Oxidative stress and cardiomyocyte apoptosis play critical roles in doxorubicin (DOX)-induced cardiotoxicity. Previous studies indicated that fibronectin type III domain-containing 5 (FNDC5) and its ...cleaved form, irisin, could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis, however, its role in DOX-induced cardiotoxicity remains unknown. Our present study aimed to investigate the role and underlying mechanism of FNDC5 on oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. Herein, we found that FNDC5 expression was downregulated in DOX-treated murine hearts and cardiomyocytes. Fndc5 deficiency resulted in increased oxidative damage and apoptosis in H9C2 cells under basal conditions, imitating the phenotype of DOX-induced cardiomyopathy in vitro, conversely, FNDC5 overexpression or irisin treatment alleviated DOX-induced oxidative stress and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, we identified that FNDC5/Irisin activated AKT/mTOR signaling and decreased DOX-induced cardiomyocyte apoptosis, and moreover, we provided direct evidence that the anti-oxidant effect of FNDC5/Irisin was mediated by the AKT/GSK3β/FYN/Nrf2 axis in an mTOR-independent manner. And we also demonstrated that heat shock protein 20 was responsible for the activation of AKT caused by FNDC5/Irisin. In line with the data in acute model, we also found that FNDC5/Irisin exerted beneficial effects in chronic model of DOX-induced cardiotoxicity (5 mg/kg, i.p., once a week for three times, the total cumulative dose is 15 mg/kg) in mice. Based on these findings, we supposed that FNDC5/Irisin was a potential therapeutic agent against DOX-induced cardiotoxicity.
Sharing commerce is an e-commerce business model where service providers (who provide possession of goods) and customers (who acquire temporary ownership for a fee) are connected through commercial ...networking systems tailored by service enablers. Research on sharing commerce to date investigate key drivers of consumer engagement in sharing commerce platforms, but relatively little attention has been given to the role of trust, and trust formation. Drawing on the socio-technical theory, the purpose of this paper is to examine the effect of social and technical enablers on consumer trust and whether trust influences users' continued use and positive word-of-mouth (WOM) in the context of sharing commerce. Results of an empirical study (N = 211 active Airbnb millennial users) indicate that social referrals, information quality and transaction safety positively affect users’ trust, which in turn facilitate their continued intention to use the sharing commerce platform and share positive word-of-mouth testimonials and postings thus sharing positive consumption experiences with other consumers. Results also suggest that transaction security is approximately four times more effective at increasing trust than social referrals and 2.68 times more effective at enhancing trust than information quality.
•The definition and business model of sharing commerce is provided.•We explore social and technical enablers on consumer trust in sharing commerce.•Transaction security is most influential in increasing trust in sharing commerce.
Although amino modified nanopolystyrene could cause toxicity on environmental organisms, the effect of amino modification on nanopolystyrene toxicity is still largely unclear. We here employed ...Caenorhabditis elegans as an animal model to compare the effects between pristine and amino modified nanopolystyrene particles in inducing reproductive toxicity. Nanopolystyrene (35 nm) could cause the damage on gonad development as indicated by the endpoints of number of total germline cells, length of gonad arm, and relative area of gonad arm. Nanopolystyrene exposure also reduced the reproductive capacity as reflected by the endpoints of brood size and number of fertilized eggs in uterus. Moreover, amino modification enhanced nanopolystyrene toxicity on both the gonad development and the reproductive capacity. Additionally, induction of germline apoptosis and formation of germline DNA damage contributed to the enhancement of nanopolystyrene toxicity in reducing reproductive capacity by amino modification. Our results highlight the potential environmental risk of amino modified nanopolystyrene in inducing reproductive toxicity on gonad development and reproductive capacity of environmental organisms.
Amino modification effectively enhanced the reproductive toxicity on both gonad development and reproductive capacity in nanopolystyrene exposed nematodes. Display omitted
•We compared reproductive toxicity between pristine and amino-modified nanopolystyrene.•Nanopolystyrene (35 nm) caused damage on gonad development and reproductive capacity.•Amino modification enhanced the nanopolystyrene toxicity in nematodes.
Amino modification enhanced the reproductive toxicity of nanopolystyrene on both gonad development and reproductive capacity in nematodes.
