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Abstract Background Our previous study found that mouse embryonic neural stem cell (NSC)–derived exosomes (EXOs) regulated NSC differentiation via the miR‐9/Hes1 axis. However, the effects of EXOs on brain microvascular endothelial cell (BMEC) dysfunction via the miR‐9/Hes1 axis remain unknown. Therefore, the current study aimed to determine the effects of EXOs on BMEC proliferation, migration, and death via the miR‐9/Hes1 axis. Methods Immunofluorescence, quantitative real‐time polymerase chain reaction, cell counting kit‐8 assay, wound healing assay, calcein‐acetoxymethyl/propidium iodide staining, and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs. Results EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. The overexpression of miR‐9 promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. Moreover, miR‐9 downregulation inhibited BMEC proliferation and migration and also promoted cell death. Hes1 silencing ameliorated the effect of amtagomiR‐9 on BMEC proliferation and migration and cell death. Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia‐induced mice. Meanwhile, EXO treatment improved cerebrovascular alterations. Conclusion NSC‐derived EXOs can promote BMEC proliferation and migration and reduce cell death via the miR‐9/Hes1 axis under hypoxic conditions. Therefore, EXO therapeutic strategies could be considered for hypoxia‐induced vascular injury.

Abstract Background Anticipated HIV stigma among men who have sex with men's (MSM) has a severe negative effect on their physical and mental health wellbeing and hence requires specific attention. The current study aims to identify the characteristics and the psychosocial influencing factors of anticipated HIV stigma in MSM using regression mixture model (RMM) and to determine the cut‐off point of the seven‐item Anticipated HIV Stigma Questionnaire (AHSQ) using the receiver operating characteristic (ROC) analysis. Methods A cross‐sectional study was conducted among HIV‐negative/unknown MSM from Blued online platform in China from December 16th, 2020 to March 1st, 2021, enrolling 1394 participants. Data were collected on demographic characteristics, perceived social support, anticipated HIV stigma, depressive symptoms, and HIV knowledge. Latent profile analysis was performed to identify different profiles of anticipated HIV stigma level. Chi‐square test, analysis of variance, and RMM analysis were conducted to explore the influencing factors in different profiles. ROC analyses were carried out to identify the cut‐off value of anticipated stigma. Results Among the participants, three profiles of anticipated stigma were identified: “low anticipated HIV stigma” (12.0%), “moderate anticipated HIV stigma” (52.1%), and “severe anticipated HIV stigma” (35.9%). RMM analysis showed that higher income and higher levels of knowledge were positively associated with moderate anticipated HIV stigma, whereas full‐time job and social support were negatively associated with moderate anticipated HIV stigma; higher income, depressive symptoms, and knowledge were positively associated with severe anticipated HIV stigma, whereas minor ethnicity and social support were negatively associated with severe anticipated HIV stigma. ROC curve of the AHSQ showed that the optimal cut‐off value of ≥16 could indicate positive anticipated HIV stigma. Conclusion The study focuses on the level of anticipated HIV stigma and its psycho‐socio influencing factors among HIV‐negative/unknown MSM. It provides evidence for implementing relevant psychological interventions to HIV‐negative/unknown MSM.

Abstract Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

Background Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. Methods and Results Deep RNA sequencing and quantitative real‐time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P

Abstract Objective To investigate the prevalence of depressive symptoms among human immunodeficiency virus (HIV)‐negative/unknown men who have sex with men (MSM) in China and explore the relationship between perceived social support, anticipated HIV stigma, and depressive symptoms. Methods Participants in this study were recruited from a gay social networking app (Blued) in China by convenience sampling from December 16, 2020 to March 1, 2021. Perceived Social Support Questionnaire, Anticipated HIV Stigma Questionnaire, and Center for Epidemiologic Studies Depression Scale were used to measure the social support, anticipated HIV stigma, and depressive symptoms of participants. Confirmatory factor analysis was performed to assess the reliability and validity of the measurement model. Structural equation modeling was employed to evaluate the association of perceived social support, anticipated HIV stigma, and depressive symptoms, as well as the mediation effects. Results Overall, 47.70% (665/1394) of the participants had depressive symptoms. Perceived social support could have both direct and indirect effects on depressive symptoms with the mediating role of anticipated HIV stigma among HIV‐negative/unknown MSM. Conclusion Tailored interventions regarding perceived social support and anticipated HIV stigma, such as group therapy, mutual support groups and mindfulness training, with the involvement of non‐governmental or governmental organizations, should be taken into account to reduce depressive symptoms and stigma among HIV‐negative/unknown MSM in China.

Abstract The mitochondrion is an important signaling hub that governs diverse cellular functions, including metabolism, energy production, and immunity. Among the hundreds of effectors translocated into host cells by the Dot/Icm system of Legionella pneumophila, several are targeted to mitochondria but the function of most of them remains elusive. Our recent study found that the effector Ceg3 inhibits the activity of ADP/ATP translocases (ANTs) by ADP‐ribosylation (ADPR). Here, we show that the effect of Ceg3 is antagonized by Larg1, an effector encoded by lpg0081, a gene that is situated next to ceg3. Larg1 functions to reverse Ceg3‐mediated ADPR of ANTs by cleaving the N‐glycosidic bond between the ADPR moiety and the modified arginine residues in ANTs, leading to restoration of their activity in ADP/ATP exchange. Structural analysis of Larg1 and its complex with ADPR reveals that this ADPR glycohydrolase harbors a unique macrodomain that catalyzes the removal of ADPR modification on ANTs. Our results also demonstrate that together with Ceg3, Larg1 imposes temporal regulation of the activity of ANTs by reversible ADPR during L. pneumophila infection.

Abstract The Legionella pneumophila effector MavC is a transglutaminase that carries out atypical ubiquitination of the host ubiquitin (Ub)‐conjugation enzyme UBE2N by catalyzing the formation of an isopeptide bond between Gln40Ub and Lys92UBE2N, which leads to inhibition of signaling in the NF‐κB pathway. In the absence of UBE2N, MavC deamidates Ub at Gln40 or catalyzes self‐ubiquitination. However, the mechanisms underlying these enzymatic activities of MavC are poorly understood at the molecular level. This study reports the structure of the MavC–UBE2N–Ub ternary complex representing a snapshot of MavC‐catalyzed crosslinking of UBE2N and Ub, which reveals the way by which UBE2N–Ub binds to the Insertion and Tail domains of MavC. Based on the structural and experimental data, the catalytic mechanism for the deamidase and transglutaminase activities of MavC is proposed. Finally, by comparing the structures of MavC and MvcA, the homologous protein that reverses MavC‐induced UBE2N ubiquitination, several essential regions and two key residues (Trp255MavC and Phe268MvcA) responsible for their respective enzymatic activities are identified. The results provide insights into the mechanisms for substrate recognition and ubiquitination mediated by MavC as well as explanations for the opposite activity of MavC and MvcA in terms of regulation of UBE2N ubiquitination.