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mTORC1 is an important regulator of muscle mass but how it is modulated by oxygen and nutrients is not completely understood. We show that loss of the prolyl hydroxylase domain isoform 1 oxygen sensor in mice (PHD1KO) reduces muscle mass. PHD1KO muscles show impaired mTORC1 activation in response to leucine whereas mTORC1 activation by growth factors or eccentric contractions was preserved. The ability of PHD1 to promote mTORC1 activity is independent of its hydroxylation activity but is caused by decreased protein content of the leucyl tRNA synthetase (LRS) leucine sensor. Mechanistically, PHD1 interacts with and stabilizes LRS. This interaction is promoted during oxygen and amino acid depletion and protects LRS from degradation. Finally, elderly subjects have lower PHD1 levels and LRS activity in muscle from aged versus young human subjects. In conclusion, PHD1 ensures an optimal mTORC1 response to leucine after episodes of metabolic scarcity.

Recently, with the rapid development of automatic driving, more and more researchers begin to explore the lightweight of image semantic segmentation network and apply it to road traffic scenes. However, the existing semantic segmentation networks are usually difficult to deploy in edge devices with limited hardware resources due to the large number of parameters. Aiming at solving this problem, a rapid and ultra-lightweight dual attention lightweight network (DALNet) composed of channel attention bottleneck backbone (CABb) network and spatial attention decoder (SAD) module is proposed in this paper, which has outstanding performance in extracting the context semantic information and spatial information of the image. The CABb network is mainly composed of channel attention bottleneck (CABt) module. Split strategy is employed in CABt to separate feature channels and process multi-scale feature maps in parallel. And channel attention mechanism is introduced for channel fusion and multi-scale semantic information extraction. The spatial attention mechanism is adopted in SAD module to guide the decoder to upsample the feature maps using bilinear interpolation and recover the edge information and detail information of segmentation target. Experimental results show that the proposed DALNet has only 0.48 million parameters and achieves 74.1% and 70.1% mean intersection over union (mIoU) in the popular urban traffic datasets of Cityscapes and CamVid. With the resolution of 512×1024, DALNet achieves 74 frame/s inference speed on a GTX 1080Ti card, which meets the speed requirements of real-time semantic segmentation adequately.

Abstract In humans, a family of 25 bitter taste receptors (TAS2Rs) mediates bitter taste perception. A common approach to characterize bitter causative agents involves expressing TAS2Rs and the appropriate signal transducers in heterologous cell systems, and monitoring changes in the intracellular free calcium levels upon ligand exposure using a fluorescence-based modality, which typically suffers from a low signal window, and is susceptible to interference by autofluorescence, therefore prohibiting its application to screening of plant or food extracts, which are likely to contain autofluorescent compounds. The aim of this study is to develop and validate a bioluminescence-based intracellular calcium release assay for TAS2Rs that has a better assay performance than a fluorescence-based assay. Furthermore, the bioluminescence-based assay enabled the evaluation of TAS2R agonists within an autofluorescent matrix, highlighting its potential utility in the assessment of the bitterness-inducing properties of plant or food fractions by the food industry. Additionally, improvement to the bioluminescence-based assay for some TAS2Rs was achieved by altering their N-terminal signal sequences, leading to signal window enhancement. Altogether, the bioluminescence-based TAS2R assay can be used to perform functional studies of TAS2Rs, evaluate TAS2R-modulating properties of autofluorescent samples, and facilitate the discovery of compounds that can function as promising bitter taste modulators.

Abstract Background Dysregulation of long noncoding RNA (lncRNA) expression is related to aging and age-associated neurodegenerative diseases, and the lncRNA expression profile in the aging hippocampus is not well characterized. In the present investigation, the changed mRNAs and lncRNAs were confirmed via deep RNA sequencing. GO and KEGG pathway analyses were conducted to investigate the principal roles of the clearly dysregulated mRNAs and lncRNAs. Subsequently, through the prediction of miRNAs via which mRNAs and lncRNAs bind together, a competitive endogenous RNA network was constructed. Results A total of 447 lncRNAs and 182 mRNAs were upregulated, and 385 lncRNAs and 144 mRNAs were downregulated. Real-time reverse transcription-polymerase chain reaction validated the reliability of mRNA and lncRNA sequencing. KEGG pathway and GO analyses revealed that differentially expressed (DE) mRNAs were associated with cell adhesion molecules (CAMs), the p53 signaling pathway (SP), phagosomes, PPAR SP and ECM—receptor interactions. KEGG pathway and GO analyses showed that the target genes of the DE lncRNAs were related to cellular senescence, the p53 signaling pathway, leukocyte transendothelial migration and tyrosine metabolism. Coexpression analyses showed that 561 DE lncRNAs were associated with DE mRNAs. A total of 58 lncRNA–miRNA–mRNA target pairs were confirmed in this lncRNA‒miRNA‒mRNA network, comprising 10 mRNAs, 13 miRNAs and 38 lncRNAs. Conclusions We found specific lncRNAs and mRNAs in the hippocampus of natural aging model rats, as well as abnormal regulatory ceRNA networks. Our outcomes help explain the pathogenesis of brain aging and provide direction for further research.

Alagille syndrome, caused by mutations in the gene encoding Jagged1 (JAG1), a ligand in the Notch signaling pathway, is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, face and skeleton. The aim of the present study is try to disclose the clinical features, management and outcomes of pulmonary artery stenosis associated with Alagille syndrome. By comprehensive literature retrieval, 38 articles involving 401 patients were recruited for this study. The pertinent variables closely related to pulmonary artery stenosis in patients with Alagille syndrome were comprehensively analyzed by following the PRISMA guidelines. The management of pulmonary artery pathologies, especially a severe type of pulmonary artery stenosis in Alagille syndrome, is a concerned matter. Publications of literature retrieval of recent 3 decades were the study material of this article. The pulmonary artery pathologies, especially the severe type of pulmonary artery stenosis in Alagille syndrome, warrant surgical or interventional treatments. After the procedures, the right ventricular to left ventricular pressure ratio was reduced by 25%. There were no intergroup differences in terms of recovery, reintervention and mortality rates between interventionally and surgically treated patients. Transcatheter treatment is preferable due to less trauma. Surgical treatment of pulmonary artery stenosis can be performed currently with intracardiac defect repair.

The aim of the present study is to describe the indications, treatment effects, and patient outcomes of percutaneous management of left ventricular pseudoaneurysm (LVPA). The study materials were based on comprehensive literature retrieval since 2004. The mechanisms of LVPA formation can be divided into surgical, percutaneous, and medial disease related. Of the surgical mechanisms, coronary artery bypass grafting prevailed. The formation time was the longest in medical disease-related LVPAs up to 44.4 months. The percutaneous procedures succeeded on the first try in 79 (84.9%) patients, whereas failures were encountered during the percutaneous manoeuvres in 14 (15.1%) patients. Percutaneous closure of LVPA was especially indicated for patients carrying a high surgical risk. The iatrogenic traumas, such as left ventricular venting, should be avoided to prevent this complication. The preliminary cut-off valves of oversize 3.3 mm and oversize ratio 1.6 should be followed for reference for device choice.

Abstract We appreciate the interest by Drs. Hagiyama and coauthors in our work entitled “Calcar fracture gapping: a reliable predictor of anteromedial cortical support failure after cephalomedullary nailing for pertrochanteric femur fractures”. They discussed several pertinent points and it is our pleasure to respond their concerns in order. Firstly, we agree that calcar fracture gap and anteromedial cortical support are different concepts, though both of them were used to evaluate the displacement of fracture reduction quality. Secondly, our primary outcome parameter was the threshold distance of calcar fracture gapping in anteroposterior and lateral fluoroscopies, which was calculated based on sensitivity and specificity by receiver operating characteristic curves. Thirdly, we took immediate post-operative fluoroscopic images in 3 views to describe the initial reduction quality as baseline to compare and calculate the changes with three-dimensional computed tomography, which was taken about one week after operation for confirming secondary stability after head-neck sliding and impaction. Lastly, the parameters selected in multivariable analysis. Future work with better study-design is needed to improve the prediction of patient outcomes.

Whether amino acids act on cellular insulin signaling remains unclear. Here, the authors find that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake and positively correlated with T2D onset.

Background and purpose: 5-fluorouracil (5-FU) is the backbone of drug for gastric cancer. Traditional high-dose 5-FU often leads to serious adverse reactions and drug resistance. The low-dose 5-FU metronomic chemotherapy can significantly reduce the toxicity of the drug without affecting the efficacy, but it is not clear which dose can achieve the best anti-tumor effect. The purpose of this study was to explore the optimal metronomic chemotherapy strategy for 5-FU and to explore the related molecular mechanisms. Methods: A nude mouse subcutaneous tumor model of SGC-7901 gastric cancer cell line was established. After tumor formation, mice were randomly divided into 4 groups: maximum tolerated dose (MTD) group, daily metronomic chemotherapy (MET-qd) group, every other day metronomic chemotherapy (MET-qod) group and twice-weekly metronomic chemotherapy (MET-biw) group. Duration of single course of treatment was 21 d, and mice received a total of 2 courses of treatment. During the treatment period, the general condition of nude mice was observed, the tumor mass was weighed and measured every week, and the tumor growth curve was drawn. Flow cytometry was used to detect circulating endothelial progenitors (CEP) in peripheral blood of nude mice; B cells, natural killer (NK) cells, tumor-associated macrophage (TAM) and myeloid-derived suppressor cell (MDSC) infiltrated in the tumor and spleen. Immunohistochemical staining was used to detect the expressions of CD11c and CD163 in the tumor. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), interleukin (IL)-10 and IL-12 in peripheral blood of nude mice. In addition, white blood cell counts and H-E stained sections of liver, lung, kidney, and heart were performed in order to monitor toxicity assessments. Results: The three metronomic chemotherapy strategies of 5-FU could inhibit the growth of xenograft tumor in nude mice similar to the MTD group, and the MET-qod group has the most obvious anti-tumor effect (P

