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1.
Plant J ; 116(6): 1842-1855, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37665679

RESUMO

Perennial monocarpic mass flowering represents as a key developmental innovation in flowering time diversity in several biological and economical essential families, such as the woody bamboos and the shrubby Strobilanthes. However, molecular and genetic mechanisms underlying this important biodiversity remain poorly investigated. Here, we generated a full-length transcriptome resource incorporated into the BlueOmics database (http://blueomics.iflora.cn) for two Strobilanthes species, which feature contrasting flowering time behaviors. Using about 112 and 104 Gb Iso-seq reads together with ~185 and ~75 Gb strand-specific RNA seq data, we annotated 80 971 and 79 985 non-redundant full-length transcripts for the perennial polycarpic Strobilanthes tetrasperma and the perennial monocarpic Strobilanthes biocullata, respectively. In S. tetrasperma, we identified 8794 transcripts showing spatiotemporal expression in nine tissues. In leaves and shoot apical meristems at two developmental stages, 977 and 1121 transcripts were differentially accumulated in S. tetrasperma and S. biocullata, respectively. Interestingly, among the 33 transcription factors showing differential expression in S. tetrasperma but without differential expression in S. biocullata, three were involved potentially in the photoperiod and circadian-clock pathway of flowering time regulation (FAR1 RELATED SEQUENCE 12, FRS12; NUCLEAR FACTOR Y A1, NFYA1; PSEUDO-RESPONSE REGULATOR 5, PRR5), hence provides an important clue in deciphering the flowering diversity mechanisms. Our data serve as a key resource for further dissection of molecular and genetic mechanisms underpinning key biological innovations, here, the perennial monocarpic mass flowering.


Assuntos
Flores , Transcriptoma , Humanos , Transcriptoma/genética , Flores/genética , Flores/metabolismo , Perfilação da Expressão Gênica , Folhas de Planta/metabolismo , RNA-Seq , Regulação da Expressão Gênica de Plantas/genética
2.
Funct Integr Genomics ; 24(2): 31, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363405

RESUMO

Numerous studies have demonstrated that regulatory T (Treg) cells play an important role in the tumour microenvironment (TME). The aim of this study was to investigate whether VEGFR2 affects the expression of miR-3200-3p in exosomes secreted by tumour cells, thereby influencing Treg senescence in the TME. The results showed that VEGFR2 expression level was the highest in Calu-1 cells, and after transfection with si-VEGFR2, the exosomes secreted from Calu-1 cells were extracted and characterised with no significant difference from the exosomes of the untransfected group, but the expression of miR-3200-3p in the exosomes of the transfected si-VEGFR2 group was elevated. The Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) results suggested that exosomes highly expressing miR-3200-3p could inhibit Treg cell viability and promote apoptosis levels when treated with Treg cells. Detection of the senescence-associated proteins p16 INK4A and MMP3 by western blot (WB) revealed that exosomes highly expressing miR-3200-3p were able to elevate their protein expression levels. Tumour xenograft experiments demonstrated that exosomes with high miR-3200-3p expression promoted Treg cell senescence and inhibited subcutaneous tumour growth in nude mice. Dual-luciferase reporter assays and RNA pull-down assays showed that miR-3200-3p could be linked with DDB1. Overexpression of DDB1 reverses changes in DCAF1/GSTP1/ROS protein expression caused by exosomes with high miR-3200-3p expression. In conclusion, inhibition of VEGFR2 expression in tumour cells promotes the expression of miR-3200-3p in exosomes secreted by tumour cells. miR-3200-3p enters the TME through exosomes and acts on DDB1 in Treg cells to promote senescence of Treg cells to inhibit tumour progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , MicroRNAs , Animais , Camundongos , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Neoplasias Pulmonares/patologia , Exossomos/genética , Exossomos/metabolismo , Camundongos Nus , Senescência de Células T , Proliferação de Células/genética , Microambiente Tumoral
3.
Plant Physiol ; 192(1): 154-169, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36721922

