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The study aims to describe the characteristics and etiologic causes of intermediate uveitis (IU) patients seen by a tertiary eye center in Singapore over 8 years.This was a retrospective analysis of the clinical records of consecutive new cases of IU that presented to the uveitis subspecialty clinic from 2004-2011 at Tan Tock Seng Hospital. Data collected included demographics, clinical and laboratory findings. Diagnoses were based on standardized clinical history, ophthalmological examination and investigations.There were 66 new cases of IU, comprising 5.7% of 1168 new uveitis patients. The median age of diagnosis was 40 years (mean 39.4±15.9), with largest subgroup of the patients in the age group of 41-60 years (36.4%). The majority was Chinese (57.6%), followed by Asian Indians (18.2%) and Malays (16.7%). The ethnicity distribution was dissimilar to our ethnic distribution in Singapore (p

Neoadjuvant chemotherapy is given before surgery to patients with primarily unresectable, advanced-stage cancers to render the tumor resectable, and to facilitate breast conservation. Previously, we have reported a prospective phase II trial for women with stage IIA-B/IIIA-B-C breast cancer with improved pathologic complete response (pCR) when using bevacizumab in the neoadjuvant setting. Chemotherapy agents are given intravenously during multiple cycles of systemic treatments. However, the effect of the treatment is only evaluated upon the completion of therapy. Here, data from a clinical trial of 40 breast cancer patients with very aggressive disease and poor prognosis were studied aiming to identify epigenetic signatures in blood-derived DNA at baseline as potential non-invasive markers to predict pCR and to determine if treatment-related changes in epigenetic profiles reflect responsiveness to therapy. We performed genome-wide DNA methylation profiling using blood-derived DNA, and found that pre-treatment methylation status of BRD9 was predictive of responsiveness to therapy. Post-treatment global methylation differences were also observed between responders and non-responders. Most differentially methylated (DM) CpGs were located in promoter CpG-island regions for responders and in the open-sea region for non-responders. In responders, DNMT3B was hypomethylated while most of the other genes were hypermethylated after 4 cycles of treatment. Hypomethylation of DNMT3B could potentially lead to the increased methylation of oncogenes and genes responsible for cell growth and proliferation, facilitating responsiveness to the therapy. These results support the possible development of BRD9 as a biomarker for treatment selection before neoadjuvant therapy with chemotherapy and bevacizumab, and indicate DNMT3B as a potential target to improve clinical response. Further prospective validation of these findings is warranted. Trial registration: ClinicalTrials.gov Identifier: NCT00203502. [ABSTRACT FROM AUTHOR]

Low unit response rates can increase bias and compromise study validity. Response rates have continued to fall over the past decade despite all efforts to increase participation. Many factors have been linked to reduced response, yet relatively few studies have employed multivariate approaches to identify characteristics that differentiate respondents from nonrespondents since it is hard to collect information on the latter. We aimed to assess factors contributing to enrollment of prostate cancer (PCa) patients. We combined data from the North Carolina-Louisiana (LA) PCa Project’s LA cohort, with additional sources such as US census tract and LA tumor registry data. We included specific analyses focusing on blacks, a group often identified as hard to enroll in health-related research. The ability to study the effect of Hurricane Katrina, which occurred amidst enrollment, as a potential determinant of nonresponse makes our study unique. Older age (≥ 70) for blacks (OR 0.65) and study phase with respect to Hurricane Katrina for both races (OR 0.59 for blacks, OR 0.48 for whites) were significant predictors of participation with lower odds. Neighborhood poverty for whites (OR 1.53) also was a significant predictor of participation, but with higher odds. Among blacks, residence in Orleans parish was associated with lower odds of participation (OR 0.33) before Katrina. The opposite occurred in whites, with lower odds (OR 0.43) after Katrina. Our results overall underscore the importance of tailoring enrollment approaches to specific target population characteristics to confront the challenges posed by nonresponse. Our results also show that recruitment-related factors may change when outside forces bring major alterations to a population's environment and demographics. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to describe the characteristics and etiologic causes of intermediate uveitis (IU) patients seen by a tertiary eye center in Singapore over 8 years. Methods: This was a retrospective analysis of the clinical records of consecutive new cases of IU that presented to the uveitis subspecialty clinic from 2004–2011 at Tan Tock Seng Hospital. Data collected included demographics, clinical and laboratory findings. Diagnoses were based on standardized clinical history, ophthalmological examination and investigations. Results: There were 66 new cases of IU, comprising 5.7% of 1168 new uveitis patients. The median age of diagnosis was 40 years (mean 39.4±15.9), with largest subgroup of the patients in the age group of 41–60 years (36.4%). The majority was Chinese (57.6%), followed by Asian Indians (18.2%) and Malays (16.7%). The ethnicity distribution was dissimilar to our ethnic distribution in Singapore (p<0.001) with an increased incidence of IU in the Asian Indian population. Most were idiopathic (59.1%) in etiology, followed by tuberculosis (TB) (15.2%). Ocular complications developed in 21 patients (31.8%), with cystoid macular edema (CME) being the commonest (28.8%). Severe vitritis occurred in 9.1% of patients, and was significantly associated with TB-associated IU (p<0.001). There was a downward trend for the incidence of the proportion of IU patients over the total uveitis patients (p = 0.021), with Spearman’s rho of −0.786. Conclusions: Despite the downward trend, TB-associated IU was still of higher prevalence compared to less endemic areas, emphasizing the need for increased TB surveillance. A high index of suspicion for TB-associated IU is required in patients with severe vitritis. Comparisons with other countries revealed disparities in the IU etiologies, indicating possible geographical differences. Prevalence of known immune-mediated etiologies of IU is less compared to the western population. Our study also suggests a probable predisposition of the Singapore local Indian population for IU. [ABSTRACT FROM AUTHOR]

Background: Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP. Methods: Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/ Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states. Results: Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified nonethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA. Conclusions: Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP. [ABSTRACT FROM AUTHOR]

