The impact of transcranial direct current stimulation combined with interim testing on spatial route learning in patients with schizophrenia.

BACKGROUND: Cognitive deficits in patients with schizophrenia have drawn widespread attention. Transcranial direct current stimulation (tDCS) can modulate cognitive processes by altering neuronal excitability. Previous studies have found that interim testing can enhance spatial route learning and memory in patients with schizophrenia. However, there has been limited research on the combined effects of these two methods on spatial route learning in these patients. OBJECTIVE: To investigate whether the combination of tDCS and interim testing can effectively contribute to the maintenance of spatial route memory in patients with schizophrenia. The study involved conducting route learning using interim testing after anodal tDCS treatment on the left dorsolateral prefrontal cortex (L-DLPFC). METHODS: Ninety-two patients with schizophrenia were recruited and divided into groups receiving anodal, sham, or no stimulation. The anodal group received L-DLPFC tDCS treatment 10 times over 5 days (twice daily for 20 min). After treatment, spatial route learning was assessed in interim testing. Correct recall rates of landmark positions and proactive interference from prior learning were compared among the groups. RESULTS: Regardless of stimulation type, the interim testing group outperformed the relearning group. Additionally, recall scores were higher following anodal stimulation, indicating the efficacy of tDCS. CONCLUSIONS: Both tDCS and interim testing independently enhance the ability to learn new information in spatial route learning for patients with schizophrenia, indicating that tDCS of the left DLPFC significantly improves memory in these patients.

Ilexgenin A inhibits lipid accumulation in macrophages and reduces the progression of atherosclerosis through PTPN2/ERK1/2/ABCA1 signalling pathway.

Macrophage lipid accumulation indicates a pathological change in atherosclerosis. Ilexgenin A (IA), a pentacyclic triterpenoid compound, plays a role in preventing inflammation, bacterial infection, and fatty liver and induces a potential anti-atherogenic effect. However, the anti-atherosclerotic mechanism remains unclear. The present study investigated the effects of IA on lipid accumulation in macrophage-derived foam cells and atherogenesis in apoE-/- mice. Our results indicated that the expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) was up-regulated by IA, promoting cholesterol efflux and reducing lipid accumulation in macrophages, which may be regulated by the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/ERK1/2 signalling pathway. IA attenuated the progression of atherosclerosis in high-fat diet-fed apoE-/- mice. PTPN2 knockdown with siRNA or treatment with an ERK1/2 agonist (Ro 67-7476) impeded the effects of IA on ABCA1 upregulation and cholesterol efflux in macrophages. These results suggest that IA inhibits macrophage lipid accumulation and alleviates atherosclerosis progression via the PTPN2/ERK1/2 signalling pathway.

NLRC5 promotes tumorigenesis by regulating the PI3K/AKT signaling pathway in cervical cancer.

Cervical cancer (CC) is the fourth most common cancer among women worldwide. NLR Family CARD Domain Containing 5 (NLRC5) plays an important role in tumorigenesis. However, its effect and mechanism in CC remains unclear. In this study, we aimed to investigate the function of NLRC5 in CC. NLRC5 was found to be down-regulated in CC tissues compared with normal cervical tissues. However, patients with higher NLRC5 expression had better prognosis, patients with higher age, HPV infection, lymph node metastasis, recurrence and histological grade had worse prognosis. Univariate and multivariate analyses showed NLRC5 to be a potential prognostic indicator for CC. Pearson correlation analysis showed that NLRC5 might exert its function in CC through autophagy related proteins, especially LC3. In vitro experiments demonstrated that NLRC5 inhibited LC3 levels and promoted the proliferation, migration, and invasion of CC cells by activating the PI3K/AKT signaling pathway. Treatment with LY294002 reversed the above phenotype. Taken together, our finding suggested that NLRC5 would participate in cervical tumorigenesis and progression by regulating PI3K/AKT signaling pathway. In addition, NLRC5 and LC3 combined as possible predictors in CC.

Joint effects of air pollution and genetic susceptibility on incident primary open-angle glaucoma.