RESUMO

Flowering transition is tightly coordinated by complex gene regulatory networks, in which AGAMOUS-LIKE 16 (AGL16) plays important roles. Here, we identified the molecular function and binding properties of AGL16 and demonstrated its partial dependency on the SUPPRESSOR OF CONSTANS 1 (SOC1) function in regulating flowering. AGL16 bound to promoters of more than 2,000 genes via CArG-box motifs with high similarity to that of SOC1 in Arabidopsis (Arabidopsis thaliana). Approximately 70 flowering genes involved in multiple pathways were potential targets of AGL16. AGL16 formed a protein complex with SOC1 and shared a common set of targets. Intriguingly, only a limited number of genes were differentially expressed in the agl16-1 loss-of-function mutant. However, in the soc1-2 knockout background, AGL16 repressed and activated the expression of 375 and 182 genes, respectively, with more than a quarter bound by AGL16. Corroborating these findings, AGL16 repressed the flowering time more strongly in soc1-2 than in the Col-0 background. These data identify a partial inter-dependency between AGL16 and SOC1 in regulating genome-wide gene expression and flowering time, while AGL16 provides a feedback regulation on SOC1 expression. Our study sheds light on the complex background dependency of AGL16 in flowering regulation, thus providing additional insights into the molecular coordination of development and environmental adaptation.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas , Flores
4.
Opt Express ; 32(6): 8638-8656, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571118

RESUMO

The laser-induced damage of ultraviolet fused silica optics is a critical factor that limits the performance enhancement of high-power laser facility. Currently, wet etching technology based on hydrofluoric acid (HF) can effectively eliminate absorbing impurities and subsurface defects, thereby significantly enhancing the damage resistance of fused silica optics. However, with an increase in the operating fluence, the redeposition defects generated during wet etching gradually become the primary bottleneck that restricts its performance improvement. The composition and morphology of redeposition defects were initially identified in this study, followed by an elucidation of their formation mechanism. A mitigation strategy was then proposed, which combines a reduction in the generation of precipitation with an acceleration of the precipitation dissolution process. Additionally, we systematically investigated the influence of various process parameters such as extrinsic impurity, etching depth, and megasonic excitation on the mitigation of deposition defects. Furthermore, a novel multiple-step dynamic etching method was developed. Through comprehensive characterization techniques, it has been confirmed that this new etching process not only effectively mitigate redeposition defects under low fluence conditions but also exhibits significant inhibition effects on high fluence precursors. Consequently, it significantly enhances the laser damage resistance performance of fused silica optics.

5.
J Exp Bot ; 75(11): 3233-3247, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38546444

RESUMO

Floral forms with an increased number of petals, also known as double-flower phenotypes, have been selected and conserved in many domesticated plants, particularly in ornamentals, because of their great economic value. The molecular and genetic mechanisms that control this trait are therefore of great interest, not only for scientists, but also for breeders. In this review, we summarize current knowledge of the gene regulatory networks of flower initiation and development and known mutations that lead to variation of petal number in many species. In addition to the well-accepted miR172/AP2-like module, for which many questions remain unanswered, we also discuss other pathways in which mutations also lead to the formation of extra petals, such as those involved in meristem maintenance, hormone signalling, epigenetic regulation, and responses to environmental signals. We discuss how the concept of 'natural mutants' and recent advances in genomics and genome editing make it possible to explore the molecular mechanisms underlying double-flower formation, and how such knowledge could contribute to the future breeding and selection of this trait in more crops.


Assuntos
Flores , Flores/genética , Flores/crescimento & desenvolvimento , Flores/anatomia & histologia , Regulação da Expressão Gênica de Plantas , Mutação , Redes Reguladoras de Genes
6.
J Exp Bot ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642399

RESUMO

Plant life-history is determined by two transitions, the germination and the flowering times, in which the phosphatidylethanolamine-binding proteins (PEBP) FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) play key regulatory roles. Compared to the highly conserved TFL1-likes, FT-like genes vary in copy numbers significantly in gymnosperms and monocots of the angiosperms, while sporadic duplications can be observed in eudicots. Here, via a systematic analysis of the PEBPs in angiosperms with a special focus on twelve representative species featuring high-quality genomes in the Lamiales order, we identified a successive lineage-specific but systematic expansion of FT-like genes in the families of core Lamiales. The first expansion event generated FT1-likes mainly via a core-Lamiales-specific whole-genome-duplication (cL-WGD), while on the other hand, a likely random duplication produced the FT2-likes in the lineages containing Scrophulariaceae and rest of the core Lamiales. Both FT1- and FT2-like genes were further amplified tandemly in some families. These expanded FT-likes featured highly diverged expression patterns and structural variation, indicating functional diversification. Intriguingly, some core Lamiales contained the relict MOTHER OF FT AND TFL1 like 2 (MFT2) that likely expanded in the common ancestor of angiosperms. Our data showcase the highly dynamic lineage-specific expansion of the FT-like genes, thus provide important and fresh evolutionary insights into the gene-regulatory-network underpinning flowering time diversity in Lamiales, and more generally, in angiosperms.

