Oxidized low-density lipoprotein (oxLDL)-induced injury and apoptosis of endothelial cells are important initial events in numerous cardiovascular diseases. Following activation by oxLDL, monocytes adhere to endothelial cells, migrate into the subendothelial spaces and then undergo differentiation into macrophages, which subsequently induces the formation of atherosclerotic lesions. However, the mechanisms underlying the activation of macrophage differentiation by oxLDL-treated endothelial cells remain unclear. In the present study, it was demonstrated that exosomal metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was increased in oxLDL-treated human umbilical vein endothelial cells. When co-cultured with monocytes, exosomes extracted from oxLDL-treated HUVECs were endocytosed. Furthermore, exosomes derived from oxLDL-treated endothelial cells were revealed to promote M2 macrophage polarization, as reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA analyses demonstrated increases in the expression of M2 macrophage markers, including macrophage mannose receptor 1 (also termed CD206), arginase-1 and interleukin (IL)-10, and decreases in the expression of the M1 macrophage marker, IL-12. Furthermore, the suppression of MALAT1 expression in monocytes was demonstrated to reverse exosome-mediated M2 macrophage polarization. In conclusion, the results of the present study revealed a novel mechanism underlying the onset of atherogenesis associated with endothelial cells and macrophages: Exosomal MALAT1 derived from oxLDL-treated endothelial cells promoted M2 macrophage polarization. This result may provide a novel scientific basis for the understanding of atherosclerosis progression.

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The transition from meiotic spermatocytes to postmeiotic haploid germ cells constitutes an essential step in spermatogenesis. The epigenomic regulatory mechanisms underlying this transition remain unclear. Here, we find a prominent transcriptomic switch from the late spermatocytes to the early round spermatids during the meiotic-to-postmeiotic transition, which is associated with robust histone acetylation changes across the genome. Among histone deacetylases (HDACs) and acetyltransferases, we find that HDAC3 is selectively expressed in the late meiotic and early haploid stages. Three independent mouse lines with the testis-specific knockout of HDAC3 show infertility and defects in meiotic exit with an arrest at the late stage of meiosis or early stage of round spermatids. Stage-specific RNA-seq and histone acetylation ChIP-seq analyses reveal that HDAC3 represses meiotic/spermatogonial genes and activates postmeiotic haploid gene programs during meiotic exit, with associated histone acetylation alterations. Unexpectedly, abolishing HDAC3 catalytic activity by missense mutations in the nuclear receptor corepressor (NCOR or SMRT) does not cause infertility, despite causing histone hyperacetylation as HDAC3 knockout, demonstrating that HDAC3 enzyme activity is not required for spermatogenesis. Motif analysis of the HDAC3 cistrome in the testes identified SOX30, which has a similar spatiotemporal expression pattern as HDAC3 during spermatogenesis. Depletion of SOX30 in the testes abolishes the genomic recruitment of the HDAC3 to the binding sites. Collectively, these results establish the SOX30/HDAC3 signaling as a key regulator of the transcriptional program in a deacetylase-independent manner during the meiotic-to-postmeiotic transition in spermatogenesis.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has tested the ability of universities to provide a high-quality, safe educational experience for students due to campuses shutting down. As a result, online learning could shift from a traditional classroom teaching mode and make education accessible to students. Previous studies have used individual online teaching cases to exploit a variety of online learning tools to ensure the continuation of medical education during this difficult time in China. However, for the first time, we have conducted a systematic review of local online teaching approaches, existing challenges, and potential solutions.Purpose: We present the issues and experience of conducting online medical teaching practices in China with the aim of communicating them to our peers in other countries or regions when examining the transition to e-learning during the COVID-19 pandemic and beyond.Methods: We searched the keywords below from public databases and reviewed relevant publications reporting on medical online teaching in China during the COVID-19 pandemic to analyze and summarize the online tools, modalities, and challenges.Results: We listed common online teaching tools and described a variety of online teaching modalities, as well as possible challenges. We also discussed potential solutions for those challenges, as well as the impact of the transition to online teaching on traditional education.Conclusion: By investigating local online medical teaching in China, we present useful tools and modalities that have been successfully exploited in education during the difficult time of COVID-19, although some challenges remain. The exploration of the transition to online teaching or learning will likely continue to have a profound impact on traditional classroom teaching.

