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1.
Cell ; 185(16): 2961-2974.e19, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35839760

RESUMO

Wheat crops are frequently devastated by pandemic stripe rust caused by Puccinia striiformis f. sp. tritici (Pst). Here, we identify and characterize a wheat receptor-like cytoplasmic kinase gene, TaPsIPK1, that confers susceptibility to this pathogen. PsSpg1, a secreted fungal effector vital for Pst virulence, can bind TaPsIPK1, enhance its kinase activity, and promote its nuclear localization, where it phosphorylates the transcription factor TaCBF1d for gene regulation. The phosphorylation of TaCBF1d switches its transcriptional activity on the downstream genes. CRISPR-Cas9 inactivation of TaPsIPK1 in wheat confers broad-spectrum resistance against Pst without impacting important agronomic traits in two years of field tests. The disruption of TaPsIPK1 leads to immune priming without constitutive activation of defense responses. Taken together, TaPsIPK1 is a susceptibility gene known to be targeted by rust effectors, and it has great potential for developing durable resistance against rust by genetic modifications.


Assuntos
Basidiomycota , Triticum , Basidiomycota/genética , Basidiomycota/metabolismo , Doenças das Plantas , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Triticum/genética , Triticum/metabolismo , Triticum/microbiologia , Virulência/genética
2.
Plant Cell ; 34(5): 1784-1803, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-34999846

RESUMO

Reactive oxygen species (ROS) are vital for plant immunity and regulation of their production is crucial for plant health. While the mechanisms that elicit ROS production have been relatively well studied, those that repress ROS generation are less well understood. Here, via screening Brachypodium distachyon RNA interference mutants, we identified BdWRKY19 as a negative regulator of ROS generation whose knockdown confers elevated resistance to the rust fungus Puccinia brachypodii. The three wheat paralogous genes TaWRKY19 are induced during infection by virulent P. striiformis f. sp. tritici (Pst) and have partially redundant roles in resistance. The stable overexpression of TaWRKY19 in wheat increased susceptibility to an avirulent Pst race, while mutations in all three TaWRKY19 copies conferred strong resistance to Pst by enhancing host plant ROS accumulation. We show that TaWRKY19 is a transcriptional repressor that binds to a W-box element in the promoter of TaNOX10, which encodes an NADPH oxidase and is required for ROS generation and host resistance to Pst. Collectively, our findings reveal that TaWRKY19 compromises wheat resistance to the fungal pathogen and suggest TaWRKY19 as a potential target to improve wheat resistance to the commercially important wheat stripe rust fungus.


Assuntos
Basidiomycota , Triticum , Basidiomycota/metabolismo , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Triticum/metabolismo
3.
Proc Natl Acad Sci U S A ; 119(20): e2122952119, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35561215

RESUMO

SignificanceQuantum anomalous Hall effect (QAHE) and magnetic skyrmion (SK), as two typical topological states in momentum (K) and real (R) spaces, attract much interest in condensed matter physics. However, the interplay between these two states remains to be explored. We propose that the interplay between QAHE and SK may generate an RK joint topological skyrmion (RK-SK), characterized by the SK surrounded by nontrivial chiral boundary states (CBSs). Furthermore, the emerging external field-tunable CBS in RK-SK could create additional degrees of freedom for SK manipulations, beyond the traditional SK. Meanwhile, external field can realize a rare topological phase transition between K and R spaces. Our work opens avenues for exploring unconventional quantum states and topological phase transitions in different spaces.

4.
Nano Lett ; 24(36): 11246-11254, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39207036

RESUMO

Magnetic skyrmions are swirl-like spin configurations that present topological properties, which have great potential as information carriers for future high-density and low-energy-consumption devices. The optimization of skyrmion-hosting materials that can be integrated with semiconductor-based circuits is the primary challenge for their industrialization. Two-dimensional van der Waals ferromagnets are emerging materials that have excellent carrier mobility and compatibility with integrated circuits, making them an ideal candidate for spintronic devices. Here, we report the realization of skyrmions at above room temperature in the 2D ferromagnet Fe3GaTe2. The thickness tunability of their skyrmion size and the formation of the skyrmion lattice are revealed. Furthermore, we demonstrate that the skyrmions can be moved by a low-density current at room temperature, together with an apparent skyrmion Hall effect, which is consistent with our quantitative micromagnetic simulation. Our work offers a promising 2D material platform for harnessing magnetic skyrmions in practical device applications.

