Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke / 神经科学通报·英文版

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

Epitope-resolved serology test differentiates the clinical outcome of COVID-19 and identifies defects in antibody response in SARS-CoV-2 variants

BACKGROUNDThe role of humoral immunity in the coronavirus disease 2019 (COVID-19) is not fully understood owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome. METHODSUsing SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution. RESULTSWe identified 54 linear epitopes from the Spike (S) and Nucleocapsid (N) protein and showed that epitopes enabled higher resolution antibody profiling than protein antigens. Specifically, we found that antibody responses to the S(811-825), S(881-895) and N(156-170) epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant B.1.1.7 altered the specificity of the corresponding epitopes. CONCLUSIONSEpitope-resolved antibody testing not only offers a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, it may also be used as predictor of clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants in both the peptide array and latex agglutination formats. FUNDINGOntario Research Fund (ORF)-COVID-19 Rapid Research Fund, the Toronto COVID-19 Action Fund, Western University, the Lawson Health Research Institute, the London Health Sciences Foundation, and the AMOSO Innovation Fund.

Research on the Anxious and Despondent Emotion in Patients with Chronic Eczema / 天津医药

Objective:To investigate the anxious and despondent emotion in patients suffering from chronic eczema,and its influence factor thereof.Methods:The patients suffering from chronic eczema were investigated with self-rating anxiety scale(SAS),self-rating depression scale(SDS)and evsenck personality questionnaire(EPQ).The healthy persons were investigated with SAS and SDS.The severity of pruritus and skin rash in patients suffering from chronic eczema was assessed by visual analogue scale (VAS)and eczema area severity index (EASI).Results:The scores of SAS and SDS were significantly higher in patients with chronic eczema than that of healthy persons(P＜0.01).The multivariate stepwise regression analysis result demonstrated that the factors influencing anxious emotion were in turn severity of pruritus,disease position and stability of emotion introverted-extroverted disposition.The factors influencing despondent emotion were in turn disease position,course of disease,concealing,stability of emotion and severity of pruritus.Conclusion:There was obvious anxious and despondent emotion in patients with chronic eczema.These emotions were closely correlated with psychosocial factors,severity of pruritus and skin rash.