Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
Pest Manag Sci ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578650

RESUMO

BACKGROUND: Bacillus, as a plant-growth-promoting rhizobacteria, can enhance the resistance of plants to phytopathogens. In our study, Bacillus strains showing excellent biocontrol were screened and used to control ginkgo leaf blight (Alternaria tenuissima). RESULTS: Four biocontrol Bacillus strains-Bsa537, Bam337, Bso544, and Bsu503-were selected from 286 isolates based on their capacity to inhibit pathogens and promote plant growth. The four Bacillus strains significantly improved the resistance of ginkgo to leaf blight. This was especially the case when the four strains were used as a mixture, which contributed to a decrease in lesion area of >40%. Hence, a mixture of Bacillus strains was used to control ginkgo leaf blight in the field. Treatment efficiency varied from 30% to 100% (average 81.5%) and was higher than that of the control (-2% to -18%, average - 8.5%); the antioxidant capacity of the treated ginkgo was also stronger. In addition, ginkgo biomass increased as a result of treatment with the Bacillus mixture, including leaf weight, area, thickness, number of lateral roots and root weight. Furthermore, the Bacillus mixture improved the ginkgo rhizosphere soil by boosting the number of beneficial microorganisms, lowering the number of pathogens and hastening soil catabolism. CONCLUSION: The Bacillus mixture improved the health status of ginkgo by protecting it from pathogen attack, promoting its growth and improving the microorganism community in the rhizosphere. This work closes a technological gap in the biological control of ginkgo leaf blight, investigates application methods for compound Bacillus biofertilizers and establishes a framework for the popularity and commercialization of these products. © 2024 Society of Chemical Industry.

6.
BMC Genomics ; 24(1): 786, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110864

RESUMO

BACKGROUND: Cymbidium sinense is an orchid that is typically used as a potted plant, given its high-grade ornamental characteristics, and is most frequently distributed in China and SE Asia. The inability to strictly regulate flowering in this economically important potted and cut-flower orchid is a bottleneck that limits its industrial development. Studies on C. sinense flowering time genes would help to elucidate the mechanism regulating flowering. There are very few studies on the genetic regulation of flowering pathways in C. sinense. Photoperiod significantly affects the flowering of C. sinense, but it was unknown how the CONSTANS gene family is involved in regulating flowering. RESULTS: In this study, eight CONSTANS-like genes were identified and cloned. They were divided into three groups based on a phylogenetic analysis. Five representative CsCOL genes (CsCOL3/4/6/8/9) were selected from the three groups to perform expression characterization and functional study. CsCOL3/4/6/8/9 are nucleus-localized proteins, and all five CsCOL genes were expressed in all organs, mainly in leaves followed by sepals. The expression levels of CsCOL3/4 (group I) were higher in all organs than other CsCOL genes. Developmental stage specific expression revealed that the expression of CsCOL3/4/9 peaked at the initial flowering stage. In contrast, the transcript level of CsCOL6/8 was highest at the pedicel development stage. Photoperiodic experiments demonstrated that the transcripts of the five CsCOL genes exhibited distinct diurnal rhythms. Under LD conditions, the overexpression of CsCOL3/4 promoted early flowering, and CsCOL6 had little effect on flowering time, whereas CsCOL8 delayed flowering of Arabidopsis thaliana. However, under SD conditions, overexpression of CsCOL4/6/8 promoted early flowering and the rosette leaves growth, and CsCOL3 induced flower bud formation in transgenic Arabidopsis. CONCLUSION: The phylogenetic analysis, temporal and spatial expression patterns, photoperiodic rhythms and functional study indicate that CsCOL family members in C. sinense were involved in growth, development and flowering regulation through different photoperiodic pathway. The results will be useful for future research on mechanisms pertaining to photoperiod-dependent flowering, and will also facilitate genetic engineering-based research that uses Cymbidium flowering time genes.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Filogenia , Fotoperíodo , Ritmo Circadiano , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Flores , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/metabolismo
7.
Eur J Med Chem ; 259: 115703, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37556948

