Enhanced interactions among gut mycobiomes with the deterioration of glycemic control.

BACKGROUND: The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control. METHODS: 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their status of glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargeted liquid chromatography mass spectrometry. FINDINGS: The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic ß-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed that increased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity. CONCLUSIONS: Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM. FUNDINGS: This study was supported by MOST and NSFC of China.

Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia.

Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.

Impact of antifibrotic therapy on disease progression, all-cause mortality, and risk of acute exacerbation in non-IPF fibrosing interstitial lung diseases: evidence from a meta-analysis of randomized controlled trials and prospective controlled studies.

BACKGROUND: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited. OBJECTIVE: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs. DESIGN: Meta-analysis. DATA SOURCES AND METHODS: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment. RESULTS: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42-0.75; p < 0.0001; I2 = 0; high-certainty evidence). Antifibrotic therapy did not significantly decrease all-cause mortality (nine trials with 1990 subjects; RR, 0.76; 95% CI, 0.55-1.03; p = 0.08; I2 = 0; low-certainty evidence). However, in patients with progressive fibrosing ILDs (PF-ILD), antifibrotic therapy decreased all-cause mortality (four trials with 1100 subjects; RR, 0.69; 95% CI, 0.48-0.98; p = 0.04; I2 = 0; low-certainty evidence). CONCLUSION: Our study supports the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. TRIAL REGISTRATION: This study protocol was registered with PROSPERO (registration number: CRD42023411272).

Implementation and effectiveness of a nurse navigation programme based on noddings' care theory in first-year undergraduate nursing students for professional identity and career planning: A quasi-experimental study.

AIMS: Development and evaluation of the effectiveness of a Nurse Navigation programme based on Noddings' Care theory on two dependent variables which were professional identity and career planning among first-year undergraduate nursing students. BACKGROUND: First-year undergraduate nursing students generally have a low sense of professional identity and career planning, resulting in a loss of nursing power after graduation. Implemention of a Nurse Navigation program based on Noddings' Care theory may be potentially useful in cultivating their professional identity and career planning. DESIGN: A quasi-experimental study. METHODS: A convenience sample of 122 first-year undergraduate nursing students from two medical universities was recruited between September 2021 and June 2022. Students in the experimental group (n = 63) participated in the Nurse Navigation programme based on Noddings' Care theory, which contained four core components, spreading over 50 lessons. Those in the control group (n = 59) underwent a traditional training programme with five components across 44 lessons. The two groups were compared in terms of their level of professional identity by Professional identity questionnaire for nurse students (PIQNS) and career planning by Career planning questionnaire (CPQ) after the training using the t-test. RESULTS: The mean score of professional identity in the experimental group increased significantly from 51.02 ± 8.46 at baseline to 58.02 ± 8.81 after the intervention (p < 0.001), with a large effect size (Cohen's d=0.810). Also, this post-intervention score was statistically significantly higher than that (52.86 ± 9.27) in the control group (p = 0.002), with a medium effect size (Cohen's d=0.571). The mean score of career planning in the experimental group increased significantly from 81.76 ± 9.86 at baseline to 94.52 ± 10.81 after the intervention (p < 0.001), with a large effect size (Cohen's d = 1.233). Also, this post-intervention score was statistically significantly higher than that (88.25 ± 9.30) in the control group (p < 0.001), with a medium effect size (Cohen's d=0.623). CONCLUSIONS: The Nurse Navigation programme based on Noddings' Care theory showed effectiveness in enhancing professional identity and career planning among first-year undergraduate nursing students in China. Further rigorous studies are needed to examine its effectiveness and long-term impacts on these students.

Integrated network pharmacology and metabolomics reveal the action mechanisms of vincristine combined with celastrol against colon cancer.

