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1.
Ecotoxicol Environ Saf ; 284: 117004, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39270416

RESUMO

With the increase of cadmium content in the environment, the losses caused by cadmium-induced intestinal diseases to animal husbandry are increasing year by year. However, most of the on-going research activities focus on zoonotic diseases rather than exploring the mechanisms of animal disease occurrence from an anthropogenic environmental perspective. In this study, stressed Hu sheep under cadmium environmental exposure were selected to explore the mechanism of inflammatory bowel disease development. 16 s, untargeted metabolomics and transcriptomic multiomics were used to analyze the changes of their intestinal tract and intestinal contents. The results showed that the beneficial microorganisms (s_Ruminococcus_sp) in the Cd group were significantly decreased and the potentially harmful microorganisms were significantly enriched, and the changes of these microorganisms affected the changes of metabolites (caprylic acid) to a certain extent, resulting in a decrease in fatty acids in the intestine. Due to the combined effect of cadmium ion and fatty acid reduction, the PPAR signaling pathway was inhibited, and the fatty acid transport and binding were further reduced, causing very serious damage to the intestine. We revealed for the first time the mechanism of intestinal injury in Hu sheeps under cadmium environmental exposure and provided new prevention and treatment methods of intestinal diseases under the environmental exposure to trace metals.


Assuntos
Cádmio , Colo , Intestino Delgado , Receptores Ativados por Proliferador de Peroxissomo , Transdução de Sinais , Animais , Cádmio/toxicidade , Transdução de Sinais/efeitos dos fármacos , Ovinos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Inflamação/induzido quimicamente , Exposição Ambiental/efeitos adversos , Doenças dos Ovinos/induzido quimicamente , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos
2.
Curr Biol ; 34(16): 3763-3777.e5, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39094571

RESUMO

Seedlessness is a crucial quality trait in table grape (Vitis vinifera L.) breeding. However, the development of seeds involved intricate regulations, and the polygenic basis of seed abortion remains unclear. Here, we combine comparative genomics, population genetics, quantitative genetics, and integrative genomics to unravel the evolution and polygenic basis of seedlessness in grapes. We generated the haplotype-resolved genomes for two seedless grape cultivars, "Thompson Seedless" (TS, syn. "Sultania") and "Black Monukka" (BM). Comparative genomics identified a ∼4.25 Mb hemizygous inversion on Chr10 specific in seedless cultivars, with seedless-associated genes VvTT16 and VvSUS2 located at breakpoints. Population genomic analyses of 548 grapevine accessions revealed two distinct clusters of seedless cultivars, and the identity-by-descent (IBD) results indicated that the origin of the seedlessness trait could be traced back to "Sultania." Introgression, rather than convergent selection, shaped the evolutionary history of seedlessness in grape improvement. Genome-wide association study (GWAS) analysis identified 110 quantitative trait loci (QTLs) associated with 634 candidate genes, including previously unidentified candidate genes, such as three 11S GLOBULIN SEED STORAGE PROTEIN and two CYTOCHROME P450 genes, and well-known genes like VviAGL11. Integrative genomic analyses resulted in 339 core candidate genes categorized into 13 functional categories related to seed development. Machine learning-based genomic selection achieved a remarkable prediction accuracy of 97% for seedlessness in grapevines. Our findings highlight the polygenic nature of seedlessness and provide candidate genes for molecular genetics and an effective prediction for seedlessness in grape genomic breeding.


Assuntos
Estudo de Associação Genômica Ampla , Genômica , Locos de Características Quantitativas , Sementes , Vitis , Vitis/genética , Vitis/crescimento & desenvolvimento , Sementes/genética , Sementes/crescimento & desenvolvimento , Genoma de Planta/genética , Herança Multifatorial/genética , Melhoramento Vegetal
3.
Biosensors (Basel) ; 14(8)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39194592