RESUMO

Aberrant FGFR4 signaling has been implicated in the development of several cancers, making FGFR4 a promising target for cancer therapy. Several FGFR4-selective inhibitors have been developed, yet none of them have been approved. Herein, we report a novel series of 1,6-naphthyridine-2-one derivatives as potent and selective inhibitors targeting FGFR4 kinase. Preliminary structure-activity relationship analysis was conducted. The screening cascades revealed that 19g was the preferred compound among the prepared series. 19g demonstrated excellent kinase selectivity and substantial cytotoxic effect against all tested colorectal cancer cell lines. 19g induced significant tumor inhibition in a HCT116 xenograft mouse model without any apparent toxicity. Notably, 19g exhibited excellent potency in disrupting the phosphorylation of FGFR4 and downstream signaling proteins mediated by FGF18 and FGF19. Compound 19g might be a potential antitumor drug candidate for the treatment of colorectal cancer.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Transdução de Sinais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular , Neoplasias Colorretais/tratamento farmacológico , Naftiridinas/farmacologia , Naftiridinas/uso terapêutico , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Hepáticas/tratamento farmacológico
8.
Plant Physiol Biochem ; 200: 107768, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37247556

RESUMO

Papain-like cysteine proteases (PLCP) play diverse roles in plant biology. In our previous studies, a VaCP17 gene from the cold-tolerant Vitis amurensis accession 'Shuangyou' was isolated and its role in cold tolerance was preliminarily verified in Arabidopsis. Here, we confirmed the function of VaCP17 in cold tolerance by stably overexpressing VaCP17 in the cold-sensitive Vitis vinifera cultivar 'Thompson Seedless' and transiently silencing VaCP17 in 'Shuangyou' leaves. The results showed that overexpression of VaCP17 improved the cold tolerance in 'Thompson Seedless' as manifested by reduced electrolyte leakage and malondialdehyde accumulation, chlorophyll homeostasis, increased antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) activitiy, and rapid up-regulation of stress-related genes (VvKIN2, VvRD29B, and VvNCED1) compared with wild-type line. Conversely, RNA interfere-mediated knockdown of VaCP17 in 'Shuangyou' leaves resulted in opposite physiological and biochemical responses and exacerbated leaves wilting compared with control. Subsequently, by yeast one-hybrid, dual-luciferase assays, and transient overexpression of VaNAC72 in 'Shuangyou' leaves, a VaCP17-interacting protein VaNAC72 was confirmed to promote the expression of VaCP17 under cold stress, which depends on abscisic acid, methyl jasmonate, and salicylic acid signaling. By yeast two-hybrids, bimolecular fluorescence complementation and luciferase complementation assays, it was found that VaNAC72 could form homodimers or heterodimers with VaCBF2. Furthermore, co-expression analysis confirmed that VaNAC72 works synergistically with VaCBF2 or VaCP17 to up-regulate the expression of VaCP17. In conclusion, the study revealed that the VaNAC72-VaCP17 module positively regulated cold tolerance in grapevine, and this knowledge is useful for further revealing the cold-tolerance mechanism of V. amurensis and grape molecular breeding.


Assuntos
Vitis , Arabidopsis/genética , Temperatura Baixa , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Vitis/genética , Vitis/metabolismo , China
9.
Int J Mol Sci ; 24(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37108700

