Manningsalisbury5246

383, 95% CI [-0.029, 0.796], p = .061, k = 5) with lack of evidence for publication bias. Given limited studies included, we were unable to determine factors affecting the efficacy of interventions. The limited focus on non-US studies and youth populations is concerning given the popularity of vaping in low- to middle-income countries (LMICs) and among youth. The findings of this meta-analysis describe the current state of the literature and prescribe specific recommendations to better address the proliferation of vaping misinformation, providing insights helpful in limiting the tobacco mortality burden and curtailing youth vaping.Faced with the threat of antimicrobial resistance, health workers are urged to reduce unnecessary prescription of antimicrobials. Clinical guidelines are expected to form the basis of prescribing decisions in practice. Emerging through evaluations of best practice - bundling clinical, technological and economic dimensions - guidelines also create benchmarks through which practice can be assessed with metrics. To understand the relationships between guidelines and practice in the prescribing and dispensing of antibiotics, ethnographic fieldwork was undertaken in lower-level health care facilities in rural Eastern Uganda for 10 months between January and October 2020, involving direct observations during and outside of clinics and interviews with staff. In a context of scarcity, where 'care' is characterised by delivery of medicines, and is constituted beyond algorithmic outputs, we observed that clinical practice was shaped by availability of resources, and professional and patient expectations, as much as by the clinical guidelines. For stewardship to care for patients as well as for medicines, a better understanding of clinical practice and expectations of care is required in relation to and beyond clinical guidelines.This paper contributes to the growing body of work on precarious labor, immigration, and social gerontology by examining the racialization of precarious employment across the life course. In particular, the authors examine the impact of precarious employment and discrimination among racialized older immigrants in Canada. Racialized older immigrants are more likely to be disadvantaged by the effects of lifelong intersections of economic and social discrimination rooted in racialization, gender, ageism, and socio-economic status. Drawing from a narrative-photovoice project that focused on the life stories of older immigrants living in Quebec and British Columbia, this paper presents the in-depth stories and photographs of four participants to highlight how intersections of race, gender, age, immigration status, and ability shape and structure experiences of aging, labor market participation and caregiving relationships.Mutations in the mitochondrial genome (mtDNA) are ubiquitous in humans and can lead to a broad spectrum of disorders. However, due to the presence of multiple mtDNA molecules in the cell, co-existence of mutant and wild-type mtDNAs (termed heteroplasmy) can mask disease phenotype unless a threshold of mutant molecules is reached. Importantly, the mutant mtDNA level can change across lifespan as mtDNA segregates in an allele- and cell-specific fashion, potentially leading to disease. Segregation of mtDNA is mainly evident in hepatic cells, resulting in an age-dependent increase of mtDNA variants, including non-synonymous potentially deleterious mutations. Here we modeled mtDNA segregation using a well-established heteroplasmic mouse line with mtDNA of NZB/BINJ and C57BL/6N origin on a C57BL/6N nuclear background. This mouse line showed a pronounced age-dependent NZB mtDNA accumulation in the liver, thus leading to enhanced respiration capacity per mtDNA molecule. Remarkably, liver-specific atg7 (autophagy rela9 ribosomal protein L19; Rps18 ribosomal protein S18; SD standard deviation; SEM standard error of the mean; SDHB succinate dehydrogenase complex, subunit B, iron sulfur (Ip); SQSTM1 sequestosome 1; Ssbp1 single-stranded DNA binding protein 1; TFAM transcription factor A, mitochondrial; Tfb1m transcription factor B1, mitochondrial; Tfb2m transcription factor B2, mitochondrial; TOMM20 translocase of outer mitochondrial membrane 20; UQCRC2 ubiquinol cytochrome c reductase core protein 2; WT wild-type.The endoplasmic reticulum (ER) carries out essential cellular functions ranging from protein trafficking to metabolite signaling. ER function is maintained in part by quality control pathways including ER degradation by selective autophagy (reticulophagy) during conditions of cellular stress. Reticulophagy is known to be important for cellular responses to starvation and protein folding stress, but no natural role during development had been identified. While investigating ER remodeling during the conserved cell differentiation process of meiosis in budding yeast, we unexpectedly observed developmentally regulated reticulophagy that was driven by expression of the autophagy receptor Atg40. This reticulophagy was coordinated with massive morphological rearrangement of the ER, including movement of most cortical ER away from the cell periphery. As meiotic reticulophagy prevents specific ER subpopulations from being inherited by gametes, we propose that it serves a quality control role, preventing deleterious material from being passed on to subsequent generations.This study aimed to explore the therapy role of procyanidin B2 (PB2) in inhibiting angiogenesis and cell growth in oral squamous cell carcinoma. After oral mucosa epithelial cell (OMEC) and human oral squamous cell carcinoma (OSCC) cell line (SCC-25) were treated with PB2 or SCC-25 were treated with PB2 and