RESUMO
INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.
RESUMO
At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.
Assuntos
Nanopartículas Metálicas , Esquizofrenia , Humanos , Cisteína/química , Células HeLa , Esquizofrenia/diagnóstico , Corantes Fluorescentes/química , Prata , Espectrometria de Fluorescência/métodos , Homocisteína , Glutationa/análiseRESUMO
Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant. Knocking out SlFAF1/2c in the EF mutant reverted the early flowering phenotype of the mutant to the normal flowering time of the wild-type tomato plants. SlFAF1/2c promoted the floral transition by shortening the vegetative phase rather than by reducing the number of leaves produced before the emergence of the first inflorescence. The COP9 signalosome subunit 5B (CSN5B) was shown to interact with FAF1/2c, and knocking out CSN5B led to an early flowering phenotype in tomato. Interestingly, FAF1/2c was found to reduce the accumulation of the CSN5B protein by reducing its protein stability. These findings imply that FAF1/2c regulates flowering time in tomato by reducing the accumulation and stability of CSN5B, which influences the expression of SINGLE FLOWER TRUSS (SFT), JOINTLESS (J) and UNIFLORA (UF). Thus, a new allele of SlFAF1/2c was discovered and found to regulate flowering time in tomato.
Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Alelos , Mutação com Ganho de Função , Mutação , Flores/genética , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Cancer remains a leading cause of mortality and poses a substantial threat to public health. Studies have revealed that Long noncoding RNA DANCR is a cytoplasmic lncRNA whose aberrant expression plays a pivotal role in various cancer types. Within tumour biology, DANCR exerts regulatory control over crucial processes such as proliferation, invasion, metastasis, angiogenesis, inflammatory responses, cellular energy metabolism reprogramming, and apoptosis. By acting as a competitive endogenous RNA for miRNAs and by interacting with proteins and mRNAs at the molecular level, DANCR contributes significantly to cancer progression. Elevated DANCR levels have also been linked to heightened resistance to anticancer drugs. Moreover, the detection of circulating DANCR holds promise as a valuable biomarker for aiding in the clinical differentiation of different cancer types. This article offers a comprehensive review and elucidation of the primary functions and molecular mechanisms through which DANCR influences tumours.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , AnimaisRESUMO
Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.
Assuntos
Hipertensão Pulmonar , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/genética , Artéria Pulmonar/metabolismo , Hipóxia/tratamento farmacológico , Hipóxia/genética , Hipóxia/complicações , Regulação da Expressão Gênica , Oxigênio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
A meta-analysis was conducted to comprehensively evaluate the impact of cluster nursing interventions on the prevention of pressure ulcers (PUs) in intensive care unit (ICU) patients. Computer searches were performed in databases including Embase, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure for randomized controlled trials (RCTs) implementing cluster nursing interventions for PUs prevention in ICU patients, with the search period covering the database inception to November 2023. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 17 RCTs involving 1463 ICU patients were included. The analysis showed that compared with conventional nursing, cluster nursing interventions significantly reduced the incidence of PUs (odds ratio: 0.24, 95% confidence intervals [CI]: 0.17-0.34, p < 0.001) and also significantly improved the levels of anxiety (standardized mean difference [SMD]: -1.39, 95% CI: -1.57 to 1.22, p < 0.001) and depression (SMD: -1.64, 95% CI: -2.02 to 1.26, p < 0.001) in ICU patients. This study indicates that the application of cluster nursing interventions in ICU patients can effectively reduce the incidence of PUs, as well as improve patients' anxiety and depression levels, thereby enhancing their quality of life, which is worth clinical promotion and application.
