Inhibition of SIRT1 with EX-527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR-211 mimic led to a significant increase in γ-H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB-mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR-211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB-induced CPDs in primary keratinocytes.
 
  These findings establish a novel MALAT1-miR-211-SIRT1 signalling axis that potentially confers protection to the 'amelanotic' keratinocytes in vitiligo.
 These findings establish a novel MALAT1-miR-211-SIRT1 signalling axis that potentially confers protection to the 'amelanotic' keratinocytes in vitiligo.Global environmental change poses threats to plant and soil biodiversity. Yet, whether soil biodiversity loss can further influence plant community's response to global change is still poorly understood. We created a gradient of soil biodiversity using the dilution-to-extinction approach, and investigated the effects of soil biodiversity loss on plant communities during and following manipulations simulating global change disturbances in experimental grassland microcosms. Grass and herb biomass was decreased by drought and promoted by nitrogen deposition, and a fast recovery was observed following disturbances, independently of soil biodiversity loss. Warming promoted herb biomass during and following disturbance only when soil biodiversity was not reduced. However, legumes biomass was suppressed by these disturbances, and there were more detrimental effects with reduced soil biodiversity. Moreover, soil biodiversity loss suppressed the recovery of legumes following these disturbances. Similar patterns were found for the response of plant diversity. The changes in legumes might be partly attributed to the loss of mycorrhizal soil mutualists. Our study shows that soil biodiversity is crucial for legume persistence and plant diversity maintenance when faced with environmental change, highlighting the importance of soil biodiversity as a potential buffering mechanism for plant diversity and community composition in grasslands.B cell targeting therapies are effective in various autoimmune diseases, among others rheumatoid arthritis, pemphigus vulgaris, and systemic lupus erythematosus. Given these successes, it is evident that B cells are central orchestrators in the processes leading to the signs and symptoms hallmarking many human autoimmune diseases. The pathways provoking the generation of such autoreactive B cells or mechanisms preventing their induction in health are, however, poorly explored. Nevertheless, such information is crucial for the development of preventative/curative interventions aiming to permanently deplete- or prohibit the emergence of autoreactive B cells. Hence, this review will focus on how B cell tolerance might be breached, and which checkpoints are at play preventing the arousal of autoreactive B cells in human. Especially antigen presentation by follicular dendritic cells, somatic hypermutation, and cross-reactivity to the microbiome/environment could operate as actors playing pivotal roles in the induction of B cell-mediated humoral autoimmunity. Moreover, we highlight the human autoimmune disease rheumatoid arthritis as a prototype where autoreactive B cells combine several mechanisms to overcome peripheral B cell checkpoints.Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is highly effective for the prevention of high-grade serous ovarian cancer (HGSOC) in BRCA1/2 pathogenic variant carriers (PVCs), but does not completely eliminate future risk of primary peritoneal cancer (PPC). The requirement to completely remove fallopian tubes at RRBSO and carefully exclude occult cancer/serous tubal intraepithelial carcinoma (STIC) lesions may not have been appreciated historically. We calculated rates of HGSOC and PPC in confirmed BRCA1/2 PVCs registered on the regional database in those who did (cases) and did not (controls) undergo RRBSO after genetic testing. Expected annual rates of ovarian/peritoneal cancer were 1% for BRCA1 ≥ 35 years and 0.5% for BRCA2 ≥ 45 years.  https://www.selleckchem.com/products/bp-1-102.html  Follow-up before 35/45 years was "risk free" and lead time excluded RRBSO less then 35 years and less then 45 years for BRCA1 and BRCA2, respectively. Women were followed from personal mutation report (controls) or RRBSO (cases) to death, ovarian/peritoneal cancer or last follow-up, whichever was sooner. In total, 891 cases (BRCA1 = 468, BRCA2 = 423) and 1302 controls had follow-up ≥35 years (BRCA1 = 736) and ≥45 years (BRCA2 = 566), respectively, over a total of 7261.1 risk eligible years (mean = 8.15 years). Twenty-one occult ovarian cancers were found at RRBSO (2.4%), 16 at stage 1. Post RRBSO, 56.97 ovarian/peritoneal cancers were expected but only 3 were observed (HR = 0.053; 95% CI = 0.013-0.14), with combined Kaplan-Meier analysis HR = 0.029 (95% CI = 0.009-0.100, P  less then  .001). Risk reduction was greater in specialist (HR = 0.03; 95% CI = 0.001-0.13) compared to non-specialist centres (HR = 0.11; 95% CI = 0.02-0.37) (P = .07). In controls, 23.35 ovarian/peritoneal cancers were expected with 32 observed (HR = 1.37; 95% CI = 0.95-1.91). RRBSO less then 35/ less then 45 years reduces the risk of ovarian/peritoneal cancer by 95% in BRCA1/2 PVCs and may be greater in specialist centres.The aim of this study was to investigate the prevalence of peritoneal human papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single-center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between March 2019 and April 2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV-DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. Two-hundred seventy-two patients had cervical and peritoneal HPV test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early stage, 28.8% in locally advanced cervical cancer (LACC) and 46.6% in the metastatic/persistent/recurrent setting (P = .001). No control patient was found to have peritoneal HPV infection.