Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 421
Filtrar
1.
Proc Natl Acad Sci U S A ; 120(22): e2220148120, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37216506

RESUMO

Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5'UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5'UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5'UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5'UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Regiões 5' não Traduzidas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Cromatografia Líquida , Proteína do X Frágil da Deficiência Intelectual/genética , Biossíntese de Proteínas , Espectrometria de Massas em Tandem
2.
Small ; 20(26): e2311130, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38247198

RESUMO

Nuclear energy holds great potential to facilitate the global energy transition and alleviate the increasing environmental issues due to its high energy density, stable energy output, and carbon-free emission merits. Despite being limited by the insufficient terrestrial uranium reserves, uranium extraction from seawater (UES) can offset the gap. However, the low uranium concentration, the complicated uranium speciation, the competitive metal ions, and the inevitable marine interference remarkably affect the kinetics, capacity, selectivity, and sustainability of UES materials. To date, massive efforts have been made with varying degrees of success to pursue a desirable UES performance on various nanomaterials. Nevertheless, comprehensive and systematic coverage and discussion on the emerging UES materials presenting the fast-growing progress of this field is still lacking. This review thus challenges this position and emphatically focuses on this topic covering the current mainstream UES technologies with the emerging UES materials. Specifically, this review elucidates the causality between the physiochemical properties of UES materials induced by the intellectual design strategies and the UES performances and further dissects the relationships of materials-properties-activities and the corresponding mechanisms in depth. This review is envisaged to inspire innovative ideas and bring technical solutions for developing technically and economically viable UES materials.

3.
Strahlenther Onkol ; 200(6): 535-543, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453699

RESUMO

PURPOSE: Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues. METHODS: The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated. RESULTS: Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells. CONCLUSION: Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN.


Assuntos
Apigenina , Glioma , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos Nus , MicroRNAs , PTEN Fosfo-Hidrolase , Tolerância a Radiação , Animais , MicroRNAs/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Apigenina/farmacologia , Apigenina/uso terapêutico , PTEN Fosfo-Hidrolase/genética , Camundongos , Glioma/radioterapia , Glioma/patologia , Glioma/genética , Glioma/tratamento farmacológico , Tolerância a Radiação/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Transdução de Sinais/efeitos dos fármacos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Radiossensibilizantes/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C
4.
Theor Appl Genet ; 137(6): 119, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709271

RESUMO

KEY MESSAGE: A candidate gene TaSP1 related to spike shape was cloned, and the gene-specific marker was developed to efficiently track the superior haplotype in common wheat. Spike shape, an important factor that affects wheat grain yield, is mainly defined by spike length (SPL), spikelet number (SPN), and compactness. Zhoumai32 mutant 1160 (ZM1160), a mutant obtained from ethyl methane sulfonate (EMS) treatment of hexaploid wheat variety Zhoumai32, was used to identify and clone the candidate gene that conditioned the spike shape. Genetic analysis of an F2 population derived from a cross of ZM1160 and Bainong207 suggested that the compact spike shape in ZM1160 was controlled by a single recessive gene, and therefore, the mutated gene was designated as Tasp1. With polymorphic markers identified through bulked segregant analysis (BSA), the gene was mapped to a 2.65-cM interval flanked by markers YZU0852 and MIS46239 on chromosome 7D, corresponding to a 0.42-Mb physical interval of Chinese spring (CS) reference sequences (RefSeq v1.0). To fine map TaSP1, 15 and seven recombinants were, respectively, screened from 1599 and 1903 F3 plants derived from the heterozygous F2 plants. Finally, TaSP1 was delimited to a 21.9 Kb (4,870,562 to 4,892,493 bp) Xmis48123-Xmis48104 interval. Only one high-confidence gene TraesCS7D02G010200 was annotated in this region, which encodes an unknown protein with a putative vWA domain. Quantitative reverse transcription PCR (qRT-PCR) analysis showed that TraesCS7D02G010200 was mainly expressed in the spike. Haplotype analysis of 655 wheat cultivars using the candidate gene-specific marker Xg010200p2 identified a superior haplotype TaSP1b with longer spike and more spikelet number. TaSP1 is beneficial to the improvement in wheat spike shape.


