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A major antiviral mechanism in plants is mediated by RNA silencing through the action of DICER-like (DCL) proteins, which cleave dsRNA into discrete small RNA fragments, and ARGONAUTE (AGO) proteins, which use the small RNAs to target single-stranded RNA. RNA silencing can also be amplified through the action of RNA-dependent RNA polymerases (RDRs), which use single stranded RNA to generate dsRNA that in turn is targeted by DCL proteins. As a counter-defense, plant viruses encode viral suppressors of RNA silencing (VSRs) that target different components in the RNA silencing pathway. The tomato Ty-1 gene confers resistance to the DNA virus tomato yellow leaf curl virus (TYLCV) and has been reported to encode an RDRγ protein. However, the molecular mechanisms by which Ty-1 controls TYLCV infection, including whether Ty-1 is involved in RNA silencing, are unknown. Here, by using a transient expression assay, we have confirmed that Ty-1 shows antiviral activity against TYLCV in Nicotiana benthamiana. Also, in transient expression-based silencing assays, Ty-1 augmented systemic transgene silencing in GFP transgenic N. benthamiana plants. Furthermore, co-expression of Ty-1 or other RDRγ proteins from N. benthamiana or Arabidopsis with various proteins resulted in lower protein expression. These results are consistent with a model wherein Ty-1-mediated resistance to TYLCV is due, at least in part, to an increase in RNA silencing activity.
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Begomovirus , Resistência à Doença , Nicotiana , Doenças das Plantas , Interferência de RNA , Solanum lycopersicum , Begomovirus/genética , Solanum lycopersicum/virologia , Solanum lycopersicum/genética , Doenças das Plantas/virologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Nicotiana/virologia , Nicotiana/genética , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Plantas Geneticamente Modificadas/virologiaRESUMO
Wire arc additive manufacturing (WAAM) offers a viable solution for fabricating large-scale metallic parts, which contain various forms of inclined thick-walled structure. Due to the variety of heat dissipation conditions at different positions, the inclined thick-walled structure is a major challenge in fabrication that may produce collapses and defects. However, there is a lack of effective sensing method for acquiring the forming appearance of individual beads in the structure. This paper proposes a novel approach for extracting individual bead profiles during the WAAM process. The approach utilizes a structured-laser sensor to capture the morphology of the surface before and after deposition, thereby enabling an accurate acquisition of the bead profile by integrating the laser stripes. Utilizing the proposed approach, the research investigated the forming mechanism of beads in inclined thick-walled components that were fabricated by various deposition parameters. The width of the overlapping area at the overhanging feature decreased as the layer number increased, while the height of the same area increased. The height of the overlapping area in each layer increased with an increase in deposition current and decreased when the deposition speed was increased. These phenomena suggest that the heat input is a major factor that influences the formation of the overhanging feature. Both the deposition current and deposition velocity influence heat input, and thereby have an effect in enhancing the geometrical accuracy of an overhanging feature. The experimental results indicate that the proposed approach facilitates morphology change investigation, providing a sufficient reference for optimizing deposition parameters.
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NSUN5, a key member of the M5C methylation family, plays a significant role in fundamental biological processes like cell proliferation and differentiation. However, its specific function and mechanisms in gastric cancer remain insufficiently understood. Initially, we examined NSUN5's differential expression in gastric cancer versus normal tissues, along with survival trends, associated signaling pathways, and immune infiltration using the TCGA database. Subsequently, we conducted immunohistochemistry experiments to assess NSUN5 expression in gastric cancer tissues. Gain-and loss-of-function experiments were carried out to investigate NSUN5's impact on the proliferation, stemness, and migratory capabilities of gastric cancer cells, as well as the expression of vital proteins in pertinent signaling pathways. Our findings demonstrate that NSUN5 is not only overexpressed in gastric cancer tissues, but also positively associated with tumor stage and inversely linked with patient prognosis. NSUN5 promotes the in vitro proliferation, stemness, and migration of gastric cancer cells, and the in vivo growth of these cells, chiefly through the activation of the WNT/ß-catenin signaling pathway. Additionally, NSUN5 appears to diminish the infiltration of CD8+ T cells in gastric cancer, contributing to immune evasion. In conclusion, NSUN5 functions as a proto-oncogene in the progression of gastric cancer and may serve as a potential therapeutic target.
