Mechanisms of action of berberine hydrochloride in planktonic cells and biofilms of Pseudomonas aeruginosa.

The increasing prevalence of extensively drug- and pan-drug-resistant Pseudomonas aeruginosa is a major concern for global public health. Therefore, it is crucial to develop novel antimicrobials that specifically target P. aeruginosa and its biofilms. In the present study, we determined that berberine hydrochloride inhibited the growth of planktonic bacteria as well as prevented the formation of biofilms. Moreover, we observed downregulation in the expression of pslA and pelA biofilm-related genes. Compared with existing antibiotics, berberine hydrochloride exhibits multiple modes of action against P. aeruginosa. Our findings suggest that berberine hydrochloride exerts its antimicrobial effects by damaging bacterial cell membranes, generating reactive oxygen species (ROS), and reducing intracellular adenosine triphosphate (ATP) levels. Furthermore, berberine hydrochloride showed minimal cytotoxicity and reduced susceptibility to drug resistance. In a mouse model of peritonitis, it significantly inhibited the growth of P. aeruginosa and exhibited a strong bacteriostatic action. In conclusion, berberine hydrochloride is a safe and effective antibacterial agent that inhibits the growth of P. aeruginosa.

Dynamic changes of IgM and IgG antibodies in asymptomatic patients as an effective way to detect SARS-CoV-2 infection.

BACKGROUND: COVID-19 has become a global pandemic, and close contacts and asymptomatic patients are worthy of attention. METHODS: A total of 1844 people in close contacts with 76 COVID-19 patients were investigated, and nasopharyngeal swabs and venous blood were collected for centralized medical quarantine observation. Real-time fluorescence was used to detect SARS-CoV-2 nucleic acid in nasopharyngeal swabs of all close contacts, and the colloidal gold method was used to detect serum-specific antibodies. Levels of IgM- and IgG-specific antibodies were detected quantitatively through chemiluminescence from the first nucleic acid turned negative date (0 week) and on weekly intervals of ≤1 week, 1-2 weeks, 2-3 weeks, 3-4 weeks, 4-5 weeks, 5-6 weeks, and 6-7 weeks. RESULTS: The total positive rate of the colloidal gold method (88.5%, 23/26) was significantly higher (χ2  = 59.182, p < 0.001) than that of the healthy control group (2.0%, 1/50). There was significant difference in IgG concentration at different time points (0-7 weeks) after negative nucleic acid conversion (χ2  = 14.034, p = 0.029). Serum IgG levels were significantly higher at weekly time points of 4-5 weeks (Z = -2.399, p = 0.016), 5-6 weeks (Z = -2.049, p = 0.040), and 6-7 weeks (Z = -2.197, p = 0.028) compared with 1-2 weeks after negative nucleic acid conversion. However, there was no significant difference (χ2  = 4.936, p = 0.552) in IgM concentration between time points tested (0-7 weeks) after negative nucleic acid conversion. The positive rates of IgM and IgG in asymptomatic patients (χ2  = 84.660, p < 0.001) were significantly higher than those in the healthy control group (χ2  = 9.201, p = 0.002) within 7 weeks of negative nucleic acid conversion. CONCLUSIONS: The IgG concentration in asymptomatic cases remained at a high level after nucleic acid turned negative. Nucleic acid detection combined with IgM and IgG antibody detection is an effective way to screen asymptomatic infections.

Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19.

BACKGROUND AND AIMS: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. METHODS: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. RESULTS: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, -3 (-4 to -1), p = 0.022], reduction in duration of fever [-1.0 (-2.0 to 0.0), p = 0.025], viral shedding [-3 (-6 to -1), p < 0.001], and hospital stay [-3 (-5 to -1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. CONCLUSION: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

Changes of serum IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in COVID-19 patients.

