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Calorie Restriction with or without Time-Restricted Eating in Weight Loss.
Liu, D, Huang, Y, Huang, C, Yang, S, Wei, X, Zhang, P, Guo, D, Lin, J, Xu, B, Li, C, et al
The New England journal of medicine. 2022;(16):1495-1504
Abstract
BACKGROUND The long-term efficacy and safety of time-restricted eating for weight loss are not clear. METHODS We randomly assigned 139 patients with obesity to time-restricted eating (eating only between 8:00 a.m. and 4:00 p.m.) with calorie restriction or daily calorie restriction alone. For 12 months, all the participants were instructed to follow a calorie-restricted diet that consisted of 1500 to 1800 kcal per day for men and 1200 to 1500 kcal per day for women. The primary outcome was the difference between the two groups in the change from baseline in body weight; secondary outcomes included changes in waist circumference, body-mass index (BMI), amount of body fat, and measures of metabolic risk factors. RESULTS Of the total 139 participants who underwent randomization, 118 (84.9%) completed the 12-month follow-up visit. The mean weight loss from baseline at 12 months was -8.0 kg (95% confidence interval [CI], -9.6 to -6.4) in the time-restriction group and -6.3 kg (95% CI, -7.8 to -4.7) in the daily-calorie-restriction group. Changes in weight were not significantly different in the two groups at the 12-month assessment (net difference, -1.8 kg; 95% CI, -4.0 to 0.4; P = 0.11). Results of analyses of waist circumferences, BMI, body fat, body lean mass, blood pressure, and metabolic risk factors were consistent with the results of the primary outcome. In addition, there were no substantial differences between the groups in the numbers of adverse events. CONCLUSIONS Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction. (Funded by the National Key Research and Development Project [No. 2018YFA0800404] and others; ClinicalTrials.gov number, NCT03745612.).
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Comparative transcriptomic analysis of contrasting hybrid cultivars reveal key drought-responsive genes and metabolic pathways regulating drought stress tolerance in maize at various stages.
Liu, S, Zenda, T, Li, J, Wang, Y, Liu, X, Duan, H
PloS one. 2020;(10):e0240468
Abstract
Drought stress is the primary environmental factor that negatively influences plant growth and yield in cereal grain crops such as maize (Zea mays L.). Crop breeding efforts for enhanced drought resistance require improved knowledge of plant drought stress responses. In this study, we applied a 12-day water-deficit stress treatment to maize plants of two contrasting (drought tolerant ND476 and drought sensitive ZX978) hybrid cultivars at four (V12, VT, R1, and R4) crop growth stages and we report key cultivar-specific and growth-stage-specific molecular mechanisms regulating drought stress responses in maize. Based on the transcriptome analysis, a total of 3451 and 4088 differentially expressed genes (DEGs) were identified in ND476 and ZX978 from the four experimental comparisons, respectively. These gene expression changes effected corresponding metabolic pathway responses related to drought tolerance in maize. In ND476, the DEGs associated with the ribosome, starch and sucrose metabolism, phenylpropanoid biosynthesis and phenylpropanoid metabolism pathways were predominant at the V12, VT, R2, and R4 stages, respectively, whereas those in ZX978 were related to ribosome, pentose and glucuronate interconversions (PGI), MAPK signaling and sulfur metabolism pathways, respectively. MapMan analysis revealed that DEGs related to secondary metabolism, lipid metabolism, and amino acid metabolism were universal across the four growth stages in ND476. Meanwhile, the DEGs involved in cell wall, photosynthesis and amino acid metabolism were universal across the four growth stages in ZX978. However, K-means analysis clustered those DEGs into clear and distinct expression profiles in ND476 and ZX978 at each stage. Several functional and regulatory genes were identified in the special clusters related to drought defense response. Our results affirmed that maize drought stress adaptation is a cultivar-specific response as well as a stage-specific response process. Additionally, our findings enrich the maize genetic resources and enhance our further understanding of the molecular mechanisms regulating drought stress tolerance in maize. Further, the DEGs screened in this study may provide a foundational basis for our future targeted cloning studies.