BACKGROUND: Air pollutants are important exogenous stimulants to eye diseases, but knowledge of associations between long-term exposure to air pollutants and the risk of primary open-angle glaucoma (POAG) is limited. This study aimed to determine whether long-term exposure to air pollutants, genetic susceptibility, and their joint effects lead to an elevated risk of incident POAG. METHODS: This is a population-based prospective cohort study from UK Biobank participants with complete measures of air pollution exposure and polygenetic risk scores. Cox proportional hazard models were fitted to assess the individual and joint effects of long-term exposure to air pollutants and genetics on the risk of POAG. In addition, the effect modification of genetic susceptibility was examined on an additive or multiplicative scale. RESULTS: Among 434,290 participants with a mean (SD) age of 56.5 (8.1) years, 6651 (1.53 %) were diagnosed with POAG during a median follow-up of 13.7 years. Long-term exposure to air pollutants was associated with an increased risk of POAG. The hazard ratios associated with per interquartile range increase in PM2.5, PM2.5 absorbance, PM10, NO2, and NOX individually ranged from 1.027 (95 % CI: 1.001-1.054) to 1.067 (95 % CI: 1.035-1.099). Compared with individuals residing in low-pollution areas and having low polygenic risk scores, the risk of incident POAG increased by 105.5 % (95 % CI: 78.3 %-136.9 %), 79.7 % (95 % CI: 56.5 %-106.5 %), 103.2 % (95 % CI: 76.9 %-133.4 %), 89.4 % (95 % CI: 63.9 %-118.9 %), and 90.2 % (95 % CI: 64.8 %-119.5 %) among those simultaneously exposed to high air pollutants levels and high genetic risk, respectively. Genetic susceptibility interacted with PM2.5 absorbance and NO2 in an additive manner, while no evidence of multiplicative interaction was found in this study. Stratification analyses revealed stronger effects in Black people and the elderly. CONCLUSION: Long-term air pollutant exposure was associated with an increased risk of POAG incidence, particularly in the population with high genetic predisposition.

SLO2.1/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy.

At the end of pregnancy, the uterus transitions from a quiescent to a highly contractile state. This is partly due to depolarization of the resting membrane potential in uterine (myometrial) smooth muscle cells (MSMCs). Experiments with human MSMCs showed that the membrane potential is regulated by a functional complex between the sodium (Na+)-activated potassium (K+) channel SLO2.1 and the Na+ Leak Channel Non-Selective (NALCN). In human MSMCs, Na+ entering through NALCN activates SLO2.1, leading to K+ efflux, membrane hyperpolarization (cells become more negative inside), and reduced contractility. Decreased SLO2.1/NALCN activity results in reduced K+ efflux, leading to membrane depolarization, Ca2+ influx via voltage-dependent calcium channels, and increased MSMC contractility. However, all of these experiments were performed with MSMCs isolated from women at term, so the role of the SLO2.1/NALCN complex early in pregnancy was speculative. To address this question here, we examined the role of the SLO2.1/NALCN complex in regulating mouse MSMC membrane potential across pregnancy. We report that Slo2.1 and Nalcn expression change along pregnancy, being more highly expressed in MSMCs from non-pregnant and early pregnant mice than in those from late-pregnant mice. Functional studies revealed that SLO2.1 channels mediate a significant portion of the K+ current in mouse MSMCs, particularly in cells from non-pregnant and early pregnant mice. Activation of SLO2.1 by Na+ influx through NALCN led to membrane hyperpolarization in MSMCs from early pregnancy but not in MSMCs from later pregnancy. Moreover, we found that the NALCN/SLO2.1 complex regulates intracellular Ca2+ responses more in MSMCs from non-pregnant and early pregnancy mice than in MSMCs from late pregnancy. Together, these findings reveal that the SLO2.1/NALCN functional complex is conserved between mouse and humans and functions throughout pregnancy. This work could open avenues for targeted pharmacological interventions in pregnancy-related complications.

Obese mice have decreased uterine contractility and altered energy metabolism in the uterus at term gestation.