BACKGROUND AND PURPOSE: Studies have shown that some cytokines in COVID-19 patients were elevated. This study aims to assess whether IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 serve as potential diagnostic biomarkers of COVID-19. METHODS: The above serum cytokines in COVID-19 patients and non-COVID-19 patients were detected by ELISA and SARS-CoV-2 IgM and IgG were detected by the chemiluminescence method. The independent-sample Mann-Whitney U test was utilised to compare cytokine levels in different groups and courses, the Levene T-test and T'-test were utilised to compare they in different genders and the Spearman correlation test was utilised to analyse the correlation between the cytokine levels with ages and SARS-CoV-2 IgG and IgM. RESULTS: Serum levels of IL-10, IL-1ß, MCP-1, TNF-α and IL-4 in COVID-19 patients were significantly higher than those in non-COVID-19 patients, while IL-6 were only significantly higher than in healthy people, IP-10 were significantly lower than in other diseases patients. AUCs of COVID-19 diagnosed by IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 were 0.735, 0.775, 0.595, 0.821, 0.848, 0.38 and 0.682, respectively. In the COVID-19 patients' serum, the levels of IL-10 and MCP-1 of male were noticeably higher than those of female, and all cytokines were significantly positively correlated with age, IL-1ß and IL-4 were significantly negatively correlated with SARS-CoV-2 IgM, while IL-10, IL-1ß, IL-6, TNF- and IP-10 were significantly negatively correlated with SARS-CoV-2 IgG. IL-10 on 43-56 days was significantly lower than at 29-42 days, TNF-α at 15-42 days was significantly higher than at 0-14 days, IP-10 at 0-14 days was the highest and IL-4 at 29-42 days was significantly higher than at 0-14 days. CONCLUSIONS: The detection of IL-10, IL-1 ß, IL-6, MCP-1, TNF-α and IL-4 would assist the clinical study of COVID-19, and IP-10 may be the cytokine of early elevation in COVID-19 patients.

Establishment method affects rice root plasticity in response to drought and its relationship with grain yield stability.

By responding to the variable soil environments in which they are grown, the roots of rice crops are likely to contribute to yield stability across a range of soil moistures, nutrient levels, and establishment methods. In this study, we explored different approaches to quantification of root plasticity and characterization of its relationship with yield stability. Using four different statistical approaches (plasticity index, slope, AMMI, and factor analytic) on a set of 17 genotypes including several recently-developed breeding lines targeted to dry direct-seeding, we identified only very few direct relationships between root plasticity and yield stability. However, genotypes identified as having combined yield stability and root plasticity showed higher grain yields across trials. Furthermore, root plasticity was expressed to a greater degree in puddled transplanted trials rather than under dry direct-seeding. Significant interactions between nitrogen and water resulted in contrasting relationships between nitrogen-use efficiency and biomass stability between puddled-transplanted and direct-seeded conditions. These results reflect the complex interaction between nitrogen, drought, and even different types of drought (as a result of the establishment method) on rice root growth, and suggest that although rice root plasticity may confer stable yield across a range of environments, it might be necessary to more narrowly define the targeted environments to which it will be most beneficial.

Matrix metalloproteinase 3 as a valuable marker for patients with COVID-19.

The situation of the coronavirus disease 2019 (COVID-19) continues to evolve, our study explored the significance of serum levels of matrix metalloproteinase 3 (MMP3) as a marker for patients with COVID-19. Sixty-two COVID-19 patients in the First Hospital of Hunan University of Chinese Medicine and Loudi Center for Diseases Prevention and Control, from January to March 2020, were sampled as the novel coronavirus pneumonia infected group. One hundred and thirty-one cases from the First Hospital of Hunan University of Chinese Medicine, including 67 healthy individuals and 64 non-COVID-19 inpatients, served as the noninfected group. Approximately every 5 days, sera from 20 cases were collected and analyzed three times, using an automatic biochemical analyzer, to detect serum MMP3 concentrations. Correlation was analyzed between MMP3 and other proinflammatory cytokines. Following normality tests, differences in serum MMP3 levels between the infected and noninfected group were analyzed via SPSS (version 25.0) software, using the Wilcoxon rank sum test. The MMP3 concentration was 44.44 (23.46 ~ 72.12) ng/mL in the infected group and 32.42 (28.16 ~ 41.21) ng/mL in the noninfected group. The difference between the two groups was statistically significant (Z = -2.799, P = .005 < .05). A positive correlation was found between MMP3 and interleukin 1ß (IL-1ß; r = .681, P = .000 < .05), and IL-6 (r = .529, P = .002 < .05). Serum MMP3 concentration, measured over three separate time points, were 55.98 (30.80 ~ 75.97) ng/mL, 34.84 (0.00 ~ 51.84) ng/mL, and 5.71 (0.00 ~ 40.46) ng/mL, respectively. Detection of serum MMP3 levels may play an important role in the development of therapeutic approaches for COVID-19 and may indicate the severity of disease.

Development and multicenter performance evaluation of fully automated SARS-CoV-2 IgM and IgG immunoassays.