7.
Anticancer Drugs ; 35(5): 418-425, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38386011

RESUMO

The clinical significance of plasma soluble programmed cell death ligand 1 (sPD-L1) and vascular endothelial growth factor (VEGF) for non-small cell lung cancer (NSCLC) treated with the combination of anti-angiogenic therapy and anti-PD-L1 antibody (Ab) remain unknown. This study aimed to explore the association between plasma sPD-L1 and VEGF levels and the prognosis of NSCLC patients treated with the combination of Envafolimab and Endostar. Peripheral blood samples were collected from 24 NSCLC patients at baseline and after 6 weeks of treatment and were detected for sPD-L1 and VEGF levels. Both baseline and posttreatment sPD-L1 were significantly higher in progressive disease (PD) group than in controlled disease (CD) group (median: 77.5 pg/ml vs. 64.6 pg/ml, P  = 0.036, median: 8451 pg/ml vs. 5563 pg/ml, P  = 0.012). In multivariate analysis, lower baseline sPD-L1 levels were significantly associated with longer progression-free survival (PFS) (HR = 6.834, 95% CI: 1.350-34.592, P  = 0.020). There were significantly higher posttreatment VEGF levels in PD group compared with CD group (median: 323.7 pg/ml vs. 178.5 pg/ml, P  = 0.009). Higher posttreatment VEGF levels were significantly associated with shorter PFS in multivariate analysis (HR = 5.911, 95% CI: 1.391-25.122, P  = 0.016). Plasma sPD-L1 and VEGF levels are associated with the clinical response and prognosis of NSCLC patients treated with the combination of PD-L1 inhibitors and anti-angiogenetic therapy.


Assuntos
Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fator A de Crescimento do Endotélio Vascular , Humanos , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/química , Antígeno B7-H1/sangue , Antígeno B7-H1/química
8.
BMC Psychiatry ; 23(1): 381, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259044

RESUMO

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) has been identified as a risk factor for obesity in both children and adolescents. However, the mechanisms underlying the relationship between ADHD and obesity are still unclear. This study aimed to test a theoretical model of whether anxiety/depression is an intermediary factor in the ADHD-obesity relationship. METHODS: Data were derived from the National Health Interview Survey (NHIS), a principal source of information on the health of the civilian noninstitutionalized population of the United States. A total of 35,108 adolescents aged 12-17 years old from 2010-2015 NHIS and 2016-2018 NHIS representing 46,550,729 individuals in the weighted population, had a parent-reported previous ADHD diagnosis, emotional problems, and height and weight data. Mediation analyses were used to explore whether anxiety/depression is an intermediary factor in the relationship between ever having ADHD and obesity. Mediation analyses were performed using multiple logistic regressions. RESULTS: The findings showed that ADHD was a predictor of obesity. This relationship was partially mediated by depression(2010-2015: ß=0.28, 95%CI:0.13-0.43; 2016-2018: ß=0.26, 95%CI:0.03-0.49), as well as anxiety (2010-2015: ß=0.28, 95%CI:0.18-0.38). CONCLUSIONS: Our study suggests the hypothetical role of depression and anxiety as underlying mechanisms in the association between ever having ADHD and obesity in adolescents. When treating children with ADHD, clinicians need to be particularly attentive to whether they show emotional problems and use interventions to eliminate anxiety/depression to protect against obesity.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Obesidade Infantil , Criança , Adolescente , Humanos , Estados Unidos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Depressão/psicologia , Ansiedade/complicações , Ansiedade/psicologia , Transtornos de Ansiedade/epidemiologia
9.
Rev Esp Enferm Dig ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982558

RESUMO

A 46-year-old male visited our hospital with blood stool and constipation. Colonoscopy revealed a broad-based protruded lesion in the rectum.The endoscopic ultrasonography showed the lesion invaded the submucosa, and the boundary between the local and intrinsic muscular layer was not clear. Transanal local excision was conducted, the pathology showed a rare case of mucosal prolapse syndrome merging chronic suppurative inflammation.

