Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 120
Filtrar
1.
ACS Appl Mater Interfaces ; 16(19): 24601-24611, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38710043

RESUMO

The Zn dendrite growth and side reactions are two major issues for the practical use of Zn metal anodes (ZMAs). Herein, an N-doped carbon-based hybrid fiber with the 3D porous skeleton and the zincophilic Cu nanoparticles (denoted as Cu@HLCF) is developed for stable ZMAs. The zincophilic Cu particles in the skeleton work as the active sites to facilitate uniform Zn nucleation. Meanwhile, the abundant pores in the framework of the hybrid fibers provide a large space to relieve the structural stress and suppress the dendrite growth. Moreover, the good mechanical characteristics of the hybrid fiber ensure its high potential applications for flexible electronics. Theoretical analysis results disclose the strong interaction between Zn and Cu sites, and experimental results demonstrate the low voltage hysteresis, high reversibility, and dendrite-free behavior of the Cu@HLCF host for Zn plating/stripping. Moreover, the solid-state Zn-ion battery (ZIB) assembled with a Cu@HLCF/Zn anode shows the prominent flexibility, impressively reliability, and outstanding cycling capability. Therefore, this work not only provides a novel design for the efficient and stable Zn metal anode but also promotes the development of flexible power sources for flexible electronics.

2.
Plant Physiol Biochem ; 211: 108670, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38703501

RESUMO

Plants would encounter various biotic and abiotic stresses during the growth and development. WRKY transcription factors (TFs) as plant-specific TFs, play an important role in responding to various adverse circumstances. Despite some advances were achieved in functional studies of WRKY TFs in tea plants, systematic analysis of the involvement of CsWRKY TFs when facing cold, salt, drought stresses and pathogen and insect attack was lacked. In present study, a total of 78 CsWRKY TFs were identified following the genomic and transcript databases. The expression patterns of CsWRKYs in various organs of tea plants and the expression profiles in response to biotic and abiotic stresses were investigated by examining representative RNA-seq data. Moreover, the effects of hormone treatments (SA and MeJA) on the transcription levels of WRKY TFs were also investigated. The phylogenetic tree of CsWRKY TFs from different species indicated the functional diversity of WRKY TFs was not closely related to their protein classification. Concurrently, CsWRKY70-2 TF was identified as a positive regulator in response to drought stress. This study provided solid and valuable information, helping us better understand the functional diversity of CsWRKY TFs, and laid the foundation for further research on the function of key WRKY genes in tea plants.

3.
Health Res Policy Syst ; 22(1): 33, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443935

RESUMO

OBJECTIVE: This work compares the marketing authorization, labels and dosage forms of medicines in the WHO Model List of Essential Medicines for Children (EMLc) in China, the Russian Federation and Brazil to urge policymakers to pay more attention to paediatric medication. METHODS: Medicines were selected from the 8th EMLc. By searching relevant databases, which include different types of medical information in China, the Russian Federation and Brazil, the marketing authorization, labels and dosage forms of paediatric medicines in the three countries were evaluated. RESULTS: A total of 485 drug products containing 312 active pharmaceutical ingredients listed in the WHO EMLc were evaluated. Among them, 344 products were approved for use in China, 286 in the Russian Federation and 264 in Brazil. Out of the 344 approved medicines, 317 (92.15%) were authorized for paediatric use in China, 224 (78.32%) in the Russian Federation and 218 (82.58%) in Brazil. In terms of guidance information labelling on drug labels, 75.08%, 83.04% and 88.07% of paediatric drugs approved in China, the Russian Federation and Brazil, respectively, clearly indicated the usage and dosage for paediatric use. Additionally, injections and tablets were the most prevalent dosage forms in these three countries. CONCLUSION: There is still scope for enhancing the marketing authorization and development of dosage forms for paediatric medicines in the three countries. Furthermore, additional measures are being implemented to enhance the information provided on drug labels for children, particularly in China.


