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Oxidative stress is a key feature in both chronic inflammation and cancer. P38 regulated/activated protein kinase (PRAK) deficiency can cause functional disorders in neutrophils and macrophages under high oxidative stress, but the precise mechanisms by which PRAK regulates reactive oxygen species (ROS) elimination and its potential impact on CD4+ T helper subset function are unclear. The present study reveals that the PRAK-NF-E2-related factor 2(NRF2) axis is essential for maintaining the intracellular redox homeostasis of T helper 17(Th17) cells, thereby promoting Th17 cell differentiation and antitumor effects. Through mechanistic analysis, we identify NRF2 as a novel protein substrate of PRAK and find that PRAK enhances the stability of the NRF2 protein through phosphorylation NRF2 Serine(S) 558 independent of protein ubiquitination. High accumulation of cellular ROS caused by loss of PRAK disrupts both glycolysis and PKM2-dependent phosphorylation of STAT3, which subsequently impairs the differentiation of Th17 cells. As a result, Prak knockout (KO) mice display significant resistance to experimental autoimmune encephalomyelitis (EAE) but impaired antitumor immunity in a MC38 tumor model. This work reveals that the PRAK-NRF2-mediated antioxidant pathway is a metabolic checkpoint that controls Th17-cell glycolysis and differentiation. Targeting PRAK is a promising strategy for maintaining an active ROS scavenging system and may lead to potent Th17 cell antitumor immunity.
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Encefalomielite Autoimune Experimental , Proteínas Quinases , Animais , Camundongos , Diferenciação Celular , Glicólise , Homeostase , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Th17/metabolismoRESUMO
Idiopathic multicentric Castleman disease (iMCD) is a rare and heterogeneous lymphoproliferative disorder that lacks standardised treatment options for patients with refractory or relapsed (r/r) disease. Blocking Bruton's tyrosine kinase (BTK) has emerged as a promising therapeutic approach for iMCD without depleting B cells. This single-centre, retrospective study enrolled 10 patients with r/r iMCD who were treated with orelabrutinib, a novel, next-generation BTK inhibitor. The median age at orelabrutinib initiation was 48 (range: 31-58) years. The overall response rate was 70% (7/10 patients, 95% CI: 34.8-93.3), with 20% (n = 2) achieving complete response and 50% (n = 5) achieving partial response. The median time to response was 9.8 (range: 5.9-20.5) months. Patients in the non-responder group also demonstrated a continuous improvement in haemoglobin (91-105 g/L) and albumin (32-38 g/L) levels at month 12 of treatment despite not fulfilling response criteria. No grade 3 or higher adverse events occurred during the median time to the next treatment of 29.0 (range: 15.0-36.2) months. No patient mortality was recorded during the median follow-up duration of 32.8 (range: 15.0-36.9) months. In conclusion, orelabrutinib is a safe and effective regimen for r/r iMCD.
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Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD-thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD-not otherwise specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD-NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed-type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD-NOS identified 103 (45.2%) patients with iMCD-IPL. The clinical features and outcomes of patients with iMCD-IPL and iMCD-NOS without IPL were compared. Patients with iMCD-IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non-severe patients in the iMCD-IPL group according to the CDCN severity classification. Compared with lymphoma-like treatments, multiple myeloma-like and IL-6-blocking treatment approaches in the iMCD-IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD-IPL and suggest that it should be considered a new subtype of iMCD-NOS.
