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This paper revisits the issue of stability analysis of neural networks subjected to time-varying delays. A novel approach, termed a compound-matrix-based integral inequality (CPBII), which accounts for delay derivatives using two adjustable parameters, is introduced. By appropriately adjusting these parameters, the CPBII efficiently incorporates coupling information along with delay derivatives within integral inequalities. By using CPBII, a novel stability criterion is established for neural networks with time-varying delays. The effectiveness of this approach is demonstrated through a numerical illustration.

This paper explored the topic of extended dissipativity analysis for Markovian jump neural networks (MJNNs) that were influenced by time-varying delays. A distinctive Lyapunov functional, distinguished by a non-zero delay-product types, was presented. This was achieved by combining a Wirtinger-based double integral inequality with a flexible matrix set. This novel methodology addressed the limitations of the slack matrices found in earlier research. As a result, a fresh condition for extended dissipativity in MJNNs was formulated, utilizing an exponential type reciprocally convex inequality in conjunction with the newly introduced nonzero delay-product types. A numerical example was included to demonstrate the effectiveness of the proposed methodology.

The primary objective of this paper is to address the challenge of designing finite-time fault-tolerant control mechanisms for nonlinear flexible spacecraft systems, which are particularly vulnerable to randomized actuator faults. Diverging from traditional methodologies, our research harnesses the capabilities of the Takagi–Sugeno (T–S) fuzzy framework. A unique feature of our model is the representation of actuator failures as stochastic signals following a Markov process, thereby offering a robust solution for addressing timeliness concerns. In this paper, we introduce a generalized reciprocally convex inequality that includes adjustable parameters, broadening the scope of previous results by accommodating them as special cases. Through the amalgamation of this enhanced inequality and flexible independent parameters, we propose an innovative controller design strategy. This approach establishes a stability standard that guarantees mean-square H∞ performance. In order to validate the efficacy of the suggested strategy, we present a numerical illustration involving a nonlinear spacecraft system, showcasing the practical advantages and feasibility of our proposed technique.

Sunitinib (SU) is widely used to treat solid tumors but it can be cardiotoxic and often leads to drug withdrawn or discontinuation. Astragaloside IV (ASIV) is the essential active component of the Chinese herb Astragalus membranaceus which shows potential cardioprotective effects. Herein, we investigated the effect of ASIV on SU-associated cardiotoxicity and its mechanisms. We showed that ASIV significantly ameliorated SU-induced myocardial injury in mice, as evidenced by an improvement in left ventricular ejection fraction (EF) and a decrease in blood pressure and serum concentration of myocardial injury markers. ASIV attenuated SU-induced myocardial inflammatory infiltration and fibrotic lesions. In addition, ASIV suppressed SU-induced myocardial oxidative stress and apoptosis both in vitro and in vivo. Furthermore, SU increased COUP-TFII expression both in mRNA and protein levels in mice myocardial tissue, primary neonatal rat cardiomyocytes (NRCMs) and H9c2 cell lines, and this effect was rescued by ASIV. Knockdown of COUP-TFII reduced the oxidative stress and apoptosis induced by SU in NRCMs and H9c2 cell lines. However, the overexpression of COUP-TFII blocked the protective effects of ASIV on SU-treated cardiomyocytes. Thus, our results demonstrated that ASIV ameliorated SU-indued cardiotoxicity by inhibiting COUP-TFII, suggesting that ASIV might be a potential therapeutic strategy for the prevention of SU-associated cardiotoxicity.

Millions of people are suffering from Alzheimer’s disease globally, but there is still no effective treatment for this neurodegenerative disease. Thus, novel therapeutic approaches for Alzheimer’s disease are needed, which requires further evaluation of the regulatory mechanisms of protein aggregate degradation. Lysosomes are crucial degradative organelles that maintain cellular homeostasis. Transcription factor EB-mediated lysosome biogenesis enhances autolysosome-dependent degradation, which subsequently alleviates neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In this review, we start by describing the key features of lysosomes, including their roles in nutrient sensing and degradation, and their functional impairments in different neurodegenerative diseases. We also explain the mechanisms — especially the post-translational modifications — which impact transcription factor EB and regulate lysosome biogenesis. Next, we discuss strategies for promoting the degradation of toxic protein aggregates. We describe Proteolysis-Targeting Chimera and related technologies for the targeted degradation of specific proteins. We also introduce a group of LYsosome-Enhancing Compounds, which promote transcription factor EB-mediated lysosome biogenesis and improve learning, memory, and cognitive function in APP-PSEN1 mice. In summary, this review highlights the key aspects of lysosome biology, the mechanisms of transcription factor EB activation and lysosome biogenesis, and the promising strategies which are emerging to alleviate the pathogenesis of neurodegenerative diseases.

