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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.
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MicroARNs , Triticum , Triticum/genética , Pan , MicroARNs/genética , ARN Mensajero , Polirribosomas , Sistemas de Lectura Abierta/genética , Grano Comestible/genética , Biosíntesis de Proteínas/genéticaRESUMEN
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.
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Sumoilación , Triticum , Triticum/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Respuesta al Choque Térmico/genética , Factores de Transcripción del Choque Térmico/metabolismoRESUMEN
The inhibition of the autophagolysosomal pathway mediated by transcription factor EB (TFEB) inactivation in proximal tubular epithelial cells (TECs) is a key mechanism of TEC injury in diabetic kidney disease (DKD). Acetylation is a novel mechanism that regulates TFEB activity. However, there are currently no studies on whether the adjustment of the acetylation level of TFEB can reduce the damage of diabetic TECs. In this study, we investigated the effect of Trichostatin A (TSA), a typical deacetylase inhibitor, on TFEB activity and damage to TECs in both in vivo and in vitro models of DKD. Here, we show that TSA treatment can alleviate the pathological damage of glomeruli and renal tubules and delay the DKD progression in db/db mice, which is associated with the increased expression of TFEB and its downstream genes. In vitro studies further confirmed that TSA treatment can upregulate the acetylation level of TFEB, promote its nuclear translocation, and activate the expression of its downstream genes, thereby reducing the apoptosis level of TECs. TFEB deletion or HDAC6 knockdown in TECs can counteract the activation effect of TSA on autophagolysosomal pathway. We also found that TFEB enhances the transcription of Tfeb through binding to its promoter and promotes its own expression. Our results, thus, provide a novel therapeutic mechanism for DKD that the alleviation of TEC damage by activating the autophagic lysosomal pathway through upregulating TFEB acetylation can, thus, delay DKD progression.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Nefropatías Diabéticas , Células Epiteliales , Inhibidores de Histona Desacetilasas , Ácidos Hidroxámicos , Túbulos Renales Proximales , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Nefropatías Diabéticas/metabolismo , Ratones , Acetilación , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Ácidos Hidroxámicos/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Masculino , Ratones Endogámicos C57BL , Autofagia/efectos de los fármacos , Apoptosis/efectos de los fármacosRESUMEN
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.
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Cobre , Neoplasias , Humanos , Resistencia a Antineoplásicos/genética , Muerte Celular , Ionóforos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , ApoptosisRESUMEN
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.
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FN-kappa B , Neoplasias , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Transducción de Señal , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Resistencia a Medicamentos , Resistencia a Antineoplásicos/genética , Línea Celular TumoralRESUMEN
Anisotropic nanoparticles such as worm-like micelles have aroused much attention due to their promising applications from templates to drug delivery. The fabrication of worm-like micelles with tunable structural stability and control over their diameter and length is of great importance but still challenging. Herein, we report a kinetically controlled ring-opening metathesis polymerization-induced self-assembly (ROMPISA) for the robust preparation of kinetically trapped worm-like micelles with tunable diameter/length at enlarged experimental windows by the rational manipulation of kinetic factors, including solvent property, temperature, and π-π stacking effects. The resultant worm structures were thermodynamically metastable and capable of excellent structural stability at room temperature due to the kinetic trapping effect. At elevated temperatures, these thermodynamically metastable worms could undergo morphology evolution into vesicular structures in a controlled manner. Moreover, the structural stability of worms could also be significantly enhanced by in situ cross-linking. Overall, this kinetically controlled ROMPISA opens a new avenue for PISA chemistry that is expected to prepare "smart" polymer materials by manipulating kinetic factors.
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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.
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Metilación de ADN , Tetraploidía , Metilación de ADN/genética , Triticum/genética , Epigénesis Genética , Transcriptoma , Regulación de la Expresión Génica de las PlantasRESUMEN
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.
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Oryza , Poaceae , Poaceae/genética , Triticum/genética , Genoma de Planta/genética , Oryza/genética , Zea mays/genética , Evolución MolecularRESUMEN
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.
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Endospermo/metabolismo , Proteínas de Plantas/metabolismo , Almidón/metabolismo , Factores de Transcripción/metabolismo , Alelos , Endospermo/genética , Glútenes/genética , Glútenes/metabolismo , Proteínas de Plantas/genética , Almidón/genética , Factores de Transcripción/genética , Triticum/genética , Triticum/metabolismoRESUMEN
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.
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Sistemas de Liberación de Medicamentos , Nanoestructuras , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/químicaRESUMEN
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.
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Avispas , Femenino , Animales , AgriculturaRESUMEN
Insulin, a main medication to control glycemia of typeâ 1 and advanced typeâ 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 20â 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.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hipoglucemia , Animales , Ratones , Insulina de Acción Prolongada , Polímeros , Hipoglucemia/epidemiología , InsulinaRESUMEN
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.
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Neoplasias Primarias Secundarias , Neoplasias Gástricas , Masculino , Humanos , Persona de Mediana Edad , Femenino , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Terapia Neoadyuvante , Tomografía Computarizada por Rayos X , Curva ROC , Gastrectomía , Estudios RetrospectivosRESUMEN
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.
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Aminoácidos , Lesiones Traumáticas del Encéfalo , Ratones , Animales , Inflamación/metabolismo , Encéfalo/metabolismo , Citocinas/metabolismo , Ratones Endogámicos C57BLRESUMEN
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.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Estudios Prospectivos , Metástasis Linfática/patología , Tomografía Computarizada por Rayos X/métodos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Estudios RetrospectivosRESUMEN
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.
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Nanoestructuras , Polímeros , Polímeros/química , Sustancias Macromoleculares , Nanoestructuras/química , Polimerizacion , Propiedades de SuperficieRESUMEN
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.
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Thysanoptera , Vigna , Masculino , Femenino , Animales , Tablas de Vida , Reproducción , BiologíaRESUMEN
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.
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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.
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Medios de Contraste , Linfografía , Animales , Medios de Contraste/química , Gadolinio/química , Linfografía/métodos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , RatonesRESUMEN
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.