Stroke and frailty index: a two-sample Mendelian randomisation study.

INTRODUCTION: Previous observational studies have found an increased risk of frailty in patients with stroke. However, evidence of a causal relationship between stroke and frailty is scarce. The aim of this study was to investigate the potential causal relationship between stroke and frailty index (FI). METHODS: Pooled data on stroke and debility were obtained from genome-wide association studies (GWAS).The MEGASTROKE Consortium provided data on stroke (N = 40,585), ischemic stroke (IS,N = 34,217), large-vessel atherosclerotic stroke (LAS,N = 4373), and cardioembolic stroke (CES,N = 7 193).Summary statistics for the FI were obtained from the most recent GWAS meta-analysis of UK BioBank participants and Swedish TwinGene participants of European ancestry (N = 175,226).Two-sample Mendelian randomization (MR) analyses were performed by inverse variance weighting (IVW), weighted median, MR-Egger regression, Simple mode, and Weighted mode, and heterogeneity and horizontal multiplicity of results were assessed using Cochran's Q test and MR-Egger regression intercept term test. RESULTS: The results of the current MR study showed a significant correlation between stroke gene prediction and FI (odds ratio 1.104, 95% confidence interval 1.064 - 1.144, P < 0.001). In terms of stroke subtypes, IS (odds ratio 1.081, 95% confidence interval 1.044 - 1.120, P < 0.001) and LAS (odds ratio 1.037, 95% confidence interval 1.012 - 1.062, P = 0.005). There was no causal relationship between gene-predicted CES and FI. Horizontal multidimensionality was not found in the intercept test for MR Egger regression (P > 0.05), nor in the heterogeneity test (P > 0.05). CONCLUSIONS: This study provides evidence for a causal relationship between stroke and FI and offers new insights into the genetic study of FI.

Development and validation of a risk prediction model for physical frailty in older adults who are disabled.

Physical frailty is highly prevalent among the older adults who are disabled. The aim of this study was to explore the risk factors for physical frailty in older adults who are disabled and construct a nomogram prediction model. The data source was the China Health and Retirement Longitudinal Study (CHARLS). The prediction model was validated with a cohort of 1183 older adults who are disabled. The results showed that sleep quality, depression, fatigue, and chronic disease were the best predictive factors. These factors were used to construct the nomogram model, which showed good concordance and accuracy. The prediction model yielded an Area under the curve (AUC) value of 0.760. Calibration curves showed significant agreement between the nomogram model and actual observations. Receiver operating characteristic (ROC) and Decision curve analysis (DCA) showed that the nomogram had good predictive performance. The nomogram is contributed to the screening of specific populations by clinicians.

Monodispersed and Organic Amine Modified La(OH)3 Nanocrystals for Superior Advanced Phosphate Removal.

Advanced phosphate removal is critical for alleviating the serious and widespread aquatic eutrophication, strongly depending on the development of superior adsorption materials to overcome low chemical affinity and sluggish mass transfer at low phosphate concentrations. Herein, the first synthesis of monodispersed and organic amine modified lanthanum hydroxide nanocrystals (OA-La(OH)3) for advanced phosphate removal by modulating inner Helmholtz plane (IHP), is reported. These OA-La(OH)3 nanocrystals with positively charged surfaces and abundant exposed La sites exhibit specific affinity toward phosphate, delivering a maximum adsorption capacity of 168 mg P g⁻1 and a wide pH adaptability from 3.0 to 11.0, as well as a robust anti-interference performance, far surpassing those of documented phosphate removal materials. The superior phosphate removal performance of OA-La(OH)3 is attributed to its protonated organic amine in IHP, which enhances the electrostatic attraction around the adsorbent-solution interface. Impressively, OA-La(OH)3 can treat ≈5 000 and ≈3 200 bed volumes of simulated and real phosphate-containing wastewater to below extremely strict standard (0.1 mg L⁻1) in a fixed-bed adsorption mode, exhibiting great potential for advanced phosphate removal. This study offers a facile modification strategy to improve phosphate removal performance of nanoscale adsorbents, and sheds light on the structure-reactivity relationship of La-based materials.

Enzyme-Assisted Ultrasonic Extraction and Antioxidant Activities of Polysaccharides from Schizochytrium limacinum Meal.

