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1.
Nat Methods ; 20(6): 824-835, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37069271

RESUMO

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings.


Assuntos
Benchmarking , Microscopia , Microscopia/métodos , Imageamento Tridimensional/métodos , Neurônios/fisiologia , Algoritmos
2.
PLoS Biol ; 21(6): e3002133, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37390046

RESUMO

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain.


Assuntos
Encéfalo , Neurociências , Animais , Humanos , Camundongos , Ecossistema , Neurônios
3.
Proc Natl Acad Sci U S A ; 120(39): e2305603120, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37722056

RESUMO

An increasing number of protein interaction domains and their targets are being found to be intrinsically disordered proteins (IDPs). The corresponding target recognition mechanisms are mostly elusive because of challenges in performing detailed structural analysis of highly dynamic IDP-IDP complexes. Here, we show that by combining recently developed computational approaches with experiments, the structure of the complex between the intrinsically disordered C-terminal domain (CTD) of protein 4.1G and its target IDP region in NuMA can be dissected at high resolution. First, we carry out systematic mutational scanning using dihydrofolate reductase-based protein complementarity analysis to identify essential interaction regions and key residues. The results are found to be highly consistent with an α/ß-type complex structure predicted by AlphaFold2 (AF2). We then design mutants based on the predicted structure using a deep learning protein sequence design method. The solved crystal structure of one mutant presents the same core structure as predicted by AF2. Further computational prediction and experimental assessment indicate that the well-defined core structure is conserved across complexes of 4.1G CTD with other potential targets. Thus, we reveal that an intrinsically disordered protein interaction domain uses an α/ß-type structure module formed through synergistic folding to recognize broad IDP targets. Moreover, we show that computational prediction and experiment can be jointly applied to segregate true IDP regions from the core structural domains of IDP-IDP complexes and to uncover the structure-dependent mechanisms of some otherwise elusive IDP-IDP interactions.


Assuntos
Proteínas Intrinsicamente Desordenadas , Proteínas Intrinsicamente Desordenadas/genética , Furilfuramida , Sequência de Aminoácidos , Mutação , Domínios e Motivos de Interação entre Proteínas
4.
Bioinformatics ; 40(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38530800

RESUMO

MOTIVATION: The full automation of digital neuronal reconstruction from light microscopic images has long been impeded by noisy neuronal images. Previous endeavors to improve image quality can hardly get a good compromise between robustness and computational efficiency. RESULTS: We present the image enhancement pipeline named Neuronal Image Enhancement through Noise Disentanglement (NIEND). Through extensive benchmarking on 863 mouse neuronal images with manually annotated gold standards, NIEND achieves remarkable improvements in image quality such as signal-background contrast (40-fold) and background uniformity (10-fold), compared to raw images. Furthermore, automatic reconstructions on NIEND-enhanced images have shown significant improvements compared to both raw images and images enhanced using other methods. Specifically, the average F1 score of NIEND-enhanced reconstructions is 0.88, surpassing the original 0.78 and the second-ranking method, which achieved 0.84. Up to 52% of reconstructions from NIEND-enhanced images outperform all other four methods in F1 scores. In addition, NIEND requires only 1.6 s on average for processing 256 × 256 × 256-sized images, and images after NIEND attain a substantial average compression rate of 1% by LZMA. NIEND improves image quality and neuron reconstruction, providing potential for significant advancements in automated neuron morphology reconstruction of petascale. AVAILABILITY AND IMPLEMENTATION: The study is conducted based on Vaa3D and Python 3.10. Vaa3D is available on GitHub (https://github.com/Vaa3D). The proposed NIEND method is implemented in Python, and hosted on GitHub along with the testing code and data (https://github.com/zzhmark/NIEND). The raw neuronal images of mouse brains can be found at the BICCN's Brain Image Library (BIL) (https://www.brainimagelibrary.org). The detailed list and associated meta information are summarized in Supplementary Table S3.


