3D porous carbon is successfully fabricated from lotus leaves, an abundant and renewable biomass, via a facile and easy-scale up route of carbonization and successive activation by mechanically ...mixing with KOH. The as-prepared carbon possesses high surface area (3601 m2/g), hierarchical porous structure with interconnected micro/meso/macropores and good level of O–N–S heteroatoms doping. These admirable features endow beneficial multiple synergistic effects for high-performance supercapacitor electrode. The as-obtained carbon exhibit an ultra-high specific capacitance of 523 F/g at 1 A/g in a three-electrode system and 294 F/g at 1.0 A/g in a two-electrode system in 6 mol/L KOH electrolyte with high rate performance of ~85% retention from 1 to 10 A/g and outstanding cycling stability of ~99% capacitance retention after 10000 cycles. These values indicate a high-performance biomass-derived carbon as supercapacitor electrode and may boost the large-scale application of 3D porous carbons doped by heteroatoms for energy storage.
•O–N–S self-doping hierarchical porous carbon was fabricated from lotus leaves.•A specific capacitance of 523 F/g at 1 A/g was achieved in three-electrode system.•A specific capacitance of 294 F/g at 1 A/g was measured in a two-electrode system.•High rate capability of 85% and recyclability of 99% were obtained.•The high performance was associated with the natural features of lotus leaves.
Heart failure is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD+ levels and NAD+-mediated ...deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 deficient mouse line that is sensitive to stress, we found mitochondrial protein hyperacetylation coupled with reduced Sirt3 and NAD+ levels in the heart before stress, suggesting that the KLF4-deficient heart is predisposed to NAD+-associated defects. Further, we demonstrated that short-term administration of Nicotinamide Mononucleotide (NMN) successfully protected the mutant mice from pressure overload-induced heart failure. Mechanically, we showed that NMN preserved mitochondrial ultrastructure, reduced ROS and prevented cell death in the heart. In cultured cardiomyocytes, NMN treatment significantly increased long-chain fatty acid oxidation despite no direct effect on pyruvate oxidation. Collectively, these results provide cogent evidence that hyperacetylation of mitochondrial proteins is critical in the pathogenesis of cardiac disease and that administration of NMN may serve as a promising therapy.
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•Cardiac deficiency of KLF4 results in hyperacetylation of mitochondrial proteins.•Hyperacetylation impairs mitochondria and predisposes heart vulnerable to stress.•NMN normalizes acetylation, improves FAO, and reduces stress-induced damage.•Administration of NMN rescues stress-induced heart failure.
In this work, a novel impedimetric immunosensor was developed based on electrophoretic deposition of polymeric self-assembled nanoparticles for the sensitive determination of carcino-embryonic ...antigen (CEA). Biocompatible polymeric nanoparticles γ-PGA-DA@CS were prepared by self-assembly of chitosan (CS) and dopamine modified poly(γ-glutamic acid) (γ-PGA-DA) under mild conditions. A dense and nanostructured nanoparticles film was obtained on the electrode surface by electrophoretic deposition of γ-PGA-DA@CS nanoparticles. Gold nanoparticles (Au NPs) were then tightly anchored on γ-PGA-DA@CS film with homogeneous dispersion due to numerous exposed dopamine adhesive dots present on the surface of γ-PGA-DA@CS. The obtained Au/γ-PGA-DA@CS nanocomposite film not only increases the electrode surface area in nanoscale dimension, but also provides a highly stable and biocompatible matrix for the convenient conjugation of antibody, thus providing a high-efficiency immunoassay platform. Monoclonal antibodies to carcinoembryonic antigen (CEA-Ab) were effectively immobilized on the Au/γ-PGA-DA@CS film and a label-free impedimetric immunosensor was fabricated successfully as the ultimate goal. Under optimal conditions, the resultant immunosensor exhibited a wide linear range from 2.0×10–14gmL−1 to 2.0×10−8gmL−1 for the detection of CEA with a low detection limit of 10fgmL−1. To the best of our knowledge, this was the lowest detection limit compared with other counterparts of label-free impedimetric immunosensors. Moreover, the immunosensor showed high specificity, good stability and satisfactory reproducibility. As a proof of concept, the proposed strategy provided a promising and versatile platform for clinical immunoassay of other tumor markers and biomolecules.
