RTA 408 ameliorates diabetic cardiomyopathy by activating Nrf2 to regulate mitochondrial fission and fusion and inhibiting NF-κB-mediated inflammation.

Diabetic cardiomyopathy (dCM) is a major complication of diabetes; however, specific treatments for dCM are currently lacking. RTA 408, a semisynthetic triterpenoid, has shown therapeutic potential against various diseases by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. We established in vitro and in vivo models using high glucose toxicity and db/db mice, respectively, to simulate dCM. Our results demonstrated that RTA 408 activated Nrf2 and alleviated various dCM-related cardiac dysfunctions, both in vivo and in vitro. Additionally, it was found that silencing the Nrf2 gene eliminated the cardioprotective effect of RTA 408. RTA 408 ameliorated oxidative stress in dCM mice and high glucose-exposed H9C2 cells by activating Nrf2, inhibiting mitochondrial fission, exerting anti-inflammatory effects through the Nrf2/NF-κB axis, and ultimately suppressing apoptosis, thereby providing cardiac protection against dCM. These findings provide valuable insights for potential dCM treatments.NEW & NOTEWORTHY We demonstrated first that the nuclear factor erythroid 2-related factor 2 (Nrf2) activator RTA 408 has a protective effect against diabetic cardiomyopathy. We found that RTA 408 could stimulate the nuclear entry of Nrf2 protein, regulate the mitochondrial fission-fusion balance, and redistribute p65, which significantly alleviated the oxidative stress level in cardiomyocytes, thereby reducing apoptosis and inflammation, and protecting the systolic and diastolic functions of the heart.

Repeated acute coronary syndrome caused by a mind-bending mural thrombus in ascending aorta: a case report and review of the literature.

BACKGROUND: Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). CASE PRESENTATION: We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. CONCLUSIONS: Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.

Metal-Oxo Electronic Tuning via In Situ CO Decoration for Promoting Methane Conversion to Oxygenates over Single-Atom Catalysts.

Direct methane conversion (DMC) to oxygenates at low temperature is of great value but remains challenging due to the high energy barrier for C-H bond activation. Here, we report that in situ decoration of Pd1-ZSM-5 single atom catalyst (SAC) by CO molecules significantly promoted the DMC reaction, giving the highest turnover frequency of 207 h-1 ever reported at room temperature and ~100 % oxygenates selectivity with H2O2 as oxidant. Combined characterizations and DFT calculations illustrate that the C-atom of CO prefers to coordinate with Pd1, which donates electrons to the Pd1-O active center (L-Pd1-O, L=CO) generated by H2O2 oxidation. The correspondingly improved electron density over Pd-O pair renders a favorable heterolytic dissociation of C-H bond with low energy barrier of 0.48 eV. Applying CO decoration strategy to M1-ZSM-5 (M=Pd, Rh, Ru, Fe) enables improvement of oxygenates productivity by 3.2-11.3 times, highlighting the generalizability of this method in tuning metal-oxo electronic structure of SACs for efficient DMC process.

Single Carbon Vacancy Traps Atomic Platinum for Hydrogen Evolution Catalysis.

The coordinated configuration of atomic platinum (Pt) has always been identified as an active site with high intrinsic activity for hydrogen evolution reaction (HER). Herein, we purposely synthesize single vacancies in a carbon matrix (defective graphene) that can trap atomic Pt to form the Pt-C3 configuration, which gives exceptionally high reactivity for HER in both acidic and alkaline solutions. The intrinsic activity of Pt-C3 site is valued with a turnover frequency (TOF) of 26.41 s-1 and mass activity of 26.05 A g-1 at 100 mV, respectively, which are both nearly 18 times higher than those of commercial 20 wt % Pt/C. It is revealed that the optimal coordination Pt-C3 has a stronger electron-capture ability and lower Gibbs free energy difference (ΔG), resulting in promoting the reduction of adsorbed H+ and the acceleration of H2 desorption, thus exhibiting the extraordinary HER activity. This work provides a new insight on the unique coordinated configuration of dispersive atomic Pt in defective C matrix for superior HER performance.