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Hiperplasia do Linfonodo Gigante , Linfadenopatia , Humanos , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/mortalidade , Hiperplasia do Linfonodo Gigante/classificação , Hiperplasia do Linfonodo Gigante/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Linfadenopatia/patologia , Linfadenopatia/etiologia , Plasmócitos/patologiaRESUMO
BACKGROUND: Soapberry (Sapindus mukorossi) is an economically important multifunctional tree species. Triterpenoid saponins have many functions in soapberry. However, the types of uridine diphosphate (UDP) glucosyltransferases (UGTs) involved in the synthesis of triterpenoid saponins in soapberry have not been clarified. RESULTS: In this study, 42 SmUGTs were identified in soapberry, which were unevenly distributed on 12 chromosomes and had sequence lengths of 450 bp to 1638 bp, with an average of 1388 bp. The number of amino acids in SmUGTs was 149 to 545, with an average of 462. Most SmUGTs were acidic and hydrophilic unstable proteins, and their secondary structures were mainly α-helices and random coils. All had conserved UDPGT and PSPG-box domains. Phylogenetic analysis divided them into four subclasses, which glycosylated different carbon atoms. Prediction of cis-acting elements suggested roles of SmUGTs in plant development and responses to environmental stresses. The expression patterns of SmUGTs differed according to the developmental stage of fruits, as determined by transcriptomics and RT-qPCR. Co-expression network analysis of SmUGTs and related genes/transcription factors in the triterpenoid saponin synthesis pathway was also performed. The results indicated potential roles for many transcription factors, such as SmERFs, SmGATAs and SmMYBs. A correlation analysis showed that 42 SmUGTs were crucial in saponin synthesis in soapberry. CONCLUSIONS: Our findings suggest optimal targets for manipulating glycosylation in soapberry triterpenoid saponin biosynthesis; they also provide a theoretical foundation for further evaluation of the functions of SmUGTs and analyses of their biosynthetic mechanisms.
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Glucosiltransferases , Filogenia , Sapindus , Saponinas , Triterpenos , Saponinas/biossíntese , Saponinas/metabolismo , Sapindus/genética , Sapindus/metabolismo , Triterpenos/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
MOTIVATION: Light-field microscopy (LFM) is a compact solution to high-speed 3D fluorescence imaging. Usually, we need to do 3D deconvolution to the captured raw data. Although there are deep neural network methods that can accelerate the reconstruction process, the model is not universally applicable for all system parameters. Here, we develop AutoDeconJ, a GPU-accelerated ImageJ plugin for 4.4× faster and more accurate deconvolution of LFM data. We further propose an image quality metric for the deconvolution process, aiding in automatically determining the optimal number of iterations with higher reconstruction accuracy and fewer artifacts. RESULTS: Our proposed method outperforms state-of-the-art light-field deconvolution methods in reconstruction time and optimal iteration numbers prediction capability. It shows better universality of different light-field point spread function (PSF) parameters than the deep learning method. The fast, accurate and general reconstruction performance for different PSF parameters suggests its potential for mass 3D reconstruction of LFM data. AVAILABILITY AND IMPLEMENTATION: The codes, the documentation and example data are available on an open source at: https://github.com/Onetism/AutoDeconJ.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Microscopia/métodos , Redes Neurais de ComputaçãoRESUMO
Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.
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Hiperplasia do Linfonodo Gigante , Sirolimo , Humanos , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Sirolimo/uso terapêutico , Sirolimo/administração & dosagem , Estudos Retrospectivos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Recidiva , Resultado do Tratamento , Seguimentos , Imunossupressores/uso terapêutico , Indução de RemissãoRESUMO
Referring to the natural succession to restore polluted land is one of the most vital assignments to solving the environmental problems. However, there is little understanding of the natural restoration of nutrient biogeochemical cycles in abandoned land with severe metal pollution. To clarify the nutrient cycling process and the influence of organisms on it, we investigated the magnitude of rhizosphere effects on soil nitrogen (N), phosphorus (P) and sulphur (S) cycles in natural restoration of an abandoned metal mine, as well as the roles of plants and microorganisms in the nutrient cycles. Our data revealed that the rhizosphere had higher levels of ammoniation than non-rhizosphere soil at both stages of restoration. In the early stage, the rhizosphere had greater levels of inorganic phosphorus and organophosphorus solubilisation, as well as sulphite oxidation, compared to non-rhizosphere soil. The bacterial composition influenced the N and S cycles, while the fungal composition had the greatest effect on the P cycles. Furthermore, rhizosphere nutrition cycles and microbial communities altered according plant strategy. Overall, the plants that colonize the early stages of natural recovery demonstrate enhanced restoration of nutrient efficiency. These results contribute to further knowledge of nutrient recovery in mining areas, as well as suggestions for selecting remedial microorganisms and plants in metal-polluted environments.