Over 35% of reproductive-age women in the US are obese, putting them at increased risk for numerous obstetric complications due to abnormal labor. While the association between maternal obesity and abnormal labor has been well documented, the mechanisms responsible for this remain understudied. The uterine smooth muscle, myometrium, has high energy needs in order to fuel regular uterine contractions during parturition. However, the precise mechanisms by which the myometrium meets its energy demands has not been defined. Here, our objective was to define the effects of obesity on energy utilization in the myometrium during labor. We generated a mouse model of maternal diet-induced obesity (DIO) and found that these mice had a higher rate of dystocia than control chow-fed (CON) mice. Moreover, compared to CON mice, DIO mice at term, both before and during labor had lower in vivo spontaneous uterine contractility. Untargeted transcriptomic and metabolomic analyses suggest that DIO is associated with elevated long-chain fatty acid uptake and utilization in the uterus, but also an accumulation of medium-chain fatty acids. DIO uteri also had an increase in the abundance of long chain-specific ß-oxidation enzymes, which may be responsible for the observed increase in long-chain fatty acid utilization. This altered energy substrate utilization may be a contributor to the observed contractile dysfunction.

The Magic and Mystery of TRIM65 in Diseases.

Tripartite-motif protein family member 65 (TRIM65) belongs to the tripartite motif (TRIM) protein family. Its typical structure consists of the RING, B-Box motif, and coiled-coil domains, which are highly conserved at the N-terminus and the variable SPRY domain at the C-terminus. TRIM65 is an E3 ubiquitin ligase that participates in physiological and pathological processes through the ubiquitination pathway, including intracellular signal transduction, protein degradation, cell proliferation, apoptosis, carcinogenesis, autophagy, and phenotypic transformation. Evidence shows that TRIM65 plays a remarkable and obscure role in diseases, including multisystem tumours, neurodegenerative diseases, immune system diseases, and inflammatory diseases. This review is devoted to elaborating on the relationship between TRIM65 and diseases and its pathogenic mechanism, providing a theoretical basis for TRIM65 as a possible pathogenic target of diseases and exploring the possible future research direction of TRIM65 and the challenges it may face.

Stereoselective and controllable C3-Amination or C1,C3-di-amination of 2-nitroglycals.

Precise and selective modification of carbohydrates is a critical strategy in producing diverse carbohydrate derivatives for exploiting their functions. We disclosed a simple, efficient, and highly regioselective and stereoselective protocol to controllable amination of 2-nitroglycals under mild conditions in 5 min. A range of 3-amino-carbohydrates including 3-arylamino-2-nitro-glycals and 1,3-di-amino-carbohydrate derivatives were obtained in good to excellent yield with excellent stereoselectivity. The produced 3-amino-2-nitro-glycals can be used as a precursor for further transformation.

Effects of elastic band resistance training on the physical and mental health of elderly individuals: A mixed methods systematic review.

OBJECTIVES: Elastic band resistance training in elderly individuals can improve physical fitness and promote mental health in addition to other benefits. This systematic review aimed to review, summarize, and evaluate quantitative, qualitative, and mixed methodological studies on the use of elastic band resistance training in elderly individuals, and to investigate the influence of elastic band resistance training on the physical and mental health of elderly individuals, as well as their preferences and obstacles in training. METHODS: A convergent separation approach was used to synthesize and integrate the results, specifically the mixed systematic review approach recommended by the Joanna Briggs Institute. The extensive search strategy included electronic database searches in the Cochrane Library, PubMed, Embase, Web of Science, Google Scholar, MEDLINE, and CINAHL. The researchers rigorously screened the literature, extracted and analyzed the data, and evaluated the quality of the included studies using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Twenty-eight studies were included, of which 25 were quantitative studies, 2 were qualitative studies, and 1 was a mixed-methods study. A total of 1,697 subjects were investigated across all studies. Quantitative evidence supports the notion that elastic band resistance training can improve upper and lower limb flexibility, endurance, upper strength, physical balance, and cardiopulmonary function and enhance the mental health of elderly individuals. Participants in the qualitative study reported some preferences and obstacles with band resistance training, but most participants reported physical benefits. CONCLUSIONS: Despite the heterogeneity between studies, this review is the first systematic review to comprehensively evaluate the effectiveness of elastic band resistance training in older adults. It not only shows the influence of elastic band resistance training on the physical and mental health of the elderly, but also emphasizes the preference and obstacles of elderly individuals face.

