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Abstract Acute liver failure (ALF) is a deadly illness due to insufficient detoxification in liver induced by drugs, toxins, and other etiologies, and the effective treatment for ALF is very limited. Among the drug-induced ALF, acetaminophen (APAP) overdose is the most common cause. However, the molecular mechanisms underlying APAP hepatoxicity remain incompletely understood. Sirtuin 6 (Sirt6) is a stress responsive protein deacetylase and plays an important role in regulation of DNA repair, genomic stability, oxidative stress, and inflammation. Here, we report that genetic and pharmacological activation of Sirt6 protects against ALF in mice. We first observed that Sirt6 expression was significantly reduced in the liver tissues of human patients with ALF and mice treated with an overdose of APAP. Then we developed an inducible Sirt6 transgenic mice for Cre-mediated overexpression of the human Sirt6 gene in systemic (Sirt6-Tg) and hepatic-specific (Sirt6-HepTg) manners. Both Sirt6-Tg mice and Sirt6-HepTg mice exhibited the significant protection against APAP hepatoxicity. In contrast, hepatic-specific Sirt6 knockout mice exaggerated APAP-induced liver damages. Mechanistically, Sirt6 attenuated APAP-induced hepatocyte necrosis and apoptosis through downregulation of oxidative stress, inflammation, the stress-activated kinase JNK activation, and apoptotic caspase activation. Moreover, Sirt6 negatively modulated the level and activity of poly (ADP-ribose) polymerase 1 (PARP1) in APAP-treated mouse liver tissues. Importantly, the specific Sirt6 activator MDL-800 exhibited better therapeutic potential for APAP hepatoxicity than the current drug acetylcysteine. Furthermore, in the model of bile duct ligation induced ALF, hepatic Sirt6-KO exacerbated, but Sirt6-HepTg mitigated liver damage. Collectively, our results demonstrate that Sirt6 protects against ALF and suggest that targeting Sirt6 activation could be a new therapeutic strategy to alleviate ALF.

Ischemic stroke is a common issue that severely affects the human health. Between the central nervous system and the enteric system, the '' Gut-Brain '' axis, the bidirectional connection involved in the neuro-immuno-endocrine network, is crucial for the occurrence and development of ischemic stroke. Ischemic stroke can lead to change in the gut microbiota and gastrointestinal hormones, which will then reversely affect the disease development. Traditional Chinese Medicine (TCM) has unique advantages with reference to the treatment for ischemic stroke. The latest research revealed that a significant portion of medicines and prescriptions of TCM exert their therapeutic effects by improving the gut microbiota and regulating the secretion of gastrointestinal hormones. The present review summarized the Chinese medicines that play a therapeutic role in cerebral ischemia through regulating the ''Gut-Brain'' axis and described the corresponding mechanisms. This study attempts to provide reference for clinical selection of Chinese medicines and helps better understand the relevant mechanisms of action.

AIM:To report our precaution practices for ocular surgeries under local anesthesia during COVID-19 outbreak and evaluate the respiration situation among the patients with medical face masks under ocular surgeries.METHODS:Sixty Chinese patients needed eye surgery treatment were recruited and given medical face masks as one of the COVID-19 precaution practices during eye surgery with local anesthesia. Oxygen supplementation and negative pressure drainage were applied to relieve the potential respiratory discomfort, and the respiratory comfort score was evaluated.RESULTS:Patients with medical face masks experienced mild to moderate respiratory discomfort with an overall mean score of 2.34±0.73. Supplementation of oxygen together with negative pressure drainage relieved this discomfort(overall mean score of 0.15±0.75; P

Honeysuckle is a commonly used Chinese medicine for treating intestinal inflammation and other diseases. Compounds that are absorbed into the blood produce pharmacodynamic effects. However, it is still unclear which compounds in honeysuckle are absorbed into the blood. Thus, the purpose of this study was to investigate the composition and in vivo absorption of active components in honeysuckle in male Sprague-Dawley rats, and develop a controlled release hydrogel system. UPLC-LTQ-Orbitrap-MS was used to determine the active ingredients of honeysuckle in vitro and in vivo. A total of 80, out of which 42 components were found to be absorbed into the blood, which includes flavonoids, iridoids, organic acids and other compounds. FTIR analysis confirmed crosslinking between hydrogel content and drug loading, and TGA and DSC analysis indicated a high thermal stability. XRD analysis showed a decrease in crystallinity following crosslinking, and SEM revealed an irregular and hard surface. The maximum swelling and drug release were observed at pH 7.4 as compared to pH 1.2. The identified blood components can be used to determine Q-markers, while the prepared hydrogels can serve as an effective and promising carrier for the controlled release of honeysuckle extracts.