Assuntos
Marketing , Humanos , Criança , Brasil , China , Federação Russa , Organização Mundial da Saúde
4.
Heliyon ; 10(2): e24399, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293370

RESUMO

Objectives: Clinicians often face the challenge of differentially diagnosing febrile patients who are suspected of infectious diseases, since the clinical manifestations of infection and cancer may overlap. A single test that can detect both pathogens and tumor could provide timely and accurate diagnostic clues to aid the treatment and management of these patients. Methods: We enrolled eight patients to evaluate the utility of metagenomic Next-Generation Sequencing for simultaneously detecting pathogens and neoplasms using body fluids and tissue samples. Patients were selected by the following criteria: 1) Tumor was not considered upon hospitalization, but mNGS testing indicated neoplasm; 2) Tumor was not excluded, but microbial infection was primarily suspected according to initial clinical assessment. Results: We detected potential pathogens in five patients, three of whom had progressed into critical infections. Moreover, abnormal chromosomal copy numbers were identified in all patients that indicated presence of neoplasms, which were pathologically confirmed. Conclusions: Although copy number variations do not render a definitive cancer diagnosis, it can prompt clinicians to conduct more focused diagnostic testing for cancer, potentially saving time and cost. As a result, integrating copy number analysis with pathogen detection in mNGS may help establish rapid and accurate diagnosis for febrile patients.

5.
BMJ Open ; 14(1): e080721, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38199633

RESUMO

INTRODUCTION: Wearing masks has proven beneficial in preventing respiratory pathogen infections in individuals with chronic obstructive pulmonary disease (COPD). However, the impact of different mask types on physiological indicators and daily physical activity in COPD patients remains uncertain. This study aims to assess the immediate effects of various mask types on cardiopulmonary function indicators, subjective perceptions and the 6-minute walking distance (6MWD) in individuals with COPD. METHODS AND ANALYSIS: This randomised controlled trial will enrol 129 stable COPD patients. Participants will be randomly divided into three groups: control, N95 mask and surgical mask groups. Each group will undergo both a 6-minute seated test and a 6-minute walk test (6MWT), without or with their respective masks. A 10-minute interval will be provided between the two phases. The primary indicators of the study include the 6MWD and blood oxygen saturation. Secondary outcomes encompass blood pressure, pulse rate, Borg score, Rate of Perceived Exertion (RPE) score and subjective perception score. Oxygen saturation, pulse rate and blood pressure will be recorded four times during the trial, while Borg and RPE scores will be compared before and after the 6MWT. Additionally, subjective perception scores will be collected after each mask-wearing stage. ETHICS AND DISSEMINATION: This study has received approval from the Ethics Committee of the Affiliated Hospital of Gansu University of Chinese Medicine (approval number: 202335). We plan to disseminate research results through publication in a peer-reviewed journal or presentation at a conference. TRIAL REGISTRATION NUMBER: ChiCTR2300074554.


Assuntos
Comissão de Ética , Doença Pulmonar Obstrutiva Crônica , Humanos , Pressão Sanguínea , Exercício Físico , Frequência Cardíaca , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Nat Commun ; 14(1): 7409, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973985

RESUMO

Ultra-high extinction ratio (ER) optical modulation is crucial for achieving high-performance fiber-optic distributed acoustic sensing (DAS) for various applications. Bulky acousto-optical modulators (AOM) as one of the key devices in DAS have been used for many years, but their relatively large volume and high power consumption are becoming the bottlenecks to hinder the development of ultra-compact and energy-efficient DAS systems that are highly demanded in practice. Here, an on-chip silicon electro-optical modulator (EOM) based on multiple coupled microrings is demonstrated with ultra-high ER of up to 68 dB while the device size and power consumption are only 260 × 185 µm2 and 3.6 mW, respectively, which are at least two orders of magnitude lower than those of a typical AOM. Such an on-chip EOM is successfully applied to DAS with an ultra-high sensitivity of -71.2 dB rad2/Hz (4 pε/√Hz) and a low spatial crosstalk noise of -68.1 dB rad2/Hz, which are very similar to those using an AOM. This work may pave the way for realization of next-generation ultra-compact DAS systems by integration of on-chip opto-electronic devices and modules with the capability of mass-production.