10.
Opt Lett ; 47(3): 653-656, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35103696

RESUMO

A photo-thermal absorption distribution probability curve based on a normal distribution model was proposed to describe the distribution of absorptive defects on fused silica surfaces under different processing conditions. Simultaneously, the maximum distribution probability absorption coefficient (MPA) and absorption distribution deviation (ADD) were used to quantitatively describe the overall absorption level and the uniformity of the absorption distribution on the fused silica surface. Based on this, the MPA (µ) and ADD (δ) were used to establish a statistical numerical relationship with the surface damage density of fused silica. The results showed that when µ ≤ 0.095 ± 0.015 and δ ≤ 0.045 ppm, the fused silica optics met the manufacturing process requirements for high laser-induced damage performance. Thus, a non-destructive approximate evaluation of the laser-induced damage density on the fused silica surface was achieved. This evaluation method provides a new, to the best of our knowledge, technology for evaluating the manufacturing process quality related to the damage performance of fused silica optics in high-power solid-state laser facilities and is an important supplement to popular destructive laser-induced damage testing methods.

11.
Microb Cell Fact ; 21(1): 147, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854349

RESUMO

BACKGROUND: Macrolactins, a type of macrolide antibiotic, are toxic to the producer strains. As such, its level is usually maintained below the lethal concentration during the fermentation process. To improve the production of macrolactins, we applied adaptive laboratory evolution technology to engineer a saline-resistant mutant strain. The hypothesis that strains with saline resistance show improved macrolactins production was investigated. RESULTS: Using saline stress as a selective pressure, we engineered a mutant strain with saline resistance coupled with enhanced macrolactins production within 60 days using a self-made device. As compared with the parental strain, the evolved strain produced macrolactins with 11.93% improvement in non-saline stress fermentation medium containing 50 g/L glucose, when the glucose concentration increased to 70 g/L, the evolved strain produced macrolactins with 71.04% improvement. RNA sequencing and metabolomics results revealed that amino acid metabolism was involved in the production of macrolactins in the evolved strain. Furthermore, genome sequencing of the evolved strain revealed a candidate mutation, hisDD41Y, that was causal for the improved MLNs production, it was 3.42 times higher than the control in the overexpression hisDD41Y strain. Results revealed that saline resistance protected the producer strain from feedback inhibition of end-product (macrolide antibiotic), resulting in enhanced MLNs production. CONCLUSIONS: In the present work, we successfully engineered a mutant strain with enhanced macrolactins production by adaptive laboratory evolution using saline stress as a selective pressure. Based on physiological, transcriptomic and genetic analysis, amino acid metabolism was found to benefit macrolactins production improvement. Our strategy might be applicable to improve the production of other kinds of macrolide antibiotics and other toxic compounds. The identification of the hisD mutation will allow for the deduction of metabolic engineering strategies in future research.


Assuntos
Bacillus , Aminoácidos/genética , Antibacterianos , Bacillus/genética , Fermentação , Macrolídeos , Engenharia Metabólica/métodos
12.
J Clin Lab Anal ; 36(10): e24679, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36045605

RESUMO

BACKGROUND: Gastrointestinal bleeding (GIB) is a potential contributing factor for poor prognosis of spontaneous basal ganglia hemorrhage (BGH). This study aimed to investigate the predictive value of new inflammatory biomarkers including neutrophil to lymphocytes (NLR) on admission and construct a nomogram for rapidly predicting GIB in acute BGH. METHODS: The retrospective study included all patients with acute BGH admitted from the emergency department in Huashan Hospital from July 2017 to January 2019. Multivariate analysis was conducted to evaluate the correlation between factors within 24 h and the occurrence of GIB within 7 days after BGH. The receiver operating characteristic (ROC) curve was performed to estimate the prediction ability of inflammatory biomarkers. A nomogram based on significant predictors was validated by ROC curve and calibration curve. RESULTS: A total of 122 patients were enrolled in this study, and the incidence of GIB was 23.0%. Patients with GIB had larger hematoma volume (≥30 ml), lower Glasgow Coma Scale (GCS) score (≤8) and increased inflammatory biomarkers on admission. ROC curve revealed that NLR had a high predictive value to the complication (area under the curve = 0.87). According to multivariate analysis, NLR, GCS score, and hematoma volume were main factors for nomogram, with good calibration and discrimination. CONCLUSIONS: Neutrophil-to-lymphocyte ratio and GCS score within 24 h after the onset of acute BGH are the independent risk factors for GIB. The nomogram developed by these predictors may assist surgeons in rapidly assessing and preventing of GIB for BGH patients in earlier stage.