Integrin subunit alpha 5 maintains mitochondrial function in ox-LDL-induced cardiac microvascular endothelial cells via activating the PI3K/AKT signaling pathway.

Cardiac microvascular endothelial cells (CMECs) assume a pivotal role in the regulation of blood flow, and their impairment precipitates a spectrum of pathological transformations. Our previous study unveiled a notable mitigation of CMECs dysfunction through the intervention of integrin subunit alpha 5 (ITGA5), a member of the integrin protein family. This study delves into the effect of ITGA5 on the mitochondrial function in CMECs and reveals the regulation pathway. CMECs were stimulated with oxidized low-density lipoprotein (ox-LDL) to mimic coronary artery disease (CAD). The effects of ITGA5 on diverse facets of CMEC behavior, encompassing viability, apoptosis, angiogenesis, oxidative stress, and mitochondrial function, was systematically ascertained. Employing the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway as a focal point of investigation, the mediation of this pathway was substantiated utilizing the PI3K inhibitor LY294002. ITGA5 overexpression exerted a mitigating influence upon the ox-LDL-induced detriment to CMECs, manifested as increased viability, angiogenesis, mitochondrial function, and diminished apoptosis and oxidative stress. The counteraction of these salubrious effects by the administration of the PI3K inhibitor attests to the engagement of the PI3K/AKT signaling pathway. Overall, this study has discerned that ITGA5 activates the PI3k/Akt signaling pathway to orchestrate mitochondrial function and diminish ox-LDL-induced CMEC dysfunction. Thus, the targeted amelioration of this cellular injury emerges as a strategically pivotal endeavor for the prevention and amelioration of this ailment.

Controllable 1,3-Bis-Functionalization of 2-Nitroglycals with High Regioselectivity and Stereoselectivity Enabled by a H-Bond Catalyst.

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.

Comparative analysis of the clinical features of nonvalvular atrial fibrillation among Tibetan, Han, and Hui patients in Qinghai Province, China.

BACKGROUND: Global nonvalvular AF rises, impacting health severely. In Qinghai, China's diverse setting, studying AF among varied ethnic groups is crucial OBJECTIVES: The purpose of this study was to compares cardiac features in AF among Tibetan, Han, and Hui patients to develop tailored prevention and treatment strategies for this region, the goal was to enhance the understanding of AF and provide an empirical basis for developing prevention and treatment strategies specific to this region METHODS: This study included a total of 3445 Tibetan, Han, and Hui patients diagnosed with nonvalvular atrial fibrillation and treated at the Qinghai Cardiovascular and Cerebrovascular Specialist Hospital, China, between January 2019 and January 2021. We analyzed the differences in cardiac structure, comorbidities, and other influencing factors among the different ethnic groups RESULTS: We found significant differences in gender, age, smoking history, lone atrial fibrillation, left heart failure, dilated cardiomyopathy, and diabetes between Tibetan, Han, and Hui patients (P < 0.05). Tibetan, Han, and Hui patients also differed with regard to left ventricular end-diastolic volume, left ventricular ejection fraction, fractional shortening, NT-proBNP, glycated hemoglobin, red blood cell distribution width, platelet count, platelet hematocrit, platelet distribution width, homocysteine (Hcy), C-reactive protein, and superoxide dismutase (SOD) (P < 0.05) CONCLUSION: Our study revealed variations in comorbidities, cardiac structure, and blood indexes among Tibetan, Han, and Hui AF patients, highlighting distinct patterns in complications and biomarker levels across ethnic groups.

Strategies to increase the coverage of influenza and pneumonia vaccination in older adults: a systematic review and network meta-analysis.

