Moreover, bacterial abundance analyses showed that genus Escherichia/Shigella was more abundant in etanercept-treated mice, and Lactobacillus, Clostridium XlVa, Tannerella were less abundant. The altered bacterial genus was correlated with TNF-α, IFN-γ, IL-6, IL-21 and IL-10. CONCLUSION Our results revealed that TNF-α antagonist treatment can reduce the abundance and diversity of gut microbiota in CIA mice. Targeted gut microbiota may be a new therapeutic strategy for the treatment of RA. © 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.Single-cell platforms provide statistically large samples of snapshot observations capable of resolving intrercellular heterogeneity. Currently, there is a growing literature on algorithms that exploit this attribute in order to infer the trajectory of biological mechanisms, such as cell proliferation and differentiation. Despite the efforts, the trajectory inference methodology has not yet been used for addressing the challenging problem of learning the dynamics of protein signaling systems. In this work, we assess this prospect by testing the performance of this class of algorithms on four proteomic temporal datasets. To evaluate the learning quality, we design new general-purpose evaluation metrics that are able to quantify performance on (i) the biological meaning of the output, (ii) the consistency of the inferred trajectory, (iii) the algorithm robustness, (iv) the correlation of the learning output with the initial dataset, and (v) the roughness of the cell parameter levels though the inferred trajectol Society for Advancement of Cytometry. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.BACKGROUND Acne vulgaris is a chronic disfiguring inflammatory disease of adolescents and adults affecting up to 90% of the population around the world. The sequence of etiopathogenesis in acne is not completely understood but involves abnormalities in sebum production, follicular plugging, proliferation of propionibacterium acnes, and chronic inflammation. AIMS This review aims to summarize the features of the topical selective RAR agonists in treating acne vulgaris with a special emphasis on the 4th generation topical retinoid trifarotene. METHODS Studies were identified by searching electronic databases (MEDLINE and PubMed) till August 2019 and reference lists of respective articles. Only articles published in English language were included. RESULTS Topical retinoids have been first line of treatment for more than 30 years now in treating mild to moderate acne vulgaris. Third generation retinoids like adapalene and tazarotene are selective RAR and γ agonists, having an additional anti-inflammatory action along with their comedolytic effects and work well in combinations with topical antibiotics, due to the stability of chemical composition. CONCLUSION Trifarotene is a new 4th generation retinoid with selective action on RAR-γ receptor alone, which is specific for skin, and it is safe for long-term maintenance therapy with good efficacy and tolerability. © 2020 Wiley Periodicals, Inc.GGGGCC repeat expansion in C9orf72 is the most common genetic cause in both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two neurodegenerative disorders in association with aging. Bidirectional repeat expansions in the noncoding region of C9orf72 have been shown to produce dipeptide repeat (DPR) proteins through repeat-associated non-ATG (RAN) translation and to reduce the expression level of the C9orf72 gene product, C9orf72 protein. Mechanisms underlying C9orf72-linked neurodegeneration include expanded RNA repeat gain of function, DPR toxicity, and C9orf72 protein loss of function. In the current study, we focus on the cellular function of C9orf72 protein. We report that C9orf72 can regulate lysosomal biogenesis and autophagy at the transcriptional level. We show that loss of C9orf72 leads to striking accumulation of lysosomes, autophagosomes, and autolysosomes in cells, which is associated with suppressed mTORC1 activity and enhanced nuclear translocation of MiT/TFE family members MITF, TFE3, and TFEB, three master regulators of lysosomal biogenesis and autophagy. We demonstrate that the DENN domain of C9orf72 specifically binds to inactive Rag GTPases, but not active Rag GTPases, thereby affecting the function of Rag/raptor/mTOR complex and mTORC1 activity. Furthermore, active Rag GTPases, but not inactive Rag GTPases or raptor rescued the impaired activity and lysosomal localization of mTORC1 in C9orf72-deficient cells. Taken together, the present study highlights a key role of C9orf72 in lysosomal and autophagosomal regulation, and demonstrates that Rag GTPases and mTORC1 are involved in C9orf72-mediated autophagy. © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.PURPOSE This prospective phase II study aimed to determine the efficacy and tolerability of sequential boost of intensity-modulated radiation therapy (IMRT) with chemotherapy for patients with inoperable esophageal squamous cell carcinoma (ESCC). METHODS Patients with histologically or cytologically proven inoperable ESCC were enrolled in this study (ChiCTR-OIC-17010485). A larger target volume for subclinical lesion was irradiated with 50 Gy, and then, a smaller target volume only including gross tumor was boosted to 66 Gy. The fraction dose was 2 Gy, and no elective node was irradiated. Concurrent and consolidation chemotherapy of fluorouracil (600 mg/m2 , days 1-3) plus cisplatin (25 mg/m2 , days 1-3) was administered every 4 weeks, for 4 cycles in total. The primary endpoint was 2-year progression-free survival (PFS). RESULTS Eighty-eight patients were enrolled in this study. The median age was 65 years (range 45-75 years), and 69 patients (78.4%) were men. With the median follow-up of 26 (range 3-95) months, the 2- and 5-year PFS were 39.3% and 36.9%, respectively, and overall survival (OS) were 57.1% and 39.2%, respectively. Tumor stage and concurrent chemotherapy were independent OS predictors. Major acute adverse events were myelosuppression and esophagitis, most of which were grades 1-2. Nine percent and 2.3% of patients had grade 3 acute esophagitis and late esophageal strictures, respectively.  https://www.selleckchem.com/Proteasome.html  CONCLUSIONS Sequential boost to 66 Gy by IMRT with chemotherapy was safe and effective for inoperable ESCC. A randomized phase III study to compare with standard dose of 50 Gy is warranted. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.