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1.
Bioorg Chem ; 150: 107514, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38870704

RESUMEN

Alzheimer's disease (AD), a progressive neurodegenerative disorder, has garnered increased attention due to its substantial economic burden and the escalating global aging phenomenon. Amyloid-ß deposition is a key pathogenic marker observed in the brains of Alzheimer's sufferers. Based on real-time, safe, low-cost, and commonly used, near-infrared fluorescence (NIRF) imaging technology have become an essential technique for the detection of AD in recent years. In this work, NIRF probes with hemicyanine structure were designed, synthesized and evaluated for imaging Aß aggregates in the brain. We use the hemicyanine structure as the parent nucleus to enhance the probe's optical properties. The introduction of PEG chain is to improve the probe's brain dynamice properties, and the alkyl chain on the N atom is to enhance the fluorescence intensity of the probe after binding to the Aß aggregates as much as possible. Among these probes, Z2, Z3, Z6, X3, X6 and T1 showed excellent optical properties and high affinity to Aß aggregates (Kd = 24.31 âˆ¼ 59.60 nM). In vitro brain section staining and in vivo NIRF imaging demonstrated that X6 exhibited superior discrimination between Tg mice and WT mice, and X6 has the best brain clearance rate. As a result, X6 was identified as the optimal probe. Furthermore, the docking theory calculation results aided in describing X6's binding behavior with Aß aggregates. As a high-affinity, high-selectivity, safe and effective probe of targeting Aß aggregates, X6 is a promising NIRF probe for in vivo detection of Aß aggregates in the AD brain.

2.
Nano Lett ; 23(7): 2964-2973, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-36947431

RESUMEN

Recent advances in intratracheal delivery strategies have sparked considerable biomedical interest in developing this promising approach for lung cancer diagnosis and treatment. However, there are very few relevant studies on the behavior and mechanism of imaging nanoparticles (NPs) after intratracheal delivery. Here, we found that nanosized perfluoro-15-crown-5-ether (PFCE NPs, ∼200 nm) exhibite significant 19F-MRI signal-to-noise ratio (SNR) enhancement than perfluorooctyl bromide (PFOB NPs) up to day 7 after intratracheal delivery. Alveolar macrophages (AMs) engulf PFCE NPs, become PFCE NPs-laden AMs, and then migrate into the tumor margin, resulting in increased tumor PFCE concentration and 19F-MRI signals. AMs-mediated translocation of PFCE NPs to lung draning lymph nodes (dLNs) decreases the background PFCE concentration. Our results shed light on the dynamic AMs-mediated translocation of intratracheally delivered PFC NPs for effective lung tumor visualization and reveal a pathway to develop and promote the clinical translation of an intratracheal delivery-based imaging strategy.


Asunto(s)
Fluorocarburos , Neoplasias Pulmonares , Nanopartículas , Humanos , Macrófagos Alveolares , Imagen por Resonancia Magnética/métodos , Neoplasias Pulmonares/tratamiento farmacológico
3.
J Am Chem Soc ; 145(3): 1924-1935, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36571792

RESUMEN

High-entropy compounds with extraordinary properties due to the synergistic effect of multiple components have exhibited great potential and attracted extensive attention in various fields, including physics, mechanical property analysis, and energy storage. Achieving universal stability and synthesis of high-entropy compounds with a wide range of components and structures continues to be difficult due to the high complexity of multicomponent mixing. Here, we propose a design strategy with high generality for realizing the stability and synthesis of high-entropy compounds that one metal site like the framework in the compound structures with bimetallic sites stabilizes another site to accommodate different elements. Several typical metal compounds with bimetallic sites, including perovskite hydroxides, layered double hydroxide, spinel sulfide, perovskite fluoride, and spinel oxides, have been synthesized into high-entropy compounds. High-entropy perovskite hydroxides (HEPHs) as representative compounds have been synthesized with a highly wide range of components even a septenary component and exhibit great oxygen evolution activity. Our work provides a design platform to develop more high-entropy compound systems with promising development potential for electrocatalysts.

