No abstract

Dietary threonine imbalance is known to reduce the growth of the small intestine, liver, and skeletal muscle in young animals, but the underlying mechanism is largely unknown. Using the pig model, this study was conducted to test the hypothesis that either a deficiency or an excess of dietary threonine impairs protein synthesis in these tissues. Young pigs (25 d of age) were fed diets containing 0.37, 0.74 (current NRC requirement) or 1.11% true ileal digestible threonine (TIDT) (n = 6/diet). Pigs receiving the 0.74 and 1.11% TIDT diets were pair-fed with the same amount of feed as pigs receiving the 0.37% TIDT diet. After a 14-d dietary treatment, the fractional synthesis rate (FSR) of protein in tissues was measured using a flooding dose of l-phenylalanine plus L-[ring-(2)H(5)]phenylalanine. The results indicated that the FSR of protein in liver was reduced (P < 0.05) in pigs fed the 0.37% TIDT diet compared with pigs fed the 0.74 or 1.11% TIDT diet, and did not differ between pigs fed the 0.74 and 1.11% TIDT diets. The FSR of protein in longissimus muscle, jejunal mucosa, and mucins was reduced (P < 0.05) in pigs fed the 0.37 or 1.11% TIDT diet compared with pigs fed the 0.74% TIDT diet. The absolute synthesis rate of protein in the jejunal mucosa and muscle was also reduced (P < 0.01) in pigs fed the 0.37 and 1.11% TIDT diets compared with the controls. The absolute synthesis rate of hepatic protein was lower (P < 0.01) in pigs fed the 0.37% TIDT diets when compared with pigs fed the 0.74% TIDT diet. Protein synthesis in skeletal muscle as well as jejunal mucosa and mucins was reduced to a greater extent than that in liver in response to an imbalance of dietary threonine. Collectively, these results indicate that either an excess or a deficiency of dietary threonine decreases protein synthesis in rapidly growing tissues of young pigs. The findings provide a mechanism for the low growth performance of animals fed a threonine-imbalanced diet.

The China Jinping Underground Laboratory (CJPL), which has the lowest cosmic-ray muon flux and the lowest reactor neutrino flux of any laboratory, is ideal to carry out low-energy neutrino experiments. With two detectors and a total fiducial mass of 2000 tons for solar neutrino physics (equivalently, 3000 tons for geo-neutrino and supernova neutrino physics), the Jinping neutrino experiment will have the potential to identify the neutrinos from the CNO fusion cycles of the Sun, to cover the transition phase for the solar neutrino oscillation from vacuum to matter mixing, and to measure the geo-neutrino flux, including the Th/U ratio. These goals can be fulfilled with mature existing techniques. Efforts on increasing the target mass with multi-modular neutrino detectors and on developing the slow liquid scintillator will increase the Jinping discovery potential in the study of solar neutrinos, geo-neutrinos, supernova neutrinos, and dark matter.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with highly aggressive behavior and early systemic metastasis. The survival rates for osteosarcoma remain unchanged over the past two decades. Studies aiming to find new or alternative therapies for patients with refractory osteosarcoma are urgently needed. Anlotinib, a novel multi‐targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging clinical activity in NSLCC and soft tissue sarcoma, whereas its effect on osteosarcoma has not been studied. In our study, we investigated the anti‐tumor activity and underlying mechanism of anlotinib in osteosarcoma. Various in vitro and in vivo models of human osteosarcoma were used to determine the anti‐proliferative, anti‐angiogenesis and anti‐metastasis efficacy of anlotinib. Our results showed that anlotinib suppressed tumor growth and increased the chemo‐sensitivity of osteosarcoma. In addition, anlotinib inhibited migration and invasion in osteosarcoma cells. Furthermore, in order to explore the anti‐tumor mechanism of anlotinib, phospho‐RTK antibody arrays were performed. These analyses confirmed that anlotinib suppressed the phosphorylation of MET, VEGFR2 and the downstream signaling pathway activation. Moreover, we demonstrated that anlotinib blocked hepatocyte growth factor (HGF)‐induced cell migration, invasion and VEGF‐induced angiogenesis. Notably, a 143B‐Luc orthotopic osteosarcoma model further showed that anlotinib significantly inhibited growth and lung metastasis of implanted tumor cells. Our preclinical work indicates that anlotinib acts as a novel inhibitor of VEGFR2 and MET that blocks tumorigenesis in osteosarcoma, which could be translated into future clinical trials.