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The objective of this study was to compare the clinical efficacy and safety of microchannel percutaneous nephrolithotripsy (MPCNL) with flexible ureteroscopic lithotripsy (FURL) in the treatment of single upper ureteral stones with a diameter of 1-2 cm and high hardness. This study retrospectively analyzed 89 patients diagnosed with a single upper ureteral stone with a 1-2 cm diameter and a computed tomography value > 1000 Hounsfield units. A propensity score matching system matched this study with factors to minimize the effect of baseline differences between patients. Ultimately, 29 patients in each of the two groups were successfully matched. The stone-free rate was marginally higher in the MPCNL group than in the FURL group (93.10% vs. 86.21%), although the difference did not reach statistical significance (P = 0.666). Furthermore, the mean operative time in the MPCNL group, although slightly longer than that in the FURL group, did not demonstrate a statistically significant difference (P = 0.833). However, patients in the MPCNL group exhibited a significantly more substantial decrease in hemoglobin than those in the FURL group (P < 0.001) and a substantially more extended postoperative hospital stay (P < 0.001). Regarding perioperative complications, the incidence of moderate pain was higher in the MPCNL group than in the FURL group (P = 0.037). The difference in overall complication rates between the two groups did not reach statistical significance (P = 0.108). MPCNL and FURL are efficacious surgical procedures for treating single upper ureteral stones with a 1-2 cm diameter and high hardness.
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Litotripsia , Nefrolitotomia Percutânea , Pontuação de Propensão , Cálculos Ureterais , Ureteroscopia , Humanos , Feminino , Masculino , Estudos Retrospectivos , Cálculos Ureterais/terapia , Cálculos Ureterais/cirurgia , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/métodos , Ureteroscopia/efeitos adversos , Ureteroscopia/métodos , Litotripsia/métodos , Litotripsia/efeitos adversos , Adulto , Resultado do Tratamento , Idoso , Duração da Cirurgia , Dureza , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação/estatística & dados numéricosRESUMO
Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy.
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Escherichia coli , Imagem Multimodal , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Escherichia coli/efeitos dos fármacos , Camundongos , Imagem Multimodal/métodos , Linhagem Celular Tumoral , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Imageamento por Ressonância Magnética/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fluorocarbonos/química , Polietilenoimina/química , Humanos , Engenharia Genética/métodos , Camundongos Endogâmicos BALB C , Técnicas Fotoacústicas/métodos , Feminino , Nanopartículas/química , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Epirubicina/química , Ácido Poliglicólico/química , Ácido Láctico/química , Ablação por Ultrassom Focalizado de Alta Intensidade/métodosRESUMO
BACKGROUND: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease. An inadequate response to ursodeoxycholic acid (UDCA) poses a high risk of progression toward end-stage liver disease. Gut dysbiosis has been implicated in PBC. Here, we aimed to investigate microbial signatures that permit risk stratification and provide mechanistic insights into novel therapies for PBC. METHODS: We prospectively recruited UDCA treatment-naive patients with PBC and performed metagenomic sequencing and metabolomic profiling using stool and serum samples obtained before (n = 132) and after (n = 59) treatment. PBC microbiome subtypes were identified using unsupervised machine learning methods and validated in two independent cohorts. FINDINGS: PBC baseline metagenomes clustered into two community subtypes characterized by varying abundances of Clostridia taxa. Compared with Clostridialow microbiomes, Clostridiahigh microbiomes were more similar to healthy controls. Notably, patients in the Clostridialow subtype exhibited a 2-fold higher UDCA non-response rate compared to those in the Clostridiahigh subtype (41% vs. 20%, p = 0.015). Integrative analysis of metagenomic and metabolomic data revealed divergent functional modules and metabolic activities between the two metacommunities. In particular, anaerobic fermentation and the production of bioactive metabolites, including tryptophan derivatives and secondary bile acids, crucial for immune regulation and gut barrier maintenance, were markedly diminished in the Clostridialow subtype. Moreover, UDCA administration reconfigured the fecal microbial and metabolic profiles only in the Clostridiahigh group. Importantly, the microbiome subtypes and their associations with UDCA response were reproducible in two independent treatment-naive PBC cohorts. CONCLUSIONS: Characterizing baseline microbiota patterns may enable the prediction of treatment outcomes in PBC and facilitate personalized treatment strategies. FUNDING: This research was mainly supported by the National Natural Science Foundation of China.