7.
Heart Surg Forum ; 26(5): E498-E511, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37920088

RESUMO

BACKGROUND: This bioinformatics report attempts to explore the cross-talk genes, transcription factors (TFs), and pathways related to myocardial ischemia-reperfusion injury (MIRI) as well as the gut microbiome. METHOD: The datasets GSE61592 (three MIRI and three sham samples) and GSE160516 (twelve MIRI and four sham samples) were selected in the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) identification (p < 0.05 and |log FC (fold change)| ≥1) together with functional annotation (p < 0.05) was implemented. The Cytoscape platform established the protein-protein interaction (PPI) network. Genes associated with gut microbiome disorder were extracted based on the DisGeNET database, and those associated with MIRI were overlapped. The Recursive Feature Elimination (RFE) algorithm was adopted for selecting features, and cross-talk genes were predicted by the Support Vector Machine (SVM) models. A network encompassing cross-talk genes along with the TFs was thereby established. RESULT: The MIRI datasets comprised 138 shared DEGs, with 101 showing up-regulation whereas 37 showing down-regulation. Notably, the PPI interwork for MIRI contained 2517 edges along with 1818 nodes. By using RFE and SVM methods, six feature genes with the highest prediction were identified: B2m, VCAM-1, PDIA4, Ptgds, Mlxipl, and ACADS. Among these genes, B2m and PDIA4 were most highly expressed in MIRI and the gut microbiome disorder. CONCLUSION: B2m and PDIA4 were identified to be significantly correlated with candidate cross-talk genes of MIRI with gut microbiome disorder, implying a similarity between MIRI and Gut microbiome disorder (GMD). These genes can serve as an experimental research basis for future studies.


Assuntos
Microbioma Gastrointestinal , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Microbioma Gastrointestinal/genética , Regulação para Baixo , Infarto do Miocárdio/genética , Biologia Computacional
8.
PLoS One ; 18(9): e0292388, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37768979

RESUMO

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common, irreversible but preventable disease characterized by persistent respiratory symptoms. The mortality rate of COPD is predicted to reach 5.4 million by the year 2060. Despite its heavy burden on healthcare expenditure worldwide, only 15% of cases are medically identified. The potential benefits of facemask-wearing for COPD patients remain a topic of debate. METHODS: We will conduct a systematic review of all randomized trials and non-randomized controlled trials to evaluate the impact of facemasks on COPD patients. Our review will be based on literature obtained through a comprehensive search strategy across multiple electronic databases, including the Cochrane Library, Embase, PubMed, Web of Science, the Chinese Biomedical Database (SinoMed), and China National Knowledge Infrastructure (CNKI), with no restrictions on language or date of publication. Two independent researchers will extract and assess all relevant data using pre-designed data extraction forms. The included studies will be assessed using the Cochrane RoB2 tool and the suggested risk of bias criteria proposed by the Effective Practice and Organization of Care reviews group of the Cochrane collaboration. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will use Review Manager 5.4 software for statistical analysis. DISCUSSION: In the context of COVID-19, it is important for COPD patients to wear facemasks. This study aims to conduct a comprehensive and systematic assessment of the impact of facemasks on the physiology and activity of COPD patients. TRIAL REGISTRATION: PROSPERO registration number CRD42022326265.


Assuntos
COVID-19 , Doença Pulmonar Obstrutiva Crônica , Humanos , Máscaras , COVID-19/prevenção & controle , Revisões Sistemáticas como Assunto , Equipamento de Proteção Individual , Doença Pulmonar Obstrutiva Crônica/terapia , Metanálise como Assunto , Literatura de Revisão como Assunto
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(10): 1197-1203, 2023 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-37730217

RESUMO

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION: NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.


Assuntos
Transtornos Cromossômicos , Variações do Número de Cópias de DNA , Gravidez , Feminino , Humanos , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Aneuploidia , Feto
10.
Int J Mol Sci ; 24(14)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37511191

RESUMO

Renal cell carcinoma (RCC) is the most common form of kidney cancer, consisting of multiple distinct subtypes. RCC has the highest mortality rate amongst the urogenital cancers, with kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe carcinoma (KICH) being the most common subtypes. The Paired-box (PAX) gene family encodes transcription factors, which orchestrate multiple processes in cell lineage determination during embryonic development and organogenesis. Several PAX genes have been shown to be expressed in RCC following its onset and progression. Here, we performed real-time quantitative polymerase chain reaction (RT-qPCR) analysis on a series of human RCC cell lines, revealing significant co-expression of PAX2, PAX6, and PAX8. Knockdown of PAX2 or PAX8 mRNA expression using RNA interference (RNAi) in the A498 RCC cell line resulted in inhibition of cell proliferation, which aligns with our previous research, although no reduction in cell proliferation was observed using a PAX2 small interfering RNA (siRNA). We downloaded publicly available RNA-sequencing data and clinical histories of RCC patients from The Cancer Genome Atlas (TCGA) database. Based on the expression levels of PAX2, PAX6, and PAX8, RCC patients were categorized into two PAX expression subtypes, PAXClusterA and PAXClusterB, exhibiting significant differences in clinical characteristics. We found that the PAXClusterA expression subgroup was associated with favorable clinical outcomes and better overall survival. These findings provide novel insights into the association between PAX gene expression levels and clinical outcomes in RCC patients, potentially contributing to improved treatment strategies for RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Fator de Transcrição PAX2/genética , Fator de Transcrição PAX2/metabolismo , Neoplasias Renais/metabolismo , Rim/metabolismo , Fatores de Transcrição/metabolismo
11.
Medicine (Baltimore) ; 102(30): e34417, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37505157

