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Background The Asia-Pacific Colorectal Screening (APCS) score is effective to screen high-risk groups of advanced colorectal neoplasia (ACN) patients but needs revising and can be combined with the fecal immunochemical test (FIT). This paper aimed to improve the APCS score and evaluate its use with the FIT in stratifying the risk of ACN. Methods This prospective and multicenter study enrolled 955 and 1201 asymptomatic Chinese participants to form the derivation and validation set, respectively. Participants received the risk factor questionnaire, colonoscopy and FIT. Multiple logistic regression was applied, and C-statistic, sensitivity and negative predictive values (NPVs) were used to compare the screening efficiency. Results A modified model was developed incorporating age, body mass index (BMI), family history, diabetes, smoking and drinking as risk factors, stratifying subjects into average risk (AR) or high risk (HR). In the validation set, the HR tier group had a 3.4-fold (95% CI 1.8–6.4) increased risk for ACN. The C-statistic for the modified score was 0.69 ± 0.04, and 0.67 ± 0.04 for the original score. The sensitivity of the modified APCS score combined with FIT for screening ACN high-risk cohorts was 76.7% compared with 36.7% of FIT alone and 70.0% of the modified APCS score alone. The NPVs of the modified score combined with FIT for ACN were 98.0% compared with 97.0% of FIT alone and 97.9% of the modified APCS score alone. Conclusions The modified score and its use with the FIT are efficient in selecting the HR group from a Chinese asymptomatic population.

The present study carries out systematic thermodynamics analysis of Grain Boundary (GB) segregation and relaxation in Nano-Grained (NG) polycrystalline alloys. GB segregation and relaxation is an internal process towards thermodynamic equilibrium, which occurs naturally in NG alloys without any applied loads, causes deformation and generates internal stresses. The analysis comprehensively investigates the multiple coupling effects among chemical concentrations and mechanical stresses in GBs and grains. A hybrid approach of eigenstress and eigenstrain is developed herein to solve the multiple coupling problem. The analysis results indicate that the GB stress and grain stress induced by GB segregation and relaxation can be extremely high in NG alloys, reaching the GPa level, which play an important role in the thermal stability of NG alloys, especially via the coupling terms between stress and concentration. The present theoretic analysis proposes a novel criterion of thermal stability for NG alloys, which is determined by the difference in molar free energy between a NG alloy and its reference single crystal with the same nominal chemical composition. If the difference at a temperature is negative or zero, the NG alloy is thermal stable at that temperature, otherwise unstable.

Objective： To study explores the effect of HLEC on the secreted proteins of epithelial ovarian cancer （EOC） cells （SKOV3-PM4） with directional highly lymphatic metastasis. Methods： Supernatants of four groups of cultured cells, namely, SKOV3 （A）, SKOV3＋HLEC （B）, SKOV3-PM4 （C）, SKOV3-PM4＋HLEC （D）, were collected, and their proteins were detected by antibody arrays and iTRAOcZD-LC-MALDI- TOF/TOF/MS. Significantly differential proteins were further analyzed via bioinformatics and validated in human serums and cell media via ELISA. Results： Results of antibody arrays and mass spectrometry demonstrated that GRN and VEGFA were upregulated in group C （compared with group A）, whereas IGFBP7 and SPARC were downregulated in group D （compared with group C）. Comprehensive bioinformatics analysis results showed that IGFBP7 and VEGFA were closely linked to each other. Further validation with serums showed statistical significance in VEGFA and IGFBP7 levels among groups of patients with ovarian cancers, benign tumors, and control groups. Two proteins were upegulated in the first group. VEGFA in the control group was downregulated. For IGFBP, upregulation in the control group and down-regulation in the first group were also observed. Conclusion： The HLEC microenvironment is closely associated with directional metastasis to lymph nodes and with differential proteins including cell stromal proteins and adhesion factors. The upregulation of VEGFA and GRN and the downregulation of SPARC and IGFBP7 are closely associated with directional metastasis to lymph nodes in EOC cells.

Background： The clinical significance of metabolic syndrome （MS） score, MS, and its individual components with respect to risk prediction of coronary artery disease （CAD） remains unclear. The objective of this study was to investigate whether and to what extent MS score, MS, and its individual components were related to the risk of CAD. Methods： Among 1191 participants who underwent coronary angiography for the confirmation of suspected myocardial ischemia, 858 were included in this study according to the inclusion criteria from September 2010 to June 2013. MS was diagnosed with the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria. The severity of coronary atherosclerosis was assessed by Gensini score. Results： The results showed that the age- and sex-adjusted odds ratios （ORs） tbr CAD were as follows： MS score, 1.327; MS, 2.013; elevated waist circumference, 1.447; reduced high-density lipoprotein cholesterol, 1.654： and elevated fasting glucose, 1.782： all P〈 0.05： whereas for elevated triglycerides, 1.324, and elevated blood pressure, 1.342, both P 〉 0.05. Alter multivariate adjustment, results showed that only MS and elevated fasting glucose were significantly associated with CAD （OR, 1.628, 95% confidence interval [CI], 1.151-2.305, P = 0.006 for elevated fasting glucose, and OR, 1.631, 95% CI, 1.208-2.203, P = 0.001 for MS）. The study showed that only MS score and elevated fasting glucose were significantly associated with Gensini score （standardized coefficient, 0.101, P = 0.031 for elevated fasting glucose and standardized coefficient, 0.103, P = 0.009 for MS score）. Conclusions： The present study demonstrated that MS score, MS, and its individual components might have different contributions to CAD prevalence and severity. MS and elevated fasting glucose were independent risk factors for the prevalence of angiographic CAD whereas MS score and elevated fasting glucose were significantly associated with the severity of CAD.