RESUMO

Surface plasmon microscopy proves to be a potent tool for capturing interferometric scattering imaging data of individual particles at both micro and nanoscales, offering considerable potential for label-free analysis of bio-particles and bio-molecules such as exosomes, viruses, and bacteria. However, the manual analysis of acquired images remains a challenge, particularly when dealing with dense samples or strong background noise, common in practical measurements. Manual analysis is not only prone to errors but is also time-consuming, especially when handling a large volume of experimental images. Currently, automated methods for sensing and analysis of such data are lacking. In this paper, we develop an accelerated approach for surface plasmon microscopy imaging of individual particles based on combining the interference scattering model of single particle and deep learning processing. We create hybrid datasets by combining the theoretical simulation of particle images with the actual measurements. Subsequently, we construct a neural network utilizing the EfficientNet architecture. Our results demonstrate the effectiveness of this novel deep learning technique in classifying interferometric scattering images and identifying multiple particles under noisy conditions. This advancement paves the way for practical bio-applications through efficient automated particle analysis.


Assuntos
Aprendizado Profundo , Nanopartículas , Técnicas Biossensoriais , Ressonância de Plasmônio de Superfície , Redes Neurais de Computação
4.
Biomed Pharmacother ; 178: 117176, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39059350

RESUMO

The class-III histone deacetylase SIRT1 is the most extensively investigated sirtuin deacetylase. It is resistant to the broad deacetylase inhibitor trichostatin A and depends on oxidized nicotinamide adenine nucleotide (NAD+). SIRT1 plays a crucial role in the tumorigenesis of numerous types of cancers, including colorectal cancer (CRC). Accumulating evidence indicates that SIRT1 is a therapeutic target for CRC; however, the function and underlying mechanism of SIRT1 in CRC still need to be elucidated. Herein, we provide a detailed and updated review to illustrate that SIRT1 regulates many processes that go awry in CRC cells, such as apoptosis, autophagy, proliferation, migration, invasion, metastasis, oxidative stress, resistance to chemo-radio therapy, immune evasion, and metabolic reprogramming. Moreover, we closely link our review to the clinical practice of CRC treatment, summarizing the mechanisms and prospects of SIRT1 inhibitors in CRC therapy. SIRT1 inhibitors as monotherapy in CRC or in combination with chemotherapy, radiotherapy, and immune therapies are comprehensively discussed. From epigenetic regulation to its potential therapeutic effect, we hope to offer novel insights and a comprehensive understanding of SIRT1's role in CRC.


Assuntos
Neoplasias Colorretais , Sirtuína 1 , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Sirtuína 1/metabolismo , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Proliferação de Células , Apoptose , Epigênese Genética
5.
Front Cell Dev Biol ; 12: 1417502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050887

RESUMO

P65, a protein subunit of NF-κB, is a widely distributed transcription factor in eukaryotic cells and exerts diverse regulatory functions. Post-translational modifications such as phosphorylation, acetylation, methylation and ubiquitination modulate p65 transcriptional activity and function, impacting various physiological and pathological processes including inflammation, immune response, cell death, proliferation, differentiation and tumorigenesis. The intricate interplay between these modifications can be antagonistic or synergistic. Understanding p65 post-translational modifications not only elucidates NF-κB pathway regulation but also facilitates the identification of therapeutic targets and diagnostic markers for associated clinical conditions.

6.
Anal Chem ; 96(27): 10911-10919, 2024 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-38916969

RESUMO

The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.


Assuntos
Técnicas Eletroquímicas , Espectroscopia de Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Tecnologia sem Fio
7.
Org Lett ; 26(27): 5833-5838, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38934368

RESUMO

Reported herein is a practical, economical, and efficient construction of 3-alkylated quinoxalin-2(1H)-ones with alkyl carboxylic acids and alkyl iodides by quinoxalin-2(1H)-one excitation and cobaloxime catalysis. Primary, secondary, and tertiary alkyl iodides and carboxylic acids all could be efficiently transferred into target products with excellent functional group tolerance. Mechanism studies reveal that the quinoxalin-2(1H)-one derivatives could be directly excited and yield alkyl carbon radicals from alkyl carboxylic acids and alkyl iodides with the aid of the cobaloxime complex.