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Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.
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Colite , Colo , Preparações de Ação Retardada , Mesalamina , Micelas , Nitrorredutases , Polímeros , Pró-Fármacos , Animais , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Mesalamina/química , Mesalamina/farmacocinética , Nitrorredutases/metabolismo , Camundongos , Colo/metabolismo , Colo/patologia , Polímeros/química , Colite/tratamento farmacológico , Colite/metabolismo , Preparações de Ação Retardada/química , NADH NADPH Oxirredutases/metabolismo , Camundongos Endogâmicos C57BL , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , MasculinoRESUMO
BACKGROUND: The International Myeloma Working Group (IMWG) consensus criteria for response assessment in multiple myeloma (MM) has methodological limitations. Whole-body diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) histogram analysis may be complementary to response assessment of MM. PURPOSE: To explore the role of histogram analysis of the ADC based on the total tumor volume (ttADC) in response assessment in patients with newly diagnosed MM (NDMM). STUDY TYPE: Retrospective. POPULATION: Thirty-six patients with NDMM. FIELD STRENGTH/SEQUENCE: 3.0T/single-shot DWI echo planar imaging (EPI) sequence with an integrated slice-by-slice shimming (iShim) technique. ASSESSMENT: Baseline (median: 1 day before treatment) and post-treatment (median: five cycles of therapy) whole-body DWI were analyzed. A region of interest (ROI) containing lesions on every section of baseline image was drawn to derive the per-patient total tumor data. Post-treatment image analysis was based on the same ROI as the corresponding baseline. Histogram metrics were extracted from both ROIs. Patients were categorized into the very good partial response or better (VGPR+) group and the less than VGPR group per the IMWG response criteria for response assessment. Progression-free survival (PFS) was also calculated. STATISTICAL TESTS: Mann-Whitney test and Fisher's exact or Chi-squared tests, Receiver operating characteristic (ROC) analysis and DeLong test, Kaplan-Meier analysis and Cox proportional hazards model. A two-tailed P-value <0.05 was considered statistically significant. RESULTS: Thirty patients were categorized into the VGPR+ group and six into the less than VGPR group. The ttADC histogram changes between post-treatment and baseline metrics (ΔttADC) revealed significant differences in all percentile values between the VGPR+ and less than VGPR groups. For distinguishing VGPR+, ΔttADC_5th percentile had the largest area under the curve (AUC) (0.950, 95% CI 0.821-0.995). Patients with lower ΔttADC_5th percentile values (cutoff point, 188.193) showed significantly longer PFS (HR = 34.911, 95% CI 6.392-190.677). DATA CONCLUSION: ttADC histogram may facilitate response assessment in patients with NDMM. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.
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A paper-based electrochemical dual-function biosensor capable of determining pH and TCO2 was synthesized for the first time using an iridium oxide pH electrode and an all-solid-state ion electrode (ASIE). In the study, to obtain highly reliable results, the biosensor was equipped with a real-time pH correction function before TCO2 measurements. Compared to traditional liquid-filling carbon dioxide detection sensors, the utilization of ferrocene endows our novel sensor with abundant positive sites, and thus greatly improves its performance. Conversely, the introduction of MXene with conductivity close to that of metals reduces electrode resistance, which is beneficial for accelerating the electrochemical reaction of the sensor and reducing LOD. After optimization, the detection range of TCO2 is 0.095 nM-0.66 M, with a detection limit of as low as 0.023 nM. In addition, the sensor was used in real serum sample-spiked recovery experiments and comparison experiments with existing clinical blood gas analyzers, which confirmed the effectiveness of its clinical application. This study provides a method for the rational design of paper-based electrochemical biosensors and a new approach for the clinical detection of blood carbon dioxide.
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Técnicas Biossensoriais , Dióxido de Carbono , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , EletrodosRESUMO
Stomata are one of the important structures for plants to alleviate metal stress and improve plant resistance. Therefore, a study on the effects and mechanisms of heavy metal toxicity to stomata is indispensable in clarifying the adaptation mechanism of plants to heavy metals. With the rapid pace of industrialization and urbanization, heavy metal pollution has been an environmental issue of global concern. Stomata, a special physiological structure of plants, play an important role in maintaining plant physiological and ecological functions. Recent studies have shown that heavy metals can affect the structure and function of stomata, leading to changes in plant physiology and ecology. However, although the scientific community has accumulated some data on the effects of heavy metals on plant stomata, the systematic understanding of the effects of heavy metals on plant stomata remains limited. Therefore, in this review, we present the sources and migration pathways of heavy metals in plant stomata, analyze systematically the physiological and ecological responses of stomata on heavy metal exposure, and summarize the current mechanisms of heavy metal toxicity on stomata. Finally, the future research perspectives of the effects of heavy metals on plant stomata are identified. This paper can serve as a reference for the ecological assessment of heavy metals and the protection of plant resources.
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Metais Pesados , Poluentes do Solo , Metais Pesados/metabolismo , Plantas/metabolismo , Poluição Ambiental , Fenômenos Fisiológicos Vegetais , Poluentes do Solo/metabolismo , Solo/químicaRESUMO
Nowadays, Mn4+-activated fluoride red phosphors with excellent luminescence properties have triggered tremendous attentions for enhancing the performance of white light-emitting diodes (WLEDs). Nonetheless, the poor moisture resistance of these phosphors impedes their commercialization. Herein, we proposed the dual strategies of "solid solution design" and "charge compensation" to design K2Nb1-xMoxF7 novel fluoride solid solution system, and synthesized the Mn4+-activated K2Nb1-xMoxF7 (0 ≤ x ≤ 0.15, x represents the mol % of Mo6+ in the initial solution) red phosphors via co-precipitation method. The doping of Mo6+ not only significantly improve the moisture resistance of the K2NbF7: Mn4+ phosphor without any passivation and surface coating, but also effectively enhance the luminescence properties and thermal stability. In particular, the obtained K2Nb1-xMoxF7: Mn4+ (x = 0.05) phosphor possesses the quantum yield of 47.22% and retains 69.95% of its initial emission intensity at 353 K. Notably, the normalized intensity of the red emission peak (627 nm) for the K2Nb1-xMoxF7: Mn4+ (x = 0.05) phosphor is 86.37% of its initial intensity after immersion for 1440 min, prominently higher than that of the K2NbF7: Mn4+ phosphor. Moreover, a high-performance WLED with high CRI of 88 and low CCT of 3979 K is fabricated by combining blue chip (InGaN), yellow phosphor (Y3Al5O12: Ce3+) and the K2Nb1-xMoxF7: Mn4+ (x = 0.05) red phosphor. Our findings convincingly demonstrate that the K2Nb1-xMoxF7: Mn4+ phosphors have a good practical application in WLEDs.
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Fluoretos , Nióbio , LuminescênciaRESUMO
The main pathological characteristics of demyelinating diseases are central nervous system (CNS) myelin damage, and the differentiation of oligodendrocyte precursor cells is the therapeutic target of myelin repair. Previous studies have found that a large number of platelet-derived growth factor receptor α(PDGFRα) positive oligodendrocyte progenitor cells (OPCs) accumulate in the lesion area of myelin injury, and differentiation is blocked. However, the therapeutic effects of drugs currently used clinically on OPCs differentiation and myelin repair are limited. The main reason is that it is difficult to reach the effective concentration of the drug in the lesion area. Therefore, efficiently delivering into the CNS lesion area is of great significance for the treatment of MS. Natural exosomes have good biocompatibility and are ideal drug carriers. The delivery of drugs to lesion areas can be achieved by giving the exosomes armed targeting ligand. Therefore, in this study, combining exosomes with PDGFA helps them accumulate in OPCs in vitro and in vivo. Further, load montelukast into exosomes to achieve targeted therapy for cuprizone-induced demyelination animal model. The implementation of this research will help provide effective treatments for demyelinating diseases and lay a theoretical foundation for its application in the clinical treatment of different demyelinating diseases.