Enzyme-assisted ultrasonic extraction (EAUE) was utilized and optimized for extracting polysaccharides from Schizochytrium limacinum meal (SLMPs) via the response surface methodology. The optimal EAUE conditions were determined as follows: enzyme concentration at 5.18%, ultrasonic temperature at 53 °C, ultrasonic duration of 40 min, ultrasonic power at 60 W, and a liquid-to-material ratio of 34 mL/g, achieving a polysaccharide extraction yield of 11.86 ± 0.61%. The purified polysaccharide component, SLMP1-1, isolated using DEAE Sepharose Fast Flow and Sephadex G-100 columns, exhibited potent antioxidant activity. SLMP1-1, with a molecular weight of 25.5 kDa, comprises glucose, mannose, arabinose, and galactose in a molar ratio of 16.39:14.75:1:693.03. 1H NMR analysis revealed the α configuration of SLMP1-1. Antioxidant assessments, including DPPH, ABTS, and ferric ion reduction assays, were detected with inhibitory values at 21.82-82.98%, 38.21-98.46%, and 3.30-20.30% at 0.2-1.0 mg/mL. This confirmed the effective antioxidant capacity of SLMP1-1, which is notably enhanced post oral and gastric digestion. The findings suggest that polysaccharides extracted from Schizochytrium limacinum meal hold significant promise as natural antioxidants.

Spatially Amplified and Rigid Junction in Diblock Copolymers: Reduced Microphase Separation Size via Interface Expansion.

We introduce an approach in diblock copolymer design, where modifying the junction point with rigid bulky monomer expands the cross-sectional area of the interface and leads to a decrease in the repeat period. Using living anionic polymerization, we synthesized a series of dialkynyl midfunctionalized poly(styrene-b-methyl methacrylate) (PSM-DA) and functionalized them using the thiol-alkyne click reaction with specifically selected rigid bulky monomers: PSS-(3-mercapto)propyl-heptaisobutyl substituted (PSS) and 1-adamantanethiol (ADA). This modification, though involving only a single monomer unit within the diblock copolymer structure, brought about a significant reduction in domain size, with PSS and ADA reducing it by 18% and 15%, respectively. The results indicate a method for reducing the domain sizes of block copolymers, which could lead to advancements in lithography and various nanotechnological applications.

Engineering the Coordination Environment of Ir Single Atoms with Surface Titanium Oxide Amorphization for Superior Chlorine Evolution Reaction.

The chlorine evolution reaction (CER) is essential for industrial Cl2 production but strongly relies on the use of dimensionally stable anode (DSA) with high-amount precious Ru/Ir oxide on a Ti substrate. For the purpose of sustainable development, precious metal decrement and performance improvement are highly desirable for the development of CER anodes. Herein, we demonstrate that surface titanium oxide amorphization is crucial to regulate the coordination environment of stabilized Ir single atoms for efficient and durable chlorine evolution of Ti monolithic anodes. Experimental and theoretical results revealed the formation of four-coordinated Ir1O4 and six-coordinated Ir1O6 sites on amorphous and crystalline titanium oxides, respectively. Interestingly, the Ir1O4 sites exhibited a superior CER performance, with a mass activity about 10 and 500 times those of the Ir1O6 counterpart and DSA, respectively. Moreover, the Ir1O4 anode displayed excellent durability for 200 h, far longer than that of its Ir1O6 counterpart (2 h). Mechanism studies showed that the unsaturated Ir in Ir1O4 was the active center for chlorine evolution, which was changed to the top-coordinated O in Ir1O6. This change of active sites greatly affected the adsorption energy of Cl species, thus accounting for their different CER activity. More importantly, the amorphous structure and restrained water dissociation of Ir1O4 synergistically prevent oxygen permeation across the Ti substrate, contributing to its long-term CER stability. This study sheds light on the importance of single-atom coordination structures in the reactivity of catalysts and offers a facile strategy to prepare highly active single-atom CER anodes via surface titanium oxide amorphization.

Cobalt Single-Atom Reverse Hydrogen Spillover for Efficient Electrochemical Water Dissociation and Dechlorination.