8.
Mamm Genome ; 35(3): 309-323, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38834923

RESUMO

Hydrogen sulfide (H2S) is recognized as the third gasotransmitter, after nitric oxide (NO) and carbon monoxide (CO). It is known for its cardioprotective properties, including the relaxation of blood vessels, promotion of angiogenesis, regulation of myocardial cell apoptosis, inhibition of vascular smooth muscle cell proliferation, and reduction of inflammation. Additionally, abnormal H2S generation has been linked to the development of cardiovascular diseases (CVD), such as pulmonary hypertension, hypertension, atherosclerosis, vascular calcification, and myocardial injury. MicroRNAs (miRNAs) are non-coding, conserved, and versatile molecules that primarily influence gene expression by repressing translation and have emerged as biomarkers for CVD diagnosis. Studies have demonstrated that H2S can ameliorate cardiac dysfunction by regulating specific miRNAs, and certain miRNAs can also regulate H2S synthesis. The crosstalk between miRNAs and H2S offers a novel perspective for investigating the pathophysiology, prevention, and treatment of CVD. The present analysis outlines the interactions between H2S and miRNAs and their influence on CVD, providing insights into their future potential and advancement.


Assuntos
Doenças Cardiovasculares , Sulfeto de Hidrogênio , MicroRNAs , Sulfeto de Hidrogênio/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Animais , Regulação da Expressão Gênica , Biomarcadores/metabolismo
9.
Hortic Res ; 11(6): uhae109, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883333

RESUMO

The economically significant genus Prunus includes fruit and nut crops that have been domesticated for shared and specific agronomic traits; however, the genomic signals of convergent and divergent selection have not been elucidated. In this study, we aimed to detect genomic signatures of convergent and divergent selection by conducting comparative population genomic analyses of the apricot-peach-plum-mei (APPM) complex, utilizing a haplotype-resolved telomere-to-telomere (T2T) genome assembly and population resequencing data. The haplotype-resolved T2T reference genome for the plum cultivar was assembled through HiFi and Hi-C reads, resulting in two haplotypes 251.25 and 251.29 Mb in size, respectively. Comparative genomics reveals a chromosomal translocation of ~1.17 Mb in the apricot genomes compared with peach, plum, and mei. Notably, the translocation involves the D locus, significantly impacting titratable acidity (TA), pH, and sugar content. Population genetic analysis detected substantial gene flow between plum and apricot, with introgression regions enriched in post-embryonic development and pollen germination processes. Comparative population genetic analyses revealed convergent selection for stress tolerance, flower development, and fruit ripening, along with divergent selection shaping specific crop, such as somatic embryogenesis in plum, pollen germination in mei, and hormone regulation in peach. Notably, selective sweeps on chromosome 7 coincide with a chromosomal collinearity from the comparative genomics, impacting key fruit-softening genes such as PG, regulated by ERF and RMA1H1. Overall, this study provides insights into the genetic diversity, evolutionary history, and domestication of the APPM complex, offering valuable implications for genetic studies and breeding programs of Prunus crops.

10.
Adv Sci (Weinh) ; 11(29): e2308523, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38816951

RESUMO

Constrained by a limited understanding of the structure and luminescence mechanisms of carbon dots (CDs), achieving precise enhancement of their photoluminescence (PL) performance without altering the emission wavelength and color remains a challenge. In this work, a deuterated CD is first achieved by simply replacing the reaction solvent from H2O to D2O. The substitution of D atoms for H atoms is not limited on the surface but also within the internal structure of CDs. Deuteration affects the formation of the π-conjugated network structure by altering the content of sp2 carbon and sp3 carbon, ultimately inducing a reconstruction for energy level structure of CDs. Both the intrinsic state and surface state emission, including quantum yield, emission intensity and lifetime, are significantly enhanced after deuteration. It benefits from the reduction in non-radiative transitions, since the lowered vibrational frequencies of D atoms and optimized local energy level distribution in CDs structure. The deuterated CDs are applied in the fabrication of white-light-emitting diodes to show their application potential. This work provides a highly versatile route for improving and controlling photoluminescence performance of CDs and has opportunities to guide the development of CDs for practical applications.