Assuntos
Úlcera por Pressão , Humanos , Úlcera por Pressão/prevenção & controle , Úlcera por Pressão/epidemiologia , Cuidados Críticos , Ansiedade , Unidades de Terapia Intensiva , SupuraçãoRESUMO
Nitrogen (N2) gas in the atmosphere is partially replenished by microbial denitrification of ammonia. Recent study has shown that Alcaligenes ammonioxydans oxidizes ammonia to dinitrogen via a process featuring the intermediate hydroxylamine, termed "Dirammox" (direct ammonia oxidation). However, the unique biochemistry of this process remains unknown. Here, we report an enzyme involved in Dirammox that catalyzes the conversion of hydroxylamine to N2. We tested previously annotated proteins involved in redox reactions, DnfA, DnfB, and DnfC, to determine their ability to catalyze the oxidation of ammonia or hydroxylamine. Our results showed that none of these proteins bound to ammonia or catalyzed its oxidation; however, we did find DnfA bound to hydroxylamine. Further experiments demonstrated that, in the presence of NADH and FAD, DnfA catalyzed the conversion of 15N-labeled hydroxylamine to 15N2. This conversion did not happen under oxygen (O2)-free conditions. Thus, we concluded that DnfA encodes a hydroxylamine oxidase. We demonstrate that DnfA is not homologous to any known hydroxylamine oxidoreductases and contains a diiron center, which was shown to be involved in catalysis via electron paramagnetic resonance experiments. Furthermore, enzyme kinetics of DnfA were assayed, revealing a Km of 92.9 ± 3.0 µM for hydroxylamine and a kcat of 0.028 ± 0.001 s-1. Finally, we show that DnfA was localized in the cytoplasm and periplasm as well as in tubular membrane invaginations in HO-1 cells. To the best of our knowledge, we conclude that DnfA is the first enzyme discovered that catalyzes oxidation of hydroxylamine to N2.
Assuntos
Alcaligenes , Amônia , Hidroxilaminas , Oxirredutases , Alcaligenes/enzimologia , Amônia/metabolismo , Proteínas de Bactérias/metabolismo , Flavina-Adenina Dinucleotídeo/metabolismo , Hidroxilaminas/metabolismo , NAD/metabolismo , Nitrogênio/metabolismo , Oxirredução , Oxirredutases/metabolismo , OxigênioRESUMO
While the global COVID-19 pandemic has subsided, microbial aerosol detection has become of high concern. Timely, accurate, and highly sensitive monitoring of microbial aerosols in indoor air is the basis for effective prevention and control of infectious diseases. At present, no commercial equipment or reliable technology can simultaneously control the detection time and limit at 6 h and 102 CFU/mL, respectively. Based on the "safety size range" of particulate matter in the air, we propose a new method of microbial dilation detection, which enables the pathogen to grow rapidly and dramatically into a polymeric microsphere, larger in size than the coexisting aerosol particles. "Like a crane standing among chickens", the microorganism can be easily visualized and counted. Different from routine chemical and biological sensing technologies, this method can achieve absolute counting of microbial particles, and the simple principles can be developed into devices for different life scenarios.
Assuntos
COVID-19 , Animais , Humanos , COVID-19/diagnóstico , Galinhas , Pandemias , Aerossóis e Gotículas Respiratórios , Material ParticuladoRESUMO
Hepatocellular carcinoma (HCC) is one of the main principal causes of cancer death, and the late definite diagnosis limits therapeutic approaches in time. The early diagnosis of HCC is essential, and the previous investigations on the biomarkers inferred that the γ-glutamyltranspeptidase (GGT) level could indicate the HCC process. Herein, a near-infrared fluorescence/photoacoustic (NIRF/PA) bimodal probe, CySO3-GGT, was developed for monitoring the GGT level and thus to image the HCC process. After the in-solution tests, the bimodal response was convinced. The various HCC processes were imaged by CySO3-GGT at the cellular level. Then, the CCl4-induced HCC (both induction and treatment) and the subcutaneous and orthotopic xenograft mice models were selected. All throughout the tests, CySO3-GGT achieved NIRF and PA bimodal imaging of the HCC process. In particular, CySO3-GGT could effectively realize 3D imaging of the HCC nodule by visualizing the boundary between the tumor and the normal tissue. The information here might offer significant guidance for the dynamic monitoring of HCC in the near future.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Corantes Fluorescentes , Imagem Óptica/métodos , XenoenxertosRESUMO
