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1.
Mol Cell ; 83(19): 3502-3519.e11, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37751742

RESUMEN

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress. We find that mTORC1 regulates MFSD12 by directly phosphorylating residue T254, while mTORC1 inhibition enhances lysosome acidification that activates CTNS. This switch modulates lysosomal cyst(e)ine levels in response to oxidative stress, fine-tuning redox homeostasis to enhance cell fitness. MFSD12-T254A mutant inhibits MFSD12 function and suppresses tumor progression. Moreover, MFSD12 overexpression correlates with poor neoadjuvant chemotherapy response and prognosis in breast cancer patients. Our findings reveal the critical role of lysosomal cyst(e)ine storage in adaptive redox homeostasis and suggest that MFSD12 is a potential therapeutic target.

2.
Nanotechnology ; 35(20)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38286015

RESUMEN

A transfer-free graphene with high magnetoresistance (MR) and air stability has been synthesized using nickel-catalyzed atmospheric pressure chemical vapor deposition. The Raman spectrum and Raman mapping reveal the monolayer structure of the transfer-free graphene, which has low defect density, high uniformity, and high coverage (>90%). The temperature-dependent (from 5 to 300 K) current-voltage (I-V) and resistance measurements are performed, showing the semiconductor properties of the transfer-free graphene. Moreover, the MR of the transfer-free graphene has been measured over a wide temperature range (5-300 K) under a magnetic field of 0 to 1 T. As a result of the Lorentz force dominating above 30 K, the transfer-free graphene exhibits positive MR values, reaching ∼8.7% at 300 K under a magnetic field (1 Tesla). On the other hand, MR values are negative below 30 K due to the predominance of the weak localization effect. Furthermore, the temperature-dependent MR values of transfer-free graphene are almost identical with and without a vacuum annealing process, indicating that there are low density of defects and impurities after graphene fabrication processes so as to apply in air-stable sensor applications. This study opens avenues to develop 2D nanomaterial-based sensors for commercial applications in future devices.

3.
Hum Brain Mapp ; 44(6): 2176-2190, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36661217

RESUMEN

Differentiating the parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (IPD) is challenging, especially in the early stages. This study aimed to investigate differences and similarities in the brain functional connectomes of IPD and MSA-P patients and use machine learning methods to explore the diagnostic utility of these features. Resting-state fMRI data were acquired from 88 healthy controls, 76 MSA-P patients, and 53 IPD patients using a 3.0 T scanner. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 116 regions, and topological properties were evaluated through graph theory approaches. Connectome measurements were used as features in machine learning models (random forest [RF]/logistic regression [LR]/support vector machine) to distinguish IPD and MSA-P patients. Regarding graph metrics, early IPD and MSA-P patients shared network topological properties. Both patient groups showed functional connectivity disruptions within the cerebellum-basal ganglia-cortical network, but these disconnections were mainly in the cortico-thalamo-cerebellar circuits in MSA-P patients and the basal ganglia-thalamo-cortical circuits in IPD patients. Among the connectome parameters, t tests combined with the RF method identified 15 features, from which the LR classifier achieved the best diagnostic performance on the validation set (accuracy = 92.31%, sensitivity = 90.91%, specificity = 93.33%, area under the receiver operating characteristic curve = 0.89). MSA-P and IPD patients show similar whole-brain network topological alterations. MSA-P primarily affects cerebellar nodes, and IPD primarily affects basal ganglia nodes; both conditions disrupt the cerebellum-basal ganglia-cortical network. Moreover, functional connectome parameters showed outstanding value in the differential diagnosis of early MSA-P and IPD.


Asunto(s)
Conectoma , Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Atrofia de Múltiples Sistemas/diagnóstico por imagen , Ganglios Basales , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos
4.
J Transl Med ; 21(1): 310, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-37158918

