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Gastric cancer is one of the most malignant digestive tract tumors worldwide and its progression is associated with gene expression and metabolic alteration. We revealed that the gastric cancer patients with lower expression level of TOB1 exhibited poorer overall survivals according to the data in Kaplan-Meier Plotter. The unphosphorylated TOB1 protein which is effective expressed lower in gastric cancer cells. The gastric cancer cells with TOB1 gene depletion performed higher abilities of proliferation, migration and invasion and lower ability of apoptosis in vitro. The TOB1 gene depletion also promoted the tumorigenesis of gastric cancer cells in vivo. The gastric cancer cells with TOB1 gene overexpression had the converse behaviors. The transcriptional and metabolic sequencing was performed. The analyzation results showed that genes correlate-expressed with TOB1 gene were enriched in the pathways related to ERK pathway, including focal adhesion pathway, which was verified using real-time quantitative PCR. After inhibiting ERK pathway, the proliferation, colony formation and migration abilities were reduced in gastric cancer cells with low phosphorylated TOB1 protein expression level. Moreover, Pearson correlation analysis was adopted to further analyze the correlation of enriched metabolic products and differentially expressed genes. The expression of Choline, UDP-N-acetylglucosamine, Adenosine and GMP were related to the function of TOB1. This study demonstrates the genes and metabolites related to focal adhesion pathway and ERK pathway are the potential diagnosis and therapeutic targets to gastric cancer with TOB1 depletion.
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Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Sistema de Señalización de MAP Quinasas , Neoplasias Gástricas , Proteínas Supresoras de Tumor , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Movimiento Celular/genética , Línea Celular Tumoral , Animales , Ratones , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Adhesiones Focales/genética , Adhesiones Focales/metabolismo , Apoptosis/genéticaRESUMEN
Background: Necrotizing enterocolitis (NEC) is a condition characterized by acquired damage to the mucosal lining, predominantly affecting premature infants. Bioinformatics assessments uncovered a notable rise in miR-155-5p expression in the intestinal tissues of infants suffering from NEC. Nevertheless, the development of NEC's underlying mechanisms and the role of miR-155-5p are still not well understood. This research aimed to explore the role of miR-155-5p in NEC and to elucidate its underlying mechanisms. Methods: To replicate NEC in vitro, lipopolysaccharide (LPS) was employed, whereas an in vivo rat model of NEC was established using formula feeding and exposure to hypoxia. Subsequently, levels of inflammatory cytokines, cell survival, and apoptosis rates were assessed. Various biochemical indicators such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were measured utilizing a purchased diagnostic kit. For the assessment of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) within FHC cells, analysis by flow cytometry was conducted. Additionally, the technique of Western blotting was utilized to analyze the levels of ferroptosis-associated proteins. Moreover, hematoxylin and eosin (H&E) staining was carried out to observe the histopathological alterations in the intestinal tissue samples from rats with necrotizing enterocolitis (NEC). Results: Reducing miR-155-5p improved the survival of FHC cells exposed to LPS, decreased cell apoptosis, inflammation, and ferroptosis, and mitigated intestinal damage in NEC rats. Furthermore, SLC7A11 was found to be a direct target of miR-155-5p. The inhibition of miR-155-5p decreased LPS-induced inflammation and ferroptosis in both FHC cells and NEC rats by promoting SLC7A11 expression. This effect was evidenced by increased levels of ferroptosis-related proteins FTH1 and GPX4, decreased COX-2 and ACSL4 levels, lower lipid peroxidation marker MDA, reduced antioxidant markers GSH, SOD, and CAT, fewer IL-6 and TNF-α, and suppression of the IκBα/NF-κB p65 signaling pathway. Conclusions: In conclusion, reducing miR-155-5p could improve intestinal damage in NEC by inhibiting inflammation and ferroptosis. These findings may provide theoretical insights for the development of new therapies for NEC.