5.
Cancer ; 130(3): 356-374, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37861451

RESUMO

BACKGROUND: This study aimed to determine the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an N6 -methyladinosine reader, in the progression and distant metastasis of breast cancer. METHODS: IGF2BP3 expression was assessed in 152 pairs of breast cancer and adjacent normal tissue (ANT) by real-time quantitative polymerase chain reaction and in 561 cases of breast cancer and 163 cases of ANT by immunohistochemistry. Survival curves were estimated using the Kaplan-Meier method and then compared statistically using the log-rank test. The prognostic role of IGF2BP3 was determined by Cox regression analysis. RESULTS: Analysis of public gene data sets revealed that IGF2PB3 predicted distant metastasis in breast cancer and was highly correlated with brain metastasis. In the clinical retrospective cohort, the positive rate of IGF2BP3 increased gradually with breast cancer progression. Positive IGF2BP3 expression was related to poor distant metastasis-free survival (DMFS, p = .030) and Cox regression analysis identified IGF2BP3 as an independent risk factor for DMFS (hazard ratio, 1.876; 95% confidence interval, 1.128-3.159; p = .019). Positive IGF2BP3 expression was markedly related to breast cancer brain metastasis (p = .011) but not to lung and bone metastasis. Moreover, patients with IGF2BP3-positive brain metastasis had lower survival than patients with IGF2BP3-negative brain metastasis (p = .041). Gene expression profiling results indicated that high IGF2BP3 expression was associated with the PD-1 checkpoint pathway, HER2-HER3 signaling, and epithelial-mesenchymal transition. CONCLUSIONS: IGF2BP3 may serve as a novel predictive biomarker and a potential therapeutic target for breast cancer brain metastasis, which warrants further investigation. PLAIN LANGUAGE SUMMARY: As an m6 A reader, IGF2BP3 is dysregulated and implicated in various cancers but its role in breast cancer has not been fully clarified. In this study, we found that IGF2BP3 was upregulated in breast cancer and IGF2BP3 expression increased gradually during breast cancer progression. IGF2BP3 expression exerted no effect on the overall survival and breast cancer-specific survival of breast cancer patients; however, IGF2BP3-positive patients were more likely to develop distant metastasis than IGF2BP3-negative patients. In addition, IGF2BP3 was associated with brain-specific metastasis in breast cancer patients. These findings warrant further investigation because they provide a rationale for novel predictive or therapeutic approaches.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Feminino , Humanos , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias da Mama/patologia , Prognóstico , Estudos Retrospectivos
6.
J Transl Med ; 22(1): 423, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704606

RESUMO

BACKGROUND: Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are known to play a crucial role in the growth, migration, recurrence, and drug resistance of tumor cells, particularly in triple-negative breast cancer (TNBC). This study aims to investigate stemness-related lncRNAs (SRlncRNAs) as potential prognostic indicators for TNBC patients. METHODS: Utilizing RNA sequencing data and corresponding clinical information from the TCGA database, and employing Weighted Gene Co-expression Network Analysis (WGCNA) on TNBC mRNAsi sourced from an online database, stemness-related genes (SRGs) and SRlncRNAs were identified. A prognostic model was developed using univariate Cox and LASSO-Cox analysis based on SRlncRNAs. The performance of the model was evaluated using Kaplan-Meier analysis, ROC curves, and ROC-AUC. Additionally, the study delved into the underlying signaling pathways and immune status associated with the divergent prognoses of TNBC patients. RESULTS: The research identified a signature of six SRlncRNAs (AC245100.6, LINC02511, AC092431.1, FRGCA, EMSLR, and MIR193BHG) for TNBC. Risk scores derived from this signature were found to correlate with the abundance of plasma cells. Furthermore, the nominated chemotherapy drugs for TNBC exhibited considerable variability between different risk score groups. RT-qPCR validation confirmed abnormal expression patterns of these SRlncRNAs in TNBC stem cells, affirming the potential of the SRlncRNAs signature as a prognostic biomarker. CONCLUSION: The identified signature not only demonstrates predictive power in terms of patient outcomes but also provides insights into the underlying biology, signaling pathways, and immune status associated with TNBC prognosis. The findings suggest the possibility of guiding personalized treatments, including immune checkpoint gene therapy and chemotherapy strategies, based on the risk scores derived from the SRlncRNA signature. Overall, this research contributes valuable knowledge towards advancing precision medicine in the context of TNBC.


