Gut cytokines modulate olfaction through metabolic reprogramming of glia.

Infection-induced aversion against enteropathogens is a conserved sickness behaviour that can promote host survival1,2. The aetiology of this behaviour remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviours against toxic microorganisms3-5. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviours remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfaction through metabolic reprogramming of ensheathing glia of the antennal lobe. Infection-induced unpaired cytokine expression in the intestine activates JAK-STAT signalling in ensheathing glia, inducing the expression of glial monocarboxylate transporters and the apolipoprotein glial lazarillo (GLaz), and affecting metabolic coupling of glia and neurons at the antennal lobe. This modulates olfactory discrimination, promotes the avoidance of bacteria-laced food and increases fly survival. Although transient in young flies, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old flies owing to age-related intestinal inflammation, which contributes to an age-related decline in olfactory discrimination. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism that causes lasting changes in a sensory system in ageing flies.

circTldc1 increases Tldc1 expression by targeting miR-485-5p to promote fibroblast-like synoviocytes proliferation in collagen-induced arthritis.

Abnormalities in the function of fibroblast-like synoviocytes (FLSs) are crucial factors leading to joint damage of rheumatoid arthritis. In recent years, the role of circular RNA (circRNA) in RA has gradually been revealed. However, the functional regulation of FLSs mediated by circRNA and its potential mechanisms remain unclear. In this study, we elucidated the expression profile of circRNA in FLSs, as well as the role and molecular mechanisms of circTldc1. Through sequencing and validation experiments on primary FLSs derived from collagen-induced arthritis (CIA) rats, we found that circTldc1 can promote FLSs proliferation and exacerbate CIA-induced joint damage. The data revealed that circTldc1's parent gene, Tldc1, is homologous to human Tldc1, and circTldc1 is located in the cytoplasm of FLSs, belonging to the exonic circRNA category. The results from bioinformatics analysis, molecular experiments on FLSs (manipulating circTldc1 expression in vitro), and animal experiments (local regulation of circTldc1 expression in vivo) collectively confirmed that circTldc1 promotes Tldc1 expression by targeting miR-485-5p. High expression of Tldc1 further enhances FLSs proliferation and inflammatory responses, thereby worsening joint damage in CIA rats. High expression of circTldc1 and its parent gene Tldc1 may serve as biomarkers for RA. Local regulation of circTldc1 and Tldc1 gene levels in the joint cavity may represent a potential strategy to improve joint damage and inflammation in RA.

In vitro dissolution profile comparison using bootstrap bias corrected similarity factor, f2.

In vitro dissolution profile has been shown to be correlated with the drug absorption and has often been considered as a metric for assessing in vitro bioequivalence between a test product and corresponding reference one. Various methods have been developed to assess the similarity between two dissolution profiles. In particular, similarity factor f2 has been reviewed and discussed extensively in many statistical articles. Although the f2 lacks inferential statistical properties, the estimation of f2 and its various modified versions were the most widely used metric for comparing dissolution profiles. In this paper, we investigated performances of the naive f2 estimate method, bootstrap f2 confidence interval method and bias corrected-accelerated (BCa) bootstrap f2 confidence interval method for comparing dissolution profiles. Our studies show that naive f2 estimate method and BCa bootstrap f2 confidence interval method are unable to control the type I error rate. The bootstrap f2 confidence interval method can control the type I error rate under a specific level. However, it will cause great conservatism on the power of the test. To solve the potential issues of the previous methods, we recommended a bootstrap bias corrected (BC) f2 confidence interval method in this paper. The type I error rate, power and sensitivity among different f2 methods were compared based on simulations. The recommended bootstrap BC f2 confidence interval method shows better control of type I error than the naive f2 estimate method and BCa bootstrap f2 confidence interval method. It also provides better power than the bootstrap f2 confidence interval method.

Levels, Distribution and Ecological Risk Assessment of PBDEs in Soils and Plants Around the Engineering Plastics Factory.

This study systematically investigated the pollution levels and migration trends of PBDEs in soils and plants around engineering plastics factory, and identified the ecological risks of PBDEs in the environment around typical pollution sources.The results showed that 13 kinds of PBDEs were widely detected in the surrounding areas, and the concentration level was higher than the general environmental pollution level. The total PBDE concentrations (∑13PBDEs) in soils ranged from 14.6 to 278.4 ng/g dry weight (dw), and in plants ranged from 11.5 to 176 ng/g dw. Both soil and plant samples showed that BDE-209 was the most important congener, the pollution level in soil and plant was similar, and the composition of PBDEs congener was similar. In the soil column (50 cm), the radial migration of PBDEs was mainly concentrated in the 0-30 cm section. Except for BDE-66, which was mainly located in the 20-30 cm soil layer, the concentration of PBDEs was the highest in the 0-10 cm region. Furthermore, the environmental risks of PBDEs in soil and plants were evaluated by hazard quotient method, and the HQ values were all < 1, which did not exhibit any ecological risk. The evaluation results also showed that the ecological risk of PBDEs in soil was higher than that of plants, especially penta-BDE, which should be paid more attention.

Clinical characteristics and risk factor analysis of Pneumocystis jirovecii pneumonia in patients with CKD: a machine learning-based approach.

Patients with chronic kidney disease (CKD) who are being treated with immunosuppressive medications are at risk for developing Pneumocystis jirovecii pneumonia (PCP). We attempted to characterize the clinical aspects of PCP in CKD patients in order to alert high-risk patients with bad prognosis. A retrospective study of CKD patients was conducted from June 2018 to June 2022. Based on PCP diagnostic criteria, these patients were divided into PCP and non-PCP groups. Using univariate and multivariate logistic regression analysis, risk indicators were evaluated, and nomogram and decision tree were developed. Of the CKD patients screened for Pneumocystis carinii nucleic acid, 1512 were included. Two-hundred forty four (16.14%) were diagnosed with PCP. Of the PCP, 88.5% was receiving glucocorticoid (GC) therapy, of which 66.3% received more than 0.5 mg/kg GC. Multivariate analysis showed that membranous nephropathy (OR 2.35, 95% CI 1.45-3.80), immunosuppressive therapy (OR 1.94, 95% CI 1.06-3.69), and ground glass opacity of CT scanning (OR 1.71, 95% CI 1.10-2.65) were associated with increased risk of Pneumocystis carinii infection. The AUC of nomogram based on logistics regression was 0.78 (0.75-0.81). The mortality in patients with PCP was 32.40%. Univariate analysis and decision tree showed that pulmonary insufficiency (PO2: OR 0.98, 95% CI 0.96-1.00), elevated APTT (OR 1.07, 95% CI 1.04-1.11), and reduced hemoglobin (OR 0.97, 95% CI 0.96-0.98) were associated with poor prognosis. PCP is not rare in CKD patients, particularly in those treated with immunosuppressive therapy. Considering the high mortality of the cases, further studies on the prevention and management of these patients are needed.

Chemical Pretreatments and Anaerobic Digestion Shape the Virome and Functional Microbiome in Fecal Sludge.

The decomposition and pathogen inactivation of fecal sludge (FS) are vitally important for safely managing onsite sanitation and protecting public and environmental health. However, the microbiome and virome assemblages in FS after chemical and biological treatments remain unclear. Here, we reported the differences in the solid reduction and microbiomes of FS subjected to potassium ferrate (PF), alkali (ALK), and sodium hypochlorite (NaClO) pretreatments and anaerobic digestion (AD). The PF and NaClO pretreatments enhanced FS hydrolysis and pathogen suppression, respectively; AD suppressed Gram-positive bacteria. Most of the viromes were those of bacteriophages, which were also shaped by chemical pretreatments and AD. Metatranscriptome analysis revealed distinct gene expression patterns between the PF- and ALK-pretreated FS and the subsequent AD. Differentially expressed gene profiles indicated that genes related to biological processes, molecular functions, and transcriptional regulators were upregulated in ALK-AD and PF-AD samples. These findings suggested that the effect of different treatment technologies on the viral diversity, pathogen abundance, and metabolic function of the core microbiome extends beyond FS decomposition and that the use of combined processes would provide possible alternatives for FS management in pandemic emergencies.

Development and validation of a novel nomogram to predict the risk of the prolonged postoperative length of stay for lumbar spinal stenosis patients.

BACKGROUND: Lumber spinal stenosis (LSS) is the increasingly reason for spine surgery for elder patients since China is facing the fastest-growing aging population. The aim of this research was to create a model to predict the probabilities of requiring a prolonged postoperative length of stay (PLOS) for lumbar spinal stenosis patients, minimizing the healthcare burden. METHODS: A total of 540 LSS patients were enrolled in this project. The outcome was a prolonged PLOS after spine surgery, defined as hospitalizations ≥ 75th percentile for PLOS, including the day of discharge. The least absolute shrinkage and selection operator (LASSO) was used to identify independent risk variables related to prolonged PLOS. Multivariable logistic regression analysis was utilized to generate a prediction model utilizing the variables employed in the LASSO approach. The receiver operating characteristic (ROC) curve's area under the curve (AUC) and the calibration curve's respective curves were used to further validate the model's calibration with predictability and discriminative capabilities. By using decision curve analysis, the resulting model's clinical effectiveness was assessed. RESULTS: Among 540 individuals, 344 had PLOS that was within the usual range of P75 (8 days), according to the interquartile range of PLOS, and 196 had PLOS that was above the normal range of P75 (prolonged PLOS). Four variables were incorporated into the predictive model, named: transfusion, operation duration, blood loss and involved spine segments. A great difference in clinical scores can be found between the two groups (P < 0.001). In the development set, the model's AUC for predicting prolonged PLOS was 0.812 (95% CI: 0.768-0.859), while in the validation set, it was 0.830 (95% CI: 0.753-0.881). The calibration plots for the probability showed coherence between the expected probability and the actual probability both in the development set and validation set respectively. When intervention was chosen at the potential threshold of 2%, analysis of the decision curve revealed that the model was more clinically effective. CONCLUSIONS: The individualized prediction nomogram incorporating five common clinical features for LSS patients undergoing surgery can be suitably used to smooth early identification and improve screening of patients at higher risk of prolonged PLOS and minimize health care.

Cytotoxic effects of different mouthwash solutions on primary human articular chondrocytes and normal human articular cartilage - an in vitro study.

OBJECTIVES: To compare the cytotoxicity of octenidine dihydrochloride and chlorhexidine gluconate at different concentrations on primary human articular chondrocytes and cartilage. MATERIALS AND METHODS: Primary cultures of human normal adult articular chondrocytes were exposed to octenidine dihydrochloride (0.001562%, 0.003125%, 0.00625%, 0.0125%, 0.025%, 0.05%, and 0.1%), chlorhexidine gluconate (0.003125%, 0.00625%, 0.0125%, 0.025%, 0.05%, 0.1%, and 0.2%), and control (Dulbecco's modified Eagle medium or phosphate-buffered saline) for 30 s. Normal human articular cartilage explants were exposed to octenidine dihydrochloride (0.1% versus control) and chlorhexidine gluconate (0.1% versus control) for 30 s. The viability of human articular chondrocytes was measured by Trypan blue staining, Cell Proliferation Reagent WST-1, and Live/Dead staining. The proliferation of human chondrocytes was measured using the Cell Proliferation Reagent WST-1. The viability of human articular cartilage explants was measured by using Live/Dead staining. RESULTS: Octenidine dihydrochloride and chlorhexidine gluconate exposure decreased cell viability and proliferation in a dose-dependent manner in primary human articular chondrocytes. Octenidine dihydrochloride and chlorhexidine gluconate exposure decreased cell viability in human articular cartilage explant cultures. CONCLUSION: The degree of toxicity varied between octenidine dihydrochloride and chlorhexidine gluconate, with chlorhexidine gluconate being less toxic than octenidine dihydrochloride at the same concentration. Additionally, both octenidine dihydrochloride and chlorhexidine gluconate evaluation had cytotoxic effects on human articular cartilage. Therefore, dosing for the antimicrobial mouthwash ingredients administration would ideally be determined to remain below IC50. CLINICAL RELEVANCE: These data support the in vitro safety of antimicrobial mouthwashes on primary adult human articular chondrocytes.

Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma.

BACKGROUND: Inositol Polyphosphate-5-Phosphatase B (INPP5B), a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P2 and/or PI(3,4,5)P3 at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD. METHODS: TCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein-protein interactions. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays. RESULT: INPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway. CONCLUSION: Our results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients. Trial registration LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People's Hospital. The Ethics Committee of Hangzhou First People's Hospital has approved this study. (registration number: IIT-20210907-0031-01; registration date: 2021.09.13).

Integrated opto-mechanical cantilever sensor with a rib waveguide.

An integrated opto-mechanical cantilever sensor with a rib waveguide is reported in this paper. The device consists of a rib waveguide cantilever with buried waveguides on silicon. The rib cantilever is introduced to match better with the buried waveguide, further for increasing the interface coupling efficiency. With this configuration, single-mode operating can be achieved in transverse direction without decreasing the width of optical waveguide cantilever. The system sensitivity is 1.1 µm-1 which is increased by about 21%, compared with the conventional structure.

The role of short-chain fatty acids in immunity, inflammation and metabolism.

Short-chain fatty acids (SCFAs) are carboxylic acids with carbon atom numbers less than 6, which are important metabolites of gut microbiome. Existing research shows that SCFAs play a vital role in the health and disease of the host. First, SCFAs are the key energy source for colon and ileum cells, and affect the intestinal epithelial barrier and defense functions by regulating related gene expression. Second, SCFAs regulate the function of innate immune cells to participate in the immune system, such as macrophages, neutrophils and dendritic cells. Third, SCFAs can also regulate the differentiation of T cells and B cells and the antigen-specific adaptive immunity mediated by them. Besides, SCFAs are raw materials for sugar and lipid synthesis, which provides a theoretical basis for studying the potential role of SCFAs in regulating energy homeostasis and metabolism. There are also studies showing that SCFAs inhibit tumor cell proliferation and promote apoptosis. In this article, we summarized in detail the role of SCFAs in immunity, inflammation and metabolism, and briefly introduced the role of SCFAs in tumor cell survival. It provides a systematic theoretical basis for the study of SCFAs as potential drugs to promote human health.

hIgDFc-Ig inhibits B cell function by regulating the BCR-Syk-Btk-NF-κB signalling pathway in mice with collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease targeting the synovium. Previous studies have found that IgD may be a potential target for the treatment of RA. We designed a new type of fusion protein, hIgDFc-Ig (DG), to block the binding of IgD to IgD receptor (IgDR). In this study, we found that DG has a significant therapeutic effect in mice with collagen-induced arthritis (CIA). DG improved the claw of irritation symptoms in these mice, inhibited the pathological changes in spleen and joint tissues, and had a moderating effect on B cell subsets at different inflammatory stages. Moreover, DG could also decrease the levels of IgA, IgD, IgM and IgG subtypes of immunoglobulin in the serum of mice with CIA. In vitro, B cell antigen receptor (BCR) knockout Ramos cells were established using the CRISPR/Cas9 technology to further study the activation of BCR signalling by IgD and the effect of DG. We found that the therapeutic effect of DG in mice with CIA may be achieved by inhibiting the activation of BCR signalling by IgD, which may be related to the activation of Igß. In summary, DG may be a potential biological agent for the treatment of RA and it has broad application prospects in the future.

Paeoniflorin-6'-o-benzene sulfonate (CP-25) improves vasculitis through inhibiting IL-17A/JAK/STAT3 signaling pathway in endothelial cells of HFD CIA rats.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.

IgD-Fc-Ig fusion protein, a new biological agent, inhibits T cell function in CIA rats by inhibiting IgD-IgDR-Lck-NF-κB signaling pathways.

IgD-Fc-Ig fusion protein, a new biological agent, is constructed by linking a segment of human IgD-Fc with a segment of human IgG1-Fc, which specifically blocks the IgD-IgDR pathway and selectively inhibits the abnormal proliferation, activation, and differentiation of T cells. In this study we investigated whether IgD-Fc-Ig exerted therapeutic effects in collagen-induced arthritis (CIA) rats. CIA rats were treated with IgD-Fc-Ig (1, 3, and 9 mg/kg) or injected with biological agents etanercept (3 mg/kg) once every 3 days for 40 days. In the PBMCs and spleen lymphocytes of CIA rats, both T and B cells exhibited abnormal proliferation; the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1(CD4+IFN-γ+), and Th17(CD4+IL-17+) were significantly increased, whereas the Treg (CD4+CD25+Foxp3+) cell percentage was decreased. IgD-Fc-Ig administration dose-dependently decreased the indicators of arthritis; alleviated the histopathology of spleen and joint; reduced serum inflammatory cytokines levels; decreased the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1 (CD4+IFN-γ+), and Th17(CD4+IL-17+); increased Treg (CD4+CD25+Foxp3+) cell percentage; and down-regulated the expression of key molecules in IgD-IgDR-Lck-NF-κB signaling (p-Lck, p-ZAP70, p-P38, p-NF-κB65). Treatment of normal T cells with IgD (9 µg/mL) in vitro promoted their proliferation. Co-treatment with IgD-Fc-Ig (0.1-10 µg/mL) dose-dependently decreased IgD-stimulated T cell subsets percentages and down-regulated the IgD-IgDR-Lck-NF-κB signaling. In summary, this study demonstrates that IgD-Fc-Ig alleviates CIA and regulates the functions of T cells through inhibiting IgD-IgDR-Lck-NF-κB signaling.

Study of the effect of culture mediums on the amino acid metabolites for Corynebacterium glutamicum using high-speed micellar electrokinetic chromatography.

Corynebacterium glutamicum (C. glutamicum) is a well-known workhorse for the industrial production of amino acids. Different carbon, nitrogen, and sulfur source may force the bacterium to produce specific metabolites. In this work, a method of high-speed MEKC with LIF detection was developed to rapidly analyze the amino acid metabolites released by C. glutamicum, which is fed with different culture mediums. Corynebacterium glutamicum was cultured in microbial fuel cells to monitor its metabolism process and collect its metabolites. In the CE system, a microliter-scale sample reservoir was designed and applied to perform tiny volume sample injection. With the assistance of microwave, the derivatization time for amino acids with FITC was greatly shortened to 6 min. Under the optimized condition, the eight candidate amino acids of metabolites could be rapidly separated within 2 min. The whole analysis process for real samples, from sampling to determination, could be shortened to less than 10 min. The results showed that C. glutamicum could produce additional l-lysine and l-valine as the metabolites when fed with glucose and l-methionine, respectively. The method proved that culture mediums used to feed C. glutamicum had great effect on the bacterium's metabolites.

Improved Optical Waveguide Microcantilever for Integrated Nanomechanical Sensor.

This paper reports on an improved optical waveguide microcantilever sensor with high sensitivity. To improve the sensitivity, a buffer was introduced into the connection of the input waveguide and optical waveguide cantilever by extending the input waveguide to reduce the coupling loss of the junction. The buffer-associated optical losses were examined for different cantilever thicknesses. The optimum length of the buffer was found to be 0.97 µm for a cantilever thickness of 300 nm. With this configuration, the optical loss was reduced to about 40%, and the maximum sensitivity was more than twice that of the conventional structure.

Separation and determination of microRNAs by high-speed capillary sieving electrophoresis.

In this work, high-speed capillary sieving electrophoresis with laser-induced fluorescence detection was applied to simultaneously determine three microRNAs. A developed manual sample introduction device for the high-speed capillary electrophoresis system was applied to perform sample injection. Strategies, including field-amplified sample injection and electrokinetic injection, were studied to improve the detection sensitivity. Under the optimal conditions, the limit of detection for DNA-159 could be lowered to 5.10 × 10-12  mol/L. In order to achieve enough separation resolution, two DNA probes were designed to have extra sequences that acted as the drag tails. Under the optimized conditions, the three DNA probes and the complexes of microRNA-156, microRNA-159, and microRNA-166 could be completely separated within 3.2 min in background electrolyte (pH 8.7) containing 2.0% m/m polyvinyl pyrrolidone and 0.4% m/m hydroxyethyl cellulose. The limits of detection for the three microRNAs were 0.051, 0.11, and 0.25 nmol/L, respectively. Then the method was applied to analyze the microRNAs spiked in the samples extracted from banana leaves. The recoveries ranged from 114.3 to 121.1% (n = 3). The results showed that the method developed in this work was an effective means for microRNA assay.

