Background
The cardiovascular and long‐term noncardiovascular safety and efficacy of SGLT2 (sodium–glucose cotransporter 2) inhibitors have not been well documented.
Methods and Results
For ...cardiovascular outcomes, we performed a meta‐analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient‐years of follow‐up. For long‐term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient‐years of follow‐up. Five studies with 351 476 patients were included in cardiovascular outcomes analysis. Meta‐analyses showed that SGLT2 inhibitors significantly reduced the risks of major adverse cardiac events (hazard ratio HR: 0.80; 95% confidence interval CI, 0.69–0.92; P=0.002), all‐cause mortality (HR: 0.67; 95% CI, 0.54–0.84; P<0.001), cardiovascular mortality (HR: 0.77; 95% CI, 0.60–0.98; P=0.03), nonfatal myocardial infarction (HR: 0.86; 95% CI, 0.76–0.98; P=0.02), hospitalization for heart failure (HR: 0.62; 95% CI, 0.55–0.69; P<0.001), and progression of albuminuria (HR: 0.68; 95% CI, 0.58–0.81; P<0.001). No significant difference in nonfatal stroke was found. Analyses limited to randomized controlled trials showed similar findings. Trial sequential analysis provided firm evidence of a 20% reduction in major adverse cardiac events, all‐cause mortality, and hospitalization for heart failure with SGLT2 inhibitors, but evidence remains inconclusive for cardiovascular mortality. Nine randomized controlled trials contributed to long‐term noncardiovascular and efficacy analyses. SGLT2 inhibitors reduced incidence of hypoglycemia and acute kidney injury but increased the risks of urinary tract and genital infections.
Conclusions
SGLT2 inhibitors showed remarkable cardiovascular‐ and renal‐protective effects and good long‐term noncardiovascular safety with sustained efficacy.
The dose-dependent toxicity to cardiomyocytes has been well recognized as a central characteristic of doxorubicin (DOX)-induced cardiotoxicity (DIC), however, the pathogenesis of DIC in the cardiac ...microenvironment remains elusive. Irisin is a new hormone-like myokine released into the circulation in response to exercise with distinct functions in regulating apoptosis, inflammation, and oxidative stress. Recent advances revealed the role of irisin as a novel therapeutic method and an important mediator of the beneficial effects of exercise in cardioprotection. Here, by using a low-dose long-term mouse DIC model, we found that the perivascular fibrosis was involved in its myocardial toxicity with the underlying mechanism of endothelial-to-mesenchymal transition (EndMT). Irisin treatment could partially reverse DOX-induced perivascular fibrosis and cardiotoxicity compared to endurance exercise. Mechanistically, DOX stimulation led to excessive accumulation of ROS, which activated the NF-κB-Snail pathway and resulted in EndMT. Besides, dysregulation of autophagy was also found in DOX-treated endothelial cells. Restoring autophagy flux could ameliorate EndMT and eliminate ROS. Irisin treatment significantly alleviated ROS accumulation, autophagy disorder, NF-κB-Snail pathway activation as well as the phenotype of EndMT by targeting uncoupling protein 2 (UCP2). Our results also initially found that irisin was mainly secreted by cardiomyocytes in the cardiac microenvironment, which was significantly reduced by DOX intervention, and had a protective effect on endothelial cells in a paracrine manner. In summary, our study indicated that DOX-induced ROS accumulation and autophagy disorders caused an EndMT in CMECs, which played a role in the perivascular fibrosis of DIC. Irisin treatment could partially reverse this phenomenon by regulating UCP2. Cardiomyocytes were the main source of irisin in the cardiac microenvironment. The current study provides a novel perspective elucidating the pathogenesis and the potential treatment of DIC.
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Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung ...cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion.
First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied.
High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs.
Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment.
This paper is concerned with the finite-time synchronization for a class of drive-response fractional-order memristive recurrent neural networks with discontinuous activation functions. By using the ...theories of fractional-order differential inclusions and set-valued map, the finite-time synchronization problem for a class of drive-response fractional-order memristive recurrent neural networks with discontinuous activation functions is formulated under the framework of Filippov solution. Then, two novel state feedback controllers are designed according to state feedback control technique. In particular, based on the fractional Lyapunov stability theory, the finite-time stability theory and Young inequality, some novel algebraic synchronization criteria are obtained to ensure the finite-time synchronization of a class of drive-response fractional-order memristive recurrent neural networks with discontinuous activation functions. Moreover, we give the estimation of the upper bound of the settling time for synchronization. Finally, a simulation example is given to show the effectiveness of our theoretical results.