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Genome-wide association studies of ionomic and agronomic traits in USDA mini core collection of rice and comparative analyses of different mapping methods.
Liu, S, Zhong, H, Meng, X, Sun, T, Li, Y, Pinson, SRM, Chang, SKC, Peng, Z
BMC plant biology. 2020;(1):441
Abstract
BACKGROUND Rice is an important human staple food vulnerable to heavy metal contamination leading to serious concerns. High yield with low heavy metal contamination is a common but highly challenging goal for rice breeders worldwide due to lack of genetic knowledge and markers. RESULTS To identify candidate QTLs and develop molecular markers for rice yield and heavy metal content, a total of 191 accessions from the USDA Rice mini-core collection with over 3.2 million SNPs were employed to investigate the QTLs. Sixteen ionomic and thirteen agronomic traits were analyzed utilizing two univariate (GLM and MLM) and two multivariate (MLMM and FarmCPU) GWAS methods. 106, 47, and 97 QTLs were identified for ionomics flooded, ionomics unflooded, and agronomic traits, respectively, with the criterium of p-value < 1.53 × 10- 8, which was determined by the Bonferroni correction for p-value of 0.05. While 49 (~ 20%) of the 250 QTLs were coinciding with previously reported QTLs/genes, about 201 (~ 80%) were new. In addition, several new candidate genes involved in ionomic and agronomic traits control were identified by analyzing the DNA sequence, gene expression, and the homologs of the QTL regions. Our results further showed that each of the four GWAS methods can identify unique as well as common QTLs, suggesting that using multiple GWAS methods can complement each other in QTL identification, especially by combining univariate and multivariate methods. CONCLUSIONS While 49 previously reported QTLs/genes were rediscovered, over 200 new QTLs for ionomic and agronomic traits were found in the rice genome. Moreover, multiple new candidate genes for agronomic and ionomic traits were identified. This research provides novel insights into the genetic basis of both ionomic and agronomic variations in rice, establishing the foundation for marker development in breeding and further investigation on reducing heavy-metal contamination and improving crop yields. Finally, the comparative analysis of the GWAS methods showed that each method has unique features and different methods can complement each other.
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Genetic architecture of fruit size and shape variation in cucurbits: a comparative perspective.
Pan, Y, Wang, Y, McGregor, C, Liu, S, Luan, F, Gao, M, Weng, Y
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik. 2020;(1):1-21
Abstract
The Cucurbitaceae family hosts many economically important fruit vegetables (cucurbits) such as cucumber, melon, watermelon, pumpkin/squash, and various gourds. The cucurbits are probably best known for the diverse fruit sizes and shapes, but little is known about their genetic basis and molecular regulation. Here, we reviewed the literature on fruit size (FS), shape (FSI), and fruit weight (FW) QTL identified in cucumber, melon, and watermelon, from which 150 consensus QTL for these traits were inferred. Genome-wide survey of the three cucurbit genomes identified 253 homologs of eight classes of fruit or grain size/weight-related genes cloned in Arabidopsis, tomato, and rice that encode proteins containing the characteristic CNR (cell number regulator), CSR (cell size regulator), CYP78A (cytochrome P450), SUN, OVATE, TRM (TONNEAU1 Recruiting Motif), YABBY, and WOX domains. Alignment of the consensus QTL with candidate gene homologs revealed widespread structure and function conservation of fruit size/shape gene homologs in cucurbits, which was exemplified with the fruit size/shape candidate genes CsSUN25-26-27a and CsTRM5 in cucumber, CmOFP1a in melon, and ClSUN25-26-27a in watermelon. In cucurbits, the andromonoecy (for 1-aminocyclopropane-1-carboxylate synthase) and the carpel number (for CLAVATA3) loci are known to have pleiotropic effects on fruit shape, which may complicate identification of fruit size/shape candidate genes in these regions. The present work illustrates the power of comparative analysis in understanding the genetic architecture of fruit size/shape variation, which may facilitate QTL mapping and cloning for fruit size-related traits in cucurbits. The limitations and perspectives of this approach are also discussed.