Assuntos
Clonagem Molecular , Mutação , Triticum , Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Metanossulfonato de Etila , Genes de Plantas , Marcadores Genéticos , Haplótipos , Fenótipo , Triticum/genética , Triticum/crescimento & desenvolvimento
5.
Nucleic Acids Res ; 50(8): 4601-4615, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35466371

RESUMO

Site-specific incorporation of distinct non-canonical amino acids into proteins via genetic code expansion requires mutually orthogonal aminoacyl-tRNA synthetase/tRNA pairs. Pyrrolysyl-tRNA synthetase (PylRS)/tRNAPyl pairs are ideal for genetic code expansion and have been extensively engineered for developing mutually orthogonal pairs. Here, we identify two novel wild-type PylRS/tRNAPyl pairs simultaneously present in the deep-rooted extremely halophilic euryarchaeal methanogen Candidatus Methanohalarchaeum thermophilum HMET1, and show that both pairs are functional in the model halophilic archaeon Haloferax volcanii. These pairs consist of two different PylRS enzymes and two distinct tRNAs with dissimilar discriminator bases. Surprisingly, these two PylRS/tRNAPyl pairs display mutual orthogonality enabled by two unique features, the A73 discriminator base of tRNAPyl2 and a shorter motif 2 loop in PylRS2. In vivo translation experiments show that tRNAPyl2 charging by PylRS2 is defined by the enzyme's shortened motif 2 loop. Finally, we demonstrate that the two HMET1 PylRS/tRNAPyl pairs can simultaneously decode UAG and UAA codons for incorporation of two distinct noncanonical amino acids into protein. This example of a single base change in a tRNA leading to additional coding capacity suggests that the growth of the genetic code is not yet limited by the number of identity elements fitting into the tRNA structure.


Assuntos
Aminoacil-tRNA Sintetases , Euryarchaeota , Aminoacil-tRNA Sintetases/metabolismo , Lisina/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Código Genético , Euryarchaeota/genética , Aminoácidos/genética
6.
Angew Chem Int Ed Engl ; 63(11): e202319370, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38224011

RESUMO

Single atom catalysts with defined local structures and favorable surface microenvironments are significant for overcoming slow kinetics and accelerating O2 electroreduction. Here, enriched tip-like FeN4 sites (T-Fe SAC) on spherical carbon surfaces were developed to investigate the change in surface microenvironments and catalysis behavior. Finite element method (FEM) simulations, together with experiments, indicate the strong local electric field of the tip-like FeN4 and the more denser interfacial water layer, thereby enhancing the kinetics of the proton-coupled electron transfer process. In situ spectroelectrochemical studies and the density functional theory (DFT) calculation results indicate the pathway transition on the tip-like FeN4 sites, promoting the dissociation of O-O bond via side-on adsorption model. The adsorbed OH* can be facilely released on the curved surface and accelerate the oxygen reduction reaction (ORR) kinetics. The obtained T-Fe SAC nanoreactor exhibits excellent ORR activities (E1/2 =0.91 V vs. RHE) and remarkable stability, exceeding those of flat FeN4 and Pt/C. This work clarified the in-depth insights into the origin of catalytic activity of tip-like FeN4 sites and held great promise in industrial catalysis, electrochemical energy storage, and many other fields.