RESUMO

The WRKY transcription factor family plays important regulatory roles in multiple biological processes in higher plants. They have been identified and functionally characterized in a number of plant species, but very little is known in Neolamarckia cadamba, a 'miracle tree' for its fast growth and potential medicinal resource in Southeast Asia. In this study, a total of 85 WRKY genes were identified in the genome of N. cadamba. They were divided into three groups according to their phylogenetic features, with the support of the characteristics of gene structures and conserved motifs of protein. The NcWRKY genes were unevenly distributed on 22 chromosomes, and there were two pairs of segmentally duplicated events. In addition, a number of putative cis-elements were identified in the promoter regions, of which hormone- and stress-related elements were shared in many NcWRKYs. The transcript levels of NcWRKY were analyzed using the RNA-seq data, revealing distinct expression patterns in various tissues and at different stages of vascular development. Furthermore, 16 and 12 NcWRKY genes were confirmed to respond to various hormone treatments and two different abiotic stress treatments, respectively. Moreover, the content of cadambine, the active metabolite used for the various pharmacological activities found in N. cadamba, significantly increased after Methyl jasmonate treatment. In addition, expression of NcWRKY64/74 was obviously upregulated, suggesting that they may have a potential function of regulating the biosynthesis of cadambine in response to MeJA. Taken together, this study provides clues into the regulatory roles of the WRKY gene family in N. cadamba.


Assuntos
Genoma de Planta , Família Multigênica , Filogenia , Genes de Plantas , Hormônios , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
10.
BMJ Open ; 13(3): e066310, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36914201

RESUMO

INTRODUCTION: Disinfecting gloves during patient care has potential benefits and risks. In recent years, disinfection of disposable medical gloves for prolonged use has occurred in clinical practice. However, there is limited high-level evidence to know if this practice can prevent nosocomial infections, reduce microbial levels on the glove surface. This concept was researched using a scoping review to explore the feasibility and effectiveness of disinfecting disposable gloves for prolonged use. METHODS AND ANALYSIS: The review will be conducted in accordance with the Arksey and O'Malley scoping review methodology framework. From the date of database construction to 10 February 2023, the following 16 electronic databases in English and Chinese will be searched: PubMed, Embase, CINAHL, Web of Science, Cochrane Library, ProQuest, China National Knowledge Infrastructure, Wanfang, SinoMed Database, Google Scholar, Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control, WHO, China CDC, International Nosocomial Infection Control Consortium and European Medicines Agency Science Medicines Health. The screening and data extraction of the study will be carried out by two reviewers (KL and SH). Differences between the two reviewers will be handled through negotiation. If there are still differences, they will be discussed with a third reviewer. Any study, for example, intervention study or observational study, that provide insights about the disinfection of disposable medical gloves for prolonged use will be included. Data charts will be used to extract relevant data from the included studies. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, to define the scope of evaluation. A narrative summary will be completed to synthesise key research findings and background information on the disinfection of gloved hands. ETHICS AND DISSEMINATION: Ethical approval will not be required because only publicly available data will be analysed. The findings from the scoping review will be published in a peer-reviewed journal and presented at scientific meetings. By highlighting the feasibility and effectiveness of the disinfection of gloved hands in the literature, this review will provide direction for future research and clinical guidelines. TRIAL REGISTRATION NUMBER: This scoping review protocol has been registered in the Open Science Framework (registration number: 10.17605/OSF.IO/M4U8N).


Assuntos
Desinfecção , Projetos de Pesquisa , Humanos , Estudos de Viabilidade , China , Estudos Observacionais como Assunto , Revisões Sistemáticas como Assunto , Literatura de Revisão como Assunto
11.
Bioorg Chem ; 132: 106358, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36642021

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high recurrence and mortality rate. In this study, a series of ß-cyclocitral-derived mono-carbonyl curcumin analogs were synthesized and their anticancer properties were evaluated. Among the series, A19 exhibited the strongest cytotoxic activity by inhibiting cell viability and colony formation, inducing cell cycle G2/M phase arrest and cell apoptosis of HCC HepG2 and Huh-7 cells, while having almost no cytotoxicity on normal liver MIHA cells. Mechanistically, our results demonstrated that A19 triggered intense DNA damage via suppression of the ERK/JNK/p38 MAPK signaling pathway. Additionally, a combination of A19 with sorafenib significantly induced synergistic cytotoxicity in HCC cells. Overall, our results indicate the potential of A19 as a novel chemotherapeutic drug administered either separately or in combined therapy for HCC treatment.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Células Hep G2 , Transdução de Sinais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proliferação de Células , Linhagem Celular Tumoral
12.
Plant Cell Rep ; 42(1): 181-196, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36318328