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Benzo (k) fluoranthene (BkF) has adverse effects on male reproduction, but its specific mechanism of action is still unclear. This study focused on the role of RNA reading protein YTHDF2 and its mechanism in BkF induced male reproductive injury. Mouse GC-2 spermatocytes were exposed to 0, 40, 80, 160 µM BkF. It was found that BkF significantly increased the apoptosis of GC-2 cell and decreased its survival rate. BCL2 in spermatocytes decreased significantly, while the expression of P53 and BAX exhibited a notable increase. Interestingly, the expression of RNA reading protein YTHDF2 progressively rose in tandem with the escalating BkF exposure dosage. Overexpression of YTHDF2 significantly reduced the viability of cells and increased the apoptosis rate. Meanwhile, there was a substantial increase in the expression of P53 and BAX, BCL2 was significantly down-regulated. On the contrary, interfering with YTHDF2 increased cell proliferation and reduced cell apoptosis. Furthermore, YTHDF2 overexpression exacerbated the decrease in cell viability under BkF exposure, while YTHDF2 knockdown was the opposite. The results from the RIP assay demonstrated a significant enhancement in the interaction of YTHDF2 protein with BCL2 mRNA following the overexpression of YTHDF2. In addition, animal experiments showed that there was an increase in apoptosis and a decrease in proliferation of testicular cells in mice in the high-dose (30 mg/kg) BkF group by TUNEL staining and Ki67 staining. Immunohistochemical analysis showed that BCL2 levels were significantly lower in the high-dose group than in the control group, while YTHDF2, P53 and BAX were dramatically increased. In summary, our study suggests that YTHDF2 has been implicated in BkF-induced male reproductive injury by promoting the degradation of BCL2.
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Hybrid metal halides represent a novel type of semiconductor light emitters with intriguing excitonic emission properties, including free exciton emission and self-trapped exciton emission. Achieving precise control over these two excitonic emissions in hybrid metal halides is highly desired yet remains challenging. Here, the complete transformation from intrinsically broadband self-trapped exciton emission to distinctively sharp free exciton emission in a quasi-one-dimensional hybrid metal halide (C2H10N2)8[Pb4Br18]·6Br with a ribbon width of n = 4, is successfully achieved based on high-pressure method. During compression, pressure-induced phonon hardening continuously reduces exciton-phonon coupling, therefore suppressing excitonic localization and quenching the original self-trapped exciton emission. Notably, further compression triggers excitonic delocalization to induce intense free exciton emission, accompanied with reduced carrier effective masses and improved charge distribution. Controlled high-pressure investigations indicate that the ribbon width of n > 2 is necessary to realize excitonic delocalization and generate free exciton emissions in similar quasi-one-dimensional hybrid metal halides. This work presents an important photophysical process of excitonic transitions from self-trapped exciton emission to free exciton emission in quasi-one-dimensional hybrid metal halides without chemical regulation, promoting the rational synthesis of hybrid metal halides with desired excitonic emissions.
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BACKGROUND: Dendrobium officinale Kimura et Migo (D. officinale) is parasitic on rocks or plants with very few mineral elements that can be absorbed directly, so its growth and development are affected by nutritional deficiencies. Previous studies found that phosphorus deficiency promotes polysaccharides accumulation in D. officinale, the expression of DoCSLA6 (glucomannan synthase gene) was positively correlated with polysaccharide synthesis. However, the molecular mechanism by which the low phosphorus environment affects polysaccharide accumulation remains unclear. RESULTS: We found that DoSPX1 can reduce phosphate accumulation in plants and promote the expression of PSIs genes, thereby enhancing plant tolerance to low phosphorus environments.Y1H and EMSA experimental show that DoMYB37 can bind the promoter of DoCSLA6. DoSPX1 interact with DoMYB37 transiently overexpressed DoSPX1 and DoMYB37 in D. officinale protocorm-like bodies, decreased the Pi content, while increased the expression of DoCSLA6. CONCLUSIONS: The signaling pathway of DoSPX1-DoMYB37-DoCSLA6 was revealed. This provides a theoretical basis for the accumulation of polysaccharide content in D. officinale under phosphorus starvation.
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Dendrobium , Regulación de la Expresión Génica de las Plantas , Fósforo , Proteínas de Plantas , Dendrobium/metabolismo , Dendrobium/genética , Fósforo/metabolismo , Fósforo/deficiencia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMEN
BACKGROUD: Bronchopulmonary dysplasia (BPD) is one of the most important complications plaguing neonates and can lead to a variety of sequelae. the ability of the HIF-1α/VEGF signaling pathway to promote angiogenesis has an important role in neonatal lung development. METHOD: Newborn rats were exposed to 85% oxygen. The effects of hyperoxia exposure on Pleomorphic Adenoma Gene like-2 (PLAGL2) and the HIF-1α/VEGF pathway in rats lung tissue were assessed through immunofluorescence and Western Blot analysis. In cell experiments, PLAGL2 was upregulated, and the effects of hyperoxia and PLAGL2 on cell viability were evaluated using scratch assays, CCK-8 assays, and EDU staining. The role of upregulated PLAGL2 in the HIF-1α/VEGF pathway was determined by Western Blot and RT-PCR. Apoptosis and ferroptosis effects were determined through flow cytometry and viability assays. RESULTS: Compared with the control group, the expression levels of PLAGL2, HIF-1α, VEGF, and SPC in lung tissues after 3, 7, and 14 days of hyperoxia exposure were all decreased. Furthermore, hyperoxia also inhibited the proliferation and motility of type II alveolar epithelial cells (AECII) and induced apoptosis in AECII. Upregulation of PLAGL2 restored the proliferation and motility of AECII and suppressed cell apoptosis and ferroptosis, while the HIF-1α/VEGF signaling pathway was also revived. CONCLUSIONS: We confirmed the positive role of PLAGL2 and HIF-1α/VEGF signaling pathway in promoting BPD in hyperoxia conditions, and provided a promising therapeutic targets.
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Células Epiteliales Alveolares , Animales Recién Nacidos , Apoptosis , Ferroptosis , Hiperoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Animales , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células Epiteliales Alveolares/metabolismo , Ferroptosis/fisiología , Hiperoxia/metabolismo , Ratas Sprague-Dawley , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación hacia Abajo , Humanos , Proliferación CelularRESUMEN
BACKGROUND: Global longitudinal strain (GLS) and atrial voltage are acknowledged markers for worse rhythm outcome after ablation of persistent atrial fibrillation (PeAF). The majority of research efforts have been directed towards the left atrium (LA), with relatively fewer studies focusing on the right atrium (RA). The aim of this study was to investigate the effect of the biatrial substrate on the outcome following radiofrequency catheter ablation (RFCA). METHODS: All patients underwent two-dimensional speckle tracking echocardiography (2D-STE) and high-density mapping (HDM) on LA and RA in preoperative and postoperative stages of RFCA. Atrial substrate was assessed by GLS, average voltage, and low voltage zone (LVZ). RESULTS: This retrospective study enrolled 48 patients. With a follow-up of 385.98 ± 161.78 days, 22.92% (11/48) of all patients had AF recurrence and 63.64% in low strain group. Left atrial-low voltage zone (LA-LVZ) prior to RFCA was 67.52 ± 15.27% and 54.21 ± 20.07%, respectively, in the recurrence group and non-recurrence group. Multivariate regression analysis showed that preoperative LA-GLS (OR 0.047, 95%CI 0.002-0.941, p = .046) was independent predictors of AF recurrence. Biatrial average voltage in preoperative and postoperative stages were positively correlated (preoperative: r = 0.563 p < .001; postoperative: r = 0.464 p = .002). There was no significant difference in the proportion of RA in the recurrence group except the septum in preoperative and postoperative stages. CONCLUSIONS: Low LA-GLS and high LA-LVZ may be predictors of RFCA recurrence in PeAF patients. Biatrial average voltage were positively correlated in preoperative and postoperative stages.
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Immune checkpoint blocking (ICB), a tumor treatment based on the mechanism of T-cell activation, has shown high efficacy in clinical trials, but not all patients benefit from it. Immune checkpoint inhibitors (ICIs) do not respond to cold tumors that lack effective T-cell infiltration but respond well to hot tumors with sufficient T-cell infiltration. How to convert an unresponsive cold tumor into a responsive hot tumor is an important topic in cancer immunotherapy. Ferroptosis, a newly discovered immunogenic cell death (ICD) form, has great potential in cancer therapy. In the process of deeply understanding the mechanism of cold tumor formation, it was found that ferroptosis showed a powerful immune-activating effect by improving T-cell infiltration, and the combination of ICB therapy significantly enhanced the anti-tumor efficacy. This paper reviews the complex relationship between T cells and ferroptosis, as well as summarizes the various mechanisms by which ferroptosis enhances T cell infiltration: reactivation of T cells and reversal of immunosuppressive tumor microenvironment (TME), as well as recent advances of ICI in combination with targeted ferroptosis therapies, which provides guidance for better improving the ICB efficacy of cold tumors.
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Bisphenol F (BPF) has been extensively utilized in daily life, which brings new hazards to male reproductive health. However, the specific functional mechanism is still unclear. Both cell and animal models were utilized for exploring the role of RNA methylation and ferroptosis and its underlying mechanisms in male reproductive injury induced by BPF. In animal model, BPF severely destroyed the integrity of the blood-testis barrier (BTB) and induced ferroptosis. Furthermore, BPF significantly affected the barrier function of TM4 cells and promoted ferroptosis. Importantly, ChIP assays revealed that BPF inhibited AR transcriptional regulation of FTO and FTO expression was downregulated in TM4 cells. Overexpression of FTO prevented the impairment of BTB by inhibiting ferroptosis in TM4 cells. Mechanistically, FTO could significantly down-regulate the m6A modification level of TfRc and SLC7A11 mRNA through MeRIP experiment. RIP experiments showed that YTHDF1 can bind to TfRc mRNA and promote its translation while YTHDF2 could bind to SLC7A11 mRNA and reduce its mRNA stability. Therefore, our results suggest that FTO plays a key role in BPF induced male reproductive toxicity through YTHDF1-TfRc axis and YTHDF2-SLC7A11 axis and may provide new ideas and methods for the prevention and treatment of male reproductive diseases associated with environmental pollutants.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Compuestos de Bencidrilo , Barrera Hematotesticular , Ferroptosis , Fenoles , Proteínas de Unión al ARN , Masculino , Animales , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Fenoles/toxicidad , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Barrera Hematotesticular/efectos de los fármacos , Barrera Hematotesticular/metabolismo , Ratones , Compuestos de Bencidrilo/toxicidad , Transducción de Señal/efectos de los fármacos , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genéticaRESUMEN
Purpose: Glypican-3 (GPC3)-targeted radioisotope immuno-positron emission tomography (immunoPET) may lead to earlier and more accurate diagnosis of hepatocellular carcinoma (HCC), thus facilitating curative treatment, decreasing early recurrence, and enhancing patient survival. We previously demonstrated reliable HCC detection using a zirconium-89-labeled murine anti-GPC3 antibody (89Zr-αGPC3M) for immunoPET. This study evaluated the efficacy of the humanized antibody successor (αGPC3H) to further clinical translation of a GPC3-based theranostic for HCC. Methods: In vitro αGPC3 binding to HepG2 cells was assessed by flow cytometry. In vivo 89Zr-αGPC3H and 89Zr-αGPC3M tumor uptake was evaluated by PET/CT and biodistribution studies in an orthotopic xenograft mouse model of HCC. Results: αGPC3H maintained binding to GPC3 in vitro and 89Zr-αGPC3H immunoPET identified liver tumors in vivo. PET/CT and biodistribution analyses demonstrated high 89Zr-αGPC3H tumor uptake and tumor-to-liver ratios, with no difference between groups. Conclusion: Humanized αGPC3 successfully targeted GPC3 in vitro and in vivo. 89Zr-αGPC3H immunoPET had comparable tumor detection to 89Zr-αGPC3M, with highly specific tumor uptake, making it a promising strategy to improve HCC detection.
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Indole-3-propionic acid (IPA) is known to be a microbe-derived compound with a similar structure to the phytohormone auxin (indole-3-acetic acid, IAA). Previous studies reported that IPA exhibited auxin-like bioactivities in plants. However, the underlying molecular mechanism is not totally understood. Here, we revealed that IPA modulated lateral root (LR) development via auxin signaling in the model plant Arabidopsis thaliana. Genetic analysis indicated that deficiency of the TIR1/AFB-Aux/IAA-ARF auxin signaling pathway abolished the effects of IPA on regulating LR development. Further biochemical, transcriptomic profiling and cell biological analyses revealed that IPA directly bound to the TIR1/AFB-Aux/IAA coreceptor complex and thus activated downstream gene expression. Therefore, our work revealed that IPA is a potential signaling molecule that modulates plant growth and development by targeting the TIR1/AFB-Aux/IAA-mediated auxin signaling pathway, providing potential insights into root growth regulation in plants.
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Directional electron flow in the photocatalyst enables efficient charge separation, which is essential for efficient photocatalysis of H2 production. Here, we report a novel class of tetracationic cyclophanes (7) incorporating bipyridine Pt(II) and selenoviologen. X-ray single-crystal structures reveal that 7 not only fixes the distances and spatial positions between its individual units but also exhibits a box-like rigid electron-deficient cavity. Moreover, host-guest recognition phenomena are observed between 7 and ferrocene, forming host-guest complexes with a 1:1 stoichiometry in MeCN. 7 exhibits good redox properties, narrow energy gaps, and strong absorption in the visible range (370-500 nm) due to containing two selenoviologen (SeV2+) units. Meanwhile, the femtosecond transient absorption (fs-TA) reveals that 7 has stabilized dicationic biradical, efficient charge separation, and facilitates directional electron flow to achieve efficient electron transfer due to the formation of rigid cyclophane and electronic architecture. Then, 7 is applied to visible-light-driven hydrogen evolution with high hydrogen production (132 µmol), generation rate (11 µmol/h), turnover number (221), and apparent quantum yield (1.7%), which provides a simplified and efficient photocatalytic strategy for solar energy conversion.
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Benzo[a]pyrene (BaP) is associated with the development of lung cancer, but the underlying mechanism has not been completely clarified. Here, we used 10⯵M BaP to induce malignant transformation of human bronchial epithelial BEAS-2B cells, named BEAS-2B-T. Results indicated that BaP (6.25, 12.5 and 25⯵M) treatment significantly promoted the migration and invasion of BEAS-2B-T cells. Meanwhile, BaP exposure inhibited ferroptosis in BEAS-2B-T, ferroptosis-related indexes Fe2+, malondialdehyde (MDA), lipid peroxidation (LPO) and reactive oxygen species (ROS) decreased significantly. The protein level of ferroptosis-related molecule transferrin receptor (TFRC) decreased significantly, while solute carrier family 7 membrane 11 (SLC7A11), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) increased significantly. The intervention of ferroptosis dramatically effected the migration and invasion of BEAS-2B-T induced by BaP. Furthermore, the expression of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was markedly increased after BaP exposure. YTHDF1 knockdown inhibited BEAS-2B-T migration and invasion by promoting ferroptosis. In the meantime, the contents of Fe2+, MDA, LPO and ROS increased significantly, TFRC was markedly increased, and SLC7A11, FTH1, and GPX4 were markedly decreased. Moreover, overexpression of YTHDF1 promoted BEAS-2B-T migration and invasion by inhibiting ferroptosis. Importantly, knockdown of YTHDF1 promoted ferroptosis and reduced BEAS-2B-T migration and invasion during BaP exposure, and overexpression of YTHDF1 increased migration and invasion of BEAS-2B-T by inhibiting ferroptosis during BaP exposure. RNA immunoprecipitation assays indicated that the binding of YTHDF1 to SLC7A11 and FTH1 markedly increased after YTHDF1 overexpression. Therefore, we concluded that BaP promotes the malignant progression of BEAS-2B-T cells through YTHDF1 upregulating SLC7A11 and FTH1 to inhibit ferroptosis. This study reveals new epigenetic and ferroptosis markers for preventing and treating lung cancer induced by environmental carcinogens.
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Benzo(a)pireno , Movimiento Celular , Ferroptosis , Ferroptosis/efectos de los fármacos , Humanos , Benzo(a)pireno/toxicidad , Movimiento Celular/efectos de los fármacos , Línea Celular , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Especies Reactivas de Oxígeno/metabolismo , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Peroxidación de Lípido/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Ferritinas , Oxidorreductasas , Antígenos CDRESUMEN
The aim of this study is to combine flaxseed oil (FO), rich in α-linolenic acid (ALA), with Sunite sheep tail fat (STF) through a lipase-catalyzed transesterification reaction, in order to produce an edible oil with a fatty acid ratio suitable for human needs. Initially, the optimal conditions for esterification were determined using the Box-Behnken design, with the measurement criterion being the content of ALA at the sn-2 position. The results indicated that the highest content of sn-2 ALA was obtained under the conditions of using 6.8 wt% Lipozyme®RMIM as the catalyst, a reaction temperature of 57°C, a reaction time of 3.3 h, and a substrate mass ratio of 5.6:4.4 for STF and FO. This led to the rapid breaking and recombining of molecular bonds, resulting in the interesterified fat (IF) with the highest content of ALA at the sn-2 position. Comparing STF and FO, IF exhibited excellent fatty acid composition and content. Furthermore, IF had a lower melting point and crystallization temperature compared to STF, and its solid fat content decreased with increasing temperature, completely melting at temperatures above 30°C. Thus, IF is a synthesized fat with excellent properties from both animal and vegetable sources.
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High TRABD expression is associated with tau pathology in patients with Alzheimer's disease; however, the function of TRABD is unknown. Human TRABD encodes a mitochondrial outer-membrane protein. The loss of TRABD resulted in mitochondrial fragmentation, and TRABD overexpression led to mitochondrial clustering and fusion. The C-terminal tail of the TRABD anchored to the mitochondrial outer membrane and the TraB domain could form homocomplexes. Additionally, TRABD forms complexes with MFN2, MIGA2, and PLD6 to facilitate mitochondrial fusion. Flies lacking dTRABD are viable and have normal lifespans. However, aging flies exhibit reduced climbing ability and abnormal mitochondrial morphology in their muscles. The expression of dTRABD is increased in aged flies. dTRABD overexpression leads to neurodegeneration and enhances tau toxicity in fly eyes. The overexpression of dTRABD also increased reactive oxygen species (ROS), ATP production, and protein turnover in the mitochondria. This study suggested that TRABD-induced mitochondrial malfunctions contribute to age-related neurodegeneration.
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Drosophila melanogaster , Homeostasis , Mitocondrias , Especies Reactivas de Oxígeno , Animales , Mitocondrias/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Drosophila melanogaster/metabolismo , Proteínas tau/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Dinámicas Mitocondriales , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Membranas Mitocondriales/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Envejecimiento/metabolismo , GTP Fosfohidrolasas/metabolismoRESUMEN
The importance of autophagy in atherosclerosis has garnered significant attention regarding the potential applications of autophagy inducers. However, the impact of TAT-Beclin1, a peptide inducer of autophagy, on the development of atherosclerotic plaques remains unclear. Single-cell omics analysis indicates a notable reduction in GAPR1 levels within fibroblasts, stromal cells, and macrophages during atherosclerosis. Tat-beclin1 (T-B), an autophagy-inducing peptide derived from Beclin1, could selectively bind to GAPR1, relieving its inhibition on Beclin1 and thereby augmenting autophagosome formation. To investigate its impact on atherosclerosic plaque progression, we established the ApoE-/- mouse model of carotid atherosclerotic plaques. Surprisingly, intravenous administration of Tat-beclin1 dramatically accelerated the development of carotid artery plaques. Immunofluorescence analysis suggested that macrophage aggregation and autophagosome formation within atherosclerotic plaques were significantly increased upon T-B treatment. However, immunofluorescence and transmission electron microscopy (TEM) analysis revealed a reduction in autophagy flux through lysosomes. In vitro, the interaction between T-B and GAPR1 was confirmed in RAW264.7 cells, resulting in the increased accumulation of p62/SQSTM1 and LC3-II in the presence of ox-LDL. Additionally, T-B treatment elevated the protein levels of p62/SQSTM1, LC3-II, and cleaved caspase 1, along with the secretion of IL-1ß in response to ox-LDL exposure. In summary, our study underscores that T-B treatment amplifies abnormal autophagy and inflammation, consequently exacerbating atherosclerotic plaque development in ApoE-/- mice.
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Apolipoproteínas E , Aterosclerosis , Autofagia , Beclina-1 , Placa Aterosclerótica , Animales , Ratones , Beclina-1/metabolismo , Beclina-1/genética , Apolipoproteínas E/metabolismo , Apolipoproteínas E/deficiencia , Aterosclerosis/metabolismo , Aterosclerosis/patología , Autofagia/efectos de los fármacos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Células RAW 264.7 , Ratones Endogámicos C57BL , Masculino , Ratones Noqueados , Macrófagos/metabolismoRESUMEN
The stability issue of Sn-based perovskite solar cells (PSCs) is expected to be resolved by involving a two-dimensional (2D) layered structure. However, Sn-based 2D PSCs, especially Dion-Jacobson (DJ)-phase ones with potentially good stability, have rarely been reported. Herein, superior DJ-phase Sn 2D perovskites with 3-aminobenzylamine (3ABA2+) or 4-aminobenzylamine (4ABA2+) π-conjugated short-chain ligands are reported to fabricate efficient 2D lead-free PSCs. Notably, the high dipole moment of the 3ABAI2 organic spacer is approved to possess faster charge transfer for forming (3ABA)FA4Sn5I16 2D perovskite with an extremely low exciton binding energy (only 84 meV). In combination with a diacetate partial substitution and methylamine iodide/bromide (MAI/MABr) post-treatment strategy to delay crystallization and improve compactness and coverage of the perovskite film, a record power conversion efficiency (PCE) of 6.81% and stability of 840 h (less than 5% degradation in a N2 atmosphere for unencapsulated devices) are acquired in eventual (3ABA)FA4Sn5I16 2D PSCs, which are among the highest PCE and the longest stability of Sn-based 2D PSCs reported to date. Our work provides a prospective molecule design and film preparation strategy of 2D Sn perovskites toward nontoxic high-performance tin-based PSCs, which pushes the almost stagnant research forward.
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Dissipative self-assembly plays a vital role in fabricating intelligent and transient materials. The selection and design of the molecular structure is critical, and the introduction of valuable stimuli-responsive motifs into building blocks would bring about a novel perspective on the fuel driven nonequilibrium assemblies. For redox-responsive surfactants, novel methods of catalytic oxidation are very important for their activation/deactivation process through designing fuel input/energy dissipation. As an enzyme with a fast catalytic rate, Fe-based coordination polymers (Fe-CPs) are found to be highly effective oxidase-like enzymes to induce a reversible switch of a ferrocene-based surfactant over a wide range of temperatures and pH. This builds a bridge between the CPs materials and surfactants. Furthermore, glucose oxidase can also induce a switchable transition of a ferrocene-based surfactant. The GOX-catalyzed, glucose-fueled transient surfactant assemblies have been fabricated for many cycles, which has a successful application in a time-controlled and autonomous DNA capture and release process. The intelligent use of enzymes including CPs and GOX in ferrocene-based surfactants will pave the way for the oxidation of redox surfactants, which extends the application of stable or transient ferrocenyl self-assemblies.