RESUMEN

BACKGROUND: Cognitive dysfunction is the most common non-motor symptom in Parkinson's disease (PD), and timely detection of a slight cognitive decline is crucial for early treatment and prevention of dementia. This study aimed to build a machine learning model based on intra- and/or intervoxel metrics extracted from diffusion tensor imaging (DTI) to automatically classify PD patients without dementia into mild cognitive impairment (PD-MCI) and normal cognition (PD-NC) groups. METHODS: We enrolled PD patients without dementia (52 PD-NC and 68 PD-MCI subtypes) who were assigned to the training and test datasets in an 8:2 ratio. Four intravoxel metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and two novel intervoxel metrics, local diffusion homogeneity (LDH) using Spearman's rank correlation coefficient (LDHs) and Kendall's coefficient concordance (LDHk), were extracted from the DTI data. Decision tree, random forest, and eXtreme gradient boosting (XGBoost) models based on individual and combined indices were built for classification, and model performance was assessed and compared via the area under the receiver operating characteristic curve (AUC). Finally, feature importance was evaluated using SHapley Additive exPlanation (SHAP) values. RESULTS: The XGBoost model based on a combination of the intra- and intervoxel indices achieved the best classification performance, with an accuracy of 91.67%, sensitivity of 92.86%, and AUC of 0.94 in the test dataset. SHAP analysis showed that the LDH of the brainstem and MD of the right cingulum (hippocampus) were important features. CONCLUSIONS: More comprehensive information on white matter changes can be obtained by combining intra- and intervoxel DTI indices, improving classification accuracy. Furthermore, machine learning methods based on DTI indices can be used as alternatives for the automatic identification of PD-MCI at the individual level.


Asunto(s)
Disfunción Cognitiva , Demencia , Enfermedad de Parkinson , Humanos , Imagen de Difusión Tensora , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/diagnóstico por imagen , Árboles de Decisión
5.
J Fluoresc ; 2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37615895

RESUMEN

Cisplatin is an important platinum drug in cancer chemotherapy in clinical practice. It is well established that the main target of cisplatin is nuclear DNA. However, recent studies have demonstrated that platinum drugs may act on some important functional proteins in the human body. E-cadherin is a newly discovered glycoprotein that has been regarded as an important sign of the occurrence and development of some tumors. This study examines the interactions between cisplatin and E-cadherin by fluorescence spectrometry and atomic force microscopy (AFM). The fluorescence spectrometry results indicated that cisplatin can efficiently quench the fluorescence of E-cadherin. The calculated binding constant Kb was 3.20 × 106 (25 ℃), 1.36 × 106(31 ℃), and 8.22 × 105 L mol-1 (37 ℃). These results reveal that the fluorescence quenching effect of cisplatin on E-cadherin is static quenching. The obtained thermodynamic parameters ΔH < 0, ΔS < 0, and ΔG < 0, indicate that the binding of cisplatin on E-cadherin is a spontaneous process dominated by hydrogen bonds and Van der Waals forces. The AFM results revealed that E-cadherins are interlaced with each other to form a spherical-chain structure. The addition of cisplatin can significantly disrupt the interlaced structure of the E-cadherin molecules.

6.
Bioorg Chem ; 135: 106488, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36989734

RESUMEN

Abnormal activation of Hedgehog (Hh) signaling pathway mediates the genesis and progression of various tumors [1]. Currently, three drugs targeting the Hh signaling component Smoothened (Smo) have been marketed for the clinical treatment of basal cell tumors or acute myeloid leukemia. However, drug resistance is a common problem in those drugs, so the study of Smo inhibitors that can overcome drug resistance has important guiding significance for clinical adjuvant drugs. MTT assay, clone formation assay and EdU assay were used to detect the proliferation inhibitory activity of the drugs on tumor cells. The effect of B13 on cell cycle and apoptosis were detected by flow cytometry. An acute toxicity test was used to detect the toxicity of B13 in vivo, and xenograft tumor model was used to detect the efficacy of B13 in vivo. The binding of B13 to Smo was studied by BODIPY-cyclopamine competitive binding assay and molecular docking. The effect of B13 on the expression and localization of downstream target gene Gli1/2 of Smo was investigated by Western Blot and immunofluorescence assay. SmoD473H mutant cell line was constructed to study the effect of B13 against drug resistance. (1) B13 had the strongest inhibitory activity against colorectal cancer cells. (2) B13 can effectively inhibit the clone formation and EdU positive rate of colon cancer cells. (3) B13 can block the cell cycle in the G2/M phase and cell apoptosis. (4) B13 has low toxicity in vivo, and its efficacy in vivo is better than that of the Vismodegib. (5) Molecular docking and BODIPY-cyclopamine experiments showed that B13 could bind to Smo protein. (6) B13 can inhibit the protein expression of Gli1, the downstream of Smo, and inhibit its entry into the nucleus. (7) B13 could inhibit the expression of Gli1 in the HEK293 cells with SmoD473H, and the molecular docking results showed that B13 could bind SmoD473H protein. B13 with the best anti-tumor activity was screened out by MTT assay. In vitro, pharmacodynamics experiments showed that B13 could effectively inhibit the proliferation and metastasis of colorectal cancer cells, induce cell cycle arrest, and induce cell apoptosis. In vivo pharmacodynamics experiments showed that B13 was superior to Vismodegib in antitumor activity and had low toxicity in vivo. Mechanism studies have shown that B13 can bind Smo protein, inhibit the expression of downstream Gli1 and its entry into the nucleus. Notably, B13 overcomes resistance caused by SmoD473H mutations.


