Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI

Background The association between perivascular space(PVS)and white matter hyperintensity(WMH)has been unclear.Normal-appearing white matter(NAWM)around WMH is also found correlated with the development of focal WMH.This study aims to investigate the topological connections among PVS,deep WMH(dWMH)and NAWM around WMH using 7 Tesla(7T)MRI.Methods Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic.We compared the PVS burden between patients with and without WMHs using a 5-point scale.Then,the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site(without WMH)in the contralateral hemisphere.In this study,we define NAWM as an area within the radius of 1 cm around each dWMH.Furthermore,we assessed the spatial relationship between dWMH and PVS.Results Higher PVS scores in the centrum semiovale were found in patients with>5 dWMHs(median 3)than subjects without dWMH(median 2,p=0.014).We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites(p<0.001,p<0.001).In addition,79.59%of the dWMHs were spatially connected with PVS.Conclusion dWMH,NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease.Future study of WMH and NAWM should not overlook MRI-visible PVS.

Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge

Coronavirus disease 2019(COviD-19)was first reported three years ago,when a group of individuals were infected with the original SARS-CoV-2 strain,based on which vaccines were developed.Here,we develop six human monoclonal antibodies(mAbs)from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain(RBD)and can inhibit the infection of SARS-CoV-2 original strain and variants of concern(VOCs)to varying degrees,including Omicron strains XBB and XBB.

Size-resolved effective density of submicron particles during summertime in the rural atmosphere of Beijing, China

Particle density is an important physical property of atmospheric particles. The information on high time-resolution size-resolved particle density is essential for understanding the atmospheric physical and chemical aging processes of aerosols particles. In the present study, a centrifugal particle mass analyzer （CPMA） combined with a differential mobility analyzer （DMA） was deployed to determine the size-resolved effective density of 50 to 350 nm particles at a rural site of Beijing during summer 2016. The measured particle effective densities decreased with increasing particle sizes and ranged from 1.43 to 1.55 g/cm3, on average. The effective particle density distributions were dominated by a mode peaked at around 1.5 g/cm3 for 50 to 350 nm particles. Extra modes with peaks at 1.0, 0.8, and 0.6 g/cm3 for 150, 240, and 350 nm particles, which might be freshly emitted soot particles, were observed during intensive primary emissions episodes. The particle effective densities showed a diurnal variation pattern, with higher values during daytime. A case study showed that the effective density of Aitken mode particles during the new particle formation （NPF） event decreased considerably, indicating the significant contribution of organics to new particle growth.

Antibody neutralization to SARS-CoV-2 and variants after 1 year in Wuhan,China

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity,but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants.Here,we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan,the earliest known epicenter.SARS-CoV-2 immunoglobulin G(IgG)was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant.However,varying degrees of immune escape was observed on the other tested variants in a patient-specific manner,with individuals showing remarkably broad neutralization potency.The immune escape can be largely attributed to several critical spike mutations.These results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation

The wide-spreading SARS-CoV-2 virus has put the world into boiling water for more than a year,however pharmacological therapies to act effectively against coronavirus disease 2019(COVID-19)remain elusive.Chloroquine(CQ),an antimalarial drug,was found to exhibit promising antiviral activity in vitro and in vivo at a high dosage,thus CQ was approved by the FDA for the emergency use authorization(EUA)in the fight against COVID-19 in the US,but later was revoked the EUA status due to the severe clinical toxicity.Herein,we show that supramolecular formulation of CQ by a macrocyclic host,curcurbit[7]uril(CB[7]),reduced its non-specific toxicity and improved its antiviral activity against coronavirus,working in synergy with CB[7].CB[7]was found to form 1:1 host-guest complexes with CQ,with a binding constant of$104 L/mol.The CQ-CB[7]formulation decreased the cytotoxicity of CQ against Vero E6 and L-02 cell lines.In particular,the cytotoxicity of CQ(60 mmol/L)against both Vero E6 cell line and L-02 cell lines was completely inhibited in the presence of 300 mmol/L and 600 mmol/L CB[7],respectively.Furthermore,the CB[7]alone showed astonishing antiviral activity in SARS-CoV-2 infected Vero E6 cells and mouse hepatitis virus strain A59(MHV-A59)infected N2 A cells,and synergistically improved the antiviral activity of CQ-CB[7],suggesting that CB[7]-based CQ formulation has a great potential as a safe and effective antiviral agent against SARS-CoV-2 and other coronavirus.