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MiR-92b-3p has been shown to take part in several disease by regulate proliferation, apoptosis, differentiation and metastasis. However, the role of miR-92b-3p in pulmonary arterial hypertension (PAH) has not been illustrated clearly. Here, we found the level of miR-92b-3p which mainly located in the smooth muscle layer was down-regulation under hypoxic condition. It can inhibit pulmonary artery smooth muscle cells (PASMCs) proliferation and cell cycle progression. Through luciferase assay, miR-92b-3p bound to the 3'-UTR of USP28. we found that there was a significant negative relation between the level of miR-92b-3p and USP28 at protein level and reversed the down regulation of miR-92b-3p by hypoxia can suppress the proliferation of pulmonary artery smooth muscle cells by targeting USP28. These results suggested that miR-92b-3p acted a potential proliferation regulator in PASMCs and it maybe a novel treatment target of PAH.

Background: Hepatocellular carcinoma (HCC) patients diagnosed with the same clinic stage by Barcelona Clinic Liver Cancer (BCLC) system show different prognosis due to coexistence of inflammation and tumor heterogeneity. Here, we aimed to seek for inflammation-related molecular biomarkers for accurately predicting diagnosis and prognosis of HCC. Methods: In this multicenter and retrospective analysis, we included 516 patients with HCC from three Chinese hospitals: Nanfang Hospital (Guangzhou, China), Zhujiang Hospital (Guangzhou, China) and Yuebei Hospital (Shaoguan, China). COMMD10 was screened out from inflammation-induced HCC using real-time PCR analysis. Nomogram based on COMMD10 and BCLC stage was established and validated. The predictive accuracy and discriminative ability of the nomogram was determined by concordance index and calibration curve. The primary endpoint was overall survival (OS). In vitro and in vivo assays were performed to investigate the role of COMMD10 in HCC. The potential molecular mechanisms of COMMD10 were determined by luciferase assay, immunofluorescence, immunoprecipitation. Findings: The nomogram based on COMMD10 and BCLC stage yielded more accuracy than BCLC stage alone for predicting OS of HCC patients in multicenter cohorts. COMMD10 can stratify early-stage HCC (BCLC stage 0 and A) patients into two risk groups with significantly different OS. Mechanistically, COMMD10 suppressed proliferation in vitro and in vivo by interacting with Rel homology domain of p65 and potentiating apoptosis by modulating Bcl-2/Bax/caspase-9/3 pathway in HCC. Interpretation: COMMD10 is a powerful prognostic biomarker and values up BCLC staging to predict OS for HCC, especially for identifying early-stage HCC patients who could benefit from individual therapy. Funding Statement: This work was supported by the National Natural Science Foundation of China [NO.81672992,81602685]; the Natural Science Foundation of Guangdong Province [NO. 2017A030313486]. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of Nanfang Hospital of Southern Medical University, and all participants provided written informed consent prior to surgery. It also conforms to the provisions of the Declaration of Helsinki.

Anaplasmosis, the most prevalent tick-transmitted disease of cattle, is caused by the rickettsial intracellular parasite Anaplasma marginale. The pathogen replicates within a parasitophorous vacuole formed from the invagination of the erythrocyte membrane. Several strains of A. marginale form "tails" or "appendages" which are attached to, and extend out from, the cytoplasmic side of the parasitophorous vacuole. Genomic analysis of the parasite antigen distributed along the appendage led to the discovery of the aaap (Anaplasma appendage associated protein) gene family located within a highly plastic region in the genome. The aaap gene family consists of aaap and several alps (for aaap-like proteins), depending on the strain. These genes/proteins are characterized by repeat sequences. To investigate locus plasticity, different versions of the locus were cloned from the same strain as well as from different strains, sequenced and aligned to identify changes. Our findings show that repeat sequences both within and between genes facilitated rearrangement events within the locus. Structural variation of the locus in the St. Maries strain was further investigated during infection of different cellular environments, i.e., bovine erythrocytes and tick cells, with a reduction in subpopulations of the aaap locus within the tick as compared to erythrocytes. Interestingly, subpopulations bearing alternative locus structures began to arise again when the pathogen was transferred from the tick environment into a naïve calf. Additionally, the Aaap protein expression profile between blood and tick samples showed a regulatory shift, indicating a host-specific response. Alignment of the protein sequences from different species of Anaplasma reveals six similar repeating motifs that appear to be unique to a few species of Anaplasma. The role the aaap locus may play in the pathogenesis of the bovine host or in tick infection/transmission remains unknown; however, the changes in aaap locus subpopulations, locus structure, and protein expression indicate that these genes have a role in strain diversification.