Objectives: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally. The laboratory diagnosis of SARS-CoV-2 infection has relied on nucleic acid testing; however, it has some limitations, such as low throughput and high rates of false negatives. Tests of higher sensitivity are needed to effectively identify infected patients. Methods: This study has developed fully automated chemiluminescent immunoassays to determine IgM and IgG antibodies to SARS-CoV-2 in human serum. The assay performance has been evaluated at 10 hospitals. Clinical specificity was evaluated by measuring 972 hospitalized patients and 586 donors of a normal population. Clinical sensitivity was assessed on 513 confirmed cases of SARS-CoV-2 by RT-PCR. Results: The assays demonstrated satisfied assay precision with coefficient of variation of less than 4.45%. Inactivation of specimen did not affect assay measurement. SARS-CoV-2 IgM showed clinical specificity of 97.33 and 99.49% for hospitalized patients and the normal population respectively, and SARS-CoV-2 IgG showed clinical specificity of 97.43 and 99.15% respectively. SARS-CoV-2 IgM showed clinical sensitivity of 82.54, 92.93, and 84.62% before 7 days, 7-14 days, and after 14 days respectively, since onset of symptoms, and SARS-CoV-2 IgG showed clinical sensitivity of 80.95, 97.98, and 99.15% respectively at the same time points above. Conclusions: We have developed fully automated immunoassays for detecting SARS-CoV-2 IgM and IgG antibodies in human serum. The assays demonstrated high clinical specificity and sensitivity, and add great value to nucleic acid testing in fighting against the global pandemic of the SARS-CoV-2 infection.

Exploring the Regulation Mechanism of Xihuang Pill, Olibanum and ß-Boswellic Acid on the Biomolecular Network of Triple-Negative Breast Cancer Based on Transcriptomics and Chemical Informatics Methodology.

BACKGROUND: Xihuang Pill (XHP) is mainly used to treat "Ru Yan (breast cancer)". Evidence-based medical evidence and showed that XHP improves the efficacy of chemotherapy and reduced chemotherapy-induced toxicity in breast cancer patients. However, the mechanism of XHP against breast cancer is not clear. METHODS: The effect of XHP extract on cell half-inhibitory concentration (IC50) and cell viability of MD-MB-231 cells was detected by CCK-8 method. The cell inhibition rate of MDA-MB-453 cells were detected by MTT method. Apoptosis was detected by flow cytometry, cell transfer ability was detected by Transwell method, and cell proliferation ability was detected by colony formation assay. The expression of Notch1, ß-catenin and c-myc mRNA in MDA-MB-453 cells were detected by real-time fluorescence quantitative PCR. Then, chemical informatics and transcriptomics methodology was utilized to predict the potential compounds and targets of XHP, and collect triple negative breast cancer (TNBC) genes and the data of Olibanum and ß-boswellic acid intervention MD-MB-231 cells (from GSE102891). The cytoscape software was utilized to undergo network construction and network analysis. Finally, the data from the network analysis was imported into the DAVID database for enrichment analysis of signaling pathways and biological processes. RESULTS: The IC50 was 15.08 g/L (for MD-MB-231 cells). After interfering with MD-MB-231 cells with 15.08 g/L XHP extract for 72 h, compared with the control group, the cell viability, migration and proliferation was significantly decreased, while early apoptosis and late apoptosis were significantly increased (P < 0.01). After interfering with MDA-MB-453 cells with 6 g/L XHP extract for 72 h, compared with the control group, the cell inhibition and apoptosis rate increased, while the expression of Notch1, ß-catenin and c-myc mRNA decreased. (P < 0.05). The chemical informatics and transcriptomics analysis showed that four networks were constructed and analyzed: (1) potential compounds-potential targets network of XHP; (2) XHP-TNBC PPI network; (3) DEGs PPI network of Olibanum-treated MD-MB 231 cells; (4) DEGs PPI network of ß-boswellic acid -treated MD-MB 231 cells. Several anti-TNBC biological processes, signaling pathways, targets and so on were obtained. CONCLUSION: XHP may exert anti-TNBC effects through regulating biological processes, signaling pathways, targets found in this study.

A novel mutation in xanthine dehydrogenase in a case with xanthinuria in Hunan province of China.

Xanthinuria is a rare genetic metabolic disorder, the biochemical mechanism of xanthinuria is the disturbance of purine to uric acid metabolism due to the deficiency of xanthine dehydrogenase/xanthine oxidase (XDH/XO) and aldehyde oxidase 1 (AOX1). Xanthinuria has large clinical variability and only about half of all patients have urolithiasis. In this article, we present one xanthinuria case from an unrelated family, which diagnosed by clinical, biochemical and finally confirmed by molecular genetics. One mutation in XDH gene c.2737C > T (p.R913W) and another mutation in SEPT9 gene (c.655C > T (p.R219W)) were identified. To our knowledge, this is the first time that these novel mutations reported in the xanthinuria patients.

Decreasing hill density combined with increasing nitrogen rate led to yield decline in hybrid rice under low-light conditions.

Low light is a common environmental factor that adversely affects rice yields. This study was conducted to evaluate the combined effect of hill density and nitrogen (N) fertilizer rate on yield attributes in hybrid rice under low-light conditions. Field experiments were conducted in 2014 and 2015. Two hybrid rice cultivars (Y-liangyou 1 and Luoyou 9348) were grown under combinations of three hill density levels (high, 40 × 104 hills ha-1; moderate, 27 × 104 hills ha-1; low, 14 × 104 hills ha-1) and two N rate levels (high, 240 kg ha-1; moderate, 143-148 kg ha-1), and shaded from heading to maturity. Grain yield was highest in the combination of high hill density and moderate N rate and significantly declined with decreasing hill density combined with increasing N rate for both cultivars in both years. Averaged across two cultivars and two years, grain yield declined by about 4% for each 10% decrease in hill density combined with each 10% increase in N rate. A significant reduction in spikelet filling percentage was observed with decreasing hill density combined with increasing N rate in Y-liangyou 1 in 2015 and Luoyou 9348 in 2014. The same trend was observed for grain weight in Y-liangyou 1 in 2014 and Luoyou 9348 in 2015. These results indicate that adopting the practice of decreasing hill density combined with increasing N rate can result in poor grain filling and consequently yield decline in hybrid rice under low-light conditions.

A comprehensive multiplex PCR based exome-sequencing assay for rapid bloodspot confirmation of inborn errors of metabolism.

BACKGROUND: Tandem mass spectrometry (MS MS) and simple fluorometric assays are currently used in newborn screening programs to detect inborn errors of metabolism (IEM). The aim of the study was to evaluate the clinical utility of exome sequencing as a second tier screening method to assist clinical diagnosis of the newborn. METHODS: A novel PCR-exome amplification and re-sequencing (PEARS) assay was designed and used to detect mutations in 122 genes associated with 101 IEM. Newborn bloodspots positive by biochemical testing were analysed by PEARS assay to detect pathogenic mutations relevant to the IEM. RESULTS: In initial validation studies of genomic DNA samples, PEARS assay correctly detected 25 known mutations associated with 17 different IEM. Retrospective gene analysis of newborns with clinical phenylketonuria (PKU), identified compound heterozygote phenylalanine hydroxylase (PAH) gene mutations in eight of nine samples (89%). Prospective analysis of 211 bloodspots correctly identified the two true PKU samples, yielding positive and negative predictive values of 100%. Testing of 8 true positive MS MS samples correctly identified potentially pathogenic compound heterozygote genotypes in 2 cases of citrullinemia type 1 and one case each of methylmalonic acidemia, isobutyryl-CoA dehydrogenase deficiency, short chain acyl-CoA dehydrogenase deficiency and glutaric acid type II and heterozygous genotypes in 2 cases of autosomal dominant methioninemia. Analysis of 11 of 12 false positive MS MS samples for other IEM identified heterozygous carriers in 8 cases for the relevant genes associated with the suspected IEM. In the remaining 3 cases, the test revealed compound heterozygote mutations in other metabolic genes not associated with the suspected IEM, indicating a misinterpretation of the original MS MS data. CONCLUSIONS: The PEARS assay has clinical utility as a rapid and cost effective second-tier test to assist the clinician to accurately diagnose newborns with a suspected IEM.

Left ventricular remodeling in patients with acute type B aortic dissection after thoracic endovascular aortic repair: Short- and mid-term outcomes.

BACKGROUND: Left ventricular (LV) remodeling remains unknown in patients with acute Type B aortic dissection (aTBAD) after thoracic endovascular aortic repair (TEVAR) during follow-up. METHODS: Between May 2004 and January 2016, 163 consecutive patients (136 males, mean preoperative age: 51.06 ±â€¯10.79 years) with aTBAD underwent TEVAR. A linear mixed model was used to evaluate risk factor influencing on LV remodeling and investigate longitudinal changes in LV thickness, diameter, volume, function and mass at preoperation, postoperation, short- and mid-term follow-up. RESULTS: Median follow-up time was 48.0 months (quartiles 1-3, 31-84 months, maximum 147 months). LV thickness and mass followed a continuous downward trend over time. Interventricular septal thickness at end-diastole significantly decreased at mid-term follow-up (time, p < 0.001: preoperative 11.59 ±â€¯0.14 mm vs mid-term 10.82 ±â€¯0.15 mm, p < 0.001; postoperative 11.40 ±â€¯0.14 mm vs mid-term 10.82 ±â€¯0.15 mm, p = 0.006). LV posterior wall thickness at end-diastole was markedly reduced at mid-term follow-up (time, p < 0.001: preoperative 10.89 ±â€¯0.11 mm vs mid-term 10.02 ±â€¯0.11 mm, p < 0.001; postoperative 10.78 ±â€¯0.13 mm vs mid-term 10.02 ±â€¯0.11 mm, p < 0.001; short-term 10.56 ±â€¯0.15 mm vs mid-term 10.02 ±â€¯0.11 mm, p = 0.021). LV mass index markedly decreased during follow-up (time, p = 0.001: preoperative 129.60 ±â€¯3.55 g/m2 vs short-term 119.26 ±â€¯3.19 g/m2, p = 0.009; preoperative 129.60 ±â€¯3.55 g/m2 vs mid-term 115.79 ±â€¯3.62 g/m2, p = 0.003). LV function was improved, but not significantly so, during follow-up. Strict blood pressure control had no influence on LV remodeling. True lumen followed a continuous enlargement trend in terms of proximal thoracic aorta and celiac trunk level during follow-up. CONCLUSIONS: TEVAR can reverse LV remodeling and LV hypertrophy in patients with aTBAD during follow-up.

Downregulation of miRNA-141 in breast cancer cells is associated with cell migration and invasion: involvement of ANP32E targeting.

MicroRNAs (miRNAs) regulate many cellular activities, including cancer development, progression, and metastasis. Some miRNAs are involved in breast cancer (BC) migration and invasion, thus affect patients' prognosis. Microarray analysis was performed to compare miRNA expression in BC tissues, and results confirmed by qPCR. BC cell migration and invasion were studied in vitro with MDA-MB-231 cells using microplate transwell assays. miRNA targeting was investigated using luciferase assays, qPCR, and Western blot analysis in cells with overexpression of miRNA mimics. Knockdown of miRNA targets was performed using target siRNA lentiviral infection. Results show that microRNA-141 (miR-141) was downregulated in breast cancer tumor tissues compared with matched surrounding tissues. Downregulation of miR-141 expression correlated with tumor stage, lymph node involvement, and expressions of PCNA, Ki67, and HER2. Overexpression of miR-141 inhibited BC cell proliferation, migration, and invasion in vitro. ANP32E gene was selected as one putative target for further studies based on results from in silico analysis. Results from a dual-luciferase reporter system suggested ANP32E as a direct target of miR-141. Overexpression of miR-141 downregulated ANP32E expression at both mRNA and protein levels in BC cells. Knockdown of ANP32E inhibited BC cell proliferation, migration, and invasion in vitro, mimicking the effect of the overexpression of miR-141. Our study revealed important roles miR-141 plays in BC growth and metastasis. Moreover, for the first time, we identified ANP32E as one of the miR-141 targets, and demonstrated its involvement in the regulation of cell proliferation, migration, and invasion.

Rice Yield and the Fate of Fertilizer Nitrogen as Affected by Addition of Earthworm Casts Collected from Oilseed Rape Fields: A Pot Experiment.

The mechanism associated with improvement of soil nutritional status by oilseed rape crop, leading to better performance of rice crop, in rice-oilseed rape cropping systems is little known. The present study was aimed to test the hypothesis that earthworm casts produced during oilseed rape-growing season have positive effects on grain yield and fertilizer nitrogen (N) utilization in the subsequent flooded rice crop. A 15N-tracing pot experiment was conducted to determine the effects of earthworm casts collected from oilseed rape fields on yield attributes in rice and the fate of fertilizer N. Soil treated with earthworm casts (soil: earthworm casts = 4: 1, w/w) (EC1) produced 39% higher grain yield than soil only (EC0). EC1 had 18% more panicle number and 10% higher spikelet filling percentage than EC0. Aboveground biomass and harvest index were higher in EC1 than in EC0 by 20% and 15%, respectively. SPAD values in flag leaves were 10% and 22% higher under EC1 than EC0 at 15 and 20 days after heading, respectively. EC1 had 19% higher total N uptake and 18% higher physiological N-use efficiency than EC0. These positive effects of earthworm casts on yield attributes offset negative effects of decreasing N rate from 0.74 g pot-1 (equivalent to the recommended field rate of 150 kg ha-1) to 0.44 g pot-1 (equivalent to 60% of the recommended rate). Fertilizer N retention rate was 7% higher while fertilizer N loss rate was 6% lower in EC1 than in EC0. Our study suggests that earthworm casts produced during oilseed rape-growing season are expected to have the following benefits on the subsequent flooded rice system: (1) improving growth and physiological processes in rice plants and consequently increasing rice grain yield, and (2) increasing fertilizer N retention rate and hence decreasing fertilizer N loss rate and reducing environmental risk.

A prospective study of impaired fasting glucose and type 2 diabetes in China: The Kailuan study.

The worldwide prevalence and incidence of diabetes and obesity are increasing in pandemic proportions. This is particularly relevant for China, where an extremely large population is growing, aging, and urbanizing. We thus conducted a prospective study to examine the prevalence and incidence of impaired fasting glucose (IFG) and diabetes, the rate at which fasting blood glucose rises, and the major modifiable risk factors associated with these outcomes in a large Chinese population from the Kailuan prospective study.A prospective cohort included 100,279 Chinese participants, aged 18 years or more, who had available information on fasting blood glucose concentrations at the start of the study (2006). Examination surveys were conducted every 2 years in 2008 and 2010. For the analyses of incident diabetes, we included 76,869 participants who were free of diabetes, cardiovascular disease, and cancer at the baseline and participants in the 2008 and/or 2010 follow-up. Diabetes was defined by a fasting blood glucose concentration ≥7 mmol/L, self-reported history, or active treatment with insulin or any oral hypoglycemic agent. IFG was defined by a fasting blood glucose concentration between 5.6 and 6.9 mmol/L.During the 4-year study, the prevalence of diabetes and IFG rose from 6.6% to 7.7%, and 17.3% to 22.6%, respectively. There were 17,811 incident cases of IFG and 4867 incident cases of diabetes. The age-standardized incident rate of IFG and diabetes were 62.6/1000 person-years (51.2/1000 person-years in women and 73.8/1000 person-years in men) and 10.0/1000 person-years (7.8/1000 person-years in women and 12.1/1000 person-years in men), respectively. We observed steady increases in fasting blood glucose with body anthropometrics and in every defined category of body mass index, including in those traditionally considered to be well within the "normal" range.In this large longitudinal study of Chinese adults, we observed a high prevalence and incidence of IFG and diabetes over 4 years of follow-up. Our findings are alarming for Chinese public health since steady rises in fasting blood glucose were seen across all permutations of body habitus, even apparently very lean individuals.

Temperature-Related Yield Constraints of Early-Rice in South China: A Cross-Location Analysis.

Warm temperature during post-heading is generally hypothesized to be the critical factor limiting grain yield of early-rice in South China. However, there is no direct evidence to confirm this hypothesis in the field. This study was conducted to determine the temperature-related yield constraints of early-rice in South China. Field experiments were carried out in Huaiji (a location in South China) and Changsha (a location in the Yangtze River basin) in 2011-2013. In each year, two rice cultivars were grown in early-rice growing season in Huaiji and in single-rice growing season in Changsha. Huaiji had higher average daily maximum temperature during post-heading than Changsha. The higher temperature during post-heading induced early plant senescence (slower crop growth rate and shorter grain filling duration), but grain weight did not reduce because it was compensated for by increased translocation of pre-heading biomass. The higher temperature during post-heading also did not cause a reduction in grain filling percentage. Huaiji had lower temperature during pre-heading than Changsha, which to some extent resulted in slower crop growth rate and consequently lower biomass production and smaller sink size in Huaiji than in Changsha. As a result, grain yield was about 30% lower in Huaiji than in Changsha. Our results indicate that grain yield of early-rice in South China is limited not by warm temperature during post-heading but partially by cool temperature during pre-heading, and suggest that enhancing sink size and meanwhile maintaining good translocation of pre-heading biomass may be an effective way to achieve high yield for early-rice in South China.