Assuntos
Simulação por Computador , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/imunologia , Prognóstico , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Feminino , Resultado do Tratamento , Animais , Estimativa de Kaplan-Meier , Redes Reguladoras de Genes , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Curva ROC , Perfilação da Expressão Gênica , Modelos de Riscos Proporcionais , Imunidade/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
7.
J Transl Med ; 22(1): 607, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951896

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a prevalent malignancy with complex heterogeneity within epithelial cells, which plays a crucial role in tumor progression and immune regulation. Yet, the clinical importance of the malignant epithelial cell-related genes (MECRGs) in ccRCC remains insufficiently understood. This research aims to undertake a comprehensive investigation into the functions and clinical relevance of malignant epithelial cell-related genes in ccRCC, providing valuable understanding of the molecular mechanisms and offering potential targets for treatment strategies. Using data from single-cell sequencing, we successfully identified 219 MECRGs and established a prognostic model MECRGS (MECRGs' signature) by synergistically analyzing 101 machine-learning models using 10 different algorithms. Remarkably, the MECRGS demonstrated superior predictive performance compared to traditional clinical features and 92 previously published signatures across six cohorts, showcasing its independence and accuracy. Upon stratifying patients into high- and low-MECRGS subgroups using the specified cut-off threshold, we noted that patients with elevated MECRGS scores displayed characteristics of an immune suppressive tumor microenvironment (TME) and showed worse outcomes after immunotherapy. Additionally, we discovered a distinct ccRCC tumor cell subtype characterized by the high expressions of PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) and SAA1 (Serum Amyloid A1), which we further validated in the Renji tissue microarray (TMA) cohort. Lastly, 'Cellchat' revealed potential crosstalk patterns between these cells and other cell types, indicating their potential role in recruiting CD163 + macrophages and regulatory T cells (Tregs), thereby establishing an immunosuppressive TME. PLOD2 + SAA1 + cancer cells with intricate crosstalk patterns indeed show promise for potential therapeutic interventions.


Assuntos
Carcinoma de Células Renais , Células Epiteliais , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Microambiente Tumoral , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Microambiente Tumoral/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Prognóstico , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Masculino , Perfilação da Expressão Gênica , Aprendizado de Máquina
8.
J Transl Med ; 22(1): 12, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166947

RESUMO

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men worldwide, and its incidence has risen substantially in recent years. Therefore, there is an urgent need to identify novel biomarkers and precise therapeutic targets for managing PCa progression and recurrence. METHODS: We investigated the clinical significance of NCAPG2 in PCa by exploring public datasets and our tissue microarray. Receiver operating characteristic (ROC) curve and survival analyses were performed to evaluate the correlation between NCAPG2 and PCa progression. Cell proliferation, wound healing, transwell, flow cytometry, cell cycle, tumor sphere formation, immunofluorescence (IF), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP) assays were conducted to further elucidate the molecular mechanism of NCAPG2 in PCa. Subcutaneous and orthotopic xenograft models were applied to investigate the effects of NCAPG2 on PCa proliferation in vivo. Tandem mass tag (TMT) quantitative proteomics was utilized to detect proteomic changes under NCAPG2 overexpression. RESULTS: NCAPG2 was significantly upregulated in PCa, and its overexpression was associated with PCa progression and unfavorable prognosis. Knockdown of NCAPG2 inhibited the malignant behavior of PCa cells, whereas its overexpression promoted PCa aggressiveness. NCAPG2 depletion attenuated the development and growth of PCa in vivo. TMT quantitative proteomics analyses indicated that c-MYC activity was strongly correlated with NCAPG2 expression. The malignancy-promoting effect of NCAPG2 in PCa was mediated via c-MYC. NCAPG2 could directly bind to STAT3 and induce STAT3 occupancy on the MYC promoter, thus to transcriptionally activate c-MYC expression. Finally, we identified that NCAPG2 was positively correlated with cancer stem cell (CSC) markers and enhanced self-renewal capacity of PCa cells. CONCLUSIONS: NCAPG2 is highly expressed in PCa, and its level is significantly associated with PCa prognosis. NCAPG2 promotes PCa malignancy and drives cancer stemness via the STAT3/c-MYC signaling axis, highlighting its potential as a therapeutic target for PCa.


