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1.
Plant Cell ; 35(10): 3889-3910, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37399070

RESUMO

Dissecting genetic components in crop plants associated with heat stress (HS) sensing and adaptation will facilitate the design of modern crop varieties with improved thermotolerance. However, the molecular mechanisms underlying the ON/OFF switch controlling HS responses (HSRs) in wheat (Triticum aestivum) remain largely unknown. In this study, we focused on the molecular action of TaHsfA1, a class A heat shock transcription factor, in sensing dynamically changing HS signals and regulating HSRs. We show that the TaHsfA1 protein is modified by small ubiquitin-related modifier (SUMO) and that this modification is essential for the full transcriptional activation activity of TaHsfA1 in triggering downstream gene expression. During sustained heat exposure, the SUMOylation of TaHsfA1 is suppressed, which partially reduces TaHsfA1 protein activity, thereby reducing the intensity of downstream HSRs. In addition, we demonstrate that TaHsfA1 interacts with the histone acetyltransferase TaHAG1 in a thermosensitive manner. Together, our findings emphasize the importance of TaHsfA1 in thermotolerance in wheat. In addition, they define a highly dynamic SUMOylation-dependent "ON/OFF" molecular switch that senses temperature signals and contributes to thermotolerance in crops.


Assuntos
Sumoilação , Triticum , Triticum/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Resposta ao Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo
2.
Plant Cell ; 35(6): 1848-1867, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-36905284

RESUMO

The dynamics of gene expression in crop grains has typically been investigated at the transcriptional level. However, this approach neglects translational regulation, a widespread mechanism that rapidly modulates gene expression to increase the plasticity of organisms. Here, we performed ribosome profiling and polysome profiling to obtain a comprehensive translatome data set of developing bread wheat (Triticum aestivum) grains. We further investigated the genome-wide translational dynamics during grain development, revealing that the translation of many functional genes is modulated in a stage-specific manner. The unbalanced translation between subgenomes is pervasive, which increases the expression flexibility of allohexaploid wheat. In addition, we uncovered widespread previously unannotated translation events, including upstream open reading frames (uORFs), downstream open reading frames (dORFs), and open reading frames (ORFs) in long noncoding RNAs, and characterized the temporal expression dynamics of small ORFs. We demonstrated that uORFs act as cis-regulatory elements that can repress or even enhance the translation of mRNAs. Gene translation may be combinatorially modulated by uORFs, dORFs, and microRNAs. In summary, our study presents a translatomic resource that provides a comprehensive and detailed overview of the translational regulation in developing bread wheat grains. This resource will facilitate future crop improvements for optimal yield and quality.


Assuntos
MicroRNAs , Triticum , Triticum/genética , Pão , MicroRNAs/genética , RNA Mensageiro , Polirribossomos , Fases de Leitura Aberta/genética , Grão Comestível/genética , Biossíntese de Proteínas/genética
3.
Drug Resist Updat ; 72: 101018, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37979442

RESUMO

Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role of copper and copper triggered cell death in the pathogenesis of cancers have attracted attentions. Cuproptosis has garnered enormous interest in cancer research communities because of its great potential for cancer therapy. Copper-based treatment exerts an inhibiting role in tumor growth and may open the door for the treatment of chemotherapy-insensitive tumors. In this review, we provide a critical analysis on copper homeostasis and the role of copper dysregulation in the development and progression of cancers. Then the core molecular mechanisms of cuproptosis and its role in cancer is discussed, followed by summarizing the current understanding of copper-based agents (copper chelators, copper ionophores, and copper complexes-based dynamic therapy) for cancer treatment. Additionally, we summarize the emerging data on copper complexes-based agents and copper ionophores to subdue tumor chemotherapy resistance in different types of cancers. We also review the small-molecule compounds and nanoparticles (NPs) that may kill cancer cells by inducing cuproptosis, which will shed new light on the development of anticancer drugs through inducing cuproptosis in the future. Finally, the important concepts and pressing questions of cuproptosis in future research that should be focused on were discussed. This review article suggests that targeting cuproptosis could be a novel antitumor therapy and treatment strategy to overcome cancer drug resistance.