7.
J Bacteriol ; 205(2): e0038522, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36695595

RESUMO

The cotranslational incorporation of pyrrolysine (Pyl), the 22nd proteinogenic amino acid, into proteins in response to the UAG stop codon represents an outstanding example of natural genetic code expansion. Genetic encoding of Pyl is conducted by the pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA, tRNAPyl. Owing to the high tolerance of PylRS toward diverse amino acid substrates and great orthogonality in various model organisms, the PylRS/tRNAPyl-derived pairs are ideal for genetic code expansion to insert noncanonical amino acids (ncAAs) into proteins of interest. Since the discovery of cellular components involved in the biosynthesis and genetic encoding of Pyl, synthetic biologists have been enthusiastic about engineering PylRS/tRNAPyl-derived pairs to rewrite the genetic code of living cells. Recently, considerable progress has been made in understanding the molecular phylogeny, biochemical properties, and structural features of the PylRS/tRNAPyl pair, guiding its further engineering and optimization. In this review, we cover the basic and updated knowledge of the PylRS/tRNAPyl pair's unique characteristics that make it an outstanding tool for reprogramming the genetic code. In addition, we summarize the recent efforts to create efficient and (mutually) orthogonal PylRS/tRNAPyl-derived pairs for incorporation of diverse ncAAs by genome mining, rational design, and advanced directed evolution methods.


Assuntos
Aminoacil-tRNA Sintetases , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/genética , Aminoacil-tRNA Sintetases/metabolismo , Código Genético , RNA de Transferência/genética , Aminoácidos/metabolismo , Methanosarcina/genética
8.
J Biol Chem ; 298(11): 102521, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36152750

RESUMO

The pyrrolysyl-tRNA synthetase (PylRS) facilitates the cotranslational installation of the 22nd amino acid pyrrolysine. Owing to its tolerance for diverse amino acid substrates, and its orthogonality in multiple organisms, PylRS has emerged as a major route to install noncanonical amino acids into proteins in living cells. Recently, a novel class of PylRS enzymes was identified in a subset of methanogenic archaea. Enzymes within this class (ΔPylSn) lack the N-terminal tRNA-binding domain that is widely conserved amongst PylRS enzymes, yet remain active and orthogonal in bacteria and eukaryotes. In this study, we use biochemical and in vivo UAG-readthrough assays to characterize the aminoacylation efficiency and substrate spectrum of a ΔPylSn class PylRS from the archaeon Candidatus Methanomethylophilus alvus. We show that, compared with the full-length enzyme from Methanosarcina mazei, the Ca. M. alvus PylRS displays reduced aminoacylation efficiency but an expanded amino acid substrate spectrum. To gain insight into the evolution of ΔPylSn enzymes, we performed molecular phylogeny using 156 PylRS and 105 pyrrolysine tRNA (tRNAPyl) sequences from diverse archaea and bacteria. This analysis suggests that the PylRS•tRNAPyl pair diverged before the evolution of the three domains of life, placing an early limit on the evolution of the Pyl-decoding trait. Furthermore, our results document the coevolutionary history of PylRS and tRNAPyl and reveal the emergence of tRNAPyl sequences with unique A73 and U73 discriminator bases. The orthogonality of these tRNAPyl species with the more common G73-containing tRNAPyl will enable future efforts to engineer PylRS systems for further genetic code expansion.


Assuntos
Aminoacil-tRNA Sintetases , Archaea , Código Genético , Lisina , Aminoacil-tRNA Sintetases/metabolismo , Archaea/enzimologia , Archaea/genética , Lisina/análogos & derivados , Lisina/genética , Methanosarcina , RNA de Transferência/genética
9.
Small ; 19(2): e2205257, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36344428

RESUMO

Nickel based materials are promising electrocatalysts to produce hydrogen from water in alkaline media. However, the stability is of great challenge, limiting its practical material functions. Herein, a new technique for electro-deposition flower-like NiCo2 S4 nanosheets on carbon-cloth (CC@NiCo2 S4 ) is proposed for energy-saving production of H2 from water/methanol coelectrolysis at high current density by constructing array architectures and regulating surface magnetism. The optimized and fine-tuned magnetism on the surface of the electrochemical in situ grown CC@NiCo2 S4 nanosheet array result in (0 1 -1) surface universally exposed, high catalytic activity for methanol electrooxidation, and long-term stability at high current density. X-ray photoelectron spectroscopy in combination of density functional theory calculations confirm the valence electron states and spin of d electrons for the surface of NiCo2 S4 , which enhance the surface stability of catalysts. This technology may be utilized to alter the surface magnetism and increase the stability of Ni-based electrocatalytic materials in general.

