A mass defect filtering combined background subtraction strategy for rapid screening and identification of metabolites in rat plasma after oral administration of Yindan Xinnaotong soft capsule.

The absorbed prototypes and metabolites of traditional Chinese medicines (TCMs) serves an important part in pharmacological action and clinical effects. However, the comprehensive characterization of which is facing actual or possible rigorous challenges due to the lack of data mining methods and the complexity of metabolite samples. Yindan Xinnaotong soft capsule (YDXNT), a typical traditional Chinese medicine prescription consisting of extracts from 8 herbal medicines, is widely used for the treatment of angina pectoris and ischemic stroke in the clinic. This study established a systematic data mining strategy based on ultra-high performance liquid chromatography tandem quadrupole-time-of-fight mass spectrometry (UHPLC-Q-TOF MS) for comprehensive metabolite profiling of YDXNT in rat plasma after oral administration. The multi-level feature ion filtration strategy was primarily conducted through the full scan MS data of plasma samples. All potential metabolites were rapidly fileted out from the endogenous background interference based on the background subtract and the chemical type specifically mass defect filter (MDF) windows including flavonoids, ginkgolides, phenolic acids, saponins, and tanshinones. As the MDF windows of certain types were overlapped, the screened-out potential metabolites were deeply characterized and identified according to their retention times (RT), integrating neutral loss filtering (NLF), diagnostic fragment ions filtering (DFIF), and further confirmed by reference standards. Thus, a total of 122 compounds, consisting of 29 prototype components (16 confirmed with reference standards) and 93 metabolites had been identified. This study provides a rapid and robust metabolite profiling method for researching complicated traditional Chinese medicine prescriptions.

FraudAuditor: A Visual Analytics Approach for Collusive Fraud in Health Insurance.

Collusive fraud, in which multiple fraudsters collude to defraud health insurance funds, threatens the operation of the healthcare system. However, existing statistical and machine learning-based methods have limited ability to detect fraud in the scenario of health insurance due to the high similarity of fraudulent behaviors to normal medical visits and the lack of labeled data. To ensure the accuracy of the detection results, expert knowledge needs to be integrated with the fraud detection process. By working closely with health insurance audit experts, we propose FraudAuditor, a three-stage visual analytics approach to collusive fraud detection in health insurance. Specifically, we first allow users to interactively construct a co-visit network to holistically model the visit relationships of different patients. Second, an improved community detection algorithm that considers the strength of fraud likelihood is designed to detect suspicious fraudulent groups. Finally, through our visual interface, users can compare, investigate, and verify suspicious patient behavior with tailored visualizations that support different time scales. We conducted case studies in a real-world healthcare scenario, i.e., to help locate the actual fraud group and exclude the false positive group. The results and expert feedback proved the effectiveness and usability of the approach.

Preventive effect of pectic oligosaccharides on acute colitis model mice: modulating epithelial barrier, gut microbiota and Treg/Th17 balance.

Pectin as a dietary fiber supplement has shown emerging potential in clinical ulcerative colitis (UC) adjuvant therapy. In this study, the preventive and prebiotic effects of enzymatically degraded pectic oligosaccharides (POS) were further explored in dextran sodium sulfate (DSS)-induced colitis mice. The POS supplement (400 mg kg-1) was significantly effective at improving preventive efficacy, promoting colonic epithelial barrier integrity and reducing inflammatory cytokines. Meanwhile, the changes in T regulatory (Treg) cells and T helper 17 (Th17) cells indicated that POS treatment regulated the Treg/Th17 balance. Gut microbiota analysis showed that the POS supplement reshaped the dysfunctional gut microbiota. Further Spearman's correlation coefficient analysis indicated that the changes of the gut microbiota were highly associated with modulating the epithelial barrier, promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. All of these results suggest that enzymatically- degraded POS is a promising therapeutic agent for UC prevention and adjuvant treatment by maintaining intestinal homeostasis.

Diagnosis and Management of Primary Prostatic Signet Ring Cell Carcinoma: Single-Center Experience.

