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1.
Proc Natl Acad Sci U S A ; 120(5): e2210038120, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36696440

RESUMO

To determine the error rate of transcription in human cells, we analyzed the transcriptome of H1 human embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing of the transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species in human cells. Our results indicate that different RNA species display different error rates, suggesting that human cells prioritize the fidelity of some RNAs over others. Cross-referencing the errors that we detected with various genetic and epigenetic features of the human genome revealed that the in vivo error rate in human cells changes along the length of a transcript and is further modified by genetic context, repetitive elements, epigenetic markers, and the speed of transcription. Our experiments further suggest that BRCA1, a DNA repair protein implicated in breast cancer, has a previously unknown role in the suppression of transcription errors. Finally, we analyzed the distribution of transcription errors in multiple tissues of a new mouse model and found that they occur preferentially in neurons, compared to other cell types. These observations lend additional weight to the idea that transcription errors play a key role in the progression of various neurological disorders, including Alzheimer's disease.


Assuntos
RNA , Transcrição Gênica , Animais , Camundongos , Humanos , RNA/genética , Transcriptoma , Proteínas/genética , Sequências Repetitivas de Ácido Nucleico
2.
BMC Neurol ; 24(1): 170, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783204

RESUMO

PURPOSE: QT interval prolongation is one of the most common electrocardiographic (ECG) abnormalities in patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether corrected QT interval (QTc) prolongation is associated with perioperative cardiac events and dismal neurological outcome in mid to long-term follow-up in patients after aSAH is insufficiently studied and remains controversial. METHODS: We retrospectively studied the adult (≥ 18 years) patients admitted to our institution between Jan 2018 and Dec 2020 for aSAH who underwent intracranial aneurysm clipping or embolization. The patients were divided into 2 groups (normal and QTc prolongation groups) according to their QTc. To minimize the confounding bias, a propensity score matching (PSM) analysis was performed to compare the neurologic outcomes between patients with normal QTc and QTc prolongation. RESULTS: After screening, 908 patients were finally included. The patients were divided into 2 groups: normal QTc groups (n = 714) and long QTc group (n = 194). Female sex, hypokalemia, posterior circulation aneurysm, and higher Hunt-Hess grade were associated with QTc prolongation. In multiple regression analysis, older age, higher hemoglobin level, posterior circulation aneurysm, and higher Hunt-Hess grade were identified to be associated with worse outcome during 1-year follow-up. Before PSM, patients with QTc prolongation had higher rate of perioperative cardiac arrest or ventricular arrhythmias. After PSM, there was no statistical difference between normal and QTc prolongation groups in perioperative cardiac events. However, patients in the QTc prolongation group still had worse neurologic outcome during 1-year follow-up. CONCLUSIONS: QTc prolongation is associated with worse outcome in patients following SAH, which is independent of perioperative cardiac events.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Síndrome do QT Longo , Hemorragia Subaracnóidea , Humanos , Masculino , Feminino , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia , Pessoa de Meia-Idade , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/complicações , Síndrome do QT Longo/etiologia , Embolização Terapêutica/métodos , Embolização Terapêutica/efeitos adversos , Adulto , Idoso , Microcirurgia/métodos , Microcirurgia/efeitos adversos , Resultado do Tratamento , Eletrocardiografia/métodos
3.
J Nanobiotechnology ; 22(1): 66, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368393

RESUMO

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.


Assuntos
Transtorno do Espectro Autista , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Exossomos/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/terapia , Transtorno do Espectro Autista/metabolismo , Hibridização in Situ Fluorescente , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Prospectivos , Distribuição Tecidual , Neurogênese , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Interferon gama/metabolismo
4.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33723074