BACKGROUND: Interleukin-17A (IL-17A), a proinflammatory cytokine primarily secreted by Th17 cells, γδT cells and natural killer T (NKT) cells, performs essential roles in the microenvironment of certain inflammation-related tumours by regulating cancer growth and tumour elimination proved in previous literature. In this study, the mechanism of IL-17A that induces mitochondrial dysfunction promoted pyroptosis has been explored in colorectal cancer cells. METHOD: The records of 78 patients diagnosed with CRC were reviewed via the public database to evaluate clinicopathological parameters and prognosis associations of IL-17A expression. The colorectal cancer cells were treated with IL-17A, and the morphological characteristics of those cells were indicated by scanning electron microscope and transmission electron microscope. After IL-17A treatment, mitochondrial dysfunction was tested by mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). The expression of pyroptosis associated proteins including cleaved caspase-4, cleaved gasdermin-D (GSDMD), IL-1ß, receptor activator of nuclear NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck like protein containing a card (ASC), and factor-kappa B was measured through western blotting. RESULTS: Positive IL-17A protein expression was observed in CRC compared to the non-tumour tissue. IL-17A expression indicates a better differentiation, earlier stage, and better overall survival in CRC. IL-17A treatment could induce mitochondrial dysfunction and stimulate intracellular reactive oxygen species (ROS) production. Furthermore, IL-17A could promote pyroptosis of colorectal cancer cells and significantly increase the secretion of inflammatory factors. Nevertheless, the pyroptosis induced by IL-17A could be inhibited through the pre-treatment with Mito-TEMPO (a mitochondria-targeted superoxide dismutase mimetic with superoxide and alkyl radical scavenging properties) or Z-LEVD-FMK (caspase-4 inhibitor, fluoromethylketone). Additionally, after being treated with IL-17A, an increasing number of CD8 + T cells showed in mouse-derived allograft colon cancer models. CONCLUSION: IL-17A, as a cytokine mainly secreted by γδT cells in the colorectal tumour immune microenvironment, can regulate the tumour microenvironment in multiple ways. IL-17A could induce mitochondrial dysfunction and pyroptosis through the ROS/NLRP3/caspase-4/GSDMD pathway, and promote intracellular ROS accumulation. In addition, IL-17A can promote the secretion of inflammatory factors such as IL-1ßãIL-18 and immune antigens, and recruit CD8 + T cells to infiltrate tumours.
Assuntos
Neoplasias Colorretais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Interleucina-17/metabolismo , Mitocôndrias/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Neoplasias Colorretais/metabolismo , Inflamassomos/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Exosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood. RESULTS: In this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway. CONCLUSIONS: Our findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine. Video Abstract.
Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Exossomos/metabolismo , Peroxirredoxinas/metabolismo , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismoRESUMO
Myocardin-related transcription factor A (MRTF-A) has an inhibitory effect on myocardial infarction; however, the mechanism is not clear. This study reveals the mechanism by which MRTF-A regulates autophagy to alleviate myocardial infarct-mediated inflammation, and the effect of silent information regulator 1 (SIRT1) on the myocardial protective effect of MRTF-A was also verified. MRTF-A significantly decreased cardiac damage induced by myocardial ischemia. In addition, MRTF-A decreased NLRP3 inflammasome activity, and significantly increased the expression of autophagy protein in myocardial ischemia tissue. Lipopolysaccharide (LPS) and 3-methyladenine (3-MA) eliminated the protective effects of MRTF-A. Furthermore, simultaneous overexpression of MRTF-A and SIRT1 effectively reduced the injury caused by myocardial ischemia; this was associated with downregulation of inflammatory factor proteins and when upregulation of autophagy-related proteins. Inhibition of SIRT1 activity partially suppressed these MRTF-A-induced cardioprotective effects. SIRT1 has a synergistic effect with MRTF-A to inhibit myocardial ischemia injury through reducing the inflammation response and inducing autophagy.