OBJECTIVE To reveal more data on the epidemiologic and clinical characteristics of coronavirus disease 2019 (COVID-19) patients outside of Wuhan, from five hospitals in east of Zhejiang province, China. DESIGN Retrospective case series. SETTING Five hospitals in east of Zhejiang province, China. PARTICIPANTS 88 cases of laboratory-confirmed and 3 cases of clinical-confirmed COVID-19 were : medRxiv preprint RESULTSOf all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 pneumonia with throat swab samples that tested positive for SARS-Cov-2 while 3 (3.30%) were clinical-diagnosed COVID-19 pneumonia cases. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample 40 (43.96%) patients had contracted the diseases from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, 8 (8.79%) cases had contacted with people from Wuhan, 11 (12.09%) cases were confirmed aircraft transmission.In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple.The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%).The median of incubation period was 6 (IQR, 3-8) days and the median time from first visit to a doctor to confirmed diagnosis was 1 (1-2) days. According to the Chest computed tomography scans, 67.03% cases had bilateral pneumonia, and 27.47% cases showed unilateral pneumonia. CONCLUSIONSocial activity cluster, family cluster and travel by airplane were how COVID-19 patients get transmitted and could be rapidly diagnosed COVID-19 in Zhejiang.

Comparing the clinical and radiographic outcomes in anterior cervical discectomy and fusion (ACDF) using a zero-profile anchored spacer (ROI-C) or a conventional cage-plate construct (CPC) for treating noncontiguous bilevel of cervical degenerative disc disease (CDDD).Overall, 46 patients with 2 noncontiguous segments of CDDD, treated with ACDF from January 2011 to October 2015, were included in this study. ROI-C was used in 22 patients (group A) and CPC in 24 patients (group B). The clinical and radiographic outcomes and complications were compared pre- and postoperatively. All patients were followed up for at least 24 months after surgery.No significant difference was found in fusion rate, cervical curvature, height of fused segment (FSDH), intraoperative blood loss, and Japanese Orthopaedic Association (JOA), and Neck Disability Index (NDI) scores between the 2 groups. Group A had a shorter operation time and significantly lower incidence of dysphagia (3 and 24 months postoperatively) than group B (P < .001 and P < .05, respectively). Moreover, group A had a higher loss of FSDH than group B, but with no difference between the 2 groups (P > .05). Two cages developed subsidence in group A (4.5%) and 2 adjacent levels developed degeneration in group B (2,8%).ACDF with ROI-C device was superior to CPC for noncontiguous bilevel of CDDD because it avoided postoperative dysphagia and required a shorter operation time. Moreover, the clinical outcomes were comparable. Prospective trials with larger samples and longer follow-up are required to confirm the results.

We present the calibration strategy for the 20 kton liquid scintillator central detector of the Jiangmen Underground Neutrino Observatory (JUNO). By utilizing a comprehensive multiple-source and multiple-positional calibration program, in combination with a novel dual calorimetry technique exploiting two independent photosensors and readout systems, we demonstrate that the JUNO central detector can achieve a better than 1% energy linearity and a 3% effective energy resolution, required by the neutrino mass ordering determination.

Frogeye leaf spot, caused by Cercospora sojina Hara, is a common disease of soybean in most soybean-growing countries of the world. In this study, we report a high-quality genome sequence of C. sojina by Single Molecule Real-Time sequencing method. The 40.8-Mb genome encodes 11,655 predicated genes, and 8,474 genes are revealed by RNA sequencing. Cercospora sojina genome contains large numbers of gene clusters that are involved in synthesis of secondary metabolites, including mycotoxins and pigments. However, much less carbohydrate-binding module protein encoding genes are identified in C. sojina genome, when compared with other phytopathogenic fungi. Bioinformatics analysis reveals that C. sojina harbours about 752 secreted proteins, and 233 of them are effectors. During early infection, the genes for metabolite biosynthesis and effectors are significantly enriched, suggesting that they may play essential roles in pathogenicity. We further identify 13 effectors that can inhibit BAX-induced cell death. Taken together, our results provide insights into the infection mechanisms of C. sojina on soybean.