11.
Plant Physiol ; 195(4): 2799-2814, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-38743633

RESUMO

The cultivated apple (Malus domestica Borkh.) is a cross-pollinated perennial fruit tree of great economic importance. Earlier versions of apple reference genomes were unphased, fragmented, and lacked comprehensive insights into the apple's highly heterozygous genome, which impeded advances in genetic studies and breeding programs. In this study, we assembled a haplotype-resolved telomere-to-telomere (T2T) reference genome for the diploid apple cultivar Golden Delicious. Subsequently, we constructed a pangenome based on 12 assemblies from wild and cultivated species to investigate the dynamic changes of functional genes. Our results revealed the gene gain and loss events during apple domestication. Compared with cultivated species, more gene families in wild species were significantly enriched in oxidative phosphorylation, pentose metabolic process, responses to salt, and abscisic acid biosynthesis process. Our analyses also demonstrated a higher prevalence of different types of resistance gene analogs (RGAs) in cultivars than their wild relatives, partially attributed to segmental and tandem duplication events in certain RGAs classes. Structural variations, mainly deletions and insertions, have affected the presence and absence of TIR-NB-ARC-LRR, NB-ARC-LRR, and CC-NB-ARC-LRR genes. Additionally, hybridization/introgression from wild species has also contributed to the expansion of resistance genes in domesticated apples. Our haplotype-resolved T2T genome and pangenome provide important resources for genetic studies of apples, emphasizing the need to study the evolutionary mechanisms of resistance genes in apple breeding.


Assuntos
Domesticação , Genoma de Planta , Malus , Telômero , Malus/genética , Genoma de Planta/genética , Telômero/genética , Genes de Plantas , Haplótipos/genética , Resistência à Doença/genética
12.
Cell Biol Toxicol ; 40(1): 24, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653919

RESUMO

Elongin B (ELOB), a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex, plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Notably, it is documented to facilitate these processes. However, the regulatory role of ELOB in breast cancer remains ambiguous. In this study, through bio-informatic analysis of The Cancer Genome Atlas and Fudan University Shanghai Cancer Center database, we demonstrated that ELOB was over-expressed in breast cancer tissues and was related to unfavorable prognosis. Additionally, pathway enrichment analysis illustrated that high expression of ELOB was associated with multiple cancer promoting pathways, like cell cycle, DNA replication, proteasome and PI3K - Akt signaling pathway, indicating ELOB as a potential anticancer target. Then, we confirmed that both in vivo and in vitro, the proliferation of breast cancer cells could be significantly suppressed by the down-regulation of ELOB. Mechanically, immunoprecipitation and in vivo ubiquitination assays prompted that, as the core element of Cullin2-RBX1-ELOB E3 ligase (CRL2) complex, ELOB regulated the ubiquitination and the subsequent degradation of oncoprotein p14/ARF. Moreover, the anticancer efficacy of erasing ELOB could be rescued by simultaneous knockdown of p14/ARF. Finally, through analyzing breast cancer tissue microarrays and western blot of patient samples, we demonstrated that the expression of ELOB in tumor tissues was elevated in compared to adjacent normal tissues. In conclusion, ELOB is identified to be a promising innovative target for the drug development of breast cancer by promoting the ubiquitination and degradation of oncoprotein p14/ARF.


Assuntos
Neoplasias da Mama , Proliferação de Células , Elonguina , Ubiquitinação , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Elonguina/metabolismo , Elonguina/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Camundongos Nus , Camundongos , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Camundongos Endogâmicos BALB C , Células MCF-7 , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
13.
Mol Plant ; 17(6): 867-883, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38678365