Efficient water dissociation to atomic hydrogen (H*) with restrained recombination of H* is crucial for improving the H* utilization for electrochemical dechlorination, but is currently limited by the lack of feasible electrodes. Herein, we developed a monolithic single-atom electrode with Co single atoms anchored on the inherent oxide layer of titanium foam (Co1-TiOx/Ti), which can efficiently dissociate water into H* and simultaneously inhibit the recombination of H*, by taking advantage of the single-atom reverse hydrogen spillover effect. Experimental and theoretical calculations demonstrated that H* could be rapidly generated on the oxide layer of titanium foam, and then overflowed to the adjacent Co single atom for the reductive dechlorination. Using chloramphenicol as a proof-of-concept verification, the resulting Co1-TiOx/Ti monolithic electrode exhibited an unprecedented performance with almost 100 % dechlorination at -1.0 V, far superior to that of traditional indirect reduction-driven commercial Pd/C (52 %) and direct reduction-driven Co1-N-C (44 %). Moreover, its dechlorination rate constant of 1.64 h-1 was 4.3 and 8.6 times more active than those of Pd/C (0.38 h-1) and Co1-N-C (0.19 h-1), respectively. Our research sheds light on the rational design of hydrogen spillover-related electrocatalysts to simultaneously improve the H* generation, transfer, and utilization for environmental and energy applications.

Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry.

BACKGROUND: Currently, noninvasive imaging techniques and circulating biomarkers are still insufficient to accurately assess carotid plaque stability, and an in-depth understanding of the molecular mechanisms that contribute to plaque instability is still lacking. METHODS: We established a clinical study cohort containing 182 patients with carotid artery stenosis. After screening, 39 stable and 49 unstable plaques were included in the discovery group, and quantitative proteomics analysis based on data independent acquisition was performed for these plaque samples. Additionally, 35 plaques were included in the validation group to validate the proteomics results by immunohistochemistry analysis. RESULTS: A total of 397 differentially expressed proteins were identified in stable and unstable plaques. These proteins are primarily involved in ferroptosis and lipid metabolism-related functions and pathways. Plaque validation results showed that ferroptosis- and lipid metabolism-related proteins had different expression trends in stable plaques versus unstable fibrous cap regions and lipid core regions. Ferroptosis- and lipid metabolism-related mechanisms in plaque stability were discussed. CONCLUSIONS: Our results may provide a valuable strategy for revealing the mechanisms affecting plaque stability and will facilitate the discovery of specific biomarkers to broaden the therapeutic scope.

Spin polarized Fe1-Ti pairs for highly efficient electroreduction nitrate to ammonia.

Electrochemical nitrate reduction to ammonia offers an attractive solution to environmental sustainability and clean energy production but suffers from the sluggish *NO hydrogenation with the spin-state transitions. Herein, we report that the manipulation of oxygen vacancies can contrive spin-polarized Fe1-Ti pairs on monolithic titanium electrode that exhibits an attractive NH3 yield rate of 272,000 µg h-1 mgFe-1 and a high NH3 Faradic efficiency of 95.2% at -0.4 V vs. RHE, far superior to the counterpart with spin-depressed Fe1-Ti pairs (51000 µg h-1 mgFe-1) and the mostly reported electrocatalysts. The unpaired spin electrons of Fe and Ti atoms can effectively interact with the key intermediates, facilitating the *NO hydrogenation. Coupling a flow-through electrolyzer with a membrane-based NH3 recovery unit, the simultaneous nitrate reduction and NH3 recovery was realized. This work offers a pioneering strategy for manipulating spin polarization of electrocatalysts within pair sites for nitrate wastewater treatment.

Ten-year experiences and outcomes of bypass surgery and endovascular therapy in the management of infrarenal aortic occlusion: a single-center retrospective cohort study.

Background: Infrarenal aortic occlusion (IAO) is a life-threatening condition that often causes lower limb ischemia. Although open surgery is the current recommendation for first-line treatment, recent technological innovations have made endovascular treatment (EVT) a promising alternative. This study aims to compare the clinical outcomes of bypass surgery and EVT in the treatment of IAO. Methods: This study is a single-center retrospective observative study at Peking Union Medical College Hospital. Consecutive 92 patients with chronic and atherosclerotic IAO were treated with either EVT (n=40) or bypass surgery (n=52) between 2011 and 2021. The baseline clinical factors (including demographic data and comorbidities), perioperative data (including Rutherford classification changes, technical success) and complication rates were evaluated. The mid-term patency and overall survival of EVT and bypass were assessed. Follow-up was defined as the time from surgery to the last outpatient visit. Continuous variables and category variables were statistically compared, respectively. Kaplan-Meier survival analyses were conducted for vascular patency. Results: The study found that the demographics and pre-operative Rutherford classification were evenly distributed between the two groups (P>0.05). As for technical success, clinical success, comorbidities, mortality, complication rate, and Rutherford classification after procedures, no significant differences were observed (P>0.05). The average post-procedure hospital stay was 5.15 days in the EVT group and was significantly shorter than that of the bypass group, which was 11.83 days (P<0.0001). As for short-term and long-term results, the 1-, 3-, and 5-year primary patency rates were 81.8%, 73.1%, and 73.1% in the EVT group and 97.8%, 80.6%, and 80.6% in the bypass group. The bypass group had significantly better primary patency (P=0.034). There was a significant difference in the secondary patency rate (Bypass 100% vs. EVT 81.6%; P=0.005). Moreover, survival rates were higher in the bypass surgery group than in the EVT group (P=0.035). Conclusions: Although EVT's primary patency rate was lower than that with the bypass surgery, its safety and efficacy were still comparable to anatomic bypass surgery for IAO with less severe perioperative complications and shorter hospital stay. Therefore, EVT could be a feasible option for IAO.