Introduction: Diabetes mellitus results in high rates of cardiovascular disease, such as microcirculation disorder of the lower limbs, with angiogenesis impairment being the main factor. The endothelium functions as a barrier between blood and the vessel wall. Vascular endothelial cell dysfunction caused by hyperglycemia is the main factor leading to angiogenesis impairment. Hydrogen sulfide (H2S) and miR-126-3p are known for their pro-angiogenesis effects; however, little is known about how H2S regulates miR-126-3p to promote angiogenesis under high-glucose conditions. Objectives: The main objective of this research was to explore how H2S regulates the miR-126-3p levels under high-glucose conditions. Methods: We evaluated the pro-angiogenesis effects of H2S in the diabetic hindlimb of an ischemia mice model and in vivo Matrigel plugs. Two microRNA datasets were used to screen microRNAs regulated by both diabetes and H2S. The mRNA and protein levels were detected through real-time PCR and Western blot, respectively. Immunofluorescent staining was also used to assess the capillary density and to evaluate the protein levels in vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were used in in vitro experiments. A scratch wound-healing assay was applied to detect the migration ability of endothelial cells. Methylated DNA immunoprecipitation combined with real-time PCR was chosen to identify the DNA methylation level in the HUVECs. Results: Exogenous H2S improved angiogenesis in diabetic mice. miR-126-3p was regulated by both diabetes and H2S. Exogenous H2S up-regulated the miR-126-3p level and recovered the migration rate of endothelial cells via down-regulating the DNMT1 protein level, which was increased by high glucose. Furthermore, DNMT1 upregulation in the HUVECs increased the methylation levels of the gene sequences upstream of miR-126-3p and then inhibited the transcription of primary-miR-126, thus decreasing the miR-126-3p level. CSE overexpression in the HUVECs rescued the miR-126-3p level, by decreasing the methylation level to improve migration. Conclusion: H2S increases the miR-126-3p level through down-regulating the methylation level, by decreasing the DNMT1 protein level induced by high glucose, thus improving the angiogenesis originally impaired by high glucose.

This study examined the cognitive mechanism underlying acute stress in creative cognition among individuals with high and low trait anxiety. Specifically, cognitive inhibition was assessed using the flanker task during acute stress. Fifty-two participants (26 with high trait anxiety, 26 with low trait anxiety, with a mean age of 18.94 years) underwent stress induction via the Trier Social Stress Test (TSST). They all completed the Alternative Uses Test (AUT) and the Remote Associates Test (RAT) before and after the TSST. Biochemical markers (salivary cortisol and salivary alpha amylase) were recorded at regular intervals. The results showed that cognitive inhibition was influenced by trait anxiety and acute stress. In low-trait anxious individuals after experiencing acute stress, there was a lack of cognitive inhibition and they performed better in AUT (fluency), compared to before experiencing acute stress, whereas high-trait anxious individuals showed a decreased interference effect and reduced performance in AUT (fluency, flexibility, and originality). In the RAT, there were shorter response times and increased accuracy after acute stress in both high- and low-trait anxiety groups. Thus, we suggest that cognitive control, which modulates changes in acute stress, influences creative cognition. These findings provide evidence that inhibition control mediates the effect of stress on the creativity of individuals with different trait anxiety.

Lysosomes are one of the major centers for regulating cargo degradation and protein quality control. Transcription factor EB (TFEB)-promoted lysosome biogenesis enhances lysosome-mediated degradation and alleviates neurodegenerative dis-eases, but the mechanisms underlying TFEB modification and activation are still poorly understood. Here, we report essential roles of TFEB acetylation in TFEB nuclear translocation and lysosome biogenesis, which are independent of TFEB dephosphorylation. By screening small molecules, we find that Trichostatin A (TSA), the pan-inhibitor of histone deacetylases (HDACs), promotes nuclear translocation of TFEB. TSA enhances the staining of cells by LysoTracker Red and increases the expression of lysosomal and autophagic genes. We identify four novel acetylated lysine residues in TFEB, which are important for TFEB nuclear translocation and lysosome biogenesis. We show that TFEB acetylation is regulated by HDACs (HDAC5, HDAC6, and HDAC9) and lysine acetyl-transferases (KATs), including ELP3, CREBBP, and HAT1. During TSA-induced cytosol-to-nucleus translocation of TFEB, acetylation is independent of TFEB dephosphorylation, since the mTORC1- or GSK3β-related phosphorylation sites on TFEB are still phosphorylated. Administration of TSA to APP/ PS1 mice increases the expression of lysosomal and autophagic genes in mouse brains and also improves memory. Accordingly, the β-amyloid plaque burden is decreased. These results show that the acetylation of TFEB, as a novel mechanism of TFEB activation, promotes lysosome biogenesis and alleviates the pathogenesis of Alzheimer's disease. Our results also suggest that HDAC inhibition can promote lysosome biogenesis, and this may be a potential therapeutic approach for the treatment of neurodegenerative diseases and disorders related to HDAC hyperactivation. [ABSTRACT FROM AUTHOR]