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Molecular Origin of the Stability Difference in Four Shark IgNAR Constant Domains.
Zhou, H, Liu, S, Yin, X, Li, Z, Yang, Z, Zhou, R
Biophysical journal. 2019;(10):1907-1917
Abstract
Improving the stability of antibodies for manufacture and shelf life is one of the main focuses of antibody engineering. One stabilization strategy is to perform specific mutations in human antibodies based on highly stable antibodies in other species. To identify the key residues for mutagenesis, it is necessary to understand the roles of these residues in stabilizing the antibody. Here, we use molecular dynamics simulations to study the molecular origin of the four shark immunoglobulin new antigen receptors constant domains (C1-C4). According to the unfolding pathways and the conformational free energy surfaces in 8 M urea at 380 K, the C2 domain is the most stable, followed by C4, C1, and C3, which agrees with the experimental findings. The C1 and C3 domains follow a common unfolding pathway in which the unfolding starts from the edge strands, particularly strand g, and then gradually progresses to the inner strands. Detailed structural analysis of the C2 domain reveals a "sandwich-like" R339-E322-R341 salt-bridge cluster on strand g, which grants ultrahigh stability to the C2 domain. We further design two sets of mutations by mutating E322 to alanine or setting all atomic charges in E322 to zero to break the salt-bridge cluster in the C2 domain, which confirms the importance of the salt bridges in stability. In the C4 domain, the D80-K104 salt bridge on strand g also strengthens the stability. On the other hand, in the C1 and C3 domains, there is no salt bridge on strand g. In addition to the salt bridges, the overall hydrophobicity score of the hydrophobic core is also positively correlated with the domain stability. Our findings provide a detailed microscopic picture of the molecular origin of the four shark immunoglobulin new antigen receptors constant domains that not only explains the differences in their structural stability but also provides important insights into future antibody design.
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Comparative Proteomics and Physiological Analyses Reveal Important Maize Filling-Kernel Drought-Responsive Genes and Metabolic Pathways.
Wang, X, Zenda, T, Liu, S, Liu, G, Jin, H, Dai, L, Dong, A, Yang, Y, Duan, H
International journal of molecular sciences. 2019;(15)
Abstract
Despite recent scientific headway in deciphering maize (Zea mays L.) drought stress responses, the overall picture of key proteins and genes, pathways, and protein-protein interactions regulating maize filling-kernel drought tolerance is still fragmented. Yet, maize filling-kernel drought stress remains devastating and its study is critical for tolerance breeding. Here, through a comprehensive comparative proteomics analysis of filling-kernel proteomes of two contrasting (drought-tolerant YE8112 and drought-sensitive MO17) inbred lines, we report diverse but key molecular actors mediating drought tolerance in maize. Using isobaric tags for relative quantification approach, a total of 5175 differentially abundant proteins (DAPs) were identified from four experimental comparisons. By way of Venn diagram analysis, four critical sets of drought-responsive proteins were mined out and further analyzed by bioinformatics techniques. The YE8112-exclusive DAPs chiefly participated in pathways related to "protein processing in the endoplasmic reticulum" and "tryptophan metabolism", whereas MO17-exclusive DAPs were involved in "starch and sucrose metabolism" and "oxidative phosphorylation" pathways. Most notably, we report that YE8112 kernels were comparatively drought tolerant to MO17 kernels attributable to their redox post translational modifications and epigenetic regulation mechanisms, elevated expression of heat shock proteins, enriched energy metabolism and secondary metabolites biosynthesis, and up-regulated expression of seed storage proteins. Further, comparative physiological analysis and quantitative real time polymerase chain reaction results substantiated the proteomics findings. Our study presents an elaborate understanding of drought-responsive proteins and metabolic pathways mediating maize filling-kernel drought tolerance, and provides important candidate genes for subsequent functional validation.