Colon cancer is associated with a high mortality rate. Vincristine (VCR) is a commonly used chemotherapeutic drug. Celastrol (CEL) is an effective component which exerts inhibitory effects on colon cancer. Combination treatment improves resistance to chemotherapeutic drugs and enhances their efficacy. Therefore, we aimed to explore the molecular mechanisms of VCR combined with CEL in colon cancer treatment. We verified the effects of VCR combined with CEL on the proliferation, cell cycle, and apoptosis of HCT-8 cells. Non-targeted metabolomic techniques were used to analyse the changes in cellular metabolites after administration. Finally, network pharmacology technology was used to screen the potential targets and pathways. VCR combined with CEL had synergistic inhibitory effects on HCT-8 colon cancer cells. Cell metabolomics identified 12 metabolites enriched in metabolic pathways, such as the phenylalanine, tyrosine and tryptophan biosynthesis pathways. Network pharmacology revealed that MAPK1, AKT1, PIK3CB, EGFR, and VEGFA were the key targets. Western blotting revealed that VCR combined with CEL activated the P53 pathway by suppressing the PI3K/AKT signalling pathway activation and Bcl-2 expression, promoting the Bax expression. Therefore, VCR combined with CEL potentially treats colon cancer by increasing the apoptosis, improving energy metabolism, and inhibiting PI3K/AKT pathway in colon cancer cells.

XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis.

Metastasis is the main cause of colorectal cancer (CRC)-related death, and the 5-year relative survival rate for CRC patients with distant metastasis is only 14%. X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a zinc-rich protein belonging to the interferon (IFN)-induced gene family. Here, we report a metastasis-promoting role of XAF1 in CRC by acting as a novel adaptor of valosin-containing protein (VCP). XAF1 facilitates VCP-mediated deubiquitination of the E3 ligase RING finger protein 114 (RNF114), which promotes K48-linked ubiquitination and subsequent degradation of junction plakoglobin (JUP). The XAF1-VCP-RNF114-JUP axis is critical for the migration and metastasis of CRC cells. Moreover, we observe correlations between the protein levels of XAF1, RNF114, and JUP in clinical samples. Collectively, our findings reveal an oncogenic function of XAF1 in mCRC and suggest that the XAF1-VCP-RNF114-JUP axis is a potential therapeutic target for CRC treatment.

Urinary beta 3-adrenoceptor as a diagnostic biomarker for overactive bladder in women.

This study was to investigate urinary beta 3-adrenoceptor concentration as a biomarker for overactive bladder (OAB) and predictor of treatment outcomes in women receiving the beta 3-adrenoceptor agonist mirabegron. The study comprised 50 women identified with OAB and 35 women considered as healthy controls. All women with OAB received daily dosage of 50 mg of mirabegron for 12 weeks. Bladder diaries, OAB-related questionnaires, and global response assessment scale (GRAS) data were collected. Urinary beta 3-adrenoceptor concentration was measured through enzyme-linked immunosorbent assay. All OAB-related questionnaires and GRAS indicated improved posttreatment urinary health. After mirabegron treatment, the frequency of micturition and urgency episodes decreased, but the urinary beta 3-adrenoceptor/creatinine (Cr) ratio increased. The urinary beta 3-adrenoceptor/creatinine ratio was identified as a sensitive biomarker for OAB with a confidence interval of 0.656 to 0.856 (p < 0.001). A negative correlation (- 0.431, p = 0.040) between this biomarker and health-related quality of life (HRQL) scores. The Beta 3-adrenoceptor/Cr levels increased significantly in the treatment-responsive group, while they remained unchanged in the unsatisfactory outcome group. This study shows that 12 weeks of mirabegron treatment improves OAB symptoms and HRQL. Furthermore, urinary beta 3-adrenoceptor concentration may be a diagnostic biomarker for OAB.

Targeting the elevated IFN-γ in vitiligo patients by human anti- IFN-γ monoclonal antibody hampers direct cytotoxicity in melanocyte.

BACKGROUND: Vitiligo is an autoimmune disease that progressively destroys melanocytes in the skin, resulting in patchy disfiguring depigmentation. The direct pathological effect of IFN-γ, CXCL10 to the melanocytes in vitiligo has been reported, but there are contradictory results to which cytokine exerts the critical cytotoxic effect on melanocytes. OBJECTIVE: The overarching goal was to study the direct toxicity of highly expressed cytokine in vitiligo skin lesions to melanocytes. METHODS: We obtained the interstitial fluid analyte from lesion and non-lesion skin of vitiligo patients and healthy control and sent for high sensitivity multiplex cytokine panel. We further performed functional study to identify the direct toxicity effect of the highly expressed cytokines. RESULTS: We found a significant elevation of IFN-γ, CXCL9, CXCL10, CXCL11 in the vitiligo skin. Ex vivo melanocyte studies support the direct role of IFN-γ per se in melanocyte cell loss, increased oxidative stress and melanogenesis disruption. Interestingly, we found that IFN-γ regulated cell death through oxidative stress-related ferroptosis cell death, which may initiate autoimmunity in vitiligo. In contrast to blocking selected cell death pathway, our in vitro study supports the rescue effect of human anti-IFN-γ monoclonal antibody 2A6Q to IFN-γ induced cell death, oxidative stress, and loss of function in melanocytes by interrupting IFN-γ signaling, which may be a potential therapeutic option for vitiligo. CONCLUSION: This study further confirms the direct of toxicity effect of IFN-γ per se towards melanocyte in vitiligo skin and the potential utility of human anti-IFN-γ monoclonal antibody in treating vitiligo.

PPDPF suppresses the development of hepatocellular carcinoma through TRIM21-mediated ubiquitination of RIPK1.

Pancreatic progenitor cell differentiation and proliferation factor (PPDPF) has been reported to play a role in tumorigenesis. However, its function in hepatocellular carcinoma (HCC) remains poorly understood. In this study, we report that PPDPF is significantly downregulated in HCC and the decreased PPDPF expression indicates poor prognosis. In the dimethylnitrosamine (DEN)-induced HCC mouse model, hepatocyte-specific depletion of Ppdpf promotes hepatocarcinogenesis, and reintroduction of PPDPF into liver-specific Ppdpf knockout (LKO) mice inhibits the accelerated HCC development. Mechanistic study shows that PPDPF regulates nuclear factor κB (NF-κB) signaling through modulation of RIPK1 ubiquitination. PPDPF interacts with RIPK1 and facilitates K63-linked ubiquitination of RIPK1 via recruiting the E3 ligase TRIM21, which catalyzes K63-linked ubiquitination of RIPK1 at K140. In addition, liver-specific overexpression of PPDPF activates NF-κB signaling and attenuates apoptosis and compensatory proliferation in mice, which significantly suppresses HCC development. This work identifies PPDPF as a regulator of NF-κB signaling and provides a potential therapeutic candidate for HCC.

PPDPF Promotes the Development of Mutant KRAS-Driven Pancreatic Ductal Adenocarcinoma by Regulating the GEF Activity of SOS1.

The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDPF is significantly increased in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and recurrence of PDAC patients. Overexpression of PPDPF promotes PDAC cell growth in vitro and in vivo, while PPDPF knockout exerts opposite effects. Pancreatic-specific deletion of PPDPF profoundly inhibits tumor development in KRASG12D -driven genetic mouse models of PDAC. PPDPF can bind GTP and transfer GTP to SOS1. Mutations of the GTP-binding sites severely impair the tumor-promoting effect of PPDPF. Consistently, mutations of the critical amino acids mediating SOS1-PPDPF interaction significantly impair the GEF activity of SOS1. Therefore, this study demonstrates a novel model of KRAS activation via PPDPF-SOS1 axis, and provides a promising therapeutic target for PDAC.

Pathogenic autoantibodies to IFN-γ act through the impedance of receptor assembly and Fc-mediated response.

Anti-interferon (IFN)-γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on IFN-γ signaling are unknown. Using a single-cell capture method, we isolated 19 IFN-γ-reactive monoclonal antibodies (mAbs) from patients with AIGAs. All displayed high-affinity (KD < 10-9 M) binding to IFN-γ, but only eight neutralized IFN-γ-STAT1 signaling and HLA-DR expression. Signal blockade and binding affinity were correlated and attributed to somatic hypermutations. Cross-competition assays identified three nonoverlapping binding sites (I-III) for AIGAs on IFN-γ. We found that site I mAb neutralized IFN-γ by blocking its binding to IFN-γR1. Site II and III mAbs bound the receptor-bound IFN-γ on the cell surface, abolishing IFN-γR1-IFN-γR2 heterodimerization and preventing downstream signaling. Site III mAbs mediated antibody-dependent cellular cytotoxicity, probably through antibody-IFN-γ complexes on cells. Pathogenic AIGAs underlie mycobacterial infections by the dual blockade of IFN-γ signaling and by eliminating IFN-γ-responsive cells.

Prostate Health Index (phi) and its derivatives predict Gleason score upgrading after radical prostatectomy among patients with low-risk prostate cancer.

To analyze the performance of the Prostate Health Index (phi) and its derivatives for predicting Gleason score (GS) upgrading between prostate biopsy and radical prostatectomy (RP) in the Chinese population, an observational, prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020. Pathological reclassification was determined by the Gleason Grade Group (GG). The area under the receiver operating characteristic curve (AUC) and logistic regression (LR) models were used to evaluate the predictive performance of predictors. In clinically low-risk patients with biopsy GG ≤2, phi (odds ratio [OR] = 1.80, 95% confidence interval [95% CI]: 1.14-2.82, P = 0.01) and its derivative phi density (PHID; OR = 2.34, 95% CI: 1.30-4.20, P = 0.005) were significantly associated with upgrading to GG ≥3 after RP, and the results were confirmed by multivariable analysis. Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG≥2. Compared to the base model (AUC = 0.59), addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients (AUC = 0.69 and 0.71, respectively, both P < 0.05). In conclusion, phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

Identification of Differentially Expressed Genes and Elucidation of Pathophysiological Relevance of ABCA1 in HaCaT Cells Induced by PM2.5.

OBJECTIVE: In order to investigate the effects of PM2.5 on proliferation, cell cycle, apoptosis, and potential mechanism of human keratinocyte cell line HaCaT. METHODS: HaCaT cells were treated with different concentrations of PM2.5 suspension for 24 hours. Cell viability was detected by the CCK-8 method. Cell cycle distribution and apoptosis were detected by flow cytometry. Microarray analyses were used to find out the microarray gene expression profiling; data processing included gene enrichment and pathway analysis. Western blot was conducted to validate the key pathways and regulators in the microarray analysis. RESULTS: The cell activity decreased, and the cell cycle was significantly inhibited with the increase in PM2.5 concentration. Also, by conducting the gene expression microarray assay, we identified 541 upregulated genes and 935 downregulated genes in PM2.5-treated HaCaT cells. Real-time qPCR and western blot confirmed that PM2.5 treatment could induce the expression of ABCA1 while inhibiting that of END1 and CLDN1. CONCLUSION: Our results showed that PM2.5 could potentially regulate cell apoptosis and cell cycle arrest via ABCA1-, END1-, ID1-, and CLDN1-mediated pathways in human HaCaT cells, which laid a good foundation for follow-up drug intervention and drug development against skin damage caused by PM2.5 exposure.

Evidence for Range Expansion and Origins of an Invasive Hornet Vespa bicolor (Hymenoptera, Vespidae) in Taiwan, with Notes on Its Natural Status.

The invasive alien species (IAS) Vespa bicolor is the first reported hornet that has established in Taiwan and is concerning as they prey on honeybee Apis mellifera, which leads to colony losses and public concerns. Thus, the aim of this study was to assess the current status of V. bicolor abundance, dispersal, and impact and to trace the origins of Taiwan's V. bicolor population. Our studies took place in five areas in northern to central Taiwan. We used mtDNA in the phylogenetic analyses. Field survey and ecological niche modeling (ENM) were used to understand the origins and current range of the invasive species. Two main subgroups of V. bicolor in the phylogenetic tree were found, and a clade with short branch lengths in Southeastern China and Taiwan formed a subgroup, which shows that the Taiwan population may have invaded from a single event. Evidence shows that V. bicolor is not a severe pest to honeybees in the study area; however, using ENM, we predict the rapid dispersion of this species to the cooler and hilly mountain areas of Taiwan. The management of V. bicolor should also involve considering it a local pest to reduce loss by beekeepers and public fear in Taiwan. Our findings highlight how the government, beekeepers, and researchers alike should be aware of the implications of V. bicolor's rapid range expansion in Taiwan, or in other countries.

Nitrates and risk of vasovagal reaction in femoral sheath removal after percutaneous intervention : A retrospective observational study.

BACKGROUND: The aim of this study was to analyze the risk factors for vasovagal reaction (VVR) in manual femoral sheath removal after percutaneous coronary intervention and to discuss methods for the prevention and control of VVR. METHODS: The data of 455 patients who underwent percutaneous intervention in four interventional centers during a period of 30 months were retrospectively analyzed. Patients were divided into a VVR group and a control group according to whether VVR developed. The clinical data of all patients were analyzed using univariate and multivariate logistic regression analysis to examine VVR -related factors. RESULTS: A total of 455 patients underwent 464 manual femoral sheath removal operations, of whom 12 developed VVR (2.59%). Of these 12 VVR patients, one had VVR during and 11 had VVR after the intervention. There were no statistically significant differences between the two groups in age, body mass index, gender, time of sheath removal, proportions of patients with hypertension, diabetes, and hyperlipemia, laboratory values of hemoglobin a1c, and ejection fraction (p > 0.05). Compared with the control group, use of nitrates was the only risk factor with a significant correlation with VVR (p = 0.012). CONCLUSION: In manual femoral sheath removal, the use of nitrates is the most important risk factor for the occurrence of VVR after percutaneous intervention.

The Diagnostic Performance of lncRNAs from Blood Specimens in Patients with Hepatocellular Carcinoma: A Meta-Analysis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) are widely involved in the carcinogenesis and development of cancers. We conducted a meta-analysis to evaluate the diagnostic performance of lncRNAs in hepatocellular carcinoma (HCC). METHODS: After the inclusion and exclusion process, relevant information was extracted. Heterogeneity between studies was evaluated, and data synthesis was conducted by employing a bivariate random-effects model. RESULTS: In total, 20 eligible studies were enrolled. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.80-0.90) and 0.88 (95% CI, 0.82-0.92), respectively. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 7.1 (95% CI, 4.9-10.2), 0.16 (95% CI, 0.11-0.23), and 44 (95% CI, 25-79), respectively. The results of the linear regression method and visual inspection of the Deeks funnel plot did not indicate significant publication bias. CONCLUSION: Our meta-analysis suggested that lncRNAs have high diagnostic performance for HCC and have the potential for clinical application.

A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy.

In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb2+)-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5fgmL-1 to 0.5ngmL-1, with a low detection limit of 0.34fgmL-1. Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis.

Intestinal SIRT3 overexpression in mice improves whole body glucose homeostasis independent of body weight.

OBJECTIVE: Intestinal metabolism might play a greater role in regulating whole body metabolism than previously believed. We aimed to enhance enterocyte metabolism in mice and investigate if it plays a role in diet-induced obesity (DIO) and its comorbidities. METHODS: Using the cre-loxP system, we overexpressed the mitochondrial NAD+ dependent protein deacetylase SIRT3 in enterocytes of mice (iSIRT3 mice). We chronically fed iSIRT3 mice and floxed-SIRT3 control (S3fl) mice a low-fat, control diet (CD) or a high-fat diet (HFD) and then phenotyped the mice. RESULTS: There were no genotype differences in any of the parameters tested when the mice were fed CD. Also, iSIRT3 mice were equally susceptible to the development of DIO as S3fl mice when fed HFD. They were, however, better able than S3fl mice to regulate their blood glucose levels in response to exogenous insulin and glucose, indicating that they were protected from developing insulin resistance. This improved glucose homeostasis was accompanied by an increase in enterocyte metabolic activity and an upregulation of ketogenic gene expression in the small intestine. CONCLUSION: Enhancing enterocyte oxidative metabolism can improve whole body glucose homeostasis.

[Analysis of on medication rules for Qi-deficiency and blood-stasis syndrome of chronic heart failure based on data mining technology].

To analyze the medication features and the regularity of prescriptions of traditional Chinese medicine in treating patients with Qi-deficiency and blood-stasis syndrome of chronic heart failure based on modern literature. In this article, CNKI Chinese academic journal database, Wanfang Chinese academic journal database and VIP Chinese periodical database were all searched from January 2000 to December 2015 for the relevant literature on traditional Chinese medicine treatment for Qi-deficiency and blood-stasis syndrome of chronic heart failure. Then a normalized database was established for further data mining and analysis. Subsequently, the medication features and the regularity of prescriptions were mined by using traditional Chinese medicine inheritance support system(V2.5), association rules, improved mutual information algorithm, complex system entropy clustering and other mining methods. Finally, a total of 171 articles were included, involving 171 prescriptions, 140 kinds of herbs, with a total frequency of 1 772 for the herbs. As a result, 19 core prescriptions and 7 new prescriptions were mined. The most frequently used herbs included Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma), Fuling(Poria), Renshen(Ginseng Radix et Rhizoma), Tinglizi(Semen Lepidii), Baizhu(Atractylodis Macrocephalae Rhizoma), and Guizhi(Cinnamomum Ramulus). The core prescriptions were composed of Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma) and Fuling(Poria), etc. The high frequent herbs and core prescriptions not only highlight the medication features of Qi-invigorating and blood-circulating therapy, but also reflect the regularity of prescriptions of blood-circulating, Yang-warming, and urination-promoting therapy based on syndrome differentiation. Moreover, the mining of the new prescriptions provide new reference and inspiration for clinical treatment of various accompanying symptoms of chronic heart failure. In conclusion, this article provides new reference for traditional Chinese medicine in the treatment of chronic heart failure.

Increased electrocatalyzed performance through hairpin oligonucleotide aptamer-functionalized gold nanorods labels and graphene-streptavidin nanomatrix: Highly selective and sensitive electrochemical biosensor of carcinoembryonic antigen.

We report a triplex signal amplification strategy for sensitive biosensing of cancer biomarker by taking advantage of hairpin-shaped oligonucleotide-functionalized gold nanorods (HO-GNRs), graphene and the avidin-biotin reation. The strategy expands electrochemical detection of carcinoembryonic antigen (CEA) by using an aptamer as biosensor's recognition element and HO-GNRs as signal enhancer. To construct this biosensor, the GNR was used as a carrier of horseradish peroxidase (HRP) and HO aptamer with a biotin at the 3'-end and a thiol at the 5'-end, which amplified the electrochemical response because of a large molar ratio of HRP to HO. In the presence of target CEA, the binding reactions of CEA with the loop portions of the HOs caused HOs' loop-stem structure opened and exposed the biotins, and then HRP-GNRs-HO conjugates were captured on graphene and streptavidin modified electrodes via the reaction between the exposed biotins and preimmobilized streptavidins. The accumulation of HRP effectively catalyzed the hydrogen peroxide-mediated oxidation of o-phenylenediamine to generate an electrochemical reduction current for CEA detection. Under optimal conditions, the electrochemical biosensor exhibited a wide dynamic range of 5pgmL(-1) and 50ngmL(-1) toward CEA standards with a low detection limit of 1.5pgmL(-1) (signal-to-noise ratio of 3). The proposed biosensor accurately detected CEA concentration in 8 human serum samples from patients with lung diseases, showing excellent correlations with standard chemiluminescence immunoassay. Furthermore, these results of target DNA detection made it abundantly clear that the proposed strategy can also be extended for detection of other relative biomarkers using different functional DNA structures, which shows great prospects in single-nucleotide polymorphisms analysis, biomedical sensing and application for accurate clinical diseases diagnostic.