Abstract The chemical fertilizer industry has made great contributions to China's food security. Existing studies mainly focus on evaluating fertilizer use efficiency at the farm level whereas little is known about the technical efficiency of Chinese firms producing fertilizer. Based on the Chinese Industrial Enterprise Database (CIED) and the Generalized True Random Effects model (GTRE), this paper estimates and decomposes the technical efficiency of Chinese fertilizer‐producing firms. Results show technical efficiency increased from 0.883 in 1998 to 0.930 in 2007, with an average of 0.898. The growth rate of persistent efficiency is lower than that of transient efficiency, implying structural problems exist in the Chinese fertilizer industry. Moreover, ownership type and firms' entry and exit are exogenous determinants of technical inefficiency. State‐owned firms perform much worse on technical efficiency. The entry of efficient firms and exit of inefficient firms, especially the exit of inefficient state‐owned firms, have improved the technical efficiency significantly.

Left ventricular pseudoaneurysm (LVPA) is a rare complication of myocardial infarction. The clinical characteristics and treatment of choice in the current era remain to be elaborated. The present article aims to give an overview of post-infarct LVPA and discuss the management strategy and outcomes. The study was based on comprehensive retrieval of literature of the recent 10 years. Myocardial infarctions as the underlying causes of LVPAs were mostly acute myocardial infarctions. The mean time for LVPA formation was 51.7 months after myocardial infarction. Postoperative and follow-up ejection fraction values were significantly higher than preoperative. In the interventional group patients, the oversize ratio of patients in whom devices remained in position was a little larger than that of those with a migrated one, but lack of a statistical significance (1.32±0.25 vs. 1.25±0.21, p=0.707). The mortality rate was significantly higher in the conservative group than in the surgical and interventional groups. Post-infarct LVPAs are curable to surgical aneurysmectomy and left ventricular reconstruction, thereby avoiding unexpected LVPA ruptures and other fatal complications. Elderly patients and patients at a high operative risk may resort to interventional therapy. The conservatively treated patients inevitably carry a considerable risk of death. An oversize ration of >1.3 might be a reference value for preventing device migration in the interventional group patients.

‘Candidatus Liberibacter asiaticus (CLas)’, which causes citrus Huanglongbing (HLB) disease, has not been successfully cultured in vitro to date. Here, a rapid multiplication system for CLas was established through in vitro regeneration of axillary buds from CLas-infected ‘Changyecheng’ sweet orange (Citrus sinensis Osbeck). Stem segments with a single axillary bud were cultured in vitro to allow CLas to multiply in the regenerating axillary buds. A high CLas titer was detected in the regenerated shoots on an optimized medium at 30 days after germination (DAG). This titer was 28.2-fold higher than in the midribs from CLas-infected trees growing in the greenhouse. To minimize contamination during in vitro regeneration, CLas-infected axillary buds were micrografted onto seedlings of ‘Changyecheng’ sweet orange and cultured in a liquid medium. In this culture, the titers of CLas in regenerated shoots rapidly increased from 7.5×104 to 1.4×108 cells μg–1 of citrus DNA during the first 40 DAG. The percentages of shoots with >1×108 CLas cells μg–1 DNA were 30 and 40% at 30 and 40 DAG, respectively. Direct tissue blot immunoassay (DTBIA) indicated that the distribution of CLas was much more uniform in regenerated plantlets than in CLas-infected trees growing in the greenhouse. The disease symptoms in the plantlets were die-back, stunted growth, leaf necrosis/yellowing, and defoliation. The death rate of the plantlets was 82.0% at 60 DAG. Our results show that CLas can effectively multiply in citrus plantlests in vitro. This method will be useful for studying plant-HLB interactions and for rapid screening of therapeutic compounds against CLas in citrus.