 and lag0–2, we observed a 17%–21% higher risk of hypertension associated with PM_(1). The effect of PM_(1)was 6%–11% higher compared with PM2.5. Linear concentration-exposure associations between PM_(1)exposure and hypertension were identified, without safety thresholds. Women and participants that engaged in physical exercise exhibited higher susceptibility, with 4%–22% greater risk than their counterparts. This large cohort study identified a detrimental relationship between chronic PM_(1)exposure and hypertension hospitalization, which was more pronounced compared with PM2.5and among certain groups.

L-GrAFT_(7) has High Accuracy in Predicting Early Allograft Failure after Liver Transplantation: A Multicenter Cohort Study in China

Background and Aims:Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation.However,consensus of definition of early allograft failure is lacking.Methods:A retrospective,multicenter study was performed to validate the Liver Graft Assessment Following Transplantation(L-GrAFT)risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers.L-GrAFT(L-GrAFT7 and L-GrAFT10)was compared with existing models:the Early Allograft Failure Simplified Estimation(EASE)score,the model of early allograft function(MEAF),and the Early Allograft Dysfunction(EAD)model.Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group.Results:L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival,significantly superior to MEAF[area under the curve(AUC=0.78,p=0.044)]and EAD(AUC=0.78,p=0.006),while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE(AUC=0.84,p>0.05).Furthermore,L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index(DRI)cases(AUC=0.83 vs.MEAF,p=0.007 vs.EAD,p=0.014)and recipients of donors after cardiac death(AUC=0.92 vs.EAD,p<0.001).Through multivariate analysis,pretransplant bilirubin level,units of packed red blood cells,and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group.Conclusions:The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort,indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum

This study aims to investigate the impact of hepatocyte nuclear factor 1β(HNF1b)on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum(PAOA-flavone)-promoted small ubiquitin-related modifier(SUMO)modification in the atheroprotective efficacy of HNF1b.HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics,dual-luciferase reporter gene assay,and chromatin immunoprecipitation.HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages,leading to a depression in atherosclerotic plaque formation in low-density lipoprotein(LDL)receptor-deficient(LDLR−/−)mice.Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification.The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages.PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1(SAE1)expression and SAE1-catalyzed SUMOylation of the HNF1b protein,which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient(ApoE−/−)mice.Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration.In summary,HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis.This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated,SAE1-catalyzed SUMOylation of the HNF1b protein.

Immunological and metabolic characteristics of the Omicron variants infection

The Omicron variants of SARS-CoV-2,primarily authenticated in November 2021 in South Africa,has initiated the 5th wave of global pandemics.Here,we systemically examined immunological and metabolic characteristics of Omicron variants infection.We found Omicron resisted to neutralizing antibody targeting receptor binding domain(RBD)of wildtype SARS-CoV-2.Omicron could hardly be neutralized by sera of Corona Virus Disease 2019(COVID-19)convalescents infected with the Delta variant.Through mass spectrometry on MHC-bound peptidomes,we found that the spike protein of the Omicron variants could generate additional CD8+T cell epitopes,compared with Delta.These epitopes could induce robust CD8+T cell responses.Moreover,we found booster vaccination increased the cross-memory CD8+T cell responses against Omicron.Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells.Consistently,a greater fraction of memory CD8+T cells existed in Omicron stimulated peripheral blood mononuclear cells(PBMCs).In addition,CD147 was also a receptor for the Omicron variants,and CD147 antibody inhibited infection of Omicron.CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia.Taken together,our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.

A review on COVID-19 transmission,epidemiological features,prevention and vaccination

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused hundreds of millions of infections and millions of deaths over past two years.Currently,many countries have still not been able to take the pandemic under control.In this review,we systematically summarized what we have done to mitigate the COVID-19 pandemic,from the perspectives of virus transmission,public health control measures,to the development and vaccination of COVID-19 vaccines.As a virus most likely coming from bats,the SARS-CoV-2 may transmit among people via airborne,faecal-oral,vertical or foodborne routes.Ourmeta-analysis suggested that the R0 of COVID-19 was 2.9(95%CI:2.7–3.1),and the estimates in Africa and Europe could be higher.The median Rt could decrease by 23–96%following the nonpharmacological interventions,including lockdown,isolation,social distance,and face mask,etc.Comprehensive intervention and lockdown were the most effective measures to control the pandemic.According to the pooled R0 in our meta-analysis,there should be at least 93.3%(95%CI:89.9–96.2%)people being vaccinated around the world.Limited amount of vaccines and the inequity issues in vaccine allocation call for more international cooperation to achieve the antiepidemic goals and vaccination fairness.

Genome-wide meta-analysis identifies ten new psoriasis susceptibility loci in the Chinese population

Psoriasis is caused by many factors and is characterized by excessive proliferation of the epidermis and erythema with silver scales on the surface of the skin and concomitant with a variety of diseases(Griffiths et al., 2021). Despite the unclear aetiology,increasing evidence has demonstrated that genetic factors play key roles in the pathogenesis of psoriasis.