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Masking the bitter taste of foods is one of the key strategies to improve their taste and palatability, particularly in the context of clean labeling, where natural compounds are preferred. Despite the demand, the availability of natural bitter-masking compounds remains limited. Here, we identified the bitter-masking compound 4'-demethyl-3,9-dihydroeucomin (DMDHE) isolated from the resin of Daemonorops draco by means of an activity-guided in vivo (sensory bitterness rating of quinine) and in vitro (cell-based bitter response assays) approach. First, a mean bitter-masking effect of -29.6 ± 6.30% on the bitterness perceived from quinine [10 ppm] was demonstrated for an organic solvent extract of the resin of D. draco (= DD [500 ppm]) in a sensory trial. The results were verified in a cell-based bitter assay in which the bitter taste receptor (TAS2R)-dependent proton secretion serves as an outcome measure of the cellular bitter response in parietal HGT-1 cells. By means of preparative RP-18 high-performance liquid chromatography (HPLC) analysis combined with activity-guided sensory evaluations, the most potent bitter-masking fractions were identified. Subsequent quantitative liquid chromatography/high-resolution mass spectrometry/charged aerosol detection/ultraviolet (LC-HRMS/CAD/UV), NMR analysis, followed by gram-scale synthesis, led to the characterization of DMDHE as bitter-masking homoisoflavanone. DMDHE decreased the sensory bitterness of quinine by 14.8 ± 5.00%. Functional involvement of TAS2R14 was demonstrated by means of a CRISPR-Cas9 approach, which revealed a reduction of the DMDHE-evoked bitter-masking effect by 40.4 ± 9.32% in HGT-1 TAS2R14ko versus HGT-1 wt cells.
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Receptores Acoplados a Proteínas G , Resinas Vegetais , Paladar , Humanos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Masculino , Feminino , Resinas Vegetais/química , Adulto , Aromatizantes/química , Adulto Jovem , Extratos Vegetais/química , Quinina/química , Quinina/análogos & derivados , Cromatografia Líquida de Alta PressãoRESUMO
Thaumatin-like proteins (TLPs) are conserved proteins involved in the defense and stress responses of plants. Previous studies showed that several TLPs were accumulated in leaf apoplast in Ammopiptanthus mongolicus in winter, indicating that TLPs might be related to the adaptation to winter climate in A. mongolicus. To investigate the roles of TLPs in winter adaptation, we first analyzed the expression pattern of TLP genes in A. mongolicus and then focused on the biological function and regulation pathway of AmTLP25 gene. Several TLP genes, including AmTLP25, were upregulated during winter and in response to both cold and osmotic stress. Overexpression of the AmTLP25 gene led to an increased tolerance of transgenic Arabidopsis to freezing and osmotic stress. Furthermore, the elevated AmWRKY14 transcription factor during winter activated AmTLP25 gene expression by specifically binding to its promoter. It is speculated that the AmWRKY14 - AmTLP25 module contributes to the adaptation to temperate winter climate in A. mongolicus. Our research advances the current understanding of the biological function and regulatory pathway of TLP genes and provides valuable information for understanding the molecular mechanism of temperate evergreen broad-leaved plants adapting to winter climate.
