Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling.

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe-/- mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro.

BACKGROUND: Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle regulation, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial. AIM: To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro. METHODS: HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria; then, PHB1 levels in the sera and liver tissues of these participates were determined using ELISA, RT-PCR, and immunohistochemistry. Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA (shRNA-PHB1) for 24-72 h. Cell proliferation was analysed with an MTT assay. Cell cycle progression and apoptosis were analysed using flow cytometry (FACS). The mRNA and protein expression levels of the cell cycle-related molecules p21, Cyclin A2, Cyclin E1, and CDK2 and the cell apoptosis-related molecules cytochrome C (Cyt C), p53, Bcl-2, Bax, caspase 3, and caspase 9 were measured by real-time PCR and Western blot, respectively. RESULTS: Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals, and decreased PHB1 was positively correlated with low differentiation, TNM stage III-IV, and alpha-fetoprotein ≥ 400 µg/L. Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner. FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis. The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells. The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41% ± 1.06%, which was significantly greater than that of apoptotic control cells (3.65% ± 0.85%, P < 0.01) and empty vector-transfected cells (4.21% ± 0.52%, P < 0.01). Similar results were obtained with SMMC-7721 cells. Furthermore, the mRNA and protein expression levels of p53, p21, Bax, caspase 3, and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2, Cyclin E1, CDK2, and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells. However, when PHB1 was upregulated in human HCC cells, Cyt C expression levels were increased in the cytosol and decreased in the mitochondria, which indicated that Cyt C had been released into the cytosol. Conversely, these effects were reversed when PHB1 was knocked down. CONCLUSION: PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

DNA-methylome-derived epigenetic fingerprint as an immunophenotype indicator of durable clinical immunotherapeutic benefits in head and neck squamous cell carcinoma.

BACKGROUND: Cancer immunotherapy provides durable response and improves survival in a subset of head and neck squamous cell carcinoma (HNSC) patients, which may due to discriminative tumor microenvironment (TME). Epigenetic regulations play critical roles in HNSC tumorigenesis, progression, and activation of functional immune cells. This study aims to identify an epigenetic signature as an immunophenotype indicator of durable clinical immunotherapeutic benefits in HNSC patients. METHODS: Unsupervised consensus clustering approach was applied to distinguish immunophenotypes based on five immune signatures in The Cancer Genome Atlas (TCGA) HNSC cohort. Two immunophenotypes (immune 'Hot' and immune 'Cold') that had different TME features, diverse prognosis, and distinct DNA methylation patterns were recognized. Immunophenotype-related methylated signatures (IPMS) were identified by the least absolute shrinkage and selector operation algorithm. Additionally, the IPMS score by deconvolution algorithm was constructed as an immunophenotype classifier to predict clinical outcomes and immunotherapeutic response. RESULTS: The 'Hot' HNSC immunophenotype had higher immunoactivity and better overall survival (p = 0.00055) compared to the 'Cold' tumors. The immunophenotypes had distinct DNA methylation patterns, which was closely associated with HNSC tumorigenesis and functional immune cell infiltration. 311 immunophenotype-related methylated CpG sites (IRMCs) was identified from TCGA-HNSC dataset. IPMS score model achieved a strong clinical predictive performance for classifying immunophenotypes. The area under the curve value (AUC) of the IPMS score model reached 85.9% and 89.8% in TCGA train and test datasets, respectively, and robustness was verified in five HNSC validation datasets. It was also validated as an immunophenotype classifier for predicting durable clinical benefits (DCB) in lung cancer patients who received anti-PD-1/PD-L1 immunotherapy (p = 0.017) and TCGA-SKCM patients who received distinct immunotherapy (p = 0.033). CONCLUSIONS: This study systematically analyzed DNA methylation patterns in distinct immunophenotypes to identify IPMS with clinical prognostic potential for personalized epigenetic anticancer approaches in HNSC patients. The IPMS score model may serve as a reliable epigenome prognostic tool for clinical immunophenotyping to guide immunotherapeutic strategies in HNSC.

Global burden of inflammatory bowel disease 1990-2019: A systematic examination of the disease burden and twenty-year forecast.