•Polymeric self-assembled nanoparticles film serves as an immunosensor platform for the first time.•The bio-polymeric nanoparticles are prepared by simply self-assembly of two polyelectrolytes under mild conditions.•A dense nanostructured nanoparticles film is obtained via electrophoretic deposition of polymeric nanoparticles.•Large amounts of Au nanoparticles are tightly anchored and well- distributed on the surface polymeric nanoparticles film.•The prepared immunosensor shows much lower LOD and wider detection range towards carcino-embryonic antigen than other reported counterparts.
Introducing lysozyme (Lys) to dopamine-modified poly (γ-glutamic acid) (PGA-DA), the self-assembled colloidal nanoparticles (Lys/PGA-DA) were obtained through the electrostatic, hydrogen bonding and ...hydrophobic interactions. After mixing vigorously colloidal nanoparticles and white oil, o/w gel-like emulsion formed. The influences of ionic strength on the properties and emulsifying performances of colloidal nanoparticles and the activity of Lys in emulsions were investigated in detail. Scanning electron microscopy (SEM) characterization and rheological measurements demonstrated that emulsifying properties of colloidal nanoparticles were significantly improved with increasing salt concentration. Moreover, fluorescence and circular dichroism (CD) measurements showed that the addition of salt might induce conformational changes of Lys in colloidal nanoparticles resulting in a more ordered secondary structure, thereby leading to an increase in enzyme activity. In vitro cytotoxicity of emulsions revealed that emulsions showed a low cytotoxicity and a high bioactivity. All results verified that the obtained emulsion could have potential application in food, pharmaceutical, and cosmetic fields.
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Necrotizing fasciitis is a rapid and severe soft tissue infection that targets subcutaneous fat tissue, muscle, and fascia. This study compares the clinical outcomes of vacuum-assisted closure (VAC) ...versus conventional dressing on necrotizing fasciitis.
We systematically searched Embase, Cochrane, and PubMed for clinical trials (published between January 1, 1995 and September 30, 2021), which compared VAC with conventional dressing for necrotizing fasciitis. The mortality rate of necrotizing fasciitis was the primary outcome of this study. The number of debridements, the total length of hospital stay, and the complication rate were secondary outcomes. A random effects model assessed all pooled data.
A total of 230 identified studies and seven controlled clinical trials met the inclusion criteria and were included in this analysis (n = 249 participants). Compared to the conventional dressing, patients treated with VAC had a significantly lower mortality rate OR = 0.27, 95% CI (0.09, 0.87) (P = 0.03). Total length of hospital stays MD = 8.46, 95% CI (- 0.53, 17.45) (P = 0.07), number of debridements MD = 0.86, 95% CI (- 0.58, 2.30) (P = 0.24), and complication rate OR = 0.64, 95% CI (0.07, 5.94) (P = 0.69) were not significant. These results did not show significant differences between both groups treated with VAC or conventional treatment.
VAC could significantly decrease the death rate compared to conventional dressing. No significant impacts were found on the number of debridements, the total length of hospital stay, and the complication rate in this study. Level of evidence Level-III. Registration Research Registry (reviewregistry1246).
Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous ...studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown. We demonstrate that treatment with the BET bromodomain inhibitor JQ1 has therapeutic effects during severe, preestablished HF from prolonged pressure overload, as well as after a massive anterior myocardial infarction in mice. Furthermore, JQ1 potently blocks agonist-induced hypertrophy in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Integrated transcriptomic analyses across animal models and human iPSC-CMs reveal that BET inhibition preferentially blocks transactivation of a common pathologic gene regulatory program that is robustly enriched for NFκB and TGF-β signaling networks, typified by innate inflammatory and profibrotic myocardial genes. As predicted by these specific transcriptional mechanisms, we found that JQ1 does not suppress physiological cardiac hypertrophy in a mouse swimming model. These findings establish that pharmacologically targeting innate inflammatory and profibrotic myocardial signaling networks at the level of chromatin is effective in animal models and human cardiomyocytes, providing the critical rationale for further development of BET inhibitors and other epigenomic medicines for HF.
Nonischemic cardiomyopathy (NICM) resulting from long-standing hypertension, valvular disease, and genetic mutations is a major cause of heart failure worldwide. Recent observations suggest that ...myeloid cells can impact cardiac function, but the role of tissue-intrinsic vs. tissue-extrinsic myeloid cells in NICM remains poorly understood. Here, we show that cardiac resident macrophage proliferation occurs within the first week following pressure overload hypertrophy (POH; a model of heart failure) and is requisite for the heart’s adaptive response. Mechanistically, we identify Kruppel-like factor 4 (KLF4) as a key transcription factor that regulates cardiac resident macrophage proliferation and angiogenic activities. Finally, we show that blood-borne macrophages recruited in late-phase POH are detrimental, and that blockade of their infiltration improves myocardial angiogenesis and preserves cardiac function. These observations demonstrate previously unappreciated temporal and spatial roles for resident and nonresident macrophages in the development of heart failure.