Assuntos
Proteínas Cromossômicas não Histona , Neoplasias da Próstata , Proteínas Proto-Oncogênicas c-myc , Humanos , Masculino , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Cromossômicas não Histona/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteômica , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo
9.
BMC Microbiol ; 24(1): 300, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135165

RESUMO

BACKGROUND: Rhododendron delavayi is a natural shrub that is distributed at different elevations in the karst region of Bijie, China, and that has an important role in preventing land degradation in this region. In this study, we determined the soil mineral element contents and soil enzyme activities. The composition of the soil bacterial community of R. delavayi at three elevations (1448 m, 1643 m, and 1821 m) was analyzed by high-throughput sequencing, and the interrelationships among the soil bacterial communities, mineral elements, and enzyme activities were determined. RESULTS: The Shannon index of the soil bacterial community increased and then decreased with increasing elevation and was highest at 1643 m. Elevations increased the number of total nodes and edges of the soil bacterial community network, and more positive correlations at 1821 m suggested stronger intraspecific cooperation. Acidobacteria, Actinobacteria and Proteobacteria were the dominant phyla at all three elevations. The Mantel test and correlation analysis showed that Fe and soil urease significantly affected bacterial communities at 1448 m; interestingly, Chloroflexi was positively related to soil urease at 1448 m, and Actinobacteria was positively correlated with Ni and Zn at 1821 m. Fe and soil urease significantly influenced the bacterial communities at lower elevations, and high elevation (1821 m) enhanced the positive interactions of the soil bacteria, which might be a strategy for R. delavayi to adapt to high elevation environments. CONCLUSION: Elevation significantly influenced the composition of soil bacterial communities by affecting the content of soil mineral elements and soil enzyme activity.


Assuntos
Bactérias , Florestas , Rhododendron , Microbiologia do Solo , Solo , Solo/química , Rhododendron/microbiologia , China , Bactérias/classificação , Bactérias/genética , Bactérias/enzimologia , Bactérias/isolamento & purificação , Metais/análise , Actinobacteria/genética , Actinobacteria/enzimologia , Actinobacteria/isolamento & purificação , Actinobacteria/classificação , Microbiota , Urease/metabolismo , Acidobacteria/genética , Acidobacteria/isolamento & purificação , Acidobacteria/enzimologia , Acidobacteria/classificação , RNA Ribossômico 16S/genética , Filogenia , Sequenciamento de Nucleotídeos em Larga Escala
10.
Respir Res ; 25(1): 164, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622598

RESUMO

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.


Assuntos
Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/terapia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Remodelação Ventricular , Ecocardiografia , Doença Crônica , Artéria Pulmonar/diagnóstico por imagem
11.
Crit Rev Food Sci Nutr ; : 1-26, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39002141