BACKGROUND: Inflammatory bowel disease (IBD) is an idiopathic intestinal disease with various levels and trends in different countries and regions. Understanding the current burden and trends of IBD in various geographical locations is essential to establish effective strategies for prevention and treatment. We report the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) in age-standardized rates (ASR) of IBD in different regions based on the Global Burden of Disease (GBD) study from 1990-2019, and the relationships between IBD and the human development index (HDI) and socio-demographic index (SDI). The prevalence trends of IBD were predicted by gender from 2019-2039. AIM: To comprehensively investigate IBD data, providing further insights into the management of this chronic disease. METHODS: We collected the information on the incidence of IBD from the GBD study from 1990-2019 to calculate the AAPC and EAPC in ASR of IBD in different regions. The relationships between IBD, HDI, and SDI were analyzed. The Nordpred and Bayesian age-period-cohort models were used to predict the prevalence trends of IBD by gender from 2019-2039, and the reliability of the results was validated. Statistics of all the data in this study were performed using R software (version 4.2.1). RESULTS: North America consistently had the highest IBD ASR, while Oceania consistently had the lowest. East Asia had the fastest average annual growth in ASR (2.54%), whereas Central Europe had the fastest decline (1.38%). Countries with a low age-standardized incidence rates in 1990 showed faster growth in IBD while there was no significant correlation in 2019. Additionally, IBD increased faster in countries with a low age-standardized death rates in 1990, whereas the opposite was true in 2019. Analysis of SDI and IBD ASR showed that countries with a high SDI generally had a higher IBD ASR. Finally, the projections showed a declining trend in the incidence of IBD from 2019-2039, but a gradual increase in the number of cases. CONCLUSION: As the global population increases and ages, early monitoring and prevention of IBD is important to reduce the disease burden, especially in countries with a high incidence of IBD.

Time-Dependent Changes in the Bladder Muscle Metabolome After Traumatic Spinal Cord Injury in Rats Using Metabolomics.

PURPOSE: The main treatment options of neurogenic bladder remains catheterization and long-term oral medications. Metabolic interventions have shown good therapeutic results in many diseases. To date, no studies have characterized the metabolites of the detrusor muscle during neurogenic bladder. Using metabolomics, new muscle metabolomic signatures were identified to reveal the temporal metabolic profile of muscle during disease progression. METHODS: We used 42 Sprague-Dawley rats (200±20 g, males) for T10 segmental spinal cord injury modeling and collected detrusor tissue and performed nontargeted metabolomics after sham surgery, 30-minute, 6-hour, 12-hour, 24-hour, 5-day, and 2-week postmodelling, to identify the dysregulated metabolic pathways and key metabolites. RESULTS: By comparing mzCloud, mzVault, MassList, we identified a total of 1,271 metabolites and enriched a total of 12 metabolism-related pathways with significant differences (P<0.05) based on Kyoto Encyclopedia of Genes and Genomes analysis. Metabolites in several differential metabolic pathways such as ascorbate and aldarate metabolism, Steroid hormone biosynthesis, and carbon metabolism are altered in a regular manner before and after ridge shock. CONCLUSION: Our study is the first time-based metabolomic study of rat forced urinary muscle after traumatic spinal cord injury, and we identified multiple differential metabolic pathways during injury that may improve long-term management strategies for neurogenic bladder and reduce costs in long-term treatment.

GALNT3 protects against vascular calcification by reducing oxidative stress and apoptosis of smooth muscle cells.