It is widely recognized that inflammation plays a critical role in cardiac hypertrophy and heart failure. However, clinical trials targeting cytokines have shown equivocal effects, indicating the ...need for a deeper understanding of the precise role of inflammation and inflammatory cells in heart failure. Leukocytes from human subjects and a rodent model of heart failure were characterized by a marked reduction in expression of Klf2 mRNA. Using a mouse model of angiotensin II-induced nonischemic cardiac dysfunction, we showed that neutrophils played an essential role in the pathogenesis and progression of heart failure. Mechanistically, chronic angiotensin II infusion activated a neutrophil KLF2/NETosis pathway that triggered sporadic thrombosis in small myocardial vessels, leading to myocardial hypoxia, cell death, and hypertrophy. Conversely, targeting neutrophils, neutrophil extracellular traps (NETs), or thrombosis ameliorated these pathological changes and preserved cardiac dysfunction. KLF2 regulated neutrophil activation in response to angiotensin II at the molecular level, partly through crosstalk with HIF1 signaling. Taken together, our data implicate neutrophil-mediated immunothrombotic dysregulation as a critical pathogenic mechanism leading to cardiac hypertrophy and heart failure. This neutrophil KLF2-NETosis-thrombosis mechanism underlying chronic heart failure can be exploited for therapeutic gain by therapies targeting neutrophils, NETosis, or thrombosis.
Oxygen delivery by Hb is essential for vertebrate life. Three amino acids in Hb are strictly conserved in all mammals and birds, but only two of those, a His and a Phe that stabilize the heme moiety, ...are needed to carry O ₂. The third conserved residue is a Cys within the β-chain (βCys93) that has been assigned a role in S-nitrosothiol (SNO)-based hypoxic vasodilation by RBCs. Under this model, the delivery of SNO-based NO bioactivity by Hb redefines the respiratory cycle as a triune system (NO/O ₂/CO ₂). However, the physiological ramifications of RBC-mediated vasodilation are unknown, and the apparently essential nature of βCys93 remains unclear. Here we report that mice with a βCys93Ala mutation are deficient in hypoxic vasodilation that governs blood flow autoregulation, the classic physiological mechanism that controls tissue oxygenation but whose molecular basis has been a longstanding mystery. Peripheral blood flow and tissue oxygenation are decreased at baseline in mutant animals and decline excessively during hypoxia. In addition, βCys93Ala mutation results in myocardial ischemia under basal normoxic conditions and in acute cardiac decompensation and enhanced mortality during transient hypoxia. Fetal viability is diminished also. Thus, βCys93-derived SNO bioactivity is essential for tissue oxygenation by RBCs within the respiratory cycle that is required for both normal cardiovascular function and circulatory adaptation to hypoxia.
Significance Oxygen delivery by RBC Hb is essential for life. Just three amino acids in Hb are conserved in all mammals and birds, but only two of those are required to carry oxygen. The third, a Cys within the β-chain, βCys93, has been assigned a role in carrying nitric oxide, which mediates vasodilation. However, the physiological importance of RBC-mediated vasoregulation is unknown. We show that blood flow and tissue oxygenation are markedly impaired in mice with a βCys93Ala mutation. The βCys93Ala mutation also results in myocardial ischemia, cardiac decompensation, and enhanced mortality. These findings support a new view of the respiratory cycle wherein, remarkably, RBCs regulate blood flow and (βCys93NO)-Hb is necessary for adequate tissue oxygenation and normal cardiovascular function.
An oil-in-water (O/W) Pickering emulsion catalysis system was prepared using a self-assembled of lipase/chitosan nanoparticles (CRL/CS NPs). The CRL/CS NPs functioned as both a stabilizer and a ...catalyst, and every droplet of the emulsion was used as a microreactor for the reactants in the oil phase. Due to an adequate oil–water interface for the “lid” opening of lipase and rapid mass transfer in the CRL/CS NPs, the Pickering emulsion exhibited excellent enzymatic activity toward the hydrolysis of olive oil, achieving 72.80% and 99.62% hydrolysis rates after 15 min and 120 min, respectively. Immobilizing lipase in the self-assembled CS NPs endowed the lipase with exceptional recyclability and provided a shield to protect the enzyme from deactivation.
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