Post-traumatic osteoarthritis is a prevalent debilitating joint disease. However, there is no FDA-approved disease-modifying osteoarthritis drug currently. Gene therapy can improve disease progression but lacks an effective delivery system. Here, we constructed an oral drug delivery system by non-virus-mediated interleukin-1β (IL-1β) short hairpin RNA (shRNA) and non-pathogenic yeast to evaluate its effect on osteoarthritis therapy. After recombinant IL-1β shRNA/yeast therapy, yeast microcapsule-mediated oral delivery of IL-1β shRNA greatly reduced the IL-1β expression in intestine macrophage, bone marrow macrophage, and articular cartilage, systematically regulate the inflammatory response. The degeneration of articular cartilage was significantly inhibited in the medial femoral condyle and medial tibial plateau of the knee joint. And the expression of osteoarthritis markers Col X and MMP13 was reduced in the knee joint. Thus, yeast microcapsule-mediated oral delivery of IL-1β shRNA may serve as a novel gene therapy strategy for treating joint degeneration through immunomodulation of the mononuclear phagocyte system from the intestine to subchondral bone marrow and ultimately preserving the articular cartilage joint.VPS33B is reported to be a tumor suppressor in hepatocellular carcinoma, nasopharyngeal carcinoma, colon cancer, and lung adenocarcinoma. Here, we observed that reduced VPS33B protein level was an unfavorable factor that promoted the pathogenesis of non-small cell lung cancer (NSCLC) in clinical specimens. We achieved lentivirus-mediated stable overexpression of VPS33B in NSCLC cells. Increased VPS33B reduced cell cycle transition and cell proliferation of NSCLC cells in vivo and in vitro. Knocking down VPS33B restored cell growth. Mechanism analysis indicated that miR-192-3p was induced by VPS33B and acted as a tumor suppressor of cell growth in NSCLC. Further, c-Myc or p53 was identified as a transcription factor that bound to the miR-192-3p promoter and regulated its expression. miR-192-3p directly targeted cell cycle-promoted factor CCNB1 and suppressed NSCLC cell growth. VPS33B modulated c-Myc/p53/miR-192-3p signaling to target CCNB1 by reducing activation of the Ras/ERK pathway. Our study reveals a novel molecular basis for VPS33B as a tumor suppressor to participate in the pathogenesis of NSCLC.Circular RNA (CircRNA) is a newly identified special class of non-coding RNA (ncRNA) that plays an important regulatory role in the progression of certain diseases. Herein, our results indicate that CircMEG3 is downregulated expression and negatively correlated with the expression of telomerase-related gene Cbf5 in human liver cancer. Moreover, CircMEG3 inhibits the growth of human liver cancer stem cells in vivo and in vitro. CircMEG3 inhibits the expression of m6A methyltransferase METTL3 dependent on HULC. Moreover, CircMEG3 inhibits the expression of Cbf5, a component of telomere synthetase H/ACA ribonucleoprotein (RNP; catalyst RNA pseudouracil modification) through METTL3 dependent on HULC. Thereby, CircMEG3 inhibits telomerase activity and shortens telomere lifespan dependent on HULC and Cbf5 in human liver cancer stem cell. Strikingly, increased Cbf5 abrogates the ability of CircMEG3 to inhibit malignant differentiation of human liver cancer stem cells. In summary, these observations provide important basic information for finding effective liver cancer therapeutic targets.Clinical investigations have demonstrated that polycystic ovary syndrome (PCOS) is often accompanied by insulin resistance (IR) in more than 70% of women with PCOS. However, the etiology of PCOS with IR remains to be characterized. Growth differentiation factor 8 (GDF8) is an intraovarian factor that plays a vital role in the regulation of follicle development and ovulation. Previous studies have reported that GDF8 is a pathogenic factor in glucose metabolism disorder in IR patients. To date, the role of GDF8 on glucose metabolism of granulosa cell in PCOS patients remains to be determined. In the current study, we demonstrated that the expression and accumulation of GDF8 in human granulosa-lutein (hGL) cells and follicular fluid from PCOS patients were higher compared with those of non-PCOS women. https://www.selleckchem.com/products/ph-797804.html GDF8 treatment caused glucose metabolism defects in hGL cells. Transcriptome sequencing results showed that SERPINE1 mediated GDF8-induced impairment of hGL glucose metabolism defects. Using pharmacological and small interfering RNA (siRNA)-mediated knockdown approaches, we demonstrated that GDF8 upregulated the expression of SERPINE1 via the ALK5-mediated SMAD2/3-SMAD4 signaling pathway. Interestingly, the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway was also activated with GDF8 treatment but did not participate in the effect of GDF8 on SERPINE1 expression. Our results also showed that TP53 was required for the GDF8-stimulated increase in SERPINE1 expression. Importantly, our study demonstrated that SB-431542 treatment significantly improved DHEA-induced PCOS-like ovaries. These findings support a potential role for GDF8 in metabolic disorders in PCOS.Phylogenetic analysis is used to analyze the evolution of species according to the characteristics of biological sequences. The analytical results are generally represented by phylogenetic trees. NJ (neighbor joining) is a frequently used algorithm for constructing phylogenetic trees because of its few assumptions, fast operation, and high accuracy, and is based on the distance between taxa. It is known that NJ usually constructs different phylogenetic trees for the same dataset with differences in input order, which are known as "tied trees." This article proposes an improved method of NJ, called ENJ (extended neighbor joining). The ENJ can join several (currently limited to three) nodes with the same minimum distance into a new node, rather than joining two nodes in one iteration, so it can construct triple phylogenetic trees. We have inferred the formulas for updating the distance values and calculating the branch lengths for the ENJ algorithm. We have tested the ENJ with simulated and real data. The experimental results show that, compared with other methods, the trees constructed by the ENJ have greater similarity to the initial trees, and the ENJ is much faster than the NJ algorithm.