RESUMO

Fasting in mammals promotes increases in circulating glucagon and decreases in circulating insulin that stimulate catabolic programs and facilitate a transition from glucose to lipid burning. The second messenger cAMP mediates effects of glucagon on fasting metabolism, in part by promoting the phosphorylation of CREB and the dephosphorylation of the cAMP-regulated transcriptional coactivators (CRTCs) in hepatocytes. In Drosophila, fasting also triggers activation of the single Crtc homolog in neurons, via the PKA-mediated phosphorylation and inhibition of salt-inducible kinases. Crtc mutant flies are more sensitive to starvation and oxidative stress, although the underlying mechanism remains unclear. Here we use RNA sequencing to identify Crtc target genes that are up-regulated in response to starvation. We found that Crtc stimulates a subset of fasting-inducible genes that have conserved CREB binding sites. In keeping with its role in the starvation response, Crtc was found to induce the expression of genes that inhibit insulin secretion (Lst) and insulin signaling (Impl2). In parallel, Crtc also promoted the expression of genes involved in one-carbon (1-C) metabolism. Within the 1-C pathway, Crtc stimulated the expression of enzymes that encode modulators of S-adenosyl-methionine metabolism (Gnmt and Sardh) and purine synthesis (ade2 and AdSl) Collectively, our results point to an important role for the CREB/CRTC pathway in promoting energy balance in the context of nutrient stress.


Assuntos
Proteínas de Drosophila/genética , Metabolismo Energético , Jejum/metabolismo , Insulina/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Animais , Carbono/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Drosophila/metabolismo , Regulação Enzimológica da Expressão Gênica , Ligação Proteica , Estresse Fisiológico , Fatores de Transcrição/metabolismo
5.
Proc Natl Acad Sci U S A ; 118(38)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34531325

RESUMO

In response to DNA replication stress, DNA replication checkpoint kinase Mec1 phosphorylates Mrc1, which in turn activates Rad53 to prevent the generation of deleterious single-stranded DNA, a process that remains poorly understood. We previously reported that lagging-strand DNA synthesis proceeds farther than leading strand in rad53-1 mutant cells defective in replication checkpoint under replication stress, resulting in the exposure of long stretches of the leading-strand templates. Here, we show that asymmetric DNA synthesis is also observed in mec1-100 and mrc1-AQ cells defective in replication checkpoint but, surprisingly, not in mrc1∆ cells in which both DNA replication and checkpoint functions of Mrc1 are missing. Furthermore, depletion of either Mrc1 or its partner, Tof1, suppresses the asymmetric DNA synthesis in rad53-1 mutant cells. Thus, the DNA replication checkpoint pathway couples leading- and lagging-strand DNA synthesis by attenuating the replication function of Mrc1-Tof1 under replication stress.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , Replicação do DNA/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Ciclo Celular/genética , Quinase do Ponto de Checagem 2/genética , Replicação do DNA/genética , DNA Fúngico/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomycetales/genética , Saccharomycetales/metabolismo
6.
Risk Anal ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39218805

RESUMO

In light of the escalating global warming and the escalating frequency of extreme weather events, the agricultural sector, being a fundamental and pivotal industry worldwide, is encountering substantial challenges due to climate change. Using Chinese provincial panel data for 2000-2021, this paper utilizes a two-way fixed-effect model to investigate the impact of Climate Risk (CR) on green total factor productivity in agriculture (AGTFP), with China's climate policy uncertainty (CPU) being introduced as a moderating variable within the research framework to scrutinize its influence in this context. The findings reveal a noteworthy adverse effect of CR on AGTFP, further exacerbated by CPU. Heterogeneity analysis results show that there is a clear regional variation in the effect of CR on AGTFP across different Chinese regions, with CR significantly inhibiting AGTFP development in the northern regions and provinces in major grain producing regions. Consequently, there is a pressing necessity to bolster the establishment of climate change monitoring infrastructures, devise tailored climate adaptation strategies at a regional level, and enhance the clarity and predictability of climate policies to fortify the resilience and sustainability of agricultural production systems.

