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1.
PLoS One ; 19(6): e0305863, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38913666

RESUMEN

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-ß, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Remodelación de las Vías Aéreas (Respiratorias) , Asma , Modelos Animales de Enfermedad , Rosuvastatina Cálcica , Transducción de Señal , Animales , Asma/tratamiento farmacológico , Asma/metabolismo , Asma/patología , Rosuvastatina Cálcica/farmacología , Rosuvastatina Cálcica/uso terapéutico , Proteínas Quinasas Activadas por AMP/metabolismo , Transducción de Señal/efectos de los fármacos , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Ratones , Ovalbúmina , Femenino , Ratones Endogámicos BALB C , Líquido del Lavado Bronquioalveolar , Enfermedad Crónica , Inflamación/tratamiento farmacológico , Inflamación/patología , Inflamación/metabolismo , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Inmunoglobulina E/sangre
4.
Biomed Pharmacother ; 175: 116788, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38772153

RESUMEN

AIMS: Penicilazaphilone C (PAC) is hypothesized to potentially serve as a therapeutic treatment for allergic airway inflammation by inhibiting the NLRP3 inflammasome and reducing oxidative stress. METHODS: An allergic asthma model was induced in female BALB/c mice of the OVA, OVA+PAC, OVA+PAC+LPS, and OVA+Dex groups by sensitizing and subsequently challenging them with OVA. The OVA+PAC and Normal+PAC groups were treated with PAC, while the OVA+PAC+LPS group also received LPS. The OVA+Dex group was given dexamethasone (Dex). Samples of serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for histological and cytological analysis. RESULTS: Allergic mice treated with PAC or Dex showed inhibited inflammation and mucus production in the lungs. There was a decrease in the number of inflammatory cells in the BALF, lower levels of inflammatory cytokines in the serum and BALF, and a reduction in the protein expression of NLRP3, ASC, cleaved caspase-1, IL-1ß, activated gasdermin D, MPO, Ly6G, and ICAM-1. Additionally, oxidative stress was reduced, as shown by a decrease in MDA and DCF, but an increase in SOD and GSH. Treatment with PAC also resulted in a decrease in pulmonary memory CD4+ T cells and an increase in regulatory T cells. However, the positive effects seen in the PAC-treated mice were reversed when the NLRP3 inflammasome was activated by LPS, almost returning to the levels of the Sham-treated mice. SIGNIFICANCE: PAC acts in a similar way to anti-allergic inflammation as Dex, suggesting it may be a viable therapeutic option for managing allergic asthma inflammation.


Asunto(s)
Asma , Líquido del Lavado Bronquioalveolar , Inflamasomas , Ratones Endogámicos BALB C , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Femenino , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Asma/tratamiento farmacológico , Asma/inmunología , Asma/inducido químicamente , Ratones , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Pulmón/inmunología , Estrés Oxidativo/efectos de los fármacos , Ovalbúmina , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Modelos Animales de Enfermedad , Dexametasona/farmacología , Antiinflamatorios/farmacología
5.
Int Immunopharmacol ; 136: 112329, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38815351

RESUMEN

PURPOSE: Our team identified a new cardiac glycoside, Toxicarioside H (ToxH), in a tropical plant. Previous research has indicated the potential of cardenolides in mitigating inflammation, particularly in the context of NETosis. Therefore, this study sought to examine the potential of ToxH in attenuating allergic airway inflammation by influencing the immune microenvironment. METHODS: An OVA-induced airway inflammation model was established in BALB/c mice. After the experiment was completed, serum, bronchoalveolar lavage fluid (BALF), and lung tissue samples were collected and further examined using H&E and PAS staining, flow cytometry, immunofluorescence observation, and Western blot analysis. RESULTS: Treatment with ToxH was found to be effective in reducing airway inflammation and mucus production. This was accompanied by an increase in Th1 cytokines (IFN-γ, IL-2, and TNF-ß), and the Th17 cytokine IL-17, while levels of Th2 cytokines (IL-4, IL-5, and IL-13) and Treg cytokines (IL-10 and TGF-ß1) were decreased in both the bronchoalveolar lavage fluid (BALF) and the CD45+ immune cells in the lungs. Additionally, ToxH inhibited the infiltration of inflammatory cells and decreased the number of pulmonary CD44+ memory T cells, while augmenting the numbers of Th17 and Treg cells. Furthermore, the neutrophil elastase inhibitor GW311616A was observed to suppress airway inflammation and mucus production, as well as alter the secretion of immune Th1, Th2, Th17, and Treg cytokines in the lung CD45+ immune cells. Moreover, our study also demonstrated that treatment with ToxH efficiently inhibited ROS generation, thereby rectifying the dysregulation of immune cells in the immune microenvironment in OVA-induced allergic asthma. CONCLUSIONS: Our findings indicate that ToxH could serve as a promising therapeutic intervention for allergic airway inflammation and various other inflammatory disorders. Modulating the balance of Th1/Th2 and Treg/Th17 cells within the pulmonary immune microenvironment may offer an effective strategy for controlling allergic airway inflammation.


