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1.
Materials (Basel) ; 17(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38730763

RESUMO

This study focuses on the prediction of concrete cover separation (CCS) in reinforced concrete beams strengthened by fiber-reinforced polymer (FRP) in flexure. First, machine learning models were constructed based on linear regression, support vector regression, BP neural networks, decision trees, random forests, and XGBoost algorithms. Secondly, the most suitable model for predicting CCS was identified based on the evaluation metrics and compared with the codes and the researcher's model. Finally, a parametric study based on SHapley Additive exPlanations (SHAP) was carried out, and the following conclusions were obtained: XGBoost is best-suited for the prediction of CCS and codes, and researchers' model accuracy needs to be improved and suffers from over or conservative estimation. The contributions of the concrete to the shear force and the yield strength of the reinforcement are the most important parameters for the CCS, where the shear force at the onset of CCS is approximately proportional to the contribution of the concrete to the shear force and approximately inversely proportional to the yield strength of the reinforcement.

2.
Sci Adv ; 10(20): eadl1947, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38748796

RESUMO

Forest canopy structural complexity (CSC) plays a crucial role in shaping forest ecosystem productivity and stability, but the precise nature of their relationships remains controversial. Here, we mapped the global distribution of forest CSC and revealed the factors influencing its distribution using worldwide light detection and ranging data. We find that forest CSC predominantly demonstrates significant positive relationships with forest ecosystem productivity and stability globally, although substantial variations exist among forest ecoregions. The effects of forest CSC on productivity and stability are the balanced results of biodiversity and resource availability, providing valuable insights for comprehending forest ecosystem functions. Managed forests are found to have lower CSC but more potent enhancing effects of forest CSC on ecosystem productivity and stability than intact forests, highlighting the urgent need to integrate forest CSC into the development of forest management plans for effective climate change mitigation.


Assuntos
Biodiversidade , Mudança Climática , Ecossistema , Florestas , Conservação dos Recursos Naturais , Árvores/crescimento & desenvolvimento
3.
Nat Commun ; 15(1): 4106, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750031

RESUMO

China's extensive planted forests play a crucial role in carbon storage, vital for climate change mitigation. However, the complex spatiotemporal dynamics of China's planted forest area and its carbon storage remain uncaptured. Here we reveal such changes in China's planted forests from 1990 to 2020 using satellite and field data. Results show a doubling of planted forest area, a trend that intensified post-2000. These changes lead to China's planted forest carbon storage increasing from 675.6 ± 12.5 Tg C in 1990 to 1,873.1 ± 16.2 Tg C in 2020, with an average rate of ~ 40 Tg C yr-1. The area expansion of planted forests contributed ~ 53% (637.2 ± 5.4 Tg C) of the total above increased carbon storage in planted forests compared with planted forest growth. This proactive policy-driven expansion of planted forests has catalyzed a swift increase in carbon storage, aligning with China's Carbon Neutrality Target for 2060.

4.
Quant Imaging Med Surg ; 14(4): 2828-2839, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617175

RESUMO

Background: Improved coronary physiological function after percutaneous coronary intervention (PCI) has been shown to improve prognosis in stable ischaemic heart disease, but has not yet been explored in ST-segment elevated myocardial infarction (STEMI). The study sought to determine whether an improvement in the quantitative flow ratio (QFR) could improve the prognosis of STEMI patients undergoing primary PCI. Methods: Patients diagnosed with STEMI who were receiving primary PCI were recruited for the study. Those with thrombolysis in myocardial infarction (TIMI) flow <2 after wiring were excluded. The ΔQFR was calculated using the following formula: ΔQFR = post-PCI QFR - pre-stent QFR. The primary endpoint was the composite event, including recurrent myocardial infarction (MI) and acute heart failure (AHF). Results: In total, 515 STEMI patients with a median follow-up of 364 days were enrolled in the study. Based on the cut-off value from the receiver operator characteristic (ROC) curve, the patients were divided into the following two groups: the lower ΔQFR group (≤0.25, N=332); and the normal ΔQFR group (>0.25, N=183). Patients with a lower ΔQFR had a relatively higher rate of MI/AHF (10.5% vs. 4.4%, P=0.019) and AHF (7.2% vs. 2.7%, P=0.044). A lower ΔQFR was significantly associated with a higher incidence of MI/AHF [hazard ratio (HR) =2.962, 95% confidence interval (CI): 1.358-6.459, P=0.006, respectively] after adjusting for potential confounders. Pre-stent angiographic microvascular resistance [odds ratio (OR) =1.027, 95% CI: 1.022-1.033, P<0.001] and the stent-to-vessel diameter ratio <1.13 (OR =1.766, 95% CI: 1.027-3.071, P=0.04) were independent predictors of a lower ΔQFR. Conclusions: An insufficient improvement in the QFR contributes to worsening outcomes and might be a useful tool for risk stratification in STEMI.

5.
Science ; 384(6693): 301-306, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38635711

RESUMO

China's massive wave of urbanization may be threatened by land subsidence. Using a spaceborne synthetic aperture radar interferometry technique, we provided a systematic assessment of land subsidence in all of China's major cities from 2015 to 2022. Of the examined urban lands, 45% are subsiding faster than 3 millimeters per year, and 16% are subsiding faster than 10 millimeters per year, affecting 29 and 7% of the urban population, respectively. The subsidence appears to be associated with a range of factors such as groundwater withdrawal and the weight of buildings. By 2120, 22 to 26% of China's coastal lands will have a relative elevation lower than sea level, hosting 9 to 11% of the coastal population, because of the combined effect of city subsidence and sea-level rise. Our results underscore the necessity of enhancing protective measures to mitigate potential damages from subsidence.

6.
Microb Pathog ; 191: 106666, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38685360

RESUMO

It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of resistant-bacteria induced by clinically recommended and prophylactic dose drugs remain largely unclear. This study aimed to observe the trends of drug resistance of the bacitracin-susceptible Staphylococcus aureus strain FS127 under exposure to bacitracin (BAC), which were induced in vitro and in chicken gut. Antimicrobial susceptibility testing was used to detect the susceptibility of S. aureus induced in vitro and in the chicken gut to gentamicin, chloramphenicol, tetracycline, doxycycline, penicillin and chloramphenicol. The research results showed that bacitracin could induce drug resistance in S. aureus both in vitro and in vivo. The bacitracin-resistance rate of S. aureus isolated from chicken gut was positively correlated with the dose and time of bacitracin administration. The findings revealed that bacitracin-resistant S. aureus induced in vivo had enhanced susceptibility to chloramphenicol but no such change in vitro. Meanwhile, RT-qPCR assay was used to detect the expression levels of vraD, braD, braR and bacA in typical strains with different bacitracin-resistance levels. It was found that BacA may play a key role in the bacitracin resistance of S. aureus. In conclusion, this work reveals the characteristics and mechanism of bacitracin-resistant S. aureus induced by bacitracin in vivo and in vitro respectively.

7.
Sci Adv ; 10(12): eadk8521, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38507491

RESUMO

The type I adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter DppABCD is believed to be responsible for the import of exogenous heme as an iron source into the cytoplasm of the human pathogen Mycobacterium tuberculosis (Mtb). Additionally, this system is also known to be involved in the acquisition of tri- or tetra-peptides. Here, we report the cryo-electron microscopy structures of the dual-function Mtb DppABCD transporter in three forms, namely, the apo, substrate-bound, and ATP-bound states. The apo structure reveals an unexpected and previously uncharacterized assembly mode for ABC importers, where the lipoprotein DppA, a cluster C substrate-binding protein (SBP), stands upright on the translocator DppBCD primarily through its hinge region and N-lobe. These structural data, along with biochemical studies, reveal the assembly of DppABCD complex and the detailed mechanism of DppABCD-mediated transport. Together, these findings provide a molecular roadmap for understanding the transport mechanism of a cluster C SBP and its translocator.


Assuntos
Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/metabolismo , Microscopia Crioeletrônica , Proteínas de Bactérias/metabolismo , Transportadores de Cassetes de Ligação de ATP/química , Trifosfato de Adenosina/metabolismo
8.
Plant Cell Rep ; 43(4): 102, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499710