Assuntos
Hemorragia dos Gânglios da Base , Neutrófilos , Biomarcadores , Hemorragia Gastrointestinal/epidemiologia , Hematoma , Humanos , Linfócitos , Prognóstico , Curva ROC , Estudos Retrospectivos
13.
Opt Express ; 29(17): 27041-27047, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615126

RESUMO

With current trends to progressively miniaturize optical systems, it is now essential to look for alternative methods to control light at extremely small dimensions. Metalenses are composed of subwavelength nanostructures and have an excellent ability to manipulate the polarization, phase, and amplitude of incident light. Although great progress of metalenses has been made, the compact metalens-integrated devices have not been researched adequately. In the study, we present compact imaging devices for near-infrared microscopy, in which a metalens is exploited. The indicators including resolution, magnification, and image quality are investigated via imaging several specimens of intestinal cells to verify the overall performance of the imaging system. The further compact devices, where the metalens is integrated directly on the CMOS imaging sensor, are also researched to detect biomedical issues. This study provides an approach to constructing compact imaging devices based on metalenses for near-infrared microscopy, micro-telecopy, etc., which can promote the miniaturization tending of futural optical systems.

15.
Syst Biol ; 69(4): 795-812, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32011711

RESUMO

A statistical framework of model comparison and model validation is essential to resolving the debates over concatenation and coalescent models in phylogenomic data analysis. A set of statistical tests are here applied and developed to evaluate and compare the adequacy of substitution, concatenation, and multispecies coalescent (MSC) models across 47 phylogenomic data sets collected across tree of life. Tests for substitution models and the concatenation assumption of topologically congruent gene trees suggest that a poor fit of substitution models, rejected by 44% of loci, and concatenation models, rejected by 38% of loci, is widespread. Logistic regression shows that the proportions of GC content and informative sites are both negatively correlated with the fit of substitution models across loci. Moreover, a substantial violation of the concatenation assumption of congruent gene trees is consistently observed across six major groups (birds, mammals, fish, insects, reptiles, and others, including other invertebrates). In contrast, among those loci adequately described by a given substitution model, the proportion of loci rejecting the MSC model is 11%, significantly lower than those rejecting the substitution and concatenation models. Although conducted on reduced data sets due to computational constraints, Bayesian model validation and comparison both strongly favor the MSC over concatenation across all data sets; the concatenation assumption of congruent gene trees rarely holds for phylogenomic data sets with more than 10 loci. Thus, for large phylogenomic data sets, model comparisons are expected to consistently and more strongly favor the coalescent model over the concatenation model. We also found that loci rejecting the MSC have little effect on species tree estimation. Our study reveals the value of model validation and comparison in phylogenomic data analysis, as well as the need for further improvements of multilocus models and computational tools for phylogenetic inference. [Bayes factor; Bayesian model validation; coalescent prior; congruent gene trees; independent prior; Metazoa; posterior predictive simulation.].


Assuntos
Modelos Biológicos , Filogenia , Animais , Reprodutibilidade dos Testes
16.
Org Biomol Chem ; 19(19): 4243-4247, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33885700

RESUMO

Benzofluorene-containing atypical angucyclines are an important family of natural products with a broad spectrum of antibacterial and cytotoxic properties. Interestingly, symmetric and asymmetric dimers showed better activity than the monomer in this class of compounds. Herein, we reported the isolation of a new asymmetric dimer nenestatin B (2) from the deep sea actinomycete Micromonospora echinospora SCSIO 04089 and a monomer nenestatin C (3) from an NmrA family regulatory protein coding gene nes18 inactivated mutant. The structural elucidation of 3 indicated the essential role of Nes18 in the biosynthetic pathway of 2, specifically in dimerization via C-C bond formation.