RESUMO

Given the escalating impact of climate change on agriculture and food security, gaining insights into the evolutionary dynamics of climatic adaptation and uncovering climate-adapted variation can empower the breeding of climate-resilient crops to face future climate change. Alfalfa (Medicago sativa subsp. sativa), the queen of forages, shows remarkable adaptability across diverse global environments, making it an excellent model for investigating species responses to climate change. In this study, we performed population genomic analyses using genome resequencing data from 702 accessions of 24 Medicago species to unravel alfalfa's climatic adaptation and genetic susceptibility to future climate change. We found that interspecific genetic exchange has contributed to the gene pool of alfalfa, particularly enriching defense and stress-response genes. Intersubspecific introgression between M. sativa subsp. falcata (subsp. falcata) and alfalfa not only aids alfalfa's climatic adaptation but also introduces genetic burden. A total of 1671 genes were associated with climatic adaptation, and 5.7% of them were introgressions from subsp. falcata. By integrating climate-associated variants and climate data, we identified populations that are vulnerable to future climate change, particularly in higher latitudes of the Northern Hemisphere. These findings serve as a clarion call for targeted conservation initiatives and breeding efforts. We also identified pre-adaptive populations that demonstrate heightened resilience to climate fluctuations, illuminating a pathway for future breeding strategies. Collectively, this study enhances our understanding about the local adaptation mechanisms of alfalfa and facilitates the breeding of climate-resilient alfalfa cultivars, contributing to effective agricultural strategies for facing future climate change.


Assuntos
Mudança Climática , Medicago sativa , Medicago sativa/genética , Medicago sativa/fisiologia , Adaptação Fisiológica/genética , Genômica , Genoma de Planta
14.
J Integr Plant Biol ; 66(7): 1408-1426, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38578160

RESUMO

Structural variations (SVs) are a feature of plant genomes that has been largely unexplored despite their significant impact on plant phenotypic traits and local adaptation to abiotic and biotic stress. In this study, we employed woolly grape (Vitis retordii), a species native to the tropical and subtropical regions of East Asia with both coastal and inland habitats, as a valuable model for examining the impact of SVs on local adaptation. We assembled a haplotype-resolved chromosomal reference genome for woolly grape, and conducted population genetic analyses based on whole-genome sequencing (WGS) data from coastal and inland populations. The demographic analyses revealed recent bottlenecks in all populations and asymmetric gene flow from the inland to the coastal population. In total, 1,035 genes associated with plant adaptive regulation for salt stress, radiation, and environmental adaptation were detected underlying local selection by SVs and SNPs in the coastal population, of which 37.29% and 65.26% were detected by SVs and SNPs, respectively. Candidate genes such as FSD2, RGA1, and AAP8 associated with salt tolerance were found to be highly differentiated and selected during the process of local adaptation to coastal habitats in SV regions. Our study highlights the importance of SVs in local adaptation; candidate genes related to salt stress and climatic adaptation to tropical and subtropical environments are important genomic resources for future breeding programs of grapevine and its rootstocks.


Assuntos
Vitis , Vitis/genética , Adaptação Fisiológica/genética , Genoma de Planta/genética , Genética Populacional , Polimorfismo de Nucleotídeo Único/genética , Tolerância ao Sal/genética , Variação Estrutural do Genoma/genética , Genômica , Genes de Plantas
15.
Opt Express ; 32(7): 12081-12091, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571041

RESUMO

The traditional analysis method for super multi-view 3D display based on geometric optics, which approximates the lenticular lenses as a series of pinhole structures, ignored the chromatic aberration. In this paper, the optimization method based on diffraction theory is proposed for super multi-view 3D display, where the wavefronts are evaluated accurately by the forward propagation method, and the chromatic aberration of the synthetic viewpoint image is reduced dramatically by the backward reconstruction optimization method (BROM). The optical experiment is performed to verify the feasibility of the method, which is consistent with numerical simulation results. It is proved that the proposed method simulates the physical propagation process of super multi-view 3D display and improves the reconstructed image quality. In the future, it can be used to achieve the super multi-view 3D light field technology with low crosstalk.

16.
J Environ Manage ; 356: 120587, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520848

RESUMO

It is challenging to differentiate bacteria residing in the same habitat by direct observation. This difficulty impedes the harvest, application and manipulation of functional bacteria in environmental engineering. In this study, we developed a novel method for rapid differentiation of living denitrifying bacteria based on derivative synchronous fluorescence spectroscopy, as exemplified by three heterotrophic nitrification-aerobic denitrification bacteria having the maximum nitrogen removal efficiencies greater than 90%. The intact bacteria and their living surroundings can be analyzed as an integrated target, which eliminates the need for the complex pre-processing of samples. Under the optimal synchronous scanning parameter (Δλ = 40 nm), each bacterium possesses a unique fluorescence spectral structure and the derivative synchronous fluorescence technique can significantly improve the spectral resolution compared to other conventional fluorescence methods, which enables the rapid differentiation of different bacteria through derivative synchronous fluorescence spectra as fast as 2 min per spectrum. Additionally, the derivative synchronous fluorescence technique can extract the spectral signals contributed by bacterial extracellular substances produced in the biological nitrogen removal process. Moreover, the results obtained from our method can reflect the real-time denitrification properties of bacteria in the biological nitrogen removal process of wastewater. All these merits highlight derivative synchronous fluorescence spectroscopy as a promising analytic method in the environmental field.


Assuntos
Desnitrificação , Nitrificação , Fluorescência , Aerobiose , Bactérias , Nitrogênio , Processos Heterotróficos , Nitritos
17.
Leukemia ; 38(6): 1390-1402, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38459169

RESUMO

G-protein coupled receptor 15 (GPR15) is expressed on T-cells. We previously reported knockout of GPR15 increased acute graft-versus-host disease (GvHD) in mice. In this study, we identified thrombin receptor activating peptide-6 (TRAP-6, peptide sequence: SFLLRN) as an activator of GPR15. GRP15 and ß-arrestin2 were needed for TRAP-6-mediated inhibition of mixed lymphocyte reactions. TRAP-6 decreased acute GvHD in allotransplant models in mice, an effect dependent on GPR15-expression in donor T-cells. RNA-seq and protein analyses indicated TRAP-6 increased binding of ß-arrestin2/TAB1 and inhibited phosphorylation of TAK1 and NF-κB-P65. GPR15 is expressed differently on CD4+ T-cells and CD8+ T-cells. TRAP-6 inhibited phosphorylation of NF-κB-P65 in CD4+ T-cells but increased granzyme B expression in CD8+ T-cells. TRAP-6 decreased acute GvHD without inhibiting graft-versus-tumor (GvT) efficacy against A20 lymphoma cells. SALLRN, a mutant of TRAP-6, preserved the anti-acute GvHD effect but avoided the adverse effects of TRAP-6. TRAP-6 and SALLRN also decreased allogeneic and xenogeneic reactions induced by human blood mononuclear cells. In conclusion, TRAP-6 activated GPR15 on T-cells and decreased acute GvHD in mice without impairing GvT efficacy.


Assuntos
Doença Enxerto-Hospedeiro , Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Camundongos , Doença Enxerto-Hospedeiro/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Doença Aguda , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia
18.
CNS Neurosci Ther ; 30(3): e14563, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38481068

RESUMO

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor in adults. TTFields is a therapy that use intermediate-frequency and low-intensity alternating electric fields to treat tumors. For patients with ndGBM, the addition of TTFields after the concurrent chemoradiotherapy phase of the Stupp regimen can improve prognosis. However, TTFields still has the potential to further prolong the survival of ndGBM patients. AIM: By summarizing the mechanism and application status of TTFields in the treatment of ndGBM, the application prospect of TTFields in ndbm treatment is prospected. METHODS: We review the recent literature and included 76 articles to summarize the mechanism of TTfields in the treatment of ndGBM. The current clinical application status and potential health benefits of TTFields in the treatment of ndGBM are also discussed. RESULTS: TTFields can interfere with tumor cell mitosis, lead to tumor cell apoptosis and increased autophagy, hinder DNA damage repair, induce ICD, activate tumor immune microenvironment, reduce cancer cell metastasis and invasion, and increase BBB permeability. TTFields combines with chemoradiotherapy has made progress, its optimal application time is being explored and the problems that need to be considered when retaining the electrode patches for radiotherapy are further discussed. TTFields shows potential in combination with immunotherapy, antimitotic agents, and PARP inhibitors, as well as in patients with subtentorial gliomas. CONCLUSION: This review summarizes mechanisms of TTFields in the treatment of ndGBM, and describes the current clinical application of TTFields in ndGBM. Through the understanding of its principle and application status, we believe that TTFields still has the potential to further prolong the survival of ndGBM patients. Thus,research is still needed to explore new ways to combine TTFields with other therapies and optimize the use of TTFields to realize its full potential in ndGBM patients.


Assuntos
Neoplasias Encefálicas , Terapia por Estimulação Elétrica , Glioblastoma , Glioma , Adulto , Humanos , Glioblastoma/patologia , Terapia Combinada , Glioma/terapia , Terapia por Estimulação Elétrica/métodos , Prognóstico , Neoplasias Encefálicas/patologia , Microambiente Tumoral
19.
J Adv Res ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38341031

RESUMO

INTRODUCTION: The long-term overuse of malachite green (MG) has potential carcinogenic, teratogenic, and mutagenic effects. The functional nanocomposite is novel and challenging to construct and implement through surface enhanced Raman scattering (SERS) strategy to reveal the contributions in application. OBJECTIVES: The novel Ag-CDs (carbon dots)-PBA (phenyl boric acid) nanocomposite was constructed by a facile route to detect toxic MG molecule with high SERS sensitivity and good uniformity. METHODS: The enhanced substrate used for the detection of MG has been successfully constructed using PBA modulated Ag-CDs on a structured surface with rich binding sites. RESULTS: The fabricated Ag-CDs-PBA substrate can be used to analyze various probe molecules exhibiting high sensitivity, good signal reproducibility, and excellent stability. The mechanism between components has been proved by calculations originating from the plasmonic Ag and active electronic transmission among the bridging CDs and PBA via the close spatial π-π effect. In addition, the accelerated separation of electron-hole pairs was triggered to further improve the SERS activity of the hybrid via a bidirectional charge transfer (CT) process. Significantly, the Ag-CDs-PBA system shows distinctive selectivity, in which PBA can hinder the interference of other species without specific hydroxyl groups. CONCLUSION: Based on this deeper insight on plasmon-mediated mechanism, the SERS substrate was successfully practiced for quantitative determination in real water and fish samples. The strategy developed promises to be a new sensor technology and has great potential for environmental and food safety applications.

20.
Plant Physiol ; 195(2): 1401-1413, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38285049

RESUMO

Plant domestication are evolutionary experiments conducted by early farmers since thousands years ago, during which the crop wild progenitors are artificially selected for desired agronomic traits along with dramatic genomic variation in the course of moderate to severe bottlenecks. However, previous investigations are mainly focused on small-effect variants, while changes in gene contents are rarely investigated due to the lack of population-level assemblies for both the crop and its wild relatives. Here, we applied comparative genomic analyses to discover gene gain and loss during grapevine domestication using long-read assemblies of representative population samples for both domesticated grapevines (V. vinifera ssp. vinifera) and their wild progenitors (V. vinifera ssp. sylvestris). Only ∼7% of gene families were shared by 16 Vitis genomes while ∼8% of gene families were specific to each accession, suggesting dramatic variations of gene contents in grapevine genomes. Compared to wild progenitors, the domesticated accessions exhibited an increased presence of genes associated with asexual reproduction, while the wild progenitors showcased a higher abundance of genes related to pollination, revealing the transition from sexual reproduction to clonal propagation during domestication processes. Moreover, the domesticated accessions harbored fewer disease-resistance genes than wild progenitors. The SVs occurred frequently in aroma and disease-resistance related genes between domesticated grapevines and wild progenitors, indicating the rapid diversification of these genes during domestication. Our study provides insights and resources for biological studies and breeding programs in grapevine.


Assuntos
Domesticação , Genoma de Planta , Genômica , Vitis , Vitis/genética , Genômica/métodos , Genes de Plantas , Produtos Agrícolas/genética
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