BACKGROUND: It is urgent to implement interventions to increase vaccination rates of influenza/pneumonia vaccines in older adults, yet the effectiveness of different intervention strategies has not been thoroughly evaluated. OBJECTIVE: We aimed to assess the effectiveness of intervention strategies for increasing the coverage of influenza/pneumonia vaccination in older adults. METHODS: PubMed, Web of Science, Cochrane Library, Embase, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang were searched from 1 January 2000 to 1 October 2022. RCTs that assessed any intervention strategies for increasing influenza/pneumonia vaccination coverage or willingness in older adults were included. A series of random-effects network meta-analysis was conducted by using frequentist frameworks. RESULTS: Twenty-two RCTs involving 385,182 older participants were eligible for further analysis. Eight types of intervention strategies were evaluated. Compared with routine notification, health education (odds ratio [OR], 1.85 [95%CI, 1.19 to 2.88]), centralised reminder (OR, 1.63 [95%CI, 1.07 to 2.47]), health education + onsite vaccination (OR, 2.89 [95%CI, 1.30 to 6.39]), and health education + centralised reminder + onsite vaccination (OR, 20.76 [95%CI, 7.33 to 58.74]) could effectively improve the vaccination rate. The evidence grade was low or very low due to the substantial heterogeneity among studies. CONCLUSIONS: Our findings suggest that health education + centralised reminder + onsite vaccination may potentially be an effective strategy regardless of cost, but the evidence level was low. More rigorous trials are needed to identify the association between strategies and vaccination rates among older adults and to integrate such evidence into clinical care to improve vaccination rates.

Genetic Basis and Evolutionary Forces of Sexually Dimorphic Color Variation in a Toad-Headed Agamid Lizard.

In the animal kingdom, sexually dimorphic color variation is a widespread phenomenon that significantly influences survival and reproductive success. However, the genetic underpinnings of this variation remain inadequately understood. Our investigation into sexually dimorphic color variation in the desert-dwelling Guinan population of the toad-headed agamid lizard (Phrynocephalus putjatai) utilized a multidisciplinary approach, encompassing phenotypic, ultrastructural, biochemical, genomic analyses, and behavioral experiments. Our findings unveil the association between distinct skin colorations and varying levels of carotenoid and pteridine pigments. The red coloration in males is determined by a genomic region on chromosome 14, housing four pigmentation genes: BCO2 and three 6-pyruvoyltetrahydropterin synthases. A Guinan population-specific nonsynonymous single nucleotide polymorphism in BCO2 is predicted to alter the electrostatic potential within the binding domain of the BCO2-ß-carotene complex, influencing their interaction. Additionally, the gene MAP7 on chromosome 2 emerges as a potential contributor to the blue coloration in subadults and adult females. Sex-specific expression patterns point to steroid hormone-associated genes (SULT2B1 and SRD5A2) as potential upstream regulators influencing sexually dimorphic coloration. Visual modeling and field experiments support the potential selective advantages of vibrant coloration in desert environments. This implies that natural selection, potentially coupled with assortative mating, might have played a role in fixing color alleles, contributing to prevalence in the local desert habitat. This study provides novel insights into the genetic basis of carotenoid and pteridine-based color variation, shedding light on the evolution of sexually dimorphic coloration in animals. Moreover, it advances our understanding of the driving forces behind such intricate coloration patterns.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

The global state of research in stem cells therapy for spinal cord injury (2003-2022): a visualized analysis.

Objective: Our study aimed to visualize the global status and frontiers in stem cell therapy for spinal cord injury by using bibliometric methodology. Methods: Publication citation information related to stem cell therapy for spinal cord injury (SCI) studies between 2003 and 2022 was retrieved from the Web of Science Core Collection database. For the visualized study, VOS viewer software and Graph Pad Prism 9.5 were used to perform bibliometric analysis of included data and publication number statistics in stem cell therapy for the SCI domain. Results: A total of 6,686 publications were retrieved. The USA and China made the highest contributions to global research with the highest number of citations and link strength. The journal Experimental Neurology ranks as the top journal, combining the publication amount and bibliometrics results. The University of Toronto, based in Canada, was the first-ranking institution. The directions of the current study could be divided into five clusters. The research of Transplantation and Regenerative Medicine and Neurosciences Mechanism Research may be the emerging frontiers in this domain. Conclusion: In summary, stem cell therapy for spinal cord injuries is poised for more valuable advances.

Nickel and Chiral Phosphoric Acid Cocatalysis Enables Synthesis of C-Acyl Glycosides.