Assuntos
Infarto do Miocárdio , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Ratos , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos Sprague-Dawley , Sirtuína 1/genética , Sirtuína 1/metabolismo , Autofagia , Inflamação , ApoptoseRESUMO
Biofilms are known to be a great challenge for their anti-bacterial activity as they obstruct drug action for deeper and more thorough bacteria-killing effects. Therefore, developing highly effective antibacterial agents to destroy biofilms and eradicate bacteria is of great significance. Herein, a new type of nanocomposites (denoted as poly(4-cyanostyrene)@silver@polylysine) is proposed, in which polylysine (PLL) could rapidly capture the biofilms and exhibit excellent antibacterial efficacy together with decorated silver (Ag) nanoparticles (NPs) through the charge effect and Ag+ release. Notably, nearly 100% antibacterial rates against Gram-positive bacterium (Staphylococcus aureus, S. aureus) and Gram-negative bacterium (Escherichia coli, E. coli) were achieved. More importantly, poly(4-cyanostyrene) with biological silent Raman imaging capacity is able to illustrate the relationship between antibacterial efficiency and biofilm breakage. In short, such novel nanocomposites can improve the bioavailability of each component and display tremendous potential in antibacterial applications.
Assuntos
Nanopartículas Metálicas , Nanocompostos , Escherichia coli , Prata/farmacologia , Polilisina/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia , BiofilmesRESUMO
Streptococcosis disease caused by Streptococcus agalactiae (Group B Streptococcus, GBS) results in a huge economic loss of tilapia culture. It is urgent to find new antimicrobial agents against streptococcosis. In this study, 20 medicinal plants were evaluated in vitro and in vivo to obtain medicinal plants and potential bioactive compounds against GBS infection. The results showed that the ethanol extracts of 20 medicinal plants had low or no antibacterial properties in vitro, with a minimal inhibitory concentration ≥256 mg/L. Interestingly, in vivo tests showed that 7 medicinal plants could significantly inhibit GBS infection in tilapia, and Sophora flavescens (SF) had the strongest anti-GBS activity in tilapia, reaching 92.68%. SF could significantly reduce the bacterial loads of GBS in different tissues (liver, spleen and brain) of tilapia after treated with different tested concentrations (12.5, 25.0, 50.0 and 100.0 mg/kg) for 24 h. Moreover, 50 mg/kg SF could significantly improve the survival rate of GBS-infected tilapia by inhibiting GBS replication. Furthermore, the expression of antioxidant gene cat, immune-related gene c-type lysozyme and anti-inflammatory cytokine il-10 in liver tissue of GBS-infected tilapia significantly increased after treated with SF for 24 h. Meanwhile, SF significantly reduced the expression of immune-related gene myd88 and pro-inflammatory cytokines il-8 and il-1ß in liver tissue of GBS-infected tilapia. The negative and positive models of UPLC-QE-MS, respectively, identified 27 and 57 components of SF. The major components of SF extract in the negative model were α, α-trehalose, DL-malic acid, D- (-)-fructose and xanthohumol, while in the positive model were oxymatrine, formononetin, (-)-maackiain and xanthohumol. Interestingly, oxymatrine and xanthohumol could significantly inhibit GBS infection in tilapia. Taken together, these results suggest that SF can inhibit GBS infection in tilapia, and it has potential for the development of anti-GBS agents.
Assuntos
Ciclídeos , Doenças dos Peixes , Plantas Medicinais , Infecções Estreptocócicas , Tilápia , Animais , Sophora flavescens , Streptococcus agalactiae/genética , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/veterinária , Infecções Estreptocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Tilápia/microbiologia , Citocinas , Ciclídeos/microbiologiaRESUMO
The high-pathogenicity island (HPI) was initially identified in Yersinia and can be horizontally transferred to Escherichia coli to produce yersiniabactin (Ybt), which enhances the pathogenicity of E. coli by competing with the host for Fe3+. Pyroptosis is gasdermin-induced necrotic cell death. It involves the permeabilization of the cell membrane and is accompanied by an inflammatory response. It is still unclear whether Ybt HPI can cause intestinal epithelial cells to undergo pyroptosis and contribute to gut inflammation during E. coli infection. In this study, we infected intestinal epithelial cells of mice with E. coli ZB-1 and the Ybt-deficient strain ZB-1Δirp2. Our findings demonstrate that Ybt-producing E. coli is more toxic and exacerbates gut inflammation during systemic infection. Mechanistically, our results suggest the involvement of the NLRP3/caspase-1/GSDMD pathway in E. coli infection. Ybt promotes the assembly and activation of the NLRP3 inflammasome, leading to GSDMD cleavage into GSDMD-N and promoting the pyroptosis of intestinal epithelial cells, ultimately aggravating gut inflammation. Notably, NLRP3 knockdown alleviated these phenomena, and the binding of free Ybt to NLRP3 may be the trigger. Overall, our results show that Ybt HPI enhances the pathogenicity of E. coli and induces pyroptosis via the NLRP3 pathway, which is a new mechanism through which E. coli promotes gut inflammation. Furthermore, we screened drugs targeting NLRP3 from an existing drug library, providing a list of potential drug candidates for the treatment of gut injury caused by E. coli.