RESUMO

Cancer-related complications pose significant challenges in the management and treatment of patients with malignancies. Several meta-analyses have indicated improving effects of probiotics on cancer complications, while some studies have reported contentious findings. The purpose of the present study was to evaluate the efficacy of probiotics in addressing cancer complications, including diarrhea, mucositis, and infections, following chemotherapy, radiotherapy, and surgery. Relevant studies were searched in the PubMed, Scopus, Embase and Web of Science databases and Google Scholar up to September 2023. All meta-analyses addressing the effects of probiotics on all cancer treatments-induced complications including infection, diarrhea and oral mucositis were included. The pooled results were calculated using a random-effects model. Analyses of subgroups, sensitivity and publication bias were also conducted. The results revealed that the probiotics supplementation was effective on reduction of total cancer complications (OR:0.53; 95% CI: 0.44, 0.62, p < 0.001; I2=79.0%, p < 0.001), total infection rate (OR:0.47; 95%CI: 0.41, 0.52, p < 0.001; I2= 48.8%, p < 0.001); diarrhea (OR:0.50; 95%CI: 0.44, 0.57, p < 0.001; I2=44.4%, p = 0.023) and severe diarrhea (OR: 0.4; 95%CI: 0.27, 0.56, p < 0.001; I2=31.3%, p = 0.178), oral mucositis (OR: 0.76; 95%CI: 0.58, 0.94, p < 0.001; I2=95.5%, p < 0.001) and severe oral mucositis (OR:0.65, 95%CI: 0.58, 0.72 p < 0.001; I2=22.1%, p = 0.274). Multi strain probiotic (OR:0.49; 95%CI: 0.32, 0.65, p < 0.001; I2=90.7%, p < 0.001) were more efficacious than single strain (OR:0.73; 95%CI: 0.66, 0.81, p < 0.001; I2=0.00%, p = 0.786). The findings of the current umbrella meta-analysis provide strong evidence that probiotic supplementation can reduce cancer complications.

12.
Microb Cell Fact ; 23(1): 269, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379932

RESUMO

BACKGROUND: Inorganic polyphosphate (polyP)-targeted polyphosphate kinase 1 (PPK1) has attracted much attention by virtue of its importance in bacterial pathogenicity and persistence, as well as its exclusive presence in microorganisms. However, only very few drugs have been found to be efficacious in inhibiting the Acinetobacter baumannii (A. baumannii) PPK1 protein. RESULTS: In this study, we identified Scutellarein (Scu), a potent PPK1 inhibitor that could significantly influence PPK1-regulated motility, biofilm formation, and bacterial persistence, which was further validated by the results of transcriptome analysis. Mechanistic explorations revealed that Scu achieved its enzyme inhibitory activity predominantly through direct engagement with the active center of PPK1. Moreover, the survival rate of Galleria mellonella larvae was increased by about 35% with 20 mg/kg of Scu treatment. The remarkable therapeutic benefits of Scu were also observed in the mouse pneumonia model, shown mainly by reduced bacterial colonization, pathological lesions, and inflammatory factors. CONCLUSION: Our results revealed that Scu could attenuate the pathogenicity and persistence of A. baumannii by interfering with its important kinase PPK1.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Fosfotransferases (Aceptor do Grupo Fosfato) , Acinetobacter baumannii/efeitos dos fármacos , Animais , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/antagonistas & inibidores , Camundongos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Mariposas/microbiologia , Feminino , Modelos Animais de Doenças
13.
Microb Cell Fact ; 23(1): 152, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790017

RESUMO

BACKGROUND: A novel plasmid-mediated resistance-nodulation-division (RND) efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae tremendously threatens the use of convenient therapeutic options in the post-antibiotic era, including the "last-resort" antibiotic tigecycline. RESULTS: In this work, the natural alkaloid harmaline was found to potentiate tigecycline efficacy (4- to 32-fold) against tmexCD1-toprJ1-positive K. pneumoniae, which also thwarted the evolution of tigecycline resistance. Galleria mellonella and mouse infection models in vivo further revealed that harmaline is a promising candidate to reverse tigecycline resistance. Inspiringly, harmaline works synergistically with tigecycline by undermining tmexCD1-toprJ1-mediated multidrug resistance efflux pump function via interactions with TMexCD1-TOprJ1 active residues and dissipation of the proton motive force (PMF), and triggers a vicious cycle of disrupting cell membrane integrity and metabolic homeostasis imbalance. CONCLUSION: These results reveal the potential of harmaline as a novel tigecycline adjuvant to combat hypervirulent K. pneumoniae infections.