We disclosed a Ni/CPA cocatalyzed protocol to access diverse C-acyl glycosides under mild conditions with broad functional group compatibility through the coupling of readily available glycosyl bromides and carboxylic esters. The potential application of the methodology was demonstrated by the C-acyl glycosylation of bioactive molecules and the transformation of products to a variety of value-added molecules. Mechanistic studies revealed that CPA might serve as a bifunctional H-bond catalyst to activate carboxylic esters and nickel catalyst.

TLN1 synergizes with ITGA5 to ameliorate cardiac microvascular endothelial cell dysfunction.

BACKGROUND: The complex process of atherosclerosis is thought to begin with endothelial cell dysfunction, and advanced atherosclerosis is the underlying cause of coronary artery disease (CAD). Uncovering the underlying mechanisms of CAD-related endothelial cell injury may contribute to the treatment. MATERIALS AND METHODS: Cardiac microvascular endothelial cells (CMVECs) were treated with oxidised low-density lipoprotein (ox-LDL) to mimic an injury model. The involvement of Talin-1 (TLN1) and integrin alpha 5 (ITGA5) in the proliferation, apoptosis, angiogenesis, inflammatory response, and oxidative stress in CMVECs were assessed. RESULTS: TLN1 overexpression assisted CMVECs in resistance to ox-LDL stimulation, with alleviated cell proliferation and angiogenesis, reduced apoptosis, inflammatory response, and oxidative stress. TLN1 overexpression triggered increased ITGA5, and ITGA5 knockdown reversed the effects of TLN1 overexpression on the abovementioned aspects. Together, TLN1 synergized with ITGA5 to ameliorate the dysfunction in CMVECs. CONCLUSIONS: This finding suggests their probable involvement in CAD, and increasing their levels is beneficial to disease relief.

Ultra-Tough and Highly Stretchable Dual-Crosslinked Eutectogel Based on Coordinated and Non-Coordinated Two Types Deep Eutectic Solvent Mixture.

Eutectogels are gaining attention in flexible device applications for their superior ionic conductivity, stability, biocompatibility, and cost-effectiveness. However, most existing eutectogels suffer from low strength and toughness. Herein, ultra-tough and highly stretchable polyacrylamide (PAM) eutectogels featuring a dual-crosslinked network comprising chemical cross-linking and physical cross-linking facilitated by metal coordination bonds and hydrogen bonds are developed. This is achieved through a controlled strategy involving polymerization of acrylamide in a coordinated metal salt-type deep eutectic solvent (DES) combined with a non-coordinated choline chloride (ChCl)-type DES mixture. By varying the molar ratio of these two types of DES, exceptional and adjustable mechanical properties of the resulting eutectogel are achieved, including a high tensile strength ranging from 2.9 to 8.2 MPa and elongation at break ranging from 1725 to 747%, at a 70 wt% DES content. Furthermore, the reversible non-covalent crosslinking in these eutectogels enables self-recovery and self-healing capabilities of eutectogels. The prepared eutectogels also exhibit outstanding ionic conductivity (3.56 mS cm-1 ), making them well-suited for use as strain sensors in human motion detection. The toughening strategy is universally effective for creating tough eutectogels using coordinated metal salt-type DES with various metal ions, as well as a diverse range of coordinatable polymers.

Non-fragile output-feedback control for time-delay neural networks with persistent dwell time switching: A system mode and time scheduler dual-dependent design.

This paper is concerned with non-fragile output-feedback control for time-delay neural networks with persistent dwell time (PDT) switching in a continuous-time setting. The main purpose is to design an output-feedback controller subject to gain fluctuations, guaranteeing both asymptotic stability and L2-gain of the closed-loop control system. To achieve reduced conservatism, the controller is formulated to depend not only on the system mode but also on a time scheduler constructed based on the PDT switching rule and minimum time span. A criterion for the asymptotic stability and L2-gain analysis is established through the application of the Gronwall-Bellman inequality and mathematical induction. Then, a numerically tractable design approach for the desired controller is proposed, utilizing a four-section piecewise time-dependent Lyapunov-Krasovskii functional and several nonlinearity decoupling techniques. For comparative purposes, a simple case, independent of the time scheduler, is also investigated, and the corresponding controller design approach is presented. Finally, a simulation example is given to illustrate the effectiveness and superiority of the proposed system mode and time scheduler dual-dependent controller design approach.