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Sirtuin 3 (SIRT3) is a type III histone deacetylase that inhibits cardiac hypertrophy. It is mainly localized in the mitochondria and is thus implicated in mitochondrial metabolism. Recent studies have shown that SIRT3 can also accumulate in the nuclear under stressed conditions, and participated in histone deacetylation of target proteins. Poly [ADP-ribose] polymerase 1 (PARP-1) functions as an important PARP isoform that was involved in cardiac hypertrophy. Our experiments showed that SIRT3 accumulated in the nuclear of cardiomyocytes treated with isoproterenol or SIRT3 overexpression. Moreover, overexpression of SIRT3 by adenovirus inhibited the expression of cardiac hypertrophic genes-ANF and BNP, as well as abrogating PARP-1 activation induced by isoproterenol or phenylephrine. In addition, co-immunoprecipitation experiments revealed that SIRT3 could interact with PARP-1, and overexpression of SIRT3 could decrease the acetylation level of PARP-1. Our results indicate that SIRT3 exerts protective effects against cardiac hypertrophy by reducing the level of acetylation and activity of PARP-1, thus providing novel mechanistic insights into SIRT3-mediated cardiprotective actions.Hirschsprung disease (HSCR), the most common enteric neuropathy, stands as a model for complex genetic disorders. It has recently been demonstrated that both ARHGEF3 and CTNNAL1 map to the RET-dependent HSCR susceptibility loci. We therefore sought to explore whether genetic variants within RET, ARHGEF3 and CTNNAL1, and their genetic interaction networks are associated with HSCR. Taking advantage of a strategy that combined the MassArray system and gene-gene interaction analysis with case-control study, we interrogated 38 polymorphisms within RET, ARHGEF3 and CTNNAL1 in 1015 subjects (502 HSCR cases and 513 controls) of Han Chinese origin. There were statistically significant associations between 20 genetic variants in these three genes and HSCR. Haplotype analysis also revealed some significant global P values, i.e. RET_ rs2435357-rs752978-rs74400468-rs2435353-rs2075913-rs17028-rs2435355 (P = 3.79×10-58). Using the MDR and GeneMANIA platforms, we found strong genetic interactions among RET, ARHGEF3, and CTNNAL1 and our previously studied GAL, GAP43, NRSN1, PTCH1, GABRG2 and RELN genes. These results offer the first indication that genetic markers of RET, ARHGEF3 and CTNNAL1 and relevant genetic interaction networks confer the altered risk to HSCR in the Han Chinese population.Perioperative neurocognitive disorders are common in elderly patients who have undergone surgical procedures. Neuroinflammation induced by microglial activation is a hallmark of these neurological disorders. Acetate can suppress inflammation in the context of inflammatory diseases. We employed an exploratory laparotomy model with isoflurane anesthesia to study the effects of acetate on perioperative neurocognitive disorders in aged mice. Neurocognitive function was assessed with open-field tests and Morris water maze tests 3 or 7 days post-surgery. Acetate ameliorated the surgery-induced cognitive deficits of aged mice and inhibited the activation of IBA-1, a marker of microglial activity. Acetate also reduced expression of inflammatory proteins (tumor necrosis factor-α, interleukin-1β and interleukin-6), oxidative stress factors (NADPH oxidase 2, inducible nitric oxide synthase and reactive oxygen species), and signaling molecules (nuclear factor kappa B and mitogen-activated protein kinase) in the hippocampus. BV2 microglial cells were used to verify the anti-inflammatory effects of acetate in vitro. Acetate suppressed inflammation in lipopolysaccharide-treated BV2 microglial cells, but not when GPR43 was silenced. These results suggest that acetate may bind to GPR43, thereby inhibiting microglial activity, suppressing neuroinflammation, and preventing memory deficits. This makes acetate is a promising therapeutic for surgery-induced neurocognitive disorders and neuroinflammation.Metastasis and recurrence are major causes of death in gastric cancer patients. Because there are no obvious clinical symptoms during the early stages of metastasis, we sought to isolate highly invasive metastatic gastric cancer cells for future drug screening. We first established a mouse model to observe gastric cancer metastasis in vivo. The incidence of peritoneal metastasis of gastric cancer was much higher than liver or lymph metastasis. Peritoneal metastatic and non-metastatic NUGC-4 cells were isolated from the mouse model. Cell proliferation was measured using CCK-8 assays, while migration and invasion were investigated in Transwell assays. Proteins involved in epithelial-mesenchymal transition were detected by Western blotting. Metastatic gastric carcinoma cells were more proliferative and invasive than primary NUGC-4 cells. The supernatants of metastatic gastric carcinoma cells notably altered the morphology of HMrSV5 peritoneal mesothelial cells and promoted their epithelial-mesenchymal transition. click here Moreover, primary or metastatic gastric cancer cells co-cultured with HMrSV5 cells markedly increased cancer cell proliferation and invasiveness. Moreover, peritoneal metastatic gastric carcinoma cells in the presence of HMrSV5 cells exhibited most malignant behaviors. Thus, peritoneal metastatic gastric carcinoma cells exhibited high capacities for proliferation and invasion, and could be used as a new drug screening tool for the treatment of advanced gastric cancer and peritoneal metastatic gastric cancer.OBJECTIVE Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease and information on disease burden of ALS in mainland China was limited. We aimed to estimate the prevalence and incidence of ALS in China. METHODS We used 2012-2016 data from China's Urban Employee Basic Medical Insurance and Urban Residence Basic Medical Insurance, covering approximately 0.43 billion individuals. ALS cases were identified by the primary diagnosis (International Classification of Diseases code or text of diagnosis) in the insurance database. RESULTS The crude prevalence and incidence in 2016 were 2.91 per 100 000 person-years (95% CI 2.31 to 3.58) and 1.65 (95% CI 1.33 to 2.01), respectively. The standardised prevalence and incidence based on 2010 Chinese census data were 2.97 (95% CI 2.91 to 3.03) and 1.62 (95% CI 1.58 to 1.67), respectively. The annual prevalence between 2013 and 2016 remained relatively constant, ranging from 2.91 (95% CI 2.31 to 3.58) in 2016 to 3.29 (95% CI 2.51 to 4.17) in 2014 (linear regression β=-0.129, p=0.104). Both rates peaked in the group aged 75-79 years. CONCLUSIONS The prevalence and incidence of ALS in mainland China were lower than those in developed countries, and maintained a relatively stable trend. The age at onset and age at diagnosis for ALS patients were younger than those in developed countries. Further research is expected to clarify the potential pathophysiological mechanism of ALS. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES Tourette syndrome is a neurodevelopmental disorder commonly associated with involuntary movements, or tics. We currently lack an ideal animal model for Tourette syndrome. In humans, clinical manifestation of tics cannot be captured via functional imaging due to motion artefacts and limited temporal resolution, and electrophysiological studies have been limited to the intraoperative environment. The goal of this study was to identify electrophysiological signals in the centromedian (CM) thalamic nucleus and primary motor (M1) cortex that differentiate tics from voluntary movements. METHODS The data were collected as part of a larger National Institutes of Health-sponsored clinical trial. Four participants (two males, two females) underwent monthly clinical visits for collection of physiology for a total of 6 months. link2 Participants were implanted with bilateral CM thalamic macroelectrodes and M1 subdural electrodes that were connected to two neurostimulators, both with sensing capabilities. MRI scans were performed preoperatively and CT scans postoperatively for localisation of electrodes. Electrophysiological recordings were collected at each visit from both the cortical and subcortical implants. RESULTS Recordings collected from the CM thalamic nucleus revealed a low-frequency power (3-10 Hz) increase that was time-locked to the onset of involuntary tics but was not present during voluntary movements. Cortical recordings revealed beta power decrease in M1 that was present during tics and voluntary movements. CONCLUSION We conclude that a human physiological signal was detected from the CM thalamus that differentiated tic from voluntary movement, and this physiological feature could potentially guide the development of neuromodulation therapies for Tourette syndrome that could use a closed-loop-based approach. link3 © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Final-year vet student Rachel Garty has opted for a variety of rewarding and enlightening placements. She encourages vets working in unusual jobs to offer students the chance to see what they do. British Veterinary Association.Throughout his long and varied career, Martin was driven by a desire to make a difference - to leave things better than he found them; to make things better for animals. He made things better for people too. British Veterinary Association.A loyal and hardworking partner who always pushed the boundaries in driving the practice forward. Kind, caring and inquisitive, he became a legend among generations of staff and clients. British Veterinary Association.The UK One Health Coordination Group (UKOHCG) met for its first meeting of the year on 11 February. BVA Policy Officer Megan Knowles-Bacon provides an update on the discussions. British Veterinary Association.Following an open nominations process, and elections run on our behalf by UK Engage, we are pleased to announce your new regional representatives. British Veterinary Association.A major focus for the Vet Futures project has been the RCVS-led Mind Matters Initiative (MMI), supported by BVA and a number of other veterinary organisations. Last month BVA junior vice president James Russell battled Storm Ciara to attend a meeting of the MMI Sarah Brown Research Project in Edinburgh. Here's his report…. British Veterinary Association.BVA Northern Ireland Branch held its annual general meeting on 12 February. BVA Policy Officer Michael McGilligan introduces the new team. British Veterinary Association.Following the General Election in December, our public affairs team contacted new MPs and newly appointed spokespeople to introduce BVA and our priority issues, writes Sally Burnell, Director of Policy, Media and Strategy. British Veterinary Association.Following the launch of our major undergraduate education position last year, BVA is embarking on a project to widen participation in UK vet schools. Sally Burnell, BVA Director of Policy, Media and Strategy, reports on a roundtable discussion. British Veterinary Association.This focus article has been prepared by members of the APHA Surveillance Intelligence Unit and the Veterinary Risk Group. British Veterinary Association.