4.
BMC Plant Biol ; 23(1): 521, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891481

RESUMEN

BACKGROUND: Microspore culture is one of the important biotechnological tools in plant breeding. The induction of microspore embryogenesis is a critical factor that affects the yield of microspore-derived embryo productions. Cold treatment has been reported to reprogram the gametophytic pathway in various plant species. However, the exact mechanism(s) underlying the effect of cold pre-treatment of floral buds on the efficiency of ME is still not clear. RESULTS: In this study, the effects of cold stress on the microspore totipotency of rice cultivar Zhonghua 11 were investigated. Our results revealed that a 10-day cold treatment is necessary for microspore embryogenesis initiation. During this period, the survival rate of microspores increased and reached a peak at 7 days post treatment (dpt), before decreasing at 10 dpt. RNA-seq analysis showed that the number of DEGs increased from 3 dpt to 10 dpt, with more downregulated DEGs than upregulated ones at the same time point. GO enrichment analysis showed a shift from 'Response to abiotic stimulus' at 3 dpt to 'Metabolic process' at 7 and 10 dpt, with the most significant category in the cellular component being 'cell wall'. KEGG analysis of the pathways revealed changes during cold treatment. Mass spectrometry was used to evaluate the variations in metabolites at 10 dpt compared to 0 dpt, with more downregulated DEMs being determined in both GC-MS and LC-MS modes. These DEMs were classified into 11 categories, Most of the DEMs belonged to 'lipids and lipid-like molecules'. KEGG analysis of DEMs indicates pathways related to amino acid and nucleotide metabolism being upregulated and those related to carbohydrate metabolism being downregulated. An integration analysis of transcriptomics and metabolomics showed that most pathways belonged to 'Amino acid metabolism' and 'Carbohydrate metabolism'. Four DEMs were identified in the interaction network, with stearidonic acid involving in the most correlations, suggesting the potential role in microspore totipotency. CONCLUSIONS: Our findings exhibited the molecular events occurring during stress-induced rice microspore. Pathways related to 'Amino acid metabolism' and 'Carbohydrate metabolism' may play important roles in rice microspore totipotency. Stearidonic acid was identified, which may participate in the initiation of microspore embryogenesis.


Asunto(s)
Respuesta al Choque por Frío , Oryza , Transcriptoma , Oryza/genética , Fitomejoramiento , Aminoácidos
5.
Plant Cell Environ ; 46(1): 288-305, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319595

RESUMEN

Powdery mildew (Pm), caused by Blumeria graminis f.sp. tritici (Bgt), is one of the most important wheat diseases. Heavy-metal-associated isoprenylated plant protein (HIPP1) has been proved playing important roles in response to biotic and a biotic stress. In present study, we proved HIPP1-V from Haynalidia villosa is a positive regulator in Pm resistance. HIPP1-V was rapidly induced by Bgt. Transiently or stably heterologous overexpressing HIPP1-V in wheat suppressed the haustorium formation and enhanced Pm resistance. HIPP1-V isoprenylation was critical for plasma membrane (PM) localization, interaction with E3-ligase CMPG1-V and function in Pm resistance. Bgt infection recruited the isoprenylated HIPP1-V and CMPG1s on PM; blocking the HIPP1 isoprenylation reduced such recruitment and compromised the resistance of OE-CMPG1-V and OE-HIPP1-V. Overexpressing HIPP1-VC148G could not enhance Pm resistance. These indicated the Pm resistance was dependent on HIPP1-V's isoprenylation. DGEs related to the ROS and SA pathways were remarkably enriched in OE-HIPP1-V, revealing their involvement in Pm resistance. Our results provide evidence on the important role of protein isoprenylation in plant defense.


Asunto(s)
Triticum , Triticum/genética
6.
Plant Cell Rep ; 42(10): 1651-1663, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37498331

RESUMEN

KEY MESSAGES: Narrowing down to a single putative target gene behind a leaf senescence mutant and constructing the regulation network by proteomic method. Leaf senescence mutant is an important resource for exploring molecular mechanism of aging. To dig for potential modulation networks during maize leaf aging process, we delimited the gene responsible for a premature leaf senescence mutant els5 to a 1.1 Mb interval in the B73 reference genome using a BC1F1 population with 40,000 plants, and analyzed the leaf proteomics of the mutant and its near-isogenic wild type line. A total of 1355 differentially accumulated proteins (DAP) were mainly enriched in regulation pathways such as "photosynthesis", "ribosome", and "porphyrin and chlorophyll metabolism" by the KEGG pathway analysis. The interaction networks constructed by incorporation of transcriptome data showed that ZmELS5 likely repaired several key factors in the photosynthesis system. The putative candidate proteins for els5 were proposed based on DAPs in the fined QTL mapping interval. These results provide fundamental basis for cloning and functional research of the els5 gene, and new insights into the molecular mechanism of leaf senescence in maize.


Asunto(s)
Senescencia de la Planta , Zea mays , Zea mays/genética , Proteómica/métodos , Transcriptoma , Hojas de la Planta/metabolismo , Regulación de la Expresión Génica de las Plantas/genética
7.
J Labelled Comp Radiopharm ; 66(14): 444-451, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37873934

RESUMEN

Nanobodies (Nbs) hold significant potential in molecular imaging due to their unique characteristics. However, there are challenges to overcome when it comes to brain imaging. To address these obstacles, collaborative efforts and interdisciplinary research are needed. This article aims to raise awareness and encourage collaboration among researchers from various fields to find solutions for effective brain imaging using Nbs. By fostering cooperation and knowledge sharing, we can make progress in overcoming the existing limitations and pave the way for improved molecular imaging techniques in the future.


Asunto(s)
Anticuerpos de Dominio Único , Anticuerpos de Dominio Único/metabolismo , Barrera Hematoencefálica/diagnóstico por imagen , Barrera Hematoencefálica/metabolismo , Imagen Molecular/métodos
8.
Nano Lett ; 22(3): 963-972, 2022 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-35073699

RESUMEN

Inefficient tumor accumulation and penetration remain as the main challenges to therapy efficacy of lung cancer. Local delivery of smart nanoclusters can increase drug penetration and provide superior antitumor effects than systemic routes. Here, we report self-assembled pH-sensitive superparamagnetic iron oxide nanoclusters (SPIONCs) that enhance in situ ferroptosis and apoptosis with radiotherapy and chemodynamic therapy. After pulmonary delivery in orthotopic lung cancer, SPIONCs disintegrate into smaller nanoparticles and release more iron ions in an acidic microenvironment. Under single-dose X-ray irradiation, endogenous superoxide dismutase converts superoxide radicals produced by mitochondria to hydrogen peroxide, which in turn generates hydroxyl radicals by the Fenton reaction from iron ions accumulated inside the tumor. Finally, irradiation and iron ions enhance tumor lipid peroxidation and induce cell apoptosis and ferroptosis. Thus, rationally designed pulmonary delivered nanoclusters provide a promising strategy for noninvasive imaging of lung cancer and synergistic therapy.


Asunto(s)
Ferroptosis , Neoplasias Pulmonares , Nanopartículas , Neoplasias , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno/farmacología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Medicina de Precisión , Microambiente Tumoral
9.
Nano Lett ; 22(16): 6492-6500, 2022 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-35950973

RESUMEN

High-entropy oxide (HEO) including multiple principal elements possesses great potential for various fields such as basic physics, mechanical properties, energy storage, and catalysis. However, the synthesis method of high-entropy compounds through the traditional heating approach is not conducive to the rapid properties screening, and the current elemental combinations of HEO are also highly limited. Herein, we report a rapid synthesis method for HEO through the Joule-heating of nickel foil with dozens of seconds. High-entropy rocksalt oxides (HERSO) with the new elemental combination, high-entropy spinel oxides (HESO), and high-entropy perovskite oxide (HEPO) have been synthesized through the Joule-heating. The synthesized HERSO with new elemental combinations proves to be a great promotion of OER activity due to the synergy of multiple components and the continuous electronic structure experimentally and theoretically. The demonstrated synthesis approach and the new component combination of HERSO provide a broad platform for the development of high-entropy materials and catalysts.

10.
Int J Mol Sci ; 24(23)2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38069082

RESUMEN

Barley is the most salt-tolerant cereal crop. However, little attention has been paid to the salt-tolerant doubled haploids of barley derived from mutagenesis combined with isolated microspore culture. In the present study, barley doubled haploid (DH) line 20, which was produced by mutagenesis combined with isolated microspore culture, showed stably and heritably better salt tolerance than the wild type H30 in terms of fresh shoot weight, dry shoot weight, K+/Na+ ratio and photosynthetic characteristics. Transcriptome and metabolome analyses were performed to compare the changes in gene expression and metabolites between DH20 and H30. A total of 462 differentially expressed genes (DEGs) and 152 differentially accumulated metabolites (DAMs) were identified in DH20 compared to H30 under salt stress. Among the DAMs, fatty acids were the most accumulated in DH20 under salt stress. The integration of transcriptome and metabolome analyses revealed that nine key biomarkers, including two metabolites and seven genes, could distinguish DH20 and H30 when exposed to high salt. The pathways of linoleic acid metabolism, alpha-linolenic acid metabolism, glycerolipid metabolism, photosynthesis, and alanine, aspartate and glutamate metabolism were significantly enriched in DH20 with DEGs and DAMs in response to salt stress. These results suggest that DH20 may enhance resilience by promoting lipid metabolism, maintaining energy metabolism and decreasing amino acids metabolism. The study provided novel insights for the rapid generation of homozygous mutant plants by mutagenesis combined with microspore culture technology and also identified candidate genes and metabolites that may enable the mutant plants to cope with salt stress.


Asunto(s)
Hordeum , Transcriptoma , Tolerancia a la Sal/genética , Hordeum/metabolismo , Metabolismo de los Lípidos/genética , Estrés Fisiológico/genética , Perfilación de la Expresión Génica , Fotosíntesis/genética , Mutagénesis , Salinidad
11.
J Integr Plant Biol ; 65(8): 1859-1873, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36988217

RESUMEN

The plant hormone abscisic acid (ABA) is crucial for plant seed germination and abiotic stress tolerance. However, the association between ABA sensitivity and plant abiotic stress tolerance remains largely unknown. In this study, 436 rice accessions were assessed for their sensitivity to ABA during seed germination. The considerable diversity in ABA sensitivity among rice germplasm accessions was primarily reflected by the differentiation between the Xian (indica) and Geng (japonica) subspecies and between the upland-Geng and lowland-Geng ecotypes. The upland-Geng accessions were most sensitive to ABA. Genome-wide association analyses identified four major quantitative trait loci containing 21 candidate genes associated with ABA sensitivity of which a basic helix-loop-helix transcription factor gene, OsbHLH38, was the most important for ABA sensitivity. Comprehensive functional analyses using knockout and overexpression transgenic lines revealed that OsbHLH38 expression was responsive to multiple abiotic stresses. Overexpression of OsbHLH38 increased seedling salt tolerance, while knockout of OsbHLH38 increased sensitivity to salt stress. A salt-responsive transcription factor, OsDREB2A, interacted with OsbHLH38 and was directly regulated by OsbHLH38. Moreover, OsbHLH38 affected rice abiotic stress tolerance by mediating the expression of a large set of transporter genes of phytohormones, transcription factor genes, and many downstream genes with diverse functions, including photosynthesis, redox homeostasis, and abiotic stress responsiveness. These results demonstrated that OsbHLH38 is a key regulator in plant abiotic stress tolerance.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Oryza , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Oryza/genética , Oryza/metabolismo , Tolerancia a la Sal/genética , Estudio de Asociación del Genoma Completo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Estrés Fisiológico/genética , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Sequías , Germinación/genética
12.
Mol Cancer ; 21(1): 212, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36457016

RESUMEN

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with primary tumors and liver metastases have substantially reduced survival. Since mesenchymal-epithelial transition factor (MET) plays a significant role in the molecular mechanisms of advanced NSCLC, small molecule MET inhibitor capmatinib (INC280) hold promise for clinically NSCLC treatment. However, the major obstacles of MET-targeted therapy are poor drug solubility and off-tumor effects, even oral high-dosing regimens cannot significantly increase the therapeutic drug concentration in primary and metastatic NSCLC. METHODS: We developed a multirooted delivery system INC280-PFCE nanoparticles (NPs) by loading INC280 into perfluoro-15-crown-5-ether for improving MET-targeted therapy. Biodistribution and anti-MET/antimetastatic effects of NPs were validated in orthotopic NSCLC and NSCLC liver metastasis models in a single low-dose. The efficacy of INC280-PFCE NPs was also explored in human NSCLC specimens. RESULTS: INC280-PFCE NPs exhibited excellent antitumor ability in vitro. In orthotopic NSCLC models, sustained release and prolonged retention behaviors of INC280-PFCE NPs within tumors could be visualized in real-time by 19F magnetic resonance imaging (19F-MRI), and single pulmonary administration of NPs showed more significant tumor growth inhibition than oral administration of free INC280 at a tenfold higher dose. Furthermore, a single low-dose INC280-PFCE NPs administered intravenously suppressed widespread dissemination of liver metastasis without systemic toxicity. Finally, we verified the clinical translation potential of INC280-PFCE NPs in human NSCLC specimens. CONCLUSIONS: These results demonstrated high anti-MET/antimetastatic efficacies, real-time MRI visualization and high biocompatibility of NPs after a single low-dose.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Hepáticas , Neoplasias Pulmonares , Nanopartículas , Humanos , Medicina de Precisión , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Distribución Tisular , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico
13.
Bioorg Chem ; 124: 105804, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35468416

RESUMEN

A novel organomediated cleavage of benzoyl group using ethane-1,2-diamine and acetic acid under neutral condition enables an efficient synthesis of 1-(6-nitropyridin-2-yl)thiourea, which previously has been challenging to prepare by conventional methods. The successful synthesis of 1-(6-nitropyridin-2-yl)thiourea as a synthon permits development of a variety of 18F labeled heterocycles as PET imaging ligands such as N-(pyridin-2-yl)thiazol-2-amine derivatives. The utility of this synthon is demonstrated with the synthesis of a 18F-labeled PET tracer for studying prion disease. In vitro autoradiography using this PET tracer on sagittal rat brain slices showed highest accumulation of radioactivity in the hippocampus, cortex, and striatum, in accordance with reported immunostaining of PrPc in rat brain.


Asunto(s)
Encéfalo , Tiourea , Animales , Encéfalo/diagnóstico por imagen , Ligandos , Tomografía de Emisión de Positrones/métodos , Ratas
14.
Int J Mol Sci ; 23(4)2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35216209

RESUMEN

N6-methyladenosine (m6A) methylation represents a new layer of the epitranscriptomic regulation of plant development and growth. However, the effects of m6A on rice responses to environmental stimuli remain unclear. In this study, we performed a methylated-RNA immunoprecipitation sequencing analysis and compared the changes in m6A methylation and gene expression in rice under salt stress conditions. Salt stress significantly increased the m6A methylation in the shoots (p value < 0.05). Additionally, 2537 and 2304 differential m6A sites within 2134 and 1997 genes were identified in the shoots and roots, respectively, under salt stress and control conditions. These differential m6A sites were largely regulated in a tissue-specific manner. A unique set of genes encoding transcription factors, antioxidants, and auxin-responsive proteins had increased or decreased m6A methylation levels only in the shoots or roots under salt stress, implying m6A may mediate salt tolerance by regulating transcription, ROS homeostasis, and auxin signaling in a tissue-specific manner. Integrating analyses of m6A modifications and gene expression changes revealed that m6A changes regulate the expression of genes controlling plant growth, stress responses, and ion transport under saline conditions. These findings may help clarify the regulatory effects of m6A modifications on rice salt tolerance.


Asunto(s)
Adenosina/análogos & derivados , Oryza/genética , Estrés Salino/genética , Tolerancia a la Sal/genética , Adenosina/genética , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas/genética , Metilación , Raíces de Plantas/genética , Factores de Transcripción/genética
15.
BMC Plant Biol ; 21(1): 579, 2021 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-34876002

RESUMEN

BACKGROUND: The Agrobacterium mediated transformation has been routinely used in lots of plant species as a powerful tool to deliver genes of interest into a host plant. However, the transformation of elite and commercially valuable cultivar is still limited by the genotype-dependency, and the efficiency of Agrobacterium infection efficiency is crucial for the success of transformation. RESULTS: In this study, the microspore-derived embryogenic calli (MDEC) of barley elite cultivars and breeding lines were employed as unique subjects to characterize the genotypic response during Agrobacterium infection process. Our results identified compatible barley genotypes (GanPi 6 and L07, assigned as GP6-L07 group) and one recalcitrant genotype (Hong 99, assigned as H99) for the Agrobacterium strain LBA4404 infection using GUS assay. The accumulation trend of reactive oxygen species (ROS) was similar among genotypes across the time course. The results of RNA-seq depicted that the average expressional intensity of whole genomic genes was similar among barley genotypes during Agrobacterium infection. However, the numbers of differentially expressed genes (DEGs) exhibited significant expressional variation between GP6-L07 and H99 groups from 6 to 12 h post-inoculation (hpi). Gene ontology (GO) enrichment analysis revealed different regulation patterns for the predicted biological processes between the early (up-regulated DEGs overrepresented at 2 hpi) and late stages (down-regulated DEGs overrepresented from 6 to 24 hpi) of infection. KEGG analysis predicted 12 pathways during Agrobacterium infection. Among which one pathway related to pyruvate metabolism was enriched in GP6 and L07 at 6 hpi. Two pathways related to plant hormone signal transduction and DNA replication showed expressional variation between GP6-L07 and H99 at 24 hpi. It was further validated by qRT-PCR assay for seven candidate genes (Aldehyde dehydrogenase, SAUR, SAUR50, ARG7, Replication protein A, DNA helicase and DNA replication licensing factor) involved in the three pathways, which are all up-regulated in compatible while down-regulated in recalcitrant genotypes, suggesting the potential compatibility achieved at later stage for the growth of Agrobacterium infected cells. CONCLUSIONS: Our findings demonstrated the similarity and difference between compatible and recalcitrant genotypes of barley MDEC upon Agrobacterium infection. Seven candidate genes involved in pyruvate metabolism, hormonal signal transduction and DNA replication were identified, which advocates the genotypic dependency during Agrobacterium infection process.


Asunto(s)
Agrobacterium/fisiología , Hordeum/microbiología , Enfermedades de las Plantas/microbiología , Transformación Genética , Agrobacterium/genética , Resistencia a la Enfermedad/genética , Perfilación de la Expresión Génica , Ontología de Genes , Genes de Plantas , Genotipo , Hordeum/genética , Enfermedades de las Plantas/genética , Especies Reactivas de Oxígeno/metabolismo , Análisis de Secuencia de ARN
16.
Small ; 17(45): e2104557, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34643326

RESUMEN

MnO2 -based material is one of the most promising cathode candidates of aqueous zinc-ion batteries (ZIBs), but its commercialization is hindered by the sluggish reaction kinetics and poor structural stability. Herein, a hierarchical framework consisting of core-shell structured carbon nanotubes@K-birnessite-MnO2 enwrapped by graphene/carbon black bicomponent networks (CNT@KMO@GC) via a simple method for ZIBs is designed and developed. The hierarchical framework characterized with favorable K+ preintercalation, δ-phase, and vertically aligned nanoflake arrays of KMO and 3D electrically conductive network shows the enhanced electronic/ionic conductivity and improved wettability with electrolyte, resulting in the fast charge/mass transport and stable structural stability of CNT@KMO@GC. When used as cathode in ZIBs, CNT@KMO@GC exhibits exciting electrochemical performance with remarkable capacity (405.5 mAh g-1 at 0.30 A g-1 ), high rate performance (166.6 mAh g-1 up to 10.0 A g-1 ), and impressive cycling stability (almost no capacity decay after 2000 cycles and 77.3% retention after 10 000 cycles at 10.0 A g-1 ). The energy storage mechanism of CNT@KMO@GC is clarified as H+ /Zn2+ coinsertion/extraction via electrochemical analysis and ex situ characterization. This study offers an innovative paradigm for the advance of ZIBs.

17.
Mol Psychiatry ; 25(1): 206-229, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31570775

RESUMEN

Increased expression of the 3.1 isoform of the KCNH2 potassium channel has been associated with cognitive dysfunction and with schizophrenia, yet little is known about the underlying pathophysiological mechanisms. Here, by using in vivo wireless local field potential recordings during working memory processing, in vitro brain slice whole-cell patching recordings and in vivo stereotaxic hippocampal injection of AAV-encoded expression, we identified specific and delayed disruption of hippocampal-mPFC synaptic transmission and functional connectivity associated with reductions of SERPING1, CFH, and CD74 in the KCNH2-3.1 overexpression transgenic mice. The differentially expressed genes in mice are enriched in neurons and microglia, and reduced expression of these genes dysregulates the complement cascade, which has been previously linked to synaptic plasticity. We find that knockdown of these genes in primary neuronal-microglial cocultures from KCNH2-3.1 mice impairs synapse formation, and replenishing reduced CFH gene expression rescues KCNH2-3.1-induced impaired synaptogenesis. Translating to humans, we find analogous dysfunctional interactions between hippocampus and prefrontal cortex in coupling of the fMRI blood oxygen level-dependent (BOLD) signal during working memory in healthy subjects carrying alleles associated with increased KCNH2-3.1 expression in brain. Our data uncover a previously unrecognized role of the truncated KCNH2-3.1 potassium channel in mediating complement activation, which may explain its association with altered hippocampal-prefrontal connectivity and synaptic function. These results provide a potential molecular link between increased KCNH2-3.1 expression, synapse alterations, and hippocampal-prefrontal circuit abnormalities implicated in schizophrenia.


Asunto(s)
Activación de Complemento/fisiología , Canal de Potasio ERG1/metabolismo , Memoria a Corto Plazo/fisiología , Animales , Encéfalo/metabolismo , Disfunción Cognitiva/genética , Activación de Complemento/inmunología , Canal de Potasio ERG1/genética , Femenino , Hipocampo/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/fisiopatología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismo , Transmisión Sináptica/fisiología , Lóbulo Temporal/metabolismo
18.
Biotechnol Appl Biochem ; 68(1): 136-147, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32100895

RESUMEN

An efficient method for the enzymatic synthesis of cephalexin (CEX) from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and d-phenylglycine methyl ester (PGME) using immobilized penicillin G acylase (IPGA) as catalyst in a suspension aqueous solution system was developed, where the reactant 7-ADCA and product CEX are mainly present as solid particles. The effects of key factors on the enzymatic synthesis were investigated. Results showed that continuous feeding of PGME was more efficient for the synthesis of CEX than the batch mode. Under the optimized conditions, the maximum 7-ADCA conversion ratio of 99.3% and productivity of 200 mmol/L/H were achieved, both of which are much superior to the homogeneous aqueous solution system. Besides, IPGA still retained 95.4% of its initial activity after 10 cycles of enzymatic synthesis, indicating the excellent stability of this approach. The developed approach shows great potential for the industrial production of CEX via an enzyme-based route.


Asunto(s)
Cefalexina , Enzimas Inmovilizadas/química , Proteínas de Escherichia coli/química , Escherichia coli/enzimología , Penicilina Amidasa/química , Catálisis , Cefalexina/síntesis química , Cefalexina/química , Cefalosporinas/química , Glicina/análogos & derivados , Glicina/química
19.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-34502018

RESUMEN

Gibberellin 2-oxidase (GA2ox) plays an important role in the GA catabolic pathway and the molecular function of the OsGA2ox genes in plant abiotic stress tolerance remains largely unknown. In this study, we functionally characterized the rice gibberellin 2-oxidase 8 (OsGA2ox8) gene. The OsGA2ox8 protein was localized in the nucleus, cell membrane, and cytoplasm, and was induced in response to various abiotic stresses and phytohormones. The overexpression of OsGA2ox8 significantly enhanced the osmotic stress tolerance of transgenic rice plants by increasing the number of osmotic regulators and antioxidants. OsGA2ox8 was differentially expressed in the shoots and roots to cope with osmotic stress. The plants overexpressing OsGA2ox8 showed reduced lengths of shoots and roots at the seedling stage, but no difference in plant height at the heading stage was observed, which may be due to the interaction of OsGA2ox8 and OsGA20ox1, implying a complex feedback regulation between GA biosynthesis and metabolism in rice. Importantly, OsGA2ox8 was able to indirectly regulate several genes associated with the anthocyanin and flavonoid biosynthetic pathway and the jasmonic acid (JA) and abscisic acid (ABA) biosynthetic pathway, and overexpression of OsGA2ox8 activated JA signal transduction by inhibiting the expression of jasmonate ZIM domain-containing proteins. These results provide a basis for a future understanding of the networks and respective phenotypic effects associated with OsGA2ox8.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Oxigenasas de Función Mixta/genética , Oryza/enzimología , Proteínas de Plantas/genética , Transducción de Señal , Estrés Fisiológico , Ácido Abscísico/metabolismo , Antocianinas/biosíntesis , Vías Biosintéticas , Ciclopentanos/metabolismo , Flavonoides/biosíntesis , Oxigenasas de Función Mixta/metabolismo , Oxigenasas de Función Mixta/fisiología , Especificidad de Órganos , Oryza/genética , Oryza/metabolismo , Oryza/fisiología , Presión Osmótica , Oxilipinas/metabolismo , Raíces de Plantas , Plantones
20.
J Am Chem Soc ; 142(45): 19259-19267, 2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33119292

RESUMEN

Developing unique single atoms as active sites is vitally important to boosting the efficiency of photocatalytic CO2 reduction, but directly atomizing metal particles and simultaneously adjusting the configuration of individual atoms remain challenging. Herein, we demonstrate a facile strategy at a relatively low temperature (500 °C) to access the in situ metal atomization and coordination adjustment via the thermo-driven gaseous acid. Using this strategy, the pyrolytic gaseous acid (HCl) from NH4Cl could downsize the large metal particles into corresponding ions, which subsequently anchored onto the surface defects of a nitrogen-rich carbon (NC) matrix. Additionally, the low-temperature treatment-induced C═O motifs within the interlayer of NC could bond with the discrete Fe sites in a perpendicular direction and finally create stabilized Fe-N4O species with high valence status (Fe3+) on the shallow surface of the NC matrix. It was found that the Fe-N4O species can achieve a highly efficient CO2 conversion when accepting energetic electrons from both homogeneous and heterogeneous photocatalysts. The optimized sample achieves a maximum turnover number (TON) of 1494 within 1 h in CO generation with a high selectivity of 86.7% as well as excellent stability. Experimental and theoretical results unravel that high valence Fe sites in Fe-N4O species can promote the adsorption of CO2 and lower the formation barrier of key intermediate COOH* compared with the traditional Fe-N4 moiety with lower chemical valence. Our discovery provides new points of view in the construction of more efficient single-atom cocatalysts by considering the optimization of the atomic configuration for high-performance CO2 photoreduction.

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