In this paper, we focus on a dynamic Cournot game in the market with a nonlinear (isoelastic) demand function. In our model, there are N competing firms featured by nonlinear cost functions, which enhances our model's resemblance to real-world scenarios. Firstly, we focus on the homogeneous case where firms' marginal costs change at equal rates. We establish analytical expressions of the market supply at equilibrium and perform comparative static analysis. In addition, we investigate the local stability under different economies of scale and show that there could be multiple stable equilibria if firms face economies of scale. The heterogeneous case where firms' marginal costs change at distinct rates is much more complex, thus we investigate the duopoly game with only two firms involved. Methods of symbolic computations such as triangular decomposition and partial cylindrical algebraic decomposition are employed in the analytical investigations of the equilibrium, which is nearly impossible by using the pencil-and-paper approach since the closed-form equilibrium is quite complicated. According to the computational results, we derive that two stable positive equilibria may coexist if both firms face economies of scale. Additionally, we conduct preliminary numerical simulations and find two different types of complex dynamics of the model considered in this paper: complex trajectories such as periodic and chaotic orbits may appear; the topological structure of the basins of attraction may be complex., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The development of the digital economy constitutes a key component of China's endeavors to advance towards "Digital China." The sports industry functions as a new catalyst for high-quality economic growth. This study systematically evaluated the integration between these two sectors., Methods: First, we conducted two levels of grey relational analysis to assess their integration between 2016 and 2021. Second, we conducted a VAR analysis to determine whether their integration between 2009 and 2021 represents a causal relationship., Results: At the macro level, the grey relational analysis reveals that the sports industry (grade = 0.770) ranked second among China's eight key economic sectors in terms of digital economy integration. At the meso level, a wide variation (ranging from 0.606 to 0.789) existed in the grade of integration between the digital economy and the sub-sectors of the sports industry. According to the VAR model, the digital economy does not Granger cause (p = 0.344) the growth of the sports industry., Conclusions: This study yielded two added values to the existing literature: First, there exists a sectoral imbalance in the digitization process; second, the explosive growth of the sports industry was not primarily caused by the digital economy. Accordingly, the "sports + digital" complex is still in the first wave of technological integration. We propose three policy recommendations, namely, sectoral synergistic development, overtaking via esports IP, and new economy and new regulation. Collectively, these findings provide updated insights for the digital transformation towards "building a leading sports nation" and "Digital China.", Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Few studies on molecular epidemiology have studied people with newly diagnosed HIV infection and ART Failure Patients at the same time in rural China. With more serious HIV epidemic than in other provinces in China, Sichuan is an area suitable for this study., Objective: To analyze the characteristics of HIV-1 molecular networks and factors related to network entry among newly diagnosed HIV infection and ART Failure Patients in three county-level cities (A, B, C) in Sichuan Province, to provide scientific basis for accurate prevention and control., Methods: Nested PCR amplification method was used to amplify HIV-1 pol gene region of 530 blood samples, Sequencer 4.9 was used to edit, clean and splice the gene sequence, Bioedit correction, Fastree 2.1.8 and Figtree 1.4.2 to construct evolutionary tree and determine genotype. HyPhy2.2.4 and Cytoscape 3.6.1 software were used to construct molecular network. Logistic regression analysis was applied., Results: 523(98.68%) pol sequences were obtained, and a total of 518 valid sequences with basic information came into the final analyses. A total of 6 genotypes were detected, namely CRF01&#95;AE (320,61.78%), CRF07&#95;BC (149,28.76%), B (30,5.79%), CRF08&#95;BC (11, 2.12%), CRF55&#95;01B (6, 1.16%) and C (2, 0.39%). 186 of 518(35.91%) sequences entered the network at a genetic distance of 0.8%, forming 42 propagation clusters. "High-risk transmitters"(connected with two and more) accounted for 21.62%. Logistic regression showed that≥50 years old (OR = 2.474) were more risky than 18-49 years old, CRF07&#95;BC sub-type (OR = 0.174) were less risky than CRF01&#95;AE sub-type, B sub-type (OR = 6.698) is higher risky than CRF01&#95;AE sub-type, and District B (OR = 0.077) less risky than that of A city., Conclusion: The sources of HIV infection in rural Sichuan are diversified and complicated. The prevention and control of HIV infection in Sichuan Province should focus on strengthening the long-term dynamic detection of elderly population, B strain sub-type, and in City A., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In 2014, the Chinese government unveiled the New Urbanization Plan and Document No. 46, which profoundly influenced the development trajectory of the regional economy and sports industry. Using the coupling coordination model, this study aimed to assess the development progress of the sports industry and urban clusters economy. This study sampled Greater Bay Area urban clusters (GBAUC) and Yangtze River Delta urban clusters (YRDUC). The statistics covered one year after the release of the policies to date. We developed a total of 15 macro indicators to evaluate the sports industry and urban cluster economy as two distinct, yet interdependent, economic systems. Using the entropy weight method, we determined the standardized values and weights for the two systems before calculating the coupling coordination degree (D). Between 2015 and 2021, the sampled sports industry and urban clusters economy exhibited coordinated high growth across all economic metrics, with multiple sports industry metrics exhibiting double-digit growth. In 2015, both showed extreme imbalance: D of GBAUC = 0.092, D of YRDUC = 0.091. In 2017, both improved to bare coordination: D of GBAUC = 0.600, D of YRDUC = 0.566. In 2019, both reached well coordination: D of GBAUC = 0.851, D of YRDUC = 0.814. By 2021, both achieved quality coordination: D of GBAUC = 0.990, D of YRDUC = 1. This study provides the first evidence from the sports industry that China's new urbanization model and Document No. 46 are highly effective for synergistic regional economic growth., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Toxoplasma gondii (T. gondii) is a zoonotic parasite that can cause serious pathology in intermediate hosts such as humans and animals. Eating undercooked or raw meat is the most important route of infection by T. gondii. Sheep are an important source of meat worldwide, and they are also susceptible to T. gondii. Mutton infected with T. gondii poses a serious threat to the food safety of consumers. At present, studies have mainly focused on the infection ratio of T. gondii in livestock; however, systematic studies have not been performed on differences in the distribution of this parasite in different muscle and viscera tissues of animals. In this study, the differences in the distribution of T. gondii in naturally infected Small-tailed Han sheep was studied. By amplifying the B1 gene of the parasite via real-time fluorescence quantification PCR (RT‒qPCR), we found that the parasite burden of T. gondii differed among different parts of the sheep, with the highest burden observed in the heart among the viscera and the external ridge among the muscle. The relative expression was ranked from high to low in our study as follows: heart, spleen, external ridge, tenderloin, lung, liver, kidney, neck meat, forelegs, cucumber strips, hind leg, lamb belly, and lamb chops. This study provided important guidance for monitoring the food safety of mutton products., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear., Method: We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al., Results: Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy., Conclusions: The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations., Competing Interests: the authors declare that they have no conflict of interest., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Serum lactate dehydrogenase levels reflect disease status in a variety of organs, but its role in indicating pulmonary function is not yet clear. Therefore, this study explored the correlation between pulmonary function and serum lactate dehydrogenase, and investigated thresholds for changes in pulmonary function indicators in the total population as well as in different strata of the population., Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 (n = 3453), univariate and stratified analyses were performed to investigate factors associated with pulmonary function, and multiple regression analysis was used to further investigate the specific relationship with serum lactate dehydrogenase. Smoothed curve fitting, threshold effect and saturation effect analysis were used to explore the threshold level of serum lactate dehydrogenase at the onset of changes in pulmonary function indicators., Results: Adjusted smoothed curve fit plots showed a linear relationship between serum lactate dehydrogenase levels and forced vital capacity and forced expiratory volume in one second: for each 1 U/L increase in serum lactate dehydrogenase levels, forced vital capacity decreased by 1.24 mL (95% CI = -2.05, -0.42, P = 0.0030) and forced expiratory volume in one second by 1.11 mL (95% CI = -1.82, -0.39, P = 0.0025)., Conclusions: Serum lactate dehydrogenase was negatively and linearly correlated with pulmonary function indices in the total population analyzed. Based on the total population and different population stratifications, this study determined the threshold values of serum lactate dehydrogenase at the onset of decline of pulmonary function in different populations. This provides a new serological monitoring indicator for patients suffering from respiratory diseases and has implications for patients with possible clinical impairment of pulmonary function. However, our cross-sectional study was not able to determine a causal relationship between these two factors, and further research is needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Proliferative Diabetic Retinopathy (PDR) is a chronic complication of Diabetes and the main cause of blindness among the world's working population at present. While there have been many studies on the pathogenesis of PDR, its intrinsic molecular mechanisms have not yet been fully elucidated. In recent years, several studies have employed bulk RNA-sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) to profile differentially expressed genes (DEGs) and cellular components associated with PDR. This study adds to this expanding body of work by identifying PDR's target genes and cellular components by conducting an integrated transcriptome bioinformatics analysis. This study integrately examined two public bulk RNA-seq datasets(including 11 PDR patients and 7 controls) and one single-cell RNA-seq datasets(including 5 PDR patients) of Fibro (Vascular) Membranes (FVMs) from PDR patients and control. A total of 176 genes were identified as DEGs between PDR patients and control among both bulk RNA-seq datasets. Based on these DEGs, 14 proteins were identified in the protein overlap within the significant ligand-receptor interactions of retinal FVMs and Protein-Protein Interaction (PPI) network, three of which were associated with PDR (CD44, ICAM1, POSTN), and POSTN might act as key ligand. This finding may provide novel gene signatures and therapeutic targets for PDR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Automatic estimation of the poses of dairy cows over a long period can provide relevant information regarding their status and well-being in precision farming. Due to appearance similarity, cow pose estimation is challenging. To monitor the health of dairy cows in actual farm environments, a multicow pose estimation algorithm was proposed in this study. First, a monitoring system was established at a dairy cow breeding site, and 175 surveillance videos of 10 different cows were used as raw data to construct object detection and pose estimation data sets. To achieve the detection of multiple cows, the You Only Look Once (YOLO)v4 model based on CSPDarkNet53 was built and fine-tuned to output the bounding box for further pose estimation. On the test set of 400 images including single and multiple cows throughout the whole day, the average precision (AP) reached 94.58%. Second, the keypoint heatmaps and part affinity field (PAF) were extracted to match the keypoints of the same cow based on the real-time multiperson 2D pose detection model. To verify the performance of the algorithm, 200 single-object images and 200 dual-object images with occlusions were tested under different light conditions. The test results showed that the AP of leg keypoints was the highest, reaching 91.6%, regardless of day or night and single cows or double cows. This was followed by the AP values of the back, neck and head, sequentially. The AP of single cow pose estimation was 85% during the day and 78.1% at night, compared to double cows with occlusion, for which the values were 74.3% and 71.6%, respectively. The keypoint detection rate decreased when the occlusion was severe. However, in actual cow breeding sites, cows are seldom strongly occluded. Finally, a pose classification network was built to estimate the three typical poses (standing, walking and lying) of cows based on the extracted cow skeleton in the bounding box, achieving precision of 91.67%, 92.97% and 99.23%, respectively. The results showed that the algorithm proposed in this study exhibited a relatively high detection rate. Therefore, the proposed method can provide a theoretical reference for animal pose estimation in large-scale precision livestock farming., Competing Interests: The authors have declared that no competing interests exist.

