The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large ...number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.
Display omitted
•Omicron, delta, and prototype SARS-CoV-2 RBDs show similar binding strength to hACE2•The complexes of SARS-CoV-2-RBD with hACE2 for omicron and delta variants were resolved•The roles of key residues in the omicron RBD for receptor recognition were identified
Structural analysis of the complexes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RBD with the human ACE2 receptor for omicron and delta reveals variant-specific binding features.
Summary Background The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated ...glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. Methods We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m2 or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. Findings 50 550 people were invited to participate, of whom 47 204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m2 was 1·7% (95% CI 1·5–1·9) and of albuminuria was 9·4% (8·9–10·0). The overall prevalence of chronic kidney disease was 10·8% (10·2–11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9–125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9% 15·1–18·7) and southwest (18·3% 16·4–20·4) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Interpretation Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. Funding The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation.
This study was aimed at monitoring beach litter using an unmanned aerial vehicle (UAV) in the coastal city of Fuzhou, China. The data analysis shows that the optical images obtained by digital ...cameras on the UAV can help to identify and monitor beach litter using remote sensing and GIS technologies. The threshold method can effectively segment the UAV image in the beach area. It is useful for quickly monitoring the distribution of beach litter in the area of interest, and hence it can help to provide effective technical support for the investigation and assessment of coastal beach litter.
•Add knowledge to the literature on use of drones for beach litter monitoring.•Main considerations when selecting drones for aerial photography of beach litter.•Interpretation algorithm of the segmentation threshold method effectively segment the UAV image for monitoring beach litter.
Fecal microbiota transplantation (FMT) has been used successfully to treat a variety of gastroenterological diseases. The alterations of microbiota in mouse models of necrotizing enterocolitis (NEC) ...as well as in patients suggested the possibility of treating NEC with FMT. Here we show that FMT caused an improvement in the histopathology and symptoms of NEC in WT mice, but not Grx1-/- mice. FMT eliminated O2•– production and promoted NO production in experimental NEC mice though the modulation of S-glutathionylation of eNOS (eNOS-SSG). FMT decreased the extent of TLR4-mediated proinflammatory signaling though TLR9 in the intestinal mucosa tissue. FMT also suppressed intestinal apoptosis and bacterial translocation across the intestinal barrier, which was accompanied by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulated lymphocyte proportions. FMT is effective in a mouse model of NEC through the modulation of oxidative stress and reduced colon inflammation.
Display omitted
•FMT eliminate O2•– production, detected in NEC, though modulation of eNOS S-glutathionylation.•In intestinal tissue, FMT suppress the TLR4-mediated proinflammatory signaling, though TLR9.•The intestinal apoptosis suppression by FMT was followed with anti-inflammatory effect of TLR9.
Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic ...susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.
Background
Non‐small‐cell lung cancer (NSCLC) is the most lethal type of cancer. Long non‐coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as crucial regulators in the development of ...NSCLC. The aim of our study was to explore the molecular mechanism of SNHG1 to enable better treatment for NSCLC patients.
Methods
Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to detect the expression of Small nucleolar RNA host gene 1 (SNHG1), miR‐361‐3p and frequently rearranged in advanced T‐cell lymphomas 1 (FRAT1). The protein level of FRAT1 was measured by western blot assay. Cell proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis was assessed by flow cytometry assay. The number of migrated and invaded cells were counted by transwell assay. The relationship between miR‐361‐3p and SNHG1 or FRAT1 was confirmed by dual‐luciferase reporter assay.
Results
Our results indicated that SNHG1 and FRAT1 were highly expressed in NSCLC tissues and cells. SNHG1 silencing inhibited proliferation, induced apoptosis and blocked migration and invasion of NSCLC cells. Also, FRAT1 downregulation suppressed proliferation, promoted apoptosis and hindered migration and invasion of NSCLC cells. Further, FRAT1 could recover the effects of SNHG1 silencing on proliferation, apoptosis, migration and invasion of NSCLC cells. SNHG1 sponged miR‐361‐3p and negatively regulated miR‐361‐3p expression. Meanwhile, miR‐361‐3p targeted FRAT1 and inversely modulated FRAT1 expression. In addition, miR‐361‐3p inhibition abated the effect of SNHG1 knockdown on FRAT1 expression.
