Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis

Myocardial infarction (MI) is the leading cause of premature death among adults. Cardiomyocyte death and dysfunction of the remaining viable cardiomyocytes are the main pathological factors of heart failure after MI. Mitochondrial complexes are emerging as critical mediators for the regulation of cardiomyocyte function. However, the precise roles of mitochondrial complex subunits in heart failure after MI remain unclear. Here, we show that NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) expression is decreased in the hearts of heart failure patients and mice with myocardial infarction. Furthermore, we found that cardiac-specific Ndufs1 overexpression alleviates cardiac dysfunction and myocardial fibrosis in the healing phase of MI. Our results demonstrated that Ndufs1 overexpression alleviates MI/hypoxia-induced ROS production and ROS-related apoptosis. Moreover, upregulation of Ndufs1 expression improved the reduced activity of complex I and impaired mitochondrial respiratory function caused by MI/hypoxia. Given that mitochondrial function and cardiomyocyte apoptosis are closely related to heart failure after MI, the results of this study suggest that targeting Ndufs1 may be a potential therapeutic strategy to improve cardiac function in patients with heart failure.Subject terms: Heart failure, Myocardial infarction, Myocardial infarction     

Oxygen-supplied mesoporous carbon nanoparticles for enhanced photothermal/photodynamic synergetic therapy against antibiotic-resistant bacterial infections

Pandemic and epidemic spread of antibiotic-resistant bacterial infections would result in a huge number of fatalities globally. To combat antibiotic-resistant pathogens, new antimicrobial strategies should be explored and developed to confront bacteria without acquiring or increasing drug-resistance. Here, oxygen saturated perfluorohexane (PFH)-loaded mesoporous carbon nanoparticles (CIL@ICG/PFH@O₂) with photothermal therapy (PTT) and enhanced photodynamic therapy (PDT) utility are developed for antibacterial applications. Ionic liquid groups are grafted onto the surface of mesoporous carbon nanoparticles, followed by anion-exchange with the anionic photosensitizer indocyanine green (ICG) and loading oxygen saturated PFH to prepare CIL@ICG/PFH@O₂. These CIL@ICG/PFH@O₂ nanoparticles exhibit effective PTT and enhanced PDT properties simultaneously upon 808 nm light irradiation. In vitro assays demonstrate that CIL@ICG/PFH@O₂ shows a synergistic antibacterial action against antibiotic-resistant pathogens (methicillin-resistant Staphylococcus aureus and kanamycin-resistant Escherichia coli). Moreover, CIL@ICG/PFH@O₂ could effectively kill drug-resistant bacteria in vivo to relieve inflammation and eliminate methicillin-resistant Staphylococcus aureus-wound infection under NIR irradiation, and the released oxygen can increase collagen deposition, epithelial tissue formation and blood vessel formation to promote wound healing while enhancing the PDT effect. This study proposes a platform with enhanced PTT/PDT effects for effective, controlled, and precise treatment of topical drug-resistant bacterial infections.

We report oxygen saturated perfluorohexane (PFH)-loaded mesoporous carbon nanoparticles (CIL@ICG/PFH@O₂) with photothermal therapy (PTT) and enhanced photodynamic therapy (PDT) utility for antibacterial applications.     

The Antioxidant and Hypolipidemic Effects of Mesona Chinensis Benth Extracts

In this study, the antioxidant and hypolipidemic effects of Mesona Chinensis Benth (MCB) extracts were evaluated. Seven fractions (F0, F10, F20, F30, F40, F50 and MTF) were obtained from the MCB ethanol extracts. Compared to the commercial antioxidants (vitamin C), MTF and F30 exhibited higher antioxidant activities in the antiradical activity test and the FRAP assay. The half-inhibition concentration (IC50) for MTF and F30 were 5.323 µg/mL and 5.278 µg/mL, respectively. MTF at 200 µg/mL significantly decreased the accumulation of TG in oleic acid (OA)-induced HepG2 cells and reversed the inhibitory effect of Compound C on AMPK (MTF and F30 significantly increased the glucose utilization of insulin-induced HepG2 cells). In addition, the components of MTF were identified by HPLC-MS, which were caffeic acid, quercetin 3-O-galactoside, isoquercetin, astragalin, rosmarinic acid, aromadendrin-3-O-rutinoside, rosmarinic acid-3-O-glucoside and kaempferol-7-O-glucoside. Through statistical correlations by Simca P software, it was found that the main antioxidant and hypolipidemic components of MCB might be caffeic acid, kaempferol-7-O-glucoside, rosmarinic acid-3-O-glucoside and aromadendrin-3-O-rutinoside, which may play important roles in the AMPK pathway. MTF and F30 in MCB could be potential health products for the treatment of hyperlipidemia.     

Metabonomics Study of the Hematopoietic Effect of Medicinal Wine Maoji Jiu on a Blood Deficiency Rat Model by Ultra-High-Performance Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry and a Pattern Recognition Approach

Maoji Jiu (MJ) is a kind of medicinal wine that has been widely used by Chinese people for many years to nourish and promote blood circulation. The purpose of this study was to investigate the hematopoietic effect of MJ on the metabolism of blood deficient rats and to explore the underlying hematopoietic regulation mechanisms. Blood deficiency model rats were induced by subcutaneous injection of N-acetylphenylhydrazine (APH) and intraperitoneal injection of cyclophosphamide (CTX). The plasma metabolic fingerprints of blood deficiency model rats with and without MJ treatment were obtained by using metabonomics based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS). Orthogonal partial least squares-discriminant analysis (OPLS–DA) was used to evaluate the hematopoietic effect of MJ and identify potential biomarkers in the plasma of blood deficiency model rats. The levels of white blood cells (WBC), red blood cells (RBC) and hemoglobin (HGB) and the activity of antioxidant capacity showed a recovery trend to the control group after MJ treatment, while the dose of 10 mL/kg showed the best effect. In this study, thirteen potential biomarkers were identified, which were mainly related to seven metabolic pathways, including linoleic acid metabolism, d-glutamine and d-glutamate metabolism, alanine, aspartate and glutamate metabolism, tryptophan metabolism, pyrimidine metabolism, porphyrin and chlorophyll metabolism and arginine biosynthesis. Metabolomics was applied frequently to reflect the physiological and metabolic state of organisms comprehensively, indicating that the rapid plasma metabonomics may be a potentially powerful tool to reveal the efficacy and enriching blood mechanism of MJ.     

一类具有Neumann边界条件的曲率方程解的估计

研究了一类具有Neumann边界条件的抛物方程解的性质,通过微分方法得到了一类边值问题解的估计,并得到了拟线性方程解的存在性.     

A MXene-derived redox homeostasis regulator perturbs the Nrf2 antioxidant program for reinforced sonodynamic therapy

Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a spatiotemporally controllable therapeutic modality in combating cancer because of its high tissue-penetration depth and minimal invasiveness. However, the elevated nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant program in cancer cells can serve as a chief reactive oxygen species (ROS) detoxification system to alleviate oxidative injury and promote tumorigenesis, and thus greatly antagonize the therapeutic efficacy of ROS-mediated anticancer therapies. Herein, we report that vanadium carbide MXene-derived carbon dots (PMQDs) can act as high-efficacy sonosensitizers to efficiently generate ROS upon US irradiation and simultaneously hinder the Nrf2 antioxidant program for enhanced sonodynamic therapy of cancer. These PMQDs show superior US-triggered ROS generating ability because of their efficient migration/separation of electron–hole pairs and narrow bandgap. Importantly, these PMQDs can serve as efficient redox homeostasis regulators to perturb the Nrf2 antioxidant mechanism and thus reduce its effects on ROS neutralization for enhanced SDT efficacy. Overall, the present study will not only provide a new paradigm to augment SDT by perturbing the Nrf2 antioxidant program, but also give valuable insights into developing high-efficacy MXene-derived nanoagents for cancer therapy.

A redox homeostasis regulator has been developed as a high-efficacy sonosensitizer to efficiently generate reactive oxygen species upon ultrasound irradiation and simultaneously hinder the Nrf2 antioxidant program for enhanced sonodynamic therapy.     

Dynamic Variation of Amino Acid Contents and Identification of Sterols in Xinyang Mao Jian Green Tea

As important biomolecules in Camellia sinensis L., amino acids (AAs) are considered to contribute to the overall green tea sensory quality and undergo dynamic changes during growth. However, limited by analytical capacity, detailed AAs composition in different growth stages remains unclear. To address this question, we analyzed the dynamic changes of 23 AAs during leaf growth in Xinyang Mao Jian (XYMJ) green tea. Using amino acid analyzer, we demonstrated that most AAs are abundant on Pure Brightness Day and Grain Rain Day. After Grain Rain, 23 AAs decreased significantly. Further analysis shows that theanine has a high level on the day before Spring Equinox and Grain Rain, accounting for 44–61% of the total free AAs content in tea leaves. Glu, Pro, and Asp are the second most abundant AAs. Additionally, spinasterol and 22,23-dihydrospinasterol are first purified and identified in ethanol extract of XYMJ by silica gel column chromatography method. This study reveals the relationship between plucking days and the dynamic changes of AAs during the growth stage and proves the rationality of the traditional plucking days of XYMJ green tea.     

Design,Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains

A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C. neoformans (MIC = 0.125, 0.0625 μg/mL), and A. fumigatus (MIC = 8.0, 4.0 μg/mL). Compound 6c also exerted superior activity to compound 5k and fluconazole in inhibiting hyphae growth of C. albicans and inhibiting drug-resistant strains of C. albicans, and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that 6c could effectively protect mice models from C. albicans infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound 6c deserves further investigation.     

3英寸6H-SiC单晶的生长

SiC是宽带隙半导体材料的典型代表,具有优良的热学、力学、化学和电学性质,不但可以用作基于GaN的蓝色发光二极管的衬底材料,同时又是制作高温、高频、大功率电子器件的最佳材料之一,因此高质量、大直径SiC单晶的生长一直是材料研究领域的热点课题。目前美国的Cree公司在SiC单晶生长领域研发方面起步早、投入大,SiC单晶的直径达到4英寸,处于领先地位。我国在“十五”期间投入了一定的人力、物力进行了SiC单晶生长的研究,在生长2英寸SiC单晶的工作中取得了一定的成绩[1],但更大直径的SiC单晶生长技术进展缓慢,至今未见国内报道。而对…     

Phenothiazine-based covalent organic frameworks with low exciton binding energies for photocatalysis

Designing delocalized excitons with low binding energy (E_b) in organic semiconductors is urgently required for efficient photochemistry because the excitons in most organic materials are localized with a high E_b of >300 meV. In this work, we report the achievement of a low E_b of ∼50 meV by constructing phenothiazine-based covalent organic frameworks (COFs) with inherent crystallinity, porosity, chemical robustness, and feasibility of bandgap engineering. The low E_b facilitates effective exciton dissociation and thus promotes photocatalysis by using these COFs. As a demonstration, we subject these COFs to photocatalytic polymerization to synthesize polymers with remarkably high molecular weight without any requirement of the metal catalyst. Our results can facilitate the rational design of porous materials with low E_b for efficient photocatalysis.

We report the construction of phenothiazine-based covalent organic frameworks, which exhibited diverse structures, the feasibility of bandgap engineering, and unprecedented ultralow exciton binding energy of ∼50 meV for photocatalytic polymerization.