Assuntos
Compressão de Dados , Neurônios , Animais , Camundongos , Tomografia Computadorizada por Raios X/métodos , Aumento da Imagem , Encéfalo , Processamento de Imagem Assistida por Computador/métodos
5.
Cell Mol Life Sci ; 81(1): 113, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436697

RESUMO

APE1 is an essential gene involved in DNA damage repair, the redox regulation of transcriptional factors (TFs) and RNA processing. APE1 overexpression is common in cancers and correlates with poor patient survival. Stress granules (SGs) are phase-separated cytoplasmic assemblies that cells form in response to environmental stresses. Precise regulation of SGs is pivotal to cell survival, whereas their dysregulation is increasingly linked to diseases. Whether APE1 engages in modulating SG dynamics is worthy of investigation. In this study, we demonstrate that APE1 colocalizes with SGs and promotes their formation. Through phosphoproteome profiling, we discover that APE1 significantly alters the phosphorylation landscape of ovarian cancer cells, particularly the phosphoprofile of SG proteins. Notably, APE1 promotes the phosphorylation of Y-Box binding protein 1 (YBX1) at S174 and S176, leading to enhanced SG formation and cell survival. Moreover, expression of the phosphomutant YBX1 S174/176E mimicking hyperphosphorylation in APE1-knockdown cells recovered the impaired SG formation. These findings shed light on the functional importance of APE1 in SG regulation and highlight the importance of YBX1 phosphorylation in SG dynamics.


Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Neoplasias Ovarianas , Grânulos de Estresse , Proteína 1 de Ligação a Y-Box , Feminino , Humanos , Endodesoxirribonucleases , Neoplasias Ovarianas/genética , Fosforilação , Grânulos de Estresse/metabolismo , Proteína 1 de Ligação a Y-Box/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo
6.
PLoS Genet ; 18(4): e1010137, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35421082

RESUMO

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.


Assuntos
COVID-19 , Processamento Alternativo/genética , COVID-19/genética , Teste para COVID-19 , Humanos , Proteômica , SARS-CoV-2/genética , Transcriptoma
7.
Am J Physiol Cell Physiol ; 327(1): C168-C183, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38826139

RESUMO

In ovarian cancer (OC), identifying key molecular players in disease escalation and chemoresistance remains critical. Our investigation elucidates the role of the DNA polymerase mu (POLM), especially G312R mutation, in propelling oncogenesis through dual pathways. POLMG312R markedly augments the ribonucleotide insertion capability of POLM, precipitating genomic instability. In addition, our research reveals that POLMG312R perturbs collagen alpha-1 (XI) chain (COL11A1) expression-a gene that plays a key role in oncogenesis-and modulates the NF-κB signaling pathway, alters the secretion of downstream inflammatory cytokines, and promotes tumor-macrophage interactions. We illustrate a bidirectional regulatory interaction between POLM, particularly its G312R variant, and COL11A1. This interaction regulates NF-κB signaling, culminating in heightened malignancy and resistance to chemotherapy in OC cells. These insights position the POLM as a potential molecular target for OC therapy, shedding light on the intricate pathways underpinning POLM variant disease progression.NEW & NOTEWORTHY Our research reveals that POLM plays an important role in ovarian cancer development, especially the mutation G312R. We uncover the POLMG312R mutation as a driver of genomic instability in ovarian cancer via aberrant ribonucleotide incorporation. We reveal that POLMG312R upregulates COL11A1 and activates NF-κB signaling, contributing to tumor progression and chemoresistance. This study identifies the POLM-COL11A1-NF-κB axis as a novel oncogenic pathway.


Assuntos
Colágeno Tipo XI , Instabilidade Genômica , NF-kappa B , Neoplasias Ovarianas , Transdução de Sinais , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Instabilidade Genômica/genética , NF-kappa B/metabolismo , NF-kappa B/genética , Colágeno Tipo XI/genética , Colágeno Tipo XI/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Mutação , Animais
8.
Neuroimage ; 292: 120609, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38614371