The purpose of the study was to retrospectively summarize the diagnosis and management of 10 primary prostatic signet ring cell carcinoma (PPSRCC) cases in our center. Ten PPSRCC patients diagnosed at the First Affiliated Hospital of Nanjing Medical University from November 2014 to December 2020 were included. Clinical characteristics, image features, therapeutic procedures, histological diagnosis, and outcomes were retrospectively analyzed. All patients received prostate-specific antigen (PSA) examination preoperatively. Nine of them accepted multiparametric magnetic resonance imaging (mpMRI) due to elevated PSA value, and further biopsied. Among them, five patients were diagnosed as prostatic adenocarcinoma and the other four cases were found a mixture of signet ring cell carcinoma (SRCC) and adenocarcinoma. Furthermore, gastrointestinal endoscope and abdominal computed tomography (CT) did not find SRCC originating in gastrointestinal tract. Therefore, these cases were considered to be PPSRCC. Nine patients accepted laparoscopic or robot-assisted RP. Only one patient with normal PSA adopted transurethral resection of the prostate. Postoperative pathological results confirmed SRCC mixed with prostatic adenocarcinoma in nine cases, and only one patient with pure SRCC. After surgery, nine patients received adjuvant hormone therapy, one of which accepted radiotherapy simultaneously. The patient with pure SRCC did not accept any adjuvant therapy postoperatively. During a mean follow-up of 31.9 months, only four patients were alive without disease progression. In summary, PPSRCC is a rare malignant tumor with few specific symptoms, rapid disease progression, and poor prognosis and is frequently accompanied by high-grade prostate adenocarcinoma patterns. There is still no clear and effective strategy to improve the prognosis.

Dietary Niacin Requirement of Juvenile Chinese Mitten Crab, Eriocheir sinensis.

Effects of dietary niacin on the growth performance, intestinal histomorphology, body composition, and antioxidant capacity were investigated in the present study to determine the optimum requirement of niacin for juvenile Eriocheir sinensis. All 360 crabs (initial average weight 1.14 ± 0.04 g) were randomly divided into 6 groups with 3 replicates in each group and 20 crabs in each replicate. Crabs were fed with the control diet (0.89 mg/kg) or niacin-supplemented diets (170.54 mg/kg, 347.05 mg/kg, 587.59 mg/kg, 784.85 mg/kg, and 1248.86 mg/kg) for 12 weeks (named as G1, G2, G3, G4, G5, and G6, respectively). The results showed that appropriate dietary niacin (above 347.05 mg/kg) significantly increased the weight gain rate (WGR) and specific growth rate (SGR) (p < 0.05), but did not affect the survival rate (SR), feed conversion ratio (FCR), daily feeding rate (DFR), and molting frequency (MF) of crabs (p > 0.05). The niacin content in the hepatopancreas of crabs in G1 and G2 was significantly lower than that of the other four groups (p < 0.05). Moreover, dietary niacin significantly affected the intestinal histomorphology of crabs, including the number of folds (NF), height of folds (HF), height of microvillus (HMV), and thickness of muscularis (TM) (p < 0.05). Additionally, moderate dietary niacin levels significantly affected the nonspecific immune responses of crabs, by improving the activity of catalase (CAT), glutathione s-transferase (GST), glutathione peroxidase (GSH-Px), and total superoxide dismutase (T-SOD) (p < 0.05). Based on the broken-line model analysis of SGR against dietary niacin level, the dietary niacin requirement of juvenile crabs was suggested to be 419.4 mg/kg.

Characterization and Application of a New ß-Galactosidase Gal42 From Marine Bacterium Bacillus sp. BY02.

ß-Galactosidase plays an important role in medicine and dairy industry. In this study, a new glycoside hydrolase family 42 (GH42) ß-galactosidase-encoding gene, gal42, was cloned from a newly isolated marine bacterium Bacillus sp. BY02 and expressed in Escherichia coli. Structural characterization indicated that the encoding ß-galactosidase, Gal42, is a homotrimer in solution, and homology modeling indicated that it retains the zinc binding sites of the Cys cluster. The reaction activity of Gal42 was significantly increased by Zn2+ (229.6%) and other divalent metal ions (Mn2+, Mg2+, and Co2+), while its activity was inhibited by EDTA (53.9%). Meanwhile, the thermo-stability of the Gal42 was also significantly enhanced by 5 and 10 mM of zinc ion supplement, which suggested that the "Cys-Zn" motif played important roles in both structural stability and catalytic function. Furthermore, Gal42 showed effective lactose hydrolysis activity, which makes the enzyme hydrolyze the lactose in milk effectively. These properties make Gal42 a potential candidate in food technology.

Preventive and Prebiotic Effect of α-Galacto-Oligosaccharide against Dextran Sodium Sulfate-Induced Colitis and Gut Microbiota Dysbiosis in Mice.

ß-Galacto-oligosaccharide (ß-GOS) showed great potential in ulcerative colitis (UC) adjuvant therapy. Herein, the preventive and prebiotic effect of enzymatic-synthesized α-linked galacto-oligosaccharide (α-GOS) was investigated in dextran sodium sulfate-induced colitis and gut microbiota dysbiosis mice. Compared with ß-GOS, the α-GOS supplement was more effective in improving preventive efficacy, promoting colonic epithelial barrier integrity, and alleviating inflammation cytokines. Moreover, the activation of the NOD-like receptor (NLR) family member NLRP3 inflammasome-mediated inflammation was significantly inhibited by both α-GOS and ß-GOS. Gut microbiota analysis showed that α-GOS treatment reshaped the dysfunctional gut microbiota. The subsequent Spearman's correlation coefficient analysis indicated that these gut microbiota changes were significantly correlated with the inflammatory parameters. These results suggested that the enzymatic-synthesized α-GOS is a promising therapeutic agent in UC prevention and adjuvant treatment by maintaining intestinal homeostasis.

Enzymatically synthesized α-galactooligosaccharides attenuate metabolic syndrome in high-fat diet induced mice in association with the modulation of gut microbiota.

The composition and structure of gut microbiota plays an important role in obesity induced by a high-fat diet (HFD) and related metabolic syndrome (MetS). Previous studies have shown that galacto-oligosaccharides (GOSs) have an effective anti-obesity effect. In this study, we aimed to investigate the effect of enzymatically synthesized α-galacto-oligosaccharides (ES-α-GOSs) on MetS and gut microbiota dysbiosis in HFD-fed mice, and to further investigate whether the attenuation of MetS is associated with the modulation of gut microbiota. Our results indicated that ES-α-GOS could notably ameliorate obesity-related MetS, including hyperlipidemia, insulin resistance and mild inflammation. The subsequent analysis of gut microbiota further showed that ES-α-GOS supplements can significantly modulate the overall composition of the gut microbiota and reverse the gut microbiota disorder caused by HFD feeding. Moreover, Spearman correlation analysis showed that 40 key bacteria reversed by ES-α-GOS were highly associated with metabolic parameters. These results suggested that ES-α-GOSs could serve as a potential candidate for preventing obesity-induced MetS in association with the modulation of gut microbiota.

Comparative iTRAQ Proteomics Reveals Multiple Effects of Selenium Yeast on Dairy Cows in Parturition.

The effects of prepartum dietary supplementation with selenium yeast on low abundant plasma proteins in postpartum dairy cows are not known. In this study, 24 healthy parturient dairy cows were divided into two groups (group C, a control group, and group T, a selenium treatment group). Low abundance proteins were extracted from plasma samples of calving cows, and 542 proteins were identified by isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis. Dietary supplementation with selenium yeast caused differential abundance of 48 proteins with a fold change of more than 1.2 or less than 0.83 (p < 0.05); 14 proteins were upregulated and 34 were downregulated. The top five gene ontology (GO) enrichment terms for the differentially expressed proteins were protein homotetramerization (or tetramerization), defense response to bacteria or fungus, acute-phase reactions, nucleotide catabolic process, and positive regulation of lipid metabolic process. All proteins involved in acute-phase reactions were downregulated, indicating that selenium ameliorates systemic inflammation. The vast majority of proteins involved in the defense response to microorganisms were downregulated, thereby affecting innate immunity. The decreased abundance of apolipoprotein A-I and apolipoprotein C-II, critical proteins for positive regulation of lipid metabolism, indicated that selenium may optimize lipid metabolism. The iTRAQ results showed that prenatal supplementation with yeast selenium can relieve systemic inflammation after parturition. Moreover, selenium may reduce the effects of metabolic diseases, which can improve glyconeogenesis and prevent ketosis and fatty liver.

Structure-based virtual screening and optimization of modulators targeting Hsp90-Cdc37 interaction.

Identification of novel Hsp90 inhibitors to disrupt Hsp90-Cdc37 protein-protein interaction (PPI) could be an alternative strategy to achieve Hsp90 inhibition. In this paper, a series of small molecules targeting Hsp90-Cdc37 complex are addressed and characterized. The molecules' key characters are determined by utilizing a structure-based virtual screening workflow, derivatives synthesis, and biological evaluation. Structural optimization and structure-activity relationship (SAR) analysis were then carried out on the virtual hit of VS-8 with potent activity, which resulted in the discovery of compound 10 as a more potent regulator of Hsp90-Cdc37 interaction with a promising inhibitory effect (IC50 = 27 µM), a moderate binding capacity (KD = 40 µM) and a preferable antiproliferative activity against several cancer lines including MCF-7, SKBR3 and A549 cell lines (IC50 = 26 µM, 15 µM and 38 µM respectively). All the data suggest that compound 10 exhibits moderate inhibitory effect on Hsp90-Cdc37 and could be regard as a first evidence of a non-natural compound targeting Hsp90-Cdc37 PPI.