The first endothelium-derived relaxing factor (EDRF) ever identified is a gasotransmitter, nitric oxide (NO). Recent studies have provided several lines of evidence to support the premise that ...hydrogen sulfide (H2S), another gasotransmitter, is a new EDRF. H2S production is catalyzed in mammalian cells by cystathionine β-synthase (CBS) and/or cystathionine γ-lyase (CSE). The expression of CSE proteins and the activity of CBS have been observed in vascular endothelial cells. A measurable amount of H2S is produced from endothelium upon muscarinic cholinergic stimulation. The endothelium-dependent vasorelaxation induced by H2S shares many common mechanistic traits with those of endothelium-derived hyperpolarizing factor (EDHF). Deficiency in CSE expression increases blood pressure in CSE knockout mice and significantly diminishes endothelium-dependent relaxation of resistance arteries. More extensive and mechanistic studies in the future will help to determine whether H2S is a new EDRF or the very EDHF.
To cultivate children's imagination, observation, thinking ability, and aesthetic consciousness, the questionnaire survey is adopted to analyze the design strategies and principles of children's ...picture books based on augmented reality (AR). Primarily, the related concepts and theories are expounded for the research content. Children in preschool aged 4-5 years are invited as primary participants in this work, and the psychological characteristics of the invited children are analyzed in depth. Then, a study is carried out on the existing AR children's picture books. The problems existing in the design of AR children's picture books are found, and then, related solutions are put forward based on the results of the questionnaire survey. Besides, a design is made on the strategies and interactive design principles of AR children's picture books on mobile terminals that are more in line with the needs of children. The results show that 41.07% of parents do not understand AR technology, and 37.5% of preschool children indicate that they do not operate mobile devices independently. However, they need the assistance of parents to use this kind of picture book. A total of 44.64% of parents believe that the main problem of AR picture books in the current market is the lack of interesting interaction. Given the above problems, five principles are proposed for the design of AR children's picture books based on mobile terminals, namely, easy operation principle, interesting principle, guiding principle, timely feedback principle, and safety principle. A set of universally applicable design methods are proposed for AR children's picture books based on mobile terminals, which provides certain theoretical guidance for the development of related types of products.
The nicotinamide adenine dinucleotide (NAD
)/reduced NAD
(NADH) and NADP
/reduced NADP
(NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous ...biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD
-consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics.
The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism.
Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD
precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.
The physiological and pathophysiological importance of endogenous hydrogen sulfide to cardiovascular health has been recognized in recent years. The signaling mechanisms underlying the multifaceted ...vascular effects of H2S, on the contrary, have been unclear. This article reviews recent literature on cellular and molecular events triggered or modulated by H2S in the vascular system over the period of 2009-2010.
H2S causes protein S-sulfhydration. The activation of ATP-sensitive K channels (KATP channels) by H2S likely occurs as the result of specific cysteine residues of KATP channel proteins being S-sulfhydrated. Produced in endothelial cells and inducing smooth muscle hyperpolarization, H2S appears to functioning as an endothelium-derived hyperpolarizing factor. The inhibition of phosphodiesterases by endogenous H2S is an additional exciting discovery, which offers answers for the differential vascular effects of this gasotransmitter due to the tissue-specific distribution of different isozymes of phosphodiesterases. Furthermore, endothelial cells and smooth muscle cells have opposite growth responses to H2S stimulation, involving the same sets of signaling molecules.
An array of signaling pathways in vascular tissues is enlisted by endogenous H2S. An insightful understanding of these signaling mechanisms would help elucidate the pathogenesis of selective cardiovascular diseases and develop related therapeutic interventions by targeting H2S metabolism.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
For many regenerative electrochemical energy‐conversion systems, hybrid electrocatalysts comprising transition metal (TM) oxides and heteroatom‐doped (e.g., nitrogen‐doped) carbonaceous materials are ...promising bifunctional oxygen reduction reaction/oxygen evolution reaction electrocatalysts, whose enhanced electrocatalytic activities are attributed to the synergistic effect originated from the TM–N–C active sites. However, it is still ambiguous which configuration of nitrogen dopants, either pyridinic or pyrrolic N, when bonded to the TM in oxides, predominately contributes to the synergistic effect. Herein, an innovative strategy based on laser irradiation is described to controllably tune the relative concentrations of pyridinic and pyrrolic nitrogen dopants in the hybrid catalyst, i.e., NiCo2O4 NPs/N‐doped mesoporous graphene. Comparative studies reveal the dominant role of pyridinic‐NCo bonding, instead of pyrrolic‐N bonding, in synergistically promoting reversible oxygen electrocatalysis. Moreover, density functional theory calculations provide deep insights into the corresponding synergistic mechanism. The optimized hybrid, NiCo/NLG‐270, manifests outstanding reversible oxygen electrocatalytic activities, leading to an overpotential different ΔE among the lowest value for highly efficient bifunctional catalysts. In a practical reversible Zn–air battery, NiCo/NLG‐270 exhibits superior charge/discharge performance and long‐term durability compared to the noble metal electrocatalysts.
An innovative strategy based on laser irradiation is developed to selectively regulate relative contents of pyridinic and pyrrolic nitrogen in NiCo2O4/N‐graphene hybrids. Strong chemical bonding forms between nitrogen and cobalt, and pyridinic‐NCo bonds, instead of pyrrolic‐NCo bonds, are identified to predominantly contribute to synergistic catalysis, leading to substantially enhanced oxygen electrocatalytic activities, outperforming a combination of benchmark noble metal catalysts.
In recent years, with the continuous development of serviceoriented computing technology, the industry has increasingly high quality requirements for service solving. A dynamic perceptual service ...composition framework is proposed for solving Web service problems. During the process, the user provides three aspects of information, including user context, user requests, and user preferences. The relevant elements in the problem are divided into multiple logical levels and processed layer by layer. The entire service process is represented through a directed graph, and specific business is represented using a vertex set. A forward step re-planning rule is established to skip business vertices. The experimental results showed that the research method had an error of only 0.071% in solving quality analysis at 20 business vertices, which was lower compared with other methods. In the multi concurrency tolerance test, the research method only experienced 5 crashes during a 500s runtime. In the analysis of packet loss rate during operation, when there was no network fluctuation, the packet loss rate of the research method fluctuated between 0.1% and 0.7%. The research method can provide service discovery results that are more in line with the actual needs and preferences, which can provide better solution results for service composition problems.
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