Assuntos
Dimerização
17.
J Immunol ; 203(4): 1012-1020, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308089

RESUMO

The evolutionarily conserved F-box family of proteins are well known for their role as the key component of SKP1-Cullin1-F-box (SCF) E3 ligase in controlling cell cycle, cell proliferation and cell death, carcinogenesis, and cancer metastasis. However, thus far, there is only limited investigation on their involvement in antiviral immunity. In contrast to the canonical function of FBXO6 associated with SCF E3 ligase complex, we report, in this study, that FBXO6 can also potently regulate the activation of IFN-I signaling during host response to viral infection by targeting the key transcription factor IFN-regulatory factor 3 (IRF3) for accelerated degradation independent of SCF in human embryonic kidney cells (HEK293T) and human lung cancer epithelial cells (A549). Structure and function delineation has further revealed that FBXO6 interacts with IAD domain of IRF3 through its FBA region to induce ubiquitination and degradation of IRF3 without the involvement of SCF. Thus, our studies have identified a general but, to our knowledge, previously unrecognized role and a novel noncanonical mechanism of FBXO6 in modulating IFN-I-mediated antiviral immune responses, which may protect the host from immunopathology of overreactive and harmful IFN-I production.


Assuntos
Proteínas Ligases SKP Culina F-Box/imunologia , Viroses/imunologia , Linhagem Celular , Humanos , Interferon Tipo I/imunologia
18.
Appl Opt ; 60(26): 8130-8136, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613076

RESUMO

Particulate contamination on the optical surface can seriously degrade the performance of optics working in the high peak power laser system. In this study, we show that the nature of optical damages on the input surface induced by particles depends on the optical property of the particles. Ceramic Al2O3 particles tend to cause micro-fractures to the optical surface, but metallic Fe particles mainly undergo ablation on the substrate. Different microscopes are used to characterize their damage morphologies, and the light distribution and thermal evolution of two different particles are simulated, focusing on better understanding their special damage morphologies.

19.
Lancet Oncol ; 21(6): 832-842, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32416073

RESUMO

BACKGROUND: Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. METHODS: ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m2 every 3 weeks) or irinotecan (180 mg/m2 every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov, NCT03099382, and is closed to new participants. FINDINGS: From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1-12·8) in the camrelizumab group and 6·2 months (3·6-10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8-9·7) in the camrelizumab group and 6·2 months (5·7-6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57-0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [<1%]), and diarrhoea (three [1%] vs nine [4%]). Serious treatment-related adverse events occurred in 37 (16%) of 228 patients in the camrelizumab group, and in 32 (15%) of 220 patients in the chemotherapy group. Ten treatment-related deaths occurred, seven (3%) in the camrelizumab group (three deaths from unknown causes, one enterocolitis, one hepatic function abnormal, one pneumonitis, and one myocarditis) and three (1%) in the chemotherapy group (two deaths from unknown causes, and one gastrointestinal haemorrhage). INTERPRETATION: Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China. FUNDING: Jiangsu Hengrui Medicine.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Irinotecano/administração & dosagem , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , China , Progressão da Doença , Docetaxel/efeitos adversos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Humanos , Irinotecano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Transdução de Sinais , Fatores de Tempo , Adulto Jovem
20.
Plant Mol Biol ; 104(1-2): 81-95, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32621166

RESUMO

KEY MESSAGE: Genome-wide identification of WD40-like genes reveals a duplication of COP1-like genes, one of the key players involved in regulation of flowering time and photomorphogenesis, with strong functional diversification in Rosaceae. WD40 proteins play crucial roles in a broad spectrum of developmental and physiological processes. Here, we conducted a systematic characterization of this family of genes in Rosa chinensis 'Old Blush' (OB), a founder genotype for modern rose domestication. We identified 187 rose WD40 genes and classified them into 5 clusters and 15 subfamilies with 11 of RcWD40s presumably generated via tandem duplication. We found RcWD40 genes were expressed differentially following stages of vegetative and reproductive development. We detected a duplication of CONSTITUTIVE PHOTOMORPHOGENIC1-like genes in rose (RcCOP1 and RcCOP1L) and other Rosaceae plants. Featuring a distinct expression pattern and a different profile of cis-regulatory-elements in the transcriptional regulatory regions, RcCOP1 seemed being evolutionarily conserved while RcCOP1L did not dimerize with RcHY5 and RcSPA4. Our data thus reveals a functional diversification of COP1-like genes in Rosacaeae plants, and provides a valuable resource to explore the potential function and evolution of WD40-like genes in Rosaceae plants.


Assuntos
Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Rosaceae/genética , Rosaceae/metabolismo , Ubiquitina-Proteína Ligases/genética , Sequência de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Cromossomos de Plantas/genética , Domesticação , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Filogenia , Plantas Geneticamente Modificadas , Rosa/genética , Rosa/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
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