Cistanche deserticola Ma (cistanche) is a traditional herb with a wide range of therapeutic properties. However, no evidence of cistanche's effect on adipogenesis has been found. The effect of cistanche that promotes the adipogenesis of 3T3-L1 preadipocytes was proved by using MTT spectrophotometry, Nile Red staining, Oil Red O staining and transcriptome sequencing technology. The mRNA level of key transcription factors for adipogenesis such as PPAR, AP2 and LPL were examined by RT-PCR. The results showed that the intracellular lipid content in cistanche treated cells were notably increased when compared with the non-treated cells. Between the differentiation and cistanche treated groups, the expression of adipogenesis related genes such as grow hormone releasing hormone (Ghrp), BCL2/adenovirus E1B interacting protein 3 (Bnip3) and Gastric inhibitory polypeptide receptor (Gipr) were significantly increased. Our findings also verified that cistanche promoted adipogenesis, which was accompanied by up-regulated level of Bnip3 and PPAR. This study could uncover new signaling pathways involved in adipogenesis regulation., Competing Interests: The authors have declared that no competing interests exist.

Microorganisms regulate the redox state of different biomolecules to precisely control biological processes. These processes can be modulated by electrochemically coupling intracellular biomolecules to an external electrode, but current approaches afford only limited control and specificity. Here we describe specific electrochemical control of the reduction of intracellular biomolecules in Escherichia coli through introduction of a heterologous electron transfer pathway. E. coli expressing cymAmtrCAB from Shewanella oneidensis MR-1 consumed electrons directly from a cathode when fumarate or nitrate, both intracellular electron acceptors, were present. The fumarate-triggered current consumption occurred only when fumarate reductase was present, indicating all the electrons passed through this enzyme. Moreover, CymAMtrCAB-expressing E. coli used current to stoichiometrically reduce nitrate. Thus, our work introduces a modular genetic tool to reduce a specific intracellular redox molecule with an electrode, opening the possibility of electronically controlling biological processes such as biosynthesis and growth in any microorganism., Competing Interests: The authors have declared that no competing interests exist.

Successful CAR T cell therapy for the treatment of solid tumors requires exemplary CAR T cell expansion, persistence and fitness, and the ability to target tumor antigens safely. Here we address this constellation of critical attributes for successful cellular therapy by using integrated technologies that simplify development and derisk clinical translation. We have developed a CAR-CD19 T cell that secretes a CD19-anti-Her2 bridging protein. This cell therapy strategy exploits the ability of CD19-targeting CAR T cells to interact with CD19 on normal B cells to drive expansion, persistence and fitness. The secreted bridging protein potently binds to Her2-positive tumor cells, mediating CAR-CD19 T cell cytotoxicity in vitro and in vivo. Because of its short half-life, the secreted bridging protein will selectively accumulate at the site of highest antigen expression, ie. at the tumor. Bridging proteins that bind to multiple different tumor antigens have been created. Therefore, antigen-bridging CAR-CD19 T cells incorporate critical attributes for successful solid tumor cell therapy. This platform can be exploited to attack tumor antigens on any cancer., Competing Interests: The authors have read the journal’s policy, and the authors of the study have the following competing interests to declare: Aleta Biotherapeutics is wholly funded by Advent Life Science Partners, a venture capital firm. Advent Life Sciences provided support in the form of salaries for authors [CA, LS, LW, FJD, AB, PDR], and paid consulting fees [RRL]. Aleta Biotherapeutics funded BJH’s research at the University of Minnesota for a period of time, resulting in a shared patent filing. The agreement with Univ Minnesota was for a one-time payment from Aleta to secure all of the patent rights (assigned by Dr Hackel to UMN). The patent is "CD19 VARIANTS" US Appln. No. 62/599,211; Filed: December 15, 2017. The research sponsorship has since ended and that financial relationship in no manner has influenced the work contained in this manuscript. Aleta Biotherapeutics paid consultancy fees to HA in the past. The consultancy has since ended and that financial relationship in no manner has influenced the work contained in this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other products in development or marketed products associated with this research to declare.

The Sm proteins are a conserved protein family with Sm motifs. The family includes Sm and Sm-like proteins, which play important roles in pre-mRNA splicing. Most research on the Sm proteins have been conducted in herbaceous plants, and less in woody plants such as Dimocarpus longan (longan). And the embryo development status significantly affects the quality and yield of longan. In this study, we conducted a genome-wide analysis of longan Sm genes (DlSm) to clarify their roles during somatic embryogenesis (SE) and identified 29 Sm genes. Phylogenetic analysis deduced longan Sm proteins clustered into 17 phylogenetic groups with the homologous Sm proteins of Arabidopsis thaliana. We also analyzed the gene structures, motif compositions, and conserved domains of the longan Sm proteins. The promoter sequences of the DlSm genes contained many light, endosperm development, hormone, and temperature response elements, which suggested their possible functions. In the non-embryogenic callus(NEC) and during early SE in longan, the alternative splicing(AS) events of DlSm genes indicated that these genes may influence SE development by changing gene structures and sequences. The kinetin(KT) hormone, and blue and white light treatments affected the differentiation and growth of longan embryonic callus(EC) probably by affecting the AS events of DlSm genes. Expression profiles showed the possible functional divergence among Sm genes, and different hormones and light qualities affected their expression levels. The expression trends of the DlSm genes determined by RNA sequencing as fragments per kilobase of exon model per million mapped reads (FPKM) and by real-time quantitative PCR(qRT-PCR) during early SE in longan showed that the expression of the DlSm genes was affected by the growth and differentiation of longan SE, and decreased as the somatic embryo differentiation progressed. The results will contributed to understanding the longan Sm gene family and provide a basis for future functional validation studies., Competing Interests: The authors have declared that no competing interests exist.