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Goal-directed fluid therapy versus conventional fluid therapy in colorectal surgery: A meta analysis of randomized controlled trials.
Xu, C, Peng, J, Liu, S, Huang, Y, Guo, X, Xiao, H, Qi, D
International journal of surgery (London, England). 2018;:264-273
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Abstract
OBJECTIVES This meta-analysis was conducted to compare the effects of goal-directed fluid therapy (GDFT) versus conventional fluid therapy (CFT) in colorectal surgery on patients' postoperative outcome and to detect whether the results differ between studies with the Enhanced Recovery After Surgery (ERAS) protocol and those without, between studies using different devices for GDFT, or between different surgical approaches (laparoscopy or laparotomy). METHODS The Cochrane Library, PubMed, Embase, Wanfang Data and ClinicalTrials.com were searched for studies from January,1990 to February, 2018. Randomized controlled trials (RCTs) comparing both two abovementioned fluid therapy protocols in colorectal surgery were included. The primary outcome was 30-day mortality after surgery. Secondary outcomes were length of hospital stay (LOS), complication rate, ICU admission and gastrointestinal indicators. RESULTS Eleven studies were included, including a total of 1281 patients: the GDFT group included 624 patients and the control group included 657 patients. No significant differences were found between groups in 30-day mortality (relative risk, RR 0.86,0.28 to 2.63, P = 0.79), LOS (weighted mean difference, WMD 0.22,-0.1 to 0.55, P = 0.18), and ICU admission (RR 0.42, 0.17 to 1.04, P = 0.06). However, the GDFT group had a lower complication rate (RR 0.84,0.71 to 0.99, P = 0.04). In subgroup analyses, time to first flatus and time to tolerate an oral diet were shorter in GDFT group than the control group in studies who did not use the ERAS protocol. No publication bias was identified according to Begg's test. CONCLUSION Compared with conventional fluid therapy, GDFT may not improve patients' postoperative outcome in colorectal surgery. However, the improvement of gastrointestinal function associated with GDFT over conventional fluid therapy was significant in the surgeries that did not use the ERAS protocol.
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The Prognostic Value of Tumor Multifocality in Clinical Outcomes of Papillary Thyroid Cancer.
Wang, F, Yu, X, Shen, X, Zhu, G, Huang, Y, Liu, R, Viola, D, Elisei, R, Puxeddu, E, Fugazzola, L, et al
The Journal of clinical endocrinology and metabolism. 2017;(9):3241-3250
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Abstract
CONTEXT Multifocality is often treated as a risk factor for papillary thyroid cancer (PTC), prompting aggressive treatments, but its prognostic value remains unestablished. OBJECTIVE To investigate the role of tumor multifocality in clinical outcomes of PTC. METHODS Multicenter study of the relationship between multifocality and clinical outcomes of PTC in 2638 patients (623 men and 2015 women) with median [interquartile range (IQR)] age of 46 (35 to 58) years and median (IQR) follow-up time of 58 (26 to 107) months at 11 medical centers in six countries. Surveillance, Epidemiology and End Results (SEER) data were used for validation. RESULTS Disease recurrence in multifocal and unifocal PTC was 198 of 1000 (19.8%) and 221 of 1624 (13.6%) (P < 0.001), with a hazard ratio of 1.55 [95% confidence interval (CI), 1.28 to 1.88], which became insignificant at 1.13 (95% CI, 0.93 to 1.37) on multivariate adjustment. Similar results were obtained in PTC variants: conventional PTC, follicular-variant PTC, tall-cell PTC, and papillary thyroid microcarcinoma. There was no association between multifocality and mortality in any of these PTC settings, whereas there was a strong association between classic risk factors and cancer recurrence or mortality, which remained significant after multivariate adjustment. In 1423 patients with intrathyroidal PTC, disease recurrence was 20 of 455 (4.4%) and 41 of 967 (4.2%) (P = 0.892) and mortality was 0 of 455 (0.0%) and 3 of 967 (0.3%) (P = 0.556) in multifocal and unifocal PTC, respectively. The results were reproduced in 89,680 patients with PTC in the SEER database. CONCLUSIONS Tumor multifocality has no independent risk prognostic value in clinical outcomes of PTC; its indiscriminate use as an independent risk factor, prompting overtreatments of patients, should be avoided.