rhVEGF, cell counting kit-8 (CCK-8) assay was used to determine the cell viability. The apoptosis, migration, invasion and angiogenesis of SCC-25 after indicated treatment were detected by Tunel, wound healing, transwell and tube formation assays. The protein expression related to apoptosis, metastasis and epithelial-mesenchymal transition (EMT) and changed expression of vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling was analyzed by Western blot. As a result, PB2 inhibited viability, invasion, migration and EMT and promoted apoptosis of SCC-25 cells. In addition, PB2 inhibited VEGF/VEGFR2 signaling and tumor itangiogenesis in OSCC. As expected, activation of VEGF/VEGFR2 signaling suppressed the effect of PB2 on growth and metastasis of OSCC cells. In conclusion, PB2 inhibited the VEGF/VEGFR2 pathway to suppress the angiogenesis and cell growth of SCC-25 cells.Ulcerative colitis (UC) is a type of chronic disease of inflammation, and matrine has anti-inflammatory activity. However, it is unclear that whether matrine can alleviate UC. This study aimed to evaluate the effect of matrine on DSS-induced intestinal epithelial cell injury. Cell viability was performed by MTT assay. Then cell apoptosis was analyzed using the TUNEL assay and flow cytometry. The levels of interleukin (IL)-2, IL-6, TNF-α, and IL-1β were evaluated using qRT-PCR. Myeloperoxidase (MPO) activity was detected using ELISA assay. Nitric oxide (NO) production was detected by the Griess reagent. Bax, cleaved caspase-3, Bcl-2, JAK2, p-JAK2, STAT3, p-STAT3, STAT5, p-STAT5 levels were measured by Western blot. Bax (6A7) was asses using immunoprecipitation and immunofluorescence assays. The results illustrated that cell viability was inhibited as the concentration of DSS increased. Matrine did not affect cell viability at the concentration of 0-2 mg/ml but inhibited cell viability in a time-independent manner. Matrine suppressed the levels of pro-inflammatory factors, MPO activity, NO production, and apoptosis of DSS-stimulated cells. Furthermore, we found that matrine inhibited the levels of p-JAK2/JAK2 and p-STAT3/STAT3 but did not affect p-STAT5/STAT5. AG490 treatment further enhanced the effect of matrine on the apoptosis and pro-inflammatory factor levels in DSS-induced cells. In summary, matrine protected NCM460 cell against injury by inactivating the JAK2/STAT3 pathway. These data suggested for the first time that matrine may effective in treating UC.Macroautophagy/autophagy plays crucial roles in aging and the pathogenesis of age-related diseases. Studies in various animal models demonstrate the conserved requirement for autophagy-related genes in multiple anti-aging interventions. A recent study from the Shirasu-Hiza lab showed that a newly designed intermittent time-restricted feeding (iTRF) dietary regimen can robustly extend fly healthspan and lifespan through circadian rhythm-dependent activation of autophagy. The night-specific induction of autophagy is both necessary and sufficient for iTRF-mediated health benefits. The study provides the intriguing possibility that novel behavioral or pharmaceutical interventions that promote night-specific autophagy can be used to promote healthy aging.Nuclear Speckles (NS) are phase-separated condensates of protein and RNA whose components dynamically coordinate RNA transcription, splicing, transport and DNA repair. NS, probed largely by imaging studies, remained historically well known as Interchromatin Granule Clusters, and biochemical properties, especially their association with Chromatin have been largely unexplored. In this study, we tested whether NS exhibit any stable association with chromatin and show that limited DNAse-1 nicking of chromatin leads to the collapse of NS into isotropic distribution or aggregates of constituent proteins without affecting other nuclear structures. Further biochemical probing revealed that NS proteins were tightly associated with chromatin, extractable only by high-salt treatment just like histone proteins. NS were also co-released with solubilised mono-dinucleosomal chromatin fraction following the MNase digestion of chromatin. We propose a model that NS-chromatin constitutes a "putative stable association" whose coupling might be subject to the combined regulation from both chromatin and NS changes.Abbreviations NS Nuclear speckles; DSB double strand breaks; PTM posttranslational modifications; DDR DNA damage repair; RBP-RNA binding proteins; TAD topologically associated domains; LCR low complexity regions; IDR intrinsically disordered regions.Chloroquine (CQ), a lysosomotropic agent, is commonly used to inhibit lysosomal degradation and macroautophagy/autophagy. Here we investigated the cell-extrinsic effects of CQ on secretion. We showed that lysosomal and autophagy inhibition by CQ altered the secretome, and induced the release of Atg8 orthologs and autophagy receptors. BI-4020 price Atg8-family proteins, in particular, were secreted inside small extracellular vesicles (sEVs) in a lipidation-dependent manner. CQ treatment enhanced the release of Atg8-family proteins inside sEVs. Using full-length ATG16L1 and an ATG16L1 mutant that enables Atg8-family protein lipidation on double but not on single membranes, we demonstrated that LC3B is released in two distinct sEV populations one enriched with SDCBP/Syntenin-1, CD63, and endosomal lipidated LC3B, and another that contains LC3B but is not enriched with SDCBP/Syntenin-1 or CD63, and which our data supports as originating from a double-membrane source. Our findings underscore the context-dependency of sEV heterogeneity and composition, and illustrate the integration of autophagy and sEV composition in response to lysosomal inhibition.