RESUMO

KEY MESSAGE: VyUSPA3 from the Chinese wild grape Vitis yeshanensis interacts with ERF105, PUB24 and NF-YB3, and overexpression of the VyUSPA3 gene in V. vinifera cv. 'Thompson Seedless' confers drought tolerance. Drought is a major abiotic stress factor that seriously affects the growth and yield of grapevine. Although many drought-related genes have been identified in Arabidopsis and other plants, the functions of only a few of their counterparts have been revealed in grape. Here, a universal stress protein (USP) A from the Chinese wild grape Vitis yeshanensis, VyUSPA3, was identified and its function was subsequently characterized by overexpressing or silencing the VyUSPA3 gene in V. vinifera cv. 'Thompson Seedless' via Agrobacterium-mediated genetic transformation. After 21 d of the drought treatment, most leaves of the untransformed (UT) 'Thompson Seedless' lines wilted, yet UT lines were less damaged compared to the RNAi-VyUSPA3 lines, nonetheless, the OE-VyUSPA3 lines were mostly unaffected. Meanwhile, OE-VyUSPA3 lines showed smaller stomatal aperture, more developed roots, higher leaf relative water content, proline content, and antioxidant enzyme activities, as well as lower malondialdehyde, H2O2 and O2•- accumulation than UT lines, but this response pattern was reversed in the RNAi-VyUSPA3 lines. Besides, the transcript levels of four drought-related genes (RD22, RD29B, DREB2A, and NCED1) in OE-VyUSPA3 lines were greater than those in the RNAi-VyUSPA3 and UT lines. In addition, a yeast two-hybrid assay and a bimolecular fluorescence complementation assay confirmed that VyUSPA3 interacted with ERF105, PUB24, and NF-YB3, respectively. This study revealed that VyUSPA3 improved drought tolerance in transgenic grapevines possibly through interaction with the hormone signaling, ubiquitination system, ethylene-responsive element binding factor and nuclear factors.


Assuntos
Resistência à Seca , Proteínas de Plantas , Vitis , Resistência à Seca/genética , Secas , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico/genética , Vitis/metabolismo
13.
Aust Crit Care ; 36(4): 464-469, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36104256

RESUMO

BACKGROUND: Patients transferred from the respiratory intensive care unit (ICU) can experience post-intensive care syndrome (PICS), which comprises cognitive, psychological, and physical disorders that seriously affect the quality of life. Therefore, it was necessary to explore the incidence of and the risk factors for PICS among respiratory ICU patients. OBJECTIVES: This study evaluated PICS among respiratory ICU patients and explored the risk factors for PICS. METHODS: This cross-sectional, prospective study was performed at one hospital in China. Using convenience sampling, 125 respiratory ICU patients from August 2018 to June 2019 were recruited for the study. The Mini-Mental State Examination, Confusion Assessment Method for the Intensive Care Unit, Hospital Anxiety and Depression Scale, Medical Research Council Scale, activities of daily living scale, Pittsburgh Sleep Quality Index, and the 14-item fatigue scale were used to comprehensively assess the patients' cognitive status, psychological status, and physiological status when entering the ICU and 2 weeks after leaving the ICU. Factors affecting PICS were measured using researcher-created questionnaires of patients' general information and disease-related information. RESULTS: Fifteen patients were lost to follow-up. Fifty-nine patients had PICS (incidence rate, 53.6%). Logistic regression showed that risk factors for PICS were age, invasive mechanical ventilation, noninvasive ventilator-assisted ventilation, and coronary heart disease (P < 0.05). CONCLUSION: The PICS incidence was high. Older age, longer invasive mechanical ventilation times, longer noninvasive ventilator times, and coronary heart disease were risk factors for PICS. ICU medical workers in China should pay more attention on PICS, know the risk factors, and implement preventive measures.


