Integrin αvß1 facilitates ACE2-mediated entry of SARS-CoV-2.

Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed to investigate how integrins facilitate the ACE2-mediated cellular entry of SARS-CoV-2. We first tested the susceptibility of a panel of human cell lines to SARS-CoV-2 infection using the spike protein pseudotyped virus assay and examined the expression levels of integrins in these cell lines by qPCR, western blot and flow cytometry. We found that integrin αvß1 was highly enriched in the SARS-CoV-2 susceptible cell lines. Additional studies demonstrated that RGD (403-405)→AAA mutant was defective in binding to integrin αvß1 compared to its wild type counterpart, and anti-αvß1 integrin antibodies significantly inhibited the entry of SARS-CoV-2 into the cells. Further studies using mouse NIH3T3 cells expressing human ACE2, integrin αv, integrin ß1, and/or integrin αvß1 suggest that integrin αvß1 was unable to function as an independent receptor but could significantly facilitate the cellular entry of SASR-CoV-2. Finally, we observed that the Omicron exhibited a significant increase in the ACE2-mediated viral entry. Our findings may enhance our understanding of the pathogenesis of SARS-CoV-2 infection and offer potential therapeutic target for COVID-19.

A pangenome reference of 36 Chinese populations.

Human genomics is witnessing an ongoing paradigm shift from a single reference sequence to a pangenome form, but populations of Asian ancestry are underrepresented. Here we present data from the first phase of the Chinese Pangenome Consortium, including a collection of 116 high-quality and haplotype-phased de novo assemblies based on 58 core samples representing 36 minority Chinese ethnic groups. With an average 30.65× high-fidelity long-read sequence coverage, an average contiguity N50 of more than 35.63 megabases and an average total size of 3.01 gigabases, the CPC core assemblies add 189 million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38. We identified 15.9 million small variants and 78,072 structural variants, of which 5.9 million small variants and 34,223 structural variants were not reported in a recently released pangenome reference1. The Chinese Pangenome Consortium data demonstrate a remarkable increase in the discovery of novel and missing sequences when individuals are included from underrepresented minority ethnic groups. The missing reference sequences were enriched with archaic-derived alleles and genes that confer essential functions related to keratinization, response to ultraviolet radiation, DNA repair, immunological responses and lifespan, implying great potential for shedding new light on human evolution and recovering missing heritability in complex disease mapping.

Association between the metabolic profile of serum fatty acids and diabetic nephropathy: a study conducted in northeastern China.

Background and purpose: With the progressive increase in the prevalence of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN) - one of the most common chronic microvascular complications - has evolved into a significant cause of death worldwide among end-stage renal disease patients. Academic researchers have for decades focused on the development of DN and recently found that free fatty acids (FFAs) constituted an independent risk factor for vascular complications in T2DM patients. It is therefore critical to determine whether the metabolic profile of FFAs is related to DN. Methods: This study comprised 611 research subjects in Dalian, a city in northeast China: 52 DN patients, 115 T2DM patients, and 444 healthy controls. We determined 15 forms of serum FFAs, including arachidonic acid (AA, C20:4), docosahexaenoic acid (DHA, C22:6), erucic acid (C22:1), nervonic acid (NA, C24:1), estimated total omega-3s, total omega-6s, the omega-3/omega-6 ratio, and total FFA content by liquid chromatography-mass spectrometry (LC-MS). Results: The levels of NA (mean = 45.27, range = 0.84-76.57) and DHA (mean = 324.58, range = 205.38-450.03) in DN patients were slightly lower than those in T2DM patients or healthy controls. The serum omega-3 polyunsaturated fatty acid (PUFA) DHA (C22:6) was significantly negatively correlated with microalbuminuria (MAU), the albumin/creatinine ratio (ACR), body mass index (BMI), fasting plasma glucose (FPG), and glycosylated hemoglobin (HbA1c). The serum monounsaturated fatty acid (MUFA) NA (C24:1) was significantly negatively correlated with BMI, FPG, and HbA1c. After adjustment of variables, multiple logistic regression analysis revealed significant odds ratios (ORs) [with confidence intervals (CIs)] for DHA (0.991, 0.985-0.997; p = 0.002) and NA (0.978, 0.958-0.999; p = 0.037). Conclusion: In this study, we ascertained that the contents of NA and DHA in patients with DN were relatively low, and that DHA was negatively correlated with MAU and the ACR. However, large-scale, population-based studies focusing on the role of NA and DHA in the pathogenesis of DN are still required in the future.