Assuntos
Cobre , Neoplasias , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Morte Celular , Ionóforos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Apoptose
4.
Drug Resist Updat ; 73: 101042, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219532

RESUMO

Drug resistance in cancer remains a major challenge in oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as a critical player in the development of drug resistance in cancer cells. This comprehensive review explores the intricate relationship between NF-κB and drug resistance in cancer. We delve into the molecular mechanisms through which NF-κB activation contributes to resistance against chemotherapeutic agents, targeted therapies, and immunotherapies. Additionally, we discuss potential strategies to overcome this resistance by targeting NF-κB signaling, such as small molecule inhibitors and combination therapies. Understanding the multifaceted interactions between NF-κB and drug resistance is crucial for the development of more effective cancer treatment strategies. By dissecting the complex signaling network of NF-κB, we hope to shed light on novel therapeutic approaches that can enhance treatment outcomes, ultimately improving the prognosis for cancer patients. This review aims to provide a comprehensive overview of the current state of knowledge on NF-κB and its role in drug resistance, offering insights that may guide future research and therapeutic interventions in the fight against cancer.


Assuntos
NF-kappa B , Neoplasias , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral
5.
New Phytol ; 242(2): 507-523, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38362849

RESUMO

Polyploidization is a major event driving plant evolution and domestication. However, how reshaped epigenetic modifications coordinate gene transcription to generate phenotypic variations during wheat polyploidization is currently elusive. Here, we profiled transcriptomes and DNA methylomes of two diploid wheat accessions (SlSl and AA) and their synthetic allotetraploid wheat line (SlSlAA), which displayed elongated root hair and improved root capability for nitrate uptake and assimilation after tetraploidization. Globally decreased DNA methylation levels with a reduced difference between subgenomes were observed in the roots of SlSlAA. DNA methylation changes in first exon showed strong connections with altered transcription during tetraploidization. Homoeolog-specific transcription was associated with biased DNA methylation as shaped by homoeologous sequence variation. The hypomethylated promoters showed significantly enriched binding sites for MYB, which may affect gene transcription in response to root hair growth. Two master regulators in root hair elongation pathway, AlCPC and TuRSL4, exhibited upregulated transcription levels accompanied by hypomethylation in promoter, which may contribute to the elongated root hair. The upregulated nitrate transporter genes, including NPFs and NRTs, also are significantly associated with hypomethylation, indicating an epigenetic-incorporated regulation manner in improving nitrogen use efficiency. Collectively, these results provided new insights into epigenetic changes in response to crop polyploidization and underscored the importance of epigenetic regulation in improving crop traits.


Assuntos
Metilação de DNA , Tetraploidia , Metilação de DNA/genética , Triticum/genética , Epigênese Genética , Transcriptoma , Regulação da Expressão Gênica de Plantas
6.
Plant Physiol ; 193(1): 578-594, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37249052

RESUMO

Intracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshape the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we developed an approach, IGTminer, that maps the evolutionary trajectories of IGTs using collinearity and gene reannotation across multiple genome assemblies. We applied IGTminer to create a nuclear organellar gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops. The resulting NOGs were verified by experiments and sequencing data sets. Our analysis revealed that most NOGs were recently transferred and lineage specific and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat (Triticum aestivum) had a higher retention rate of NOGs than maize (Zea mays) and rice (Oryza sativa), and the retained NOGs were likely involved in photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during 2 rounds of polyploidization, contributing to the genetic diversity among modern wheat accessions. We implemented an interactive web server to facilitate the exploration of NOGs in Poaceae. In summary, this study provides resources and insights into the roles of IGTs in shaping interspecies and intraspecies genome variation and driving plant genome evolution.


Assuntos
Oryza , Poaceae , Poaceae/genética , Triticum/genética , Genoma de Planta/genética , Oryza/genética , Zea mays/genética , Evolução Molecular
7.
Plant Cell ; 33(3): 603-622, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955492

RESUMO

In wheat (Triticum aestivum L.), breeding efforts have focused intensively on improving grain yield and quality. For quality, the content and composition of seed storage proteins (SSPs) determine the elasticity of wheat dough and flour processing quality. Moreover, starch levels in seeds are associated with yield. However, little is known about the mechanisms that coordinate SSP and starch accumulation in wheat. In this study, we explored the role of the endosperm-specific NAC transcription factor TaNAC019 in coordinating SSP and starch accumulation. TaNAC019 binds to the promoters of TaGlu-1 loci, encoding high molecular weight glutenin (HMW-GS), and of starch metabolism genes. Triple knock-out mutants of all three TaNAC019 homoeologs exhibited reduced transcript levels for all SSP types and genes involved in starch metabolism, leading to lower gluten and starch contents, and in flour processing quality parameters. TaNAC019 directly activated the expression of HMW-GS genes by binding to a specific motif in their promoters and interacting with the TaGlu-1 regulator TaGAMyb. TaNAC019 also indirectly regulated the expression of TaSPA, an ortholog of maize Opaque2 that activates SSP accumulation. Therefore, TaNAC019 regulation of starch- and SSP-related genes has key roles in wheat grain quality. Finally, we identified an elite allele (TaNAC019-BI) associated with flour processing quality, providing a candidate gene for breeding wheat with improved quality.


Assuntos
Endosperma/metabolismo , Proteínas de Plantas/metabolismo , Amido/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Endosperma/genética , Glutens/genética , Glutens/metabolismo , Proteínas de Plantas/genética , Amido/genética , Fatores de Transcrição/genética , Triticum/genética , Triticum/metabolismo
8.
Langmuir ; 40(14): 7286-7299, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38535519

RESUMO

As a unique unimolecular nanoobject, molecular bottlebrushes (MBBs) have attracted great interest from researchers in nanocarriers attributed to their defined structure, size, and shape. MBBs with various architectures have been proposed and constructed with well-defined domains for loading "cargos", including core, shell, and periphery functional groups. Compared with nanomaterials based on self-assembly, MBBs have lots of advantages, including facile synthesis, flexible compositions, favorable stability, and tunable size and shape, that make them a promising nanoplatform for various applications. This paper summarizes the recent progress during the past decade, with a focus on developments within the last five years in the synthesis of MBBs with different architectures, and uses them as nanocarriers in drug delivery, biological imaging, and other emerging applications.


Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química
9.
Parasitology ; 151(2): 185-190, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38186337

RESUMO

Parasitoid wasps, notably egg parasitoids of the family Eupelmidae (Hymenoptera: Chalcidoidea), a key natural enemy of insect pests, offer a sustainable approach to pest management in agriculture. This study investigated the venom apparatus's developmental dynamics across 4 species of eupelmid egg parasitoids: Anastatus. japonicus, Anastatus fulloi, Mesocomys trabalae and Mesocomys albitarsis. A comprehensive anatomical investigation revealed differences in the dimensions of the venom apparatus across different developmental stages in adult females. We found that the venom apparatus of these 4 studied species consists of a venom gland and a reservoir with an associated Dufour's gland. As the length of post-emergence increases, a significant enlargement in the venom apparatus is evident across all the studied parasitoid species. Notably, M. albitarsis consistently exhibites the shortest venom gland length, whereas that of A. fulloi is the longest among the observed species. At the high day age, the width of venom glands of the 2 Mesocomys species surpasses those of the Anastatus species; for the volume of the venom reservoir, there is a steady increase in all 4 species before the age of 6­7 days, with a decline on 8th day, especially for A. japonicus. This research provided new insights into the developmental trajectories of venom apparatus in eupelmid egg parasitoids and the potential impact of venom potency on their success.


Assuntos
Vespas , Feminino , Animais , Agricultura
10.
Chemistry ; 29(12): e202203460, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36445789

RESUMO

Insulin, a main medication to control glycemia of type 1 and advanced type 2 diabetes, faces problems of a short half-life and poor stability during its clinical use. Zwitterionic polymer shows unique properties of antifouling and low immunogenicity. Here, we have synthesized a new insulin-zwitterionic polymer conjugate (INS-PMPC) through grafting-from strategy by controlled radical polymerization. Apart from showing excellent stability upon mechanical agitation, the resulting INS-PMPC conjugate provided over 20 h of glycemic control due to improved pharmacokinetics in diabetic mice with one single subcutaneous injection. Most importantly, this insulin-zwitterionic polymer conjugate significantly decreases the incidence of hypoglycemia.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hipoglicemia , Animais , Camundongos , Insulina de Ação Prolongada , Polímeros , Hipoglicemia/epidemiologia , Insulina
11.
BMC Cancer ; 23(1): 1157, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012547

RESUMO

OBJECTIVE: To compare the computed tomography (CT) images of patients with locally advanced gastric cancer (GC) before and after neoadjuvant chemotherapy (NAC) in order to identify CT features that could predict pathological response to NAC. METHODS: We included patients with locally advanced GC who underwent gastrectomy after NAC from September 2016 to September 2021. We retrieved and collected the patients' clinicopathological characteristics and CT images before and after NAC. We analyzed CT features that could differentiate responders from non-responders and established a logistic regression equation based on these features. RESULTS: We included 97 patients (69 [71.1%] men; median [range] age, 60 [26-75] years) in this study, including 66 (68.0%) responders and 31 (32.0%) non-responders. No clinicopathological variable prior to treatment was significantly associated with pathological response. Out of 16 features, three features (ratio of tumor thickness reduction, ratio of reduction of primary tumor attenuation in arterial phase, and ratio of reduction of largest lymph node attenuation in venous phase) on logistic regression analysis were used to establish a regression equation that demonstrated good discrimination performance in predicting pathological response (area under receiver operating characteristic curve 0.955; 95% CI, 0.911-0.998). CONCLUSION: Logistic regression equation based on three CT features can help predict the pathological response of patients with locally advanced GC to NAC.


Assuntos
Segunda Neoplasia Primária , Neoplasias Gástricas , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Terapia Neoadjuvante , Tomografia Computadorizada por Raios X , Curva ROC , Gastrectomia , Estudos Retrospectivos
12.
Biomacromolecules ; 24(2): 909-920, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36629517

RESUMO

Following brain trauma, secondary injury from molecular and cellular changes causes progressive cerebral tissue damage. Acute/chronic neuroinflammation following traumatic brain injury (TBI) is a key player in the development of secondary injury. Rapidly elevated cell-free DNAs (cfDNAs) due to cell death could lead to production of inflammatory cytokines that aggravate TBI. Herein, we designed poly(amino acid)-based cationic nanoparticles (cNPs) and applied them intravenously in a TBI mice model with the purpose of scavenging cfDNA in the brain and suppressing the acute inflammation. In turn, these cNPs could effectively eliminate endogenous cfDNA, inhibit excessive activation of inflammation, and promote neural functional recovery.


Assuntos
Aminoácidos , Lesões Encefálicas Traumáticas , Camundongos , Animais , Inflamação/metabolismo , Encéfalo/metabolismo , Citocinas/metabolismo , Camundongos Endogâmicos C57BL
13.
Eur Radiol ; 33(12): 8948-8956, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37389605