Assuntos
Atividades Cotidianas , Qualidade de Vida , Humanos , Estudos Prospectivos , Incidência , Estudos Transversais , População do Leste Asiático , Unidades de Terapia Intensiva , Fatores de Risco
14.
PLoS One ; 17(11): e0277139, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36395269

RESUMO

The generation of massive data puts forward higher requirements for storage technology. DNA storage is a new storage technology which uses biological macromolecule DNA as information carrier. Compared with traditional silicon-based storage, DNA storage has the advantages of large capacity, high density, low energy consumption and high durability. DNA coding is to store data information with as few base sequences as possible without errors. Coding is a key technology in DNA storage, and its results directly affect the performance of storage and the integrity of data reading and writing. In this paper, a Levy Equilibrium Optimizer (LEO) algorithm is proposed to construct a DNA storage code set that satisfies combinatorial constraints. The performance of the proposed algorithm is tested on 13 benchmark functions, and 4 new global optima are obtained. Under the same constraints, the DNA storage code set is constructed. Compared with previous work, the lower bound of DNA storage code set is improved by 4-13%.


Assuntos
Algoritmos , DNA , DNA/genética , Análise de Sequência de DNA/métodos , Sequência de Bases
15.
Plant Physiol Biochem ; 192: 218-229, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36272189

RESUMO

Cultivated grapes, one of the most important fruit crops in the world, are sensitive to low temperature. Since Chinese wild grape Vitis amurensis is highly tolerant to cold, it is imperative to study and utilize its cold-tolerance genes for molecular breeding. Here, a VaMYC2 gene from V. amurensis was cloned, and its function was investigated by expressing VaMYC2 in the cold-sensitive V. vinifera cultivar 'Thompson Seedless'. The expression of VaMYC2 could be induced by cold stress, methyl jasmonate and ethylene treatment, but was inhibited by abscisic acid in leaves of V. amurensis. When transgenic grape lines expressing VaMYC2 were subjected to cold stress (-1 °C) for 41 h, the transgenic lines showed less freezing injury and lower electrolyte leakage and malondialdehyde content, but higher contents of soluble sugars, soluble proteins and proline, and antioxidant enzyme activities compared with wild-type. Moreover, the expression of some cold-tolerance related genes increased in transgenic lines. Besides, the interactions of VaMYC2 with VaJAZ1 and VaJAZ7B were confirmed by yeast two-hybrid and bimolecular fluorescence complementation assays. Yeast one-hybrid and dual luciferase assays showed that VaMYC2 can bind to the promoters of VaCBF1 and VaP5CS and activate their expressions. In conclusion, expression of VaMYC2 in V. vinifera enhances cold tolerance of transgenic grapes which is attributed to enhanced accumulation of osmotic regulatory substances, cell membrane stability, antioxidant enzyme activity, and expression of cold tolerance-related genes. Also, VaMYC2 interacts with VaJAZ1 and VaJAZ7, and activates the expression of VaCBF1 and VaP5CS to mediate cold tolerance in grapes.

