Polydatin has attracted much attention as a potential cardioprotective agent against ischemic heart disease and diabetic cardiomyopathy. However, the effect and mechanism of polydatin supplementation ...on alcoholic cardiomyopathy (ACM) are still unknown. This study aimed to determine the therapeutic effect of polydatin against ACM and to explore the molecular mechanisms with a focus on SIRT6-AMP-activated protein kinase (AMPK) signaling and mitochondrial function. The ACM model was established by feeding C57/BL6 mice with an ethanol Lieber-DeCarli diet for 12 weeks. The mice received polydatin (20 mg kg
−1
) or vehicle treatment. We showed that polydatin treatment not only improved cardiac function but also reduced myocardial fibrosis and dynamin-related protein 1 (Drp-1)-mediated mitochondrial fission, and enhanced PTEN-induced putative kinase 1 (PINK1)-Parkin-dependent mitophagy in alcohol-treated myocardium. Importantly, these beneficial effects were mimicked by SIRT6 overexpression but abolished by the infection of recombinant serotype 9 adeno-associated virus (AAV9) carrying SIRT6-specific small hairpin RNA. Mechanistically, alcohol consumption induced a gradual decrease in the myocardial SIRT6 level, while polydatin effectively activated SIRT6-AMPK signaling and modulated mitochondrial dynamics and mitophagy, thus reducing oxidative stress damage and preserving mitochondrial function. In summary, these data present new information regarding the therapeutic actions of polydatin, suggesting that the activation of SIRT6 signaling may represent a new approach for tackling ACM-related cardiac dysfunction.
Polydatin attenuates cardiac remodeling and mitochondrial dysfunction in an alcoholic cardiomyopathy model
via
SIRT6 signaling.
Recurrent spontaneous abortion (RSA) is a common and complicated pregnancy-related disease that lacks a suitable biomarker to predict its recrudescence.
Tandem mass tag (TMT) analysis was conducted ...to obtain quantitative proteomic profiles in follicular fluid from patients with a history of RSA and from control group. ELISA validation of candidate differentially expressed proteins was conducted in a larger group of patients.
A total of 836 proteins were identified by TMT analysis; 51 were upregulated and 47 were downregulated in follicular fluid from cases of RSA versus control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed several important pathways were enriched, involving a dysregulated immunoglobulin Fc receptor signaling pathway and overactivated complement cascade pathways. ELISA validated the differential expression of two proteins, histidine-rich globulin (HRG) and complement C4-B (C4B), which were downregulated and upregulated, respectively, in follicular fluid of patients with RSA. We performed receiver operating characteristic curve analysis of the ELISA results with the outcomes of current IVF cycles as classification variables. The area under the curve results for HRG alone, C4B alone and HRG-C4B combined were 0.785, 0.710 and 0.895, respectively.
TMT analysis identified 98 differentially expressed proteins in follicular fluid from patients with RSA, indicating follicle factors that act as early warning factors for the occurrence of RSA. Among them, HRG and C4B provide candidate markers to predict the clinical outcomes of IVF/ICSI cycles, and the potential for modeling an early detection system for RSA.
Engineering cyanobacteria for production of chemicals from solar energy, CO2 and water is a potential approach to address global energy and environment issues such as greenhouse effect. To date, more ...than 20 chemicals have been synthesized by engineered cyanobacteria using CO2 as raw materials, and these studies have been well reviewed. However, unlike heterotrophic microorganisms, the low CO2 fixation rate makes it a long way to go from cyanochemicals to cyanofactories. Here we review recent progresses on improvement of carbon fixation and redistribution of intercellular carbon flux, and discuss the challenges for developing cyanofactories in the future.
Abstract
Line-intensity mapping (LIM) is a promising technique to constrain the global distribution of galaxy properties. To combine LIM experiments probing different tracers with traditional galaxy ...surveys and fully exploit the scientific potential of these observations, it is necessary to have a physically motivated modeling framework. As part of developing such a framework, in this work, we introduce and model the conditional galaxy property distribution (CGPD), i.e., the distribution of galaxy properties conditioned on the host halo mass and redshift. We consider five galaxy properties, including the galaxy stellar mass, molecular gas mass, galaxy radius, gas-phase metallicity, and star formation rate (SFR), which are important for predicting the emission lines of interest. The CGPD represents the full distribution of galaxies in the five-dimensional property space; many important galaxy distribution functions and scaling relations, such as the stellar mass function and SFR main sequence, can be derived from integrating and projecting it. We utilize two different kinds of cosmological galaxy simulations, a semi-analytic model and the IllustrisTNG hydrodynamic simulation, to characterize the CGPD and explore how well it can be represented using a Gaussian mixture model (GMM). We find that with just a few (approximately three) Gaussian components, a GMM can describe the CGPD of the simulated galaxies to high accuracy for both simulations. The CGPD can be mapped to LIM or other observables by constructing the appropriate relationship between galaxy properties and the relevant observable tracers, which will be discussed in future works.
