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1.
Development ; 151(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39082949

RESUMO

In wheat, the transition of the inflorescence meristem to a terminal spikelet (IM→TS) determines the spikelet number per spike (SNS), an important yield component. In this study, we demonstrate that the plant-specific transcription factor LEAFY (LFY) physically and genetically interacts with WHEAT ORTHOLOG OF APO1 (WAPO1) to regulate SNS and floret development. Loss-of-function mutations in either or both genes result in significant and similar reductions in SNS, as a result of a reduction in the rate of spikelet meristem formation per day. SNS is also modulated by significant genetic interactions between LFY and the SQUAMOSA MADS-box genes VRN1 and FUL2, which promote the IM→TS transition. Single-molecule fluorescence in situ hybridization revealed a downregulation of LFY and upregulation of the SQUAMOSA MADS-box genes in the distal part of the developing spike during the IM→TS transition, supporting their opposite roles in the regulation of SNS in wheat. Concurrently, the overlap of LFY and WAPO1 transcription domains in the developing spikelets contributes to normal floret development. Understanding the genetic network regulating SNS is a necessary first step to engineer this important agronomic trait.


Assuntos
Regulação da Expressão Gênica de Plantas , Meristema , Proteínas de Plantas , Fatores de Transcrição , Triticum , Triticum/genética , Triticum/metabolismo , Triticum/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Meristema/metabolismo , Meristema/genética , Meristema/crescimento & desenvolvimento , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Mutação/genética , Inflorescência/genética , Inflorescência/crescimento & desenvolvimento , Inflorescência/metabolismo
2.
Langmuir ; 40(21): 11056-11066, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38739782

RESUMO

The anti-aging agent TiO2-polyacrylonitrile (PAN) and the mechanical strengthening agent CSW-PAN were prepared by radical polymerization using rutile nano-titanium dioxide (TiO2) and anhydrous calcium sulfate whisker (CSW) as raw materials. The structures of TiO2-PAN and CSW-PAN were characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Simultaneously, the mechanical properties, aging properties, and thermal stability of TiO2-PAN/CSW-PAN/polypropylene (PP) composites were studied, and the results showed that the surfaces of nano-titanium dioxide and calcium sulfate whiskers were successfully grafted with acrylonitrile. Owing to the introduction of new elements, such as acrylonitrile, nano-titanium dioxide and calcium sulfate whiskers have anti-aging properties. In comparison of the impact strength and tensile strength of TiO2-PAN/PP and TiO2-PAN/CSW-PAN/PP before aging, it can be proven that adding CSW-PAN can significantly enhance the mechanical properties of TiO2-PAN/CSW-PAN/PP. After 1000 h of aging, the tensile strength of the ternary composite TiO2-PAN/CSW-PAN/PP was 19.88 MPa when the addition amount of TiO2-PAN and CSW-PAN was 3%. Moreover, the impact strength of the ternary composite material TiO2-PAN/CSW-PAN/PP after 1000 h of aging is even better than that of non-aging pure PP materials, proving that the service life of improved PP products is extended, unnecessary waste and environmental pollution can be relieved, and the needs of specific engineering fields can be met.

3.
Biomacromolecules ; 25(7): 4329-4343, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38833553

RESUMO

The development of nanotherapy targeting mitochondria to alleviate oxidative stress is a critical therapeutic strategy for vascular calcification (VC) in diabetes. In this study, we engineered mitochondria-targeted nanodrugs (T4O@TPP/PEG-PLGA) utilizing terpinen-4-ol (T4O) as a natural antioxidant and mitochondrial protector, PEG-PLGA as the nanocarrier, and triphenylphosphine (TPP) as the mitochondrial targeting ligand. In vitro assessments demonstrated enhanced cellular uptake of T4O@TPP/PEG-PLGA, with effective mitochondrial targeting. This nanodrug successfully reduced oxidative stress induced by high glucose levels in vascular smooth muscle cells. In vivo studies showed prolonged retention of the nanomaterials in the thoracic aorta for up to 24 h. Importantly, experiments in diabetic VC models underscored the potent antioxidant properties of T4O@TPP/PEG-PLGA, as evidenced by its ability to mitigate VC and restore mitochondrial morphology. These results suggest that these nanodrugs could be a promising strategy for managing diabetic VC.