7.
Molecules ; 29(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38675658

RESUMO

Zirconia (ZrO2) is a ceramic material with high-temperature resistance and good insulating properties. Herein, for the first time, the surface of ZrO2 was modified with docosanoic acid (DCA) to improve its self-cleaning and hydrophobic properties. This surface modification transformed the surface of ZrO2 from hydrophilic to superhydrophobic. A two-step spraying method was used to prepare the superhydrophobic surface of ZrO2 by sequentially applying a primer and a topcoat. The primer was a solution configured using an epoxy resin as the adhesive and polyamide as the curing agent, while the topcoat was a modified ZrO2 solution. The superhydrophobic surface of ZrO2 exhibited a contact angle of 154° and a sliding angle of 4°. Scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and other analytical techniques were used to characterize the prepared zirconia particles and their surfaces. Moreover, results from surface self-cleaning and droplet freezing tests showed that DCA-modified ZrO2 can be well combined, and its coatings show good self-cleaning and anti-icing properties on TA2 bases.

8.
BMC Genomics ; 24(1): 228, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131143

RESUMO

BACKGROUND: Single-cell RNA sequencing is a state-of-the-art technology to understand gene expression in complex tissues. With the growing amount of data being generated, the standardization and automation of data analysis are critical to generating hypotheses and discovering biological insights. RESULTS: Here, we present scRNASequest, a semi-automated single-cell RNA-seq (scRNA-seq) data analysis workflow which allows (1) preprocessing from raw UMI count data, (2) harmonization by one or multiple methods, (3) reference-dataset-based cell type label transfer and embedding projection, (4) multi-sample, multi-condition single-cell level differential gene expression analysis, and (5) seamless integration with cellxgene VIP for visualization and with CellDepot for data hosting and sharing by generating compatible h5ad files. CONCLUSIONS: We developed scRNASequest, an end-to-end pipeline for single-cell RNA-seq data analysis, visualization, and publishing. The source code under MIT open-source license is provided at https://github.com/interactivereport/scRNASequest . We also prepared a bookdown tutorial for the installation and detailed usage of the pipeline: https://interactivereport.github.io/scRNAsequest/tutorial/docs/ . Users have the option to run it on a local computer with a Linux/Unix system including MacOS, or interact with SGE/Slurm schedulers on high-performance computing (HPC) clusters.


Assuntos
Ecossistema , Perfilação da Expressão Gênica , Perfilação da Expressão Gênica/métodos , Análise da Expressão Gênica de Célula Única , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Software , Editoração
9.
Small ; : e2307829, 2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38044585

RESUMO

Photoacoustic imaging (PAI) and photothermal therapy (PTT) conducted over the near-infrared-II (NIR-II) window offer the benefits of noninvasiveness and deep tissue penetration. This necessitates the development of highly effective therapeutic agents with NIR-II photoresponsivity. Currently, the predominant organic diagnostic agents used in NIR-II PAI-guided PTT are conjugated polymeric materials. However, they exhibit a low in vivo clearance rate and long-term biotoxicity, limiting their clinical translation. In this study, an organic small molecule (CY-1234) with NIR-II absorption and nanoencapsulation (CY-1234 nanoparticles (NPs)) for PAI-guided PTT is reported. Extended π-conjugation is achieved in the molecule by introducing donor-acceptor units at both ends of the molecule. Consequently, CY-1234 exhibits a maximum absorption peak at 1234 nm in tetrahydrofuran. Nanoaggregates of CY-1234 are synthesized via F-127 encapsulation. They exhibit an excellent photothermal conversion efficiency of 76.01% upon NIR-II light irradiation. After intravenous injection of CY-1234 NPs into tumor-bearing mice, strong PA signals and excellent tumor ablation are observed under 1064 nm laser irradiation. This preliminary study can pave the way for the development of small-molecule organic nanoformulations for future clinical applications.