Background: High on-treatment platelet reactivity (HPR) represents a strong risk factor for thrombotic events after PCI. We aim to evaluate the efficacy and safety of individualizing intensified dual antiplatelet therapy (DAPT) in PCI-treated patients with HPR based on platelet function testing (PFT). Methods: Electronic databases were searched for randomized control trials that reported the clinical outcomes of using an intensified antiplatelet protocol with P2Y 12 receptor inhibitor comparing with standard maintenance dose of clopidogrel on the basis of platelet function testing. Clinical endpoints were assessed. Results: From 2005 to 2016, thirteen clinical studies comprising 7290 patients were included for analysis. Compared with standard antiplatelet therapy with clopidogrel, the intensified protocol based on platelet function testing was associated with a significant reduction in major adverse cardiovascular events (RR:0.55, 95% CI: 0.36-0.84, p = 0.005), cardiovascular death (RR:0.60, 95% CI: 0.38-0.96, p = 0.03), stent thrombosis (RR:0.58, 95% CI: 0.36-0.93, p = 0.02) and target vessel revascularization (RR:0.33, 95% CI: 0.14-0.76, p = 0.009). No significant difference was found in the rate of bleeding events between intensified and standard protocol. Conclusions: Compared with standard clopidogrel therapy, individualized intensified antiplatelet therapy on the basis of platelet reactivity testing reduces the incidence of cardiovascular events in patient undergoing PCI, without increasing the risk of bleeding.

This study aimed to examine clinical features, sleep, abnormal sleep-wake transition and non-sleep disturbances as well as lab tests in Chinese fatal familial insomnia (FFI) subjects. Patients with confirmed clinical and laboratory diagnosis of FFI have been retrospectively reviewed. The clinical features and the results of the complementary tests, including polysomnography (PSG), brain imaging and genetic analysis, were used. Two male and three female patients were recruited in this study. Three of the five patients had more comprehensive family medical records. The most typical clinical manifestations in all 5 patients were sleep disturbances, including insomnia, laryngeal stridor, sleep breath disturbance, and sleep-related involuntary movements. PSG of all these five cases showed reduction in total sleep time, sleep fragmentation, abnormal short non-rapid eye movement - rapid eye movement (REM) cycling, REM sleep reduction or loss, and REM sleep instruction in wakefulness. Patient 2's emission tomography scan demonstrated a reduction in glucose uptake in the left thalamus and bilateral inferior parietal lobe. In summary, Chinese FFI patients are typically characterized by organic sleep related symptoms, rapidly progressive dementia and sympathetic symptoms. We propose that structural damages in the thalamus and cortex are mostly responsible for clinical manifestations of FFI.

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Aim: Primary Sj€ ogren's syndrome (pSS) is an autoimmune disease affecting exocrine glands. Both autoreactive T cells and B cells are involved in the development of pSS, but their exact contribution to the pathogenesis is not clear. Here, we aimed to investigate the association of B-cell activating factor (BAFF) and interleukin (IL)-17A with subphenotypes of pSS.Methods: Peripheral blood samples were collected from 31 pSS patients and 28 healthy controls. The serum levels of BAFF and IL-17A were quantified by sandwich ELISA. Results:The increased circulating BAFF levels are associated with higher immunoglobulin G (IgG) levels (P = 0.0167) and anti-Ro/SS antigen A autoantibody (P = 0.032), while the elevated circulating levels of IL-17A are associated with lower C3 levels (P = 0.0213) and higher focus score of salivary gland tissue (P = 0.002). Conclusion:Our results show that BAFF and IL-17A are associated with different subphenotypes of pSS, suggesting both humoral and cellular immune response are involved in the pathogenesis of pSS.