The effect of Ca addition on the solidification microstructure of hypoeutectic Al-Si casting alloys was investigated using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) methods with pa...The effect of Ca addition on the solidification microstructure of hypoeutectic Al-Si casting alloys was investigated using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) methods with particular attention focused on the change of morphologies of primary α-Al and eutectic silicon. Meanwhile,solute distribution in solid-liquid was simulated according to Scheil-Gulliver law. Results showed that primary α-Al and eutectic silicon were refined as Ca content increased because of the variation of the solute concentration in liquid. The addition of Ca increased the nucleation sites like Al3Ti or Al2Cu to promote the nucleation of primary α-Al. Affected by modification effect of Ca, the shape of eutectic silicon changed from flake to fibrous structure. In addition, coarse plate Ca-rich phases could be found along the grain boundary with high Ca content.展开更多
It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart disease...It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart disease.Here,in an adaptive,31-center,randomized,double-blind trial invoving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI),a kind of polyphamacological drug with high quality control,or placebo(0.9%saline),with 76-day following-up,we firstly confrmed that DHl couldincrease the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire(ASAQ-AF220)(12.78%at Day 30,95%confidence interval[C]5.86-19.71%,P=0.0003,13.82%at Day 6C0,95%CI 6.82-20.82%,P=0.0001and 8.95%at Day 90,95%CI 2.06-15.85%,P=0.01).We also found that there were no significant differences in new-onset major vascularevents(P=0.8502)and serious adverse events(P=0.9105)between DHl and placebo.After performing the RNA sequencing in 62 selectedpatients,we developed a systemic modular approach tp identfy differentilly expressed modules(DEMs)of DHI with the Z_(summay)valueless than 0 compared with the control group,calculated by weighted gene co-expression network analysis(WGCNA),and sketched out thebasic framework on a modular map with 25 functional modules targeted by DII.Furthermore,the effective therapeutic module(ETM),defined as the highest corelation value with the phenotype alteration(SAQ-AF,the change in SAQ-AF at Day 30 from baseline)calculatedby WGCNA,was identifed in the population with the best effect(ASAQ-AF240),which is related to anticoagulation and regulation ofcholesterol metabolism.We assessed the modular flexbility of this ETM using the global topological D value based on Euclidean distance,which is corelated with phenotype alteration(r^(2):0.8204,P=0.019)by linear regression.Our study identified the ant-angina therapeuticmodule in the effective population treated by the multi-target drug.Modular methods facilitate the discovery of network pharmacologicalmechanisms and the advancement of precision medicine.(ClinicalTrials.gov identifier:NCTO1681316).展开更多
基金financially supported by the National Natural Science Foundation of China(Grant No.51775297)the National Science and the Tsinghua University Initiative Scientific Research Program(20151080370)the UK Royal Academy of Engineering/Royal Society through the Newton International Fellowship Scheme
文摘The effect of Ca addition on the solidification microstructure of hypoeutectic Al-Si casting alloys was investigated using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) methods with particular attention focused on the change of morphologies of primary α-Al and eutectic silicon. Meanwhile,solute distribution in solid-liquid was simulated according to Scheil-Gulliver law. Results showed that primary α-Al and eutectic silicon were refined as Ca content increased because of the variation of the solute concentration in liquid. The addition of Ca increased the nucleation sites like Al3Ti or Al2Cu to promote the nucleation of primary α-Al. Affected by modification effect of Ca, the shape of eutectic silicon changed from flake to fibrous structure. In addition, coarse plate Ca-rich phases could be found along the grain boundary with high Ca content.
基金funded by China National Science and Technology Major Project for"Significant New Drugs Development"(2011ZX09304-07)National Natural Science Foundation of China(81673833)China Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ0908029).
文摘It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart disease.Here,in an adaptive,31-center,randomized,double-blind trial invoving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI),a kind of polyphamacological drug with high quality control,or placebo(0.9%saline),with 76-day following-up,we firstly confrmed that DHl couldincrease the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire(ASAQ-AF220)(12.78%at Day 30,95%confidence interval[C]5.86-19.71%,P=0.0003,13.82%at Day 6C0,95%CI 6.82-20.82%,P=0.0001and 8.95%at Day 90,95%CI 2.06-15.85%,P=0.01).We also found that there were no significant differences in new-onset major vascularevents(P=0.8502)and serious adverse events(P=0.9105)between DHl and placebo.After performing the RNA sequencing in 62 selectedpatients,we developed a systemic modular approach tp identfy differentilly expressed modules(DEMs)of DHI with the Z_(summay)valueless than 0 compared with the control group,calculated by weighted gene co-expression network analysis(WGCNA),and sketched out thebasic framework on a modular map with 25 functional modules targeted by DII.Furthermore,the effective therapeutic module(ETM),defined as the highest corelation value with the phenotype alteration(SAQ-AF,the change in SAQ-AF at Day 30 from baseline)calculatedby WGCNA,was identifed in the population with the best effect(ASAQ-AF240),which is related to anticoagulation and regulation ofcholesterol metabolism.We assessed the modular flexbility of this ETM using the global topological D value based on Euclidean distance,which is corelated with phenotype alteration(r^(2):0.8204,P=0.019)by linear regression.Our study identified the ant-angina therapeuticmodule in the effective population treated by the multi-target drug.Modular methods facilitate the discovery of network pharmacologicalmechanisms and the advancement of precision medicine.(ClinicalTrials.gov identifier:NCTO1681316).