10.
Sleep Breath ; 27(5): 1819-1828, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36826736

RESUMO

INTRODUCTION: To date, many studies have shown a link between siesta and cardiovascular events. Little is known regarding the connection between siesta and brachial-ankle pulse wave velocity (baPWV) levels, even though baPWV can determine the degree of atherosclerosis and vascular stiffness. Thus, we examined the relationship between siesta time and baPWV in a cross-sectional study. METHODS: Interviews, physical examinations, lab testing, and electron beam computed tomography were all part of the baseline evaluation for participants aged older than 35. Baseline data were compared for 3 different siesta habits: irregular or no siestas, daily short siestas (1 h or less), and daily long siestas (> 1 h). Utilizing logistic regression models and multivariate linear regression, the link between siesta time and baPWV was determined. RESULTS: Among all 6566 participants, the different siesta groups had a significant difference of the degrees of AS (P < 0.001). The same outcome was true for both males (P < 0.001) and females (P < 0.001). Numerous cardiovascular risk variables and markers of subclinical atherosclerosis were positively correlated with daily extended siestas. Results from the fully adjusted model showed that long siestas (> 60 min, OR = 1.18, 95%CI: 1.06-1.31, P = 0.002) were linked to a more severe level of the baPWV. For age or gender stratification, we found significant differences between non-siesta and > 60 min siesta groups. Multiple linear regression analysis revealed a positive connection between siesta duration and baPWV (ß = 0.197, P = 0.038). CONCLUSIONS: An elevated risk of atherosclerosis was shown to accompany prolonged siestas. These results need to be followed up on with prospective studies and additional lab work.


Assuntos
Aterosclerose , Rigidez Vascular , Masculino , Feminino , Humanos , Idoso , Estudos Transversais , Índice Tornozelo-Braço/métodos , Estudos Prospectivos , Fatores de Risco , Análise de Onda de Pulso/métodos , China , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia
11.
BMC Anesthesiol ; 23(1): 189, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259069

RESUMO

BACKGROUND: Decreased bioavailability of nitric oxide (NO) under hypoxic conditions can lead to endothelial dysfunction. NO supplementation may protect endothelial function in ischemia-reperfusion (IR) injury. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to verify the protective effect of NO donors on endothelium in IR injury. METHODS: Medline, Embase, Cochrane Library, and Web of Science databases were searched from inception to April 1, 2023. The specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing NO donors with placebo control groups; and (3) trials reporting the effects of these interventions on vascular endothelial functional outcomes in IR injury. Random-effects models were used to assess pooled effect sizes, which were expressed as standardized mean differences (SMD). RESULTS: Seven studies satisfied the inclusion criteria and consisted of a total of 149 participants. NO donors were protective of endothelial function in IR injury (SMD: - 1.60; 95% confidence interval [CI]: - 2.33, - 0.88, P < 0.0001; heterogeneity [I2 = 66%, P = 0.001]). Results of the subgroup analysis showed the following: absence of protective effect of NO donor use following ischemia on endothelial function in IR injury - 1.78 (95% CI: - 2.50, - 1.07) and loss of protective effect on endothelial function after prolonged NO donor use - 0.89 (95% CI: - 2.06, 0.28). CONCLUSION: The short-period use of NO donors before the onset of ischemia can protect endothelial function in IR injury.


Assuntos
Doadores de Óxido Nítrico , Traumatismo por Reperfusão , Humanos , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Endotélio Vascular , Traumatismo por Reperfusão/prevenção & controle , Óxido Nítrico
12.
Molecules ; 28(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37570716

RESUMO

Lung cancer seriously threatens human health. To explore the molecular mechanism of 20(S)-Protopanaxadiol (PPD) on human non-small cell lung cancer cells, we investigated the transcriptional profile of PPD-treated NCI-H1299 cells. Cell proliferation, cell cycle, and apoptosis were detected using cell counting kit-8 and flow cytometry, respectively. Differentially expressed genes (DEGs) between PPD-treated and untreated cells were determined using RNA sequencing and bioinformatic analysis. Protein phosphorylation was detected using Western blotting. Data of mRNA expression profiles of lung cancer were from The Cancer Genome Atlas (TCGA) and analyzed using R software version 4.3.1. PPD showed an inhibitory effect on the proliferation of NCI-H1299 cells and induced apoptosis. There were 938 upregulated genes and 466 downregulated genes in PPD-treated cells, and DEGs were primarily enriched in the MAPK signaling pathway. The detection of phosphorylation revealed that the phosphorylation of ERK and p38 MAPK was significantly reduced in PPD-treated cells. Further comparison of PPD-regulated DEGs with clinical data of lung adenocarcinoma demonstrated that most downregulated genes in tumor tissues were upregulated in PPD-treated cells or vice versa. Two PPD-downregulated genes HSPA2 and EFNA2 were associated with patients' overall survival. Therefore, PPD could inhibit NCI-H1299 cells by affecting gene expression and regulating ERK and p38 MAPK pathways.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Perfilação da Expressão Gênica
13.
Breast Cancer Res Treat ; 196(1): 45-56, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36056297

RESUMO

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Inibidores de Checkpoint Imunológico , Ligantes , Linfócitos do Interstício Tumoral , Mutação , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/terapia , Tirosina/metabolismo
14.
Bioinformatics ; 37(20): 3670-3672, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33901288

RESUMO

SUMMARY: We developed Quickomics, a feature-rich R Shiny-powered tool to enable biologists to fully explore complex omics statistical analysis results and perform advanced analysis in an easy-to-use interactive interface. It covers a broad range of secondary and tertiary analytical tasks after primary analysis of omics data is completed. Each functional module is equipped with customizable options and generates both interactive and publication-ready plots to uncover biological insights from data. The modular design makes the tool extensible with ease. AVAILABILITY AND IMPLEMENTATION: Researchers can experience the functionalities with their own data or demo RNA-Seq and proteomics datasets by using the app hosted at http://quickomics.bxgenomics.com and following the tutorial, https://bit.ly/3rXIyhL. The source code under GPLv3 license is provided at https://github.com/interactivereport/Quickomics for local installation. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

15.
BMC Cardiovasc Disord ; 22(1): 493, 2022 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404303

RESUMO

BACKGROUND: Drug-coated balloon (DCB) is a novel and effective device for coronary artery disease patients with in-stent restenosis (ISR). However, the incidence and possible influencing factors associated with binary restenosis have not yet been adequately assessed. METHODS: The data are extracted from a prospective, multicenter, randomized controlled trial. A total of 211 patients with ISR were enrolled at 13 centers from August 2017 to October 2018 and treated with DCB. At the 9-month coronary angiographic follow-up, patients were divided into restenosis and non-restenosis groups, and demographic data, lesion features, and laboratory tests were retrospectively reviewed. Furthermore, logistic regression analysis was used to identify possible influencing factors. RESULTS: All patients successfully underwent treatment, and 166 patients with 190 lesions took part in angiography follow-ups at 9 months. Of these, 41 patients with 44 target lesions developed restenosis following treatment, and the incidence of ISR was 24.7%. There were significant differences in the average length of target lesions and the number of multivessel lesions and fasting plasma glucose (FBG) between the two groups (p < 0.05). Demographic data, cardiac risk factors, left ventricular ejection fractions (LVEF), blood routine tests, biochemical tests, and other features of devices and lesions showed no difference. Logistic regression analyses showed that FBG > 6.1 mmol/L (OR: 7.185 95% CI: 2.939-17.567 P < 0.001) and length of lesion (OR:1.046 95% CI: 1.001-1.093 P = 0.046) were associated risk factors. CONCLUSIONS: The longer length of lesions, more target lesions and FBG > 6.1 mmol/L per individual may be characteristics of patients showing ISR following treatment. Studies with larger sample size, and more complete follow-up data are needed in the future to expend on these findings. TRIAL REGISTRATION: No.: NCT04213378, first posted date (30/12/2019).


Assuntos
Angioplastia com Balão , Reestenose Coronária , Humanos , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/epidemiologia , Reestenose Coronária/etiologia , Incidência , Estudos Retrospectivos , Estudos Prospectivos , Angioplastia com Balão/efeitos adversos , Constrição Patológica/complicações
16.
Ann Diagn Pathol ; 61: 152047, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36156357