10.
Mol Cell Biochem ; 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773303

RESUMO

High levels of YAP1 and ferroptosis activation in castration-resistant prostate cancer (CRPC) can inhibit CRPC progression and improve its sensitivity toward chemotherapeutics drugs. However, whether YAP1 regulates ferroptosis in CRPC cells and the underlying mechanisms are unknown. The protein levels of YAP1, SLC1A5, and GLS1 in benign prostatic hyperplasia (BPH), prostate cancer (PCa) that did not progress to CRPC, and CRPC tissue samples were evaluated using western blotting. In PC-3 and DU-145 cells, YAP1 overexpression vector, small-interfering RNA, specific inhibitor verteporfin, ferroptosis-inducer RSL3, SLC1A5-inhibitor V-9302, and GLS1-inhibitor CB-839 were used. Immunofluorescence, flow cytometry, dual-luciferase reporter gene, and related kits were used to investigate the effect of YAP1 on the ferroptosis activity in CRPC cells and its underlying mechanisms. YAP1 promoted extracellular glutamine uptake and subsequent production of glutamate and glutathione (GSH), and increases the GPX4 activity. For the activation of ferroptosis by RSL3, YAP1 decreased the levels of reactive oxygen species, malondialdehyde, and lipid peroxidation, and the proportion of dead cells. Mechanistically, YAP1 promoted the expression of SCL1A5 and GLS1 and further increased the GSH levels and GPX4 activity. Thus, inhibiting SLC1A5 or GLS1 activity could alleviate the antagonistic effect of YAP1 on the ferroptosis of RSL3-induced CRPC cells. In CRPC, the YAP1 level is high, which enters the nucleus and promotes the expressions of SLC1A5 and GLS1, thereby promoting cellular glutamine uptake and metabolism to generate glutamate and further synthesizing GSH, increasing GPX4 activity, improving cellular antioxidant capacity, and inhibiting cell death.

11.
Rapid Commun Mass Spectrom ; 37 Suppl 1: e9528, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37106523

RESUMO

RATIONALE: Microbial metabolites are widely used in agriculture, food, environment, and medicine. However, there is a lack of high-throughput, nonclogging, and simple methods for the identification of microbial metabolites and their subspecies using ambient mass spectrometry (MS). Here, we proposed a method for analyzing the microbial metabolites and identifying their species using the array ballpoint electrospray ionization (aBPESI) technique. METHODS: The previously developed BPESI was combined with the array analysis technique to form a high-throughput analysis technique called aBPESI. The bacteria cultured on the plate medium were directly analyzed using MS with aBPESI. Principal component analysis-linear discriminant analysis (PCA-LDA) algorithm was used to analyze the different subspecies groups. RESULTS: The results showed that aBPESI was capable of completing a sample analysis within 30 s, and the level of metabolite detection was comparable to existing techniques. The accuracy of bacterial subspecies identification was 90% (Pseudomonas aeruginosa) and 100% (Serratia marcescens). CONCLUSIONS: A new high-throughput and robust MS technique aBPESI was proposed. It does not require sample pretreatment and greatly reduces the sample analysis time. aBPESI shows a strong ability in microbial analysis and is expected to be further applied in other research fields.


