Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 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 vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Observation of triplet superconductivity in CoSi2/TiSi2 heterostructures.

Unconventional superconductivity and, in particular, triplet superconductivity have been front and center of topological materials and quantum technology research. Here, we report our observation of triplet pairing in nonmagnetic CoSi2/TiSi2 heterostructures on silicon. CoSi2 undergoes a sharp superconducting transition at a critical temperature T c ≃ 1.5 K, while TiSi2 is a normal metal. We investigate conductance spectra of both two-terminal CoSi2/TiSi2 contact junctions and three-terminal T-shaped CoSi2/TiSi2 superconducting proximity structures. Below T c, we observe (i) a narrow zero-bias conductance peak on top of a broad hump, accompanied by two symmetric side dips in the contact junctions, (ii) a narrow zero-bias conductance peak in T-shaped structures, and (iii) hysteresis in the junction magnetoresistance. These three independent and complementary observations point to chiral p-wave pairing in CoSi2/TiSi2 heterostructures. The excellent fabrication compatibility of CoSi2 and TiSi2 with present-day silicon-based integrated-circuit technology suggests their potential use in scalable quantum-computing devices.