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The process of aging is characterized by structural degeneration and functional decline, as well as diminished adaptability and resistance. The aging kidney exhibits a variety of structural and functional impairments. In aging mice, thinning and graying of fur were observed, along with a significant increase in kidney indices compared to young mice. Biochemical indicators revealed elevated levels of creatinine, urea nitrogen and serum uric acid, suggesting impaired kidney function. Histological analysis unveiled glomerular enlargement and sclerosis, severe hyaline degeneration, capillary occlusion, lymphocyte infiltration, tubular and glomerular fibrosis, and increased collagen deposition. Observations under electron microscopy showed thickened basement membranes, altered foot processes, and increased mesangium and mesangial matrix. Molecular marker analysis indicated upregulation of aging-related ß-galactosidase, p16-INK4A, and the DNA damage marker γH2AX in the kidneys of aged mice. In metabolomics, a total of 62 significantly different metabolites were identified, and 10 pathways were enriched. We propose that citrulline, dopamine, and indoxyl sulfate have the potential to serve as markers of kidney damage related to aging in the future. Phosphoproteomics analysis identified 6656 phosphosites across 1555 proteins, annotated to 62 pathways, and indicated increased phosphorylation at the Ser27 site of Minichromosome maintenance complex component 2 (Mcm2) and decreased at the Ser284 site of heterogeneous nuclear ribonucleoprotein K (hnRNP K), with these modifications being confirmed by western blotting. The phosphorylation changes in these molecules may contribute to aging by affecting genome stability. Eleven common pathways were detected in both omics, including arginine biosynthesis, purine metabolism and biosynthesis of unsaturated fatty acids, etc., which are closely associated with aging and renal insufficiency.
Assuntos
Envelhecimento , Instabilidade Genômica , Rim , Componente 2 do Complexo de Manutenção de Minicromossomo , Animais , Envelhecimento/metabolismo , Envelhecimento/genética , Envelhecimento/patologia , Instabilidade Genômica/genética , Camundongos , Fosforilação , Rim/metabolismo , Rim/patologia , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Camundongos Endogâmicos C57BL , Masculino , Metabolômica/métodos , Dano ao DNA , MultiômicaRESUMO
For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order cycloaddition and catalytic asymmetric cycloaddition of BCBs have been long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions for the divergent synthesis of bridged bicyclic frameworks. The dppb ligand facilitates the formal (5+3) cycloaddition of BCBs and vinyl oxiranes, yielding valuable eight-membered ethers with bridged bicyclic scaffolds in 100% regioselectivity. The Cy-DPEphos ligand promotes selective hetero-[2σ+2σ] cycloadditions to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, the corresponding catalytic asymmetric synthesis of O-BCHeps with 94-99% ee has been achieved using chiral (S)-DTBM-Segphos, representing the first catalytic asymmetric cross-dimerization of two strained rings. The obtained O-BCHeps are promising bioisosteres for ortho-substituted benzenes.
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Photocatalysis is one of the effective ways to degrade pollutant antibiotics. Agar is used as the adsorption module to provide abundant pore structure. Carbon dots (CDs) are selected as light energy conversion components. Graphitic carbon nitride (g-C3N4) is used as the main material of the catalyst. Agar/CDs/g-C3N4-functionalized aerogel with a unique 3D pore structure is assembled. The Agar/CDs/g-C3N4 aerogel shows the highest photocurrent density, which is 3.7 times that of agar, 2.4 times that of 3-g-C3N4 and 1.6 times that of Agar/g-C3N4 aerogel. Compared with 3-g-C3N4 and Agar/g-C3N4 aerogel, which can completely remove AMX after 75 min, Agar/CDs/g-C3N4 aerogel can degrade amoxicillin (AMX) completely after 45 min of illumination. The reason is that Agar/CDs/g-C3N4 aerogel has a larger specific surface area, richer functional groups, a wider spectral range, higher photocurrent density and better carrier migration and separation efficiency. It is a good strategy with which to combine the effects of each component in the ternary system for the efficient photocatalysis of organic pollutants.
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Surface reconstruction of electrocatalysts is an effective strategy to modulate the space charge distribution to enhance the electrocatalytic activity. The p-n heterostructured FeP/CoP-2D octagonal nanoplates were successfully constructed by cation-exchange method. The space charge effect caused by the p-n heterojunction accelerated the electron transfer, optimized the electronic structure, and improved the activity of the active sites during the oxygen evolution reaction process. As a result, FeP/CoP-2D required only 247 mV overpotential to achieve a current density of 10 mA cm-2 with a Tafel slope as low as 68 mV dec-1. Density-functional theory calculations confirmed that the construction of p-n heterojunctions can enhance the adsorption of *OH in the active centers and optimize the Gibbs free energy of the OER reaction. This study provides an effective and feasible strategy for constructing p-n heterojunctions to modulate the space charge state for optimizing the OER performance of electrocatalysts.
RESUMO
The Belt and Road Initiative (BRI) is an open platform for international cooperation proposed by China to promote common global development and prosperity. The BRI can promote the optimal allocation of resources and promote in-depth cooperation in international trade. Meanwhile, it can establish a green supply chain cooperation network to help BRI countries achieve green transformation. BRI has made a notable contribution to the rapid growth of cross-border trade. However, it has also brought environmental impacts. Given that little attention has been paid to the trade-embodied particulate matter 2.5 related human health impacts (PM2.5-HHI) throughout the BRI, this study accounts for and traces the embodied PM2.5-HHI flows between the BRI countries and non-Belt and Road Initiative (non-BRI) countries. Moreover, this study also uncovers the critical socioeconomic drivers of PM2.5-HHI changes in BRI countries during 1990-2015, based on the multi-regional input-output based structural decomposition analysis (MRIO-SDA). Results show that, firstly, BRI countries had significantly increased their economic added value by exporting products to the non-BRI countries. They also have brought PM2.5-HHI to themselves. Secondly, the final demand of BRI countries was the largest potential driving force of PM2.5-HHI of BRI countries. Thirdly, the emission intensity change of BRI is the key socioeconomic factor for reducing PM2.5-HHI. While per capita final demand level change of BRI and production structure change of non-BRI are the key socioeconomic factors for increasing PM2.5-HHI. The study's findings on the one hand can help reduce the PM2.5-HHI and impacts of environmental pollution of BRI countries from a global perspective by providing scientific support. On the other hand, they can help provide relevant policy recommendations for the green transformation of BRI and the construction of green BRI.
Assuntos
Comércio , Internacionalidade , Humanos , China , Meio Ambiente , Material Particulado/análise , Desenvolvimento Econômico , Dióxido de Carbono/análiseRESUMO
In order to adapt to the rapid development of high-speed imaging technology in recent years, it is very important to develop scintillators with an ultrafast time response. Because of its radiation-induced ultrafast decay time, ZnO has become an important material for radiation detection and dosimetry. According to different detection sources and application scenarios, ZnO is used in various radiation detectors in different structures, including nanoarrays and nanocomposites. In this paper, the synthesis methods and research status of various nanostructured ZnO-based materials and their applications in the detection of high-energy rays (X-rays, γ-rays) and high-energy particles (α, ß and neutron) are reviewed. The performance discussion mainly includes spatial resolution, decay time and detection efficiency.
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Ochratoxin A (OTA) contamination in various agro-products poses a serious threat to the global food safety and human health, leading to enormous economic losses. Enzyme-mediated OTA degradation is an appealing strategy, and the search for more efficient enzymes is a prerequisite for achieving this goal. Here, a novel amidohydrolase, termed PwADH, was demonstrated to exhibit 7.3-fold higher activity than that of the most efficient OTA-degrading ADH3 previously reported. Cryo-electron microscopy structure analysis indicated that additional hydrogen-bond interactions among OTA and the adjacent residue H163, the more compact substrate-binding pocket, and the wider entry to the substrate-access cavity might account for the more efficient OTA-degrading activity of PwADH compared with that of ADH3. We conducted a structure-guided rational design of PwADH and obtained an upgraded variant, G88D, whose OTA-degrading activity was elevated by 1.2-fold. In addition, PwADH and the upgraded G88D were successfully expressed in the industrial yeast Pichia pastoris, and their catalytic activities were compared to those of their counterparts produced in E. coli, revealing the feasibility of producing PwADH and its variants in industrial yeast strains. These results illustrate the structural basis of a novel, efficient OTA-degrading amidohydrolase and will be beneficial for the development of high-efficiency OTA-degrading approaches.