The recent Zika virus （ZIKV） epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the ...fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal （i.p.） injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial gila cells （RGs） of dorsal ventricular zone of the fetuses, the primary neural progenitors responsi- ble for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports l;he conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies.
Cancer is a destructive disease that causes high levels of morbidity and mortality. Doxorubicin (DOX) is a highly efficient antineoplastic chemotherapeutic drug, but its use places survivors at risk ...for cardiotoxicity. Many studies have demonstrated that multiple factors are involved in DOX-induced acute cardiotoxicity. Among them, oxidative stress and cell death predominate. In this review, we provide a comprehensive overview of the mechanisms underlying the source and effect of free radicals and dependent cell death pathways induced by DOX. Hence, we attempt to explain the cellular mechanisms of oxidative stress and cell death that elicit acute cardiotoxicity and provide new insights for researchers to discover potential therapeutic strategies to prevent or reverse doxorubicin-induced cardiotoxicity.
Our work aims to elucidate the effect how microRNA‐148b (miR‐148b) participated in myocardial ischemia/reperfusion (I/R) injury via regulation of Wnt/β‐catenin signaling pathway. The in vivo ...myocardial I/R models of SD rats and in vitro hypoxia/reoxygenation (H/R) models of H9C2 cells were established. The heart function and infarction area of rats and lactic dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), and superoxide dismutase (SOD) levels were evaluated. Myocardial cell viability was measured using positron emission tomography combined with computer tomography and (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, and the apoptosis was assessed by terminal deoxynucleotidyl transferase‐mediated nick‐end labeling method and flow cytometry; quantitative reverse‐transcription polymerase chain reaction and western blot were used to detect the related molecules expressions. The myocardial infarction area of rats was significantly increased with reductions in LVSP, + dp/dtmax, − dp/dtmax, LVFS%, LVEF% and standardized uptake value and elevation in left ventricular developed pressure after ischemia/reperfusion (I/R), and the LDH, CK, and MDA levels were enhanced with the decreased SOD. The apoptotic rates were higher in I/R rats and H/R H9C2 cells with upregulated miR‐148b and cleaved caspase‐3, but decreased Bcl‐2/Bax ratio; and meanwhile, the Wnt/β‐catenin pathway was inhibited. Additionally, the H/R‐induced H9C2 cells also exhibited decreased cell viability. MiR‐148b overexpression further aggravated I/R injury of rats, whereas inhibition of miR‐148b reduced I/R and H/R injury through activation of Wnt/β‐catenin pathway. In addition, Wnt‐1 small interfering RNA exposure abolished the effect of miR‐148b inhibitor on H/R injury of H9C2 cells. Inhibition of miR‐148b improved the antioxidative ability and myocardial cell survival to suppress its apoptosis by activating Wnt/β‐catenin signaling pathway, thus ameliorating the myocardial I/R injury.
Inhibition of miR‐148b can elevate the antioxidative ability, suppress myocardial cell apoptosis, promote cell viability, and reduce the myocardial infarction area through targeted activation of Wnt/β‐catenin signaling pathway, thereby mitigating the myocardial I/R injury.