RESUMO

KEY MESSAGE: The transcriptomic, phenotypic and metabolomic analysis of transgenic plants overexpressing GhMPK31 in upland cotton revealed the regulation of H2O2 burst and the synthesis of defensive metabolites by GhMPK31. Mitogen-activated protein kinases (MAPKs) are a crucial class of protein kinases, which play an essential role in various biological processes in plants. Upland cotton (G. hirsutum) is the most widely cultivated cotton species with high economic value. To gain a better understanding of the role of the MAPK gene family, we conducted a comprehensive analysis of the MAPK gene family in cotton. In this study, a total of 55 GhMPK genes were identified from the whole genome of G. hirsutum. Through an investigation of the expression patterns under diverse stress conditions, we discovered that the majority of GhMPK family members demonstrated robust responses to abiotic stress, pathogen stress and pest stress. Furthermore, the overexpression of GhMPK31 in cotton leaves led to a hypersensitive response (HR)-like cell death phenotype and impaired the defense capability of cotton against herbivorous insects. Transcriptome and metabolomics data analysis showed that overexpression of GhMPK31 enhanced the expression of H2O2-related genes and reduced the accumulation of defensive related metabolites. The direct evidence of GhMPK31 interacting with GhRBOHB (H2O2-generating protein) were found by Y2H, BiFC, and LCI. Therefore, we propose that the increase of H2O2 content caused by overexpression of GhMPK31 resulted in HR-like cell death in cotton leaves while reducing the accumulation of defensive metabolites, ultimately leading to a decrease in the defense ability of cotton against herbivorous insects. This study provides valuable insights into the function of MAPK genes in plant resistance to herbivorous insects.


Assuntos
Gossypium , Peróxido de Hidrogênio , Gossypium/metabolismo , Peróxido de Hidrogênio/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia
9.
Nat Struct Mol Biol ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548954

RESUMO

Oligopeptide permease, OppABCD, belongs to the type I ABC transporter family. Its role is to import oligopeptides into bacteria for nutrient uptake and to modulate the host immune response. OppABCD consists of a cluster C substrate-binding protein (SBP), OppA, membrane-spanning OppB and OppC subunits, and an ATPase, OppD, that contains two nucleotide-binding domains (NBDs). Here, using cryo-electron microscopy, we determined the high-resolution structures of Mycobacterium tuberculosis OppABCD in the resting state, oligopeptide-bound pre-translocation state, AMPPNP-bound pre-catalytic intermediate state and ATP-bound catalytic intermediate state. The structures show an assembly of a cluster C SBP with its ABC translocator and a functionally required [4Fe-4S] cluster-binding domain in OppD. Moreover, the ATP-bound OppABCD structure has an outward-occluded conformation, although no substrate was observed in the transmembrane cavity. Here, we reveal an oligopeptide recognition and translocation mechanism of OppABCD, which provides a perspective on how this and other type I ABC importers facilitate bulk substrate transfer across the lipid bilayer.

10.
Redox Biol ; 72: 103130, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522110

RESUMO

Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.


Assuntos
NAD(P)H Desidrogenase (Quinona) , Oxirredução , Estresse Oxidativo , Pró-Fármacos , Sulfetos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Estresse Oxidativo/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/metabolismo , Oxirredução/efeitos dos fármacos , Sulfetos/química , Sulfetos/farmacologia , Humanos , Animais , Espectrometria de Massas em Tandem , Cisplatino/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Camundongos
11.
Comput Biol Med ; 171: 108186, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38394804

RESUMO

BACKGROUND: Segmenting colorectal polyps presents a significant challenge due to the diverse variations in their size, shape, texture, and intricate backgrounds. Particularly demanding are the so-called "camouflaged" polyps, which are partially concealed by surrounding tissues or fluids, adding complexity to their detection. METHODS: We present CPSNet, an innovative model designed for camouflaged polyp segmentation. CPSNet incorporates three key modules: the Deep Multi-Scale-Feature Fusion Module, the Camouflaged Object Detection Module, and the Multi-Scale Feature Enhancement Module. These modules work collaboratively to improve the segmentation process, enhancing both robustness and accuracy. RESULTS: Our experiments confirm the effectiveness of CPSNet. When compared to state-of-the-art methods in colon polyp segmentation, CPSNet consistently outperforms the competition. Particularly noteworthy is its performance on the ETIS-LaribPolypDB dataset, where CPSNet achieved a remarkable 2.3% increase in the Dice coefficient compared to the Polyp-PVT model. CONCLUSION: In summary, CPSNet marks a significant advancement in the field of colorectal polyp segmentation. Its innovative approach, encompassing multi-scale feature fusion, camouflaged object detection, and feature enhancement, holds considerable promise for clinical applications.