Interleukin 11 (IL11) is a profibrotic cytokine, secreted by myofibroblasts and damaged epithelial cells. Smooth muscle cells (SMCs) also secrete IL11 under pathological conditions and express the IL11 receptor. Here we examined the effects of SMC-specific, conditional expression of murine IL11 in a transgenic mouse (Il11SMC). Within days of transgene activation, Il11SMC mice developed loose stools and progressive bleeding and rectal prolapse, which was associated with a 65% mortality by two weeks. The bowel of Il11SMC mice was inflamed, fibrotic and had a thickened wall, which was accompanied by activation of ERK and STAT3. In other organs, including the heart, lung, liver, kidney and skin there was a phenotypic spectrum of fibro-inflammation, together with consistent ERK activation. To investigate further the importance of stromal-derived IL11 in the inflammatory bowel phenotype we used a second model with fibroblast-specific expression of IL11, the Il11Fib mouse. This additional model largely phenocopied the Il11SMC bowel phenotype. These data show that IL11 secretion from the stromal niche is sufficient to drive inflammatory bowel disease in mice. Given that IL11 expression in colonic stromal cells predicts anti-TNF therapy failure in patients with ulcerative colitis or Crohn's disease, we suggest IL11 as a therapeutic target for inflammatory bowel disease., Competing Interests: S.A.C. and S.S. are co-inventors of the patent applications ‘Treatment of fibrosis’ (WO/2017/103108). S.A.C., S.S., W.W.L. and B.N. are co-inventors of the patent application ‘Treatment of SMC mediated disease’ (WO/2019/073057). S.A.C. and S.S. are co-founders and shareholders of Enleofen Bio PTE LTD, a company (which S.A.C. is a director of) that develops anti-IL11 therapeutics. All other authors declare no competing interests.

Numerous factors affect reaction times to vibrotactile cues. Therefore, it is important to consider the relative magnitudes of these time delays when designing vibrotactile displays for real-time applications. The objectives of this study were to quantify reaction times to typical vibrotactile stimuli parameters through direct comparison within a single experimental setting, and to determine the relative importance of these factors on reaction times. Young (n = 10, 21.9 ± 1.3 yrs) and older adults (n = 13, 69.4 ± 5.0 yrs) performed simple reaction time tasks by responding to vibrotactile stimuli using a thumb trigger while frequency, location, auditory cues, number of tactors in the same location, and tactor type were varied. Participants also performed a secondary task in a subset of the trials. The factors investigated in this study affected reaction times by 20-300 ms (reaction time findings are noted in parentheses) depending on the specific stimuli condition. In general, auditory cues generated by the tactors (<20 ms), vibration frequency (<20 ms), number of tactors in the same location (<30 ms) and tactor type (<50 ms) had relatively small effects on reaction times, while stimulus location (20-120 ms) and secondary cognitive task (>130 ms) had relatively large effects. Factors affected young and older adults' reaction times in a similar manner, but with different magnitudes. These findings can inform the development of vibrotactile displays by enabling designers to directly compare the relative effects of key factors on reaction times., Competing Interests: The authors have declared that no competing interests exist.

Objective: The purpose of this study was to evaluate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cardiovascular disease (CVD) risk factors in adults with overweight and obesity., Methods: Twenty-two articles were included by searching six databases, the total number of subjects was 620 in these articles. Outcomes were synthesised using a random-effects meta-analysis of the Standardized mean difference (SMD) in CVD risk factors., Results: HIIT and MICT resulted in statistically significant reductions in Weight, BMI, fat%, total cholesterol(TC), and improvement in VO2max. Compared with MICT, subgroup of durations of HIIT training interval ≥2 min can significantly increase VO2max (SMD = 0.444, 95% CI:0.037~0.851,P = 0.032), subgroup of energy expenditure of HIIT equal to MICT can significantly increase VO2max (SMD = 0.399, 95% CI:0.106~0.692,P = 0.008)., Conclusions: HIIT appears to provide similar benefits to MICT for improving body composition, VO2maxand TC, but HIIT spent less time than MICT by 9.7 min on one session. HIIT is superior to MICT in improving cardiopulmonary fitness when durations of HIIT training interval ≥2 min or energy expenditure of HIIT same as MICT. PROSPERO ID: CRD42016045835., Competing Interests: The authors have declared that no competing interests exist.

Certain organs are capable of containing the replication of various types of viruses. In the liver, infection of Hepatitis B virus (HBV), the etiological factor of Hepatitis B and hepatocellular carcinoma (HCC), often remains asymptomatic and leads to a chronic carrier state. Here we investigated how hepatocytes contain HBV replication and promote their own survival by orchestrating a translational defense mechanism via the stress-sensitive SUMO-2/3-specific peptidase SENP3. We found that SENP3 expression level decreased in HBV-infected hepatocytes in various models including HepG2-NTCP cell lines and a humanized mouse model. Downregulation of SENP3 reduced HBV replication and boosted host protein translation. We also discovered that IQGAP2, a Ras GTPase-activating-like protein, is a key substrate for SENP3-mediated de-SUMOylation. Downregulation of SENP3 in HBV infected cells facilitated IQGAP2 SUMOylation and degradation, which leads to suppression of HBV gene expression and restoration of global translation of host genes via modulation of AKT phosphorylation. Thus, The SENP3-IQGAP2 de-SUMOylation axis is a host defense mechanism of hepatocytes that restores host protein translation and suppresses HBV gene expression., Competing Interests: The co-authors Dr. Yan Han and Dr. Ji Wan are currently employed by CuraCloud Corporation, which had no role or any financial interest in the submitted manuscript. Their current employment does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents or products in development to declare. The other authors declare no competing interests.

Large currents are injected into the earth from grounding poles of HVDC systems under monopole ground return mode. The currents change the earth surface potential and result in DC currents in AC systems. This paper proposes a computationally efficient decoupled circuital calculation method for assessing the unwanted DC currents in AC grids. Firstly, the earth resistive network is acquired by simulating the DC grounding current distribution using Finite Element Method (FEM). Secondly, the earth resistive network and AC grid are combined to develop a decoupled circuital model of the overall system. The acquired model is used to calculate the DC currents in AC grids by solving a set of linear equations. The proposed method is computationally more efficient as compared to field-circuit coupled methods. In addition, its accuracy is proved by showing a close agreement between our results and field-circuit coupled model as well as the actual measurements. Finally, in Shanghai area power grid the DC currents are calculated using the proposed technique. Based on these calculations, remedial measures for reducing the DC currents in AC grid are suggested. Our research results indicate that DC currents in AC systems can be reduced by operating the two HVDC projects with opposite polarities., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Shanghai Electric Power Company provided support in the form of salaries for authors CF, DZ, and LS. State Grid Chengdu Power Supply Company provided support in the form of salaries for author HL. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Our purpose is to evaluate the efficacy and safety of pharmacologic thromboprophylaxis following caesarean section (CS)., Methods: We searched PubMed, Embase, and the Cochrane Library. Then the systematic review was performed by analysing studies that met the eligibility criteria., Results: Seven studies with 1243 participants were included, including 6 RCTs and 1 prospective cohort. Results from the meta-analysis showed that low molecular weight heparin (LMWH) was associated with no obvious decrease in the risk of thrombus compared with UHF and negative control. However, LMWH was observed to be associated with a definite increase in the risk of bleeding or haematomas in comparison to negative control (RR: 8.47, CI: 1.52-47.11)., Conclusion: According to current evidences, the efficacy of pharmacologic thromboprophylaxis which increases the risk of bleeding or hematomas remains controversial., Competing Interests: The authors have declared that no competing interests exist.