Aims Variants of the junctional cadherin 5 associated (JCAD) locus associate with acute coronary syndromes. JCAD promotes experimental atherosclerosis through the large tumor suppressor kinase 2 (LATS2)/Hippo pathway. This study investigates the role of JCAD in arterial thrombosis. Methods and results JCAD knockout (Jcad−/−) mice underwent photochemically induced endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) treated with JCAD small interfering RNA (si JCAD), LATS2 small interfering RNA (si LATS2) or control siRNA (siSCR) were employed for in vitro assays. Plasma JCAD was measured in patients with chronic coronary syndrome or ST-elevation myocardial infarction (STEMI). Jcad −/− mice displayed reduced thrombogenicity as reflected by delayed time to carotid occlusion. Mechanisms include reduced activation of the coagulation cascade [reduced tissue factor (TF) expression and activity] and increased fibrinolysis [higher thrombus embolization episodes and D-dimer levels, reduced vascular plasminogen activator inhibitor (PAI)-1 expression]. In vitro , JCAD silencing inhibited TF and PAI-1 expression in HAECs. JCAD-silenced HAECs (si JCAD) displayed increased levels of LATS2 kinase. Yet, double JCAD and LATS2 silencing did not restore the control phenotype. si- JCAD HAECs showed increased levels of phosphoinositide 3-kinases (PI3K)/ proteinkinase B (Akt) activation, known to downregulate procoagulant expression. The PI3K/Akt pathway inhibitor—wortmannin—prevented the effect of JCAD silencing on TF and PAI-1, indicating a causative role. Also, co-immunoprecipitation unveiled a direct interaction between JCAD and Akt. Confirming in vitro findings, PI3K/Akt and P -yes-associated protein levels were higher in Jcad−/− animals. Lastly, as compared with chronic coronary syndrome, STEMI patients showed higher plasma JCAD, which notably correlated positively with both TF and PAI-1 levels. Conclusions JCAD promotes arterial thrombosis by modulating coagulation and fibrinolysis. Herein, reported translational data suggest JCAD as a potential therapeutic target for atherothrombosis. [ABSTRACT FROM AUTHOR]

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy. [ABSTRACT FROM AUTHOR]

Delayed recovery from ulcerative colitis is mainly due to impaired healing of the intestinal epithelium after inflammation. The circadian rhythm controls cell proliferation and energy metabolism. However, the role of circadian genes in inflammatory bowel disease is largely unknown. The purpose of this study was to investigate whether disrupting the circadian rhythm in mice can worsen colitis by altering mitochondrial energy metabolism. Mice in the experimental groups were under physiologic stress with an 8-h light shift jet-lag schedule every 3 days, whereas those in the control group were not. Subsequently, half of the mice in the control and jet-lagged groups were given dextran sodium sulfate (DSS) to induce colitis. Mice in each group were euthanized at zeitgeber time (ZT)0, ZT4, ZT8, ZT12, ZT16, and ZT20. To investigate the effects of jet lag on the mice, colon specimens were subjected to hematoxylin and eosin staining to analyse mRNA and protein expression of core circadian clock genes (Bmal1 , Clock , Per1 , Per2 , Cry1 , Cry2 , and Nr1d1). We analysed the mitochondrial morphology, adenosine triphosphate (ATP) levels, and the expression of dynamin-related protein 1 (Drp1) and ser637-phosphorylated (p)-Drp1, which are closely related to ATP production. We further investigated the effect of PER2 knock-down in the colon epithelial cells (CCD 841 CoN) by measuring ATP and cell proliferation levels. Disrupting the circadian rhythm changed the oscillation of clock genes in the colon of mice, altered the mitochondrial morphology of the colon specimens, decreased the expression of p-Drp1, reduced ATP production, and exacerbated inflammatory responses in mice with DSS-induced colitis. Additionally, silencing of PER2 in the colon epithelial cells reduced ATP production and cell proliferation. Disrupting the circadian rhythm in mice decreases mitochondrial energy metabolism in the colon and exacerbates symptoms of colitis. [ABSTRACT FROM AUTHOR]

With the increasing number of underwater pipeline investigation activities, the research on automatic pipeline detection is of great significance. At this stage, object detection algorithms based on Deep Learning (DL) are widely used due to their abilities to deal with various complex scenarios. However, DL algorithms require massive representative samples, which are difficult to obtain for pipeline detection with sub-bottom profiler (SBP) data. In this paper, a zero-shot pipeline detection method is proposed. First, an efficient sample synthesis method based on SBP imaging principles is proposed to generate samples. Then, the generated samples are used to train the YOLOv5s network and a pipeline detection strategy is developed to meet the real-time requirements. Finally, the trained model is tested with the measured data. In the experiment, the trained model achieved a mAP@0.5 of 0.962, and the mean deviation of the predicted pipeline position is 0.23 pixels with a standard deviation of 1.94 pixels in the horizontal direction and 0.34 pixels with a standard deviation of 2.69 pixels in the vertical direction. In addition, the object detection speed also met the real-time requirements. The above results show that the proposed method has the potential to completely replace the manual interpretation and has very high application value. [ABSTRACT FROM AUTHOR]

Retraction note to: BMC Gastroenterol 2013, 13:126 https://doi.org/10.1186/1471-230X-13-126 The Editor has retracted this article after a number of concerns were raised, including: Overlapping panels in Figures 2 and 3 Inaccurate description of Figure 2 parts A-C in the figure legend Lack of discussion of the difference between the behaviour of the cell line COLO205 compared with the other cell lines used Lack of methodological information relating to the 9 paired colorectal cancer tissue samples No description of normal cell lines used and inconsistencies in the descriptions of colorectal cell lines The Editor no longer has confidence in the results and conclusions presented. Jun-Ling Liu, Zheng-Gen Wang, Ling Shi, Ting-Ting Li, Xiao-Hui Zhao, Xiu-Ting Chen and Yan-Qing Ding have not responded to correspondence from the Editor about this retraction. [Extracted from the article]