Asunto(s)
Citocinas , Pulmón , Ratones Endogámicos BALB C , Ovalbúmina , Animales , Ovalbúmina/inmunología , Citocinas/metabolismo , Pulmón/inmunología , Pulmón/patología , Pulmón/efectos de los fármacos , Ratones , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Femenino , Modelos Animales de Enfermedad , Asma/inmunología , Asma/tratamiento farmacológico , Neutrófilos/inmunología , Neutrófilos/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Humanos , Moco/metabolismo , Moco/inmunología , Alérgenos/inmunología
6.
Zool Res ; 45(3): 586-600, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38766743

RESUMEN

The placenta plays a crucial role in successful mammalian reproduction. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons, essential for full-term fetal development. The cow placenta harbors at least two trophoblast cell populations: uninucleate (UNC) and binucleate (BNC) cells. However, the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches, and the molecular mechanisms governing trophoblast differentiation and functionalization. To fill this knowledge gap, we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation, attaining high-resolution, spatially resolved gene expression profiles. Based on clustering and cell marker gene expression analyses, key transcription factors, including YBX1 and NPAS2, were shown to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, spatial modules and co-variant genes that help shape specific tissue structures were identified. Together, these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.


Asunto(s)
Perfilación de la Expresión Génica , Placenta , Placentación , Transcriptoma , Animales , Bovinos/genética , Femenino , Embarazo , Placenta/metabolismo , Trofoblastos/metabolismo
9.
Front Public Health ; 12: 1335692, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680931

RESUMEN

Background: Frequent social participation among older adults is associated with greater health. Although understanding how sex and gender influence social participation is important, particularly in developing sex-inclusive health promotion and preventive interventions, little is known about factors influencing engagement of older women and men in social activities. Aim: This study thus aimed to examine factors influencing social activities of older women and men. Methods: A mixed-method systematic review was conducted in nine electronic databases from inception to March 2023. The studies had to define social participation as activities with others and examine its influencing factors among community-dwelling older women and men. Data were analyzed using convergent synthesis design from a socio-ecological perspective. Results: Forty-nine studies, comprising 42 quantitative, five qualitative and two mixed method design were included. Themes identified concerned: (a) sociodemographic factors, (b) personal assets, (c) interpersonal relationships and commitments, (d) physical environment, and (e) societal norms and gender expectations. The findings identified the heterogeneous needs, preferences and inequalities faced by older women and men, considerations on sociocultural expectations and norms of each gender when engaging in social activities, and the importance of having adequate and accessible social spaces. Overall, this review identified more evidence on factors influencing social participation among women than in men. Conclusion: Special attention is needed among community care providers and healthcare professionals to co-design, implement or prescribe a combination of sex and gender-specific and neutral activities that interest both older women and men. Intersectoral collaborative actions, including public health advocates, gerontologists, policymakers, and land use planners, are needed to unify efforts to foster social inclusion by creating an age-friendly and sustainable healthy environment. More longitudinal studies are required to better understand social participation trajectories from a sex and gender perspective and identify factors influencing it. Systematic reviews registration: http://www.crd.york.ac.uk/PROSPERO, identifier [CRD42023392764].


Asunto(s)
Vida Independiente , Participación Social , Humanos , Anciano , Femenino , Masculino , Factores Sexuales , Anciano de 80 o más Años , Relaciones Interpersonales
10.
Aging (Albany NY) ; 16(7): 6613-6626, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38613804

RESUMEN

Ubiquitination of the proteins is crucial for governing protein degradation and regulating fundamental cellular processes. Deubiquitinases (DUBs) have emerged as significant regulators of multiple pathways associated with cancer and other diseases, owing to their capacity to remove ubiquitin from target substrates and modulate signaling. Consequently, they represent potential therapeutic targets for cancer and other life-threatening conditions. USP43 belongs to the DUBs family involved in cancer development and progression. This review aims to provide a comprehensive overview of the existing scientific evidence implicating USP43 in cancer development. Additionally, it will investigate potential small-molecule inhibitors that target DUBs that may have the capability to function as anti-cancer medicines.


Asunto(s)
Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Animales , Ubiquitinación , Endopeptidasas/metabolismo , Enzimas Desubicuitinizantes/metabolismo , Transducción de Señal , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
11.
PLoS One ; 19(3): e0299571, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38466744

RESUMEN

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.


Asunto(s)
Neoplasias de la Mama , Ferroptosis , Femenino , Humanos , Neoplasias de la Mama/genética , Coenzima A Ligasas/genética , Ferroptosis/genética , Peroxidación de Lípido , Monoéster Fosfórico Hidrolasas , Fosforilación , Piruvato Deshidrogenasa (Lipoamida)-Fosfatasa/metabolismo
12.
J Pers Med ; 14(3)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38541004

RESUMEN

BACKGROUND: Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. METHODS: This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. RESULTS: A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause-effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. CONCLUSIONS: Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

13.
Europace ; 26(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38457487

RESUMEN

AIMS: Aveir VR performance and predictors for its pacing threshold (PCT) in a real-world cohort were investigated. METHODS: Electrical measurements at various stages of an Aveir VR implant were prospectively collected. Predictors for 3-month PCT were studied. A retrospective cohort of consecutive 139 Micra implants was used to compare the PCT evolution. High PCT was defined as ≥1.5 V, using a pulse width of 0.4 ms for Aveir and 0.24 ms for Micra. Excellent PCT was defined as ≤0.5 V at the respective pulse width. RESULTS: Among the 123 consecutive Aveir VR implant attempts, 122 (99.2%) were successful. The majority were of advanced age (mean 79.7) and small body size (mean BSA 1.60). Two patients (1.6%) experienced complications, including one pericardial effusion after device reposition and one intraoperative device dislodgement. Eighty-eight patients reached a 3-month follow-up. Aveir 3-month PCT was correlated with impedance at mapping (P = 0.015), tether mode (P < 0.001), end-of-procedure (P < 0.001), and mapping PCT (P = 0.035), but not with PCTs after fixation (P > 0.05). Tether mode impedance >470 ohms had 88% sensitivity and 71% specificity in predicting excellent 3-month PCT. Although it is more common for Aveir to have high PCT at end of procedure (11.5% for Aveir and 2.2% for Micra, P = 0.004), the rate at 3 months was similar (2.3% for Aveir and 3.1% for Micra, P = 1.000). CONCLUSION: Aveir VR demonstrated satisfactory performance in this high-risk cohort. Pacing thresholds tend to improve to a greater extent than Micra after implantation. The PCT after fixation, even after a waiting period, has limited predictive value for the chronic threshold. Low-mapping PCT and high intraoperative impedance predict chronic low PCT.


Asunto(s)
Marcapaso Artificial , Realidad Virtual , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Diseño de Equipo , Estimulación Cardíaca Artificial/efectos adversos , Estimulación Cardíaca Artificial/métodos
14.
Adv Sci (Weinh) ; 11(16): e2306659, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38359005

RESUMEN

High-coverage mass spectrometry analysis of single-cell metabolomics remains challenging due to the extremely low abundance and wide polarity of metabolites and ultra-small volume in single cells. Herein, a novel concentric hybrid ionization source, nanoelectrospray ionization-atmospheric pressure chemical ionization (nanoESI-APCI), is ingeniously designed to detect polar and nonpolar metabolites simultaneously in single cells. The source is constructed by inserting a pulled glass capillary coaxially into a glass tube that acts as a dielectric barrier layer. Benefitting from the integrated advantages of nanoESI and APCI, its limit of detection is improved by one order of magnitude to 10 pg mL-1. After the operational parameter optimization, 254 metabolites detected in nanoESI-APCI are tentatively identified from a single cell, and 82 more than those in nanoESI. The developed nanoESI-APCI is successively applied to study the metabolic heterogeneity of human hepatocellular carcinoma tissue microenvironment united with laser capture microdissection (LCM), the discrimination of cancer cell types and subtypes, the metabolic perturbations to glucose starvation in MCF7 cells and the metabolic regulation of cancer stem cells. These results demonstrated that the nanoESI-APCI not only opens a new avenue for high-coverage and high-sensitivity metabolomics analysis of single cell, but also facilitates spatially resolved metabolomics study coupled with LCM.


Asunto(s)
Metabolómica , Análisis de la Célula Individual , Espectrometría de Masa por Ionización de Electrospray , Metabolómica/métodos , Humanos , Análisis de la Célula Individual/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Presión Atmosférica , Nanotecnología/métodos , Células MCF-7 , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo
15.
Front Oncol ; 14: 1345322, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38357197

RESUMEN

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

16.
Oncologist ; 29(4): e487-e497, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37874924

RESUMEN

BACKGROUND: The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy. The differences between long-term prognoses of the 2 groups were compared. Subgroup analysis was performed in 173 HCC patients who met the criteria for surgical resection following down-staging. RESULTS: Multivariable analysis of all patients showed that surgical therapy, hazard ratio (HR): 0.289, 95% confidence interval, CI, 0.136-0.613) was a protective factor for overall survival (OS), but not for event-free survival (EFS). Multivariable analysis of 173 intermediate-advanced HCC patients who met the criteria for surgical resection after conversion therapy showed that surgical therapy (HR: 0.282, 95% CI, 0.121-0.655) was a protective factor for OS, but not for EFS. Similar results were obtained after propensity score matching. For patients with Barcelona Clinic Liver Cancer stage B (HR: 0.171, 95% CI, 0.039-0.751) and C (HR: 0.269, 95% CI, 0.085-0.854), surgical therapy was also a protective factor for OS. CONCLUSIONS: Overall, for patients with intermediate-advanced HCC who underwent local-plus-systemic therapies, surgical therapy is a protective factor for long-term prognosis and can prolong OS, and for those who met the surgical resection criteria after conversion therapy, surgical therapy is recommended.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Pronóstico , Hepatectomía
17.
Small ; : e2308676, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38072780

RESUMEN

Highly emissive semiconductor nanocrystals, or so-called quantum dots (QDs) possess a variety of applications from displays and biology labeling, to quantum communication and modern security. Though ensembles of QDs have already shown very high photoluminescent quantum yields (PLQYs) and have been widely utilized in current optoelectronic products, QDs that exhibit high absorption cross-section, high emission intensity, and, most important, nonblinking behavior at single-dot level have long been desired and not yet realized at room temperature. In this work, infrared-emissive MAPbI3 -based halide perovskite QDs is demonstrated. These QDs not only show a ≈100% PLQY at the ensemble level but also, surprisingly, at the single-dot level, display an extra-large absorption cross-section up to 1.80 × 10-12 cm2 and non-blinking single photon emission with a high single photon purity of 95.3%, a unique property that is extremely rare among all types of quantum emitters operated at room temperature. An in-depth analysis indicates that neither trion formation nor band-edge carrier trapping is observed in MAPbI3 QDs, resulting in the suppression of intensity blinking and lifetime blinking. Fluence-dependent transient absorption measurements reveal that the coexistence of non-blinking behavior and high single photon purity in these perovskite QDs results from a significant repulsive exciton-exciton interaction, which suppresses the formation of biexciton, and thus greatly reduces photocharging. The robustness of these QDs is confirmed by their excellent stability under continuous 1 h electron irradiation in high-resolution transmission electron microscope inspection. It is believed that these results mark an important milestone in realizing nonblinking single photon emission in semiconductor QDs.

18.
Sci Rep ; 13(1): 21916, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38081931

RESUMEN

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target.


Asunto(s)
Ferroptosis , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Fibroblastos/metabolismo , Sistema de Transporte de Aminoácidos y+/genética
19.
ACS Nano ; 17(24): 25552-25564, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38096149

RESUMEN

Photomemristors have been regarded as one of the most promising candidates for next-generation hardware-based neuromorphic computing due to their potentials of fast data transmission and low power consumption. However, intriguingly, so far, photomemristors seldom display truly nonvolatile memory characteristics with high light sensitivity. Herein, we demonstrate ultrasensitive photomemristors utilizing two-dimensional (2D) Ruddlesden-Popper (RP) perovskites with a highly polar donor-acceptor-type push-pull organic cation, 4-(5-(2-aminoethyl)thiophen-2-yl)benzonitrile+ (EATPCN+), as charge-trapping layers. High linearity and almost zero-decay retention are observed in (EATPCN)2PbI4 devices, which are very distinct from that of the traditional 2D RP perovskite devices consisting of nonpolar organic cations, such as phenethylamine+ (PEA+) and octylamine+ (OA+), and traditional 3D perovskite devices consisting of methylamine+ (MA+). The 2-fold advantages, including desirable spatial crystal arrangement and engineered energetic band alignment, clarify the mechanism of superior performance in (EATPCN)2PbI4 devices. The optimized (EATPCN)2PbI4 photomemristor also shows a memory window of 87.9 V and an on/off ratio of 106 with a retention time of at least 2.4 × 105 s and remains unchanged after >105 writing-reading-erasing-reading endurance cycles. Very low energy consumptions of 1.12 and 6 fJ for both light stimulation and the reading process of each status update are also demonstrated. The extremely low power consumption and high photoresponsivity were simultaneously achieved. The high photosensitivity surpasses that of a state-of-the-art commercial pulse energy meter by several orders of magnitude. With their outstanding linearity and retention, rabbit images have been rebuilt by (EATPCN)2PbI4 photomemristors, which truthfully render the image without fading over time. Finally, by utilizing the powerful ∼8 bits of nonvolatile potentiation and depression levels of (EATPCN)2PbI4 photomemristors, the accuracies of the recognition tasks of CIFAR-10 image classification and MNIST handwritten digit classification have reached 89% and 94.8%, respectively. This study represents the first report of utilizing a functional donor-acceptor type of organic cation in 2D RP perovskites for high-performance photomemristors with characteristics that are not found in current halide perovskites.

20.
ACS Appl Mater Interfaces ; 15(37): 44033-44042, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37694918

RESUMEN

Three organic conjugated small molecules, DTA-DTPZ, Cz-DTPZ, and DTA-me-DTPZ comprising an antiaromatic 5,10-ditolylphenazine (DTPZ) core and electron-donating peripheral substituents with high HOMOs (-4.2 to -4.7 eV) and multiple reversible oxidative potentials are reported. The corresponding films sandwiched between two electrodes show unipolar and switchable hysteresis current-voltage (I-V) characteristics upon voltage sweeping, revealing the prominent features of nonvolatile memristor behaviors. The numerical simulation of the I-V curves suggests that the carriers generated by the oxidized molecules lead to the increment of conductance. However, the accumulated carriers tend to deteriorate the device endurance. The electroactive sites are fully blocked in the dimethylated molecule DTA-me-DTPZ, preventing the irreversible electrochemical reaction, thereby boosting the endurance of the memristor device over 300 cycles. Despite the considerable improvement in endurance, the decrement of on/off ratio from 105 to 101 after 250 cycles suggests that the excessive charge carriers (radical cations) remains a problem. Thus, a new strategy of doping an electron-deficient material, CN-T2T, into the unipolar active layer was introduced to further improve the device stability. The device containing DTA-me-DTPZ:CNT2T (1:1) blend as the active layer retained the endurance and on/off ratio (∼104) upon sweeping 300 cycles. The molecular designs and doping strategy demonstrate effective approaches toward more stable metal-free organic conjugated small-molecule memristors.

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