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Acetatos/farmacologia , Ciclopropanos/farmacologia , Doenças Desmielinizantes/metabolismo , Vesículas Extracelulares/metabolismo , Quinolinas/farmacologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Sulfetos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula , Cuprizona , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Exossomos/metabolismo , Técnicas In Vitro , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Básica da Mielina/metabolismo , Bainha de Mielina/metabolismo , Neurônios/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Oligodendroglia/metabolismo , Fagocitose , Regeneração , Células-Tronco/metabolismoRESUMO
Anacardic acid (AA) is a phenolic acid extract found in a number of plants, crops, and fruits. It exhibits a wide range of biological activities. This study displayed that AA effectively alleviated EAE, a classical mouse model of multiple sclerosis. AA administered to the EAE greatly decreased inflammatory cell infiltration to the CNS and protected the myelin integrity in the white matter of the spinal cord. AA could block lipopolysaccharide-induced DC activation. inhibited the polarization of 2D2 mice-derived T cells by inhibiting the DCs activity. Immunoblot results indicated that the phosphorylation of NF-κB is significantly suppressed in AA-treated DCs. This work displayed that AA possessed a potential anti-inflammatory therapeutic effect for the treatment of autoimmune disease.
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Encefalomielite Autoimune Experimental , Ácidos Anacárdicos , Animais , Células Dendríticas , Encefalomielite Autoimune Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias , Medula EspinalRESUMO
Phytopathogens can manipulate plant hormone signaling to counteract immune responses; however, the underlying mechanism is mostly unclear. Here, we report that Pseudomonas syringae pv tomato (Pst) DC3000 induces expression of C2H2 zinc finger transcription factor ZAT18 in a jasmonic acid (JA)-signaling-dependent manner. Biochemical assays further confirmed that ZAT18 is a direct target of MYC2, which is a very important regulator in JA signaling. CRISPR/Cas9-generated zat18-cr mutants exhibited enhanced resistance to Pst DC3000, while overexpression of ZAT18 resulted in impaired disease resistance. Genetic characterization of ZAT18 mutants demonstrated that ZAT18 represses defense responses by inhibiting the accumulation of the key plant immune signaling molecule salicylic acid (SA), which is dependent on its EAR motif. ZAT18 exerted this inhibitory effect by directly repressing the transcription of Enhanced Disease Susceptibility 1 (EDS1), which is the key signaling component of pathogen-induced SA accumulation. Overexpression of ZAT18 resulted in decreased SA content, while loss of function of ZAT18 showed enhanced SA accumulation upon pathogen infection. Furthermore, enhanced resistance and SA content in zat18-cr mutants was abolished by the mutation in EDS1. Our data indicate that pathogens induce ZAT18 expression to repress the transcription of EDS1, further antagonising SA accumulation for bacterial infection.