16.
Plant Physiol Biochem ; 190: 24-34, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36088784

RESUMO

Dendrobium officinale, which is a medicine food homology plant, contains many metabolites, especially polysaccharides and flavonoids. Unlike flowers and stems, which are the most frequently harvested organs for a variety of uses, leaves tend to be discarded. This study assessed main metabolites in leaves to identify the most appropriate timing of collection during harvest, which was divided into three stages (S1-S3: 8, 10, and 11 months after sprouting, respectively). Metabolomic and transcriptomic analyses of S1-S3 were performed. Water-soluble polysaccharides (WSPs), flavonoids and free amino acids (FAAs) were detected in leaves. WSPs decreased from S1 to S3 but flavonoids and some FAAs (e.g., phophoserine) increased from S1 to S2, then decreased from S2 to S3. In all three stages, mannose was the dominant monosaccharide among WSPs, followed by glucose. In S2, 35 flavonoids were identified, the most abundant being rutin, schaftoside and vitexin, while 34 FAAs were identified in all three stages, the most abundant being tyrosine, phosphoserine and alanine. A total of 2584, 3414 and 2032 differentially expressed genes (DEGs) were discovered in S1 vs S2, S1 vs S3 and S1 vs S3, respectively. Correlation analysis revealed that five DEGs (DoSUS, DoXYLA, DoFRK, DoGMP, and DoCSLA), two DEGs (DoDFR, and DoANS) and a single DEG (DoPGAM) were involved in the metabolism of WSPs, flavonoids and phosphoserine, respectively. The findings of this study lay a foundation for the commercial exploitation of metabolites in the harvested leaves of D. officinale, and the use of detected DEGs in applied genetic studies.


Assuntos
Dendrobium , Alanina/metabolismo , Dendrobium/genética , Dendrobium/metabolismo , Flavonoides/metabolismo , Glucose/metabolismo , Manose/metabolismo , Monossacarídeos/metabolismo , Fosfosserina/metabolismo , Polissacarídeos/metabolismo , Rutina/metabolismo , Transcriptoma , Tirosina/metabolismo , Água/metabolismo
17.
Chem Biol Interact ; 367: 110200, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36170914

RESUMO

Osteosarcoma (OS) is a group of malignant tumors with high rates of malignancy and metastasis. OS most commonly affects adolescents and young individuals. However, owing to the lack of effective targeted treatments, the 5-year survival rate for OS is still around 20%. Thus, it is essential to develop effective drugs with low toxicity for OS treatment. In the present study, we investigated the antitumor effect and underlying mechanism of cyy260 in OS via suppressing PDGFR-ß and its downstream pathway. We demonstrated that cyy260 inhibits OS cell proliferation and promotes apoptosis via inducing DNA damage and causing cell cycle arrest. More importantly, cyy260 also significantly inhibits tumor migration. Further analysis of molecular mechanisms confirmed that PDGFR-ß and its downstream AKT, STAT3, and ERK were involved in the cyy260-mediated antitumor effect. Analysis of subcutaneously transplanted tumors in mice showed that cyy260 suppressed tumor cell growth and exhibited low toxicity in vivo. Collectively, these findings proved that cyy260 could serve as a promising PDGFR-ß inhibitor for the treatment of OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Animais , Apoptose , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Camundongos , Osteossarcoma/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
18.
Front Pediatr ; 10: 834241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692977

RESUMO

Objective: Primary hypomagnesemia with secondary hypocalcemia (HSH) is caused by loss-of-function mutations in the TRPM6 gene encoding the epithelial magnesium channel. It is characterized by hypomagnesemia and secondary hypocalcemia associated with neurological symptoms. Here, we aimed to investigate the genetic defects of the TRPM6 gene found in a girl from China. Methods: The genomic DNA of the proband and the parents was extracted for whole-exome sequencing. Sanger sequencing was further performed to validate the candidate variants. Subsequently, the TRPM6 gene deletion was verified by quantitative PCR (qPCR) experiment. The effect of the variant on mRNA splicing was analyzed through a minigene splice assay and reverse transcription PCR (RT-PCR) in vitro. Results: The proband presented with the symptoms of generalized seizures, tetany, and muscle spasms, which were refractory to anticonvulsant treatment. Phenotypic data indicated that the patient had hypomagnesemia, poor parathyroid hormone response, and resultant hypocalcemia. The trio whole-exome sequencing identified that the proband carried compound heterozygous variants in the TRPM6 gene, a paternally derived exon 6 deletion, and a maternally derived splicing variant (c.1638+7T>C) in exon 14. The minigene splice assay confirmed that the c.1638+7T>C variant resulted in exon 14 skipping, which caused the alteration of TRPM6 mRNA splicing. Conclusion: Our results support that the compound heterozygous variants in TRPM6 are responsible for HSH in this patient. A novel pathogenic splicing variant (c.1638+7T>C) in the intron 14 disturbs the normal TRPM6 mRNA splicing, suggesting that the non-classical splice variant plays a critical role in HSH. This variant is essential for future effective genetic diagnosis.