Objective: To assess the quality and diagnostic accuracy of monochromatic images combined with adaptive statistical iterative reconstruction (ASIR) performed via spectral computed tomography (CT) in patients with Budd-Chiari syndrome (BCS)., Methods: Sixty-two patients with BCS underwent pectral CT with upper abdominal two-phase contrast-enhanced scanning to generate a 60keV monochromatic energy level combined with ASIR (ranging from 0% -100%) during the portal venous phase (PVP) and the hepatic venous phase (HVP). One-way ANOVA was used to compare vessel-to-liver contrast-to-noise ratio (CNR) for the portal vein (PV), hepatic vein (HV), and inferior vena cava (IVC). Subjective evaluations of the images in the three groups were conducted by image quality assessors and compared via Kruskal-Wallis H test., Results: The CNR values of the PV trunk, HV, IVC, liver parenchyma and pancreas were within ASIR (ranging from 0% - 100%) weight, and the difference were statistically significant (p <0.05). The highest overall image score was distributed at 50% ASIR weight value. Higher CNR values of HV, hepatic parenchyma and pancreas were obtained in the IVC type than in mixed and HV types (respective p values = 0.035, 0.019 and 0.042). Higher CNR values of the IVC were obtained in the HV type than in mixed and IVC types (p = 0.032). The CNR value of the IVC in the mixed type was less than that of the HV type (p = 0.028). The CNR values of the HV and liver parenchyma in mixed type were lower than those of the IVC type (p = 0.016 and 0.038, respectively). The CNR value of pancreas in IVC type was higher than that of the HV type (p = 0.037). The diagnostic value of CNR in patients with the IVC type was higher than that in patients with mixed and HV type, while the diagnostic value of CNR was found to be the lowest for the HV type (p = 0.043)., Conclusion: A monochromatic energy level of 60 keV with 50% ASIR can significantly improve image quality in cases of BCS., Competing Interests: The authors have declared that no competing interests exist.

Titin (TTN) Truncating variants (TTNtv) in the A-band of TTN predispose the mouse heart to systolic dysfunction when subjected to pressure-loading. However, the effects of TTNtv of the Z-disc are largely unexplored. A rat model of pressure-loaded heart is developed by trans-aortic constriction (TAC). Rats with TTNtv of the Z-disc were randomly assigned to TAC (Z-TAC) or sham-surgery (Z-Sham) and wildtype (WT) littermates served as controls (WT-TAC or WT-Sham). Left ventricular (LV) function was assessed by echocardiography. Pressure volume (PV) loops, histology and molecular profiling were performed eight months after surgery. Pressure-load by TAC increased LV mass in all cases when compared with Sham animals. Notably, systolic function was preserved in TAC animals throughout the study period, which was confirmed by terminal PV loops. Diastolic function was impaired in Z-disc TTNtv rats at baseline as compared to WT and became impaired further after TAC (dp/dtmin, mmHg/s): Z-TAC = -3435±763, WT-TAC = -6497±1299 (p<0.01). Z-TAC animals had greater cardiac fibrosis, with elevated collagen content and decreased vascular density as compared to WT-TAC animals associated with enhanced apoptosis of myocyte and non-myocyte populations. In the context of pressure overload, Z-disc TTNtv is associated with cardiac fibrosis, diastolic dysfunction, and capillary rarefaction in the absence of overt systolic dysfunction., Competing Interests: The authors have declared that no competing interests exist.

Aim: Critical care ultrasound (CCUS) has been used by many Intensive Care Units(ICUs) worldwide, so as to guiding the diagnosis and the treatment. However, none of the publications currently systematically describe the utilization of CCUS to analyze the characteristics of hemodynamics and lung pathology upon the new admission to ICU and its potential role in patients' prognosis prediction. In this retrospective clinical study, we have demonstrated and analyzed the characteristics of hemodynamics and lung pathology assessed by CCUS and investigated its potential to predict patient outcome., Methods: We have described and analyzed the epidemic characteristics of hemodynamics and lung pathology assessed by CCUS on ICU admission, which based on our database of 451 cases from the biggest medical center in Western China, between November 2014 and October 2015. The patients' demographics, clinical characteristics, prognosis and ultrasonic pattern of hemodynamics and lung pathology had been analyzed. A bivariate logistic regression model was established to identify the correlation between the ultrasonic variables on admission and the ICU mortality., Results: The mean age of the 451 patients was 56.7±18.7 years; the mean APACHE II score was 19.0±7.9, the ICU mortality was 30.6%. Patients received CCUS examination of pericardial, right ventricle (RV) wall motion, left ventricle (LV) wall motion, LV systolic function, LV diastolic function, lung and volume of inferior vena cava (IVC) were 423(93.8%), 418(92.7%), 392(86.9%), 389(86.3%), 383(84.9%), 440(97.6%), 336(74.5%), respectively; The univariate analysis revealed that length of mechanical ventilation was significantly correlated with the diameter of IVC, tricuspid annular plane systolic excursion(TAPSE), mitral annular plane systolic excursion(MAPSE), early diastolic transmitral velocity to early mitral annulus diastolic velocity(E/e') (p = 0.016, 0.011, 0.000, 0.049, respectively); The TAPSE, ejection fraction(EF), MAPSE, lung ultrasound score (LUS score) (p = 0.000, 0.028, 0.000, 0.011, respectively) were significantly related to ICU mortality. The multivariate analysis demonstrated that APACHE II, age, TAPSE, E/e' are the independent risk factors for ICU mortality in our study., Conclusion: CCUS examination on ICU admission which performed by the experienced physician provide valuable information to assist the caregivers in understanding the comprehensive outlook of the characteristics of hemodynamics and lung pathology. Those key variables obtained by CCUS predict the possible prognosis of patients, hence deserve more attention in clinical decision making.

GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer.

Isoflavonoids are secondary metabolites that play a variety of roles in plant-microbe interactions and plant defenses against abiotic stresses. Here we report a new MYB transcription factor (TF) gene, GmMYBJ3, that is involved in the isoflavonoids biosynthesis. The GmMYBJ3 gene is 1,002 bp long and encodes a protein of 333 amino acids. Amino acid sequence analysis showed that GmMYBJ3 is a typical R2R3 MYB TF. Yeast expression experiment demonstrated that GmMYBJ3 has its transcription activity in the nucleus and is transiently expressed in onion epidermal cells. The GmMYBJ3 gene was transformed into soybean and the expression activity of the GmMYBJ3 gene was significantly positively correlated with total isoflavonoid accumulation in soybean. Transient expression assays indicated that GmMYBJ3 can activate CHS8 expression. Furthermore, we analyzed the expressions of several genes known involved in the isoflavonoid biosynthesis, including CHS8, CHI1A, PAL1, IFS2 and F3H, in the GmMYBJ3 transgenic plants. The results showed that the expression levels of CHS8 and CHI1A were significantly increased in the transgenic plants compared to wild-type plants, but those of PAL1, IFS2 and F3H remained similar between the transgenic and wild-type plants. These results suggest that GmMYBJ3 participates in the isoflavonoid biosynthesis through regulation of CHS8 and CHI1A in soybean.

Transformation is the main platform for genetic improvement and gene function studies in plants. However, the established somatic embryo transformation system for grapevines is time-consuming and has low efficiency, which limits its utilization in functional genomics research. Vitis amurensis is a wild Vitis species with remarkable cold tolerance. The lack of an efficient genetic transformation system for it has significantly hindered the functional identification of cold stress related genes in the species. Herein, an efficient method was established to produce transformed calli of V. amurensis. Segments of petioles from micropropagated plantlets of V. amurensis exhibited better capacity to differentiate calli than leaf-discs and stem segments, and thus was chosen as target tissue for Agrobacterium-mediated transformation. Both neomycin phosphotransferase II (NPTII) and enhanced green fluorescent protein (eGFP) genes were used for simultaneous selection of transgenic calli based on kanamycin resistance and eGFP fluorescence. Several parameters affecting the transformation efficiency were optimized including the concentration of kanamycin, Agrobacterium stains, bacterial densities, infection treatments and co-cultivation time. The transgenic callus lines were verified by checking the integration of NPTII gene into calli genomes, the expression of eGFP gene and the fluorescence of eGFP. Up to 20% of the petiole segments produced transformed calli after 2 months of cultivation. This efficient transformation system will facilitate the functional analysis of agronomic characteristics and related genes not only in V. amurensis but also in other grapevine species.