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Proteínas de Arabidopsis , Arabidopsis , Infecções Bacterianas , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Oxilipinas/metabolismo , Doenças das Plantas/microbiologia , Pseudomonas syringae/fisiologia , Ácido Salicílico/metabolismoRESUMO
Leaf senescence is the final stage of leaf development and is influenced by numerous internal and environmental factors. CLE family peptides are plant-specific peptide hormones that regulate various developmental processes. However, the role of CLE in regulating Arabidopsis leaf senescence remains unclear. Here, we found that CLE42 is a negative regulator of leaf senescence by using a CRISPR/Cas9-produced CLE mutant collection. The cle42 mutant displayed earlier senescence phenotypes, while overexpression of CLE42 delayed age-dependent and dark-induced leaf senescence. Moreover, application of the synthesized 12-amino-acid peptide (CLE42p) also delayed leaf senescence under natural and dark conditions. CLE42 and CLE41/44 displayed functional redundancy in leaf senescence, and the cle41 cle42 cle44 triple mutant displayed more pronounced earlier senescence phenotypes than any single mutant. Analysis of differentially expressed genes obtained by RNA-Seq methodology revealed that the ethylene pathway was suppressed by overexpressing CLE42. Moreover, CLE42 suppressed ethylene biosynthesis and thus promoted the protein accumulation of EBF, which in turn decreased the function of EIN3. Accordingly, mutation of EIN3/EIL1 or overexpression of EBF1 suppressed the earlier senescence phenotypes of the cle42 mutant. Together, our results reveal that the CLE peptide hormone regulates leaf senescence by communicating with the ethylene pathway.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Mutação/genética , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/fisiologia , Senescência VegetalRESUMO
OBJECTIVES: We aimed to systematically evaluate the prognostic prediction accuracy of radiomics features extracted from pre-treatment imaging in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Radiomics literature on overall survival (OS) prediction of PDAC were all included in this systematic review. A further meta-analysis was performed on the effect size of first-order entropy. Methodological quality and risk of bias of the included studies were assessed by the radiomics quality score (RQS) and prediction model risk of bias assessment tool (PROBAST). RESULTS: Twenty-three studies were finally identified in this review. Two (8.7%) studies compared prognosis prediction ability between radiomics model and TNM staging model by C-index, and both showed a better performance of the radiomics. Twenty-one (91.3%) studies reported significant predictive values of radiomics features. Nine (39.1%) studies were included in the meta-analysis, and it showed a significant correlation between first-order entropy and OS (HR 1.66, 95%CI 1.18-2.34). RQS assessment revealed validation was only performed in 5 (21.7%) studies on internal datasets and 2 (8.7%) studies on external datasets. PROBAST showed that 22 (95.7%) studies have a high risk of bias in participants because of the retrospective study design. CONCLUSION: First-order entropy was significantly associated with OS and might improve the accuracy of PDAC prognosis prediction. Existing studies were poorly validated, and it should be noted in future studies. Modification of PROBAST for radiomics studies is necessary since the strict requirements of prospective study design may not be applicable to the demand for a large sample size in the model construction stage. KEY POINTS: ⢠Radiomics based on the primary lesion holds great potential for prognosis prediction. First-order entropy was significantly associated with the overall survival of PDAC and might improve the accuracy of current PDAC prognosis prediction. ⢠We strongly recommend that at least an internal validation should be conducted in any radiomics study. Attention should be paid to the complex relationships between radiomics features. ⢠Due to the close relationship between radiomics and big data, the strict requirement of prospective study design in PROABST may not be appropriate for radiomics studies. A balance between study types and sample sizes for radiomics studies needs to be found in the model construction stage.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Prognóstico , Neoplasias Pancreáticas/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Biomarcadores , Neoplasias PancreáticasRESUMO
BACKGROUND: Gastrointestinal cancers are a critical global cancer burden, and tracking their trends would inform the health policies. METHODS: Trends of years of life lost (YLLs) and years lived with disability (YLDs) caused by three common gastrointestinal cancers were estimated using annual percentage change (EAPC) and age-standardized rate (ASR). Data was extracted from the Global Burden of Disease study 2019. RESULTS: The ASR per 100,000 population-year of YLLs caused by esophageal cancer, stomach cancer, and colorectal cancer were 137.98, 264.15, and 282.51 in 2019, respectively. Their overall trends of YLLs declined during 1990-2019, with the respective EAPCs being - 1.42 (95% Confidence Interval [CI]: - 1.71 to - 1.13), - 2.13 (95%CI: - 2.29 to - 1.96), and - 0.25 (95%CI: - 0.30 to - 0.19). Meanwhile, decreasing trends of YLDs caused by esophageal cancer and stomach cancer were observed, in which the EAPCs were - 0.67 (95%: - 0.94 to - 0.40) and - 0.85 (95%CI: - 0.97 to - 0.73), respectively. However, an increasing trend was seen in that of colorectal cancer (EAPC = 0.83, 95%CI: 0.77 to 0.89). Among countries, the largest decrease in trend of YLLs was that of stomacher cancer in the Republic of Korea (EAPC = - 5.88, 95%CI: - 6.07 to - 5.69). However, pronounced increasing trend of YLDs caused by colorectal cancer occurred in China (EAPC = 4.40, 95%CI: 4.07 to 4.72). CONCLUSIONS: Decreasing trends in YLLs and YLDs caused by esophageal cancer, stomach cancer, and colorectal cancer were observed in most countries and regions, indicating that the great progress had been achieved over the past decades. However, the cancer burden was geographical heterogeneity, and cost-effective measures were still required to decline the burden caused by gastrointestinal cancers.
