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AMP-activated protein kinase alpha 2 (AMPKα2) regulates energy metabolism, protein synthesis, and glucolipid metabolism myocardial cells. Ketone bodies produced by fatty acid ß-oxidation, especially ß-hydroxybutyrate, are fatty energy-supplying substances for the heart, brain, and other organs during fasting and long-term exercise. They also regulate metabolic signaling for multiple cellular functions. Lysine ß-hydroxybutyrylation (Kbhb) is a ß-hydroxybutyrate-mediated protein posttranslational modification. Histone Kbhb has been identified in yeast, mouse, and human cells. However, whether AMPK regulates protein Kbhb is yet unclear. Hence, the present study explored the changes in proteomics and Kbhb modification omics in the hearts of AMPKα2 knockout mice using a comprehensive quantitative proteomic analysis. Based on mass spectrometry (LC-MS/MS) analysis, the number of 1181 Kbhb modified sites in 455 proteins were quantified between AMPKα2 knockout mice and wildtype mice; 244 Kbhb sites in 142 proteins decreased or increased after AMPKα2 knockout (fold change >1.5 or <1/1.5, p < 0.05). The regulation of Kbhb sites in 26 key enzymes of fatty acid degradation and tricarboxylic acid cycle was noted in AMPKα2 knockout mouse cardiomyocytes. These findings, for the first time, identified proteomic features and Kbhb modification of cardiomyocytes after AMPKα2 knockout, suggesting that AMPKα2 regulates energy metabolism by modifying protein Kbhb.
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Ácido 3-Hidroxibutírico , Proteínas Quinases Ativadas por AMP , Miocárdio , Animais , Humanos , Camundongos , Ácido 3-Hidroxibutírico/química , Ácido 3-Hidroxibutírico/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Cromatografia Líquida , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Proteômica , Espectrometria de Massas em TandemRESUMO
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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The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94% yield and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.
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Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications.
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Exossomos , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Exossomos/metabolismo , Cordão Umbilical , Proteômica , Remodelação Vascular , Células-Tronco Mesenquimais/metabolismo , AortaRESUMO
The application of LuBO3:Ce3+ (LBO:Ce) crystal as an excellent scintillation material has been limited due to its poor phase stability at high temperature or high pressure, so improving the phase stability is essential for promoting its development. Ga stabilized LuBO3:Ce3+ (LGBO:Ce) is synthesized by solid-state reaction at 1200 °C. Powder X-ray diffraction patterns and Raman spectra at ambient pressure show that all the samples are pure calcite phase. In situ high-pressure synchrotron radiation XRD patterns illustrate that calcite phase LGBO:Ce exhibits more excellent phase stability than that of LBO:Ce under high pressure due to the superior compressibility of the [GaO6] octahedral unit. The optical band gap of LGBO decreases from 5.58 to 4.64 eV after introducing 10% Ga, which leads to the decreased nonradiative transition and about double luminescence intensity as expected. More interestingly, the charge transition from O2- to Ce4+ is observed at about 290 nm in the absorption spectra. The X-ray photoelectron spectroscopy spectra indicate the ratio of Ce4+/Ce3+ increases with increasing concentration of Ga3+, which can be attributed to the variation of energy separation between the 4f ground state of Ce3+ and the Fermi energy level position. In contrast to the enhancement of PL intensity, the integrated X-ray excited luminescence intensity decreases after Ga3+ incorporation attributing to the result of both decreased effective atomic number and ionization energy between 5d1 level and conduction band. The thermal luminescence spectra show that after the incorporation of Ga3+ the oxygen vacancy and intrinsic defects in LBO remain unchanged but that the concentration of oxygen vacancy significantly reduces. The mechanism of Ga3+ incorporation on phase stability and luminescence properties of LBO:Ce has been proposed and discussed systematically.
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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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Petroleum pollution has become a prominent global environmental problem, restricting the coordinated development of the economy and the ecological environment. Although bioremediation has the advantages of low carbon, high efficiency, and safety, the complexity and severity of the pollution makes it difficult to achieve the remediation purpose with a single bioremediation. Ecological remediation based on bioremediation can integrate carbon neutrality and ecological environmental protection, synergistically promote pollution reduction and carbon reduction, ensure the sustainability of soil and sediment to fulfil ecosystem service functions, and ultimately achieve soil health and sediment health. Therefore, the transition from bioremediation to ecological restoration is the optimal choice for environmental management and ecosystem maintenance at this stage. Here, we first analyzed the micro-removal mechanism of petroleum hydrocarbons in different bioremediation techniques and discussed the types and characteristics of different bioremediation techniques from an ecological point of view. Based on this, the necessity of bioremediation for ecological restoration was analyzed in detail. Finally, a reasonable outlook on the development of ecological remediation is given to provide theoretical support for optimizing ecological remediation of petroleum pollution.
