Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (D500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-beta levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-beta responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.Peer reviewe

Modification effect of changes in cardiometabolic traits in association between kidney stones and cardiovascular events

BackgroundsWhether longitudinal changes in metabolic status influence the effect of kidney stones on cardiovascular disease (CVD) remains unclarified. We investigated the modification effect of status changes in metabolic syndrome (MetS) in the association of kidney stones with risk of incident CVD events.MethodsWe performed a prospective association and interaction study in a nationwide cohort including 129,172 participants aged ≥ 40 years without CVDs at baseline and followed up for an average of 3.8 years. Kidney stones information was collected by using a questionnaire and validated by medical records. The repeated biochemical measurements were performed to ascertain the metabolic status at both baseline and follow-up.Results4,017 incident total CVDs, 1,413 coronary heart diseases (CHDs) and 2,682 strokes were documented and ascertained during follow-up. Kidney stones presence was significantly associated with 44%, 70% and 31% higher risk of CVDs, CHDs and stroke, respectively. The stratified analysis showed significant associations were found in the incident and sustained MetS patients, while no significant associations were found in the non-MetS at both baseline and follow-up subjects or the MetS remission ones, especially in women. For the change status of each single component of the MetS, though the trends were not always the same, the associations with CVD were consistently significant in those with sustained metabolic disorders, except for the sustained high blood glucose group, while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups; while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups.ConclusionsA history of kidney stones in women with newly developed MetS or long-standing MetS associated with increased risk of CVD. The mechanisms link kidney stones and CVD risk in the metabolic and non-metabolic pathways were warranted for further studies

The Relative Body Weight Gain From Early to Middle Life Adulthood Associated With Later Life Risk of Diabetes: A Nationwide Cohort Study

AimTo determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk.Methods35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes.ResultsAfter 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P <0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; PInteraction=0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036).ConclusionsThe early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years

Mechanical Properties of Domestic T700 Grade Carbon Fibers/QY9611 BMI Matrix Composites

The morphologies,surface energies and surface chemical properties of the domestic T700 grade carbon fiber and the T700S carbon fiber were characterized by using scanning electronic microscopy (SEM), inverse gas chromatography(IGC) and X-ray photoelectron spectroscopy (XPS)respectively.The mechanical properties of the two carbon fibers/QY9611 composites were also discussed. The results indicate that the surface properties of carbon fibers have an important influence on the interfacial properties of composites. The interfacial properties of domestic T700 grade carbon fibers/QY9611 composite at room temperature/dry conditions are superior to T700S/QY9611 composite. The toughness of domestic T700 grade carbon fibers/QY9611composite is outstanding as well. The value of CAI has reached the level of foreign advanced composite IM7/5250-4. After hydrothermal treatment,the interfacial strength of domestic T700 grade carbon fibers/QY9611 composite is equal to that of T700S/QY9611 composite. It shows that domestic T700 grade carbon fibers/QY9611 composite has good hydrothermal-resistant properties

Interleukin-35 inhibits human umbilical vein endothelial cell injury induced by sera from pre-eclampsia patients by up-regulating S100A8 protein expression

Objectives The protective effects of interleukin(IL)-35 against injury to human umbilical vein endothelial cells (HUVECs) induced by the serum of pre-eclampsia patients were analyzed. Methods This cross-sectional study included 24 patients with pre-eclampsia (PE) and 24 normotensive pregnant women. Results Compared to normotensive pregnant women, patients with pre-eclampsia had lower IL-35 levels (P < 0.05). In addition, our in vitro experiments, IL-35 inhibited the PE serum-induced apoptosis of HUVECs and the levels of reactive oxygen species in HUVECs. Conclusion Decreases in the serum IL-35 level may play an important role in the pathogenesis of endothelial dysfunction in patients with pre-eclampsia

Magnetic and optical anisotropy in the infinite-chains iron oxide Sr

We perform first-principles calculations of electronic structure, magnetic structure and linear optical response in Sr2FeO3 based on the density functional theory (DFT) employing the generalized gradient approximation (GGA) plus on-site Coulomb repulsion method. For its special 1D Fe-O chains structure with iron square-planar coordination, the magnetic interaction and linear dielectric function show significant anisotropic behavior. In particular, giant optical anisotropy is found