A comparative transcriptome analysis of two sets of backcross inbred lines differing in lint-yield derived from a Gossypium hirsutum × Gossypium barbadense population.

Upland cotton (Gossypium hirsutum L.) is the most important fiber crop, and its lint-yield improvement is impeded due to its narrow genetic base and the lack of understanding of the genetic basis of yield. Backcross inbred lines (BILs) or near-isogenic lines (NILs) in the same genetic background differing in lint yield, developed through advanced backcrossing, provide an important genomic resource to study the molecular genetic basis of lint yield. In the present study, a high-yield (HY) group and a low-yield (LY) group each with three BILs were selected from a BIL population between G. hirsutum and G. barbadense. Using a microarray-based comparative transcriptome analysis on developing fibers at 10 days post-anthesis (DPA) between the two groups, 1486 differentially expressed genes (DEGs) were identified. A total of 212 DEGs were further mapped in the regions of 24 yield QTL and 11 yield trait QTL hotspots as reported previously, and 81 DEGs mapped with the 7 lint-yield QTL identified in the BIL population from which the two sets of BILs were selected. Gene Ontology annotations and Blast-Mapping-Annotation-KEGG analysis via Blast2GO revealed that more DEGs were associated with catalytic activity and binding, followed by transporters, nucleic acid binding transcription factors, structural molecules and molecular transducer activities. Six DEGs were chosen for a quantitative RT-PCR assay, and the results were consistent with the microarray analysis. The development of DEGs-based markers revealed that 7 single strand conformation polymorphism-based single nucleotide polymorphic (SSCP-SNP) markers were associated with yield traits, and 3 markers with lint yield. In the present study, we identified a number of yield and yield component QTL-co-localizing DEGs and developed several DEG-based SSCP-SNP markers for the traits, thereby providing a set of candidate genes for molecular breeding and genetic manipulation of lint yield in cotton.

Potential Yield Increase of Hybrid Rice at Five Locations in Southern China.

BACKGROUND: A number of field studies have demonstrated that the yield potential of hybrid rice cultivars is higher than that of inbred cultivars, although the magnitude of difference between hybrid and inbred cultivars at different yield levels has not been described. The objective of this study is to compare the yield increase potential at different yield levels between hybrid and conventional rice. Ten field experiments were conducted at five locations in southern China in 2012 and 2013. At each location, two hybrid and two inbred cultivars were grown at three N levels: high (225 kg/hm(2)), moderate (161-191 kg/hm(2)) and the control, zero N (0 kg/hm(2)). RESULTS: Hybrid rice yielded approximately 8 % more grain than did inbred cultivars in Huaiji, Binyang and Haikou; approximately 7 % more in Changsha; and approximately 19 % more in Xingyi. The high grain yields observed for hybrid rice cultivars were attributed to high grain weight and biomass accumulation at maturity. On average, rice yields were approximately 6.0-7.5 t ha(-1) (medium yield) in Huaiji, Binyang and Haikou; approximately 9.0 t ha(-1) in Changsha (high yield); and approximately 12.0 t ha(-1) (super high yield) in Xingyi. The yield gaps among Huaiji, Binyang and Haikou and Changsha were attributed to the differences in spikelets m(-2) and biomass production, whereas the yield gap between Changsha and Xingyi was caused by the differences in grain-filling percentage, grain weight and harvest index. The differences in biomass production among sites were primarily due to variation in crop growth rate induced by varied temperatures and accumulative solar radiation. CONCLUSIONS: The yield superiority of hybrid rice was relatively small in comparison with that of inbred cultivars at medium and high yield levels, but the difference was large at super high yield levels. Improving rice yields from medium to high should focus on spikelets m(-2) and biomass, whereas further improvement to super high level should emphasize on grain-filling percentage, grain weight and harvest index. Favorable environmental conditions are essential for high yields in hybrid rice.

Nannocystin†A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti-Cancer Properties.

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti-fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF-1α) as the primary target for this compound class. Nannocystin A (1) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti-cancer compound didemnin B on EF-1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.

MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-γ.

BACKGROUND: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-γ (SNCG). MATERIALS AND METHODS: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. RESULTS: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. CONCLUSIONS: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.