Rupture of vulnerable plaques is the main trigger of acute cardio-cerebral vascular events, but mechanisms responsible for transforming a stable atherosclerotic into a vulnerable plaque remain largely unknown. Melatonin, an indoleamine hormone secreted by the pineal gland, plays pleiotropic roles in the cardiovascular system; however, the effect of melatonin on vulnerable plaque rupture and its underlying mechanisms remains unknown. Here, we generated a rupture-prone vulnerable carotid plaque model induced by endogenous renovascular hypertension combined with low shear stress in hypercholesterolemic ApoE −/− mice. Melatonin (10 mg/kg/d by oral administration for 9 weeks) significantly prevented vulnerable plaque rupture, with lower incidence of intraplaque hemorrhage (42.9% vs. 9.5%, P = 0.014) and of spontaneous plaque rupture with intraluminal thrombus formation (38.1% vs. 9.5%, P = 0.029). Mechanistic studies indicated that melatonin ameliorated intraplaque inflammation by suppressing the differentiation of intraplaque macrophages toward the proinflammatory M1 phenotype, and circadian nuclear receptor retinoid acid receptor-related orphan receptor-α (RORα) mediated melatonin-exerted vasoprotection against vulnerable plaque instability and intraplaque macrophage polarization. Further analysis in human monocyte-derived macrophages confirmed the role of melatonin in regulating macrophage polarization by regulating the AMPKα-STATs pathway in a RORα-dependent manner. In summary, our data provided the first evidence that melatonin-RORα axis acts as a novel endogenous protective signaling pathway in the vasculature, regulates intraplaque inflammation, and stabilizes rupture-prone vulnerable plaques. K E Y W O R D S atherosclerosis, macrophage polarization, melatonin, nuclear receptor, RAR-related orphan receptor, vulnerable plaques 2 of 15 | DING et al. 12 of 15 | DING et al. F I G U R E 7 Melatonin regulates macrophage polarization through the signal transducer and activator of transcription (STAT) pathway.A, Flow cytometry analysis of cell surface markers for M1 (CD80 and CD197) and M2 (CD163 and CD206) macrophages during M1 and M2 polarization with vehicle or melatonin/SR3335 treatment. The results showed that co-culture with melatonin significantly reduced IFN-γ and LPSinduced CD80 and CD197 expression, whereas RORα agonism with SR3335 markedly promoted M1 polarization (n = 6 per group). *P < 0.05 or **P < 0.01 versus monocyte; # P < 0.05 versus M0. B and C, Western blotting was conducted on cell lysates with antibodies against P-STAT1, P-STAT3, and P-STAT6; total STAT1, STAT3, and STAT6; and GAPDH. Relative densities of phosphorylated STAT compared with total STAT are shown as histograms (n = 6 per group). *P < 0.05 or **P < 0.01 versus control; ##P < 0.01 versus M1 + siRORα in C. D and E, Western blotting was conducted on cell lysates with antibodies against RORα, P-AMPKα, total AMPKα, and GAPDH. *P < 0.05 versus Mel (0 mmol/L); ##P < 0.01 versus control siRNA

Wireless capsule endoscopy (WCE) can directly take digital images in the gastrointestinal tract of a patient. It has opened a new chapter in small intestine examination. However, a major problem associated with this technology is that too many images need to be manually examined by clinicians. Currently, there is no standard for capsule endoscopy image interpretation and classification. Most state-of-the-art CAD methods often suffer from poor performance, high computational cost, or multiple empirical thresholds. In this paper, a new method for rapid bleeding detection in the WCE video is proposed. We group pixels through superpixel segmentation to reduce the computational complexity while maintaining high diagnostic accuracy. Feature of each superpixel is extracted using the red ratio in RGB space and fed into support vector machine for classification. Also, the influence of edge pixels has been removed in this paper. Comparative experiments show that our algorithm is superior to the existing methods in terms of sensitivity, specificity, and accuracy.

Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.

This study aimed to investigate the effects of creatine monohydrate (CMH) and guanidinoacetic acid (GAA) supplementation on the growth performance, meat quality, and creatine metabolism of finishing pigs. The pigs were randomly allocated to three treatment groups: the control group, CMH group, and GAA group. In comparison to the control group, CMH treatment increased average daily feed intake and GAA treatment increased average daily feed intake and average daily gain of pigs. In addition, CMH and GAA treatment increased pH, myofibrillar protein solubility, and calpain 1 mRNA expression level and decreased the drip loss and shear force value in longissimus dorsi or semitendinosus muscle. Moreover, CMH and GAA supplementation increased the concentrations of creatine and phosphocreatine and the mRNA expressions of guanidinoacetate N-methyltransferase and creatine transporter in longissimus dorsi muscle, semitendinosus muscle, liver, or kidneys and decreased the mRNA expressions of arginine:glycine amidinotransferase in kidneys. In conclusion, CMH and GAA supplementation could improve the growth performance and meat quality and alter creatine metabolism of finishing pigs.

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Background. Postcholecystectomy syndrome (PCS) has become a common postoperative syndrome that requires systematic and comprehensive therapy to achieve adequate clinical control. Acupuncture and related therapies have shown clinical effects for PCS in many studies. However, systematic reviews/meta-analyses (SRs/MAs) for them are lacking. Objective. To evaluate the efficacy and safety of acupuncture in the treatment of PCS using randomized controlled trials (RCTs). Methods. Potentially eligible studies were searched in the following electronic databases up to 1 February 2020: PubMed, Embase, Cochrane Library, Web of Science (WoS), Chinese databases (Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), and China Science and Technology Journal Database (VIP)), and other sources (WHO ICTRP, ChiCTR, Clinical Trials, and Grey Literature Database). The RevMan 5.3 was employed for analyses. The Cochrane Collaboration’ risk of bias tool was used to assess the risk of bias (ROB). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of the evidence. Results. A total of 14 RCTs with 1593 participants were included in this SR. MA showed that acupuncture in combination with conventional medicine (CM) did not show statistical differences in reduction in pain. However, acupuncture in combination with CM significantly reduced the incidence of postoperative nausea and vomiting (PONV) (RR, 0.71; 95% CI, 0.55–0.92) and improved gastrointestinal function recovery compared to the CM group. Acupuncture combined with traditional Chinese medicine and CM, and acupuncture as monotherapy may improve gastrointestinal function recovery with acceptable adverse events. Conclusion. Acupuncture may be an effective and safe treatment for PCS. However, this study lacks conclusive evidence due to poor quality evidence, limited data, and clinical heterogeneity of acupuncture methods in the included studies.

Measuring phase and polarization singularities of light individually or simultaneously.

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