RESUMO

Current diagnostic systems for Alzheimer's disease (AD) rely upon clinical signs and symptoms, despite the fact that the multiplicity of clinical symptoms renders various neuropsychological assessments inadequate to reflect the underlying pathophysiological mechanisms. Since putative neuroimaging biomarkers play a crucial role in understanding the etiology of AD, we sought to stratify the diverse relationships between AD biomarkers and cognitive decline in the aging population and uncover risk factors contributing to the diversities in AD. To do so, we capitalized on a large amount of neuroimaging data from the ADNI study to examine the inflection points along the dynamic relationship between cognitive decline trajectories and whole-brain neuroimaging biomarkers, using a state-of-the-art statistical model of change point detection. Our findings indicated that the temporal relationship between AD biomarkers and cognitive decline may differ depending on the synergistic effect of genetic risk and biological sex. Specifically, tauopathy-PET biomarkers exhibit a more dynamic and age-dependent association with Mini-Mental State Examination scores (p<0.05), with inflection points at 72, 78, and 83 years old, compared with amyloid-PET and neurodegeneration (cortical thickness from MRI) biomarkers. In the landscape of health disparities in AD, our analysis indicated that biological sex moderates the rate of cognitive decline associated with APOE4 genotype. Meanwhile, we found that higher education levels may moderate the effect of APOE4, acting as a marker of cognitive reserve.


Assuntos
Doença de Alzheimer , Apolipoproteínas E , Disfunção Cognitiva , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Apolipoproteínas E/genética , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Imageamento por Ressonância Magnética , Neuroimagem , Tomografia por Emissão de Pósitrons
9.
J Am Chem Soc ; 146(14): 10052-10059, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38536668

RESUMO

Spin-polarized electrons can improve the efficiency and selectivity of photo- and electro-catalytic reactions, as demonstrated in the past with magnetic or magnetized catalysts. Here, we present a scheme in which spin-polarized charge separation occurs at the interfaces of nonmagnetic semiconductors and molecular films in the absence of a magnetic field. We take advantage of the spin-valley-locked band structure and valley-dependent optical selection rule in group VI transition metal dichalcogenide (TMDC) monolayers to generate spin-polarized electron-hole pairs. Photoinduced electron transfer from WS2 to fullerene (C60) and hole transfer from MoSe2 to phthalocyanine (H2Pc) are found to result in spin polarization lifetimes that are 1 order of magnitude longer than those in the TMDC monolayers alone. Our findings connect valleytronic properties of TMDC monolayers to spin-polarized interfacial charge transfer and suggest a viable route toward spin-selective photocatalysis.

10.
Mol Med ; 30(1): 78, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844873

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is a life-threatening renal disease and needs urgent therapies. Wogonin is renoprotective in DN. This study aimed to explore the mechanism of how wogonin regulated high glucose (HG)-induced renal cell injury. METHODS: Diabetic mice (db/db), control db/m mice, and normal glucose (NG)- or HG-treated human tubule epithelial cells (HK-2) were used to evaluate the levels of suppressor of cytokine signaling 3 (SOCS3), Toll-like receptor 4 (TLR4), inflammation and fibrosis. Lentivirus was used to regulate SOCS3 and TLR4 expressions. After oral gavage of wogonin (10 mg/kg) or vehicle in db/db mice, histological morphologies, blood glucose, urinary protein, serum creatinine values (Scr), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH), and reactive oxygen species (ROS) were assessed. RT-qPCR and Western blot evaluated inflammation and fibrosis-related molecules. RESULTS: HG exposure induced high blood glucose, severe renal injuries, high serumal Src and BUN, low SOD and GSH, and increased ROS. HG downregulated SOCS3 but upregulated TLR4 and JAK/STAT, fibrosis, and inflammasome-related proteins. Wogonin alleviated HG-induced renal injuries by decreasing cytokines, ROS, Src, and MDA and increasing SOD and GSH. Meanwhile, wogonin upregulated SOCS3 and downregulated TLR4 under HG conditions. Wogonin-induced SOCS3 overexpression directly decreased TLR4 levels and attenuated JAK/STAT signaling pathway-related inflammation and fibrosis, but SOCS3 knockdown significantly antagonized the protective effects of wogonin. However, TLR4 knockdown diminished SOCS3 knockdown-induced renal injuries. CONCLUSION: Wogonin attenuates renal inflammation and fibrosis by upregulating SOCS3 to inhibit TLR4 and JAK/STAT pathway.