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Patients with gout differ from healthy subjects in renal response to changes in serum uric acid.
Liu, S, Perez-Ruiz, F, Miner, JN
Joint bone spine. 2017;(2):183-188
Abstract
OBJECTIVE Our objectives were to determine whether a change in serum uric acid (sUA) resulted in a corresponding change in the fractional excretion of uric acid (FEUA) and whether the renal response was different in patients with gout versus healthy subjects. METHODS FEUA was calculated from previously published studies and four new phase I studies in healthy subjects and/or patients with gout before and after treatment to lower or raise sUA. Treatments included xanthine oxidase inhibitors to lower sUA as well as infusion of uric acid and provision of a high-purine diet to raise sUA. Plots were created of FEUA versus sUA before and after treatment. For the phase I studies, percent change in FEUA per mg/dL change in sUA was calculated separately for healthy subjects and patients with gout, and compared using Student's t test. RESULTS Analysis of previously published data and the new phase I clinical data indicates that changing sUA by a non-renal mechanism leads to a change in FEUA. The magnitude of change is greater in subjects with higher baseline FEUA versus patients with gout. Healthy subjects excrete more urate than do patients with gout at physiological urate-filtered load; this difference disappears when the urate-filtered load is decreased to ∼5000mg/24hours. CONCLUSION These observations are consistent with a less saturated urate reabsorption system in patients with gout versus healthy subjects, resulting in elevated retention of uric acid. Further investigation could lead to the discovery of mechanisms responsible for the etiology of hyperuricemia/gout.
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A comparative study of Danhong injection and Salvia miltiorrhiza injection in the treatment of cerebral infarction: A systematic review and meta-analysis.
Wang, K, Zhang, D, Wu, J, Liu, S, Zhang, X, Zhang, B
Medicine. 2017;(22):e7079
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BACKGROUND To evaluate systematically the clinical effectiveness and safety of Danhong injection (DI) and Salvia miltiorrhiza injection (SMI) in the treatment of cerebral infarction. METHODS A literature search was conducted for retrieving randomized controlled trials (RCTs) on cerebral infarction treated by Danhong injection and SMI in the Cochrane Library, PubMed, Embase, China Biology Medicine disc, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Wanfang Database up to January 22, 2017. Two reviewers extracted information and independently assessed the quality of included RCTs by the Cochrane Risk of Bias Assessment Tool; then data were analyzed with Review Manager 5.3 software. RESULTS Twelve RCTs involving 1044 patients were included. The result of DI group was about 27% superior to SMI group in the clinical total effective rate (relative risk 1.27, 95% confidence interval 1.19-1.35, P < .00001). In addition, DI could prefect neurologic impairment (standardized mean difference -1.22, 95% confidence interval -1.90 to -0.54, P = .0004), and adjust hemorheological parameters. Three RCTs occurred 4 cases of adverse drug reactions/adverse drug events, but there were no serious adverse drug reactions/adverse drug events. CONCLUSION Comparing with SMI combined with western medicine, DI combined with conventional therapy is more effective in improving the clinical total effective rate and neurologic impairment, but more evidence-based medicine research needed to support our study further.