Comparison of the replication and neutralization of different SARS-CoV-2 Omicron subvariants in vitro

Background:New Omicron subvariants are emerging rapidly from BA.1 to BA.4 and BA.5.Their pathogenicity has changed from that of wild-type(WH-09)and Omicron variants have over time become globally dominant.The spike proteins of BA.4 and BA.5 that serve as the target for vaccine-induced neutralizing antibodies have also changed compared to the previous subvariants,which is likely to cause immune es-cape and the reduction of the protective effect of the vaccine.Our study addresses the above issues and provides a basis for formulating relevant prevention and control strategies.Methods:We collected cellular supernatant and cell lysates and measured the viral titers,viral RNA loads,and E subgenomic RNA(E sgRNA)loads in different Omicron subvariants grown in Vero E6 cells,using WH-09 and Delta variants as a reference.Additionally,we evaluated the in vitro neutralizing activity of different Omicron sub-variants and compared it to the WH-09 and Delta variants using macaque sera with different types of immunity.Results:As the SARS-CoV-2 evolved into Omicron BA.1,the replication ability in vitro began to decrease.Then with the emergence of new subvariants,the replication ability gradually recovered and became stable in the BA.4 and BA.5 subvariants.In WH-09-inactivated vaccine sera,geometric mean titers of neutralization antibodies against different Omicron subvariants declined by 3.7~15.4-fold compared to those against WH-09.In Delta-inactivated vaccine sera,geometric mean titers of neutrali-zation antibodies against Omicron subvariants declined by 3.1~7.4-fold compared to those against Delta.Conclusion:According to the findings of this research,the replication efficiency of all Omicron subvariants declined compared with WH-09 and Delta variants,and was lower in BA.1 than in other Omicron subvariants.After two doses of inactivated(WH-09 or Delta)vaccine,cross-neutralizing activities against various Omicron subvariants were seen despite a decline in neutralizing titers.

Infection with SARS-CoV-2 can cause pancreatic impairment

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes.Herein,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients.Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans.Minor and limited phenotypic and histopathological changes were observed in adult models.Systemic proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio levels.Furthermore,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic dysfunction.In contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

Polydopamine/Imogolite Nanotubes(PDA/INTs)Interlayer Modulated Thin Film Composite Forward Osmosis Membrane for Minimizing Internal Concentration Polarization

Forward osmosis(FO)as an energy-saving membrane process has attracted much attention in food concentration,water treatment,and desalination.Thin film composite(TFC)membrane is the most popular FO membrane,but it suffers from the internal concentration polarization(ICP),which significantly limits the water flux and FO efficiency.In this report,we demonstrate a novel and high-performing thin film nanocomposite(TFN)membrane that employs a hydrophilic interlayer composed of imogolite nanotubes(INTs)and polydopamine(PDA).The INTs can be adhered to the porous substrate by the self-polymerization of PDA,and the as-prepared PDA/INTs interlayer displays a nanostructured network with outstanding hydrophilicity.The detailed investigation was conducted to understand the relationship between the structure and property of the PDA/INTs interlayer and the morphology and performance of the TFN membrane.The TFN membrane with the PDA/INTs interlayer performs a thinner and smoother polyamide selective layer.Correspondingly,the TFN membrane shows a water flux of 18.38 L·m^(-2)·h^(-1),which is 2.18 times of the pristine TFC membrane.Moreover,the TFN membrane has a minimized structural parameter(577μm),almost a half of that of the pristine one(949μm).It reveals that the ICP effect of TFC membrane can be effectively alleviated by using a hydrophilic PDA/INTs interlayer.This TFN membrane with a satisfactory water permeability is promising in terms of future applications.

Optical Trapping of a Single Molecule of Length Sub-1 nm in Solution

Plasmonic optical manipulation has emerged as an affordable alternative to manipulate single chemical and biological molecules in nanoscience.Although the theoretical models of sub-5 nm single-molecule trapping have been considered promising,the experimental strategies remain a challenge due to the Brownian motions and weak optical gradient forces with significantly reduced molecular polarizability.Herein,we address direct trapping and in situ sensing of single molecules with unprecedented size,down to∼5Åin solution,by employing an adjustable plasmonic optical nanogap and single-molecule conductance measurement.The theoretical simulations demonstrate that local fields with a high enhancement factor,over 103,were generated at such small nanogaps,resulting in optical forces as large as several piconewtons to suppress the Brownian motion and trap a molecule of length sub-1 nm.This work demonstrates a strategy for directly manipulating the small molecule units,promising a vast multitude of applications in chemical,biological,and materials sciences at the single-molecule level.

基于呼吸图法的环氧树脂基超滑液体灌注防冰涂层

通过呼吸图法构筑了多孔环氧树脂基底,并在此基础上通过聚二甲基硅氧烷改性以及二甲基硅油润滑液灌注制备了具有优异润滑性的液体灌注涂层.实验结果表明,基底表面孔径及孔隙率随着环境湿度增大而增大,且涂层在不同金属基底上都有良好的黏附性能.基于上述基底所制备的液体灌注涂层具有较低的滚动角(2°),且对多种液体具有良好的滑动性.该涂层被用于冰黏附的防治,展现出较低的冰黏附强度(175 kPa)及较长的延迟结冰时间(>600 s),表明其具有优异的防冰性能.

Integrated histopathological,lipidomic,and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is transmitted on mink farms between minks and humans in many countries.However,the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown.Here,we demonstrated that minks were largely permissive to SARS-CoV-2,characterized by severe and diffuse alveolar damage,and lasted at least 14 days post inoculation(dpi).We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular,hepatobiliary,urinary,endocrine,digestive,and immune systems.The viral protein partially co-localized with activated Mac-2+macrophages throughout the body.Moreover,we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks,especially at 6 dpi,and were similar to that of patients with severe and fatal COVID-19.Particularly,altered metabolic pathways,abnormal digestion,and absorption of vitamins,lipids,cholesterol,steroids,amino acids,and proteins,consistent with hepatic dysfunction,highlight metabolic and immune dysregulation.Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation.Melatonin,which has significant anti-inflammatory and immunomodulating effects,was significantly downregulated at 6 dpi and displayed potential as a targeted medicine.Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients,delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies,vaccine research,and potential biomarkers.