Assuntos
Nefropatias Diabéticas , Flavanonas , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Receptor 4 Toll-Like , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Animais , Transdução de Sinais/efeitos dos fármacos , Camundongos , Humanos , Masculino , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Linhagem Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças
11.
Anal Chem ; 96(3): 1223-1231, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38205554

RESUMO

Oral squamous cell carcinoma (OSCC) has become a global health problem due to its increasing incidence and high mortality rate. Early intervention through monitoring of the diagnostic biomarker levels during OSCC treatment is critical. Extracellular vesicles (EVs) are emerging surrogates in intercellular communication through transporting biomolecule cargo and have recently been identified as a potential source of biomarkers such as phosphoproteins for many diseases. Here, we developed a multiple reaction monitoring cubed (MRM3) method coupled with a novel sample preparation strategy, extracellular vesicles to phosphoproteins (EVTOP), to quantify phosphoproteins using a minimal amount of saliva (50 µL) samples from OSCC patients with high specificity and sensitivity. Our results established differential patterns in the phosphopeptide content of healthy, presurgery, and postsurgery OSCC patient groups. Notably, we discovered significantly increased salivary phosphorylated alpha-amylase (AMY) in the postsurgery group compared to the presurgery group. We hereby present the first targeted MS method with extremely high sensitivity for measuring endogenous phosphoproteins in human saliva EVs.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/diagnóstico , Biomarcadores Tumorais/análise , Saliva/química , Neoplasias Bucais/diagnóstico , Vesículas Extracelulares/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fosfoproteínas/análise
12.
Bioinformatics ; 39(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36571479

RESUMO

MOTIVATION: Precise reconstruction of neuronal arbors is important for circuitry mapping. Many auto-tracing algorithms have been developed toward full reconstruction. However, it is still challenging to trace the weak signals of neurite fibers that often correspond to axons. RESULTS: We proposed a method, named the NeuMiner, for tracing weak fibers by combining two strategies: an online sample mining strategy and a modified gamma transformation. NeuMiner improved the recall of weak signals (voxel values <20) by a large margin, from 5.1 to 27.8%. This is prominent for axons, which increased by 6.4 times, compared to 2.0 times for dendrites. Both strategies were shown to be beneficial for weak fiber recognition, and they reduced the average axonal spatial distances to gold standards by 46 and 13%, respectively. The improvement was observed on two prevalent automatic tracing algorithms and can be applied to any other tracers and image types. AVAILABILITY AND IMPLEMENTATION: Source codes of NeuMiner are freely available on GitHub (https://github.com/crazylyf/neuronet/tree/semantic_fnm). Image visualization, preprocessing and tracing are conducted on the Vaa3D platform, which is accessible at the Vaa3D GitHub repository (https://github.com/Vaa3D). All training and testing images are cropped from high-resolution fMOST mouse brains downloaded from the Brain Image Library (https://www.brainimagelibrary.org/), and the corresponding gold standards are available at https://doi.brainimagelibrary.org/doi/10.35077/g.25. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Software , Animais , Camundongos , Neurônios , Neuritos , Encéfalo
13.
Plant Physiol ; 192(1): 648-665, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36760172

RESUMO

Cold stress is a key environmental constraint that dramatically affects the growth, productivity, and quality of tomato (Solanum lycopersicum); however, the underlying molecular mechanisms of cold tolerance remain poorly understood. In this study, we identified REDUCED CHLOROPLAST COVERAGE 2 (SlREC2) encoding a tetratricopeptide repeat protein that positively regulates tomato cold tolerance. Disruption of SlREC2 largely reduced abscisic acid (ABA) levels, photoprotection, and the expression of C-REPEAT BINDING FACTOR (CBF)-pathway genes in tomato plants under cold stress. ABA deficiency in the notabilis (not) mutant, which carries a mutation in 9-CIS-EPOXYCAROTENOID DIOXYGENASE 1 (SlNCED1), strongly inhibited the cold tolerance of SlREC2-silenced plants and empty vector control plants and resulted in a similar phenotype. In addition, foliar application of ABA rescued the cold tolerance of SlREC2-silenced plants, which confirms that SlNCED1-mediated ABA accumulation is required for SlREC2-regulated cold tolerance. Strikingly, SlREC2 physically interacted with ß-RING CAROTENE HYDROXYLASE 1b (SlBCH1b), a key regulatory enzyme in the xanthophyll cycle. Disruption of SlBCH1b severely impaired photoprotection, ABA accumulation, and CBF-pathway gene expression in tomato plants under cold stress. Taken together, this study reveals that SlREC2 interacts with SlBCH1b to enhance cold tolerance in tomato via integration of SlNCED1-mediated ABA accumulation, photoprotection, and the CBF-pathway, thus providing further genetic knowledge for breeding cold-resistant tomato varieties.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Repetições de Tetratricopeptídeos , Melhoramento Vegetal , Ácido Abscísico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação/genética , Regulação da Expressão Gênica de Plantas , Temperatura Baixa
14.
Analyst ; 149(12): 3416-3424, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38716512