RESUMO

BACKGROUND: About 70% to 80% of epilepsy cases are related to genetic factors. Genetic research has revealed the genetic etiology and molecular mechanisms of childhood epilepsy, which has increased our understanding of childhood epilepsy. METHODS: We searched the core collection of Web of Science for relevant papers on genetic research on childhood epilepsy published since 2010 on November 30, 2022. In this study, original articles and reviews in English were included. Using CiteSpace and VOSviewer online tools, we conducted a bibliometric analysis of the countries, institutions, journals, co-cited journals, co-cited references, keywords, and research hotspots. RESULTS: We evaluated 2500 literatures on epilepsy genomics in children. Among them, 96 countries published relevant articles, with the United States ranking the most. A total of 389 institutions have contributed relevant publications, and the University of Melbourne has published the most papers. Epilepsy journals were the most commonly cited. The references of papers were clustered into 9 categories: gene testing, epileptic encephalopathy, Dravet syndrome, focal cortical dysplasia, Rolandic epilepsy, copy number variation, ketogenic diet, monogenic epilepsy, and ptt2 mutation. Burst keywords represent the frontier of research, including developmental and epileptic encephalopathy (2021-2022), neurodevelopmental disorders (2020-2022), gene testing (2020-2022), and whole-exome sequencing (2019-2022). CONCLUSION: This study conducted a systematic and objective bibliometric analysis of the literature on epilepsy gene research in children. More importantly, it revealed the hot spot, frontier, and future developmental trends in the field. It will help pediatricians and geneticists further understand the dynamic evolution of genetic research on pediatric epilepsy.


Assuntos
Epilepsia Generalizada , Epilepsia Rolândica , Criança , Humanos , Variações do Número de Cópias de DNA , Bibliometria , Pesquisa em Genética
12.
Molecules ; 28(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37175367

RESUMO

Exploration of highly efficient and robust catalyst is pivotal for electrocatalytic degradation of dye wastewater, but it still is a challenge. Here, we develop a three-dimensional self-supported SnO2-Mn2O3 hybrid nanosheets grown on carbon cloth (noted by SnO2-Mn2O3@CC) electrode via a simple hydrothermal method and annealing treatment. Benefitting from the interlaced nanosheets architecture that enlarges the surface area and the synergetic component effect that accelerates the interfacial electronic transfer, SnO2-Mn2O3@CC electrode exhibits a superior electrocatalytic degradation efficiency for cationic blue X-GRRL dye in comparison with the single metal oxide electrode containing SnO2@CC and Mn2O3@CC. The degradation efficiency of cationic blue X-GRRL on SnO2-Mn2O3@CC electrode can reach up to 97.55% within 50 min. Furthermore, self-supported architecture of nanosheets on carbon cloth framework contributes to a robust stability compared with the traditional electrode via the multiple dip/brush coating accompanied by the thermal decomposition method. SnO2-Mn2O3@CC electrode exhibits excellent recyclability, which can still retain a degradation efficiency of 94.12% after six cycles. This work may provide a new pathway for the design and exploration of highly efficient and robust electrooxidation catalysts for dye degradation.