Conclusion
In conclusion, LncRNA SNHG1 promoted the proliferation, repressed apoptosis and enhanced migration and invasion of NSCLC cells by regulating FRAT1 expression via sponging miR‐361‐3p.
•We study the sedimentary effects of eolian-fluvial interactions.•We focus on the spatial variability of the physicochemical characteristics of the sediments.•The interaction of wind and water ...enhanced sediment mixing.•The sand sources of the study area are mainly local.
Eolian-fluvial interactions are a common geomorphic phenomenon and Earth surface process in arid regions. We selected the “Three Rivers and One Dune” region, in the Kuye River Basin, in the northeastern Mu Us Sandy Land in Northern China, for a study of eolian-fluvial interactions, based on a geomorphological survey and analysis of the grain size and chemical element contents of surface sediments. The results showed that the interactions of wind and water flow enhanced have caused the mixing of the surface sediments, which is reflected by the spatial heterogeneity of their physicochemical properties, which are different from those of the local parent rock and local sandy environments. In detail, the variations of the chemical weathering-related indicators, including the CIA, CIW, CPA, Na/K and Rb/Sr, along four transects all indicated that the degree of chemical weathering was generally low in the region (CIA < 50), implying that the materials are unweathered or in an incipient chemical weathering state. Combined with the grain size results, in the upper reaches (transect KYH-1) the mean grain size was coarser, the degree of sorting was lower, and there was a lower degree of chemical weathering. Transect KYH-4, located in the most southeasterly part of the study area, has the lowest mean grain size and is relatively well sorted; hence, it has undergone a greater degree of chemical weathering. Transects KYH-2, KYH-3 and KYH-4 span the “Three Rivers”, and their sediments are relatively well mixed and heavily influenced by locally-derived materials. The differences in physicochemical properties between the transects can be attributed to the diversity of slope directions and of the angles between the wind direction and the river flow. Overall, our results, combined with regional comparisons, indicate that the sand sources of the dunes in the study area are mainly locally derived.
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and inflammation. Patients often have dry mouth and dry eye symptoms, which seriously ...affect their lives. Improving dry mouth and eye symptoms has become a common demand from patients. For this reason, researchers have conducted many studies on external secretory glands. In this paper, we summarize recent studies on the salivary glands of pSS patients from the perspective of the immune microenvironment. These studies showed that hypoxia, senescence, and chronic inflammation are the essential characteristics of the salivary gland immune microenvironment. In the SG of pSS, genes related to lymphocyte chemotaxis, antigen presentation, and lymphocyte activation are upregulated. Interferon (IFN)-related genes, DNA methylation, sRNA downregulation, and mitochondrial-related differentially expressed genes are also involved in forming the immune microenvironment of pSS, while multiple signaling pathways are involved in regulation. We further elucidated the regulation of the salivary gland immune microenvironment in pSS and relevant, targeted treatments.
Although many psychological factors have been associated with health-related quality of life (HRQoL), the mediator role of resilience between psychological predictors (i.e., coping styles and ...perceived social support) and HRQoL has rarely been explored in breast cancer survivors (BCSs).
A total of 231 BCSs participated in this cross-sectional survey. Pearson correlation was performed to analyze the relationships among coping styles (confrontation, avoidance, and resignation), perceived social support, resilience, and HRQoL. A multivariate linear regression analysis was applied to identify the psychological predictors of HRQoL and resilience, respectively. A structural equation modeling (SEM) was employed to examine the mediating role of resilience between coping styles, perceived social support, and HRQoL.
Perceived social support and resilience were positively associated with confrontation. Resilience was positively associated with perceived social support. HRQoL had positive correlations with confrontation/avoidance, perceived social support, and resilience. Resilience and resignation/avoidance were significant independent predictors of HRQoL, while resignation/confrontation and perceived social support were significant independent predictors of resilience. Confrontation/resignation, perceived social support, and resilience had significant direct effects on HRQoL; confrontation/resignation and perceived social support had significant direct effects on resilience; resilience had significant mediator roles between confrontation/resignation, perceived social support, and HRQoL.
Resilience was a significant mediator between coping styles, perceived social support, and HRQoL. A resilience-oriented intervention is recommended to alleviate the detrimental influences of low resilience on HRQoL, providing a new strategy for improving the health status of BCSs.
PDF
