Influence of edaravone on growth arrest and DNA damage-inducible protein 34 expression following focal cerebral ischemia-reperfusion in rats

Objective:To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34(GADD34).Methods:A total of 108 healthy male Sprague-Dawlcy rats were randomly divided into sham operation group,model group and edaravone.group(36 cases for each group).Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawlev rats.Then.GAOD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats.Results:The GADD34 expression was detected in the peri-infaret regions of rats 1 h after reperfusion,which reached its peak 24 h after reperfusion.And edaravone could significantly down-regulate the GAOD34 expression.Conclusions:Edaravon could down-regulate GADD34 expression,which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

Specific pupylation as IDEntity reporter(SPIDER)for the identification of protein-biomolecule interactions

Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are available,highly robust and reliable methods are always desired.By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin(SA)-biotin system,we developed the Specific Pupylation as IDEntity Reporter(SPIDER)method for identifying protein-biomolecule interactions.Using SPIDER,we validated the interactions between the known binding proteins of protein,DNA,RNA,and small molecule.We successfully applied SPIDER to construct the global protein interactome for m^(6)A and m RNA,identified a variety of uncharacterized m^(6)A binding proteins,and validated SRSF7 as a potential m^(6)A reader.We globally identified the binding proteins for lenalidomide and Cob B.Moreover,we identified SARS-CoV-2-specific receptors on the cell membrane.Overall,SPIDER is powerful and highly accessible for the study of proteinbiomolecule interactions.

Venous Sinus Dysplasia Masking the Diagnosis of Cryptococcal Meningitis

To the Editor:On November 12,2015,a 63-year-old woman was referred to a local hospital with a 2-week history of headache and vomiting.She described her headache as generalized and without photophobia or any other visual abnormalities.She was afebrile over the course of the disease.An examination of the cerebrospinal fluid (CSF) was performed 2 days after admission and revealed a white blood cell (WBC) count of 3.8 × 107 cells/L,intracranial pressure of 30 cmH2O (1 cmH2O =0.098 kPa),normal biochemistry,andabsence of Cryptococcus.

COVID-ONE-hi:The One-stop Database for COVID-19-specific Humoral Immunity and Clinical Parameters

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the“START”button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

Systematic evaluation of IgG responses to SARS-CoV-2 spike protein-derived peptides for monitoring COVID-19 patients

Serological tests play an essential role in monitoring and combating the COVID-19 pandemic.Recombinant spike protein(S protein),especially the S1 protein,is one of the major reagents used for serological tests.However,the high cost of S protein production and possible cross-reactivity with other human coronaviruses pose unavoidable challenges.By taking advantage of a peptide microarray with full spike protein coverage,we analyzed 2,434 sera from 858 COVID-19 patients,63 asymptomatic patients and 610 controls collected from multiple clinical centers.Based on the results,we identified several S protein-derived 12-mer peptides that have high diagnostic performance.In particular,for monitoring the IgG response,one peptide(aa 1148-1159 or S2-78)exhibited a sensitivity(95.5%,95%CI 93.7-96.9%)and specificity(96.7%,95%CI 94.8-98.0%)comparable to those of the S1 protein for the detection of both symptomatic and asymptomatic COVID-19 cases.Furthermore,the diagnostic performance of the S2-78(aa 1148-1159)IgG was successfully validated by ELISA in an independent sample cohort.A panel of four peptides,S1-93(aa 553-564),S1-97(aa 577-588),S1-101(aa 601-612)and S1-105(aa 625-636),that likely will avoid potential cross-reactivity with sera from patients infected by other coronaviruses was constructed.The peptides identified in this study may be applied independently or in combination with the S1 protein for accurate,affordable,and accessible COVID-19 diagnosis.

GCH1 variants contribute to the risk and earlier age-at-onset of Parkinson's disease:a two-cohort case-control study

Background:Common and rare variants of guanosine triphosphate cyclohydrolase 1(GCH1)gene may play important roles in Parkinson's disease(PD).However,there is a lack of comprehensive analysis of GCH1 genotypes,especially in non-coding regions.The aim of this study was to explore the genetic characteristics of GCH1,including rare and common variants in coding and non-coding regions,in a large population of PD patients in Chinese mainland,as well as the phenotypic characteristics of GCH1 variant carriers.Methods:In the first cohort of this case-control study,we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls;then in the second cohort,whole-genome sequencing was performed in sporadic late-onset PD samples(1962 patients),as well as 1279 controls.Variants at target GCH1 regions were extracted,and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test.We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset(AAO)in PD patients.Results:For coding variants,we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls(1.2%VS 0.1%,P<0.0001).In the analysis of possible regulatory variants in GCH1 non-coding regions,rs12323905(P=0.001,odds ratio=1.19,95%CI 1.07-1.32)was significantly associated with PD,and variant sets in untranslated regions and intron regions,GCH1 brain-specific expression quantitative trait loci,and two possible promoter/enhancer(GH14J054857 and GH14J054880)were suggestively associated with PD.Genotype phenotype correlation analysis revealed that the carriers of GCH1 deleterious variants manifested younger AAO(P<0.0001),and had milder motor symptoms,milder fatigue symptoms and more autonomic nervous dysfunctions.Meta-analysis of six studies demonstrated 6.4-year earlier onset in GCH1 deleterious variant carriers(P=0.0009).Conclusions:The results highlight the importance of deleterious variants and non-coding variants of GCH1 in PD in Chinese mainland and suggest that GCH1 mutation can influence the PD phenotype,which may help design experimental studies to elucidate the mechanisms of GCH1 in the pathogenesis of PD.

Systematic profiling of SARS-CoV-2-specific IgG epitopes at amino acid resolution

There is a worldwide pandemic of COVID-19 caused by SARS-CoV-2.1 By January 28,2021,more than 100 million cases had been diagnosed,and more than 2 million deaths had been reported(https://coronavirus.jhu.edu/map.html).The comprehensive and in-depth elucidation of SARS-CoV-2-specific IgG responses will help us to better understand COVID-19 immunity and facilitate the precise development of neutralizing antibodies and vaccines.