19.
Plant Cell Rep ; 41(8): 1673-1691, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35666271

RESUMO

KEY MESSAGE: Heterologous expression of VaMYB44 gene in Arabidopsis and V. vinifera cv. 'Thompson Seedless' increases cold sensitivity, which is mediated by the interaction of VaMYC2 and VaTIFY5A with VaMYB44 MYB transcription factors play critical roles in plant stress response. However, the function of MYB44 under low temperature stress is largely unknown in grapes. Here, we isolated a VaMYB44 gene from Chinese wild Vitis amurensis acc. 'Shuangyou' (cold-resistant). The VaMYB44 is expressed in various organs and has lower expression levels in stems and young leaves. Exposure of the cold-sensitive V. vinifera cv. 'Thompson Seedless' and cold-resistant 'Shuangyou' grapevines to cold stress (-1 °C) resulted in differential expression of MYB44 in leaves with the former reaching 14 folds of the latter after 3 h of cold stress. Moreover, the expression of VaMYB44 was induced by exogenous ethylene, abscisic acid, and methyl jasmonate in the leaves of 'Shuangyou'. Notably, the subcellular localization assay identified VaMYB44 in the nucleus. Interestingly, heterologous expression of VaMYB44 in Arabidopsis and 'Thompson Seedless' grape increased freezing-induced damage compared to their wild-type counterparts. Accordingly, the transgenic lines had higher malondialdehyde content and electrolyte permeability, and lower activities of superoxide dismutase, peroxidase, and catalase. Moreover, the expression levels of some cold resistance-related genes decreased in transgenic lines. Protein interaction assays identified VaMYC2 and VaTIFY5A as VaMYB44 interacting proteins, and VaMYC2 could bind to the VaMYB44 promoter and promote its transcription. In conclusion, the study reveals VaMYB44 as the negative regulator of cold tolerance in transgenic Arabidopsis and transgenic grapes, and VaMYC2 and VaTIFY5A are involved in the cold sensitivity of plants by interacting with VaMYB44.


Assuntos
Arabidopsis , Vitis , Arabidopsis/metabolismo , China , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Vitis/metabolismo
20.
Math Biosci Eng ; 19(6): 5576-5590, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35603369

RESUMO

The precise segmentation of tumor regions plays a pivotal role in the diagnosis and treatment of brain tumors. However, due to the variable location, size, and shape of brain tumors, the automatic segmentation of brain tumors is a relatively challenging application. Recently, U-Net related methods, which largely improve the segmentation accuracy of brain tumors, have become the mainstream of this task. Following merits of the 3D U-Net architecture, this work constructs a novel 3D U-Net model called SGEResU-Net to segment brain tumors. SGEResU-Net simultaneously embeds residual blocks and spatial group-wise enhance (SGE) attention blocks into a single 3D U-Net architecture, in which SGE attention blocks are employed to enhance the feature learning of semantic regions and reduce possible noise and interference with almost no extra parameters. Besides, the self-ensemble module is also utilized to improve the segmentation accuracy of brain tumors. Evaluation experiments on the Brain Tumor Segmentation (BraTS) Challenge 2020 and 2021 benchmarks demonstrate the effectiveness of the proposed SGEResU-Net for this medical application. Moreover, it achieves DSC values of 83.31, 91.64 and 86.85%, as well as Hausdorff distances (95%) of 19.278, 5.945 and 7.567 for the enhancing tumor, whole tumor, and tumor core on BraTS 2021 dataset, respectively.


Assuntos
Neoplasias Encefálicas , Processamento de Imagem Assistida por Computador , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Aprendizagem , Redes Neurais de Computação , Semântica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA