Background:Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.Methods:To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (ABCB1) gene expression between the NPR group and the HPR group. Metagenomic and metabolomic analyses of fecal samples showed that HPR patients had higher microbial richness and diversity. Transplantation of the gut microbiota from HPR donors to microbiota-depleted mice obviously decreased plasma concentration of ticagrelor.Results:Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.Conclusions:Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMIFunding:NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.

The paper is based on the numerical solution of Euler's method to deal with the initial value problems for Erbium doped fiber amplifiers'(EDFAs)rate equations, and their gain dependences are discussed. Simulation of the propagation of the signal and pump power versus the amplifier length has been done. Modifying the input pump power and input signal power has obtained the gain profile of the PCF based EDFAs. Fiber designs which allow us to have large gain are presented and demonstrated that the PCF based Erbium doped amplifiers may deliver gain 54dB with small losses. The gain is greater than the conventional EDFAs.Index Terms-Photonic crystal fiber, erbium doped fiber amplifiers, gain.

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Based on the research results at home and abroad, this paper studies the influencing factors and evaluation system of Strategy Adaptation Ability. The study considers that enterprises need to grasp the changes of the external environment accurately and make correct adjustments timely with the uncertainty of the external environment. The key is to improve four ability for four aspects: environmental awareness ability, situation judgment ability, strategic decision-making ability and organizational adaptability. This paper provides theoretical support and application tools for enterprises to improve their strategic management level and enhance their sustainable development capabilities. IntroductionWith the development of industrial revolution and technological revolution, the future development situation is changing increasingly. The uncertainty of business environment is becoming stronger. The static strategy can no longer meet the needs of enterprise development. It needs that the strategy can respond to environment changes quickly in order to seize strategic opportunities and achieve rapid development. So it is of great significance to improve strategy adaptation ability.The analysis and enterprise strategy adaptation ability has always been the focus of academic circles. From the perspective of contingency theory, Miles and Snow (1994) considered that successful companies are organizations that match the environment organically. From the perspective of population ecology, Hannan and Freeman (1977) believed that the environment defines the strategies and paths that an organization must follow. From the perspective of strategic choice theory, Schindehutte and Morris (2001) argued that environmental conditions couldn't be considered as a direct source of differences in organizational structure, and managers have the right of judgment and higher decision-making. From the perspective of cognition, Chen and Chen (2007) believed that the strategic adjustment of the senior management team consisted of the ability to target and the ability to coordinate. The former is determined by heterogeneous cognitive ability, and the latter is influenced by the level of recognition of strategic adjustment programs by executive team members. Wei and Chen (2011) found that the external environment, internal resources and capabilities, corporate concept and innovation, corporate strategy, core competitiveness and sustainable competitive advantage are the main factors that affected the enterprise strategy adaptation ability.In general, the current research on enterprise strategy adaptation ability has achieved rich results, but most of them are qualitative studies, and quantitative description and evaluation of strategy adaptation ability are few. In view of this, based on the existing research results, this paper studies the influencing factors and evaluation of strategy adaptation ability, and provides theoretical support and application tools for enterprises, to improve their strategic management level and enhance their sustain...

Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone secreted primarily by the liver and is considered a major regulator of energy homeostasis. Recent research has revealed that FGF21 could play an important role in cardiac pathological remodeling effects and prevention of cardiomyopathy; however, the underlying mechanism remains largely unknown. This study aimed to determine the mechanism underlying the cardioprotective effects of FGF21. We engineered FGF21 knock out mice and subsequently elucidated the effects of FGF21 and its downstream mediators using western blotting, qRT-PCR, and mitochondrial morphological and functional analyses. FGF21 knockout mice showed cardiac dysfunction, accompanied by a decline in global longitudinal strain (GLS) and ejection fraction (EF), independent of metabolic disorders. Mitochondrial quality, quantity, and function were abnormal, accompanied by decreased levels of optic atrophy-1 (OPA1) in FGF21 KO mice. In contrast to FGF21 knockout, cardiac-specific overexpression of FGF21 alleviated the cardiac dysfunction caused by FGF21 deficiency. In an in vitro study, FGF21 siRNA deteriorated mitochondrial dynamics and impaired function induced by cobalt chloride (CoCl2). Both recombinant FGF21 and adenovirus-mediated FGF21 overexpression could alleviate CoCl2-induced mitochondrial impairment by restoring mitochondrial dynamics. FGF21 was essential for maintaining mitochondrial dynamics and function of the cardiomyocytes. As a regulator of cardiomyocyte mitochondrial homeostasis under oxidative stress, FGF21 could be an important new target for therapeutic options for patients with heart failure.