A contrast-enhanced CT-based radiomic nomogram for the differential diagnosis of intravenous leiomyomatosis and uterine leiomyoma.

Objective: Uterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM. Methods: 124 patients (37 IVL and 87 LM) were retrospectively enrolled in the study. Radiomic features were extracted from contrast-enhanced CT before surgery. Clinical, radiomic, and combined models were developed using LightGBM (Light Gradient Boosting Machine) algorithm to differentiate IVL and LM. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC) and decision curve analysis (DCA). Results: Clinical factors, such as symptoms, menopausal status, age, and selected imaging features, were found to have significant correlations with the differential diagnosis of IVL and LM. A total of 108 radiomic features were extracted from contrast-enhanced CT images and selected for analysis. 29 radiomics features were selected to establish the Rad-score. A clinical model was developed to discriminate IVL and LM (AUC=0.826). Radiomic models were used to effectively differentiate IVL and LM (AUC=0.980). This radiological nomogram combined the Rad-score with independent clinical factors showed better differentiation efficiency than the clinical model (AUC=0.985, p=0.046). Conclusion: This study provides evidence for the utility of a radiomic nomogram integrating clinical and radiomic signatures for differentiating IVL and LM with improved diagnostic accuracy. The nomogram may be useful in clinical decision-making and provide recommendations for clinical treatment.

Photochemical Acceleration of Ammonia Production by Pt1-Ptn-TiN Reduction and N2 Activation.

Stable metal nitrides (MN) are promising materials to fit the future "green" ammonia-hydrogen nexus. Either through catalysis or chemical looping, the reductive hydrogenation of MN to MN1-x is a necessary step to generate ammonia. However, encumbered by the formation of kinetically stable M-NH1─3 surface species, this reduction step remains challenging under mild conditions. Herein, we discovered that deleterious Ti-NH1─3 accumulation on TiN can be circumvented photochemically with supported single atoms and clusters of platinum (Pt1-Ptn) under N2-H2 conditions. The photochemistry of TiN selectively promoted Ti-NH formation, while Pt1-Ptn effectively transformed any formed Ti-NH into free ammonia. The generated ammonia was found to originate mainly from TiN reduction with a minor contribution from N2 activation. The knowledge accrued from this fundamental study could serve as a springboard for the development of MN materials for more efficient ammonia production to potentially disrupt the century-old fossil-powered Haber-Bosch process.

Visible Light-Driven Conversion of Carbon-Sequestrated Seawater into Stoichiometric CO and HClO with Nitrogen-Doped BiOCl Atomic Layers.

Seawater is one of the most important CO2 sequestration media for delivering value-added chemicals/fuels and active chlorine; however, this scenario is plagued by sluggish reaction rates and poor product selectivity. Herein, we first report the synthesis of nitrogen-doped BiOCl atomic layers to directly split carbon-sequestrated natural seawater (Yellow Sea, China) into stoichiometric CO (92.8 µmol h-1 ) and HClO (83.2 µmol h-1 ) under visible light with selectivities greater than 90 %. Photoelectrons enriched on the exposed BiOCl{001} facet kinetically facilitate CO2 -to-CO reduction via surface-doped nitrogen bearing Lewis basicity. Photoholes, mainly located on the lateral facets of van der Waals gaps, promote the selective oxidation of Cl- into HClO. Sequestrated CO2 also maintains the pH of seawater at around 4.2 to prevent the alkaline earth cations from precipitating. The produced HClO can effectively kill typical bacteria in the ballast water of ocean-going cargo ships, offering a green and safe way for onsite sterilization.