Asunto(s)
Neoplasias Colorrectales , Proteínas Hedgehog , Humanos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Proteína con Dedos de Zinc GLI1/farmacología , Células HEK293 , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Proliferación Celular
7.
Int J Med Sci ; 20(6): 810-817, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37213666

RESUMEN

Interferon gamma (IFNγ) is a cytokine implicated in the pathogenesis of autoimmune diseases. SAM and HD domain-containing protein 1 (SAMHD1) is an IFNγ-inducible protein that modulates cellular dNTP levels. Mutations in the human SAMHD1 gene cause Aicardi-Goutières (AG) syndrome, an autoimmune disease sharing similar clinical features with systemic lupus erythematosus (SLE). Klotho is an anti-inflammatory protein which suppresses aging through multiple mechanisms. Implication of Klotho in autoimmune response is identified in rheumatologic diseases such as SLE. Little information exists regarding the effect of Klotho in lupus nephritis, one of the prevalent symptoms of SLE. The present study verified the effect of IFNγ on SAMHD1 and Klotho expression in MES-13 glomerular mesangial cells, a special cell type in glomerulus that is critically involved in lupus nephritis. IFNγ upregulated SAMHD1 expression in MES-13 cells through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT1) and the nuclear factor kappa B (NFκB) signaling pathways. IFNγ decreased Klotho protein expression in MES-13 cells. Treatment of MES-13 cells with recombinant Klotho protein inhibited SAMHD1 expression by blocking IFNγ-induced NFκB nuclear translocation, but showed no effect on JAK-STAT1 signaling. Collectively, our findings support the protective role of Klotho in attenuating lupus nephritis through the inhibition of IFNγ-induced SAMHD1 expression and IFNγ downstream signaling in MES-13 cells.


Asunto(s)
Nefritis Lúpica , FN-kappa B , Humanos , Células Cultivadas , Interferón gamma/metabolismo , Nefritis Lúpica/genética , Células Mesangiales/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/genética , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/farmacología , Receptor de Interferón gamma
8.
Immunopharmacol Immunotoxicol ; 45(5): 549-557, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36942663

RESUMEN

BACKGROUND AND AIMS: Mesenchymal stem cell (MSC) therapy is a promising strategy for treating osteoarthritis (OA). However, the inflammatory microenvironment, apoptosis of transplanted cells, and shear forces during direct injection limit the therapeutic efficacy. This study aimed to explore the role of rapamycin combined with human umbilical-cord-derived mesenchymal stem cells (hUMSCs) in OA rabbits in vivo. METHODS: OA rabbits received an intra-articular injection of a collagenase solution. Gross observations, X-ray examinations, and histological examinations were performed to detect cartilage degradation levels. The fluorescent membrane dye DiR was used to label hUMSCs. In the combination therapy group, rapamycin was injected into the rabbit knee joint one day post the intra-articular injection of hUMSCs. Bioinformatics and transcriptome profiling of the knee meniscus were used to evaluate the potential molecular mechanisms of the combination therapy. RESULTS: Our study shows that rapamycin combined with hUMSCs significantly ameliorated OA severity in vivo, enhancing matrix synthesis and promoting cartilage repair. The combination therapy was more efficient than rapamycin or hUMSC treatment alone. Moreover, bioinformatics and transcriptomic analyses revealed that combination therapy might enhance autophagy in chondrocytes, partially by inhibiting the mTOR pathway. CONCLUSIONS: Our study indicates that the combination therapy of rapamycin and hUMSCs may promote cartilage repair in OA rabbits through the mTOR pathway and offers a novel approach for OA therapy. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study provides new evidence to support the use of hUMSCs in combination with rapamycin as a potential candidate for OA treatment.


Asunto(s)
Cartílago Articular , Células Madre Mesenquimatosas , Osteoartritis , Animales , Humanos , Conejos , Sirolimus/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Cartílago Articular/metabolismo , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Osteoartritis/metabolismo , Células Madre Mesenquimatosas/metabolismo
9.
Sensors (Basel) ; 23(3)2023 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-36772538

RESUMEN

Internet of Things (IoT) finance extends financial services to the whole physical commodity society with the help of IoT technology to realize financial automation and intelligence. However, the security of IoT finance still needs to be improved. Blockchain has the characteristics of decentralization, immutability, faster settlement, etc., and has been gradually applied to the field of IoT finance. Blockchain is also considered to be an effective way to resolve the problems of the traditional supply chain finance industry, such as the inability to transmit core enterprise credit, the failure of full-chain business information connections and the difficulty of clearing and settlement. Supply chain finance allows the strongest enterprise in the supply chain to apply for credit guarantee from the bank to obtain bank loans, and use the funds for circulation in the supply chain to ensure that each enterprise in the whole supply chain can obtain working capital to realize profits, so as to maximize common interests. In this paper, a financial management platform based on the integration of blockchain and supply chain has been designed and implemented. Blockchain is used to integrate supply chain finance to synchronize the bank account payment system, realize the automatic flow of funds, process supervision and automatically settle account periods based on smart contracts. The four functional modules of the system are designed using unified modeling language (UML), and the model view controller (MVC) architecture is selected as the main architecture of the system. The results of the system test show that the proposed platform can effectively improve the system security, and can use the information in the blockchain to provide multi-level financing services for enterprises in supply chain finance.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(8): 877-883, 2023 Aug 15.
Artículo en Zh | MEDLINE | ID: mdl-37668038

RESUMEN

Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.


Asunto(s)
Trastorno del Espectro Autista , COVID-19 , Epidemias , Problema de Conducta , Humanos , Niño
11.
Clin Endocrinol (Oxf) ; 97(5): 604-611, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35274757

RESUMEN

OBJECTIVE: Idiopathic hypogonadotropic hypogonadism (IHH) is rare and can either be associated with normal or defective olfactory sensation, classified as normosmic IHH (nIHH) or Kallmann syndrome (KS). We do not yet understand the central processing pathways in the olfactory system. We aimed to compare the resting-state structural and functional connectivity (FC) of olfactory neural pathways in patients with IHH. We hypotheses that alterations of structural connectivity and FC may exist in the olfactory cortex pathways in IHH patients. DESIGN: STRUCTURAL AND FUNCTIONAL CONNECTIVITY DATA RESULTS BETWEEN TWO GROUPS WERE ANALYZED: Patients: Twenty-five IHH patients (13 nIHH patients and 12 KS patients) were recruited from the Department of Endocrinology and were assessed. A total of 25 age-matched healthy male controls were recruited from the community. MEASUREMENTS: All subjects underwent diffusion tensor imaging and functional magnetic resonance imaging (fMRI) scans. Structural and functional connectivity data analyses were then performed. Pearson's correlation analyses were performed to investigate the correlations between the fractional anisotropy (FA) value and FC strength, showing significant differences among the three groups separately. RESULTS: Compared with the HC group, FA value in the right uncinate fasciculus (UF) decreased significantly in the IHH group. The olfactory cortex FC values of the right gyrus rectus, orbitofrontal cortex (OFC) and right middle temporal gyrus in the IHH group were decreased compared with those in the HC group. Moreover, there were significant negative correlations between right UF FA and olfactory cortex-FC to both the gyrus rectus and OFC within the HC group (p < .05). CONCLUSION: Our findings suggest that alterations of structural and FC support the presence of neurobiological disruptions in IHH patients, particularly a specific structural-functional asymmetry disruption may exist in the olfactory cortex pathways in IHH patients.


Asunto(s)
Hipogonadismo , Síndrome de Kallmann , Imagen de Difusión Tensora , Humanos , Sistema Límbico , Masculino
12.
J Environ Manage ; 312: 114899, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35334402

RESUMEN

Ozone (O3) pollution poses health risks and premature mortality, and gas stations are one of the largest sources of urban volatile organic compounds (VOCs, the main precursor to O3). This paper investigates whether the government's call for night refueling, which can be regarded as a green nudge, can guide changes in consumer behavior and consequently improve environmental quality. Using a difference-in-differences (DID) estimation and weekly monitoring site air quality panel data, we analyze the effect of the Night Refueling Preferential Policy on O3 concentrations. We find that the policy can reduce O3 concentrations by 10% by encouraging consumers to refuel at night. The reduction in O3 has brought great benefits to human health, leading to a 4-5‰ reduction in non-accidental mortality and a 6-8‰ reduction in cardiovascular mortality in Jiangsu province. The economic benefits of this policy would be approximately 62-189 billion Chinese Yuan (CNY) if it were implemented nationwide. The findings of this study suggest that the government can influence consumer behavior to promote environmental quality.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/prevención & control , China , Monitoreo del Ambiente , Humanos , Ozono/análisis , Políticas , Compuestos Orgánicos Volátiles/análisis
13.
Molecules ; 27(11)2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35684492

RESUMEN

In this work, the extraction procedure of a natural pigment from the flower of Ceiba speciosa (A. St.-Hil.) was optimized by response surface methodology. It is the first time that the extraction of the flower pigment of C. speciosa (FPCS) has been reported, along with an evaluation of its stability and biological activity under various conditions, and an exploration of its potential use as a food additive and in medicine. Specifically, the effects of ethanol concentration, solid-liquid ratio, temperature and time on the extraction rate of FPCS were determined using a Box-Behnken design. The optimum extraction conditions for FPCS were 75% ethanol with a solid-liquid ratio of 1:75 mg/mL) at 66 °C for 39 min. The purification of FPCS using different macroporous resins showed that D101 performed best when the initial mass concentration of the injection solution was 1.50 mg/mL, resulting in a three-fold increase in color value. The yield of dry flowers was 9.75% of fresh petals and the FPCS extraction efficiency was 43.2%. The effects of light, solubility, pH, temperature, sweeteners, edible acids, redox agents, preservatives and metal ions on FPCS were also investigated. Furthermore, the characteristics of FPCS were determined by spectrophotometry at a specific wavelength using the Lambert-Beer law to correlate the mass of FPCS with its absorbance value. An acute toxicological test performed according to Horne's method showed that FPCS is a non-toxic extract and thus may be used as a food additive or in other ingestible forms. Finally, western blotting showed that FPCS prevents lipopolysaccharide-induced hippocampal oxidative stress in mice. The study suggests that FPCS may function as an antioxidant with applications in the food, cosmetics and polymer industries.


Asunto(s)
Ceiba , Animales , Antioxidantes/farmacología , Etanol , Flores , Aditivos Alimentarios , Ratones , Extractos Vegetales/farmacología
14.
Pharmazie ; 77(2): 59-66, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35209965

RESUMEN

Background: Patients with prostate cancer often develop resistance to androgen deprivation therapy, a condition called castration-resistant prostate cancer (CRPC). Enzalutamide (MDV3100) can prolong the survival of patients with CRPC after chemotherapy, but ∼50% of patients eventually relapse and develop resistance to MDV3100. Thus, it is necessary to explore new treatment methods to improve the therapeutic effect of MDV3100. Tyrosine kinases play an essential role in the pathogenesis of CRPC. Methods: MTT assay was used to detect the inhibitory effects of MDV3100 and tyrosine kinase inhibitor on prostate cancer cells. CompuSyn version 1.0 was used to calculate the combination index (CI) values using the Chou-Talalay method. Clone formation and EdU assay were used to detect the effect of afatinib combined with MDV3100 on the proliferation of 22Rv1 cells. RT-qPCR and Western blot were used to explore the mechanism of drug combination. The aim of the present study was to determine the effects of several tyrosine kinase inhibitors (TKIs) when used in combination with MDV3100 in vitro. Results: The results demonstrated that TKIs combined with MDV3100 exerted a synergistic effect on a variety of PCa cells. Afatinib combined with MDV3100 could suppress the proliferation and migration of 22RV1 cells, as well as cause their cell cycle arrest and apoptosis. Mechanistically, afatinib effectively reduced the protein expression levels of HER2 and HER3 and inhibited EGFR phosphorylation, thereby enhancing the effect of MDV3100 and suppressing CRPC. Conclusions: These findings suggested that afatinib treatment improved the effect of MDV3100 on 22RV1 cells, highlighting this drug as a potential therapeutic strategy for patients with CRPC.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Afatinib/farmacología , Afatinib/uso terapéutico , Antagonistas de Andrógenos , Benzamidas , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Humanos , Masculino , Recurrencia Local de Neoplasia , Nitrilos/farmacología , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Receptores Androgénicos/uso terapéutico
15.
Hum Brain Mapp ; 42(13): 4314-4326, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34060682