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Aging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.
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Bacterial communities are highly sensitive to environmental changes, but their metabolic functions may be convergent under similar ecological conditions. In order to test this environmental attribute of the bacterial community and verify the feasibility in using the bacterial metabolic data to divide functional units at the river basin scale, the surface sediments in three continuous spatial units of the main stream (MS), left tributary (LT), and right tributary (RT) of the Duliujian River basin were selected as the research objects. Therefore, 16S rDNA high-throughput sequencing and the PICRUSt platform were used to analyze the bacterial diversity and metabolic function of sediments in different units. The results showed that there were no significant differences for the Shannon and Simpson indices between the different river channels (P>0.05); however, the bacterial diversity indices of Chao1, ACE, Observed_species, and PD_whole_tree of LT and RT were significantly higher than those of the MS (P<0.05). Moreover, the dominant bacterial phyla were not significantly different among the different river channels. In the present study, a total of 41 metabolic pathways were predicted based on the KEGG database, among which 34 metabolic pathways such as membrane transport, amino acid metabolism, and carbohydrate metabolism were significantly different. The functional metabolic abundance was higher in MS than that in RT and LT (P<0.05); however, there was no significant difference between those of RT and LT (P>0.05). Except for exchangeable phosphorus and nitrate nitrogen, there were no significant differences in other physicochemical properties among the different river channels (P>0.05). Furthermore, pH and iron/aluminum-phosphorus were found to significantly affect the bacterial structure, and SOM and TN were found to significantly affect the bacterial metabolic function. Overall, the sediments of MS and tributaries (LT and RT) of the river were clearly divided into level-1 and level-2 groups, indicating that the metabolic abundance of the bacterial community can be used as the key indicator in the division of functional units at the river basin scale. This study provided a theoretical basis and technical support for ecological functional division and management in coastal river basins.
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Bactérias , Rios , Bactérias/genética , DNA Ribossômico , Nitrogênio , Fósforo , Rios/microbiologiaRESUMO
Both sodium alginate and polyethyleneimine (PEI) have a good ability to adsorb heavy metal ions. PEI and sodium alginate were used as important precursors to synthesize positively charged carbon nanoparticles (p-CNDs) with hydroxyl and carboxyl, and negatively charged carbon nanoparticles (n-CNDs) with amino, respectively. The carbon nanoparticles (CNDs) aerogel with a large specific surface area and rich functional groups were constructed by self-assembled p-CNDs and n-CNDs via electrostatic attraction for adsorption of heavy metal ions in water. The results show that CNDs aerogel has good adsorption properties for Pb2+ (96%), Cu2+ (91%), Co2+ (86%), Ni2+ (82%), and Cd2+ (78%). Furthermore, the fluorescence emission intensity of CNDs aerogel will gradually decrease with the increase in the adsorption rate, indicating that it can detect the adsorption process synchronously. In addition, the cytotoxicity test reveals that CNDs have good biocompatibility and will not cause secondary damage to biological cells.
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Carbon dots (CDs) as new fluorescent materials with excellent fluorescence properties have shown enormous potential applications, especially in anticounterfeiting and cell imaging. Herein, nitrogen-doped CDs (NCDs) with excellent biocompatibility were prepared by a simple thermal sintering method. An extremely large red shift (â¼130 nm) of the emission peak was observed when the excitation wavelength changes from 355 to 550 nm, indicating that NCDs are excellent fluorescent labeling materials for multiple cell imaging. On the other hand, NCDs showed obvious changes of emission intensity and peak position when the temperature increased from 223 to 323 K and the pH values changed from 1 to 13, respectively, which has been demonstrated by the "horse" pattern printed with NCD water-soluble fluorescent inks. The nontoxic NCDs dispersed in a multiple matrix are highly sensitive to excitation wavelength, temperature, and pH, indicating their great potential application in multiple anticounterfeiting and multiple cell imaging.