13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(6): 648-654, 2023 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-37211997

RESUMO

OBJECTIVE: To assess the diagnostic value of whole exome sequencing (WES) for patients with intellectual disability (ID) or global developmental delay (GDD). METHODS: 134 individuals with ID or GDD who presented at Chenzhou First People's Hospital between May 2018 and December 2021 were selected as the study subjects. WES was carried out on peripheral blood samples of the patients and their parents, and candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq) and co-segregation analysis. The pathogenicity of the variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: A total of 46 pathogenic single nucleotide variants (SNVs) and small insertion/deletion (InDel) variants, 11 pathogenic genomic copy number variants (CNVs), and 1 uniparental diploidy (UPD) were detected, which yielded an overall detection rate of 43.28% (58/134). The 46 pathogenic SNV/InDel have involved 62 mutation sites in 40 genes, among which MECP2 was the most frequent (n = 4). The 11 pathogenic CNVs have included 10 deletions and 1 duplication, which have ranged from 0.76 to 15.02 Mb. A loss of heterozygosity (LOH) region of approximately 15.62 Mb was detected in 15q11.2q12 region in a patient, which was validated as paternal UPD based on the result of trio-WES. The patient was ultimately diagnosed as Angelman syndrome. CONCLUSION: WES can detect not only SNV/InDel, but also CNV and LOH. By integrating family data, WES can accurately determine the origin of the variants and provide a useful tool for uncovering the genetic etiology of patients with ID or GDD.


Assuntos
Deficiência Intelectual , Humanos , Sequenciamento do Exoma , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Variações do Número de Cópias de DNA , Mutação , Perda de Heterozigosidade
14.
Int J Mol Sci ; 24(7)2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37047232

RESUMO

Increased expression of NUSAP1 has been identified as a robust prognostic biomarker in prostate cancer and other malignancies. We have previously shown that NUSAP1 is positively regulated by E2F1 and promotes cancer invasion and metastasis. To further understand the biological function of NUSAP1, we used affinity purification and mass spectrometry proteomic analysis to identify NUSAP1 interactors. We identified 85 unique proteins in the NUSAP1 interactome, including ILF2, DHX9, and other RNA-binding proteins. Using proteomic approaches, we uncovered a function for NUSAP1 in maintaining R-loops and in DNA damage response through its interaction with ILF2. Co-immunoprecipitation and colocalization using confocal microscopy verified the interactions of NUSAP1 with ILF2 and DHX9, and RNA/DNA hybrids. We showed that the microtubule and charged helical domains of NUSAP1 were necessary for the protein-protein interactions. Depletion of ILF2 alone further increased camptothecin-induced R-loop accumulation and DNA damage, and NUSAP1 depletion abolished this effect. In human prostate adenocarcinoma, NUSAP1 and ILF2 mRNA expression levels are positively correlated, elevated, and associated with poor clinical outcomes. Our study identifies a novel role for NUSAP1 in regulating R-loop formation and accumulation in response to DNA damage through its interactions with ILF2 and hence provides a potential therapeutic target.


Assuntos
Neoplasias da Próstata , Estruturas R-Loop , Humanos , Masculino , Dano ao DNA , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína do Fator Nuclear 45/genética , Proteína do Fator Nuclear 45/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteômica
15.
J Agric Food Chem ; 71(12): 4901-4914, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36938622

RESUMO

Pecan (Carya illinoinensis) is a popular tree nut. Its fruit development undergoes slow growth, rapid expansion, core hardening, and kernel maturation stages. However, little is known about how pecan initiates fruit development and enlargement after pollination. In this study, we performed the first large-scale identification of potential phosphorylation sites and proteins at early development of pecan fruit by a label-free phosphoproteomic quantification technique. A total of 2155 phosphosites were identified from 1953 phosphopeptides covering 1311 phosphoproteins in unpollinated pistils and fruits at 5 and 9 weeks after pollination. Of these, 699 nonredundant phosphoproteins were differentially phosphorylated (DP). Furthermore, the phosphorylation intensity of DP proteins in brassinolide (BR) and auxin signaling were analyzed, and the function of CiBZR1 was investigated. Ectopic expression of CiBZR1 resulted in BR response phenotypes with curled leaves and fruit, while enlarged seed size in Arabidopsis. Subcellular localization and transcriptional activation activity assay demonstrated that CiBZR1 distributed in both the nucleus and cytoplasm with transcriptional activity. When two phosphosites mutated, CiBZR1S201P,S205G moved to the nucleus completely, while the transcriptional activity remained unchanged. Taken together, our data reveal extensive phosphoproteins and lay a foundation to comprehensively dissect the potential post-translational regulation mechanism of early development of pecan fruit.


