Mitochondrial dysfunction has been implicated in the development of heart failure. Oxidative metabolism in mitochondria is the main energy source of the heart, and the inability to generate and ...transfer energy has long been considered the primary mechanism linking mitochondrial dysfunction and contractile failure. However, the role of mitochondria in heart failure is now increasingly recognized to be beyond that of a failed power plant. In this Review, we summarize recent evidence demonstrating vicious cycles of pathophysiological mechanisms during the pathological remodeling of the heart that drive mitochondrial contributions from being compensatory to being a suicide mission. These mechanisms include bottlenecks of metabolic flux, redox imbalance, protein modification, ROS-induced ROS generation, impaired mitochondrial Ca2+ homeostasis, and inflammation. The interpretation of these findings will lead us to novel avenues for disease mechanisms and therapy.
This paper first proposes the discourse system of ideological and political education in colleges and universities, which mainly includes discourse goal innovation, discourse structure innovation, ...discourse paradigm innovation and discourse behavior innovation. Secondly, to facilitate the analysis and comparison of the data set, it is necessary to standardize various data and construct a similar relationship matrix based on the standardized data. Then, the correlation between teachers’ and students’ characteristics is incorporated to cluster the users to derive the user similarity and the final predicted rating of the Civic Education resources. Simulation experiments and statistical analysis validate the Kruskal algorithm-based example study of Civic Education discourse in colleges and universities. The results show that the measures of value perception and discourse power are in a reasonable interval, with a minimum value of 1 and a maximum value of 5, and the mean values are between 3.72 and 4.03, and the standard deviations are all greater than 0.75, reflecting the wide distribution of the samples, indicating that this study can improve the efficiency of the recommendation of Civic Education resources and the accuracy of discourse power analysis.
Alterations in cardiac energy metabolism contribute to the severity of heart failure. However, the energy metabolic changes that occur in heart failure are complex and are dependent not only on the ...severity and type of heart failure present but also on the co-existence of common comorbidities such as obesity and type 2 diabetes. The failing heart faces an energy deficit, primarily because of a decrease in mitochondrial oxidative capacity. This is partly compensated for by an increase in ATP production from glycolysis. The relative contribution of the different fuels for mitochondrial ATP production also changes, including a decrease in glucose and amino acid oxidation, and an increase in ketone oxidation. The oxidation of fatty acids by the heart increases or decreases, depending on the type of heart failure. For instance, in heart failure associated with diabetes and obesity, myocardial fatty acid oxidation increases, while in heart failure associated with hypertension or ischemia, myocardial fatty acid oxidation decreases. Combined, these energy metabolic changes result in the failing heart becoming less efficient (ie, a decrease in cardiac work/O
consumed). The alterations in both glycolysis and mitochondrial oxidative metabolism in the failing heart are due to both transcriptional changes in key enzymes involved in these metabolic pathways, as well as alterations in NAD redox state (NAD
and nicotinamide adenine dinucleotide levels) and metabolite signaling that contribute to posttranslational epigenetic changes in the control of expression of genes encoding energy metabolic enzymes. Alterations in the fate of glucose, beyond flux through glycolysis or glucose oxidation, also contribute to the pathology of heart failure. Of importance, pharmacological targeting of the energy metabolic pathways has emerged as a novel therapeutic approach to improving cardiac efficiency, decreasing the energy deficit and improving cardiac function in the failing heart.
Seasonal influenza still greatly threatens public health worldwide, leading to significant morbidity and mortality. Antiviral medications for influenza treatment are limited and accompanied by ...increased drug resistance. In severe influenza virus infection, hyperinflammation and hypoxia may be the significant threats associated with mortality, so the development of effective therapeutic methods to alleviate excessive inflammation while reducing viral damage is highly pursued. Here, a multifunctional MOF‐based nanohybrid of Cu─TCPP@Mn3O4 as a novel drug against influenza A virus infection (MOF = metal−organic framework; TCPP = tetrakis (4‐carboxyphenyl) porphyrin) is designed. Cu─TCPP@Mn3O4 exhibits potent inhibitory capability against influenza A virus infection in vitro and in vivo. The mechanism study reveals that Cu─TCPP@Mn3O4 inhibits the virus entry by binding to the HA2 subunit of influenza A virus hemagglutinin. In addition, the nanoparticles of Mn3O4 in Cu─TCPP@Mn3O4 can scavenge intracellular ROS with O2 generation to downregulate inflammatory factors and effectively inhibit cytokines production. By reconstructing the antioxidant microenvironment, Cu─TCPP@Mn3O4 features as a promising nanomedicine with anti‐inflammatory and anti‐viral synergistic effects.
A multifunctional MOF‐based nanohybrid of Cu─TCPP@Mn3O4 as a novel drug against influenza A virus infection is designed. Cu─TCPP@Mn3O4 exhibits potent inhibitory capability against influenza A virus infection in vitro and in vivo. By reconstructing the antioxidant microenvironment, Cu─TCPP@Mn3O4 features as a promising nanomedicine with anti‐viral, anti‐inflammatory, and anti‐oxidant synergistic effects.
Conventional lithium‐ion batteries (LIBs) with graphite anodes are approaching their theoretical limitations in energy density. Replacing the conventional graphite anodes with high‐capacity Si‐based ...anodes represents one of the most promising strategies to greatly boost the energy density of LIBs. However, the inherent huge volume expansion of Si‐based materials after lithiation and the resulting series of intractable problems, such as unstable solid electrolyte interphase layer, cracking of electrode, and especially the rapid capacity degradation of cells, severely restrict the practical application of Si‐based anodes. Over the past decade, numerous reports have demonstrated that polymer binders play a critical role in alleviating the volume expansion and maintaining the integrity and stable cycling of Si‐based anodes. In this review, the state‐of‐the‐art designing of polymer binders for Si‐based anodes have been systematically summarized based on their structures, including the linear, branched, crosslinked, and conjugated conductive polymer binders. Especially, the comprehensive designing of multifunctional polymer binders, by a combination of multiple structures, interactions, crosslinking chemistries, ionic or electronic conductivities, soft and hard segments, and so forth, would be promising to promote the practical application of Si‐based anodes. Finally, a perspective on the rational design of practical polymer binders for the large‐scale application of Si‐based anodes is presented.
Polymer binders play a crucial role in alleviating the volume expansion and maintaining the integrity and stable cycling of Si‐based anodes. This review presents the state‐of‐the‐art designing of polymer binders for Si‐based anodes based on the linear, branched, crosslinked, conjugated polymer structures. Besides, the multifunctional design of polymer binders for the practical application of Si‐based anodes has been discussed.
Novel targets for mitochondrial medicine Wang, Wang; Karamanlidis, Georgios; Tian, Rong
Science translational medicine,
2016-Feb-17, Letnik:
8, Številka:
326
Journal Article
Recenzirano
Odprti dostop
Mitochondria-classically viewed as the powerhouses of the cell-have taken center stage in disease pathogenesis and resolution. Mitochondrial dysfunction, which originates from primary defects within ...the organelle or is induced by environmental stresses, plays a critical role in human disease. Despite their central role in human health and disease, there are no approved drugs that directly target mitochondria. We present possible new druggable targets in mitochondrial biology, including protein modification, calcium ion (Ca(2+)) transport, and dynamics, as we move into a new era of mitochondrial medicine.
Enhanced ultraviolet radiation (UV) and elevated tropospheric ozone (O3) may individually cause reductions in the growth and productivity of important agricultural crops. However, research regarding ...their combined effects on important agricultural crops is still scarce, especially on changes in secondary metabolites and endogenous hormones, which are important protective substances and signal components that control plant responses to environment stresses. In this study, using an experimental setup of open top chambers, we monitored the responses of seed yield per plant, leaf secondary metabolites and leaf endogenous hormones under the stress of elevated O3 and enhanced UV radiation individually, as well as their combined stress. The results indicated that elevated O3 (110 ± 10 nmol mol-1 for 8 hours per day) and enhanced UV radiation (1.73 kJ h-1 m-2) significantly decreased seed yield per plant. Concentrations of rutin, queretin and total flavonoids were significantly increased under the elevated O3 treatment or the enhanced UV radiation treatment or the combination treatment at flowering and podding stages, and concentrations of rutin, queretin and total flavonoids showed significant correlations with seed yield per plant. Concentrations of ABA and IAA decreased under the three treatments. There was a significant positive correlation between the ABA concentration and seed yield and a negative correlation between the IAA concentration and seed yield. We concluded that the combined stress of elevated O3 and UV radiation significantly decreased seed yield per plant. Yield reduction was associated with changes in the concentrations of flavonoids, ABA and IAA in soybean leaves. The effects of the combined O3 and UV stress were always greater than those of the individual stresses alone.
A new type of molecularly imprinted polymer (MIP)-based room-temperature phosphorescence (RTP) optosensor was developed by anchoring the MIP layer on the surface of Mn-doped ZnS quantum dots (QDs) ...via a surface molecular imprinting process. The synergetic combination of the RTP property of the Mn-doped ZnS QDs and the merits of the surface imprinting polymers not only improves the RTP selectivity of the Mn-doped ZnS QDs but also makes the MIP-based RTP optosensor also applicable to selective detecting of those nonphosphorescent analytes without the need for any inducers and derivatization. The new MIP-based RTP sensing protocol was applied to detect trace pentachlorophenol (PCP) in water samples without the interference of autofluorescence and scattering light of matrixes. The detection limit for PCP was 86 nM, and the precision for five replicate detections of 0.4 μM PCP was 2.8% (relative standard deviation). The recovery of spiked PCP in river water samples ranged from 93% to 106%.
Leigh syndrome is a mitochondrial disease characterized by neurological disorders, metabolic abnormality and premature death. There is no cure for Leigh syndrome; therefore, new therapeutic targets ...are urgently needed. In Ndufs4-KO mice, a mouse model of Leigh syndrome, we found that Complex I deficiency led to declines in NAD
levels and NAD
redox imbalance. We tested the hypothesis that elevation of NAD
levels would benefit Ndufs4-KO mice. Administration of NAD
precursor, nicotinamide mononucleotide (NMN) extended lifespan of Ndufs4-KO mice and attenuated lactic acidosis. NMN increased lifespan by normalizing NAD
redox imbalance and lowering HIF1a accumulation in Ndufs4-KO skeletal muscle without affecting the brain. NMN up-regulated alpha-ketoglutarate (KG) levels in Ndufs4-KO muscle, a metabolite essential for HIF1a degradation. To test whether supplementation of KG can treat Ndufs4-KO mice, a cell-permeable KG, dimethyl ketoglutarate (DMKG) was administered. DMKG extended lifespan of Ndufs4-KO mice and delayed onset of neurological phenotype. This study identified therapeutic mechanisms that can be targeted pharmacologically to treat Leigh syndrome.
We identified a novel circovirus (human-associated circovirus 2 HuCV2) from the blood of 2 intravenous drug users in China who were infected with HIV-1, hepatitis C virus, or both. HuCV2 is most ...closely related to porcine circovirus 3. Our findings underscore the risk for HuCV2 and other emerging viruses among this population.
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