RESUMO

OBJECTIVES: There still remain challenges to accurate diagnosis of lymph node (LN) involvement in gastric cancer (GC) on conventional CT. This study evaluated the quantitative data derived from dual-layer spectral detector CT (DLCT) for preoperative diagnosis of metastatic LNs compared to conventional CT images. METHODS: Patients with adenocarcinoma scheduled for gastrectomy were enrolled in this prospective study from July, 2021, to February, 2022. Regional LNs were labeled on preoperative DLCT. The LNs were located and matched using carbon nanoparticle solution during surgery according to their locations and anatomic landmarks on preoperative images. The matched LNs were randomly split into training and validation cohorts in a ratio of 2:1. The DLCT quantitative parameters in the training cohort were investigated using logistic regression models to identify independent predictors of metastatic LNs, and these predictors were subsequently applied to the validation cohort. Receiver operating characteristic curves were compared between the DLCT parameters and conventional CT images. RESULTS: Fifty-five patients were included in the study, with 267 successfully matched LNs (90 metastatic, 177 nonmetastatic). Independent predictors included arterial phase CT attenuation on 70-keV images, venous phase electron density, and clustered feature. These combination predictors had areas under the curve (AUC) of 0.855 and 0.907 in the training and validation cohorts, respectively. Compared to conventional CT criteria alone, the model had higher AUC and accuracy (0.741 vs. 0.907, 75.28% vs. 87.64%; p < 0.01) for LN diagnosis. CONCLUSION: Incorporating DLCT parameters improved preoperative diagnosis of LN metastasis in GC, increasing the accuracy of clinical N stage. CLINICAL RELEVANCE STATEMENT: Compared to conventional CT criteria, quantitative parameters from dual-layer spectral detector CT showed higher diagnostic efficacy for the preoperative diagnosis of lymph node metastases in gastric cancer, increasing the accuracy of clinical N stage. KEY POINTS: • Quantitative parameters from dual-layer spectral detector CT are useful for the preoperative diagnosis of lymph node metastases in gastric adenocarcinoma, increasing the accuracy of clinical N stage. • The values for metastatic lymph nodes are higher than those of nonmetastatic ones. The arterial phase of CT attenuation on 70-keV images, venous phase of electron density, and clustered feature independently predicted lymph node metastases. • Prediction model had area under the curve of 0.907, sensitivity of 81.82%, specificity of 91.07%, and accuracy of 87.64% for the preoperative diagnosis of lymph node metastasis.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estudos Prospectivos , Metástase Linfática/patologia , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Estudos Retrospectivos
14.
Macromol Rapid Commun ; 44(23): e2300362, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37625446

RESUMO

Molecular bottlebrush (MBB) refer to a synthetic macromolecule, in which a mass of polymeric side chains (SCs) are covalently connected to a macromolecular backbone densely, representing an important type of unimolecular nanomaterial. The chemical composition, size, shape, and surface property of MBB can be precisely tailored by varying the backbones and SCs as well as the grafting density (Gdst ). Meanwhile, the topological structure of backbones and SCs can also significantly affect the chemical and physical properties of MBBs. For the past few years, by combining the structure features of MBB, the polymers with diverse architectures using MBB as building block are synthesized, including linear, branched, and cyclic MBB etc. These promising architectural features will bring MBBs with diverse architectures and lots of applications in advanced materials. For this reason, this work is interested in giving a briefly summary of the recent progress on tailor of well-defined MBBs with diverse architectures using grafting-onto strategy combined with controlled polymerization technique.


Assuntos
Nanoestruturas , Polímeros , Polímeros/química , Substâncias Macromoleculares , Nanoestruturas/química , Polimerização , Propriedades de Superfície
15.
Bull Entomol Res ; 113(4): 555-564, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37350316