RESUMEN

Data from both animal models and deaf children provide evidence for that the maturation of auditory cortex has a sensitive period during the first 2-4 years of life. During this period, the auditory stimulation can affect the development of cortical function to the greatest extent. Thus far, little is known about the brain development trajectory after early auditory deprivation within this period. In this study, independent component analysis (ICA) technique was used to detect the characteristics of brain network development in children with bilateral profound sensorineural hearing loss (SNHL) before 3 years old. Seven resting-state networks (RSN) were identified in 50 SNHL and 36 healthy controls using ICA method, and further their intra-and inter-network functional connectivity (FC) were compared between two groups. Compared with the control group, SNHL group showed decreased FC within default mode network, while enhanced FC within auditory network (AUN) and salience network. No significant changes in FC were found in the visual network (VN) and sensorimotor network (SMN). Furthermore, the inter-network FC between SMN and AUN, frontal network and AUN, SMN and VN, frontal network and VN were significantly increased in SNHL group. The results implicate that the loss and the compensatory reorganization of brain network FC coexist in SNHL infants. It provides a network basis for understanding the brain development trajectory after hearing loss within early sensitive period.


Asunto(s)
Encéfalo , Conectoma , Red en Modo Predeterminado , Pérdida Auditiva Sensorineural/fisiopatología , Imagen por Resonancia Magnética , Red Nerviosa , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Encéfalo/fisiopatología , Preescolar , Conectoma/métodos , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/crecimiento & desarrollo , Red en Modo Predeterminado/fisiopatología , Femenino , Pérdida Auditiva Sensorineural/diagnóstico por imagen , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/crecimiento & desarrollo , Red Nerviosa/fisiopatología
16.
Exp Eye Res ; 212: 108695, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34228966

RESUMEN

OBJECTIVE: The aim of this study is to evaluate the cellular biomechanical properties and MMP-2 expression changes in rabbit scleral fibroblasts using two modes of riboflavin and ultraviolet A (UVA) collagen cross-linking (CXL). METHODS: Twenty-four New Zealand white rabbits were randomly divided into two groups, A and B. The left eye was chosen for the experimental group and the right eye for the control group. In group A, the eyes were irradiated for 30 min, with a power density of 3.0 mW/cm2. In group B, the eyes were irradiated for 9 min, with a power density of 10.0 mW/cm2. One week after CXL, full-field electroretinography was performed. Sixty days after CXL, the rabbits were sacrificed, and scleral fibroblasts were extracted from the CXL-treated sclera area and corresponding parts of control sclera and cultured. Cellular biomechanical properties were evaluated using the micropipette aspiration technique, and the MMP-2 protein expression was determined by Western blot analysis. RESULTS: There was no statistical difference in the amplitude and latency of the dark adaptation 3.0 and light adaptation 3.0 between the CXL and control eyes of groups A and B (P > 0.05). Compared with the control groups, the Young's modulus of the fibroblasts and apparent viscosity of the experimental eyes in groups A and B were increased after CXL (P < 0.05), but there was no significant difference between the two groups under different irradiation modes (P > 0.05). The MMP-2 expression in scleral fibroblasts from experimental eyes was significantly higher than that in scleral fibroblasts from control eyes in groups A and B. Under the two different irradiation modes, the MMP-2 expression in the scleral fibroblasts from experimental eyes in group A was significantly higher than that in the scleral fibroblasts from experimental eyes in group B. CONCLUSION: The riboflavin-UVA scleral CXL conducted in two different modes produced no significant side effects on the retina and could strengthen the cell biomechanical properties as well as increase the MMP-2 expression of scleral fibroblasts significantly.


Asunto(s)
Colágeno/farmacología , Reactivos de Enlaces Cruzados/farmacología , Metaloproteinasa 2 de la Matriz/biosíntesis , Miopía/tratamiento farmacológico , Riboflavina/farmacología , Esclerótica/patología , Rayos Ultravioleta , Animales , Adaptación a la Oscuridad , Modelos Animales de Enfermedad , Elasticidad , Electrorretinografía , Fibroblastos/metabolismo , Fibroblastos/patología , Miopía/metabolismo , Miopía/fisiopatología , Fármacos Fotosensibilizantes/farmacología , Conejos , Esclerótica/metabolismo
17.
Nanotechnology ; 31(50): 505201, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-32996469

RESUMEN

Being a new class of materials, transition metal dichalcogenides are paving the way for applications in atomically thin optoelectronics. However, the intrinsically weak light-matter interaction and the lack of manipulation ability has lead to poor light emission and tunable behavior. Here, we investigate the fluorescence characteristic of monolayer molybdenum disulfide on a metal narrow-slit grating, where a highly efficient, 471 times photoluminescence enhancement are realized, based on the hybrid surface plasmon polaritons resonances and the decreased influence of substrate. Moreover, the emitted intensity and polarization are controllable due to the polarization-dependent characteristic and anisotropy of grating. The manipulations of light-matter interactions in this special system provide a new insight into the fluorescent emission process and open a new avenue for high-performance low dimensional materials devices designs.

18.
Opt Express ; 27(23): 33326-33332, 2019 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-31878403

RESUMEN

Towards better imaging through fog for vehicles, we developed an off-axis spatiotemporally gated multimode laser scanning imaging system. Utilizing fog mimicking liquid suspension, we tested the imaging system with different levels of scattering. The experimental results suggest that the system can yield high quality images at seven scattering path lengths, which far exceeds the capability of conventional imaging systems. We also found that the multimode detection can not only make the system robust in the presence of aberration but also help to reduce the speckles in images for the case of coherent illumination.

19.
Appl Opt ; 58(17): 4637-4641, 2019 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-31251282

RESUMEN

A 2×2 optofluidic switch chip with an air shutter is proposed. It has a simple structure, small volume, small crosstalk, large extinction ratio, small polarization-dependent loss, and broad operation waveband (400-1700 nm). This 2×2 switch chip has good scalability and can form a number of optical switches by using different microfluidic driving technologies. The research results show that the microchannel width has great influence on the switch performances in "on" state, where the comprehensive performances of the optical switch are the best at 4.0 µm width. By replacing the original symmetrical structure with an optimized semi-tapered structure, the switch performances are further improved. After the structure and parameters are optimized, for 1310 nm wavelength, the insertion losses of the proposed switch are 0.41 dB in "on" state and 0.15 dB in "off" state, the extinction ratios are 52.5 dB in "on" state and 28.3 dB in "off" state, and the crosstalks are -28.8 dB in "on" state and -52.6 dB in "off" state.

20.
BMC Med Inform Decis Mak ; 19(Suppl 2): 62, 2019 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-30961595

RESUMEN

BACKGROUND: Gender information frequently exists in the eligibility criteria of clinical trial text as essential information for participant population recruitment. Particularly, current eligibility criteria text contains the incompleteness and ambiguity issues in expressing transgender population, leading to difficulties or even failure of transgender population recruitment in clinical trial studies. METHODS: A new gender model is proposed for providing comprehensive transgender requirement specification. In addition, an automated approach is developed to extract and summarize gender requirements from unstructured text in accordance with the gender model. This approach consists of: 1) the feature extraction module, and 2) the feature summarization module. The first module identifies and extracts gender features using heuristic rules and automatically-generated patterns. The second module summarizes gender requirements by relation inference. RESULTS: Based on 100,134 clinical trials from ClinicalTrials.gov , our approach was compared with 20 commonly applied machine learning methods. It achieved a macro-averaged precision of 0.885, a macro-averaged recall of 0.871 and a macro-averaged F1-measure of 0.878. The results illustrated that our approach outperformed all baseline methods in terms of both commonly used metrics and macro-averaged metrics. CONCLUSIONS: This study presented a new gender model aiming for specifying the transgender requirement more precisely. We also proposed an approach for gender information extraction and summarization from unstructured clinical text to enhance transgender-related clinical trial population recruitment. The experiment results demonstrated that the approach was effective in transgender criteria extraction and summarization.


Asunto(s)
Almacenamiento y Recuperación de la Información , Selección de Paciente , Personas Transgénero , Ensayos Clínicos como Asunto , Heurística , Humanos , Aprendizaje Automático
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