Glucagon-Like Peptide-1 (GLP-1) Rescue Diabetic Cardiac Dysfuntions in Human iPSC-Derived Cardiomyocytes.

Glucagon-like peptide-1 (GLP-1) can improve cardiac function and cardiovascular outcomes in diabetic cardiomyopathy; however, the beneficial effect of GLP-1 on human diabetic cardiomyocytes (DCMs) and its mechanism have not been fully elucidated. Here, the DCMs model by human-induced pluripotent stem cells-derived cardiomyocytes is developed. Two subtypes of GLP-1, GLP-17-36 and GLP-19-36 , are evaluated for their efficacy on the DCMs model. Diabetogenic condition is sufficient to induce most characteristics of diabetic cardiomyopathy in vitro, such as cardiac hypertrophy, lipid accumulation, impaired calcium transients, and abnormal electrophysiological properties. GLP-17-36 and GLP-19-36 can restore cardiomyocyte hypertrophic phenotype, impaired calcium transient frequency, abnormal action potential amplitude, depolarization, and repolarization velocity. Interestingly, RNA-seq reveals different pathways altered by GLP-17-36 and GLP-19-36 , respectively. Differentially expressed gene analysis reveals that possible targets of GLP-17-36 involve the regulation of mitotic nuclear division and extracellular matrix-receptor interaction, while possible targets of GLP-19-36 involve kinetochore assembly, and the complement and coagulation cascades. This study demonstrates the therapeutic effects of GLP-1 on human DCMs and provides a novel platform to unveil the cellular mechanisms of diabetic cardiomyopathy, shedding light on discovering better targets for novel therapeutic interventions.

Midterm Results of a Surgeon-Modified Device to Preserve the Flow of the Internal Iliac Artery During Endovascular Repair of Aneurysm: Single-Center Experiences.

BACKGROUND: During endovascular aneurysm repair (EVAR), commercial iliac branch devices (IBDs) have become an inescapable alternative for preserving antegrade internal iliac artery (IIA) blood flow. Due to the different morphological features of aneurysms, commercial IBDs may not be suitable for all patients. Reported experience with the implantation of the new surgeon-modified IBD (sm IBD) is limited. This investigation describes the indications, efficacy, and safety of the sm IBD. METHODS: Data from consecutive elective implantations of IBDs in patients between March 2011 and May 2021 in a single center were incorporated. The sm IBDs were indicated in patients with common iliac artery aneurysms (CIAAs) and with a challenging anatomy and in those patients with or without abdominal aortic aneurysm (AAA). RESULTS: Fifteen patients (15 male, mean age 67.6 ± 7.9 years) were included. Fifteen sm IBDs were implanted in 1 procedure (100%). Fourteen (93.3%) patients had simultaneous endovascular aneurysm repair (EVAR) and 1 (6.7%) patient previously had a bilateral CIAAs repair by EVAR. The mean common iliac artery (CIA) diameter was 36.6 ± 12.5 mm. Technical success was obtained in all patients (100%). The median operation time was 189.7 ± 78.6 min, with a median fluoroscopy time of 45.3 ± 15.9 min. Axillary artery access was used in 11 (73.3%) procedures. The mean total hospital stay was 5.6 ± 2.8 days, and the postoperative follow-up was 35.4 months (range 2-120). The estimated IIA bridge stent patency at 1 year after operation was 100% and 85.7% ± 13.2% 5 years postoperatively. One (6.7%) IIA branch was occluded, and this patient remained asymptomatic. One patient (6.7%) needed reintervention, and another (6.7%) patient had type II leakage, which is currently under close surveillance. CONCLUSIONS: Using an IBD to maintain the pelvic blood flow is an effective and feasible intravascular technique, especially for patients with an abnormal iliac artery anatomy. This novel technique has similar midterm procedural success rate compared to the use of commercial IBDs. Therefore, these devices are more suitable for patients with certain anatomic challenges and can be used as an alternative treatment.

Single Atom Ru Monolithic Electrode for Efficient Chlorine Evolution and Nitrate Reduction.

Fabricating single-atom electrodes via atomic dispersion of active metal atoms into monolithic metal supports is of great significance to advancing the lab-to-fab translation of the electrochemical technologies. Here, we report an inherent oxide anchoring strategy to fasten ligand-free isolated Ru atoms on the amorphous layer of monolithic Ti support by regulating the electronic metal-support interactions. The prepared Ru single atom electrode exhibited exceptional electrochemical chlorine evolution activity, three orders of magnitude higher mass activity than that of commercial dimensionally stable anode, and also selectively reduced nitrate to ammonia with an unprecedented ammonia yield rate of 22.2 mol g-1 h-1 at -0.3 V. Furthermore, the Ru single atom monolithic electrode can be scaled up from 2×2 cm to 25×15 cm at least, thus demonstrating great potential for industrial electrocatalytic applications.

Epicardial injection of allogeneic human-induced-pluripotent stem cell-derived cardiomyocytes in patients with advanced heart failure: protocol for a phase I/IIa dose-escalation clinical trial.

INTRODUCTION: Heart failure (HF) is a growing global public health burden. However, due to the very limited regenerative capacity of mature cardiomyocytes in the adult mammalian heart, conventional treatments can only improve the symptoms of HF but fail to restore cardiac function. Heart transplantation is limited by a severe shortage of donors. Cell-based transplantation for the treatment of HF has become a promising strategy. Human-induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been tested in animal models to assess safety and efficacy. This study aims at evaluating the safety and efficacy of epicardial injection of hiPSC-CMs in patients with advanced HF during coronary artery bypass grafting (CABG) surgery. METHODS: This study is a dose-escalation, placebo-controlled, single-centre phase I/IIa clinical trial. Dose escalation will be guided by a modified 3+3 design for three doses (1×108, 2×108 and 4×108 cells, sequentially). Patients with advanced heart failure will be enrolled and randomly allocated to receive epicardial injection of hiPSC-CMs during CABG surgery or CABG surgery alone, followed by a 12-month follow-up investigation. The primary endpoint is to assess the safety of hiPSC-CMs transplantation, including haemodynamic compromised sustained ventricular arrhythmias and newly formed tumours during 6 months postoperatively. The secondary endpoint is to evaluate the efficacy of epicardial injection of hiPSC-CMs and CABG surgery combination by comparison with CABG surgery alone. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Ethical Committee of Nanjing Drum Tower Hospital (No. SC202000102) and approved by National Health Commission of the PRC (MR-32-21-014649). Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. TRIAL REGISTRATION NUMBER: NCT03763136.

Irisin Suppresses Nicotine-Mediated Atherosclerosis by Attenuating Endothelial Cell Migration, Proliferation, Cell Cycle Arrest, and Cell Senescence.

Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe -/- mice through the integrin αVß5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, ß-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVß5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.

Fault tolerant control for strict-feedback nonlinear system via event-triggered adaptive algorithms.

In this paper, the event-triggered adaptive fault tolerant tracking control for the strict-feedback nonlinear system with mismatched unknown parameters, external disturbances and actuator faults is addressed. A novel adaptive fault tolerant mechanism is presented to overcome the difficulty arising from the actuator faults and mismatched parameters, where the parameters estimators are generated from discrete state governed by the state dependent event-triggered mechanism. Furthermore, by introducing the auxiliary dynamic, it is shown that all the signals of the system are ultimately bounded and the asymptotical output tracking error is within a small residual set including origin which can be modified arbitrarily small by tuning the control coefficients. Based on the presented adaptive fault tolerant mechanism, the robust event-triggered mechanism and adaptive algorithm are further developed and the boundedness of all the variables of the system is shown. What is more, it is proved that both of the presented event-triggered mechanisms are Zeno-free. Finally, the control effectiveness of the proposed fault tolerant strategy is discussed and verified by a numerical example and the single-link manipulator.

Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells.

Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have not been fully understood. In this study, we show that nicotinamide plays multiplex roles in mesoderm differentiation of human embryonic stem cells (hESCs). Nicotinamide promotes cardiomyocyte fate from mesoderm progenitor cells, and suppresses the emergence of other cell types. Independent of its functions in PARP and Sirtuin pathways, nicotinamide modulates differentiation through kinase inhibition. A KINOMEscan assay identifies 14 novel nicotinamide targets among 468 kinase candidates. We demonstrate that nicotinamide promotes cardiomyocyte differentiation through p38 MAP kinase inhibition. Furthermore, we show that nicotinamide enhances cardiomyocyte survival as a Rho-associated protein kinase (ROCK) inhibitor. This study reveals nicotinamide as a pleiotropic molecule that promotes the derivation and survival of cardiomyocytes, and it could become a useful tool for cardiomyocyte production for regenerative medicine. It also provides a theoretical foundation for physicians when nicotinamide is considered for treatments for pregnant women.