Background: Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR)., Methods: SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure., Results: We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group., Conclusions: Radiofrequency-mediated perivascular RDN may become a feasible procedure against hypertension, and provide similar anti-hypertensive and target organ protective effects as does the chemical ablation.

Liraglutide is administered as glucagon-like peptide-1 (GLP-1) receptor agonist for diabetic patients and can protect pancreatic β-cells by inhibiting their apoptosis. MicroRNA-139-5p (miRNA-139-5p) participates in the regulation of cancer cell apoptosis. However, it is not clear whether miR-139-5p contributes to the anti-apoptotic effect of liraglutide in β-cells. The objective of the present study was to investigate the role of miR-139-5p on apoptosis of pancreatic β-cells. MicroRNA levels in pancreatic tissue from diabetic rats and INS-1 cells treated with liraglutide were measured by real-time quantitative RT-PCR. The role of miR-139-5p on apoptosis was studied by transfecting INS-1 cells with miR-139-5p mimics. The mRNA and protein expression of the target gene, insulin receptor substrate-1 (IRS1), were measured by qRT-PCR and Western blot, respectively. Apoptosis in rat pancreatic tissue and INS-1 cells was detected by TUNEL and annexin V/propidium iodide costaining. Apoptosis of pancreatic tissue from diabetic rats and INS-1 cells was decreased by administration of liraglutide. The expression of miR-139-5p increased in the pancreas of diabetic rats and decreased with liraglutide treatment. Incubation with liraglutide (100 nM) for 48 h attenuated the expression of miR-139-5p and increased the mRNA and protein levels of IRS1. Direct regulatory effects of miR-139-5p on IRS1 were found by a dual-luciferase reporter assay. Transfection of INS-1 cells with miR-139-5p mimics led to decreases in the mRNA and protein expression of IRS1. In conclusion, our observations suggest that decreased miR-139-5p expression contributes to the anti-apoptotic effect of liraglutide on the diabetic rat pancreas and INS-1 cells by targeting IRS1.

Background and Aims: Recent studies reveal the accumulation of myeloid derived suppressor cells (MDSCs) in human peripheral blood mononuclear cells (PBMCs) following HCV infection, which may facilitate and maintain HCV persistent infection. The mechanisms by which HCV induces MDSCs are poorly understood. In the present study, we investigated the mechanisms by which HCV induces MDSCs that lead to suppression of T cell proliferation and expansion of CD4+Foxp3+ regulatory T cells., Methods: Purified monocytes from healthy donors were cultured with HCV core protein (HCVc) or cell culture-derived HCV virions (HCVcc), and characterized the phenotype and function of these monocytes by flow cytometry, quantitative PCR, ELISA and western blot assays. In addition, peripheral blood from healthy donors and chronic HCV infected patients was collected, and MDSCs and CD4+CD25+CD127- regulatory T cells were analyzed by flow cytometry., Results: Both HCVc and HCVcc induced expression of IDO1, PD-L1 and IL-10, and significantly down-regulated HLA-DR expression in human monocytes. HCVc-treated monocytes triggered CD4+Foxp3+ Tregs expansion, and inhibited autologous CD4+ T cell activation in an IDO1-dependent fashion. Our results showed that HCV virions or HCV core proteins induced MDSC-like suppressive monocytes via the TLR2/PI3K/AKT/STAT3 signaling pathway. Monocytes derived from patients with chronic HCV infection displayed MDSCs characteristics. Moreover, the percentages of CD14+ MDSCs and CD4+CD25+CD127- Tregs in chronic HCV infected patients were significantly higher than healthy individuals, and the frequency of MDSCs correlated with CD4+CD25+CD127- Tregs., Conclusions: HCV induced MDSC-like suppressive monocytes through TLR2/PI3K/AKT/STAT3 signaling pathway to induce CD4+Foxp3+ regulatory T cells and inhibit autologous CD4+ T cell activation. It will be of interest to test whether antagonizing suppressive functions of MDSCs could enhance immune responses and virus control in chronic HCV infection., Competing Interests: The authors have declared that no competing interests exist.

Nonalcoholic fatty liver disease (NAFLD) has been found to be highly prevalent in psoriatic patients. Adult onset psoriasis could be divided into either early or late onset psoriasis. The associations between NAFLD and related metabolic comorbidities and age at onset of psoriasis have not yet been investigated. Our study was to evaluate the associations between prevalence of NAFLD and related metabolic conditions and early, late, and childhood onset psoriasis. A cross-sectional observational study was conducted on patients with moderate to severe plaque psoriasis. Data on clinical characteristics of NAFLD and related metabolic diseases (diabetes, hypertriglyceridemia, hyperuricemia, and metabolic syndrome) were collected. The prevalence of NAFLD in 439 patients (mean: 51±14 years, range: 18-85 years) was 55.8%. NAFLD was frequently identified in early onset patients (74.2%), and this diagnosis was particularly common in patients currently younger than 40 (85.3%). Diabetes was the least prevalent component of metabolic syndrome in early onset patients with metabolic syndrome but the most often found component in late onset ones. Patients with childhood onset psoriasis had the lowest frequencies of all metabolic comorbidities except hyperuricemia among the three groups. In the multivariate analyses, early onset was independently and positively associated with NAFLD, hypertriglyceridemia and hyperuricemia and independently and negatively associated with diabetes among early and late onset patients. The results suggested prevalence of NAFLD and related metabolic comorbidities was associated with age at onset of moderate to severe plaque psoriasis. Early onset of psoriasis was independently associated with greater odds of NAFLD, hypertriglyceridemia, hyperuricemia and smaller odds of diabetes compared to late onset. Early onset patients have metabolic syndrome mainly related to lipid disorders and abnormal glucose metabolism was not often involved., Competing Interests: The authors have declared that no competing interests exist.

SLC7A5, who is also named LAT-1, has been validated as a promoter regulated by miRNA-126 in our previous research for gastric cancer cells. However, the mechanisms driving SLC7A5 to affect the bio-function of gastric cancer cells are unclear, remaining us lots of to elucidate. The aim of this study is to investigate the regulating effect of CRKL, one of the critical genes involving with gastric cancer progression, on SLC7A5 expression. By studying the gastric cancer cell lines and clinical pathological specimens, we found that the expression of SLC7A5 was significantly correlated to CRKL. By depleting CRKL in gastric cancer SGC-7901 cells, the SLC7A5 expression was impaired, and the invasion and migration of SGC-7901 cells were suppressed. Ectopic expression of SLC7A5 could drastically rescue the phenotypes induced by CRKL depletion in this study. Accordingly, we conclude that SLC7A5 functions as a promoter in gastric cancer metastasis, and CRKL could be one of its regulators modulating the expression of SLC7A5 and consequentially affect the metastatic feature of SGC-7901 cells. The findings in this study indicate a regulation relationship between CRKL and SLC7A5, and provide useful evidence for gastric cancer therapeutic strategies., Competing Interests: The authors have declared that no competing interests exist.

MicroRNAs (miRNAs) have been widely accepted as a class of gene expression regulators which post-translationally regulate protein expression. These small noncoding RNAs have been proved closely involved in the modulation of various pathobiological processes in cancer. In this research, we demonstrated that miR-148a expression was significantly down-regulated in gastric cancer tissues in comparison with the matched normal mucosal tissues, and its expression was statistically associated with lymph node metastasis. Ectopic expression of miR-148a inhibited tumor cell proliferation and migration in vitro, and inhibited tumor formation in vivo. Subsequently, we identified cholecystokinin B receptor (CCK-BR) as a direct target of miR-148a using western blot and luciferase activity assay. More importantly, siRNA-induced knockdown of CCK-BR elicited similar anti-oncogenic effects (decreased proliferation and migration) as those induced by enforced miR-148a expression. We also found that miR-148a-mediated anti-cancer effects are dependent on the inhibition of STAT3 and Akt activation, which subsequently regulates the pathways involved in cell proliferation and migration. Taken together, our results suggest that miR-148a serves as a tumor suppressor in human gastric carcinogenesis by targeting CCK-BR via inactivating STAT3 and Akt.