The text describes improvements made to the random forest model to enhance its distinctiveness in addressing tax risks within the real estate industry, thereby tackling issues related to tax losses. ...Firstly, the paper introduces the potential application of the random forest model in identifying tax risks. Subsequently, the experimental analysis focuses on the selection of indicators for tax risk. Finally, the paper develops and utilizes actual taxpayer data to test a risk identification model, confirming its effectiveness. The experimental results indicate that the model's output report includes basic taxpayer information, a summary of tax compliance risks, value-added tax refund situations, directions of suspicious items, and detailed information on common indicators. This paper comprehensively presents detailed taxpayer data, providing an intuitive understanding of tax-related risks. Additionally, the paper reveals the level of enterprise risk registration assessment, risk probability, risk value, and risk assessment ranking. Further analysis shows that enterprise risk points primarily exist in operating income, selling expenses, financial expenses, and total profit. Additionally, the results indicate significant differences between the model's judgment values and declared values, especially in the high-risk probability of total operating income and profit. This implies a significant underreporting issue concerning corporate income tax for real estate enterprises. Therefore, this paper contributes to enhancing the identification of tax risks for real estate enterprises. Using the optimized random forest model makes it possible to accurately assess enterprises' tax compliance risks and identify specific risk points.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Single‐atom catalysts (SACs), distinguished by their maximum atom efficiency and precise control over the coordination and electronic properties of individual atoms, show great promise in ...electrocatalysis. Gaining a comprehensive understanding of the electrochemical performance of SACs requires the screening of electron transfer process at micro/nano scale. This research pioneers the use of electrogenerated chemiluminescence microscopy (ECLM) to observe the electrocatalytic reactions at individual SACs. It boasts sensitivity at the single photon level and temporal resolution down to 100 ms, enabling real‐time capture of the electrochemical behavior of individual SACs during potential sweeping. Leveraging the direct correlation between ECL emission and heterogeneous electron transfer processes, we introduced photon flux density for quantitative analysis, unveiling the electrocatalytic efficiency of individual SACs. This approach systematically reveals the relationship between SACs based on different metal atoms and their peroxidase (POD)‐like activity. The outcomes contribute to a fundamental understanding of SACs and pave the way for designing SACs with diverse technological and industrial applications.
We pioneer the use of real‐time electrogenerated chemiluminescence microscopy (ECLM) to observe the electrochemical processes at individual single‐atom catalysts (SACs) with single photon sensitivity.
In this paper, we derive the analytical expression for the sensitivity of grating-based surface plasmon resonance (SPR) sensors working in wavelength interrogation. The theoretical analysis shows ...that the sensitivity increases with increasing wavelength and is saturated beyond a certain wavelength for Au and Ag gratings, while it is almost constant for Al gratings in the wavelength range of 500 to 1000 nm. More importantly, the grating period (P) and the diffraction order (m) dominate the value of sensitivity. Higher sensitivity is possible for SPR sensors with a larger grating period and lower diffraction order. At long wavelengths, a simple expression of P/|m| can be used to estimate the sensor sensitivity. Moreover, we perform experimental measurements of the sensitivity of an SPR sensor based on an Al grating to confirm the theoretical calculations.
Aging is an important risk factor for cardiovascular diseases, and aging‐related cardiac dysfunction serves as a major determinant of morbidity and mortality in elderly populations. Our previous ...study has identified fibronectin type III domain‐containing 5 (FNDC5) and its cleaved form, irisin, as the cardioprotectant against doxorubicin‐induced cardiomyopathy. Herein, aging or matched young mice were overexpressed with FNDC5 by adeno‐associated virus serotype 9 (AAV9) vectors, or subcutaneously infused with irisin to uncover the role of FNDC5 in aging‐related cardiac dysfunction. To verify the involvement of nucleotide‐binding oligomerization domain‐like receptor with a pyrin domain 3 (NLRP3) and AMP‐activated protein kinase α (AMPKα), Nlrp3 or Ampkα2 global knockout mice were used. Besides, young mice were injected with AAV9‐FNDC5 and maintained for 12 months to determine the preventive effect of FNDC5. Moreover, neonatal rat cardiomyocytes were stimulated with tumor necrosis factor‐α (TNF‐α) to examine the role of FNDC5 in vitro. We found that FNDC5 was downregulated in aging hearts. Cardiac‐specific overexpression of FNDC5 or irisin infusion significantly suppressed NLRP3 inflammasome and cardiac inflammation, thereby attenuating aging‐related cardiac remodeling and dysfunction. In addition, irisin treatment also inhibited cellular senescence in TNF‐α‐stimulated cardiomyocytes in vitro. Mechanistically, FNDC5 activated AMPKα through blocking the lysosomal degradation of glucagon‐like peptide‐1 receptor. More importantly, FNDC5 gene transfer in early life could delay the onset of cardiac dysfunction during aging process. We prove that FNDC5 improves aging‐related cardiac dysfunction by activating AMPKα, and it might be a promising therapeutic target to support cardiovascular health in elderly populations.
FNDC5 is downregulated in aging hearts, and cardiac‐specific overexpression of FNDC5 or irisin infusion attenuates aging‐related inflammation, cardiac remodeling, and dysfunction. Mechanistically, FNDC5 activates AMPKα through blocking the lysosomal degradation of GLP‐1R.
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