This article explores the exponential stabilization issue of a class of state-based switched inertial complex-valued neural networks with multiple delays via event-triggered control. First, the ...state-based switched inertial complex-valued neural networks with multiple delays are modeled. Second, by separating the real and imaginary parts of complex values, the state-based switched inertial complex-valued neural networks are transformed into two state-based switched inertial real-valued neural networks. Through the variable substitution method, the model of the second-order inertial neural networks is transformed into a model of the first-order neural networks. Third, an event-triggered controller with the transmission sequence is designed to study the exponential stabilization issue of neural networks constructed above. Then, by constructing the Lyapunov functions and based on some inequalities, we obtain sufficient conditions for exponential stabilization of the proposed neural networks. Furthermore, it is proved that the Zeno phenomenon cannot happen under the designed event-triggered controller. Finally, a simulation example is given to illustrate the correctness of the results.
This paper deals with global synchronization problem of multiple discrete-time Markovian jump memristor-based neural networks (DTMJMNNs) with mixed mode-dependent delays via a novel event-triggered ...impulsive coupling control (ETICC). The parameters of the multiple DTMJMNNs and the mixed time delays (both discrete and distributed delays) switch randomly according to a Markov chain. In the ETICC strategy, the controller does not work all the time, but only works at impulse instants determined by specific events. In particular, the coupling matrix can be non-Laplacian. By using the Lyapunov stability theory, linear matrix inequalities (LMIs), and the Kronecker product, some sufficient conditions for global synchronization of multiple DTMJMNNs under the event-triggered strategy are derived. Two examples are presented to test the validity of the theoretical analysis results.
Advances in polymeric matrices with ultralong and color-tunable phosphorescence were recently made, but their luminescence mechanism was not yet thoroughly understood. The current experimental and ...theoretical studies show that the red-shift of phosphorescence spectrum is caused by increasing the C–N and C=O of carbon dots in the polymeric matrix. In addition, theoretical calculations explain the charge transfer and spin orbit coupling of carbon dots in a system containing different covalent bonds. The phosphorescence emission color and lifetime can be modulated, which is applied into triple anti-counterfeiting of photo-stimulated-dependent color, time-dependent color, and time-dependent phosphorescence lifetime. In the application, the phosphorescence color of carbon dots in the polymeric matrix can be varied from deep blue (431 nm) to red (620 nm) with a maximal lifetime of 2.02 s and a maximum phosphorescence quantum yield of 20.1%. This work provides a new direction for the development of carbon dots with efficient and color-tunable ultra-long phosphorescence.
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•The phosphorescence color of carbon dots can be varied from deep blue (431 nm) to red (620 nm) with a maximal lifetime of 2.02 s and a maximum phosphorescence quantum yield of 20.1%.•Theoretical calculations explain the charge transfer and spin orbit coupling of carbon dots in a system containing different covalent bonds.•The phosphorescence emission color and lifetime can be modulated, which is applied into triple anti-counterfeiting.
This paper is focused on the global exponential adaptive synchronization problem of two stochastic memristive chaotic neural networks with both stochastic disturbance and time-varying delays. First, ...in order to develop the guaranteed cost control, a periodically alternate adaptive rule is designed. Then, by constructing appropriate Lyapunov–Krasovskii functionals, several easily verified synchronization criteria are derived to guarantee exponential adaptive synchronization of drive-response stochastic memristive chaotic recurrent neural networks. Lastly, a numerical simulation is carried out to demonstrate the effectiveness of the proposed results.
Surface-enhanced Raman spectroscopy (SERS) finds wide applications in the field of organic molecule detection. However, reliable SERS detection of organic molecules and
monitoring of organic ...reactions under natural conditions by metal colloids are still challenging due to the formation of unstable nanoparticle clusters in solution and the low solubility of the organic molecules. Here, we approach the problems by introducing calcium ions to aggregate silver nanoparticles to form stable hot spots and acetone to promote uniform distribution of organic molecules on the nanoparticle surface. Significantly, our method exhibits stable SERS detection of up to 6 types of organic molecules in liquid. With acetone signals as an internal standard, we are able to determine molecule concentrations as well as monitor 3 kinds of organic reactions
. Our method shows potential for biomedical analysis, environmental analysis, and organic catalysis research.
This paper solves the exponential synchronization problem of two memristive recurrent neural networks with both stochastic disturbance and time-varying delays via periodically alternate state ...feedback control. First, a periodically alternate state feedback control rule is designed. Then, on the basis of the Lyapunov stability theory, some novel sufficient conditions guaranteeing exponential synchronization of drive-response stochastic memristive recurrent neural networks via periodically alternate state feedback control are derived. In contrast to some previous works about synchronization of memristive recurrent neural networks, the obtained results in this paper are not difficult to be validated, and complement, extend and generalize the earlier papers. Lastly, an illustrative example is provided to indicate the effectiveness and applicability of the obtained theoretical results.
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