Assuntos
Antioxidantes , Mitocôndrias , Estresse Oxidativo , Calcificação Vascular , Animais , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia , Estresse Oxidativo/efeitos dos fármacos , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Camundongos , Masculino , Polietilenoglicóis/química , Ratos , Humanos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo
4.
RSC Adv ; 14(9): 6041-6047, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38362080

RESUMO

By employing the radical polymerization method, acrylonitrile (AN) was grafted on the surface of nano titanium dioxide (TiO2), and the calcium sulfate whisker (CSW) was modified using the coupling agent KH570 to provide ultraviolet (UV)-absorption capacity. The prepared TiO2-PAN and CSW-PAN materials can improve the anti-aging performance and mechanical properties of polypropylene (PP) and meet the application requirements of high-performance polypropylene. Further, the obtained PP composites show prolonged service life and application scope, which can effectively reduce white waste and avoid both resource waste and environmental pollution.

5.
J Mater Chem B ; 12(12): 3063-3078, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38441636

RESUMO

Lipid accumulation is a factor contributing to the pathogenesis of acute kidney injury (AKI), yet there are currently no approved pharmacotherapies aside from adjuvant therapy. A developed reactive oxygen species (ROS)-responsive drug delivery system (NPSBG@Cur) was developed to deliver the autophagy activator curcumin (Cur) in order to alleviate AKI by activating autophagy and promoting lipid droplet degradation. The nanoparticles were shown to be ROS-responsive in the H2O2 medium and demonstrate ROS-responsive uptake in palmitate (PA)-induced oxidative stress-damaged cells. NPSBG@Cur was found to effectively inhibit lipid accumulation by autophagosome transport in kidney tubular cells. Additionally, in a mouse AKI model, NPSBG@Cur was observed to significantly ameliorate renal damage by activating autophagy flux and improving lipid transport. These results suggest that the ROS-responsive drug delivery system augmented the therapeutic effect of Cur on AKI by improving lipid metabolism through autophagy activation. Therefore, targeting lipid metabolism with NPSBG@Cur may be a promising AKI treatment strategy.


Assuntos
Injúria Renal Aguda , Curcumina , Nanopartículas , Camundongos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Injúria Renal Aguda/tratamento farmacológico , Lipídeos
6.
Sci Rep ; 14(1): 14767, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926539

RESUMO

Heart disease is the world's leading cause of death. Diagnostic models based on electrocardiograms (ECGs) are often limited by the scarcity of high-quality data and issues of data imbalance. To address these challenges, we propose a conditional generative adversarial network (CECG-GAN). This strategy enables the generation of samples that closely approximate the distribution of ECG data. Additionally, CECG-GAN addresses waveform jitter, slow processing speeds, and dataset imbalance issues through the integration of a transformer architecture. We evaluated this approach using two datasets: MIT-BIH and CSPC2020. The experimental results demonstrate that CECG-GAN achieves outstanding performance metrics. Notably, the percentage root mean square difference (PRD) reached 55.048, indicating a high degree of similarity between generated and actual ECG waveforms. Additionally, the Fréchet distance (FD) was approximately 1.139, the root mean square error (RMSE) registered at 0.232, and the mean absolute error (MAE) was recorded at 0.166.


Assuntos
Eletrocardiografia , Humanos , Eletrocardiografia/métodos , Cardiopatias/diagnóstico , Redes Neurais de Computação , Algoritmos , Processamento de Sinais Assistido por Computador , Bases de Dados Factuais
7.
ACS Synth Biol ; 13(6): 1679-1693, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38819389

RESUMO

Immune-checkpoint blockade (ICB) reinvigorates T cells from exhaustion and potentiates T-cell responses to tumors. However, most patients do not respond to ICB therapy, and only a limited response can be achieved in a "cold" tumor with few infiltrated lymphocytes. Synthetic biology can be used to engineer bacteria as controllable bioreactors to synthesize biotherapeutics in situ. We engineered attenuated Salmonella VNP20009 with synthetic gene circuits to produce PD-1 and Tim-3 scFv to block immunosuppressive receptors on exhausted T cells to reinvigorate their antitumor response. Secreted PD-1 and Tim-3 scFv bound PD-1+ Tim-3+ T cells through their targeting receptors in vitro and potentiated the T-cell secretion of IFN-γ. Engineered bacteria colonized the hypoxic core of the tumor and synthesized PD-1 and Tim-3 scFv in situ, reviving CD4+ T cells and CD8+ T cells to execute an antitumor response. The bacteria also triggered a strong innate immune response, which stimulated the expansion of IFN-γ+ CD4+ T cells within the tumors to induce direct and indirect antitumor immunity.


