A photochemical flow reactor for large scale syntheses of aglain and rocaglate natural product analogues

Published in final edited form as: Bioorg Med Chem. 2017 Dec 1; 25(23): 6197–6202. Published online 2017 Jun 11. doi: [10.1016/j.bmc.2017.06.010]Herein, we report the development of continuous flow photoreactors for large scale ESIPT-mediated [3+2]-photocycloaddition of 2-(p-methoxyphenyl)-3-hydroxyflavone and cinnamate-derived dipolarophiles. These reactors can be efficiently numbered up to increase throughput two orders of magnitude greater than the corresponding batch reactions.Financial support from Boston University and National Institutes of Health (ABB R33AI105944) is gratefully acknowledged. We thank Dr. Norman Lee (Boston University) for high-resolution mass spectrometry data. NMR (CHE-0619339) and MS (CHE-0443618 facilities at Boston University are supported by the NSF. (Boston University; ABB R33AI105944 - National Institutes of Health; CHE-0619339 - NSF; CHE-0443618 - NSF)Accepted manuscrip

Workflow-based Fast Data-driven Predictive Control with Disturbance Observer in Cloud-edge Collaborative Architecture

Data-driven predictive control (DPC) has been studied and used in various scenarios, since it could generate the predicted control sequence only relying on the historical input and output data. Recently, based on cloud computing, data-driven predictive cloud control system (DPCCS) has been proposed with the advantage of sufficient computational resources. However, the existing computation mode of DPCCS is centralized. This computation mode could not utilize fully the computing power of cloud computing, of which the structure is distributed. Thus, the computation delay could not been reduced and still affects the control quality. In this paper, a novel cloud-edge collaborative containerised workflow-based DPC system with disturbance observer (DOB) is proposed, to improve the computation efficiency and guarantee the control accuracy. First, a construction method for the DPC workflow is designed, to match the distributed processing environment of cloud computing. But the non-computation overheads of the workflow tasks are relatively high. Therefore, a cloud-edge collaborative control scheme with DOB is designed. The low-weight data could be truncated to reduce the non-computation overheads. Meanwhile, we design an edge DOB to estimate and compensate the uncertainty in cloud workflow processing, and obtain the composite control variable. The UUB stability of the DOB is also proved. Third, to execute the workflow-based DPC controller and evaluate the proposed cloud-edge collaborative control scheme with DOB in the real cloud environment, we design and implement a practical workflow-based cloud control experimental system based on container technology. Finally, a series of evaluations show that, the computation times are decreased by 45.19% and 74.35% for two real-time control examples, respectively, and by at most 85.10% for a high-dimension control example.Comment: 58 pages and 23 figure

Serum creatinine/cystatin C ratio as a prognostic indicator for patients with colorectal cancer

BackgroundThis study aimed to explore the relationship between creatinine/cystatin C ratio and progression-free survival (PFS) and overall survival (OS) in colorectal cancer (CRC) patients undergoing surgical treatment.MethodsA retrospective analysis was conducted on 975 CRC patients who underwent surgical resection from January 2012 to 2015. Restricted three-sample curve to display the non-linear relationship between PFS/OS and creatinine-cystatin C ratio. Cox regression model and Kaplan-Meier method were used to evaluate the effect of the creatinine-cystatin C ratio on the survival of CRC patients. Prognostic variables with p-value ≤0.05 in multivariate analysis were used to construct prognostic nomograms. The receiver operator characteristic curve was used to compare the efficacy of prognostic nomograms and the traditional pathological stage.ResultsThere was a negative linear relationship between creatinine/cystatin C ratio and adverse PFS in CRC patients. Patients with low creatinine/cystatin C ratio had significantly lower PFS/OS than those with high creatinine/cystatin C ratio (PFS, 50.8% vs. 63.9%, p = 0.002; OS, 52.5% vs. 68.9%, p < 0.001). Multivariate analysis showed that low creatinine/cystatin C ratio was an independent risk factor for PFS (HR=1.286, 95%CI = 1.007–1.642, p=0.044) and OS (HR=1.410, 95%CI=1.087–1.829, p=0.010) of CRC patients. The creatinine/cystatin C ratio-based prognostic nomograms have good predictive performance, with a concordance index above 0.7, which can predict the 1–5-year prognosis.ConclusionCreatinine/cystatin C ratio may be an effective prognostic marker for predicting PFS and OS in CRC patients, aid in pathological staging, and along with tumour markers help in-depth prognostic stratification in CRC patients

