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1.
Artículo en Inglés | MEDLINE | ID: mdl-39302810

RESUMEN

The use of a bipolar membrane (BPM) in a hybrid acid/alkali electrolyzer is widely considered as a promising energy technology for efficient hydrogen production. The stability of a BPM is often believed to be largely limited by the anion exchange layer (AEL) due to the hydrophilic attack of AEL polymers by hydroxide groups in alkaline. In this study, we employ X-ray computed tomography (CT) to investigate the degradation behaviors of BPM and found that the cation exchange layer (CEL) experiences more pronounced degradation compared with the AEL during water splitting operations. Despite its chemical stability in both acidic and alkaline environments, the CEL is more prone to electrochemical corrosion under the influence of applied voltages. This susceptibility leads to the formation of micropores and a consequent increase in the porosity. The results of this work provide a new perspective on and highlight the complexity of the degradation behaviors of BPMs in hybrid acid/alkali electrolyzers.

2.
Acta Pharmacol Sin ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223366

RESUMEN

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. In this study we investigated the effects and mechanisms of tumor intrinsic INHBA on carcinogenesis, tumor immunity and PD-L1 blockade. Bioinformatic analysis on the TCGA database revealed that INHBA expression levels were elevated in 33 cancer types, including breast cancer (BRCA) and colon adenocarcinoma (COAD). In addition, survival analysis also corroborated that INHBA expression was negatively correlated with the prognosis of many types of cancer patients. We demonstrated that gain or loss function of Inhba did not alter in vitro growth of colorectal cancer CT26 cells, but had striking impact on mouse tumor models including CT26, MC38, B16 and 4T1 models. By using the TIMER 2.0 tool, we figured out that in most cancer types, Inhba expression in tumors was inversely associated with the infiltration of CD4+ T and CD8+ T cells. In CT26 tumor-bearing mice, overexpression of tumor INHBA eliminated the anti-tumor effect of the PD-L1 antibody atezolizumab, whereas INHBA deficiency enhanced the efficacy of atezolizumab. We revealed that tumor INHBA significantly downregulated the interferon-γ (IFN-γ) signaling pathway. Tumor INHBA overexpression led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 treatment. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment (TME). Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade.

3.
Int J Biol Macromol ; 277(Pt 3): 134485, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39102926

RESUMEN

The blood glucose concentration in aquatic organisms, a crucial indicator reflecting their health status, holds significant importance for detecting glucose levels in serum in terms of processing and quality monitoring. In this study, a novel POD biomimetic enzyme (p-BEs) with horseradish peroxidase catalytic properties was designed, optimized, and its mechanism was discussed in detail. Based on this, a portable system has been developed capable of determining glucose levels in three ways: quantitatively analyzed through UV-Vis/MD, quantitatively analyzed on-site using a mobile phone RGB, and semi-quantitatively analyzed through a drip plate. Meanwhile, compared with other catalytic methods for detecting glucose, we achieved a lower limit of detection (0.03 µM) and shorter detection time (12 min), with high catalytic activity. This study provides new insights into the design of efficient and reliable cascade catalytic systems responsive to glucose, offering a low-cost, simplicity of operation method for glucose detection.


Asunto(s)
Técnicas Biosensibles , Peroxidasa de Rábano Silvestre , Técnicas Biosensibles/métodos , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Glucosa/análisis , Glucemia/análisis , Catálisis , Materiales Biomiméticos/química , Límite de Detección , Biomimética/métodos , Biocatálisis
4.
Sci Adv ; 10(29): eadn8706, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028816

RESUMEN

Poly(l-lactic acid) (PLLA) is a widely used U.S. Food and Drug Administration-approved implantable biomaterial that also possesses strong piezoelectricity. However, the intrinsically low stability of its high-energy piezoelectric ß phase and random domain orientations associated with current synthesis approaches remain a critical roadblock to practical applications. Here, we report an interfacial anchoring strategy for fabricating core/shell PLLA/glycine (Gly) nanofibers (NFs) by electrospinning, which show a high ratio of piezoelectric ß phase and excellent orientation alignment. The self-assembled core/shell structure offers strong intermolecular interactions between the -OH groups on Gly and C=O groups on PLLA, which promotes the crystallization of oriented PLLA polymer chains and stabilizes the ß phase structure. As-received core/shell NFs exhibit substantially enhanced piezoelectric performance and excellent stability. An all NF-based nonwoven fabric is fabricated and assembled as a flexible nanogenerator. The device offers excellent conformality to heavily wrinkled surfaces and thus can precisely detect complex physiological motions often found from biological organs.


Asunto(s)
Materiales Biocompatibles , Nanofibras , Poliésteres , Nanofibras/química , Materiales Biocompatibles/química , Poliésteres/química , Prótesis e Implantes , Textiles , Glicina/química
5.
Polymers (Basel) ; 16(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38891484

RESUMEN

In this study, a highly efficient magnetic molecularly imprinted polymer nanocomposite material was prepared using multi-walled carbon nanotubes as carriers. The characterization of the obtained nanocomposite material was conducted using Fourier transform infrared spectroscopy, a vibrating sample magnetometer, a thermogravimetric analyzer, a scanning electron microscope, and a transmission electron microscope. The adsorption properties of the nanocomposite material were evaluated through adsorption experiments, including static adsorption, dynamic adsorption, and selective recognition studies. The prepared nanocomposite material, serving as a selective adsorbent, was applied in magnetic solid-phase extraction. Subsequently, the derivatized samples were analyzed for glucose in fish serum using liquid chromatography-tandem mass spectrometry. Under optimal conditions, the detection limit was 0.30 ng/mL, the quantitation limit was 0.99 ng/mL, satisfactory spiked recovery rates were obtained, and the relative standard deviation was less than 1.1%. Using 2-deoxy-D-ribose as the template molecule and a structural analog of glucose allowed us to eliminate the potential template leakage in qualitative and quantitative analyses, effectively avoiding the issues of false positives and potential quantitative errors, compared to traditional methods. A method for detecting glucose levels in fish serum based on molecularly imprinted polymer technology has been successfully developed to determine the stress and health levels of fish.

6.
Cell Metab ; 36(9): 2054-2068.e14, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38906140

RESUMEN

Low-density lipoprotein receptor-related protein-1 (LRP1) is an endocytic/signaling cell-surface receptor that regulates diverse cellular functions, including cell survival, differentiation, and proliferation. LRP1 has been previously implicated in the pathogenesis of neurodegenerative disorders, but there are inconsistencies in its functions. Therefore, whether and how LRP1 maintains brain homeostasis remains to be clarified. Here, we report that astrocytic LRP1 promotes astrocyte-to-neuron mitochondria transfer by reducing lactate production and ADP-ribosylation factor 1 (ARF1) lactylation. In astrocytes, LRP1 suppressed glucose uptake, glycolysis, and lactate production, leading to reduced lactylation of ARF1. Suppression of astrocytic LRP1 reduced mitochondria transfer into damaged neurons and worsened ischemia-reperfusion injury in a mouse model of ischemic stroke. Furthermore, we examined lactate levels in human patients with stroke. Cerebrospinal fluid (CSF) lactate was elevated in stroke patients and inversely correlated with astrocytic mitochondria. These findings reveal a protective role of LRP1 in brain ischemic stroke by enabling mitochondria-mediated astrocyte-neuron crosstalk.


Asunto(s)
Factor 1 de Ribosilacion-ADP , Astrocitos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Mitocondrias , Neuronas , Animales , Humanos , Masculino , Ratones , Factor 1 de Ribosilacion-ADP/metabolismo , Astrocitos/metabolismo , Células Cultivadas , Glucólisis , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Ácido Láctico/metabolismo , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Neuronas/metabolismo
7.
Neurobiol Dis ; 199: 106583, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38942324

RESUMEN

After ischemic stroke (IS), secondary injury is intimately linked to endoplasmic reticulum (ER) stress and body-brain crosstalk. Nonetheless, the underlying mechanism systemic immune disorder mediated ER stress in human IS remains unknown. In this study, 32 candidate ER stress-related genes (ERSRGs) were identified by overlapping MSigDB ER stress pathway genes and DEGs. Three Key ERSRGs (ATF6, DDIT3 and ERP29) were identified using LASSO, random forest, and SVM-RFE. IS patients with different ERSRGs profile were clustered into two groups using consensus clustering and the difference between 2 group was further explored by GSVA. Through immune cell infiltration deconvolution analysis, and middle cerebral artery occlusion (MCAO) mouse scRNA analysis, we found that the expression of 3 key ERSRGs were closely related with peripheral macrophage cell ER stress in IS and this was further confirmed by RT-qPCR experiment. These ERS genes might be helpful to further accurately regulate the central nervous system and systemic immune response through ER stress and have potential application value in clinical practice in IS.


Asunto(s)
Biología Computacional , Estrés del Retículo Endoplásmico , Aprendizaje Automático , Humanos , Estrés del Retículo Endoplásmico/genética , Estrés del Retículo Endoplásmico/fisiología , Ratones , Animales , Accidente Cerebrovascular/genética , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/metabolismo , Masculino
8.
J Colloid Interface Sci ; 674: 108-117, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38917711

RESUMEN

Large-scale hydrogen production by electrocatalytic water splitting still remains as a critical challenge due to the severe catalyst degradation during the oxygen evolution reaction (OER) in acidic media. In this study, we investigate the structural impacts on catalyst degradation behaviors using three iridium-based oxides, namely SrIrO3, Sr2IrO4, and Sr4IrO6 as model catalysts. These Ir oxides possess different connection configurations of [IrO6] octahedra units in their structure. Stable OER performance is observed on SrIrO3 and attributed to the edge-linked [IrO6] structure and rapid formation of a continuous IrOx layer on its surface, which functions not only as the "real" catalyst but also a shield preventing continuous cation leaching (with <1.0 at.% of Ir leaching). In comparison, both Sr2IrO4 and Sr4IrO6 catalysts demonstrate quick current fading with structure transformation to rutile IrO2 and formation of inconducive SrSO4 precipitates on surface, blocking the reactive sites. Nevertheless, over 60 at.% of Ir leaching is detected from the Sr4IrO6 catalyst due to its isolated [IrO6] structure configuration. Results of this work highlight the structural impacts on the catalyst stability in acidic OER conditions.

9.
Nanotechnology ; 35(33)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38701761

RESUMEN

The decay rate of charge in the friction layer is one of the key factors affecting the output performance of triboelectric nanogenerators (TENG). Reducing the decay rate of the triboelectric charge can increase the charge-carrying capacity of the friction layer and improve the output current and voltage of the TENG. This makes a friction generator more suitable for discontinuous driving environments. In contrast, increasing the decay rate of the charge in the friction layer can greatly improve the recovery time of the device, although it reduces the output performance of the generator. This is conducive to the application of friction generator in the field of sensors. In this study, polystyrene (PS) and carbon nanotubes (CNTs) were added to polyvinylidene fluoride (PVDF) nanofibers to adjust the charge decay time in the friction layer, thereby regulating the output performance of the friction generator and sensor. When the amount of added PS in the PVDF nanofiber reached 20%, the charge density on the friction surface increased by 1.9 times, and the charge decay time decreased by 64 times; when 0.1 wt% CNTs were added in the PVDF nanofiber, the charge decay time increased by more than 10 times. The former is more conducive to improving the power generation performance of the TENG, and the latter significantly improves the stability and repeatability of TENG-based sensors.

10.
Nat Commun ; 15(1): 4113, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750029

RESUMEN

Stretchable phosphorescence materials potentially enable applications in diverse advanced fields in wearable electronics. However, achieving room-temperature phosphorescence materials simultaneously featuring long-lived emission and good stretchability is challenging because it is hard to balance the rigidity and flexibility in the same polymer. Here we present a multiphase engineering for obtaining stretchable phosphorescent materials by combining stiffness and softness simultaneously in well-designed block copolymers. Due to the microphase separation, copolymers demonstrate an intrinsic stretchability of 712%, maintaining an ultralong phosphorescence lifetime of up to 981.11 ms. This multiphase engineering is generally applicable to a series of binary and ternary initiator systems with color-tunable phosphorescence in the visible range. Moreover, these copolymers enable multi-level volumetric data encryption and stretchable afterglow display. This work provides a fundamental understanding of the nanostructures and material properties for designing stretchable materials and extends the potential of phosphorescence polymers.

11.
Nanomaterials (Basel) ; 14(9)2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38727392

RESUMEN

Lead-cooled fast reactors exhibit strong inherent safety performance and good economic features, while material degradation due to corrosion and irradiation is still challenging. Oxide dispersion-strengthened steels are one of the promising candidates for fuel cladding materials. The effects of both irradiation and corrosion on ODS steel need to be further studied. In this work, MX-ODS steel was irradiated by Fe ions at 500 °C up to 46 dpa. Later, the as-received specimen and the irradiated specimen were used to conduct corrosion tests in oxygen-saturated Pb at 550 °C for 1 h. In the as-received specimen, discontinuous oxides penetrated by Pb and Pb in contact with steel matrix were observed, demonstrating unsatisfactory corrosion resistance of the material. However, in the irradiated specimen after corrosion experiment, a protective oxide layer formed and prevented Pb attack. The oxidation behavior differences between the two specimens can be attributed to the defects produced by irradiation and the structural discrepancy in oxides caused by the formation process. A possible mechanism of irradiation on the corrosion is discussed. In the as-received specimen, Fe atoms loss led to voids in the oxides, and lead penetrated the oxides through these voids. In the irradiated specimen, defects left by previous irradiation helped to form a more uniform oxide layer. The adhesive outer magnetite oxide and the Fe ions generated from where grain boundary oxidation developed retarded the presence of voids and made the oxide layer protective.

12.
Appl Radiat Isot ; 207: 111249, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38428203

RESUMEN

The 71Ga(n,γ)72Ga reaction-based epithermal neutron flux detectors are novel instruments developed to measure the epithermal neutron flux of boron neutron capture therapy (BNCT) treatment beams. In this study, a spherical epithermal neutron flux detector using 71Ga(n,γ)72Ga reaction was prototyped. The performance of the detector was experimentally evaluated at an accelerator-based BNCT (AB-BNCT) device developed by Lanzhou University, China. Based on the experimental results and related analysis, we demonstrated that the detector is a reliable tool for the quality assurance of BNCT treatment beams.


Asunto(s)
Terapia por Captura de Neutrón de Boro , Humanos , Terapia por Captura de Neutrón de Boro/métodos , Neutrones , Dosificación Radioterapéutica , Rayos gamma , Método de Montecarlo
13.
Med Phys ; 51(6): 4524-4535, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38299670

RESUMEN

BACKGROUND: In boron neutron capture therapy (BNCT)-a form of binary radiotherapy-the primary challenge in treatment planning systems for dose calculations arises from the time-consuming nature of the Monte Carlo (MC) method. Recent progress, including the use of neural networks (NN), has been made to accelerate BNCT dose calculations. However, this approach may result in significant dose errors in both the tumor and the skin, with the latter being a critical organ in BNCT. Furthermore, owing to the lack of physical processes in purely NN-based approaches, their reliability for clinical dose calculations in BNCT is questionable. PURPOSE: In this study, a physically constrained MC-NN (PCMC-NN) coupling algorithm is proposed to achieve fast and accurate computation of the BNCT three-dimensional (3D) therapeutic dose distribution. This approach synergizes the high precision of the MC method with the speed of the NN and utilizes physical conservation laws to constrain the coupling process. It addresses the time-consuming issue of the traditional MC method while reducing dose errors. METHODS: Clinical data were collected from 113 glioblastoma patients. For each patient, the 3D dose distributions for both the coarse and detailed dose grids were calculated using the MC code PHITS. Among these patients, the data from 14 patients were allocated to the test set, 9 to the validation set, and the remaining to the training set. A neural network, 3D-Unet, was built based on the coarse grid dose and patient CT information to enable fast and accurate computation of the 3D detailed grid dose distribution of BNCT. RESULTS: Statistical evaluations, including relative deviation, dose deviation, mean absolute error (MAE), and mean absolute percentage error (MAPE) were conducted. Our findings suggested that the PCMC-NN algorithm substantially outperformed the traditional NN and interpolation methods. Furthermore, the proposed algorithm significantly reduced errors, particularly in the skin and GTV, and improved computational accuracy (hereinafter referred to simply as 'accuracy') with a MAPE range of 1.6%-4.0% and a maximum MAE of 0.3 Gy (IsoE) for different organs. The dose-volume histograms generated by the PCMC-NN aligned well with those obtained from the MC method, further validating its accuracy. CONCLUSIONS: The PCMC-NN algorithm enhanced the speed and accuracy of BNCT dose calculations by combining the MC method with the NN algorithm. This indicates the significant potential of the proposed algorithm for clinical applications in optimizing treatment planning.


Asunto(s)
Algoritmos , Terapia por Captura de Neutrón de Boro , Método de Montecarlo , Redes Neurales de la Computación , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Terapia por Captura de Neutrón de Boro/métodos , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosis de Radiación
14.
ACS Appl Mater Interfaces ; 16(3): 3901-3910, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38206311

RESUMEN

Achieving both high sensitivity and wide detecting range is significant for the applications of triboelectric nanogenerator-based self-powered pressure sensors (TPSs). However, most of the previous designs with high sensitivity usually struggle in a narrow pressure detection range (<30 kPa) while expanding the detection range normally sacrifices the sensitivity. To overcome this well-known obstacle, herein, piezopotential enhanced triboelectric effect realized by a rationally designed PDMS/ZnO NWs hierarchical wrinkle structure was exploited to develop a TPS (PETPS) with both high sensitivity and wide detecting range. In this PETPS design, the piezopotential derived from the deformation of ZnO NWs enhances its tribo-charge transferring ability; meanwhile, the hierarchical structure helps to establish a dynamically self-adjustable contact area. Benefiting from these advantages, the PETPS simultaneously achieves high sensitivity (0.26 nC cm-2 kPa-1 from 1 to 25 kPa, and 0.02 nC cm-2 kPa-1 from 25 to 476 kPa), fast response (46 ms), wide sensing range (1 to 476 kPa), and good stability (over 4000 cycles). In addition, the output charge density that is independent of the speed rate of driven force was adopted as the sensing signal of PETPS to replace the commonly used peak voltage/current values, enabling it more adaptive to accurately detect pressure variation in real applications.

15.
Appl Radiat Isot ; 205: 111184, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38215645

RESUMEN

Boron neutron capture therapy (BNCT) combines neutron irradiation with boron compounds that are selectively uptaken by tumor cells. Boronophenylalanine (BPA) is a boron compound used to treat malignant brain tumors. The determination of boron concentration in cells is of great relevance to the field of BNCT. This study was designed to develop a novel method for simultaneously measuring the uptake of BPA by U87 and U251 cells (two brain tumor cell lines) and number of cells using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results revealed a linear correlation between phosphorus intensity and the numbers of U87 and U251 cells, with correlation coefficients (R2) of 0.9995 and 0.9994, respectively. High accuracy and reliability of phosphorus concentration standard curve were also found. Using this new method, we found that BPA had no significant effect on phosphorus concentration in either U87 or U251 cells. However, BPA increased the boron concentration in U87 and U251 cells in a concentration-dependent manner, with the boron concentration in U87 cells being higher than that in U251 cells. In both U87 and U251 cells, boron was mainly distributed in the cytoplasm and nucleus, accounting for 85% and 13% of the total boron uptake by U87 cells and 86% and 11% of the total boron uptake by U251 cells, respectively. In the U87 and U251 cell-derived xenograft (CDX) animal model, tumor exhibited higher boron concentration values than blood, heart, liver, lung, and brain, with a tumor/blood ratio of 2.87 for U87 cells and 3.11 for U251 cells, respectively. These results suggest that the phosphorus concentration in U87 and U251 cells can represent the number of cells and BPA is easily uptaken by tumor cells as well as in tumor tissue.


Asunto(s)
Terapia por Captura de Neutrón de Boro , Neoplasias Encefálicas , Animales , Humanos , Espectrofotometría Atómica , Boro , Reproducibilidad de los Resultados , Neoplasias Encefálicas/radioterapia , Encéfalo , Compuestos de Boro , Fósforo , Terapia por Captura de Neutrón de Boro/métodos
16.
Clinics (Sao Paulo) ; 79: 100314, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38219533

RESUMEN

OBJECTIVE: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. METHODS: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. RESULTS: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. CONCLUSION: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.


Asunto(s)
MicroARNs , Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Retroalimentación , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
17.
Adv Mater ; 36(18): e2310663, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38267010

RESUMEN

Organic phosphorescent scintillating materials have shown great potential for applications in radiography and radiation detection due to their efficient utilization of excitons. However, revealing the relationship between molecule stacking and the phosphorescent radioluminescence of scintillators is still challenging. This study reports on two phenothiazine derivatives with polymorphism-dependent phosphorescence radioluminescence. The experiments reveal that molecule stacking significantly affects the non-radiation decay of the triplet excitons of scintillators, which further determines the phosphorescence scintillation performance under X-ray irradiation. These phosphorescent scintillators exhibit high radio stability and have a low detection limit of 278 nGys-1. Additionally, the potential application of these scintillators in X-ray radiography, based on their X-ray excited radioluminescence properties, is demonstrated. These findings provide a guideline for obtaining high-performance phosphorescent scintillating materials by shedding light on the effect of crystal packing on the radioluminescence of organic molecules.

18.
Chem Biol Drug Des ; 103(1): e14363, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37793997

RESUMEN

Hepatocellular carcinoma (HCC) is a life-threatening disease for which there is no cure. Traditional Chinese medicine is a treasure trove of Medicinals that has been used for thousands of years. In China, the traditional herb pair, Curcumae Rhizoma and Sparganii Rhizoma (CR-SR) represent a classic herbal combination used for the treatment of HCC. However, the drug targets and pharmacological mechanism of action of CR-SR in the treatment of HCC are unclear. To address this, we screened the active components and drug targets of CR-SR from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and a high-throughput experiment- and reference-guided database of traditional Chinese medicines (HERB database). Combined with the weighted co-expression network analysis of dataset GSE76427, we constructed an active component-target-disease regulatory network. It was found that CR-SR's active components for HCC treatment included trans-gondoic acid, beta-sitosterol, stigmasterol, hederagenin, and formononetin. These compounds specifically targeted the genes Estrogen Receptor 1 (ESR1), Cyclin A2 (CCNA2), Checkpoint Kinase 1 (CHEK1), and Nuclear Receptor Coactivator 2 (NCOA2). ESR1, CCNA2, and CHEK1 genes showed significant differences in survival prognosis, expression levels, and statistical significance during the pathological stage. Moreover, their high affinity for formononetin was determined through molecular docking analysis. Cell assays and high-throughput sequencing were performed to reveal that the inhibitory effect of formononetin on HepG2 cell proliferation was related to hepatocyte metabolism and cell cycle regulation-related pathways. This study provides insights into potential HCC treatments.


Asunto(s)
Carcinoma Hepatocelular , Medicamentos Herbarios Chinos , Isoflavonas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Farmacología en Red , Simulación del Acoplamiento Molecular , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico
19.
Clinics ; 79: 100314, 2024. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1528431

RESUMEN

ABSTRACT Objective: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. Methods: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. Results: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. Conclusion: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.

20.
J Med Virol ; 95(11): e29244, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-38010649

RESUMEN

Cervical cancers are the fourth most common and most deadly cancer in women worldwide. Despite being a tremendous public health burden, few novel approaches to improve care for these malignancies have been introduced. We discuss the potential for proliferating cell nuclear antigen (PCNA) inhibition to address this need as well as the advantages and disadvantages for compounds that can therapeutically inhibit PCNA with a specific focus on cervical cancer.


Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Antígeno Nuclear de Célula en Proliferación
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