Glutamate decarboxylase (GAD) catalyzes the irreversible decarboxylation of L-glutamate to the valuable food supplement γ-aminobutyric acid (GABA). In this study, GAD from Escherichia coli K12, a pyridoxal phosphate (PLP)-dependent enzyme, was overexpressed in E. coli. The GAD produced in media supplemented with 0.05 mM soluble vitamin B6 analog pyridoxine hydrochloride (GAD-V) activity was 154.8 U mL-1, 1.8-fold higher than that of GAD obtained without supplementation (GAD-C). Purified GAD-V exhibited increased activity (193.4 U mg-1, 1.5-fold higher than that of GAD-C), superior thermostability (2.8-fold greater than that of GAD-C), and higher kcat/Km (1.6-fold higher than that of GAD-C). Under optimal conditions in reactions mixtures lacking added PLP, crude GAD-V converted 500 g L-1 monosodium glutamate (MSG) to GABA with a yield of 100%, and 750 g L-1 MSG with a yield of 88.7%. These results establish the utility of pyridoxine supplementation and lay the foundation for large-scale enzymatic production of GABA.

Background: The efficacy of short-term antiarrhythmic drugs (AADs) use compared with no-AADs prescription after catheter ablation of atrial fibrillation (AF) in preventing atrial arrhythmia recurrence is uncertain., Methods: We searched PubMed, Embase, and the Cochrane Library through December 2015 to identify randomized controlled trials (RCTs) which evaluated the efficacy of short-term AADs use compared with no-AADs prescription after AF ablation in preventing atrial arrhythmia recurrence. The primary outcome was labeled as early atrial arrhythmia recurrence within 3 months after ablation. Secondary outcome was defined as late recurrence after 3 months of ablation. Random-effects model or fixed-effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs)., Results: Six RCTs with 2,667 patients were included into this meta-analysis. Compared with no-AADs administration after AF ablation, short-term AADs use was associated with significant reduction of early atrial arrhythmia recurrence (RR, 0.68; 95% CI, 0.52-0.87; p = 0.003). Trial sequential analysis (TSA) showed that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit, establishing sufficient and conclusive evidence. However, compared with no-AADs prescription, short-term AADs use after AF ablation didn't significantly reduce the risk of late atrial arrhythmia recurrence (RR, 0.92; 95% CI, 0.83-1.03; p = 0.15). TSA supported this result; meanwhile the estimated required information size (1,486 patients) was also met., Conclusion: Short-term use of AADs after AF ablation can significantly decrease the risk of early atrial arrhythmia recurrence but not lead to corresponding reduction in risk of late atrial arrhythmia recurrence.

Soil salinity is a major abiotic stressor affecting plant growth. Salinity affects nitrification and ammonification in the soil, however, limited information is available on the influence of different N sources on N metabolism during salt stress. To understand the N metabolism changes in response to different N sources during moderate salt stress, we investigated N uptake, assimilation and the transcript abundance of associated genes in Populus simonii seedlings treated with moderate salt stress (75mM NaCl) under hydroponic culture conditions with nitrate (NO3-) or ammonium (NH4+). Salt stress negatively affected plant growth in both NH4+-fed and NO3--fed plants. Both NH4+ uptake and the total N concentration were significantly increased in the roots of the NH4+-fed plants during salt stress. However, the NO3- uptake and nitrate reductase (NR) and nitrite reductase (NiR) activity primarily depended on the NO3- supply and was not influenced by salt stress. Salt stress decreased glutamine synthetase (GS) and glutamate synthase (GOGAT) activity in the roots and leaves. Most genes associated with NO3-uptake, reduction and N metabolism were down-regulated or remained unchanged; while two NH4+ transporter genes closely associated with NH4+ uptake (AMT1;2 and AMT1;6) were up-regulated in response to salt stress in the NH4+-fed plants. The accumulation of different amino acid compounds was observed in the NH4+- and NO3-- fed plants during salt treatment. The results suggested that N metabolism in P. simonii plants exposed to salt enhanced salt resistance in the plants that were fed with NO3- instead of NH4+ as the sole N source.

Simulation models of leaf area index (LAI) and yield for cotton can provide a theoretical foundation for predicting future variations in yield. This paper analyses the increase in LAI and the relationships between LAI, dry matter, and yield for cotton under three soil conditioners near Korla, Xinjiang, China. Dynamic changes in cotton LAI were evaluated using modified logistic, Gaussian, modified Gaussian, log normal, and cubic polynomial models. Universal models for simulating the relative leaf area index (RLAI) were established in which the application rate of soil conditioner was used to estimate the maximum LAI (LAIm). In addition, the relationships between LAIm and dry matter mass, yield, and the harvest index were investigated, and a simulation model for yield is proposed. A feasibility analysis of the models indicated that the cubic polynomial and Gaussian models were less accurate than the other three models for simulating increases in RLAI. Despite significant differences in LAIs under the type and amount of soil conditioner applied, LAIm could be described by aboveground dry matter using Michaelis-Menten kinetics. Moreover, the simulation model for cotton yield based on LAIm and the harvest index presented in this work provided important theoretical insights for improving water use efficiency in cotton cultivation and for identifying optimal application rates of soil conditioners.

Sporadic HFMD (hand foot and mouth disease, HFMD) cases and outbreaks caused by etiologic agents other than EV71 and CA16 have increased globally. We conducted this study to investigate the prevalence and genetic characteristics of enteroviruses, especially the non-EV71 and non-CA16 enteroviruses, causing HFMD in Shanghai. Clinical specimens were collected from patients with a diagnosis of HFMD. A partial length of VP1 was amplified with RT-PCR and subjected to direct sequencing. Phylogenetic analyses were performed using MEGA 5.0. The ages of the HFMD cases ranged from 3 to 96 months, and the male/female ratio was 1.41. The median hospital stay was 2.96 days. Up to 18.0% of patients had neurologic system complications such as encephalitis, meningoencephalitis or meningitis. Of the 480 samples, 417 were positive for enterovirus (86.9%) with RT-PCR. A total of 13 enterovirus genotypes were identified. The most frequent genotypes were CA6 (31.9%), EV71 (30.6%), CA16 (8.8%) and CA10 (7.5%). Infections with CA6, EV71, CA16 and CA10 were prevalent throughout the years of study, while the proportion of CA6 notably increased from Sep. 2012 to Dec. 2013. Phylogenetic analyses showed that EV71 strains belonged to the C4a subgenogroup and CA16 was identified as B1b subgenogroup. The CA6 strains were assigned to genogroup F, whereas the CA10 strains were assigned to genogroup D. Patients infected with CA6 were typically younger, had a shorter hospital stay and had a lower incidence of neurologic system complications when compared to patients infected with EV71. Our study demonstrates that the enterovirus genotypes causing HFMD were diversified, and there was an increasing prevalence of the non-EV71 and non-CA16 enteroviruses from 2012 to 2013. CA6 was the most predominant pathogen causing HFMD from Sep. 2012 to Dec. 2013, and it often caused relatively mild HFMD symptoms. Most severe HFMD cases were associated with EV71 infection.

Background/aim: Recent genome-wide association studies have identified several loci influencing lipid levels. The present study focused on the triglycerides (TG)-associated locus, the APOA4-APOA5-ZNF259-BUD13 gene cluster on chromosome 11, to explore the role of genetic variants in this gene cluster in the development of increasing TG levels and coronary heart disease (CHD)., Methodology/principal Findings: Six single nucleotide polymorphisms (SNPs), rs4417316, rs651821, rs6589566, rs7396835, rs964184 and rs17119975, in the APOA4-APOA5-ZNF259-BUD13 gene cluster were selected and genotyped in 5374 healthy Chinese subjects. There were strong significant associations between the six SNPs and TG levels (P < 1.0 × 10(-8)). Moreover, a weighted genotype score was found to be associated with TG levels (P = 3.28 × 10(-13)). The frequencies of three common haplotypes were observed to be significantly different between the high TG group and the low TG group (P < 0.05). However, no significant effects were found for the SNPs regarding susceptibility to CHD in the Chinese case-control populations., Conclusions/significance: This study highlights the genotypes, genotype scores and haplotypes of the APOA4-APOA5-ZNF259-BUD13 gene cluster that were associated with TG levels in a Chinese population; however, the genetic variants in this gene cluster did not increase the risk of CHD in the Chinese population.

Objective: Higher selenium level has been hypothesized to have the potential to reduce the risk of cardiovascular diseases including dyslipidemia. However, results from previous studies are inconsistent. This study aims to determine the association between selenium level and dyslipidemia in elderly Chinese with relatively low selenium status., Methods: A cross-sectional study of 1859 participants aged 65 or older from four rural counties in China was conducted. Serum total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDLC) and low-density lipoprotein-cholesterol (LDLC), nail selenium concentration and APOE genotype were measured in all subjects. The four types of dyslipidemia were defined as >5.17 mmol/L for High-TC, >1.69 mmol/L for High-TG, >3.36 mmol/L for High-LDLC, and <1.04 mmol/L for Low-HDLC according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. Logistic models adjusting for age, gender, APOE genotype, body mass index, alcohol consumption, smoking, physical activity, medication use for cardiovascular diseases were used to examine the relationship between selenium levels and the risk of dyslipidemia., Results: Mean nail selenium concentration was 0.465 μg/gin this sample. Rates for High-TC, High-LDLC, High-TG, Low-HDLC were 18.13%, 13.23%, 12.21% and 32.76% respectively. Results from logistic models indicated that higher selenium levels were significantly associated with higher risk of High-TC, High-LDLC and lower risk of Low-HDLC adjusting for covariates (p < 0.0001). Compared with the lowest selenium quartile group, participants in selenium quartile groups 2, 3 and 4 had significantly higher rates of High-TC, High-LDLC, High-TG, and lower rate of Low-HDLC adjusting for covariates. No significant association was observed between selenium level and the risk of High-TG. APOEε4 carriers had higher rates of High-TC and High-LDLC. There was no interaction between selenium level and APOE with the rates of dyslipidemia., Conclusions: Our results suggest long-term selenium exposure level may be associated with the risk of dyslipidemia in elderly population. Future studies are needed to examine the underlying mechanism of the association.

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.

Background: Catheter ablation (CA) for atrial fibrillation (AF) is now an important therapeutic modality for patients with AF. However, data regarding changes in left atrial (LA) function after CA have indicated conflicting results depending on the AF types, follow-up period, and the analytical imaging tools. The objective of this review was to analyze the effect of CA on the LA size and function for patients with AF., Methods: We searched for studies regarding LA size and function pre- and post-ablation in PubMed, Embase, the Cochrane Library, and Web of Knowledge through May 2014. LA function was measured by LA ejective fraction (LAEF), LA active ejective fraction (LAAEF), or both. Total and subgroup analyses were implemented using Cochrane Review Manager Version 5.2. Weighted mean differences with 95% confidence intervals were used to express the results of continuous outcomes using fixed or random effect models. I2 was used to calculate heterogeneity. To assess publication bias, Egger's test and Begg's funnel plot were performed using Stata 12.0., Results: Twenty-five studies (2040 enrolled patients) were selected for this meta-analysis. The LA diameter (LAD), maximum LA volume, and minimal LA volume were significantly decreased post-ablation, as compared with those at a pre-ablation visit. Compared with the pre-ablation outcomes, we found no significant differences in LAEF/LAAEF at a post-ablation follow-up. Decreases in LA volume and LAEF remained significant post-ablation for paroxysmal AF (PAF); however, the LAEF was insignificant changes in persistent AF (PeAF). Heterogeneity was significant in spite which individual study was excluded. A publication bias was not found. In a meta-regression analysis, we did not find any factor that contributed to the heterogeneity., Conclusion: With CA, LA volumes and LAD were decreased significantly in patients with AF; LAEF was not significant changes in patients with PeAF but decreased in those with PAF.

Background: Genetic factors are important in the pathogenesis of Tourette syndrome (TS). Notably, Dopamine receptor D2 (DRD2) gene has been suggested as a possible candidate gene for this disorder. Several studies have demonstrated that DRD2/ANKK1 TaqIA polymorphism is associated with an increased risk of developing TS. However, past results remain conflicting. We addressed this controversy by performing a meta-analysis of the relationship between DRD2/ANKK1 TaqIA polymorphism and TS., Methods: Literature was searched in multiple databases including PUBMED, COCHRANE and WEB OF SCIENCE up to July 2014. The number of the genotypes for DRD2/ANKK1 TaqIA in the TS and control subjects was extracted and statistical analysis was performed using Review Manager 5.0.16 and Stata 12.0 software. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were utilized to calculate the risk of TS with DRD2/ANKK1 TaqIA. Stratified analysis based on ethnicity was also conducted., Results: 523 patients with TS, 564 controls and 87 probands plus 152 relatives from five published studies were finally involved in this meta-analysis. Combined analysis revealed that the overall ORs for the DRD2/ANKK1 TaqIA A1 allele were 1.69 (95%CIs = 1.42-2.00) in the fixed-effect model and 1.66 (95%CIs = 1.33-2.08) in the random-effects model. Stratification by ethnicity indicated the TaqIA A1 allele was significantly associated with TS in Caucasians (fixed-effect model: OR=1.75, 95%CI = 1.43-2.16; random-effect model: OR=1.69, 95%CI = 1.25-2.28) and in Asians (OR=1.54, 95%CI = 1.12-2.10). Meta-analysis of the A1A1 vs. A2A2 (homozygous model), A1A2 vs. A2A2 (heterozygous model) and A1A1+A1A2 vs. A2A2 (dominant model) of this polymorphism revealed a significant association with TS in overall populations and Caucasians., Conclusions: This meta-analysis suggested that the DRD2/ANKK1 TaqIA polymorphism might contribute to TS susceptibility, especially in Caucasian population. However, further investigation with a larger number of worldwide studies should be conducted to verify the association.

Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I2 index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05-3.30) using a random-effects model (I(2) = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73-0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67-0.82) and 0.64 (95% CI, 0.52-0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35-3.95) using a fixed-effects model (I(2) = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75-0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58-0.82) and 0.77 (95% CI, 0.55-0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment.

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

To explore the patterns of gene expression in gastric cancer, a total of 26 paired gastric cancer and noncancerous tissues from patients were enrolled for gene expression microarray analyses. Limma methods were applied to analyze the data, and genes were considered to be significantly differentially expressed if the False Discovery Rate (FDR) value was < 0.01, P-value was <0.01 and the fold change (FC) was >2. Subsequently, Gene Ontology (GO) categories were used to analyze the main functions of the differentially expressed genes. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we found pathways significantly associated with the differential genes. Gene-Act network and co-expression network were built respectively based on the relationships among the genes, proteins and compounds in the database. 2371 mRNAs and 350 lncRNAs considered as significantly differentially expressed genes were selected for the further analysis. The GO categories, pathway analyses and the Gene-Act network showed a consistent result that up-regulated genes were responsible for tumorigenesis, migration, angiogenesis and microenvironment formation, while down-regulated genes were involved in metabolism. These results of this study provide some novel findings on coding RNAs, lncRNAs, pathways and the co-expression network in gastric cancer which will be useful to guide further investigation and target therapy for this disease.

Objectives: The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies., Methods: Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured., Results: The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively., Conclusions: Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic., Trial Registration: ClinicalTrial.gov identifier NCT01818830.