Association of polymorphisms in LEPR with type 2 diabetes and related metabolic traits in a Chinese population

Abstract Background Leptin acts as a mediator of inflammation and energy homeostasis by activating leptin receptor (LEPR). We conducted this study to explore the association of polymorphisms in LEPR with type 2 diabetes mellitus (T2DM) and its related metabolic traits. Methods We performed a case–control study to investigate the association of polymorphisms in LEPR with T2DM and related metabolic traits in a Chinese population, with a total of 922 T2DM patients and 1031 nondiabetic subjects. Polymorphisms were genotyped using MassARRAY assay. Results The G allele of rs1327118 was associated with a decreased risk of T2DM in men (P = 0.044, odds ratio = 0.707, 95% confidence interval = 0.504–0.991) and the G allele of rs3806318 was associated with increased systolic blood pressure (SBP) in men with T2DM. Besides, the women patients carrying the G allele of rs1327118 showed increased SBP and diastolic blood pressure (DBP) levels, but decreased high density lipoprotein cholesterol (HDL-C) level. Conclusion Our results suggest that rs1327118 may be associated with SBP, DBP and HDL-C levels in women with T2DM, and rs3806318 may be associated with T2DM and SBP level in men with T2DM. Further studies with larger sample size or functional experiments focused on exact mechanism are required to verify our observations

High electron mobility fluorinated indacenodithiophene small molecule acceptors for organic solar cells

Indacenodithiophene (IDT) derivatives are kinds of the most representative and widely used cores of small molecule acceptors (SMAs) in organic solar cells (OSCs). Here we systematically investigate the influence of end-group fluorination density and position on the photovoltaic properties of the IDT-based SMAs IDIC-nF (n = 0, 2, 4). The absorption edge of IDIC-nF red-shifts with the pi-pi stacking and crystallinity improvement, and their electronic energy levels downshift with increasing n. Due to the advantages of J(sc) and FF as well as acceptable V-oc, the difluorinated IDIC-2F acceptor based OSCs achieve the highest power conversion efficiency (PCE) of 13%, better than the OSC devices based on IDIC and IDIC-4F as acceptors. And the photovoltaic performance of the PTQ10: IDIC-2F OSCs is insensitive to the active layer thickness: PCE still keep high values of 12.00% and 11.46% for the devices with active layer thickness of 80 and 354 nm, respectively. This work verifies that fine and delicate modulation of the SMAs molecular structure could optimize photovoltaic performance of the corresponding OSCs. Meanwhile, the thickness-insensitivity property of the OSCs has potential for large-scale and printable fabrication technology. (C) 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved

Unveiling the Selenization Reaction Mechanisms in Ambient Air-Processed Highly Efficient Kesterite Solar Cells

International audienceThe selenization annealing process is vital for highly efficient kesterite solar cells. Generally, SnS is added during the selenization process, but excessive S and related defects are introduced. Meanwhile, the path of supplementing Sn has never been elucidated. Herein, in order to solve the above problems, a combination of strategies involving SnS and Sn or SnSe or SnSe2 is put forward. And the composition of the vapor inhibiting Sn loss (gaseous SnSe3) and the pathway through which SnSe3 facilitates the formation of Cu2ZnSn(SxSe1-x)(4) (CZTSSe) are clarified. When SnSe2 is added to SnS in the selenization process, grain fusion is effectively promoted. The high crystalline quality kesterite absorber makes the band bending at the GBs optimal and the interface recombination be effectively suppressed. Moreover, cation disorder is remarkably reduced. Therefore, the open-circuit voltage (V-oc) is significantly elevated from 508 to 546 mV with increased fill factor (FF) and short-circuit current density (J(sc)). A state-of-the-art ambient air-processed kesterite device with 12.89% efficiency is achieved, and the unveiled reaction mechanisms have guiding significance for further optimizing selenization atmosphere and elevating the efficiency of CZTSSe solar cells