The site‐specific activation of bioorthogonal prodrugs has provided great opportunities for reducing the severe side effects of chemotherapy. However, the precise control of activation location, ...sustained drug production at the target site, and high bioorthogonal reaction efficiency in vivo remain great challenges. Here, we propose the construction of tumor cell membrane reactors in vivo to solve the above problems. Specifically, tumor‐targeted liposomes with efficient membrane fusion capabilities are generated to install the bioorthogonal trigger, the amphiphilic tetrazine derivative, on the surface of tumor cells. These predecorated tumor cells act as many living reactors, transforming the tumor into a “drug factory” that in situ activates an externally delivered bioorthogonal prodrug, for example intratumorally injected transcyclooctene‐caged doxorubicin. In contrast to the rapid elimination of cargo that is encapsulated and delivered by liposomes, these reactors permit stable retention of bioorthogonal triggers in tumor for 96 h after a single dose of liposomes via intravenous injection, allowing sustained generation of doxorubicin. Interestingly, an additional supplement of liposomes will compensate for the trigger consumed by the reaction and significantly improve the efficiency of the local reaction. This strategy provides a solution to the efficacy versus safety dilemma of tumor chemotherapy.
Tumor cell membrane reactors are constructed in vivo for the precise location control of prodrug activation, sustained drug production at the target site, and high bioorthogonal reaction efficiency. Here, tumor‐targeting liposomes install the bioorthogonal trigger on the surface of tumor cells. These predecorated tumor cells act as living reactors, transforming the tumor into a “drug factory” that activates an externally delivered prodrug in situ.
Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of ...icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.
•Uniformity of Fe-Ni films along thickness direction were firstly studied.•Dual phases exhibit a gradient growth behavior along thickness direction.•Inclined fcc/bcc interface was induced by the ...faster deposition rate of fcc grains.•Modifying electrodeposition technics can restrain the variation.
In order to investigate the performance of Fe-Ni magnetic cores within embedded inductor in 3D package, a series of Fe-Ni films with compositions ranging from 15 wt% to 80 wt% iron were electrodeposited on 8-inch silicon wafer. The uniformity on brightness, phase structure and grain size of Fe-Ni magnetic films were investigated through SEM (scanning electron microscopy) and XRD (X-ray diffraction). A gradient growth behavior of fcc (face-centered cubic) and bcc (body-centered cubic) phase was revealed when Fe content ranges 50–75 wt% within Fe-Ni films, which can be attributed to the slightly faster growth rate of fcc phase. As also revealed in TEM (transmission electron microscope) observation, the fcc phase gradually spread over bcc phase region during the electroplating process, and formed an interface with a slight tilt angle to the substrate on the thickness direction. Several methods, such as increasing solution stirring, temperature or decreasing the current density, were proposed to restrain the gradient growth behavior of Fe-Ni film in wafer level.
A cascade C−N, C−C and C−O multiple‐bond‐formation reaction to synthesize 3‐acylindoles from 2‐alkenylanilines with DMF (N,N‐dimethylformamide) as a one‐carbon synthon is described. This approach ...employed dioxygen as a terminal oxidant and oxygen donor, generally provided the 3‐acylindoles in moderate to good yields. Moreover, the mechanistic investigation unambiguously revealed that the 2‐carbon of 3‐acylindole was derived from the N‐methyl group of DMF.
Background How to promote the health (especially mental health) growth of left-behind children has become a hot social issue. Physical exercise is usually considered as a positive role in improving ...the physical and mental health of children, which can be considered to be integrated into the living environment of left-behind children. Objective To discuss the changes of left-behind children in psychological health before and after the exercise-based intervention, thus providing a practical approach to improve the psychological growth of this disadvantaged group. Methods An exercise-based social intervention experiment was designed and conducted in a township middle school in China, and 200 left-behind children with relatively low psychological health participated in the experiment. Results Physical exercise had positive effects on rural left-behind children’s sense of hope, self-esteem, self-efficiency, and self-concept, and it seems that the positive effects are durative due to the optimization of living environment. There was no significant difference in the psychological promotion effect of different programs (football and table tennis) on left-behind children. Hope, self-esteem, and self-efficiency significantly mediated the relationship between physical exercise and self-concept of left-behind children. Conclusion Physical exercise contributes to promoting the development of rural left-behind children’s positive psychology such as hope, self-esteem, self-efficiency, and thus relieving the negative psychology caused by long-term parental-child separation and improving self-concept.
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