Assuntos
Pólipos do Colo , Humanos , Pólipos do Colo/diagnóstico por imagem , Colo , Processamento de Imagem Assistida por Computador
12.
Sci Rep ; 14(1): 2568, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297076

RESUMO

The freshness of vegetable soybean (VS) is an important indicator for quality evaluation. Currently, deep learning-based image recognition technology provides a fast, efficient, and low-cost method for analyzing the freshness of food. The RGB (red, green, and blue) image recognition technology is widely used in the study of food appearance evaluation. In addition, the hyperspectral image has outstanding performance in predicting the nutrient content of samples. However, there are few reports on the research of classification models based on the fusion data of these two sources of images. We collected RGB and hyperspectral images at four different storage times of VS. The ENVI software was adopted to extract the hyperspectral information, and the RGB images were reconstructed based on the downsampling technology. Then, the one-dimensional hyperspectral data was transformed into a two-dimensional space, which allows it to be overlaid and concatenated with the RGB image data in the channel direction, thereby generating fused data. Compared with four commonly used machine learning models, the deep learning model ResNet18 has higher classification accuracy and computational efficiency. Based on the above results, a novel classification model named ResNet-R &H, which is based on the residual networks (ResNet) structure and incorporates the fusion data of RGB and hyperspectral images, was proposed. The ResNet-R &H can achieve a testing accuracy of 97.6%, which demonstrates a significant enhancement of 4.0% and 7.2% compared to the distinct utilization of hyperspectral data and RGB data, respectively. Overall, this research is significant in providing a unique, efficient, and more accurate classification approach in evaluating the freshness of vegetable soybean. The method proposed in this study can provide a theoretical reference for classifying the freshness of fruits and vegetables to improve classification accuracy and reduce human error and variability.


Assuntos
Glycine max , Verduras , Humanos , Frutas , Aprendizado de Máquina , Nutrientes
13.
J Exp Biol ; 227(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38284767

RESUMO

Heart rate is a crucial physiological indicator for fish, but current measurement methods are often invasive or require delicate manipulation. In this study, we introduced two non-invasive and easy-to-operate methods based on photoplethysmography, namely reflectance-type photoplethysmography (PPG) and remote photoplethysmography (rPPG), which we applied to the large yellow croaker (Larimichthys crocea). PPG showed perfect synchronization with electrocardiogram (ECG), with a Pearson's correlation coefficient of 0.99999. For rPPG, the results showed good agreement with ECG. Under active provision of green light, the Pearson's correlation coefficient was 0.966, surpassing the value of 0.947 under natural light. Additionally, the root mean square error was 0.810, which was lower than the value of 1.30 under natural light, indicating not only that the rPPG method had relatively high accuracy but also that green light may have the potential to further improve its accuracy.


Assuntos
Eletrocardiografia , Fotopletismografia , Frequência Cardíaca/fisiologia , Fotopletismografia/métodos , Processamento de Sinais Assistido por Computador
14.
Front Cardiovasc Med ; 10: 1247053, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38155983

RESUMO

Background: The relationship between the optical flow ratio (OFR) and clinical outcomes in patients with coronary artery disease (CAD) after percutaneous coronary stent implantation (PCI) remains unknown. Objective: To examine the correlation between post-PCI OFR and clinical outcomes in patients with CAD following PCI. Methods: Patients who underwent optical coherence tomography (OCT) guided PCI at Guangdong Provincial People's Hospital were retrospectively and continuously enrolled. Clinical data, post-PCI OCT characteristics, and OFR measurements were collected and analyzed to identify predictors of target vessel failure (TVF) after PCI. Results: Among 354 enrolled patients, 26 suffered TVF during a median follow-up of 484 (IQR: 400-774) days. Post-PCI OFR was significantly lower in the TVF group than in the non-TVF group (0.89 vs. 0.93; P = 0.001). In multivariable Cox regression analysis, post-PCI OFR (HR per 0.1 increase: 0.60; 95% CI: 0.41-0.89; P = 0.011), large stent edge dissection (HR: 3.85; 95% CI: 1.51-9.84; P = 0.005) and thin-cap fibroatheroma (TCFA) (HR: 2.95; 95% CI: 1.19-7.35; P = 0.020) in the non-stented segment were independently associated with TVF. In addition, the inclusion of post-PCI OFR to baseline characteristics and post-PCI OCT findings improved the predictive power of the model to distinguish subsequent TVF after PCI (0.838 vs. 0.796; P = 0.028). Conclusion: The post-PCI OFR serves as an independent determinant of risk for TVF in individuals with CAD after PCI. The inclusion of post-PCI OFR assessments, alongside baseline characteristics and post-PCI OCT findings, substantially enhances the capacity to differentiate the subsequent manifestation of TVF in CAD patients following PCI.