Highly Efficient Asymmetric Multiple Resonance Thermally Activated Delayed Fluorescence Emitter with EQE of 32.8 % and Extremely Low Efficiency Roll-Off.

Multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters show great potentials for high color purity organic light-emitting diodes (OLEDs). However, the simultaneous realization of high photoluminescence quantum yield (PLQY) and high reverse intersystem crossing rate (kRISC ) is still a formidable challenge. Herein, a novel asymmetric MR-TADF emitter (2Cz-PTZ-BN) is designed that fully inherits the high PLQY and large kRISC values of the properly selected parent molecules. The resonating extended π-skeleton with peripheral protection can achieve a high PLQY of 96 % and a fast kRISC of above 1.0×105  s-1 , and boost the performance of corresponding pure green devices with an outstanding external quantum efficiency (EQE) of up to 32.8 % without utilizing any sensitizing hosts. Remarkably, the device sufficiently maintains a high EQE exceeding 23 % at a high luminance of 1000 cd m-2 , representing the highest value for reported green MR-TADF materials at the same luminescence.

Association study of S100A9 gene polymorphisms with Parkinson's disease risk and age of disease onset.

PURPOSE: Intestinal inflammation is associated with several neurodegenerative diseases, including Parkinson's disease (PD). Intestinal inflammation is also closely related to genetic and environmental factors. S100 calcium-binding protein A9 (S100A9) is also thought to be genetically associated with intestinal inflammation and PD risk. This study investigated the association between S100A9 gene polymorphisms and PD risk and age of disease onset. METHODS: This study used a case-control method and included 242 PD patients and 242 healthy participants. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed. S100A9 expression in the serum of the patients and controls was detected using reverse transcription­quantitative PCR (RT-qPCR). RESULTS: The CC genotype and C allele of the rs3014866 polymorphism in S100A9 had significantly higher distribution in PD patients. The recessive and dominant models demonstrated that the patients carrying the rs3014866 C allele had a significantly increased risk of developing PD as compared with patients homozygous for the TT genotype. The generalized linear model results demonstrated that rs3014866 was associated with the age of disease onset independent of environmental exposure factors (smoking and toxins). Furthermore, the S100A9 mRNA transcription level in the patients' serum was significantly higher than that of the controls. Moreover, the serum of patients with the CC genotype had higher S100A9 expression levels. CONCLUSIONS: The results combined the relationship between S100A9 and PD susceptibility and age of disease onset. The findings might suggest new ideas for PD clinical diagnosis and treatment.

Variable Control and Its Influence Before Urine Sample Analysis in a Field Environment.

Background and Objectives: The aim of the study was to store urine samples at different temperatures and humidity levels and analyze common biochemical test results and point-of-care testing (POCT) indicators according to different storage times and evaluate whether the samples should be centrifuged to study the best storage conditions for urine samples. Methods: Random midstream urine samples (100 mL) were collected from 10 healthy individuals. A portion of the samples was centrifuged. The remaining samples were not centrifuged and were stored under different temperature and humidity conditions for different periods. We measured urine indicators ([Na+], [K+], [Cl-], gamma-glutamyl transpeptidase [GGT], urea, and creatinine [Cr]) at 2, 4, 24, and 72 hours and 7 and 55 days, and we used POCT to measure myoglobin (Mb) and microalbumin (mAlb) concentrations. Results: Centrifugation of urine samples decreased the measured GGT and increased the measured Mb. In urine samples stored at 4°C and room temperature, electrolyte concentrations were scarcely affected by storage time. After storage at 50°C for 24 hours, the measured [Na+] and [Cl-] levels changed. Metabolites (urea and Cr) underwent no obvious change across temperatures. GGT did not change during long-term storage at 4°C. The mAlb level changed significantly only after storage at 4°C. When stored at 4°C, Mb changed little within 4 hours. Under humid conditions, [Na+] and [Cl-] increased significantly after 24 hours, and urea decreased significantly after 7 days of storage. Under dry storage conditions, urinary Cr and GGT decreased, and under humid conditions, these concentrations increased. At high humidity, mAlb increased significantly after 72 hours. Conclusions: Electrolyte and amino acid metabolite concentrations were less affected by storage time at 4°C and room temperature than at other temperatures. Some proteins are sensitive to environmental changes; samples collected for quantification of these proteins can be stored briefly at 4°C after centrifugation. Normal humidity conditions meet most physiological testing requirements.

The Role of Pyroptosis in Coronary Heart Disease.

The incidence and mortality of cardiovascular diseases, of which coronary heart disease (CHD) is a significant cardiovascular burden, are on the rise. Pyroptosis as an incipient programmed cell death mediated by inflammasomes can sense cytoplasmic contamination or interference and is typically marked by intracellular swelling, plasma membrane blistering and intense inflammatory cytokine release. As research on pyroptosis continues to progress, there is mounting evidence that pyroptosis is a vital participant in the pathophysiological basis of CHD. Atherosclerosis is the major pathophysiological basis of CHD and involves pyroptosis of endothelial cells, macrophages, vascular smooth muscle cells, and other immune cells, often in association with the release of pro-inflammatory factors. When cardiomyocytes are damaged, it will eventually lead to heart failure. Previous studies have covered that pyroptosis plays a critical role in CHD. In this review, we describe the properties of pyroptosis, summarize its contribution and related targets to diseases involving angina pectoris, myocardial infarction, myocardial ischemia in perfusion injury and heart failure, and highlight potential drugs for different heart diseases.

Impacts of root exudates on the toxic response of Chrysanthemum coronarium L. to the co-pollution of nanoplastic particles and tetracycline.

Nano polystyrene (PS) particles and antibiotics universally co-exist, posing a threat to crop plants and hence human health, nevertheless, there is limited research on their combined toxic effects along with major influential factors, especially root exudates, on crop plants. This study aimed to investigate the response of Chrysanthemum coronarium L. to the co-pollution of nanoplastics and tetracycline (TC), as well as the effect of root exudates on this response. Based on a hydroponic experiment, the biochemical and physiological indices of Chrysanthemum coronarium L. were measured after 7 days of exposure. Results revealed that the co-pollution of TC and PS caused significant oxidative damage to the plants, resulting in reduced biomass. Amongst the two contaminants, TC played a more prominent role. PS could enter the root tissue, and the uptake of TC and PS by plant roots was synergetic. Malic acid, oxalic acid, and formic acid could explain 65.1% of the variation in biochemical parameters and biomass of the roots. These compounds affected the photosynthesis and biomass of Chrysanthemum coronarium L. by gradually lowering root reactive oxygen species (ROS) and leaf ROS. In contrast, the impact of rhizobacteria on the toxic response of the plants was relatively minor. These findings suggested that root exudates could alleviate the toxic response of plants to the co-pollution of TC and PS. This study enhances our understanding of the role of root exudates, providing insights for agricultural management and ensuring food safety.

Integrated single-cell and bulk RNA sequencing revealed an epigenetic signature predicts prognosis and tumor microenvironment colorectal cancer heterogeneity.