Assuntos
Carya , Frutas , Frutas/genética , Nozes , Sementes , Fenótipo
16.
Circ Res ; 132(5): 545-564, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36744494

RESUMO

OBJECTIVE: Mutations in BMPR2 (bone morphogenetic protein receptor 2) are associated with familial and sporadic pulmonary arterial hypertension (PAH). The functional and molecular link between loss of BMPR2 in pulmonary artery smooth muscle cells (PASMC) and PAH pathogenesis warrants further investigation, as most investigations focus on BMPR2 in pulmonary artery endothelial cells. Our goal was to determine whether and how decreased BMPR2 is related to the abnormal phenotype of PASMC in PAH. METHODS: SMC-specific Bmpr2-/- mice (BKOSMC) were created and compared to controls in room air, after 3 weeks of hypoxia as a second hit, and following 4 weeks of normoxic recovery. Echocardiography, right ventricular systolic pressure, and right ventricular hypertrophy were assessed as indices of pulmonary hypertension. Proliferation, contractility, gene and protein expression of PASMC from BKOSMC mice, human PASMC with BMPR2 reduced by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation were compared to controls, to investigate the phenotype and underlying mechanism. RESULTS: BKOSMC mice showed reduced hypoxia-induced vasoconstriction and persistent pulmonary hypertension following recovery from hypoxia, associated with sustained muscularization of distal pulmonary arteries. PASMC from mutant compared to control mice displayed reduced contractility at baseline and in response to angiotensin II, increased proliferation and apoptosis resistance. Human PASMC with reduced BMPR2 by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation showed a similar phenotype related to upregulation of pERK1/2 (phosphorylated extracellular signal related kinase 1/2)-pP38-pSMAD2/3 mediating elevation in ARRB2 (ß-arrestin2), pAKT (phosphorylated protein kinase B) inactivation of GSK3-beta, CTNNB1 (ß-catenin) nuclear translocation and reduction in RHOA (Ras homolog family member A) and RAC1 (Ras-related C3 botulinum toxin substrate 1). Decreasing ARRB2 in PASMC with reduced BMPR2 restored normal signaling, reversed impaired contractility and attenuated heightened proliferation and in mice with inducible loss of BMPR2 in SMC, decreasing ARRB2 prevented persistent pulmonary hypertension. CONCLUSIONS: Agents that neutralize the elevated ARRB2 resulting from loss of BMPR2 in PASMC could prevent or reverse the aberrant hypocontractile and hyperproliferative phenotype of these cells in PAH.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Animais , Humanos , Camundongos , beta-Arrestina 2/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Proliferação de Células , Células Cultivadas , Células Endoteliais/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Hipertensão Pulmonar/metabolismo , Hipóxia/complicações , Hipóxia/genética , Hipóxia/metabolismo , Miócitos de Músculo Liso/metabolismo , Hipertensão Arterial Pulmonar/genética , Artéria Pulmonar/metabolismo , RNA/metabolismo
17.
J Agric Food Chem ; 71(5): 2377-2389, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36695193

RESUMO

Salicylic acid (SA) is an important plant hormone and signal required for establishing resistance to diverse pathogens and plant diseases. The abundant polyphenols in tea plants also defend plants from biotic and abiotic stresses. However, whether exogenous SA would increase the resistance of tea plants to adversity and the relationship between SA and polyphenols are still poorly understood. Here, we carried out SA treatment on tea seedlings and performed transcriptome sequencing. SA treatment inhibited the phenylpropanoid and flavonoid metabolic pathways but promoted the lignin metabolic pathways. The increased accumulation of lignin in tea leaves after treating with SA indicated that lignin might coordinate SA, enhance, and improve plant defense and disease resistance. Simultaneously, an SA-inducible flavonoid glucosyltransferase (CsUGT0554) specifically involved in 7-OH site glycosylation was characterized in vitro. These results provided valuable information about the effects of SA on tea seedlings and the molecular basis for SA-mediated immune responses.


Assuntos
Camellia sinensis , Camellia sinensis/metabolismo , Ácido Salicílico/metabolismo , Lignina/metabolismo , Proteínas de Plantas/metabolismo , Flavonoides/metabolismo , Polifenóis/metabolismo , Folhas de Planta/metabolismo , Chá/metabolismo , Regulação da Expressão Gênica de Plantas
18.
Exp Anim ; 72(2): 262-273, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-36543206