Assuntos
Células Epiteliais , Infecções por Escherichia coli , Escherichia coli , Mucosa Intestinal , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Animais , Camundongos , Enterócitos/metabolismo , Enterócitos/microbiologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Escherichia coli/metabolismo , Escherichia coli/patogenicidade , Infecções por Escherichia coli/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologiaRESUMO
In this paper, we focus on developing a high efficient algorithm for solving d-dimension time-fractional diffusion equation (TFDE). For TFDE, the initial function or source term is usually not smooth, which can lead to the low regularity of exact solution. And such low regularity has a marked impact on the convergence rate of numerical method. In order to improve the convergence rate of the algorithm, we introduce the space-time sparse grid (STSG) method to solve TFDE. In our study, we employ the sine basis and the linear element basis for spatial discretization and temporal discretization, respectively. The sine basis can be divided into several levels, and the linear element basis can lead to the hierarchical basis. Then, the STSG can be constructed through a special tensor product of the spatial multilevel basis and the temporal hierarchical basis. Under certain conditions, the function approximation on standard STSG can achieve the accuracy order O(2-JJ) with O(2JJ) degrees of freedom (DOF) for d=1 and O(2Jd) DOF for d>1, where J denotes the maximal level of sine coefficients. However, if the solution changes very rapidly at the initial moment, the standard STSG method may reduce accuracy or even fail to converge. To overcome this, we integrate the full grid into the STSG, and obtain the modified STSG. Finally, we obtain the fully discrete scheme of STSG method for solving TFDE. The great advantage of the modified STSG method can be shown in the comparative numerical experiment.
RESUMO
Tomato (Solanum lycopersicum) is a highly valuable fruit crop, and yield is one of the most important agronomic traits. However, the genetic architecture underlying tomato yield-related traits has not been fully addressed. Based on â¼4.4 million single nucleotide polymorphisms obtained from 605 diverse accessions, we performed a comprehensive genome-wide association study for 27 agronomic traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many previously reported and additional genes related to vegetative and reproductive development, were identified, and these loci explained an average of â¼8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection during tomato domestication and improvement. Furthermore, a candidate gene, Sl-ACTIVATED MALATE TRANSPORTER15, that encodes an aluminum-activated malate transporter was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation, thereby affecting photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.
Assuntos
Domesticação , Genoma de Planta , Estudo de Associação Genômica Ampla , Fenótipo , Polimorfismo de Nucleotídeo Único , Solanum lycopersicum/fisiologia , Características de História de Vida , Solanum lycopersicum/genética , Locos de Características QuantitativasRESUMO
Trichomes are specialized glandular or non-glandular structures that provide physical or chemical protection against insect and pathogen attack. Trichomes in Arabidopsis have been extensively studied as typical non-glandular structures. By contrast, the molecular mechanism underlying glandular trichome formation and elongation remains largely unknown. We previously demonstrated that Hair is essential for the formation of type I and type VI trichomes. Here, we found that overexpression of Hair increased the density and length of tomato trichomes. Biochemical assays revealed that Hair physically interacts with its close homolog SlZFP8-like (SlZFP8L), and SlZFP8L also directly interacts with Woolly. SlZFP8L-overexpressing plants showed increased trichome density and length. We further found that the expression of SlZFP6, which encodes a C2H2 zinc finger protein, is positively regulated by Hair. Using chromatin immunoprecipitation, yeast one-hybrid, and dual-luciferase assays we identified that SlZFP6 is a direct target of Hair. Similar to Hair and SlZFP8L, the overexpression of SlZFP6 also increased the density and length of tomato trichomes. Taken together, our results suggest that Hair interacts with SlZFP8-like to regulate the initiation and elongation of trichomes by modulating SlZFP6 expression in tomato.
Assuntos
Dedos de Zinco CYS2-HIS2 , Solanum lycopersicum , Solanum lycopersicum/genética , TricomasRESUMO
PURPOSE: Neuroendocrine cervical carcinoma (NECC) is an uncommon malignancy of the female reproductive system. This study aimed to evaluate cancer-specific mortality and to construct prognostic nomograms for predicting the survival of patients with NECC. METHODS: we assembled the patients with NECC diagnosed between 2004 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, we identified other patients with NECC from the Wenling Maternal and Child Health Care Hospital between 2002 to 2017. Fine and Gray's test and Kaplan-Meier methods were used to evaluate cancer-specific mortality and overall survival (OS) rates, respectively. Nomograms were constructed for predicting cancer-specific survival (CSS) and OS for patients with NECC. The developed nomograms were validated both internally and externally. RESULTS: a total of 894 patients with NECC were extracted from the SEER database, then classified into the training cohort (n = 628) and the internal validation cohort (n = 266). Besides, 106 patients from the Wenling Maternal and Child Health Care Hospital served as an external validation cohort. Nomograms for predicting CSS and OS were constructed on clinical predictors. The validation of nomograms was calculated by calibration curves and concordance indexes (C-indexes). Furthermore, the developed nomograms presented higher areas under the receiver operating characteristic (ROC) curves when compared to the FIGO staging system. CONCLUSIONS: we established the first competing risk nomograms to predict the survival of patients with NECC. Such a model with high predictive accuracy could be a practical tool for clinicians.
Assuntos
Carcinoma Neuroendócrino/mortalidade , Nomogramas , Medição de Risco/normas , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Programa de SEER , Taxa de SobrevidaRESUMO
The evidence for the safety and efficacy of adding rituximab to intensive chemotherapy in pediatric patients with aggressive mature B cell non-Hodgkin lymphoma/leukemia (B-NHL/B-AL) is not yet robust. In this prospective multi-institutional trial, 419 evaluable patients ≤ 16 years of age with newly diagnosed B-NHL/B-AL were enrolled. Patients were stratified into 4 risk groups according to stage, resection status, and serum lactate dehydrogenase. Patients in group R1 received 3 therapy courses in the treatment order A-B-A. Patients in group R2 received 5 courses A-B-A-B-A. Patients in group R3 received 6 courses A-BB-AA-BB-AA-BB. For patients in group R4, rituximab was added to the chemotherapy backbone for patients in R3 (A-RBB-RAA-RBB-RAA-BB). At a median follow-up of 54 months, the 4-year event-free survival (EFS) for the entire group was 88.3 ± 1.6% (76.0 ± 4.3% in the historical study). The EFS rates according to the intention-to-treat principle were 100%, 98.6 ± 1.2%, 94.2 ± 1.8%, and 73.5 ± 3.7% for patients in treatment groups R1, R2, R3, and R4, respectively (P < 0.001). There were 9 (2.1%) toxic deaths due to infection during treatment. Regarding the toxicities of rituximab, grade 3/4 thrombocytopenia, mucositis, and infection occurred in 44.0%, 33.3%, and 64.0% after courses R-BB and grade 3/4 neutropenia, thrombocytopenia, and infection occurred in 96.3%, 77.8%, and 54.1% after courses RAA. The addition of rituximab to intensive chemotherapy is feasible even in a developing country. EFS was significantly improved when compared with the historical data. clinicals.gov identifier: NCT02405676.