Chromosomal translocations constitute driver mutations in solid tumors and leukemias. The mechanisms of how related or even identical gene fusions drive the pathogenesis of various tumor types remain elusive. One remarkable example is the presence of EWSR1 fusions with CREB1 and ATF1, members of the CREB family of transcription factors, in a variety of sarcomas, carcinomas and mesotheliomas. To address this, we have developed in vitro models of oncogenic fusions, in particular, EWSR1-CREB1 and EWSR1-ATF1, in human embryonic stem (hES) cells, which are capable of multipotent differentiation, using CRISPR-Cas9 technology and HDR together with conditional fusion gene expression that allows investigation into the early steps of cellular transformation. We show that expression of EWSR1-CREB1/ATF1 fusion in hES cells recapitulates the core gene signatures, respectively, of angiomatoid fibrous histiocytoma (AFH) and gastrointestinal clear cell sarcoma (GI-CCS), although both fusions lead to cell lethality. Conversely, expression of the fusions in hES cells differentiated to mesenchymal progenitors is compatible with prolonged viability while maintaining the core gene signatures. Moreover, in the context of a mesenchymal lineage, the proliferation of cells expressing the EWSR1-CREB1 fusion is further extended by deletion of the tumor suppressor TP53. We expect the generation of isogenic lines carrying oncogenic fusions in various cell lineages to expand our general understanding of how those single genetic events drive tumorigenesis while providing valuable resources for drug discovery.Colorectal cancer (CRC) cells have low or absent tumor cell PD-L1 expression that we previously demonstrated can confer chemotherapy resistance. Here, we demonstrate that PD-L1 depletion enhances JNK activity resulting in increased BimThr116 phosphorylation and its sequestration by MCL-1 and BCL-2. Activated JNK signaling in PD-L1-depeted cells was due to reduced mRNA stability of the CYLD deubiquitinase. PD-L1 was found to compete with the ribonuclease EXOSC10 for binding to CYLD mRNA. Thus, loss of PD-L1 promoted binding and degradation of CYLD mRNA by EXOSC10 which enhanced JNK activity. An irreversible JNK inhibitor (JNK-IN-8) reduced BimThr116 phosphorylation and unsequestered Bim from MCL-1 and BCL-2 to promote apoptosis. In cells lacking PD-L1, treatment with JNK-IN-8, an MCL-1 antagonist (AZD5991), or their combination promoted apoptosis and reduced long-term clonogenic survival by anticancer drugs. Similar effects of the JNK inhibitor on cell viability were observed in CRC organoids with suppression of PD-L1. These data indicate that JNK inhibition may represent a promising strategy to overcome drug resistance in CRC cells with low or absent PD-L1 expression.Mycobacterium tuberculosis (Mtb) has different features depending on different geographic areas. We collected Mtb strains from patients with smear-positive pulmonary tuberculosis in Da Nang, central Vietnam. Using a whole genome sequencing platform, including genome assembly complemented by long-read-sequencing data, genomic characteristics were studied. Of 181 Mtb isolates, predominant Vietnamese EAI4_VNM and EAI4-like spoligotypes (31.5%), ZERO strains (5.0%), and part of EAI5 (11.1%) were included in a lineage-1 (L1) sublineage, i.e., L1.1.1.1. These strains were found less often in younger people, and they genetically clustered less frequently than other modern strains. Patients infected with ZERO strains demonstrated less lung infiltration. A region in RD2bcg spanning six loci, i.e., PE_PGRS35, cfp21, Rv1985c, Rv1986, Rv1987, and erm(37), was deleted in EAI4_VNM, EAI4-like, and ZERO strains, whereas another 118 bp deletion in furA was specific only to ZERO strains. L1.1.1.1-sublineage-specific deletions in PE_PGRS4 and PE_PGRS22 were also identified. RD900, seen in ancestral lineages, was present in majority of the L1 members. All strains without IS6110 (5.0%) had the ZERO spoligo-pattern. Distinctive features of the ancestral L1 strains provide a basis for investigation of the modern versus ancestral Mtb lineages and allow consideration of countermeasures against this heterogeneous pathogen.(+)-7-iso-Jasmonoyl-L-isoleucine (JA-Ile) is a lipid-derived phytohormone implicated in plant development, reproduction, and defense in response to pathogens and herbivorous insects. All these effects are instigated by the perception of JA-Ile by the COI1-JAZ co-receptor in the plant body, which in Arabidopsis thaliana is profoundly influenced by the short JAZ degron sequence (V/L)P(Q/I)AR(R/K) of the JAZ protein. Here, we report that SlJAZ-SlCOI1, the COI1-JAZ co-receptor found in the tomato plant, relies on the extended JAZ degron sequence (V/L)P(Q/I)AR(R/K)XSLX instead of the canonical JAZ degron. This finding illuminates our understanding of the mechanism of ligand perception by JA-Ile in this plant, and will inform both efforts to improve it by genetic modification of the SlCOI1-SlJAZ co-receptor, and the development of the synthetic agonists/antagonists.Safe surgical care, including anesthesia, obstetrics, and trauma, is an essential component of a functional health system, yet five billion people lack access to high-quality, timely and affordable surgical care. As health decision makers are grappling with how to make appropriate investments for crisis readiness and resilience, investments in surgical care should be considered for their compounding benefits to meet a country's diverse health goals.  https://www.selleckchem.com/products/ccs-1477-cbp-in-1-.html  National Surgical, Obstetric, and Anesthesia Plans (NSOAPs) are developed through global partnerships and multi-stakeholder consensus and provide a dynamic framework for surgical scale-up that also improves the resilience of the larger health system. Our paper applies principles from the literature on health system resilience to surgical systems and examines the unique capabilities of the surgical workforce and infrastructure to be redeployed during times of crisis, using examples from the current pandemic.Depression is a common psychiatric disorder. Although many risk factors for depression have been reported, the associations of biochemical and anthropometric indices with depressive disorder remain unclear. The objective of this study was to assess whether there are significant associations of depressive disorder with biochemical and obesity indices. This study was based on data from the Korea National Health and Nutrition Examination Survey from 2007 to 2018, and logistic regression was performed to examine the association of depression with biochemical and obesity indices. A total of 33,993 subjects were included in the analyses. Study subjects consisted of 13,178 men in the control group (mean age of 51.12 years), 509 men in the depression group (53.67), 18,279 women in the control group (50.5), and 2027 women in the depression group (55.39). Among men, the depression group was significantly more likely to have a lower height and weight than the control group. Compared to the control group, the depression group was more likely to have higher triglyceride levels and tended to have lower hematocrit and blood urea nitrogen (BUN) levels.