RESUMO

Some invasive breast carcinomas are surrounded by a clear space that separate the tumor cells from the adjacent stroma, similar to invasive micropapillary carcinoma (IMPC), but lack the thin strands of connective tissue that separate the cells and characteristic "inside-out" growth pattern of IMPC on immunohistochemical stain for EMA. We consider the presence of the retraction clefts a common phenomenon that may present as a precursor stage of IMPC (PSIMPC). In this study, a total of 2497 cases of invasive breast carcinomas were prospectively collected. Among 2497 cases of breast cancer, 949 (38.0 %) cases were PSIMPC, 200 (8.0 %) cases were IMPC and 1348 (54.0 %) cases were IBC-NST. LVI was seen in128 of 200 (64 %) IMPC and 364 of 948 (38.0 %) PSIMPC, in contrast to 246 of 1341 (18 %) IBC-NST (P < 0.001). Lymph node metastasis was seen in 147 of 200 (73.4 %) IMPC and 551 of 949 (58 %) PSIMPC, in contrast to 563 of 1345 (42 %) IBC-NST (P < 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) of PSIMPC were 76.8 % and 87.6 %, compared to 63.2 % and 85.9 % in IMPC, 86.2 % and 93.7 % in IBC-NST. PSIMPC demonstrated a more favorable DFS and OS compared to IMPC, but worse DFS and OS compared to IBC-NST. Cox and logistic regression analysis showed that PSIMPC was an independent predictor of DFS and OS. Our findings suggest that the presence of retraction clefts is a precursor state of IMPC, exhibiting IMPC-like features, such as higher incidence of lymphovascular invasion, lymph node metastasis and more aggressive clinical behavior.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Papilar , Carcinoma , Humanos , Feminino , Metástase Linfática , Neoplasias da Mama/patologia , Carcinoma Papilar/patologia , Intervalo Livre de Doença , Carcinoma Ductal de Mama/patologia
17.
Molecules ; 27(15)2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35956952

RESUMO

The mechanism of ginsenoside Rh3 activity against cancer remains unclear. This study aimed to investigate the underlying mechanism. The effects of Rh3 on the cell proliferation, migration and invasion, and cycle and apoptosis were analyzed using CCK-8 assay, transwell migration assay and flow cytometry, respectively. The RNA transcriptome was sequenced and data were analyzed by R software. Protein expression and protein-protein interactions were determined by Western blotting and co-immunoprecipitation, respectively. The results showed Rh3 inhibited HCT116 cell proliferation, invasion, and migration, arrested cells at G1 phase; and increased apoptosis. Rh3 downregulated 314 genes and upregulated 371 genes. Gene Set Enrichment Analysis (GSEA) using The Kyoto Encyclopedia of Genes Genomics ranked DNA replication first, while GSEA using Gene Ontology ranked the initiation of DNA replication first. Compared with tumor data from The Cancer Genome Atlas (TCGA), most of genes related to DNA replication were oppositely regulated by Rh3. Furthermore, Rh3 down-regulated key protein expression related to DNA replication (Orc6, Cdt1, and Mcm2), but did not affect the loading of Mcm complexes onto ORC complexes nor the phosphorylation at ser139 of Mcm2. Therefore, Rh3 may inhibit colorectal cancer HCT116 cells by downregulation of genes related to DNA replication.


Assuntos
Neoplasias Colorretais , Ginsenosídeos , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica , Ginsenosídeos/farmacologia , Células HCT116 , Humanos
18.
Environ Monit Assess ; 195(1): 90, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350456

RESUMO

Ecological security assessment can effectively reflect the ecological status of a region and reveal its level of sustainable development. In this paper, an ecological security-oriented evaluation system was constructed, and the ecological security level of the Dongjiangyuan region from 2000 to 2020 was evaluated based on catastrophe theory and GIS. The results were as follows: (1) As shown in the land use and cover maps, by 2020, the forestland area had decreased the most, and the artificial surface area had increased the most. (2) The ecological security index of the Dongjiangyuan region showed a low trend in the artificial surface area and its surrounding areas. The quite low values of the ecological security index in 2000 and 2010 were improved in 2020 due to the increase in ecological services capacity. The increased vegetation cover from 2000 to 2020 promoted the improved ecological service capacity. (3) The rapid urbanization process in the Dongjiangyuan region resulted in a lower ecological sensitivity index value. Notably, the ecological sensitivity index of the study area had a slightly decreasing trend. (4) The spatial autocorrelation showed that the proportion of hot and cold spots from 2000 to 2020 decreased by 2.96% and 6.91%, respectively. This study can provide a scientific basis and decision-making guidance for ecological management in the Dongjiangyuan region in the future.