RESUMO

Nonhuman primates are used extensively in a variety of nonclinical safety evaluation studies of new drugs. In those studies, intravenous infusion is a common treatment method, a noninvasive telemetry system is usually used for cardiovascular safety and pharmacology evaluation, and blood samples are repeatedly collected for various analysis. Intravenous infusion, vest wearing, and repeated intravenous blood collection can caused a stress response in cynomolgus monkeys, which may lead to changes in clinical pathology parameters in them. Here, we aimed to test the effects of the above operations on clinical pathology parameters in cynomolgus monkeys. Twenty monkeys (10 male/10 female) were administered 0.9% sodium chloride injections via intravenous infusions on Days 1 and 10. Each animal wore a vest before each dosing, and the vest was removed at 24 h after each dosing. Blood samples were collected before the first dose and at 2 min, 24 h, 48 h, 72 h, and 168 h after each dosing. As compared to values before the first dose (D-1) increases in reticulocytes (percentage and absolute count) and decreases in erythrocytes (red blood cells, hemoglobin, and hematocrit) were noted after dosing. The decrease in erythrocytes and increase in reticulocytes were considered to the related to the repeated intravenous blood collection. Increases in leukocytes (white blood cells and absolute count and percentage of neutrophils) and platelets (mean platelet volume and platelet distribution width) were noted at 2 min or 24 h post dose. Increases in aspartate aminotransferase, direct bilirubin, creatine kinase, C-reactive protein, and human cardiac troponin I and decreases in inorganic phosphate were noted at 2 min to 72 h post dose.


Assuntos
Infusões Intravenosas , Masculino , Feminino , Humanos , Animais , Macaca fascicularis
19.
Biosens Bioelectron ; 220: 114879, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36368141

RESUMO

Circulating microRNAs (miRNAs) can be regarded as reliable noninvasive biomarkers in body fluids for the early diagnosis, prognosis, and monitoring of cancers. By combining target triggered bipedal DNAzyme walker cleavage cycling amplification and planar intercalated methylene blue (MB) molecules amplification, a versatile ratiometric electrochemical biosensing system is constructed for miRNAs detection. Using the microRNA-21 (miRNA-21) as a triggered model target from breast cancer cells (MCF-7) and cervical cancer cells (HeLa), the sensitivity and feasibility of the ratiometric biosensing strategy were verified on the basis of decreased streptavidin-conjugated cupric sulfide@platinum (CuS@Pt-SA) nanozyme signal with cleaved Zn2+-dependent DNAzyme walkers as well as enhanced duplex section of MB signal, which were assisted by the modification of high electronic conductivity and specific surface area of metallic WSe2 nanoflowers on the electrode. Hence, the introduced sensing strategy of higher cleavage activity of the bipedal DNAzyme walker cyclic amplification resulted into the remarkable sensitive measurement which had a detection limit of 0.16 fM from 1 fM to 1 nM for miRNA-21. Benefiting from the precise design of the capture Hairpin DNA, this proposed method showed excellent specificity to distinguish miRNA-21 from other miRNAs sequences, in addition to possessing good stability and reproducibility. Thus, this versatility platform can be utilized to sense various miRNAs biomarkers by simple of the redesigning the capture Hairpin DNA, hence presents a great promise in clinical application towards early cancer diagnosis, biological analysis and prognosis.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , MicroRNAs , DNA Catalítico/química , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos , DNA/química , MicroRNAs/análise , Técnicas Eletroquímicas/métodos , Limite de Detecção
20.
Food Chem ; 399: 133933, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36037684

RESUMO

A series of incubation systems of (+) - catechin (Cat), ascorbic acid (AA) and polyphenol oxidase (PPO) of lotus rhizome at 40 °C were performed to investigate the effect and oxidation pathway of AA on the stability of Cat. The results showed that after the enzymatic or non-enzymatic oxidation of Cat, the products of the two reactions were the same, namely epicatechin, catechin dimer and dehydrogenated catechin dimer. After adding AA, the protective effect of AA on catechin increased first and then decreased with the increase of AA concentration. 0.1 mmolL(exp)-1 AA can inhibit PPO activity in a short time. Within 24 h, 1 mmolL(exp)-1 AA can keep Cat content at 87.88 %. At the concentration of 10 mmolL(exp)-1 AA, excessive AA is oxidized to form a large amount of dehydroascorbic acid (DHAA), which forms an adduct with Cat, promoting the consumption of Cat. The effect of AA on the stability of Cat is time-dependent and dose-dependent.


Assuntos
Ácido Ascórbico , Catequina , Ácido Ascórbico/metabolismo , Catecol Oxidase/metabolismo , Ácido Desidroascórbico , Oxirredução
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...