BACKGROUND: Colorectal cancer (CRC) prognosis prediction is currently a major challenge. Epigenetic regulation has been widely reported for its role in cancer development. AIM: To construct a robust prognostic signature, we used developed and validated across datasets. METHODS: After constructing the signature, the prognostic value of the signature was evaluated in the TCGA cohort and six independent datasets (GSE17526, GSE17537, GSE33113, GSE37892, GSE39048 and GSE39582). The clinical, genomic and transcriptomic features related to the signature were identified. The correlations of the signature score with immune cell infiltration and cell-cell interactions were analyzed. The correlations between the signature score and the sensitivity to different drugs were also predicted. RESULTS: In the TCGA cohort, patients in the low-risk group according to the signature score had longer survival than those in the high-risk group, and this finding was validated in the validation datasets. The signature was a prognostic factor independent of age and sex and was correlated with stage and PD-1/PD-L1 expression. Area under the receiving operating characteristic curve was 0.72. Genomic association analyses revealed that samples from high-risk patients exhibited chromosomal instability. Transcriptomic analyses revealed that the signature score was significantly associated with multiple cellular pathways. Bulk RNA-seq and single-cell sequencing data revealed that the signature reflected differences in infiltrating immune cell-tumor cell interactions, especially for macrophages. The signature also predicted the putative drug sensitivity of CRC samples. CONCLUSION: The signature is a valuable biomarker for predicting CRC prognosis and reflects multiple features of CRC, especially macrophage infiltration in the microenvironment.

Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis.

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

An electron-hole rich dual-site nickel catalyst for efficient photocatalytic overall water splitting.

Photocatalysis offers an attractive strategy to upgrade H2O to renewable fuel H2. However, current photocatalytic hydrogen production technology often relies on additional sacrificial agents and noble metal cocatalysts, and there are limited photocatalysts possessing overall water splitting performance on their own. Here, we successfully construct an efficient catalytic system to realize overall water splitting, where hole-rich nickel phosphides (Ni2P) with polymeric carbon-oxygen semiconductor (PCOS) is the site for oxygen generation and electron-rich Ni2P with nickel sulfide (NiS) serves as the other site for producing H2. The electron-hole rich Ni2P based photocatalyst exhibits fast kinetics and a low thermodynamic energy barrier for overall water splitting with stoichiometric 2:1 hydrogen to oxygen ratio (150.7 µmol h-1 H2 and 70.2 µmol h-1 O2 produced per 100 mg photocatalyst) in a neutral solution. Density functional theory calculations show that the co-loading in Ni2P and its hybridization with PCOS or NiS can effectively regulate the electronic structures of the surface active sites, alter the reaction pathway, reduce the reaction energy barrier, boost the overall water splitting activity. In comparison with reported literatures, such photocatalyst represents the excellent performance among all reported transition-metal oxides and/or transition-metal sulfides and is even superior to noble metal catalyst.

The effect of ivabradine therapy on dilated cardiomyopathy patients with congestive heart failure: a systematic review and meta-analysis.

Background: Ivabradine improves cardiac function in patients with heart failure, but its effect on dilated cardiomyopathy (DCM) remains unclear. We performed a systematic review and meta-analysis to study the efficacy and potential mechanisms of ivabradine's effect on cardiac function and prognosis in patients with DCM. Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, and four registers through September 28, 2022. All controlled trials of ivabradine for the treatment of DCM with congestive heart failure were included. Articles were limited to English, with the full text and necessary data available. We performed random- or fixed effects meta-analyses for all included outcome measures and compared the effect sizes for outcomes in patients treated with and without ivabradine. The quality of the studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB2.0). Findings: Five trials with 357 participants were included. The pooled risk ratio was 0.48 [95% confidence interval (CI) (0.18, 1.25)] for all-cause mortality and 0.38 [95% CI (0.12, 1.23)] for cardiac mortality. The pooled mean difference was -15.95 [95% CI (-19.97, -11.92)] for resting heart rate, 3.96 [95% CI (0.99, 6.93)] for systolic blood pressure, 2.93 [95% CI (2.09, 3.77)] for left ventricular ejection fraction, -5.90 [95% CI (-9.36, -2.44)] for left ventricular end-systolic diameter, -3.41 [95% CI (-5.24, -1.58)] for left ventricular end-diastolic diameter, -0.81 [95% CI (-1.00, -0.62)] for left ventricular end-systolic volume, -0.67 [95% CI (-0.86, -0.48)] for left ventricular end-diastolic volume, -11.01 [95% CI (-19.66, -2.35)] for Minnesota Living with Heart Failure score, and -0.52 [95% CI (-0.73, -0.31)] for New York Heart Association class. Interpretation: Ivabradine reduces heart rate and ventricular volume, and improves cardiac function in patients with DCM, but showed no significant effect on the prognosis of patients.

Highly efficient ammonia synthesis at low temperature over a Ru-Co catalyst with dual atomically dispersed active centers.

The desire for a carbon-free society and the continuously increasing demand for clean energy make it valuable to exploit green ammonia (NH3) synthesis that proceeds via the electrolysis driven Haber-Bosch (eHB) process. The key for successful operation is to develop advanced catalysts that can operate under mild conditions with efficacy. The main bottleneck of NH3 synthesis under mild conditions is the known scaling relation in which the feasibility of N2 dissociative adsorption of a catalyst is inversely related to that of the desorption of surface N-containing intermediate species, which leads to the dilemma that NH3 synthesis could not be catalyzed effectively under mild conditions. The present work offers a new strategy via introducing atomically dispersed Ru onto a single Co atom coordinated with pyrrolic N, which forms RuCo dual single-atom active sites. In this system the d-band centers of Ru and Co were both regulated to decouple the scaling relation. Detailed experimental and theoretical investigations demonstrate that the d-bands of Ru and Co both become narrow, and there is a significant overlapping of t2g and eg orbitals as well as the formation of a nearly uniform Co 3d ligand field, making the electronic structure of the Co atom resemble that of a "free-atom". The "free-Co-atom" acts as a bridge to facilitate electron transfer from pyrrolic N to surface Ru single atoms, which enables the Ru atom to donate electrons to the antibonding π* orbitals of N2, thus resulting in promoted N2 adsorption and activation. Meanwhile, H2 adsorbs dissociatively on the Co center to form a hydride, which can transfer to the Ru site to cause the hydrogenation of the activated N2 to generate N2H x (x = 1-4) intermediates. The narrow d-band centers of this RuCo catalyst facilitate desorption of surface *NH3 intermediates even at 50 °C. The cooperativity of the RuCo system decouples the sites for the activation of N2 from those for the desorption of *NH3 and *N2H x intermediates, giving rise to a favorable pathway for efficient NH3 synthesis under mild conditions.

Long noncoding RNA AOC4P regulates tumor cell proliferation and invasion by epithelial-mesenchymal transition in gastric cancer.

BACKGROUND: The clinical relevance and biological role of tissular AOC4P in gastric cancer (GC) remains to be clarified. METHODS: The association between AOC4P expression and clinicopathological characteristics was investigated. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to explore the biological effects of AOC4P on GC cell proliferation, migration, invasion, and apoptosis in MGC-803 and BGC-823 cell lines. In vivo, animal experiments were conducted to confirm the in vitro findings. Quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence were used to investigate the potential mechanisms. RESULTS: Expression levels of AOC4P were significantly higher in tumor tissues than in noncancerous tissues, and patients with high levels of AOC4P had poor overall and disease-free survival. AOC4P expression was correlated with lymphovascular invasion. In vitro, knockdown of AOC4P inhibited tumor cell proliferation, migration, and invasion, and promoted apoptosis of MGC-803 and BGC-823 cells. In vivo, BGC-823 cells transfected with AOC4P siRNA formed smaller and lighter tumors than BGC-823 cells transfected with negative control siRNA in severe combined immunodeficiency mice. Additionally, the si-AOC4P group had less proliferating cells and more apoptotic cells in tumor xenografts compared with the negative control. Mechanistically, knockdown of AOC4P decreased the expression of vimentin and MMP9, while increasing the expression of E-cadherin. Immunofluorescence confirmed the relationship between AOC4P expression and E-cadherin, vimentin, and MMP9 levels in clinical GC specimens. CONCLUSIONS: AOC4P promotes tumorigenesis and progression partly through epithelial-mesenchymal transition in GC. Additionally, AOC4P may serve as a prognostic biomarker for clinical decision making.