Assuntos
Conservação dos Recursos Naturais , Ecologia , Ecologia/métodos , Conservação dos Recursos Naturais/métodos , Sistemas de Informação Geográfica , Monitoramento Ambiental , Ecossistema , China
19.
Environ Monit Assess ; 194(9): 616, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35900589

RESUMO

Carbon emissions and economic growth are two contradictions in urban development, and their decoupling is related to the sustainable development of cities. This paper took urban agglomeration in the middle reaches of the Yangtze River (UAMRYR), China, as the study area. The Kaya model, the Tapio decoupling model, and the Logarithmic Mean Divisia Index (LMDI) model were adopted to analyze the spatiotemporal differentiation of carbon emissions, the decoupling of economic activities, and driving factors. The results indicate that (1) carbon emissions increased by 66% in the study period, but the growth momentum was curbed after 2015. Low level and medium level areas continue to decrease, and relatively high level area gradually become dominant. (2) Spatially, carbon emissions are in a pattern of middle-hot and east-cold. Jiangxi is in the sub-cold and coldspot area, while the hotspot area is driven by the transformation from Wuhan's single-core to Wuhan and Changsha's dual-core. (3) Since 2010, most cities have been in a good decoupling state, and weak decoupling cities have risen from 35.5% in the initial period to 87.1% in 2010-2011, but the decoupling situation of industrial cities with more high-energy-consuming industries still rebounded slightly. (4) The economic level and energy intensity effect had the most significant impact on the economic decoupling of carbon emissions, whose absolute contribution rates were greater than 35%. Urbanization and economic level both play a positive role in promoting carbon emissions, and the energy intensity plays a negative role in retarding carbon emissions. The population effect was mainly manifested in carbon increase from 2006 to 2011, and 45.2% of the cities from 2011 to 2017 turned into carbon suppression. Finally, we suggest that decoupling carbon emissions from economic growth requires developing green urbanization and a decarbonized economy, optimizing the structure of energy consumption and guiding rational population flow.


Assuntos
Carbono , Desenvolvimento Econômico , Carbono/análise , Dióxido de Carbono/análise , China , Monitoramento Ambiental , Urbanização
20.
Environ Monit Assess ; 194(7): 515, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35731371

RESUMO

Urbanization is a critical factor affecting regional carbon emissions. Clarifying the linkage between urbanization and carbon emissions can provide a decision-making reference to realize China's goal of carbon neutrality. This article examines the spatiotemporal patterns of urbanization and carbon emissions in the Yangtze River Delta urban agglomeration from 2008 to 2018. A complete set of variables is considered to construct relevant land and ecological urbanization variables, and the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model and spatial Durbin model (SDM) are adopted to explore the impact of various driving factors on carbon emissions. The results indicate that (1) during the study period, the carbon emissions in the Yangtze River Delta urban agglomeration exhibited a fluctuating increase and that the incremental carbon emissions followed a downward trend. (2) Carbon emissions exhibited a positive spatial correlation. Cold- and hotspot areas indicated a three-gradient pattern from west to east, and a concentric circle radiation pattern occurred with Shanghai as the core. Carbon emissions were spatially imbalanced, but the centre of gravity slightly fluctuated, with a total migration distance of 38.48 km, indicating a migration trend towards the southeast. (3) Regarding the two considered dimensions of urbanization, all driving factors except urbanization played a role in carbon emission enhancement. Consequently, for every 1% increase in economic factors, the carbon emissions correspondingly increased by 0.43-0.57%. Hence, economic factors are the most important factors promoting increased carbon emissions. In the ecological urbanization dimension, urbanization caused a non-significant decrease in carbon emissions, while there was no spillover effect on carbon emissions in neighbouring areas. Accordingly, carbon emission reduction efforts should promote the transformation of urbanization from a land-driven process to an ecologically driven process and realize the synergies among carbon emission reductions, urban development, and land use.


Assuntos
Carbono , Rios , Carbono/análise , China , Cidades , Desenvolvimento Econômico , Monitoramento Ambiental , Urbanização
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