Assuntos
Antibacterianos , Reposicionamento de Medicamentos , Harmalina , Infecções por Klebsiella , Klebsiella pneumoniae , Tigeciclina , Klebsiella pneumoniae/efeitos dos fármacos , Tigeciclina/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Animais , Camundongos , Antibacterianos/farmacologia , Harmalina/farmacologia , Harmalina/análogos & derivados , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Feminino
14.
J Nucl Cardiol ; : 102051, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39368661

RESUMO

BACKGROUND: The additional prognostic value of 18F-flurodeoxyglucose positron emission tomography (18F-FDG PET) myocardial ischemic memory imaging for patients with suspected unstable angina (UA) is not well established. This study aimed to determine whether 18F-FDG PET imaging provides incremental prognostic information for predicting major adverse cardiac events (MACEs) compared to clinical risk factors, Global Registry of Acute Coronary Events (GRACE) score, and coronary artery calcium score (CACS) in patients with suspected UA. METHODS: In this post hoc analysis of a prospective study, 265 patients suspected with UA (62.3% male, mean age: 65.0±9.4 years) were enrolled. 18F-FDG positivity was defined as focal or focal on diffuse uptake patterns. MACEs included cardiovascular death, acute myocardial infarction, heart failure, rehospitalization for UA, and stroke. Multivariable Cox regression was used to identify predictors of MACEs, and the incremental prognostic value of 18F-FDG PET imaging was assessed using the Concordance Index (C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Over a median follow-up of 25 months, 51 patients (19.2%) experienced MACEs. 18F-FDG positivity (hazard ratio [HR]=3.220, 95% confidence interval [CI]: 1.630-6.360, P<.001), as well as 18F-FDG standardized uptake ratio (HR=1.330, 95% CI: 1.131-1.564, P=.0006) and Extent (HR=1.045, 95% CI: 1.028-1.062, P<.0001), were independent predictors of MACE. The addition of 18F-FDG PET imaging significantly improved risk stratification beyond clinical factors, the GRACE score, and CACS, with improved C-index (.769 vs .688, P=.045), NRI (.324, P=.020), and IDI (.055, P=.027). CONCLUSION: 18F-FDG PET myocardial ischemic memory imaging significantly improves prognostic assessment for patients with suspected UA, providing valuable additional risk stratification beyond clinical risk factors, GRACE score, and CACS.

15.
Arch Sex Behav ; 53(9): 3365-3378, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134733

RESUMO

Attentional bias toward addiction-related stimuli has been implicated in the development and maintenance of addiction disorders. Several previous studies have reported an attentional bias toward pornographic cues in individuals with problematic pornography use (PPU). Since attentional bias can occur without conscious awareness, the purpose of this study was to use electroencephalography to examine whether individuals with a high tendency for PPU exhibit attentional bias at the level of the preconscious processing. Event-related potentials (ERPs) were recorded while male participants with high (n = 24) and low (n = 23) levels of subclinical PPU performed a masked version of the dot-probe task measuring attentional bias toward subliminally presented pornographic stimuli. Behavioral data revealed that participants from both groups with high and low tendencies for PPU reacted faster to probes replacing pornographic images than to probes replacing neutral images. ERPs revealed that individuals with a high tendency for PPU exhibited larger probe-locked P1 amplitudes following masked pornographic images (valid condition) compared with masked neutral images (invalid condition). Additionally, PPU symptom severity correlated positively with the P1 amplitude difference between valid and invalid conditions. These results highlight the automaticity of attentional capture by pornographic stimuli and support the hypothesis of an addiction-related attentional bias during preconscious processes. The implication of these findings for understanding the clinical phenomenon of out-of-control addictive behavior are discussed.