Effects of zinc oxide and condensed tannins on the growth performance and intestinal health of weaned piglets in ETEC-challenged environment

This experiment was conducted to evaluate effects of zine oxide (ZnO) and condensed tannins (CT), independently or in combination, on the growth performance and intestinal health of weaned piglets in enterotoxigenic Escherichia coli (ETEC-K88)-challenged environment. Randomly divided 72 weaned piglets into 4 groups. Dietary treatments included the following: basic diet group (CON), 1,500 mg/kg zinc oxide group (ZnO), 1,000 mg/kg condensed tannins group (CT), and 1,500 mg/kg zinc oxide +1,000 mg/kg condensed tannins group (ZnO + CT). Dietary ZnO supplementation decreased diarrhea rate from 0 to 14 days, 15 to 28 days, and 0 to 28 days (p < 0.05) and no significant on growth performance. The effect of CT on reducing diarrhea rate and diarrhea index was similar to the results of ZnO. Compared with the CON group, ZnO increased the ileum villus height and improved intestinal barrier function by increasing the content of mucin 2 (MUC-2) in jejunum and ileum mucosa and the mRNA expression of zonula occludens-1 (ZO-1) in jejunum (p < 0.05) and the expression of Occludin in duodenum and ileum (p < 0.05). The effects of CT on intestinal barrier function genes were similar to that of ZnO. Moreover, the mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) in jejunum and ileum was reduced in ZnO group (p < 0.05). And CT was also capable of alleviating diarrhea by decreasing CFTR expression and promote water reabsorption by increasing AQP3 expression (p < 0.05). In addition, pigs receiving ZnO diet had higher abundance of phylum Bacteroidetes, and genera Prevotella, and lower phylum Firmicutes and genera Lactobacillus in colonic contents. These results indicated that ZnO and CT can alleviate diarrhea and improve intestinal barrier function of weaned pigs in ETEC-challenged environment. In addition, the application of ZnO combined with CT did not show synergistic effects on piglet intestinal health and overall performance. This study provides a theoretical basis for the application of ZnO in weaning piglet production practices, we also explored effects of CT on the growth performance and intestinal health of weaned piglets in ETEC-challenged environment

A‐to‐I RNA editing in Klebsiella pneumoniae regulates quorum sensing and affects cell growth and virulence

Millions of adenosine (A) to inosine (I) RNA editing events are reported and well-studied in eukaryotes; however, many features and functions remain unclear in prokaryotes. By combining PacBio Sequel, Illumina whole-genome sequencing, and RNA Sequencing data of two Klebsiella pneumoniae strains with different virulence, a total of 13 RNA editing events are identified. The RNA editing event of badR is focused, which shows a significant difference in editing levels in the two K. pneumoniae strains and is predicted to be a transcription factor. A hard-coded Cys is mutated on DNA to simulate the effect of complete editing of badR. Transcriptome analysis identifies the cellular quorum sensing (QS) pathway as the most dramatic change, demonstrating the dynamic regulation of RNA editing on badR related to coordinated collective behavior. Indeed, a significant difference in autoinducer 2 activity and cell growth is detected when the cells reach the stationary phase. Additionally, the mutant strain shows significantly lower virulence than the WT strain in the Galleria mellonella infection model. Furthermore, RNA editing regulation of badR is highly conserved across K. pneumoniae strains. Overall, this work provides new insights into posttranscriptional regulation in bacteria

Childhood Sexual Abuse and the Development of Recurrent Major Depression in Chinese Women

Background Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Method Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. Results We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19–5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58–3.15), genital (OR 5.24, 95% CI 3.52–8.15) and intercourse (OR 10.65, 95% CI 5.56–23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11–2.27) and phobia (OR 1.41, 95%CI 1.09–1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20–1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02–2.02). Intercourse (OR 3.47, 95%CI 1.66–8.22), use of force and threats (OR 1.95, 95%CI 1.05–3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20–1.64) were significantly associated with recurrent MD

Associations of Educational Attainment, Occupation, Social Class and Major Depressive Disorder among Han Chinese Women

Background The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. Principal findings We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25–0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77–0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86–0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. Conclusions In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype