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ositive prognostic markers, while HIF-1α is a negative prognostic marker of breast cancer. Conclusions Our study identifies TFEB as a master regulator of TAMs in breast cancer. TFEB controls TAM gene expression and function through multiple autophagy/lysosome-dependent and independent pathways. Therefore, pharmacological activation of TFEB would be a promising therapeutic approach to improve the efficacy of existing treatment including immune therapies for breast cancer by favorably modulating TAM function and the TME.Background The prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptably low. This study aimed to determine the efficacy, safety and predictive biomarkers of the immune checkpoint inhibitor nivolumab in combination with chemotherapy in advanced BTCs. Methods In this open-label, single-arm, phase II trial, a chemotherapy and immunotherapy combination consisting of gemcitabine 1000 mg/m2, cisplatin 75 mg/m2 and nivolumab 3 mg/kg was administered every 3 weeks for up to six cycles. Maintenance treatment with gemcitabine plus nivolumab was administered to patients achieving disease control following the combination therapy. The primary outcome was the objective response rate. Secondary outcomes included safety, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). The exploratory objective was to assess biomarkers for predicting clinical response and prognosis. Results Thirty-two patients with a median age of 60 (range 27-69) years were enrol cisplatin offers promising efficacy and a manageable safety profile for patients with advanced BTCs. Trial registration number NCT03311789.Trastuzumab deruxtecan may be effective in solid cancers in addition to breast cancer. In a randomized phase II trial of HER2-positive gastric and gastroesophageal junction cancers, the agent significantly extended overall survival and progression-free survival compared with standard chemotherapy. It also elicited high response rates in phase II trials of HER2-mutant non-small cell lung cancer and HER2-positive colorectal cancer.Adjuvant treatment with the tyrosine kinase inhibitor osimertinib will likely become a new standard of care in patients with EGFR-mutant non-small cell lung cancer. In the phase III ADAURA trial, 90% of patients with stage II-IIIA disease who received osimertinib were alive and free of cancer at 2 years, compared with 44% who received a placebo-results considered so striking that researchers unblinded the trial early.Objective The current study was done to determine the prevalence, determinants, disclosure status and help-seeking behaviour of spousal violence using a nationally representative sample of ever-married women in India. Methods We have analysed the most recent National Family Health Survey-4 data (2015-2016) gathered from the Demographic Health Survey programme. Stratification and clustering in the sample design were accounted using svyset command. Point estimates were reported as proportions with 95% CI. Results A total of 66 013 ever-married women aged 15-49 years were included. Lifetime prevalence of spousal violence in India was 31% (95% CI 30.4% to 31.7%). Physical violence was the most common form accounting for 27.4% of victims followed by emotional (12.7%) and sexual violence (6.7%). Higher women's age, Muslim religion, low education, employed women, lower socioeconomic status, presence of substance use among women and husbands, lower education and unemployed husbands, history of family violence and women in Central and Eastern states had a significant association with one or more forms of spousal violence with significant p value. https://www.selleckchem.com/products/pci-34051.html Prevalence of help-seeking behaviour among women who faced spousal violence in India was 13.5% (95% CI 12.8% to 14.2%). Widowed/separated/divorced women, employed and highly educated women, and women in Northern states had significantly higher prevalence of help-seeking behaviour with respect to all the forms of spousal violence (p less then 0.001). Conclusion One in three women in India faces spousal violence. Only 1 in 10 women seeks help following violence. Efforts should be made to ensure people working in formal institutions screen for spousal violence and know how to respond to women facing it.Membrane traffic maintains the organization of the eukaryotic cell and delivers cargo proteins to their subcellular destinations such as sites of action or degradation. Membrane vesicle formation requires ARF GTPase activation by the SEC7 domain of ARF guanine-nucleotide exchange factors (ARF-GEFs), resulting in the recruitment of coat proteins by GTP-bound ARFs. In vitro exchange assays were done with monomeric proteins, although ARF-GEFs form dimers in vivo. This feature is conserved across the eukaryotes, however its biological significance is unknown. Here we demonstrate FRET-FLIM detectable proximity of ARF1•GTPs in vivo and we show that this is mediated through coordinated activation by ARF-GEF dimers such as Arabidopsis GNOM involved in polar recycling of PIN1. Mutational disruption of ARF1 spacing as detected by FRET-FLIM interfered with ARF1-dependent trafficking but not coat protein recruitment in Arabidopsis. A mutation impairing the interaction of one of the two SEC7 domains of GNOM ARF-GEF dimer with its ARF1 substrate reduced the efficiency of coordinated ARF1 activation. Our results suggest a model of coordinated activation-dependent membrane insertion of ARF1•GTP molecules required for coated membrane vesicle formation. Considering the evolutionary conservation of ARFs and ARF-GEFs, this initial regulatory step of membrane trafficking might well occur in eukaryotes in general.The switch from dark- to light-mediated development is critical for the survival and growth of seedlings, but the underlying regulatory mechanisms are incomplete. Here, we show that the steroids phytohormone brassinosteroids play crucial roles during this developmental transition by regulating chlorophyll biosynthesis to promote greening of etiolated seedlings upon light exposure. Etiolated seedlings of the brassinosteroids-deficient det2-1 (de-etiolated2) mutant accumulated excess protochlorophyllide, resulting in photo-oxidative damage upon exposure to light. Conversely, the gain-of-function mutant bzr1-1D (brassinazole-resistant 1-1D) suppressed the protochlorophyllide accumulation of det2-1, thereby promoting greening of etiolated seedlings. Genetic analysis indicated that phytochrome-interacting factors (PIFs) were required for BZR1-mediated seedling greening. Furthermore, we reveal that GROWTH REGULATING FACTOR 7 (GRF7) and GRF8 are induced by BZR1 and PIF4 to repress chlorophyll biosynthesis and promote seedling greening.
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