Assuntos
Bactérias , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização por Electrospray/métodos , Bactérias/metabolismo
12.
Proc Natl Acad Sci U S A ; 117(30): 17924-17931, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32661175

RESUMO

Antibiotic resistance frequently evolves through fitness trade-offs in which the genetic alterations that confer resistance to a drug can also cause growth defects in resistant cells. Here, through experimental evolution in a microfluidics-based turbidostat, we demonstrate that antibiotic-resistant cells can be efficiently inhibited by amplifying the fitness costs associated with drug-resistance evolution. Using tavaborole-resistant Escherichia coli as a model, we show that genetic mutations in leucyl-tRNA synthetase (that underlie tavaborole resistance) make resistant cells intolerant to norvaline, a chemical analog of leucine that is mistakenly used by tavaborole-resistant cells for protein synthesis. We then show that tavaborole-sensitive cells quickly outcompete tavaborole-resistant cells in the presence of norvaline due to the amplified cost of the molecular defect of tavaborole resistance. This finding illustrates that understanding molecular mechanisms of drug resistance allows us to effectively amplify even small evolutionary vulnerabilities of resistant cells to potentially enhance or enable adaptive therapies by accelerating posttreatment competition between resistant and susceptible cells.


Assuntos
Evolução Biológica , Resistência a Medicamentos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Variação Genética , Modelos Moleculares , Conformação Proteica , Relação Estrutura-Atividade
13.
Angew Chem Int Ed Engl ; 62(21): e202302950, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36946249

RESUMO

Converting carbon-based molecular fuels into electricity efficiently and cleanly without emitting CO2 remains a challenge. Conventional fuel cells using noble metals as anode catalysts often suffer performance degradation due to CO poisoning and a host of problems associated with CO2 production. This study provides a CO2 -emission-free direct formaldehyde fuel cell. It enables a flow of electricity while producing H2 and valuable formate. Unlike conventional carbon-based molecules electrooxidation, formaldehyde 1-electron oxidation is performed on the Cu anode with high selectivity, thus generating formate and H2 without undergoing CO2 pathway. In addition, the fuel cell produces 0.62 Nm3 H2 and 53 mol formate per 1 kWh of electricity generated, with an open circuit voltage of up to 1 V and a peak power density of 350 mW cm-2 . This study puts forward a zero-carbon solution for the efficient utilization of carbon-based molecule fuels that generates electricity, hydrogen and valuable chemicals in synchronization.

14.
J Lipid Res ; 63(12): 100302, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36265716

RESUMO

Oxylipins are important biological regulators that have received extensive research attention. Due to the extremely low concentrations, large concentration variations, and high structural similarity of many oxylipins, the quantitative analysis of oxylipins in biological samples is always a great challenge. Here, we developed a liquid chromatography-tandem mass spectrometry-based method with high sensitivity, wide linearity, and acceptable resolution for quantitative profiling of oxylipins in multiple biological samples. A total of 104 oxylipins, some with a high risk of detection crosstalk, were well separated on a 150 mm column over 20 min. The method showed high sensitivity with lower limits of quantitation for 87 oxylipins, reaching 0.05-0.5 pg. Unexpectedly, we found that the linear range for 16, 18, and 17 oxylipins reached 10,000, 20,000, and 40,000 folds, respectively. Due to the high sensitivity, while reducing sample consumption to below half the volume of previous methods, 74, 78, and 59 low-abundance oxylipins, among which some were difficult to detect like lipoxins and resolvins, were well quantified in the tested mouse plasma, mouse liver, and human plasma samples, respectively. Additionally, we determined that analytes with multifarious concentrations of over a 1,000-fold difference could be well quantified simultaneously due to the wide linearity. In conclusion, most likely due to the instrumental advancement, this method effectively improves the quantitative sensitivity and linear range over existing methods, which will facilitate and advance the study of the physiological and pathophysiological functions of oxylipins.