RESUMO

Two thrips, Megalurothrips usitatus (Bagnall) and Frankliniella intonsa (Trybom) are major pests of cowpea in South China. To realistically compare the growth, development and reproductive characteristics of these two thrips species, we compared their age-stage, two-sex life tables on cowpea pods under summer and winter natural environmental regimes. The results showed that the total preadult period of M. usitatus was 8.09 days, which was significantly longer than that of F. intonsa (7.06 days), while the adult female longevity of M. usitatus (21.14 days) was significantly shorter than that of F. intonsa (25.77 days). Significant differences were showed in male adult longevity (10.68 days for F. intonsa and 16.95 days for M. usitatus) and the female ratio of offspring (0.67 for F. intonsa and 0.51 for M. usitatus), and the total preadult period of M. usitatus (16.20 days) was significantly longer than that of F. intonsa (13.66 days) in the winter regime. The net reproductive rate (summer: R0 = 85.62, winter: R0 = 105.22), intrinsic rate of increase (summer: r = 0.3020 day-1, winter: r = 0.2115 day-1), finite rate of increase (summer: λ = 1.3526 day-1, winter: λ = 1.2356 day-1) and gross reproduction rate (summer: GRR = 139.34, winter: GRR = 159.88) of F. intonsa were higher than those of M. usitatus (summer: R0 = 82.91, r = 0.2741, λ = 1.3155, GRR = 135.71; winter: R0 = 80.62, r = 0.1672, λ = 1.1820, GRR = 131.26), and the mean generation times (summer: T = 14.73 days, winter: T = 22.01 days) of F. intonsa were significantly shorter than those of M. usitatus (summer: T = 16.11 days, winter: T = 26.25 days). These results may contribute to a better understanding of the bioecology of different thrips species, especially the interspecific competition between two economically important cowpea thrips with the same ecological niche in a changing environment.


Assuntos
Tisanópteros , Vigna , Masculino , Feminino , Animais , Tábuas de Vida , Reprodução , Biologia
16.
Sensors (Basel) ; 23(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37896601

RESUMO

Anomaly detection tasks involving time-series signal processing have been important research topics for decades. In many real-world anomaly detection applications, no specific distributions fit the data, and the characteristics of anomalies are different. Under these circumstances, the detection algorithm requires excellent learning ability of the data features. Transformers, which apply the self-attention mechanism, have shown outstanding performances in modelling long-range dependencies. Although Transformer based models have good prediction performance, they may be influenced by noise and ignore some unusual details, which are significant for anomaly detection. In this paper, a novel temporal context fusion framework: Temporal Context Fusion Transformer (TCF-Trans), is proposed for anomaly detection tasks with applications to time series. The original feature transmitting structure in the decoder of Informer is replaced with the proposed feature fusion decoder to fully utilise the features extracted from shallow and deep decoder layers. This strategy prevents the decoder from missing unusual anomaly details while maintaining robustness from noises inside the data. Besides, we propose the temporal context fusion module to adaptively fuse the generated auxiliary predictions. Extensive experiments on public and collected transportation datasets validate that the proposed framework is effective for anomaly detection in time series. Additionally, the ablation study and a series of parameter sensitivity experiments show that the proposed method maintains high performance under various experimental settings.

17.
Nano Lett ; 22(10): 4090-4096, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35549497

RESUMO

Magnetic resonance (MR) imaging is very important for noninvasive lymphography. However, the present MR contrast agents still cannot supply strong enough tissue contrast and long observation window. To improve the performance of contrast agents, we introduce one-dimensional unimolecular nanoparticles with a confined and compact poly(acrylic acid) core as nanoparticulate chelates of gadolinium ions. Thus, obtained nanoparticulate T1 contrast agents give r1 relaxivity as high as 136.3 mM-1·s-1 under 3.0 T. By injection at the footpad of mice, the contrast agents provide excellent contrast enhancement of lymphatic drainage and they may arrive at popliteal lymph nodes within 30 min and reside for more than 80 h. High performance of the present contrast agent is attributed to the confined and compact core of materials that increase hydration number, intershell water diffusion, and decrease rotational motion.