RESUMO

Extracellular vesicles (EVs) in urine are a promising source for developing non-invasive biomarkers. However, urine concentration and content are highly variable and dynamic, and actual urine collection and handling often is nonideal. Furthermore, patients such as those with prostate diseases have challenges in sample collection due to difficulties in holding urine at designated time points. Here, we simulated the actual situation of clinical sample collection to examine the stability of EVs in urine under different circumstances, including urine collection time and temporary storage temperature, as well as daily urine sampling under different diet conditions. EVs were isolated using functionalized EVtrap magnetic beads and characterized by nanoparticle tracking analysis (NTA), western blotting, electron microscopy, and mass spectrometry (MS). EVs in urine remained relatively stable during temporary storage for 6 hours at room temperature and for 12 hours at 4 °C, while significant fluctuations were observed in EV amounts from urine samples collected at different time points from the same individuals, especially under certain diets. Sample normalization with creatinine reduced the coefficient of variation (CV) values among EV samples from 17% to approximately 6% and facilitated downstream MS analyses. Finally, based on the results, we applied them to evaluate potential biomarker panels in prostate cancer by data-independent acquisition (DIA) MS, presenting the recommendation that can facilitate biomarker discovery with nonideal handling conditions.


Assuntos
Vesículas Extracelulares , Neoplasias da Próstata , Proteômica , Coleta de Urina , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Coleta de Urina/métodos , Masculino , Proteômica/métodos , Neoplasias da Próstata/urina , Espectrometria de Massas/métodos , Biomarcadores/urina , Temperatura
15.
Inorg Chem ; 63(19): 8919-8924, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38698558

RESUMO

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

16.
Inorg Chem ; 63(26): 12240-12247, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946338

RESUMO

An unusual crystalline porous framework constructed from four types of cages, including all-inorganic Keggin-type polyoxometalate (POM) cages [H3W12O40]5-, organic hexamethylenetetramine (Hmt) cages, nanosized silver-Hmt coordination cages, and giant POM-silver-Hmt cages, was hydrothermally synthesized and structurally characterized. The framework features a highly symmetrical structure with one-dimensional nanoscale channels and holds good thermal/solvent stability, which endow it with proton conduction properties and heterogeneous catalytic activity for pyrazole. This paper not only contributes to broadening the structural diversity of cage-based crystalline porous framework materials but also sheds new light on the design of new functional framework materials.

17.
Inorg Chem ; 63(12): 5681-5688, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38484383

RESUMO

Three new POM-based compounds, with formulae [Na0.63Ag3(Htba)2.37(tba)0.63(H2O)2(PMo12O40)]·4H2O (Ag3PMo), [Ag4(Htba)4(H2O)2(PMo12O40)](NO3)·H2O (Ag4PMo), and [Ag3(Htba)2(tba)(PW12O40)0.5](NO3)0.5·13H2O (Ag3PW), were prepared with a 3-(4H-1,2,4-triazol-4-yl)benzoic acid (Htba) ligand, Keggin-type anions ([PMo12O40]3-/[PW12O40]3-), and a silver ion (Ag+). The structural features of these compounds are particularly different from the multinuclear subunits, which are [Ag3(tba)3] clusters in Ag3PMo, [Ag4(tba)3] chains in Ag4PMo, and [Ag3(tba)3]2 clusters in Ag3PW, connected by multidonor atom tba ligands and Ag+ ions. Meanwhile, in these compounds, polyanions act as polydentate ligands to link adjacent Ag-tba metal-organic units and expand their spatial dimensions. These compounds, as heterogeneous catalysts, exhibit high stability and excellent catalytic activity to construct benzimidazoles. Ag3PMo could efficiently catalyze the condensation of benzene-1,2-diamines and benzaldehydes and produce benzimidazoles in good yields. In addition, Ag3PMo could be reused up to 7 times and was suitable for gram-scale reactions.