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Adaptação Fisiológica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Estações do Ano , Fatores de Transcrição , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Adaptação Fisiológica/genética , Plantas Geneticamente Modificadas , Arabidopsis/genética , Arabidopsis/metabolismo , Pressão Osmótica , Temperatura BaixaRESUMO
Increased efforts in neuroscience seek to understand how macro-anatomical and physiological connectomes cooperatively work to generate cognitive behaviors. However, the structure-function coupling characteristics in normal aging individuals remain unclear. Here, we developed an index, the Coupling in Brain Structural connectome and Functional connectome (C-BSF) index, to quantify regional structure-function coupling in a large community-based cohort. C-BSF used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) data from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (PRECISE) cohort (2007 individuals, age: 61.15 ± 6.49 years) and the Sydney Memory and Ageing Study (MAS) cohort (254 individuals, age: 83.45 ± 4.33 years). We observed that structure-function coupling was the strongest in the visual network and the weakest in the ventral attention network. We also observed that the weaker structure-function coupling was associated with increased age and worse cognitive level of the participant. Meanwhile, the structure-function coupling in the visual network was associated with the visuospatial performance and partially mediated the connections between age and the visuospatial function. This work contributes to our understanding of the underlying brain mechanisms by which aging affects cognition and also help establish early diagnosis and treatment approaches for neurological diseases in the elderly.
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Envelhecimento , Encéfalo , Cognição , Conectoma , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Idoso , Envelhecimento/fisiologia , Pessoa de Meia-Idade , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Idoso de 80 Anos ou mais , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologiaRESUMO
INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a prevalent comorbidity among patients with end-stage kidney disease. Although sodium-glucose cotransporter 2 inhibitors are validated in treating heart failure and ameliorating left ventricular hypertrophy among non-dialysis patients, the effects on dialysis patients are unknown. We previously investigated the pharmacokinetics of henagliflozin in patients undergoing haemodialysis (HD) or peritoneal dialysis (PD) and clarified its safety. METHODS AND ANALYSIS: This multicentre, randomised, double-blind, placebo-controlled trial is being conducted at three hospitals in Shanghai, China. A target of 108 HD or PD patients with HFpEF are randomly allocated to treatment group (henagliflozin 5 mg/day in addition to standard therapy) or control group (placebo with standard therapy) at a ratio of 1:1. All subjects will be followed up for 24 weeks. The primary outcome is change in echocardiography-measured left ventricular mass index. The secondary interests include changes in left atrial volume index, E/e', e' and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Intergroup comparisons of change in echocardiography-related outcomes from baseline to 24 weeks are based on a linear regression model adjusted for baseline values (analysis of covariance), and repeated measure analysis of variance with Bonferroni adjustment is employed for comparison of change in NT-proBNP. Subgroup analyses of the primary and secondary outcomes are conducted to determine whether the effect of henagliflozin varies according to dialysis modality. The χ2 method is used to compare the occurrence of adverse events and severe adverse events. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University (LY2023-127-B). All participants provide written informed consent before screening. The results of the trial will be disclosed completely in international peer-reviewed journals. Both positive and negative results will be reported. TRIAL REGISTRATION NUMBER: ChiCTR2300073169.
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Insuficiência Cardíaca , Falência Renal Crônica , Diálise Renal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China , Método Duplo-Cego , Ecocardiografia , Insuficiência Cardíaca/tratamento farmacológico , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/efeitos dos fármacosRESUMO
Geminiviruses infect numerous crops and cause extensive agricultural losses worldwide. During viral infection, geminiviral C4/AC4 proteins relocate from the plasma membrane to chloroplasts, where they inhibit the production of host defense signaling molecules. However, mechanisms whereby C4/AC4 proteins are transported to chloroplasts are unknown. We report here that tomato (Solanum lycopersicum) COAT PROTEIN COMPLEX I (COPI) components play a critical role in redistributing Tomato yellow leaf curl virus C4 protein to chloroplasts via an interaction between the C4 and ß subunit of COPI. Coexpression of both proteins promotes the enrichment of C4 in chloroplasts that is blocked by a COPI inhibitor. Overexpressing or downregulating gene expression of COPI components promotes or inhibits the viral infection, respectively, suggesting a proviral role of COPI components. COPI components play similar roles in C4/AC4 transport and infections of two other geminiviruses: Beet curly top virus and East African cassava mosaic virus. Our results reveal an unconventional role of COPI components in protein trafficking to chloroplasts during geminivirus infection and suggest a broad-spectrum antiviral strategy in controlling geminivirus infections in plants.