Assuntos
Viés de Atenção , Sinais (Psicologia) , Eletroencefalografia , Literatura Erótica , Potenciais Evocados , Humanos , Masculino , Literatura Erótica/psicologia , Viés de Atenção/fisiologia , Potenciais Evocados/fisiologia , Adulto , Adulto Jovem , Comportamento Aditivo/psicologia , Comportamento Aditivo/fisiopatologia , Atenção/fisiologia , Tempo de Reação/fisiologia , Estimulação Subliminar
16.
Phytopathology ; 114(1): 211-219, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37486148

RESUMO

Stripe rust, a fungal disease caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive diseases affecting wheat production areas worldwide. In recent years in China, wheat stripe rust has caused huge yield losses throughout the vast Huang-Huai-Hai region, including the eastern coast regions, especially Shandong province. The aim of the present study was to explore the population structure and potential inoculum sources of the pathogen in this region. A total of 234 Pst isolates in 2021 were collected and isolated from seven provinces and identified for virulence phenotypes using 19 Chinese differentials and for genotypes using 17 single-nucleotide polymorphism-based Kompetitive allele-specific PCR markers. The virulence phenotype tests identified predominant races CYR34 (18.0%) and CYR32 (16.0%) in Shandong, which were similar to the results in Henan province, also with the predominant races CYR34 (21.9%) and CYR32 (18.8%). Based on the virulence data of phenotyping, the Pst populations in Shandong, Hubei, and Henan were similar. The genotypic analysis revealed remarkable gene flows among the Shandong, Hubei, Henan, Yunnan, and Guizhou populations, showing a migration of Pst from the southwestern oversummering regions to Shandong through the winter spore production regions. Genetic structure analysis also indicated an additional migration route from the northwestern oversummering regions through winter spore production regions to Shandong. The results are useful for understanding stripe rust epidemiology in the eastern coast region and improving control of the disease throughout the country.


Assuntos
Basidiomycota , Doenças das Plantas , Puccinia , China , Doenças das Plantas/microbiologia , Genótipo , Fenótipo
17.
J Nanobiotechnology ; 22(1): 235, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725031

RESUMO

Different from most of the conventional platforms with dissatisfactory theranostic capabilities, supramolecular nanotheranostic systems have unparalleled advantages via the artful combination of supramolecular chemistry and nanotechnology. Benefiting from the tunable stimuli-responsiveness and compatible hierarchical organization, host-guest interactions have developed into the most popular mainstay for constructing supramolecular nanoplatforms. Characterized by the strong and diverse complexation property, cucurbit[8]uril (CB[8]) shows great potential as important building blocks for supramolecular theranostic systems. In this review, we summarize the recent progress of CB[8]-based supramolecular theranostics regarding the design, manufacture and theranostic mechanism. Meanwhile, the current limitations and corresponding reasonable solutions as well as the potential future development are also discussed.


Assuntos
Hidrocarbonetos Aromáticos com Pontes , Imidazóis , Nanomedicina Teranóstica , Nanomedicina Teranóstica/métodos , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Humanos , Animais , Nanopartículas/química , Compostos Heterocíclicos com 2 Anéis , Compostos Macrocíclicos , Imidazolidinas
18.
BMC Public Health ; 24(1): 2298, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256716

RESUMO

BACKGROUND: Understanding the impact of environmental factors on physical activity (PA) and physical fitness (PF) is crucial for promoting a healthy lifestyle among children and adolescents. This study examines how awareness of sports policies, school, family, and community environments influence PA and PF in Chinese youth. METHODS: A cross-sectional study was conducted with 2747 children and adolescents (mean age 12.90 ± 2.49; 48.2% male) from 17 schools across five Chinese cities. Environmental factors were assessed via questionnaires, and PA levels were measured using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). PF metrics, including BMI, waist-to-height ratio, grip strength, vertical jump, and 20-m shuttle run test (20-mSRT), were measured onsite. Structural Equation Modeling (SEM) was used to explore relationships between environmental factors and PA/PF outcomes. RESULTS: The school environment scored highest (78.0 ± 9.5), while the community environment scored lowest (38.7 ± 18.0). Family environment positively influenced low-intensity PA (LPA) (ß = 0.102, P < 0.001) but negatively affected moderate-to-vigorous PA (MVPA) (ß = -0.055, P = 0.035). Community environment and awareness of sports policies positively impacted MVPA (ß = 0.216, P < 0.001; ß = 0.072, P = 0.009, respectively). Family environment positively influenced BMI reduction (ß = -0.103, P < 0.001) but negatively affected grip strength (ß = -0.063, P = 0.018). Community environment improved grip strength and 20-mSRT performance (ß = 0.088, P = 0.002; ß = 0.065, P = 0.027). CONCLUSIONS: School environments, despite high scores, do not significantly impact PA and PF. Community environments, though scoring lower, positively affect MVPA, grip strength, and 20-mSRT. Awareness of sports policies boosts MVPA, while family environments support LPA and BMI but are inversely related to MVPA and grip strength. Integrated strategies involving community infrastructure, family support, and policy awareness are essential for promoting active lifestyles among children and adolescents.


Assuntos
Exercício Físico , Aptidão Física , Instituições Acadêmicas , Esportes , Humanos , Masculino , Adolescente , Feminino , Estudos Transversais , Aptidão Física/fisiologia , Criança , China , Análise de Classes Latentes , Família , Inquéritos e Questionários , Características de Residência/estatística & dados numéricos , Política de Saúde
19.
Proc Natl Acad Sci U S A ; 118(19)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33952701

RESUMO

To efficiently integrate cutting-edge terahertz technology into compact devices, the highly confined terahertz plasmons are attracting intensive attention. Compared to plasmons at visible frequencies in metals, terahertz plasmons, typically in lightly doped semiconductors or graphene, are sensitive to carrier density (n) and thus have an easy tunability, which leads to unstable or imprecise terahertz spectra. By deriving a simplified but universal form of plasmon frequencies, here, we reveal a unified mechanism for generating unusual n-independent plasmons (DIPs) in all topological states with different dimensions. Remarkably, we predict that terahertz DIPs can be excited in a two-dimensional nodal line and one-dimensional nodal point systems, confirmed by the first-principle calculations on almost all existing topological semimetals with diverse lattice symmetries. Besides n-independence, the feature of Fermi velocity and degeneracy factor dependencies in DIPs can be applied to design topological superlattice and multiwalled carbon nanotube metamaterials for broadband terahertz spectroscopy and quantized terahertz plasmons, respectively. Surprisingly, high spatial confinement and quality factor, also insensitive to n, can be simultaneously achieved in these terahertz DIPs. Our findings pave the way for developing topological plasmonic devices for stable terahertz applications.

20.
Ecotoxicol Environ Saf ; 280: 116536, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38833983

RESUMO

The anomalies of cadmium (Cd) in karst region pose a severe threat to plant growth and development. In this study, the responses of Rhododendron decorum to Cd stress were investigated at physiological, molecular, and endophytic microbial levels, and the potential correlation among these responses was assessed. The Cd stress impeded R. decorum growth and led to an increase in malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels, as well as enhanced superoxide dismutase (SOD) and catalase (CAT) activities. Meanwhile, Cd stress increased the Cd (up to 80 times compared to the control), sodium (Na), aluminum (Al), and zinc (Zn) contents, while decreased the magnesium (Mg) and manganese (Mn) contents in R. decorum leaves. Transcriptome suggested that Cd significantly regulated the pathways including "protein repair", "hormone-mediated signaling pathway", and "ATP-binding cassette (ABC) transporters". Additionally, q-PCR analysis showed that Cd stress significantly up-regulated the expressions of ABCB19-like and pleiotropic drug resistance, while down-regulated the expressions of indole-3-acetic acid-amido synthetase and cytokinin dehydrogenase. The Cd stress influenced the composition of endophytic microbial communities in R. decorum leaves and enhanced the interspecific bacterial associations. Furthermore, the bacterial genera Achromobacter, Aureimonas and fungal genus Vishniacozyma exhibited a high degree of connectivity with other nodes in networks constructed by the metal element contents, differentially expressed genes (DEGs), and microbial communities, respectively. These findings provide a comprehensive insight into the response of R. decorum to Cd-induced stress, which might facilitate the breeding of the Cd-tolerant R. decorum.


Assuntos
Cádmio , Microbiota , Rhododendron , Transcriptoma , Cádmio/toxicidade , Rhododendron/microbiologia , Rhododendron/genética , Transcriptoma/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Poluentes do Solo/toxicidade , Estresse Fisiológico/efeitos dos fármacos , Malondialdeído/metabolismo , Peróxido de Hidrogênio/metabolismo
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