15.
Nat Commun ; 14(1): 7467, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978191

RESUMO

Increasing drought frequency and severity in a warming climate threaten forest ecosystems with widespread tree deaths. Canopy structure is important in regulating tree mortality during drought, but how it functions remains controversial. Here, we show that the interplay between tree size and forest structure explains drought-induced tree mortality during the 2012-2016 California drought. Through an analysis of over one million trees, we find that tree mortality rate follows a "negative-positive-negative" piecewise relationship with tree height, and maintains a consistent negative relationship with neighborhood canopy structure (a measure of tree competition). Trees overshadowed by tall neighboring trees experienced lower mortality, likely due to reduced exposure to solar radiation load and lower water demand from evapotranspiration. Our findings demonstrate the significance of neighborhood canopy structure in influencing tree mortality and suggest that re-establishing heterogeneity in canopy structure could improve drought resiliency. Our study also indicates the potential of advances in remote-sensing technologies for silvicultural design, supporting the transition to multi-benefit forest management.


Assuntos
Ecossistema , Árvores , Árvores/fisiologia , Secas , Florestas , Água
16.
Structure ; 31(10): 1158-1165.e3, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37619560

RESUMO

The human pathogen, Mycobacterium tuberculosis (Mtb) relies heavily on trehalose for both survival and pathogenicity. The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the only trehalose import pathway in Mtb. Conformational dynamics of ABC transporters is an important feature to explain how they operate, but experimental structures are determined in a static environment. Therefore, a detailed transport mechanism cannot be elucidated because there is a lack of intermediate structures. Here, we used single-particle cryo-electron microscopy (cryo-EM) to determine the structure of the Mycobacterium smegmatis (M. smegmatis) trehalose-specific importer LpqY-SugABC complex in five different conformations. These structures have been classified and reconstructed from a single cryo-EM dataset. This study allows a comprehensive understanding of the trehalose recycling mechanism in Mycobacteria and also demonstrates the potential of single-particle cryo-EM to explore the dynamic structures of other ABC transporters and molecular machines.

17.
Proc Natl Acad Sci U S A ; 120(35): e2307625120, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37603751

RESUMO

Trehalose plays a crucial role in the survival and virulence of the deadly human pathogen Mycobacterium tuberculosis (Mtb). The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the sole pathway for trehalose to enter Mtb. The substrate-binding protein, LpqY, which forms a stable complex with the translocator SugABC, recognizes and captures trehalose and its analogues in the periplasmic space, but the precise molecular mechanism for this process is still not well understood. This study reports a 3.02-Å cryoelectron microscopy structure of trehalose-bound Mtb LpqY-SugABC in the pretranslocation state, a crystal structure of Mtb LpqY in a closed form with trehalose bound and five crystal structures of Mtb LpqY in complex with different trehalose analogues. These structures, accompanied by substrate-stimulated ATPase activity data, reveal how LpqY recognizes and binds trehalose and its analogues, and highlight the flexibility in the substrate binding pocket of LpqY. These data provide critical insights into the design of trehalose analogues that could serve as potential molecular probe tools or as anti-TB drugs.


Assuntos
Mycobacterium tuberculosis , Humanos , Microscopia Crioeletrônica , Trealose , Transportadores de Cassetes de Ligação de ATP , Sondas Moleculares
18.
Cell Signal ; 110: 110844, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37544634

RESUMO

Non-SMC condensin II complex subunit G2 (NCAPG2) is one of the three non-SMC subunits in condensin II, which plays a vital role in regulating chromosome condensation and segregation. Although the tumor-promoting role of NCAPG2 has been reported in several solid malignancies, its function in breast invasive carcinoma (BRCA) remains unknown. Data both from GEPIA and GSE36295 indicated that NCAPG2 mRNA expression was abnormally upregulated in cancer tissues, which was further verified in 40 paired BRCA and para-carcinoma samples. Kaplan-Meier Plotter further illustrated that BRCA patients with higher NCAPG2 expression have a poorer prognosis. Functional experiments carried out in two BRCA cell lines (MCF-7 and T-47D) showed that NCAPG2-silenced BRCA cells acquired less aggressive behavior - weakened growth and metastasis both in vitro and in vivo. Label-free proteomics quantified the protein expression patterns in MCF-7 cells, and the results revealed 684 differentially expressed proteins (|log2FC| > 1 and P < 0.05) downstream to NCAPG2. Interestingly, poly(C)-binding protein 2 (PCBP2), an RNA binding protein previously known to increase RNA stability of its target genes, was found to directly bind to and protect NCAPG2 mRNA from degradation-PCBP2 knockdown accelerated the degradation half-life time of NCAPG2 mRNA from approximately 8 h to 5 h. Taken together, our study indicates that NCAPG2 acts as a novel contributor to BRCA growth and metastasis under the regulation of PCBP2, providing insights into BRCA treatment.


Assuntos
Neoplasias da Mama , Carcinoma , Humanos , Feminino , Linhagem Celular Tumoral , Neoplasias da Mama/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , Proteínas Cromossômicas não Histona/metabolismo
19.
J Neurooncol ; 164(1): 157-170, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37523046

RESUMO

OBJECTIVE: Recent studies have increasingly shown that glioma stem cells (GSCs) are extremely important for developing and treating glioblastoma multiforme (GBM). The Broad-complex, Tram-track, and Bric-a-brac protein family is functionally related to a variety of tumor stem cells, and the role of SPOPL as a member of this family in GSCs deserves to be investigated. METHODS: To investigate the expression of SPOPL in GSCs and its impact on the prognosis of GBM patients by using clinical specimens, patient-derived primary GSCs and public databases. In vivo and in vitro, the effect of SPOPL on the proliferation, self-renewal, and differentiation ability of GSCs was explored. Probing the mechanism by which SPOPL affects the biological function of GSCs using RNA sequencing (RNA-seq) and rescue experiments. RESULTS: The expression of SPOPL was significantly upregulated in GSCs and GBM, and patients with high SPOPL expression had a poorer prognosis. SPOPL enhanced the proliferation and self-renewal ability of GSCs and enhanced the tumorigenicity of GSCs. The Notch signaling pathway was significantly inhibited in SPOPL knockdown GSCs. Activation or inhibition of the Notch signaling pathway rescued changes in the biological function of GSCs caused by altered SPOPL expression. CONCLUSION: SPOPL can be used as a potential prognostic biomarker for GBM in clinical work and promotes the proliferation and stemness of GSCs by activating the Notch signaling pathway, which may be a potential molecule for targeting GSCs to treat GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Glioblastoma/patologia , Glioma/patologia , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/genética
20.
Carcinogenesis ; 44(5): 369-382, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37326327

RESUMO

Downregulation of ARHGAP25 was found in the tumor samples from breast cancer patients and five breast cancer cell lines. However, its precise role and molecular mechanisms in breast cancer remain completely unknown. Herein, we found that knockdown of ARHGAP25 in breast cancer cells promoted proliferation, migration and invasion of breast cancer cells. Mechanistically, ARHGAP25 silence facilitated the activation of the Wnt/ß-catenin pathway and the upregulation of its downstream molecules (including c-Myc, Cyclin D1, PCNA, MMP2, MMP9, Snail and ASCL2) by directly regulating Rac1/PAK1 in breast cancer cells. In vivo xenograft experiments indicated ARHGAP25 silence promoted tumor growth and activated the Wnt/ß-catenin pathway. In contrast, overexpression of ARHGAP25 in vitro and in vivo impeded all of the above cancer properties. Intriguingly, ASCL2, a downstream target of the Wnt/ß-catenin pathway, transcriptionally repressed the expression of ARHGAP25 and therefore constituted a negative feedback loop. Moreover, bioinformatics analysis indicated that ARHGAP25 was significantly correlated with tumor immune cell infiltration and the survival of patients with different immune cell subgroups in breast cancer. Collectively, our work revealed that ARHGAP25 suppressed tumor progression of breast cancer. It provides a novel insight for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Proteínas Ativadoras de GTPase , beta Catenina , Feminino , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , beta Catenina/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Retroalimentação , Regulação Neoplásica da Expressão Gênica , Proteínas Ativadoras de GTPase/genética , Regulação para Cima , Via de Sinalização Wnt/genética
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