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Cloroplastos , Geminiviridae , Doenças das Plantas , Solanum lycopersicum , Cloroplastos/metabolismo , Cloroplastos/virologia , Doenças das Plantas/virologia , Geminiviridae/patogenicidade , Solanum lycopersicum/virologia , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Begomovirus/fisiologia , Begomovirus/patogenicidade , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Transporte ProteicoRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused the biggest public health crises in recent history. Many expect future coronavirus introductions into the human population. Hence, it is essential to understand the basic biology of these viruses. In natural infection, the SARS-CoV-2 Spike (S) glycoprotein is co-expressed with all other viral proteins, which modify cellular compartments to maximize virion assembly. By comparison, most of S is degraded when the protein is expressed in isolation, as in current molecular vaccines. To probe the maturation pathway of S, we redirected its maturation by fusing S to the tetraspanin protein CD81. CD81 is a defining constituent of extracellular vesicles (EVs) or exosomes. EVs are generated in large numbers by all cells, extruded into blood and lymph, and transfer cargo between cells and systemically (estimated 1012 EVs per mL plasma). EVs, like platelets, can be transfused between unrelated donors. When fusing the proline-stabilized form of strain Delta S into the flexible, large extracellular loop of CD81 rather than being degraded in the lysosome, S was extruded into EVs. CD81-S fusion containing EVs were produced in large numbers and could be isolated to high purity. Purified CD81::S EVs bound ACE2, and S displayed on individual EV was observed by cryogenic electron microscopy (EM). The CD81::S-fusion EVs were non-toxic and elicited an anti-S trimer and anti-RBD antibody response in mice. This report shows a design path to maximize viral glycoprotein assembly and release without relying on the co-expression of potentially pathogenic nonstructural viral proteins. IMPORTANCE: The severe acute respiratory syndrome coronavirus 2 pandemic caused the biggest public health crises in recent history. To understand the maturation pathway of S, we fused S to the tetraspanin protein CD81. The resulting molecule is secreted in extracellular vesicles and induces antibodies in mice. This may be a general design path for viral glycoprotein vaccines.
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SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Tetraspanina 28 , Animais , Humanos , Camundongos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , COVID-19/virologia , COVID-19/imunologia , Vesículas Extracelulares/metabolismo , Transporte Proteico , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Tetraspanina 28/metabolismo , Tetraspanina 28/genéticaRESUMO
Jojoba is an industrial oil crop planted in tropical arid areas, and its low-temperature sensitivity prevents its introduction into temperate areas. Studying the molecular mechanisms associated with cold acclimation in jojoba is advantageous for developing breeds with enhanced cold tolerance. In this study, metabolomic analysis revealed that various flavonols accumulate in jojoba during cold acclimation. Time-course transcriptomic analysis and weighted correlation network analysis (WGCNA) demonstrated that flavonol biosynthesis and jasmonates (JAs) signaling pathways played crucial roles in cold acclimation. Combining the biochemical and genetic analyses showed that ScMYB12 directly activated flavonol synthase gene (ScFLS). The interaction between ScMYB12 and transparent testa 8 (ScTT8) promoted the expression of ScFLS, but the negative regulator ScJAZ13 in the JA signaling pathway interacted with ScTT8 to attenuate the transcriptional activity of the ScTT8 and ScMYB12 complex, leading to the downregulation of ScFLS. Cold acclimation stimulated the production of JA in jojoba leaves, promoted the degradation of ScJAZ13, and activated the transcriptional activity of ScTT8 and ScMYB12 complexes, leading to the accumulation of flavonols. Our findings reveal the molecular mechanism of JA-mediated flavonol biosynthesis during cold acclimation in jojoba and highlight the JA pathway as a promising means for enhancing cold tolerance in breeding efforts.