Vascular calcification (VC) is the pathological deposition of calcium and phosphate minerals in blood vessels, which is a common complication of atherosclerosis. Polypeptide N-acetylgalactosamine transferase 3 (GALNT3) initiates O-glycosylation of proteins through addition of GalNAc to specific serine or threonine residues. Our previous studies revealed the potent role of GALNT3 in atherosclerosis, whereas the precise mechanisms remain obscure. This study investigated the regulatory effect and mechanism of GALNT3 on VC. Firstly, GALNT3 was overexpressed and knocked down by adenovirus in high-phosphate induced calcified HASMCs and overexpressed by adeno-associated virus in vitamin D3-induced arterial calcification mice. We showed that the calcium deposition and mRNA expression of osteogenic markers MSX2, ALPL, and Runx2 were all significantly reduced with GALNT3 overexpression. Moreover, overexpression of GALNT3 significantly down-regulated the expression of the oxidative stress markers Nox2 and Nox4, up-regulated total antioxidant capacity, decreased the expression of pro-inflammatory factors IL-1ß, TNF-α and IL-8, matrix metalloproteinases MMP2 and MMP9, as well as reduced the apoptosis of cells in phosphate induced HASMCs. Furthermore, Vicia Villosa Lectin (VVL) pull down and TNFR1 immunoprecipitation assays showed that GALNT3 overexpression increased O-GalNAcylation of TNFR1 and blocked the activation of NF-κB signaling pathway. In addition, GALNT3 attenuates vitamin D3-induced aortic calcification in mice by alleviating oxidative stress and apoptosis of smooth muscle cells. In conclusion, this study indicates that GALNT3 protects against VC by reducing oxidative stress, vascular inflammation, and apoptosis of smooth muscle cells through the TNFR1/NF-κB signaling pathway. Thus, GALNT3 may be a potential therapeutic target for VC.

Elevated Fibroblast Growth Factor 23 Impairs Endothelial Function through the NF-κB Signaling Pathway.

AIM: Roles of fibroblast growth factor 23 (FGF23) in endothelial dysfunction remain controversial, and evidence from population-based studies is lacking. The present study aimed to explore the effects of FGF23 on endothelial dysfunction on the basis of both clinical data of patients with coronary artery disease (CAD) and the in vitro research in human umbilical vein endothelial cells (HUVECs). METHODS: A total of 321 CAD patients were enrolled after coronary angiography, brachial artery flow-mediated dilation (FMD) was assessed using ultrasound equipment. Serum FGF23, nitric oxide (NO), and endothelin-1 (ET-1) were detected via enzyme-linked immunosorbent assay. Apoptosis was determined using the annexin V-fluorescein isothiocyanate/propidium lodide apoptosis detection kit. Cell migration was evaluated by wound healing and transwell migration assays. Reactive oxide species levels were determined using fluorescent probes, and NF-κB p65 nuclear translocation was assessed via immunofluorescence. RESULTS: Serum FGF23 was significantly increased in CAD patients combined with severe endothelial dysfunction (FMD ＜2%) compared to those with FMD ≥ 2% (P＜0.001). Furthermore, the levels of FGF23 were negatively correlated with NO, whereas positively correlated with ET-1 both in unadjusted analysis and multivariate-adjusted analysis. In HUVECs, FGF23 interfered with the bioavailability of NO via increased oxidative stress. Moreover, FGF23 directly impaired the endothelium by promoting HUVECs apoptosis and attenuating the migration of HUVECs. Additional experiments showed that FGF23 induced endothelial injury through activation of the NF-κB signaling pathway. CONCLUSIONS: Elevated FGF23 is clinically associated with endothelial dysfunction in CAD patients, and FGF23 impairs endothelial function through activation of the NF-κB signaling pathway.

Sofosbuvir-based direct-acting antivirals and changes in cholesterol and low density lipoprotein-cholesterol.

Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann-Whitney's test. 487 patients were treated with Harvoni (SOF-based, 206 patients), Epclusa (SOF-based, 124 patients), Maviret (non-SOF-based, 122 patients), or Zepatier (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni, Epclusa, and Maviret induced statistically significant elevation of TC and LDL-C, but Zepatier did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI 1.84-4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL-C (95% CI 1.39-3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12.

Self-Propagating High-Temperature Synthesis of Magnesium Aluminate Spinel Using Mg-Al Alloy.

In this study, magnesium aluminate spinel (MgAl2O4) was synthesized by a self-propagating high-temperature synthesis method using Mg-Al alloy with a Mg/Al mass ratio of 50:50 as raw material. Synthesized MgAl2O4 was characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, UV-vis diffused reflectance spectroscopy, photoluminescence, and thermogravimetric differential scanning calorimetry techniques. The results show that synthesized products are of high purity and excellent crystallinity. However, the particle size is not uniform and there is obvious agglomeration. The crystallite size of spinel phase is calculated to be 37.78 nm. In the UV band, the synthesized MgAl2O4 has a certain absorption capacity, and the extrapolated band gap is 4.02 eV. The synthesis mechanism was studied, and continued rupture and growth of the oxidation layer is thought to be responsible for grain refinement.