Assuntos
Oxilipinas , Espectrometria de Massas em Tandem , Humanos , Animais , Camundongos , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos
15.
J Proteome Res ; 21(12): 2969-2978, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36301320

RESUMO

IgA nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of chronic kidney disease. The pathogenic mechanism of IgAN remains largely unknown and thus a specific therapeutic target is lacking. Here, we reported that the cytochrome P450 (CYP) epoxygenase/epoxide hydrolase (EH) axis was activated in the patients and is likely a therapeutic target for IgAN. Specifically, quantitative profiling of the plasma from IgAN patients and healthy controls revealed significant changes in plasma levels of CYP/EH-mediated lipid epoxides and diols. Subsequently, CYP2C8, CYP2C18, CYP2J2, EPHX1, and EPHX2 were found to be significantly increased in whole blood cells at mRNA levels from the IgAN patients when compared with those of healthy controls. Immunohistochemical analysis showed that all five CYPs and two EHs were upregulated in the kidney tissue from IgAN patients when compared with normative renal tissue, but the expression locations of the proteins were different with most of them. Treatment of HK-2 cells with IgA1 increased cell viability, compressed cell apoptosis, and increased the protein levels of CYP2C9, EPHX1, and EPHX2. All the results agreed that CYPs/EHs axis is likely the prophylactic and therapeutic target for IgAN, providing IgAN patients with a new intervention strategy.


Assuntos
Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/metabolismo , Epóxido Hidrolases/genética , Epóxido Hidrolases/metabolismo , Citocromo P-450 CYP2J2 , Imunoglobulina A , Sistema Enzimático do Citocromo P-450/genética , Metabolômica
16.
J Am Chem Soc ; 144(26): 11530-11535, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35748598

RESUMO

The electrocatalytic C-N coupling for one-step urea synthesis under ambient conditions serves as the promising alternative to the traditional urea synthetic protocol. However, the hydrogenation of intermediate species hinders the efficient urea synthesis. Herein, the oxygen vacancy-enriched CeO2 was demonstrated as the efficient electrocatalyst with the stabilization of the crucial intermediate of *NO via inserting into vacant sites, which is conducive to the subsequent C-N coupling process rather than protonation, whereas the poor selectivity of C-N coupling with protonation was observed on the vacancy-deficient catalyst. The oxygen vacancy-mediated selective C-N coupling was distinguished and validated by the in situ sum frequency generation spectroscopy. The introduction of oxygen vacancies tailors the common catalyst carrier into an efficient electrocatalyst with a high urea yield rate of 943.6 mg h-1 g-1, superior than that of partial noble-metal-based electrocatalysts. This work provides novel insights into the catalyst design and developments of coupling systems.


Assuntos
Oxigênio , Catálise , Hidrogenação
17.
Small ; 18(40): e2204100, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35996763

RESUMO

Pt-Co electrocatalysts have attracted significant attention because of their excellent performance in many electrochemical reactions. This review focuses on Pt-Co electrocatalysts designed and prepared for electrocatalytic applications. First, the various synthetic methods and synthesis mechanisms are systematically summarized; typical examples and core synthesis parameters are discussed for regulating the morphology and structure. Then, starting with the design and structure-activity relationship of catalysts, the research progress of the morphologies and structures of Pt-Co electrocatalysts obtained based on various strategies, the structure-activity relationship between them, and their properties are summarized. In addition, the important electrocatalytic applications and mechanisms of Pt-Co catalysts, including electrocatalytic oxidation/reduction and bifunctional catalytic reactions, are described and summarized, and their high catalytic activities are discussed on the basis of their mechanism and active sites. Moreover, the advanced electrochemical in situ characterization techniques are summarized, and the challenges and direction concerning the development of high-performance Pt-Co catalysts in electrocatalysis are discussed.


Assuntos
Técnicas Eletroquímicas , Catálise , Técnicas Eletroquímicas/métodos , Oxirredução
18.
Mol Pharm ; 19(7): 1927-1951, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35499303

RESUMO

Glioma is the most common and aggressive primary intracranial tumor within the central nervous system. The blood-brain barrier (BBB) has been a great hurdle for an effective glioma treatment. To effectively treat glioma, various strategies have been applied to deliver drugs to the brain by crossing the BBB. Nanocarrier-mediated drug delivery is emerging as an effective and noninvasive system to treat glioma, showing great potential in glioma therapy. In this review, we will provide a comprehensive overview on nanocarrier-mediated drug delivery and related glioma therapy. Following an initial overview of the BBB and blood-brain-tumor barrier (BBTB) structure and characteristics, nanocarrier-mediated drug delivery strategies (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, biomimetic nanoparticles, and exosomes) for crossing the BBB are discussed. Finally, nanotherapeutic techniques (imaging-mediated chemotherapy, photothermal therapy, photodynamic therapy, gene therapy, immunotherapy, ferroptosis therapy, sonodynamic therapy, chemodynamic therapy, and combination therapy) in treating glioma are summarized. In addition, this review provides some perspectives on the clinical applications of nanomedicines.


Assuntos
Neoplasias Encefálicas , Glioma , Nanopartículas , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Sistemas de Liberação de Medicamentos/métodos , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Lipossomos/uso terapêutico , Nanopartículas/química
19.
Phys Chem Chem Phys ; 24(30): 18083-18093, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35876809

RESUMO

Cesium (Cs+) and strontium (Sr2+) ions are the main fission byproducts in the reprocessing of spent nuclear fuels for nuclear power plants. Their long half-live period (30.17 years for 137Cs and 28.80 years for 90Sr) makes them very dangerous radionuclides. Hence the solidification of Cs+ and Sr2+ is of paramount importance for preventing them from entering the human food chain through water. Despite tremendous efforts for solidification, the long-term stability remains a great challenge due to the experimental limitation and lack of good evaluation indicators for such long half-life radionuclides. Using density functional theory (DFT), we investigate the origin of long-term stability for the solidification of Cs+ and Sr2+ inside sodalite and establish that the exchange energy and the diffusion barrier play an important role in gaining the long-term stability both thermodynamically and kinetically. The acidity/basicity, solvation, temperature, and diffusion effect are comprehensively studied. It is found that solidification of Cs+ and Sr2+ is mainly attributed to the solvation effect, zeolitic adsorption ability, and diffusion barriers. The present study provides theoretical evidence to use geopolymers to adsorb Cs+ and Sr2+ and convert the adsorbed geopolymers to zeolites to achieve solidification of Cs+ and Sr2+ with long-term stability.


Assuntos
Césio , Zeolitas , Adsorção , Difusão , Humanos , Estrôncio
20.
J Environ Manage ; 316: 115208, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35550957

RESUMO

A modified sodium bentonite geosynthetic clay liner (GCL) designed for acid-and-alkaline resistance was evaluated for its potential application in the containment of bauxite residue leachate. A modified fluid loss test was employed to quickly evaluate the hydraulic conductivity (k) of the GCL using distilled water, tap water, and four bauxite liquors (BLs, leachate from bauxite residue reservoirs). The effects of swelling capacity of bentonite, prehydration, hydraulic gradient (i), ionic strength (I), and relative abundance of monovalent and multivalent cations (RMD) on the hydraulic conductivity of the GCL were analyzed. The results indicated that the BLs significantly decreased free swell index of the bentonite. As compared to increasing i, prehydration obviously enhanced hydraulic performance of the GCL. The four BLs increased k of the GCL by a factor of 4-12 relative to the tap water permeation condition, and the resultant k exceeded upper limit of 5.0 × 10-11 m/s for GCLs. The increase in k was attributed to compression in diffuse double layer of the bentonite and dissolution in clay minerals in ion-rich and hyperalkaline BLs, manifesting that further modification on the GCL is needed. The I was found a better indicator than the RMD on correlation with chemical compatibility of the GCL.


Assuntos
Bentonita , Eliminação de Resíduos , Óxido de Alumínio , Silicatos de Alumínio , Argila , Eliminação de Resíduos/métodos , Água
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa