miR-181a Post-Transcriptionally Downregulates Oncogenic RalA and Contributes to Growth Inhibition and Apoptosis in Chronic Myelogenous Leukemia (CML)

MicroRNAs (miRNAs) are a class of short RNAs that regulate gene expression through either translational repression or mRNA cleavage. miRNA-181a (miR-181a), one of the many miRNAs conserved among vertebrates, is differentially expressed in a variety of leukemia. However, its function in leukemia, particularly chronic myelogenous leukemia (CML), is poorly understood. Here we have reported the identification of miR-181a targets by combining TargetScan software prediction and expression profiling through overexpression of miR-181a mimic in leukemic K562 cells. Four overlapping genes were found to be the likely targets of miR-181a. Among the four genes, RalA is a downstream molecule of bcr-abl fusion protein in ras signaling pathway. However, its role in CML remains elusive. Luciferase reporter and Western blot assays confirmed that RalA is a direct target of miR-181a. overexpression of miR-181a effectively suppresses cell growth and induces G2-phase arrest and apoptosis partially by targeting RalA in leukemic K562 cells. Using the KEGG database combined with recent publications, downstream signaling pathway of RalA was graphed by cytoscape software. Therefore, our study is the first to report that RalA is directly regulated by miR-181a and plays an important role in CML. The approach of computational prediction combined with expression profiling might be valuable for the identification of miRNA targets in animal

PERIOPERATIVE DEXMEDETOMIDINE REDUCES DELIRIUM IN ELDERLY PATIENTS AFTER LUNG CANCER SURGERY

Background: Delirium, which is one of the most disturbing postoperative complications in elderly patients, shows high morbidity in patients undergoing lung cancer surgery. Dexmedetomidine (DEX) is considered a potential prophylactic agent for preventing patients’ delirium after lung cancer surgery. Subjects and methods: Medical records of lung cancer patients over 65 years old with radical pulmonary resection at Henan Provincial People’s Hospital from January 2015 to December 2017, China, were evaluated. Patients, care-providers, and investigators were all blinded to group assignment. DEX was administered in the preoperative and intraoperative periods. The incidence of delirium was calculated based on the Intensive Care Delirium Screening Checklist (ICDSC). Scores of ≥4 and 1-3 points represent the diagnoses of delirium and a pre -delirious state, respectively. Results: During postoperative day 1 (POD 1) to POD 7, delirium occurs in both groups. During postoperative POD 1 to POD 7, the incidence of delirium is lower in the DEX group than that in the control group. Furthermore, there are more mild delirium patients but fewer moderate and severe delirium patients in the DEX group compared with the control group. Finally, patients in the DEX group have a shorter duration of delirium, lower numeric pain rating scale during movement and better sleep quality. Conclusion: Preoperative and intraoperative application of DEX can reduce the incidence and intensity of delirium after pulmonary resection in elderly patients with lung cancer

Mapping the potential distribution of the schistosomiasis intermediate host Biomphalaria straminea in China

Biomphalaria straminea is native to Brazil but has established a population in Guangdong Province China. Its potential of expanding and transmitting Schistosoma mansoni is of great concern. We seek to map S. mansoni transmission potential by predicting ecological dimensions and potential distributions of B. straminea using state-of-the-art ecological niche model approaches. Two environmental datasets were selected to fit individual and ensemble niche models, together with the evaluation of niche conservatism during B. straminea invasion in China. A small area is still occupied by the introduced population compared to that in Brazil. A vast space with suitable climate remains unfilled and might be available to B. straminea. Contrasting results of niche conservatism evaluation were attained based on the two environmental datasets. The coastal areas in southern China, together with south-western Yunnan and southern Hainan and Taiwan were consistent supported by multiple model approaches, showing high climate suitability for B. straminea. Attention should be paid to the possibility of S. mansoni epidemic in these identified areas, as high pressure due to propagation and future climate change may further complicate conditions. Our results call for rigorous monitoring and supervising along these areas in China

Molecular characterization of Listeria monocytogenes strains isolated from imported food in China from 14 countries/regions, 2003-2018

Listeria monocytogenes (Lm) is associated with severe foodborne infections and ubiquitous in the nature. Identification of characteristics of Lm transmission through trading of food products is essential for rapidly tracking Lm sources and controlling dissemination of listeriosis. In this study, a total of 44 Lm strains were isolated from food products originating from 14 countries/regions during 2003-2018 at the Shanghai port. The genomes of these Lm strains were sequenced by high-throughput sequencing. Multilocus sequence typing (MLST) analysis showed that 43 isolates were divided into 17 sequence types (STs). The distribution of STs was decentralized, with the dominant ST2 accounting for only 18.18% of the strains. The LM63 strain did not match with any of the existing STs. Core-genome MLST (cgMLST) analysis based on 1748 core genes categorized the 44 strains into 30 cgMLST types (CTs), with CT10153 and CT7892 as the most predominant CTs. Notably, LM63 and LM67 shared the same CT in the cgMLST analysis. The phylogenetic analysis based on single-copy homologous genes revealed that the 44 Lm strains were primarily classified into two lineages. The SNP analysis also indicated that these strains were roughly divided into two clades, with strains in the first clade mainly collected earlier than those in the second clade, which were predominantly collected from 2010 onwards. The analysis using the virulence factor database (VFDB) indicated that the virulence gene inlJ was the most prevalent among these 44 strains. Notably, ddrA, msbA, and sugC were enriched in this dataset, requiring further clarification of their roles in Listeria through future studies. These results might provide a clue for understanding of the global epidemiology and surveillance of Lm and present insights for implementing effective measures to reduce or prevent Listeria contamination outbreaks in imported food products

Discovery of the Consistently Well-Performed Analysis Chain for SWATH-MS Based Pharmacoproteomic Quantification

Sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) has emerged as one of the most popular techniques for label-free proteome quantification in current pharmacoproteomic research. It provides more comprehensive detection and more accurate quantitation of proteins comparing with the traditional techniques. The performance of SWATH-MS is highly susceptible to the selection of processing method. Till now, ≥27 methods (transformation, normalization, and missing-value imputation) are sequentially applied to construct numerous analysis chains for SWATH-MS, but it is still not clear which analysis chain gives the optimal quantification performance. Herein, the performances of 560 analysis chains for quantifying pharmacoproteomic data were comprehensively assessed. Firstly, the most complete set of the publicly available SWATH-MS based pharmacoproteomic data were collected by comprehensive literature review. Secondly, substantial variations among the performances of various analysis chains were observed, and the consistently well-performed analysis chains (CWPACs) across various datasets were for the first time generalized. Finally, the log and power transformations sequentially followed by the total ion current normalization were discovered as one of the best performed analysis chains for the quantification of SWATH-MS based pharmacoproteomic data. In sum, the CWPACs identified here provided important guidance to the quantification of proteomic data and could therefore facilitate the cutting-edge research in any pharmacoproteomic studies requiring SWATH-MS technique

Assessing the Effectiveness of Direct Data Merging Strategy in Long-Term and Large-Scale Pharmacometabonomics

Because of the extended period of clinic data collection and huge size of analyzed samples, the long-term and large-scale pharmacometabonomics profiling is frequently encountered in the discovery of drug/target and the guidance of personalized medicine. So far, integration of the results (ReIn) from multiple experiments in a large-scale metabolomic profiling has become a widely used strategy for enhancing the reliability and robustness of analytical results, and the strategy of direct data merging (DiMe) among experiments is also proposed to increase statistical power, reduce experimental bias, enhance reproducibility and improve overall biological understanding. However, compared with the ReIn, the DiMe has not yet been widely adopted in current metabolomics studies, due to the difficulty in removing unwanted variations and the inexistence of prior knowledges on the performance of the available merging methods. It is therefore urgently needed to clarify whether DiMe can enhance the performance of metabolic profiling or not. Herein, the performance of DiMe on 4 pairs of benchmark datasets was comprehensively assessed by multiple criteria (classification capacity, robustness and false discovery rate). As a result, integration/merging-based strategies (ReIn and DiMe) were found to perform better under all criteria than those strategies based on single experiment. Moreover, DiMe was discovered to outperform ReIn in classification capacity and robustness, while the ReIn showed superior capacity in controlling false discovery rate. In conclusion, these findings provided valuable guidance to the selection of suitable analytical strategy for current metabolomics

Dietary Betaine Mitigates Hepatic Steatosis and Inflammation Induced by a High-Fat-Diet by Modulating the Sirt1/Srebp-1/Pparɑ Pathway in Juvenile Black Seabream (Acanthopagrus schlegelii)

The present study aimed to elucidate the mechanism of dietary betaine, as a lipid-lowering substance, on the regulation of lipid metabolism and inflammation in juvenile black seabream (Acanthopagrus schlegelii) fed a high fat diet. An 8-week feeding trial was conducted in black seabream with an initial weight of 8.39 ± 0.01g fed four isonitrogenous diets including Control, medium-fat diet (11%); HFD, high-fat diet (17%); and HFD supplemented with two levels (10 and 20 g/kg) of betaine, HFD+B1 and HFD+B2, respectively. SGR and FE in fish fed HFD+B2 were significantly higher than in fish fed HFD. Liver histology revealed that vacuolar fat droplets were smaller and fewer in bream fed HFD supplemented with betaine compared to fish fed HFD. Betaine promoted the mRNA and protein expression levels of silent information regulator 1 (Sirt1), up-regulated mRNA expression and protein content of lipid peroxisome proliferator-activated receptor alpha (pparα), and down-regulated mRNA expression and protein content of sterol regulatory element-binding protein-1(srebp-1). Furthermore, the mRNA expression levels of anti-inflammatory cytokines in liver and intestine were up-regulated, while nuclear factor kB (nf-kb) and pro-inflammatory cytokines were down-regulated by dietary betaine supplementation. Likewise, in fish that received lipopolysaccharide (LPS) to stimulate inflammatory responses, the expression levels of mRNAs of anti-inflammatory cytokines in liver, intestine and kidney were up-regulated in fish fed HFD supplemented with betaine compared with fish fed HFD, while nf-kb and pro-inflammatory cytokines were down-regulated. This is the first report to suggest that dietary betaine could be an effective feed additive to alleviate hepatic steatosis and attenuate inflammatory responses in black seabream fed a high fat diet by modulating the Sirt1/Srebp-1/Pparɑ pathway

Dietary fenofibrate attenuated high-fat-diet-induced lipid accumulation and inflammation response partly through regulation of pparα and sirt1 in juvenile black seabream (Acanthopagrus schlegelii)

An 8-week feeding trail was conducted in Acanthopagrus schlegelii with an initial body weight of 8.34±0.01g. Three isonitrogenous diets were formulated, (1) Control: medium-fat diet (12%); (2) HFD: high-fat diet (18%); (3) HFD+FF: high-fat diet with fenofibrate (0.15%). Liver histological analysis revealed that, compared to HFD, vacuolar fat drops were smaller and fewer in fish fed fenofibrate. Expression of lipid catabolism regulator peroxisome proliferator-activated receptor alpha (pparα) was up-regulated by fenofibrate compared with HFD. In addition, fenofibrate significantly increased the expression level of silent information regulator 1 (sirt1). Meanwhil e, the expression level of anti-inflammatory cytokine interleukin 10 (il-10) in intestine was up-regulated, while pro-inflammatory cytokine interleukin 1β (il-1β) in liver and intestine were down-regulated by dietary fenofibrate supplementation. Overall, the present study indicated that fenofibrate reduced fat deposition and attenuated inflammation response caused by HFD partly through a pathway involving regulation of pparα and sirt1

2D Black Phosphorus: from Preparation to Applications for Electrochemical Energy Storage

Black phosphorus (BP) is rediscovered as a 2D layered material. Since its first isolation in 2014, 2D BP has triggered tremendous interest in the fields of condensed matter physics, chemistry, and materials science. Given its unique puckered monolayer geometry, 2D BP displays many unprecedented properties and is being explored for use in numerous applications. The flexibility, large surface area, and good electric conductivity of 2D BP make it a promising electrode material for electrochemical energy storage devices (EESDs). Here, the experimental and theoretical progress of 2D BP is presented on the basis of its preparation methods. The structural and physiochemical properties, air instability, passivation, and EESD applications of 2D BP are discussed systemically. Specifically, the latest research findings on utilizing 2D BP in EESDs, such as lithium‐ion batteries, supercapacitors, and emerging technologies (lithium–sulfur batteries, magnesium‐ion batteries, and sodium‐ion batteries), are summarized. On the basis of the current progress, a few personal perspectives on the existing challenges and future research directions in this developing field are provided