[Application of UPLC-QTOF-MS non-targeted metabonomics in mechanism study of property differences of ginseng and American ginseng].

This study adopted ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS)-based untargeted metabolomic approaches for exploring the changes in endogenous metabolites of rat serum related to property differences between ginseng and American ginseng. Then the action mechanisms of them with warm and cool properties and the effects of processing on their property changes were investigated. Based on principal component analysis(PCA), the differences in metabolite profiles between ginseng, red ginseng, American ginseng, and red American ginseng were compared. After that, 16 potential differential endogenous biomarkers were identified by orthogonal partial least squares discriminant analysis(OPLS-DA) and online database searching. And the related metabolic pathways were systematically analyzed. By comparing content variations of these 16 potential differential endogenous biomarkers, we have found that 10 potential differential biomarkers were responsible for the warm property of ginseng and red ginseng, and 9 were related to the cool property of American ginseng and red American ginseng. As demonstrated by in-depth analysis of related metabolic pathways of differential biomarkers, ginseng and American ginseng mainly played a role in regulating the energy metabolism of amino acid, glycolysis, and fatty acids, during which they exhibited differences in property. The comparison of content variations of these differential endogenous between groups revealed that the energy metabolism of red ginseng group was stronger than that of ginseng group, consistent with the traditional processing theory that the warming and tonifying effects of ginseng could be enhanced after processing. The property of red American ginseng was similar to that of American ginseng, both cool in property, but American ginseng was cooler than red American ginseng. It can be seen that non-targeted metabolomic approaches can be utilized to study mechanisms underlying property differences of Chinese medicines and the effects of processing on their property changes.

A highly conductive self-assembled multilayer graphene nanosheet film for electronic tattoos in the applications of human electrophysiology and strain sensing.

Highly conductive, conformable and gel-free electrodes are desirable in human electrophysiology. Besides, intimately coupling with human skin, wearable strain sensors can detect numerous physiological signals, such as wrist pulse and breath. In this study, a multilayer graphene nanosheet film (MGNF) with high conductivity was prepared by the Marangoni self-assembly for using in tattoo dry electrodes (TDEs) and in a graphene tattoo strain sensor (GTSS). Compared to commercial Ag/AgCl gel electrodes, TDEs have lower skin-electrode contact impedance and could detect human electrocardiogram for 24-hour wearing more accurately as well as electromyogram. Through designing a slim serpentine ribbon structure, a resistance-type GTSS, without deterioration even after 2000 cycles, is well demonstrated for human wrist pulse and breath sensing. With the advantages of high conductivity and conformability, MGNF provides support to fabricate low-cost, customizable, and high-performance electronic tattoos for human electrophysiology and strain sensing.

Application of Immune Infiltration Signature and Machine Learning Model in the Differential Diagnosis and Prognosis of Bone-Related Malignancies.

Bone-related malignancies, such as osteosarcoma, Ewing's sarcoma, multiple myeloma, and cancer bone metastases have similar histological context, but they are distinct in origin and biological behavior. We hypothesize that a distinct immune infiltrative microenvironment exists in these four most common malignant bone-associated tumors and can be used for tumor diagnosis and patient prognosis. After sample cleaning, data integration, and batch effect removal, we used 22 publicly available datasets to draw out the tumor immune microenvironment using the ssGSEA algorithm. The diagnostic model was developed using the random forest. Further statistical analysis of the immune microenvironment and clinical data of patients with osteosarcoma and Ewing's sarcoma was carried out. The results suggested significant differences in the microenvironment of bone-related tumors, and the diagnostic accuracy of the model was higher than 97%. Also, high infiltration of multiple immune cells in Ewing's sarcoma was suggestive of poor patient prognosis. Meanwhile, increased infiltration of macrophages and B cells suggested a better prognosis for patients with osteosarcoma, and effector memory CD8 T cells and type 2 T helper cells correlated with patients' chemotherapy responsiveness and tumor metastasis. Our study revealed that the random forest diagnostic model based on immune infiltration can accurately perform the differential diagnosis of bone-related malignancies. The immune microenvironment of osteosarcoma and Ewing's sarcoma has an important impact on patient prognosis. Suppressing the highly inflammatory environment of Ewing's sarcoma and promoting macrophage and B cell infiltration may have good potential to be a novel adjuvant treatment option for osteosarcoma and Ewing's sarcoma.

Fluorinating Dopant-Free Small-Molecule Hole-Transport Material to Enhance the Photovoltaic Property.

For the stability and commercial development of the perovskite solar cells (PVK-SCs), synthesizing high-efficiency dopant-free hole-transport materials (DF-HTMs) and exploring how the DF-HTM structure affects the photovoltaic performance is inevitable. Two small-molecule DF-HTMs based on 2,2'-bithiophene as a central part (denoted by BT-MTP and DFBT-MTP) were designed and synthesized. DFBT-MTP, with two more fluorine atoms substituted on the 2,2'-bithiophene group, exhibited enhanced photovoltaic property as DF-HTMs, including larger backbone planarity, declining highest occupied molecular orbit (HOMO) energy level, increasing hole transportation, more effective passivation, and efficient charge extraction. With fluorinated DFBT-MTP being applied as DF-HTMs in p-i-n PVK-SCs, an efficiency of 20.2% was achieved, showing ∼35% efficiency increase compared with the nonfluorinated BT-MTP-based devices. The leading power conversion efficiency (PCE) indicates that the fluorinated compounds should be a promising direction for exploring high-performance DF-HTMs in the p-i-n PVK-SCs.

Hippocampal LASP1 ameliorates chronic stress-mediated behavioral responses in a mouse model of unpredictable chronic mild stress.

Substantial evidence has revealed that abnormalities in synaptic plasticity play important roles during the process of depression. LASP1 (LIM and SH3 domain protein 1), a member of actin-binding proteins, has been shown to be associated with the regulation of synaptic plasticity. However, the role of LASP1 in the regulation of mood is still unclear. Here, using an unpredictable chronic mild stress (UCMS) paradigm, we found that the mRNA and protein levels of LASP1 were decreased in the hippocampus of stressed mice and that UCMS-induced down-regulation of LASP1 was abolished by chronic administration of fluoxetine. Adenosine-associated virus-mediated hippocampal LASP1 overexpression alleviated the UCMS-induced behavioral results of forced swimming test and sucrose preference test in stressed mice. It also restored the dendritic spine density, elevated the levels of AKT (a serine/threonine protein kinase), phosphorylated-AKT, insulin-like growth factor 2, and postsynaptic density protein 95. These findings suggest that LASP1 alleviates UCMS-provoked behavioral defects, which may be mediated by an enhanced dendritic spine density and more activated AKT-dependent LASP1 signaling, pointing to the antidepressant role of LASP1.

Precipitating factors causing hyperbilirubinemia during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir.

BACKGROUND: Hepatic decompensation is a fatal on-treatment side effect during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Prompt bilirubin testing can reveal hepatic failure in susceptible patients, and clinical parameters precipitating early elevation of bilirubin can warn clinicians to avoid PrOD prescription. METHODS: This retrospective study included 169 Hepatitis C virus (HCV)-genotype 1b patients who underwent a 12-week course of PrOD with or without ribavirin. Laboratory data underwent χ analysis with Fisher's exact test to determine the precipitating factors causing hyperbilirubinemia in patients who had received 1 week of treatment. RESULTS: Sustained viral response was achieved in 164 patients (97.0%). Total bilirubin was ≥2 mg/dL (21.3%) in 36 patients after 1 week of treatment. Pretreatment white blood cell (WBC) <4500/µL and platelet <100,000/µL correlated with total bilirubin ≥2 mg/dL (relative risk [RR]: 21.64, 95% CI: 5.23-89.64, p < 0.001) after 1 week of treatment. Pretreatment platelet ≥100 000/µL and WBC <4500/µL correlated with direct bilirubin ≥0.45 mg/dL (RR: 6.56, 95% CI: 1.42-30.38, p = 0.016) and indirect bilirubin ≥0.6 mg/dL (RR: 4.77, 95% CI: 1.03-22.15, p = 0.046). Pretreatment platelet <100,000/µL with F3/F4 fibrosis correlated with first week total bilirubin ≥2 mg/dL (RR: 3.57, 95% CI: 1.35-9.09, p = 0.010). CONCLUSION: PrOD is an effective antiviral regimen for HCV genotype 1b patients. Total bilirubin ≥2 mg/dL after 1 week of treatment serves as an early warning of irreversible progression toward hepatic decompensation, and the current study provides a guide by which to monitor chronic hepatitis C patients undergoing PrOD treatment.