Assuntos
Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Salmonella , Inibidores de Checkpoint Imunológico/farmacologia , Animais , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Camundongos , Salmonella/imunologia , Salmonella/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/genética , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Humanos , Interferon gama/metabolismo , Interferon gama/imunologia , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/farmacologia , Camundongos Endogâmicos C57BL , Biologia Sintética/métodos , Linfócitos T CD4-Positivos/imunologia , Imunoterapia/métodos
8.
Plant Commun ; 5(5): 100883, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38491771

RESUMO

Spelt (Triticum aestivum ssp. spelta) is an important wheat subspecies mainly cultivated in Europe before the 20th century that has contributed to modern wheat breeding as a valuable genetic resource. However, relatively little is known about the origins and maintenance of spelt populations. Here, using resequencing data from 416 worldwide wheat accessions, including representative spelt wheat, we demonstrate that European spelt emerged when primitive hexaploid wheat spread to the west and hybridized with pre-settled domesticated emmer, the putative maternal donor. Genomic introgression regions from domesticated emmer confer spelt's primitive morphological characters used for species taxonomy, such as tenacious glumes and later flowering. We propose a haplotype-based "spelt index" to identify spelt-type wheat varieties and to quantify utilization of the spelt gene pool in modern wheat cultivars. This study reveals the genetic basis for the establishment of the spelt wheat subspecies in a specific ecological niche and the vital role of the spelt gene pool as a unique germplasm resource in modern wheat breeding.


Assuntos
Pool Gênico , Genoma de Planta , Melhoramento Vegetal , Triticum , Triticum/genética , Haplótipos , Genômica , Evolução Molecular
9.
Diabetes ; 73(8): 1325-1335, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38771941

RESUMO

An important factor in the development of type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9), in ß-cells. Therefore, modulation of pancreas-infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating new-onset T1D. We genetically engineered macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict islet autoreactive T lymphocytes and protect ß-cells from destruction. Intriguingly, overexpression of Gal-9 stimulated macrophage polarization to the M2 phenotype with immunosuppressive attributes. Alternatively, both PD-L1- and Gal-9-presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhered to T cells via the interaction of programmed cell death protein 1/PD-L1 or T-cell immunoglobulin mucin 3/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T-cell apoptosis and splenic regulatory T (Treg) cell formation in vitro. Notably, PD-L1-Gal-9 aEVs efficaciously reversed new-onset hyperglycemia in NOD mice, prevented T1D progression, and decreased the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas, which together contributed to the preservation of residual ß-cell survival and mitigation of hyperglycemia.


Assuntos
Antígeno B7-H1 , Diabetes Mellitus Tipo 1 , Vesículas Extracelulares , Galectinas , Camundongos Endogâmicos NOD , Animais , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Vesículas Extracelulares/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Camundongos , Galectinas/metabolismo , Galectinas/genética , Células Secretoras de Insulina/metabolismo , Macrófagos/metabolismo , Linfócitos T Reguladores/imunologia , Bioengenharia/métodos , Feminino
10.
ACS Omega ; 8(51): 48825-48842, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38162735

RESUMO

The research on intrinsic flame retardant has become a hot topic in the field of flame retardant. The synthesis of reactive flame-retardant monomer is one of the effective methods to obtain an intrinsic flame retardant. In addition, in view of the small molecular flame retardant easily migrates from the polymer during the use process, which leads to the gradual reduction of the flame retardant effect and even the gradual loss of flame retardant performance, and the advantages of atom transfer radical polymerization (ATRP) technology in polymer structure design and function customization, we first synthesized reactive flame retardant monomer 6-(hydroxymethyl)dibenzo[c,e][1,2]oxaphosphinine 6-oxide (FAA-DOPO), then synthesized polystyrene bromine (PS148-Br) macromolecular initiator by ATRP technology, and finally obtained block copolymer polystyrene-b-poly{6-(hydroxymethyl)dibenzo[c,e][1,2]oxaphosphinine 6-oxide} (PS-b-PFAA-DOPO) by the polymerization of FAA-DOPO initiated by macromolecular initiator PS148-Br by ATRP technology. The chemical structure of FAA-DOPO was characterized by 1D and 2D NMR (1H, 13C, DEPT 135, HSQC, COSY, NOE, and HMBC) spectra, Fourier transform infrared spectroscopy (FTIR), liquid chromatography-tandem mass spectrometry (LC-MS) and X-ray photoelectron spectroscopy (XPS). The chemical structure and molecular weight of PS-b-PFAA-DOPO were characterized by FTIR and gel permeation chromatography (GPC). The thermal and flame-retardant properties of PS-b-PFAA-DOPO were characterized by thermogravimetry analysis (TG), UL-94, limiting oxygen index (LOI), and microscale combustion calorimetry (MCC). It was found that FAA-DOPO could be used as a monomer for polymerization, although FAA-DOPO had a large steric hindrance from the chemical structure of FAA-DOPO, the UL-94 grade of PS-b-PFAA-DOPO reached the V-0 grade, and the LOI increased by 59.12% compared with PS148-Br.

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