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Vascular surgery faces a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency particularly applies to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs holds great promise as a solution to organ shortage for transplantation. To achieve this, it is imperative to (re-)construct a biocompatible and non-thrombogenic vascular network within these organs. In this systematic review, we identify, classify and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue engineered organs and tissues. We conducted a pre-registered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines, comprising a systematic data extraction, in-depth analysis and risk of bias assessment of 116 included studies. We identified shaking (n=28), flow loop (n=17), ex vivo (arterio-venous shunt, n=33) and dynamic in vitro models (n=38) as main approaches for thrombogenicity assessment. This comprehensive review unveils a prevalent lack of standardization and serves as a valuable guide in the design of standardized experimental setups.
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Plant samples with irregular morphology are challenging for longitudinal tissue sectioning. This has restricted the ability to gain insight into some plants using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Herein, we develop a novel technique termed electromagnetic field-assisted frozen tissue planarization (EMFAFTP). This technique involves using a pair of adjustable electromagnets on both sides of a plant tissue. Under an optimized electromagnetic field strength, nondestructive planarization and regularization of the frozen tissue is induced, allowing the longitudinal tissue sectioning that favors subsequent molecular profiling by MALDI-MSI. As a proof of concept, flowers, leaves and roots with irregular morphology from six plant species are chosen to evaluate the performance of EMFAFTP for MALDI-MSI of secondary metabolites, amino acids, lipids, and proteins among others in the plant samples. The significantly enhanced MALDI-MSI capabilities of these endogenous molecules demonstrate the robustness of EMFAFTP and suggest it has the potential to become a standard technique for advancing MALDI-MSI into a new era of plant spatial omics.
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Campos Eletromagnéticos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Folhas de Planta/metabolismo , Folhas de Planta/química , Congelamento , Raízes de Plantas/metabolismo , Raízes de Plantas/química , Plantas/metabolismo , Plantas/química , Flores/metabolismo , Flores/químicaRESUMO
Phytohormones possess unique chemical structures, and their physiological effects are regulated through intricate interactions or crosstalk among multiple phytohormones. MALDI-MSI enables the simultaneous detection and imaging of multiple hormones. However, its application for tracing phytohormones is currently restricted by low abundance of hormone in plant and suboptimal matrix selection. 2,4-Dihydroxy-5-nitrobenzoic acid (DHNBA) was reported as a new MALDI matrix for the enhanced detection and imaging of multiple phytohormones in plant tissues. DHNBA demonstrates remarkable sensitivity improvement when compared to the commonly used matrix, 2,5-dihydroxybenzoic acid (DHB), in the detection of isoprenoid cytokinins (trans-zeatin (tZ), dihy-drozeatin (DHZ), meta-topolin (mT), and N6-(Δ2-isopentenyl) adenine (iP)), jasmonic acid (JA), abscisic acid (ABA), and 1-aminocyclo-propane-1-carboxylic acid (ACC) standards. The distinctive properties of DHNBA (i.e. robust UV absorption, uniform matrix deposition, negligible background interference, and high ionization efficiency of phytohormones) make it as an ideal matrix for enhanced detection and imaging of phytohormones, including tZ, DHZ, ABA, indole-3-acetic acid (IAA), and ACC, by MALDI-MSI in various plant tissues, for example germinating seeds, primary/lateral roots, and nodules. Employing DHNBA significantly enhances our capability to concurrently track complex phytohormone biosynthesis pathways while providing precise differentiation of the specific roles played by individual phytohormones within the same category. This will propel forward the comprehensive exploration of phytohormonal functions in plant science.