Assuntos
Meios de Contraste , Linfografia , Animais , Meios de Contraste/química , Gadolínio/química , Linfografia/métodos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Camundongos
18.
Angew Chem Int Ed Engl ; 62(43): e202310401, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37661193

RESUMO

The development of lipid nanoparticles (LNPs) has enabled a successful clinical application of mRNA vaccines. However, disclosure of design principles for the core component-ionizable lipids (ILs), improving the delivery efficacy and organ targeting of LNPs, remains a formidable challenge. Herein, we report a powerful strategy to modulate ILs in one-step chemistry using the Ugi four-component reaction (Ugi-4CR) under mild conditions. A large IL library of new structures was established simply and efficiently through a multidimensional approach, allowing us to identify the top-performing ILs in delivering mRNA via the formulated LNPs. Adjusting the skeleton of ILs has transformed the organ-specific and robust transfection in mRNA delivery from the liver to the spleen following different administration routes. Of note, a series of isomeric ILs were prepared and we found that the isomers mattered greatly in the performance of LNPs for mRNA delivery. Furthermore, owing to the bis-amide bonds formed in the Ugi-4CR reaction, the ILs within LNPs may form hydrogen bonding intermolecularly, facilitating the colloidal stabilization of LNPs. This work provides clues to the rapid discovery and rational design of IL candidates, assisting the application of mRNA therapeutics.

19.
J Cell Mol Med ; 26(18): 4768-4780, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35957621

RESUMO

tRNA-derived fragments (tRFs), non-coding RNAs that regulate protein expression after transcription, have recently been identified as potential biomarkers. We identified differentially expressed tRFs in gastric cancer (GC) and the biological properties of tRFs in predicting the malignancy status of GCs as possible biomarkers. Until 15 February 2022, two independent reviewers did a thorough search in electronic databases of Scopus, EMBASE and PubMed. The QUADAS scale was used for quality assessment of the included studies. Ten articles investigating the clinical significance of tRFs, including 928 patients, were analysed. In 10 GC studies, seven tRFs were considerably upregulated and five tRFs were significantly downregulated when compared to controls. Risk of bias was rated low for index test, and flow as well as timing domains in relation to the review question. The applicability of the index test, flow and timing and patient selection for 10 studies was deemed low. In this study, we review the advances in the study of tRFs in GC and describe their functions in gene expression regulation, such as suppression of translation, cell differentiation, proliferation and the related signal transduction pathways associated with them. Our findings may offer researchers new ideas for cancer treatment as well as potential biomarkers for further research in GC.


Assuntos
Neoplasias Gástricas , Biomarcadores , Diferenciação Celular , Regulação da Expressão Gênica , Humanos , RNA de Transferência/genética , Neoplasias Gástricas/genética
20.
Plant J ; 107(3): 817-830, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34009654

RESUMO

Leaf width (LW) is an important component of plant architecture that extensively affects both light capture during photosynthesis and grain yield, particularly under dense planting conditions. However, the genetic and molecular mechanisms regulating LW remain largely elusive in maize (Zea mays L.). In this study, qLW4a, a major quantitative trait locus controlling LW, was identified in a population constructed with maize inbred lines PH6WC, with wide leaves, and Lin387, with narrow leaves. Map-based cloning revealed that ZmNL4, a kelch-repeat superfamily gene, emerged to be the candidate for qLW4a, and a single-base deletion in the conserved SMC_prok_B domain of ZmNL4 in Lin387 caused a frame shift, leading to premature termination. Consistently, the knockout of ZmNL4 by CRISPR/Cas9 editing significantly reduced the LW, which was attributed to a reduction in the cell number instead of cell size, indicating a role of ZmNL4 in regulating cell division. Transcriptomic comparison of ZmNL4 knockout lines with the wild type B73-329 revealed that ZmNL4 might participate in cell wall biogenesis, asymmetric cell division, metabolic processes, transmembrane transport and response to external stimulus, etc. These results provide insights into the genetic and molecular mechanisms of ZmNL4 in controlling LW and could potentially contribute to optimizing plant architecture for maize breeding.


Assuntos
Regulação da Expressão Gênica de Plantas/fisiologia , Folhas de Planta/anatomia & histologia , Folhas de Planta/genética , Proteínas de Plantas/metabolismo , Zea mays/anatomia & histologia , Zea mays/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Ligação Genética , Estudo de Associação Genômica Ampla , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Locos de Características Quantitativas , Zea mays/crescimento & desenvolvimento
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