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Neoplasias Colorretais , Neoplasias Esofágicas , Neoplasias Gastrointestinais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiologia , Anos de Vida Ajustados por Deficiência , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Colorretais/epidemiologiaRESUMO
BACKGROUND: Neonatal disorders (ND) are a significant global health issue. This article aimed to track the global trends of neonatal disorders in 204 countries/territories from 1990 to 2019. METHODS: Data was explored from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were calculated to quantify the trends of neonatal disorders and their specific causes, mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). RESULTS: In 2019, there were 23,532.23 × 103 incident cases of ND, and caused 1882.44 × 103 death worldwide. During 1990-2019, trends in the overall age-standardized incidence rate (ASIR) of ND was relatively stable, but that of age-standardized death rate (ASDR) declined (EAPC = -1.51, 95% confidence interval [CI]: -1.66 to -1.36). Meanwhile, decreasing trends of ASDR were observed in most regions and countries, particularly Cook Islands and Estonia, in which the respective EAPCs were -9.04 (95%CI: -9.69 to -8.38) and -8.12 (95%CI: -8.46 to -7.77). Among the specific four causes, only the NPB showed decreasing trends in the ASIR globally (EAPC = -0.19, 95%CI: -0.26 to -0.11). Decreasing trends of ASDR caused by ND underlying specific causes were observed in most regions, particularly the HD in Armenia, with the EAPC was -13.08 (95%CI: -14.04 to -12.11). CONCLUSIONS: Decreasing trends of death caused by neonatal disorders were observed worldwide from 1990 to 2019. However, the burden of neonatal disorders is still a considerable challenge, especially in low-resource settings, which need more effective health strategies.
Assuntos
Carga Global da Doença , Nascimento Prematuro , Feminino , Saúde Global , Humanos , Incidência , Recém-Nascido , Gravidez , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: This study aimed to examine (1) The courses of Chinese cancer patients' unmet supportive care needs (psychological, physical and daily living, health system and information, patient care and support, and sexual) from the first cancer diagnosis until the end of medical treatment; (2) The predictive role of socio-demographic and medical characteristics (i.e., age, gender, and cancer stage) in the courses of unmet needs; and (3) The associations of courses of unmet needs with courses of depressive and anxiety symptoms. METHODS: A longitudinal study was performed at Shaanxi Provincial Tumour Hospital in Xi'an, China. A total of 153 heterogeneous cancer patients were assessed after the first diagnosis (T1), at the beginning (T2) and the end (T3) of the receipt of medical treatment. Latent growth curve models were used to examine the research questions. RESULTS: Psychological needs and health system and information needs showed a decrease over time, whereas physical needs, patient care needs and sexual needs remained stable. Younger and female patients tended to report higher levels of unmet psychological needs at T1 and experienced slower decreases from T1 to T3. Only the courses of unmet psychological needs were associated with the courses of depressive and anxiety symptoms from T1 to T3. CONCLUSIONS: More attention can be given to young and female cancer patients, as they were more likely to suffer from high unmet psychological needs over the disease trajectory. Future research may focus more on addressing unmet needs reported by Chinese cancer patients.