18.
Fish Shellfish Immunol ; 148: 109495, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38461876

RESUMO

Ube3a is a member of the E3 ubiquitin ligase HECTc family, and its role has been established in neurodevelopmental disorders. However, studies on its role in Japanese flounder are scarce. Thus, in this study, the ube3a of Japanese flounder was cloned, and its role in conferring resistance against Chinook salmon bafnivirus (CSBV) was analyzed. Japanese flounder ube3a encoded a protein containing 834 amino acids. Interestingly, its homology with the Atlantic halibut was determined to be 94%. In addition, there were differential expressions of ube3a in different tissues of Japanese flounder, with the highest expression level observed in the fin, followed by the gills and skin (P ≤ 0.05). Subcellular localization analysis revealed that Ube3a is a cytoplasmic protein. We established an in vitro CSBV infection model using Japanese flounder gill cell line (FG). After ube3a overexpression, the viral load was significantly lower than that of the control group (P ≤ 0.05). Contrastingly, after incubation of FG cells with an E3 ubiquitin ligase inhibitor, the viral load was significantly higher than in the control group (P ≤ 0.01). Then, the expression levels of nf-κb, traf3, and tnf-α after incubation with an E3 ubiquitin ligase inhibitor were examined. The results demonstrated that ube3a may exerted a significant antiviral effect in Japanese flounder via the ubiquitination pathway.


Assuntos
Linguado , Animais , Linguado/genética , Imunidade Inata/genética , Fator de Necrose Tumoral alfa/genética , Linhagem Celular , Ubiquitina-Proteína Ligases/genética , Filogenia
19.
Inorg Chem ; 63(19): 8889-8898, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38693871

RESUMO

Phosphor-in-glass represents a promising avenue for merging the luminous efficiency of high-quality phosphor and the thermal stability of a glass matrix. Undoubtedly, the glass matrix system and its preparation are pivotal factors in achieving high stability and preserving the original performance of embedded phosphor particles. In contrast to the well-established commercial Y3Al5O12:Ce3+ oxide phosphor, red nitride phosphor, which plays a critical role in high-quality lighting, exhibits greater structural instability during the high-temperature synthesis of inorganic glasses. A telluride glass with a refractive index (RI = 2.15@615 nm) akin to that of nitride phosphor (∼2.19) has been devised, demonstrating high efficiency in photon utilization. The lower glass-transition temperature plays a crucial role in safeguarding phosphor particles against erosion resulting from exposure to high-temperature melts. Phosphor-in-glass retains 93% of the quantum efficiency observed for pure phosphor. The assembled white light-emitting diodes module has precise color tuning capabilities, achieving an optimal color rendering index of 93.7, a luminous efficacy of 80.4 lm/W, and a correlated color temperature of 5850 K. These outcomes hold potential for advancing the realm of inorganic package and high-quality white light illumination.

20.
Org Biomol Chem ; 22(4): 784-789, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38168690

RESUMO

This paper reports a novel method for the visible-light-mediated synthesis of quinazolinones from the reaction of benzyl bromides with 2-aminobenzamides. The reaction proceeded efficiently at room temperature upon irradiation with an 18 W blue light-emitting diode in air without photocatalysts or additives. By varying the solvent type, substrate molar ratio, and reaction time, the optimal reaction conditions, including the use of methanol solvent, room temperature, and reaction time of 28 h, were identified. Under these conditions, various quinazolinones were obtained using 18 substrates, with the highest yield of 93%. To determine the industrial value of the proposed method, a scale-up reaction was performed and 80% product yield was achieved. Mechanistic studies revealed that the reaction likely proceeded via a radical pathway and that the hydrogen bromide by-product generated during the first step of the reaction of benzyl bromide with 2-aminobenzamide promoted the subsequent step.

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