The high cost and poor atom utilization efficiency of noble metal catalysts have limited their industrial applications. Herein, we designed CeO2-supported single Au（Ⅲ） ion catalysts with ultra-low gold loading that can enhance the utilization efficiency of gold atoms and bridge the gap between homogeneous and heterogeneous gold catalysis. These catalysts were highly active and reusable for the reaction of 1,3-dicarbonyls with alcohols. The catalytic turnover number of CeO2-supported single Au（III） ion catalysts was much higher than that of the homogeneous catalyst NaAuCI4. In addition, the effects of gold loading and the drying method for the catalysts on the organic reactions were systematically explored. In-depth investigation of the structure-property relationship by high- resolution transmission electron microscop~ hydrogen temperature-programmed reduction, X-ray absorption near edge structure analysis, UV-vis diffuse reflectance spectroscopy, and X-ray photoelectron spectroscopy revealed that the isolated Au（III） ions were related to the active sites for the synthesis of β-substituted cyclohexenone and that CeO2 was responsible for yielding ketonic ester.

In the present work, the JCOE forming is investigated using the finite element (FE) method. A two-dimensional FE model is established for the plane strain condition by FE code ABAQUS, and the FE model is validated by experiments. The aim of this research is to investigate forming quality states in the JCOE forming process; in particular, the effects of technological parameters on forming quality are evaluated. Taking the JCOE forming process of X80 steel Φ 1 219 mm × 22 mm × 12 000 mm welding pipe for instance, the deformation characteristics of JCOE forming are analyzed, in which the geometry of the formed pipe, residual stress distributions and effects of process parameters on JCOE forming quality can be obtained. Thus, the presented results of this research provide an effective approach to improve welding pipe forming quality.

Screening of microorganisms producing flocculating substances was carried out. A strain secreting a large amount of bioflocculant was isolated from wastewater samples collected from the Little Moon River in Beijing. Based on the morphological properties and 16S rDNA sequence analysis, the isolate （designated W31） was classified as Vagococcus sp. A bioflocculant （named MBFW31） produced by W31 was extracted from the culture broth by ethanol precipitation and purified by gel chromatography. MBFW31 was heat-stable and had strong flocculating activity in a wide range of pH with relatively low dosage requirement. MBFW31 was identified as a polysaccharide with molecular weight over 2×10^6. It contained neutral sugar and uronic acid as its major and minor components, respectively. Infrared spectra showed the presence of hydroxyl, carboxyl and methoxyl group in its molecules. The present results suggested that MBFW31 had potential application in wastewater treatment.

Over half of patients with BRCAl-deficient cancers do not respond to treatment with poly（ADP-ribose） poiymerase （PARP） inhibitors. In this study, we report that a combination of 53BP1 and BRCA1 may serve as a biomarker of PARP inhibitor sensitivity. Based on the mRNA levels of four homologous recombination repair （HR） genes and PARP inhibitor sensitivity, we selected BRCAl-deficient MDA-MB-436 cells to conduct RNA interference. Reducing expression of 53BP1, but not the other three HR genes, was found to lower simmiparib sensitivity. Additionally, we generated 53BP1-/-/BRCA1-/- clonal variants by the transcription activator-like effector nuclease （TALEN） technique and found that depleting 53BP1 impaired PARP inhibitor sensitivity with a 36.7-fold increase in their ICso values. Consistent with its effect on PARP inhibitor sensitivity, 53BP1 loss alleviated cell cycle arrest and apoptosis and partially restored HR function. Importantly, 53BP1 depletion dramatically reduced the ability of PARP inhibitors to suppress tumor growth in vivo. The inhibition rate of simmiparib was 74.16% for BRCAl-deficient MDA-MB-436 xenografts, but only 7.79% for 53BP1/BRCA1- deficient xenografts. Re-expressing 53BP1 in the dual-deficient cells restored PARP inhibitor sensitivity and the levels of HR regulators. Considering that at least 10% of BRCAl-deficient breast and ovarian cancers have reduced expression of 53BP1, using a combination of 53BP1 with BRCA1 as a biomarker for patient selection should reduce the number of patients undergoing futile treatment with PARP inhibitors.

Poly‐ADP‐ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA‐deficient tumors. However, over 40% of BRCA‐deficient patients fail to respond to PARPi. Here, we report that thioparib, a next‐generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi‐sensitive and ‐resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo . Thioparib treatment elicited PARP1‐dependent DNA damage and replication stress, causing S‐phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR‐mediated DNA repair while increasing RAD51 foci formation. Notably, the on‐target inhibition of PARP7 by thioparib‐activated STING/TBK1‐dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome‐scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next‐generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier‐generation PARPi. Synopsis PARP inhibitors (PARPi) resistance is ubiquitous in the clinic. A newly discovered pan‐PARP inhibitor, thioparib, is highly effective against olaparib‐resistant cancer models, which suggests that therapeutic vulnerabilities still exist in PARPi‐resistant tumors. Thioparib is a novel, potent, and orally bioavailable pan‐PARP inhibitor. Thioparib overcomes primary and acquired olaparib resistance in vitro and in vivo . Thioparib suppresses HR‐mediated DNA repair. Thioparib induces a robust type I interferon response. Graphical Abstract PARP inhibitors (PARPi) resistance is ubiquitous in the clinic. A newly discovered pan‐PARP inhibitor, thioparib, is highly effective against olaparib‐resistant cancer models, which suggests that therapeutic vulnerabilities still exist in PARPi‐resistant tumors.