Performance Evaluation and Optimization of Dyes Removal using Rice Bran-Based Magnetic Composite Adsorbent.

Although several studies have explored green adsorbent synthesized from many types of agriculture waste, this study represents the first attempt to prepare an environmentally friendly rice bran/SnO2/Fe3O4-based absorbent with economic viability and material reusability, for the promotion of sustainable development. Here, rice bran/SnO2/Fe3O4 composites were successfully synthesized and applied for adsorption of reactive blue 4 (RB4) and crystal violet (CV) dyes in aqueous solutions. The adsorption data were well-fitted by the Langmuir isotherm model and the pseudo-second-order kinetic model. The maximum adsorption capacities of the RB4 and CV dyes as indicated by the Langmuir isotherm model were 218.82 and 159.24 mg/g, respectively. As results of response surface methodology (RSM) showed, the quadratic model was appropriate to predict the performance of RB4 dye removal. The findings exhibited that an optimum removal rate of 98% was achieved at 60 °C for pH 2.93 and adsorption time of 360 min. Comparative evaluation of different agricultural wastes indicated that the rice bran/SnO2/Fe3O4 composite appeared to be a highly promising material in terms of regeneration and reusability, and showed that the composite is a potential adsorbent for dye removal from aqueous solutions. Overall, the study results clearly suggest that an adsorbent synthesized from rice bran/SnO2/Fe3O4 magnetic particle composites provides encouraging adsorption capacity for practical applications for environmental prevention.

Friend or foe: Multiple roles of adipose tissue in cancer formation and progression.

Obesity is well-known as the second factor for tumorigenesis after smoking and is bound up with the malignant progression of several kinds of cancers, including esophageal cancer, liver cancer, colorectal cancer, kidney cancer, and ovarian cancer. The increased morbidity and mortality of obesity-related cancer are mostly attributed to dysfunctional adipose tissue. The possible mechanisms connecting dysfunctional adipose tissue to high cancer risk mainly focus on chronic inflammation, obesity-related microenvironment, adipokine secretion disorder, and browning of adipose tissue, and so forth. The stromal vascular cells in adipose tissue trigger chronic inflammation through secreting inflammatory factors and promote cancer cell proliferation. Hypertrophic adipose tissues lead to metabolic disorders of adipocytes, such as abnormal levels of adipokines that mediate cancer progression and metastasis. Cancer patients often show adipose tissue browning and cancerous cachexia in an advanced stage, which lead to unsatisfied chemotherapy effect and poor prognosis. However, increasing evidence has shown that adipose tissue may display quite opposite effects in cancer development. Therefore, the interaction between cancers and adipose tissue exert a vital role in mediates adipose tissue dysfunction and further leads to cancer progression. In conclusion, targeting the dysfunction of adipose tissue provides a promising strategy for cancer prevention and therapy.

Identification of Plant-Pathogenic Fungi Using Fourier Transform Infrared Spectroscopy Combined with Chemometric Analyses.

Identification of plant-pathogenic fungi is time-consuming due to cultivation and microscopic examination and can be influenced by the interpretation of the micro-morphological characters observed. The present investigation aimed to create a simple but sophisticated method for the identification of plant-pathogenic fungi by Fourier transform infrared (FTIR) spectroscopy. In this study, FTIR-attenuated total reflectance (ATR) spectroscopy was used in combination with chemometric analysis for identification of important pathogenic fungi of horticultural plants. Mixtures of mycelia and spores from 27 fungal strains belonging to nine different families were collected from liquid PD or solid PDA media cultures and subjected to FTIR-ATR spectroscopy measurements. The FTIR-ATR spectra ranging from 4 000 to 400 cm-1 were obtained. To classify the FTIR-ATR spectra, cluster analysis was compared with canonical vitiate analysis (CVA) in the spectral regions of 3 050～2 800 and 1 800～900 cm-1. Results showed that the identification accuracies achieved 97.53% and 99.18% for the cluster analysis and CVA analysis, respectively, demonstrating the high potential of this technique for fungal strain identification.