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Reguladores de Crescimento de Plantas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Gentisatos/metabolismo , Gentisatos/químicaRESUMO
Non-line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects, allowing a wide range of applications. Existing NLOS systems rely on pulsed lasers and time-resolved single-photon detectors to capture the information encoded in the time of flight of scattered photons. Despite remarkable advances, the pulsed time-of-flight LIDAR approach has limited temporal resolution and struggles to detect the frequency-associated information directly. Here, we propose and demonstrate the coherent scheme-frequency-modulated continuous wave calibrated by optical frequency comb-for high-resolution NLOS imaging, velocimetry, and vibrometry. Our comb-calibrated coherent sensor presents a system temporal resolution at subpicosecond and its superior signal-to-noise ratio permits NLOS imaging of complex scenes under strong ambient light. We show the capability of NLOS localization and 3D imaging at submillimeter scale and demonstrate NLOS vibrometry sensing at an accuracy of dozen Hertz. Our approach unlocks the coherent LIDAR techniques for widespread use in imaging science and optical sensing.
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BACKGROUND: Insulin resistance (IR) is of growing concern yet its association with white matter integrity remains controversial. We aimed to investigate the association between IR and white matter integrity in nondiabetic adults. METHODS: This cross-sectional analysis was conducted based on the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study. A total of 1709 nondiabetic community-dwelling adults with available diffusion-weighted imaging based on brain magnetic resonance imaging and completed oral glucose tolerance test were included. IR was measured noninvasively by insulin sensitivity indices (ISI), including ISIcomposite and ISI0,120, as well as homeostasis model assessment of insulin resistance (HOMA-IR). White matter microstructure abnormalities were identified by diffusion-weighted imaging along with tract-based spatial statistical analysis to compare diffusion metrics between groups. The multivariable linear regression models were applied to measure the association between white matter microstructure abnormalities and IR. RESULTS: A total of 1709 nondiabetic individuals with a mean age of 60.8 ± 6.4 years and 54.1% female were included. We found that IR was associated with a significant increase in mean diffusivity, axial diffusivity, and radial diffusivity extensively in cerebral white matter in regions such as the anterior corona radiata, superior corona radiata, anterior limb of internal capsule, external capsule, and body of corpus callosum. The pattern of associations was more marked for ISIcomposite and ISI0,120. However, the effect of IR on white matter integrity was attenuated after, in addition, adjustment for history of hypertension and cardiovascular disease and antihypertensive medication use. CONCLUSION: Our findings indicate a significant association between IR and white matter microstructural abnormalities in nondiabetic middle-aged community residents, while these associations were greatly influenced by the history of hypertension and cardiovascular disease, and antihypertensive medication use. Further investigation is needed to clarify the role of IR in white matter integrity, whereas prophylactic strategies of maintaining a low IR status may ameliorate disturbances in white matter integrity. DATA ACCESSIBILITY STATEMENT: The data that support the findings of this study are available from the corresponding authors upon reasonable request.
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Silicon nitride is utilized clinically as a bioceramic for spinal fusion cages, owing to its high strength, osteoconductivity, and antibacterial effects. Nevertheless, silicon nitride exhibits suboptimal damping properties, a critical factor in mitigating traumatic bone injuries and fractures. In fact, there is a scarcity of spinal implants that simultaneously demonstrate proficient damping performance and support osteogenesis. In our study, we fabricated a novel sodium alginate-silicon nitride/poly(vinyl alcohol) (SA-SiN/PVA) composite scaffold, enabling enhanced energy absorption and rapid elastic recovery under quasi-static and impact loading scenarios. Furthermore, the study demonstrated that the incorporation of physical and chemical cross-linking significantly improved stiffness and recoverable energy dissipation. Concerning the interaction between cells and materials, our findings suggest that the addition of silicon nitride stimulated osteogenic differentiation while inhibiting Staphylococcus aureus growth. Collectively, the amalgamation of ceramics and tough hydrogels facilitates the development of advanced composites for spinal implants, manifesting superior damping, osteogenic potential, and antibacterial properties. This approach holds broader implications for applications in bone tissue engineering.