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Background The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. Objectives We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. Methods We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. Results Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85–1.04; modulation: RR: 0.90; 95% CI: 0.81–1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76–0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15–1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96–1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51–0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. Conclusion Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

A series of mechanophores were studied computationally by employing the AFIR (Artificial Force Induced Reaction) method, which applies an artificial force on the molecule to trigger reactions, and meanwhile with a tensile force to simulate a mechanochemical reaction. The calculation results were both qualitatively and quantitatively consistent to those reported experimentally, indicating that the AFIR is a reliable approach to studying mechanochemical reactions. It was then applied to the study of retro-Diels-Alder reactions for the theoretical predictions of activation force levels which are currently unavailable. Moreover, it also helped to reveal the favored geometry for the enhancement of force effect. Later, the AFIR method was employed to study the mechanodegradation of generic polymers. The substituents effect and the polymer tacticity in strengthening the mechanical responsiveness, were highlighted by our study. Given the importance of cross-linker molecules in the double-network (DN) hydrogels, a fully automatic search of mechanochemical transformation pathways of a commonly used cross-linker molecule, N,N'-methylenebisacrylamide (MBAA), was also performed by the AFIR method. Through the work described in this article, we demonstrated that, in the field of polymer mechanochemistry, the AFIR method utilizing two forces is a simple but effective tool to give accurate predictions of activation force levels at any given timescale. In the meantime, the mechanistic study of mechanochemical reactions shown in this article is believed to provide insightful suggestions for the further design and application of mechanophores.

Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk.Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched.Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included.Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension.In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low.Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

The hygro-thermo-mechanical behavior of a ultra-high strength steel (UHSS) gasket under radial mechanical loads is investigated. By adopting an appropriate displacement function, the displacement, ...

Triglyceride (TG) and its related metabolic indices, all recognized as surrogates of insulin resistance, have been demonstrated to be relevant to clinical prognosis. However, the relative value of these TG-related indices for predicting cardiovascular events among patients with acute coronary syndrome (ACS) has not been examined.The TG, the triglyceride-glucose (TyG) index, the atherogenic index of plasma, TG to high-density lipoprotein cholesterol ratio, and the lipoprotein combine index were assessed in 1694 ACS patients undergoing percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular event (MACE), which was the composite of all-cause mortality, stroke, myocardial infarction, or unplanned repeat revascularization.During a median follow-up of 31 months, 345 patients (20.4%) had MACE. The risk of the MACE was increased with higher TG and the four TG-derived metabolic indices [TG-adjusted hazard ratio (HR) = 1.002, 95% CI: 1.001-1.003; TyG index-adjusted HR = 1.736, 95% CI: 1.398-2.156; atherogenic index of plasma-adjusted HR = 2.513, 95% CI: 1.562-4.043; TG to high-density lipoprotein cholesterol ratio-adjusted HR = 1.148, 95% CI: 1.048-1.258; and lipoprotein combine index-adjusted HR = 1.009, 95% CI: 1.004-1.014;TG and TG-derived metabolic indices were all strongly associated with MACE among ACS patients undergoing percutaneous coronary intervention. Among all the indices, TyG index showed the best ability to predict the risk of MACE.

Soil abiotic stresses can trigger bottom-up effects on insect pests. However, it remains unknown whether the bottom-up effects differentially affect leaf chewers and sap-feeders, and whether abiotic stresses alter the extent of indirect interactions between insect herbivores sharing a host plant. We carried out a set of manipulative experiments to investigate how abiotic and biotic stresses affected performance associated with insect herbivory (eating by leaf chewer or sap-feeder) and plant physiological conditions (manipulating water and/or salt inputs). We examined the performance of response species (sap-feeder Macrosiphum euphorbiae and leaf chewer Tuta absoluta) on tomato plants Solanum lycopersicum that were exposed to eight conditions in a full factorial design based on (1) optimal or limited water inputs, (2) with or without 100 mM NaCl, and (3) with or without pre-infestation by insect herbivors showing distinct feeding habit. Water and salt stresses slowed down plant growth in terms of plant height and node number, which subsequently negatively affected the herbivores via bottom-up effects. Tuta absoluta larval development was adversely affected by water limitation, while M. euphorhiae survival and fertility were adversely affected by salinity stress. After pre-infestation by the inducing species (i.e. feeding activity on the plant), the test species (either M. euphorbiae or T. absoluta) exhibited a lower performance, that is, lower M. euphorbiae survival and fewer offspring, and extended T. absoluta developmental duration and reduced pupal weight. These results suggested an apparent competition between the herbivores; however, neither water limitation nor salt stress affected the magnitude of the negative indirect interactions between the two insect species. Our findings shed light on how cascading force(s) and induced indirect resistance(s) could be used to improve integrated pest management programs.

Instantaneous patterning on soft material surfaces, such as hydrogels, is important in various research fields; however, it is extremely challenging. Existing strategies for soft material surface patterning are time-consuming and have poor chemical versatility. Herein, we show how micropatterns can be rapidly created on tough double-network (DN) hydrogel surfaces via sacrificial bonds and mechanical force-triggered radical polymerisation. Micropatterning is performed by local mechanical forces, which initiate radical polymerisation in a process zone in the presence of unsaturated monomers, resulting in on-demand functional patterns with a variety of geometries and chemistries. Such force-triggered activation occurs within seconds and is applicable to diverse monomers. To demonstrate potential applications, we engineered topographies and chemistries on DN hydrogel surfaces to control cell adhesion and water droplet directional transport.

Double-network (DN) hydrogels have recently been demonstrated to generate numerous radicals by the homolytic bond scission of the brittle first network under the influence of an external force. The mechanoradicals thus generated can be utilized to trigger polymerization inside the gels, resulting in significant mechanical and functional improvements to the material. Although the concentration of mechanoradicals in DN gels is much higher than that in single-network hydrogels, a further increase in the mechanoradical concentration in DN gels will widen their application. In the present work, we incorporate an azoalkane crosslinker into the first network of DN gels. Compared with the traditional crosslinker N,N'-methylenebis(acrylamide), the azoalkane crosslinker causes a decrease in the yield stress but significantly increases the mechanoradical concentration of DN gels after stretching. In the azoalkane-crosslinked DN gels, the concentration of mechanoradicals can reach a maximum of similar to 220 mu M, which is 5 times that of the traditional crosslinker. In addition, DN gels with the azoalkane crosslinker show a much higher energy efficiency for mechanoradical generation. Interestingly, DN gels crosslinked by a mixture of azoalkane crosslinker and traditional crosslinker also exhibit excellent radical generation performance. The increase in the mechanoradical concentration accelerates polymerization and can broaden the application range of force-responsive DN gels to biomedical devices and soft robots.