Separation and determination of peptide metabolite of Bacillus licheniformis in a microbial fuel cell by high-speed capillary micellar electrokinetic chromatography.

A method using high-speed capillary micellar electrokinetic chromatography and a microbial fuel cell was applied to determine the metabolite of the peptides released by Bacillus licheniformis. Two peptides, l-carnosine and l-alanyl-l-glutamine were used as the substrate to feed Bacillus licheniformis in a microbial fuel cell. The metabolism process of the bacterium was monitored by analyzing the voltage outputs of the microbial fuel cell. A home-made spontaneous injection device was applied to perform high-speed capillary micellar electrokinetic chromatography. Under the optimized conditions, tryptophan, glycine, valine, tyrosine and the two peptides could be rapidly separated within 2.5 min with micellar electrokinetic chromatography mode. Then the method was applied to analyze the solutions sampled from the microbial fuel cell. After 92 h running, valine, as the metabolite, was successfully detected with concentration 3.90 × 10-5 M. The results demonstrated that Bacillus licheniformis could convert l-carnosine and l-alanyl-l-glutamine into valine. The method employed in this work was proved to have great potential in analysis of metabolites, such as amino acids, for microorganisms.

A marginal rank-based inverse normal transformation approach to comparing multiple clinical trial endpoints.

The increase in incidence of obesity and chronic diseases and their health care costs have raised the importance of quality diet on the health policy agendas. The healthy eating index is an important measure for diet quality which consists of 12 components derived from ratios of dependent variables with distributions hard to specify, measurement errors and excessive zero observations difficult to model parametrically. Hypothesis testing involving data of such nature poses challenges because the widely used multiple comparison procedures such as Hotelling's T(2) test and Bonferroni correction may suffer from substantial loss of efficiency. We propose a marginal rank-based inverse normal transformation approach to normalizing the marginal distribution of the data before employing a multivariate test procedure. Extensive simulation was conducted to demonstrate the ability of the proposed approach to adequately control the type I error rate as well as increase the power of the test, with data particularly from non-symmetric or heavy-tailed distributions. The methods are exemplified with data from a dietary intervention study for type I diabetic children. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Prediction of octanol-air partition coefficients for polychlorinated biphenyls (PCBs) using 3D-QSAR models.

Based on the experimental data of octanol-air partition coefficients (KOA) for 19 polychlorinated biphenyl (PCB) congeners, two types of QSAR methods, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), are used to establish 3D-QSAR models using the structural parameters as independent variables and using logKOA values as the dependent variable with the Sybyl software to predict the KOA values of the remaining 190 PCB congeners. The whole data set (19 compounds) was divided into a training set (15 compounds) for model generation and a test set (4 compounds) for model validation. As a result, the cross-validation correlation coefficient (q(2)) obtained by the CoMFA and CoMSIA models (shuffled 12 times) was in the range of 0.825-0.969 (>0.5), the correlation coefficient (r(2)) obtained was in the range of 0.957-1.000 (>0.9), and the SEP (standard error of prediction) of test set was within the range of 0.070-0.617, indicating that the models were robust and predictive. Randomly selected from a set of models, CoMFA analysis revealed that the corresponding percentages of the variance explained by steric and electrostatic fields were 23.9% and 76.1%, respectively, while CoMSIA analysis by steric, electrostatic and hydrophobic fields were 0.6%, 92.6%, and 6.8%, respectively. The electrostatic field was determined as a primary factor governing the logKOA. The correlation analysis of the relationship between the number of Cl atoms and the average logKOA values of PCBs indicated that logKOA values gradually increased as the number of Cl atoms increased. Simultaneously, related studies on PCB detection in the Arctic and Antarctic areas revealed that higher logKOA values indicate a stronger PCB migration ability. From CoMFA and CoMSIA contour maps, logKOA decreased when substituents possessed electropositive groups at the 2-, 3-, 3'-, 5- and 6- positions, which could reduce the PCB migration ability. These results are expected to be beneficial in predicting logKOA values of PCB homologues and derivatives and in providing a theoretical foundation for further elucidation of the global migration behaviour of PCBs.