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Differential phase contrast (DPC) imaging relies on computational analysis to extract quantitative phase information from phase gradient images. However, even modest noise level can introduce errors that propagate through the computational process, degrading the quality of the final phase result and further reducing phase sensitivity. Here, we introduce the noise-corrected DPC (ncDPC) to enhance phase sensitivity. This approach is based on a theoretical DPC model that effectively considers most relevant noise sources in the camera and non-uniform illumination in DPC. In particular, the dominating shot noise and readout noise variance can be jointly estimated using frequency analysis and further corrected by block-matching 3D (BM3D) method. Finally, the denoised images are used for phase retrieval based on the common Tikhonov inversion. Our results, based on both simulated and experimental data, demonstrate that ncDPC outperforms the traditional DPC (tDPC), enabling significant improvements in both phase reconstruction quality and phase sensitivity. Besides, we have demonstrated the broad applicability of ncDPC by showing its performance in various experimental datasets.
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Supercapacitor is an important energy storage device widely used in the automobile industry, military production, and communication equipment because of its fast charge-discharge rate, and high power density. Herein, carbon quantum dots modified and Y3+ doped Ni3(NO3)2(OH)4 (NiY@CQDs) nanospheres are prepared by a solvothermal method and used as an electrode material. The electrochemical properties of NiY@CQDs were measured in a three-electrode system. An asymmetric supercapacitor (ASC) cell was assembled with activated carbon (AC) as the anode and NiY@CQDs as the cathode. The electrochemical properties of the ASC device were measured in a two-electrode system. Experimental results show the shape of NiY@CQDs is petal-shaped and the introducing carbon quantum dots and doping Y3+ significantly increases the specific surface area, conductivity, and specific capacitance of Ni3(NO3)2(OH)4. The mass-specific capacitance of NiY@CQDs reaches up to 2944â F g-1 at a current density of 1â A g-1. The asymmetric supercapacitor of NiY@CQDs//AC has a high energy density of 138.65â Wh kg-1 at a power density of 1500â W kg-1, displaying a wide range of application prospects in the energy storage area.
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This study aimed to examine the association between sex hormone-binding globulin (SHBG) and osteoporosis through a cross-sectional study and a two-sample bidirectional Mendelian randomization (MR). We used the National Health and Nutrition Examination Survey (NHANES) 2013-2014 and 2015-2016 data, with exposure as serum SHBG and outcome as osteoporosis and performed multivariate logistic regression to test the correlation between SHBG and osteoporosis. To determine the causal relationship between SHBG and osteoporosis, a two-sample bidirectional MR was employed. The genome-wide association study (GWAS) dataset for SHBG (n = 189,473) was obtained from the IEU database, and the GWAS dataset for osteoporosis (n = 212,778) was obtained from the FinnGen bioBank. The principal MR technique was inverse-variance weighting (IVW). In MR analyses, the MR-Egger intercept and Cochran Q test were used to detect multiple validity and horizontal heterogeneity. 1249 older adult participants (age ≥ 60) were involved in the cross-sectional study, including 113 osteoporosis cases. We identified a significant relationship between circulating SHBG concentration and osteoporosis risk [OR 3.963, 95% CI (2.095-7.495), P < 0.05]. Subgroup analysis indicated that SHBG was closely linked to the risk of osteoporosis in the female population [OR 1.008, 95% CI (1.002-1.013), P = 0.005] but not in males (P = 0.065). In addition, The IVW approach suggested a causal connection between SHBG and increased osteoporosis risk [OR 1.479, 95% CI (1.144-1.912), P = 0.003], and the MR-Egger intercept and the Cochran Q test validated the consistency of the MR results. Finally, the reverse MR analysis declined to identify a causal relation between SHBG and osteoporosis. Our research demonstrates a significant causal connection between circulating SHBG levels and increased osteoporosis risk. These results indicate that high SHBG may be associated with the risk of osteoporosis in postmenopausal women, but more research is needed.
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Osteoporose , Globulina de Ligação a Hormônio Sexual , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Nonoxinol , Inquéritos Nutricionais , Osteoporose/epidemiologia , Osteoporose/genética , Globulina de Ligação a Hormônio Sexual/genéticaRESUMO
BACKGROUND: Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular nucleus (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine. METHODS: A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition. RESULTS: Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRHPVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRHPVN neurons was attenuated by the α2-receptor antagonist yohimbine. CONCLUSIONS: The results indicate that the anxiety-like effects of dexmedetomidine are mediated via α2-adrenergic receptor-triggered inhibition of CRHPVN neuronal excitability in the hypothalamus.
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Ansiedade , Dexmedetomidina , Neurônios , Núcleo Hipotalâmico Paraventricular , Estresse Psicológico , Animais , Masculino , Camundongos , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Hormônio Liberador da Corticotropina/metabolismo , Dexmedetomidina/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Estresse Psicológico/psicologiaRESUMO
OBJECTIVES: To evaluate the combined performance of orbital MRI and intracranial visual pathway diffusion kurtosis imaging (DKI) in diagnosing dysthyroid optic neuropathy (DON). METHODS: We retrospectively enrolled 61 thyroid-associated ophthalmopathy (TAO) patients, including 25 with DON (40 eyes) and 36 without DON (72 eyes). Orbital MRI-based apical muscle index (MI), diameter index (DI) of the optic nerve (ON), area index (AI) of the ON, apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) of the ON, DKI-based kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) of the optic tract (OT), optic radiation (OR), and Brodmann areas (BAs) 17, 18, and 19 were measured and compared between groups. The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses and compared using the DeLong test. RESULTS: TAO patients with DON had significantly higher apical MI, apical AI, and SIR of the ON, but significantly lower ADC of the ON than those without DON (p < 0.05). Meanwhile, the DON group exhibited significantly lower KFA across the OT, OR, BA17, BA18, and BA19 and lower MK at the OT and OR than the non-DON group (p < 0.05). The model integrating orbital MRI and intracranial visual pathway DKI parameters performed the best in diagnosing DON (AUC = 0.926), with optimal diagnostic sensitivity (80%) and specificity (94.4%), followed by orbital MRI combination (AUC = 0.890), and then intracranial visual pathway DKI combination (AUC = 0.832). CONCLUSION: Orbital MRI and intracranial visual pathway DKI can both assist in diagnosing DON. Combining orbital and intracranial imaging parameters could further optimize diagnostic efficiency. CLINICAL RELEVANCE STATEMENT: The novel finding could bring novel insights into the precise diagnosis and treatment of dysthyroid optic neuropathy, accordingly, contributing to the improvement of the patients' prognosis and quality of life in the future. KEY POINTS: ⢠Orbital MRI and intracranial visual pathway diffusion kurtosis imaging can both assist in diagnosing dysthyroid optic neuropathy. ⢠Combining orbital MRI and intracranial visual pathway diffusion kurtosis imaging optimized the diagnostic efficiency of dysthyroid optic neuropathy.
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Oftalmopatia de Graves , Doenças do Nervo Óptico , Vias Visuais , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Oftalmopatia de Graves/diagnóstico por imagem , Doenças do Nervo Óptico/diagnóstico por imagem , Vias Visuais/diagnóstico por imagem , Adulto , Imageamento por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Sensibilidade e Especificidade , Nervo Óptico/diagnóstico por imagem , Idoso , Órbita/diagnóstico por imagemRESUMO
Using molecular dynamics simulations, this study investigates the equilibrium properties and flow behaviors of entangled polymer nanoparticle composites (PNCs) within a nanotube. The results show that the density distribution of nanoparticles (NPs), displacement of polymer chains and NPs, and the moduli of PNCs remain relatively unaffected when NP volume fractions (ΦN) ≤0.10. However, the flow behavior of entangled PNCs deviates from the ideal parabolic profile seen in unentangled PNCs, displaying plug-like flow characteristics with a significant platform region, indicating the presence of shear bands. Interestingly, entangled PNCs at intermediate ΦN values undergo a significant alteration in NP distribution under steady flow, resulting in notable NP aggregation. At ΦN = 0.30, a distinct change in the static structure of PNCs occurs, reducing the equilibrium distance between neighboring NPs. Consequently, the motion of both polymer chains and NPs becomes restricted, leading to an increase in the moduli of PNCs resembling solid-like behavior. Additionally, the entangled PNCs experience a complete absence of flow, indicating the entry into a jamming state. This study contributes to the understanding of PNCs flow behavior and provides insights into fundamental aspects and practical implications of PNCs.
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Simulação de Dinâmica Molecular , Nanopartículas , Nanotubos , Polímeros , Polímeros/química , Nanopartículas/química , Nanotubos/química , Tamanho da PartículaRESUMO
Metal-organic framework compounds are extensively utilized in various fields, such as electrode materials, owing to their distinctive porous structure and significant specific surface area. In this study, NiCoAl-MOF metal-organic framework precursors were synthesized by a solvothermal method, and NiAl2O4/NiCo2O4 electrode materials were prepared by the subsequent calcination of the precursor. These materials were characterized by XRD, XPS, BET tests, and SEM, and the electrochemical properties of the electrode materials were tested by CV and GCD methods. BET tests showed that NiAl2O4/NiCo2O4 has an abundant porous structure and a large specific surface area of up to 105 m2 g-1. The specific capacitance of NiAl2O4/NiCo2O4 measured by the GCD method reaches up to 2870.83 F g-1 at a current density of 1 A g-1. The asymmetric supercapacitor NiAl2O4/NiCo2O4//AC assembled with activated carbon electrodes has a maximum energy density of 166.98 W h kg-1 and a power density of 750.00 W kg-1 within a voltage window of 1.5 V. In addition, NiAl2O4/NiCo2O4 materials have good cycling stability. These advantages make it a good candidate for the application of high-performance supercapacitors.
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Carbon dioxide (CO2) stands as the primary driver of Earth's greenhouse effect, and it's suggested that the global contribution of CO2 emissions from lakes cannot be ignored. Despite the numerous estimations of CO2 fluxes from lakes, limited focus has been directed towards the carbon isotopes (δ13C) of dissolved CO2 in lake water. Particularly, the potential use of δ13C values in tracing the CO2 concentrations in lake water remains as an understudied area, warranting further exploration and investigation. In this study, we conducted an analysis of the concentrations and δ13C values of dissolved CO2 in 33 lakes located at the Tibetan Plateau, Chinese Loess Plateau, and Yangtze Plain (among which high-resolution spatial investigations were performed in 6 lakes through in-situ continuous monitoring). Our findings revealed spatial variations in both the CO2 concentrations and δ13C values in lakes. Additionally, notable differences are observed among lakes in different regions of China, with lakes in the Yangtze Plain exhibiting considerably higher CO2 concentrations, and the overall CO2 δ13C values in lakes on the Tibetan Plateau tend to be more positive, while those in lakes on the Chinese Loess Plateau tend to be more negative. The pH values, dissolved oxygen, and dissolved organic carbon are likely crucial factors influencing the CO2 concentrations and δ13C values in the lakes. Furthermore, lake water CO2 concentrations are negatively correlated with δ13C values of CO2 and dissolved inorganic carbon (DIC) both within a single lake with high spatial resolutions or in lake groups across different regions. These results highlight that the CO2/DIC δ13C values can be applied to trace the concentration variations of dissolved CO2 in lakes.
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In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent inâ vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G0/G1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA-seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF-κB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML-099. Moreover, pretreatment of ML-099 on A549 cells could reverse the grifolin-induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS-mediated multiple signaling pathways.
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Proliferação de Células , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Transdução de Sinais , Humanos , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Células A549 , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Relação Dose-Resposta a Droga , Movimento Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , TerpenosRESUMO
Understanding the water resource vulnerability (WRV) in global mountain regions under climate change is crucial for water resources management and socio-economic development. However, the WRV in the high-mountain Third Pole region (with quite a few transboundary river basins) remains largely unclear. Here, we have applied a comprehensive assessment framework of WRV to a Third Pole high-mountain river basin (Nujiang-Salween River, NSR) and its dependent downstream. The framework consisted of sensitivity, exposure, adaptability, hazard, and water stress indices, considering climate change, socio-economics, government effectiveness, natural disasters, and water supply capacity of the target river basin. Our results indicate that the downstream area (with intensive human activities) often exhibited significantly higher WRV than the mountain region; while the WRV shows an M-shaped change with increasing elevation, with the highest vulnerability occurring in a relatively low elevation range (e.g., 500-1500 m for the NSR basin). In the near future, we find that the spatial pattern of WRV in the basin is alternately influenced by adaptation, water scarcity, and exposure; whereas climate change serves as the main driver affecting the WRV in the far future. These findings enhance our understanding of the WRV in high-mountain transboundary basins of the Third Pole under global change.
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Mudança Climática , Rios , Recursos Hídricos , Abastecimento de Água , HumanosRESUMO
In the human body, carboxylesterases (CEs) play crucial roles in xenobiotic metabolism and lipid homeostasis. But abnormal expression of CEs is highly associated with some diseases, such as hyperlipidemia, diabetes, and liver cancer. Therefore, it is of great importance to develop an efficient tool for the accurate detection of CEs in living organisms. Herein, an innovative near-infrared (NIR) fluorescent probe, TTAP-AB, was designed for CE detection based on the aggregation-induced emission (AIE) mechanism. This probe exhibits rapid response (2 min), excellent sensitivity (limit of detection = 8.14 × 10-6 U/mL), and high selectivity to CEs. Additionally, owing to its good biocompatibility, the TTAP-AB probe enables the monitoring of dynamic changes in CE levels under drug-induced modulation in living cells and zebrafish. More importantly, the TTAP-AB probe was successfully employed to image liver tumors and assist in tumor resection through the real-time monitoring of CEs, indicating that TTAP-AB is promising to guide liver cancer surgery. Therefore, the TTAP-AB probe can not only enrich the strategies for CE detection in biological systems but also has great potential for some clinical imaging applications, including medical diagnosis, preclinical research, and imaging-guided surgery.
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Hidrolases de Éster Carboxílico , Corantes Fluorescentes , Peixe-Zebra , Animais , Corantes Fluorescentes/química , Camundongos , Humanos , Hidrolases de Éster Carboxílico/metabolismo , Imagem Óptica/métodos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Linhagem Celular TumoralRESUMO
Hypochlorite (ClO-) and viscosity both affect the physiological state of mitochondria, and their abnormal levels are closely related to many common diseases. Therefore, it is vitally important to develop mitochondria-targeting fluorescent probes for the dual sensing of ClO- and viscosity. Herein, we have explored a new fluorescent probe, XTAP-Bn, which responds sensitively to ClO- and viscosity with off-on fluorescence changes at 558 and 765 nm, respectively. Because the emission wavelength gap is more than 200 nm, XTAP-Bn can effectively eliminate the signal crosstalk during the simultaneous detection of ClO- and viscosity. In addition, XTAP-Bn has several advantages, including high selectivity, rapid response, good water solubility, low cytotoxicity, and excellent mitochondrial-targeting ability. More importantly, probe XTAP-Bn is successfully employed to monitor the dynamic change in ClO- and viscosity levels in the mitochondria of living cells and zebrafish. This study not only provides a reliable tool for identifying mitochondrial dysfunction but also offers a potential approach for the early diagnosis of mitochondrial-related diseases.
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Corantes Fluorescentes , Ácido Hipocloroso , Mitocôndrias , Peixe-Zebra , Ácido Hipocloroso/análise , Corantes Fluorescentes/química , Animais , Mitocôndrias/metabolismo , Viscosidade , Humanos , Imagem Óptica/métodos , Células HeLaRESUMO
Two experiments were conducted to determine net energy (NE) values of wheat bran ingredients and develop a prediction equation for NE of wheat bran. In each experiment, 12 multiparous pregnant sows were allocated to two 3 × 6 Youden squares with three consecutive periods and six diets in each square. The study consisted of six diets, including a corn-soybean meal basal diet and five diets formulated with 29.2% wheat bran. Each period lasted for 10 d, with 5 d allocated for adaptation and followed by 5 d for heat production measurement. Sows were provided feed at 604 kJ/kg BW0.75·d-1. On day 10, sows underwent fasting to measure fasting heat production. Results indicated that the inclusion of wheat bran in the diets significantly reduced digestibility of energy and nutrients in (p < 0.05). The average net energy (NE) content of wheat bran was determined to be 8.8 MJ/kg DM. A regress equation NE = 7.968 + 0.28 × CP + 0.607 × EE - 0.782 × ash - 0.05 × hemicellulose (R2 = 0.98, p < 0.01) was found to accurately predit the NE value when feeding pregnant sows with wheat bran-based diets. In conclusion, the net energy content of wheat bran fed to pregnant sows ranged from 7.24 to 10.67 MJ/kg DM and can be effectively estimated using proximate analysis methods.
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Long-term treatment of anemia involving frequent blood transfusions and intravenous iron administration increases the risks of hepatic iron overload and steatosis in the patients undergoing hemodialysis.Pathological accumulation of iron damages hepatocytes,not only elevating the risks of progressive hepatic fibrosis and cirrhosis but also potentially accelerating the process of hepatic steatosis.Iron overload and steatosis may interact with each other,exacerbating liver damage and ultimately leading to further deterioration of hepatic fibrosis and cirrhosis.MRI characterized by non-invasiveness and high repeatability,enables the simultaneous quantitative assessment of hepatic iron and fat content,providing crucial information for early diagnosis and intervention of liver diseases.In recent years,researchers have achieved significant advances in the application of MRI in the diagnosis and treatment of liver diseases.MRI can accurately reflect the extent of hepatic iron overload and steatosis in patients and predict the risk of liver diseases.This article reviews the latest advances,challenges,and perspectives in the application of MRI in assessing hepatic iron overload and steatosis in the patients undergoing hemodialysis,aiming to offer valuable references for clinical practice.
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Fígado Gorduroso , Sobrecarga de Ferro , Imageamento por Ressonância Magnética , Diálise Renal , Humanos , Sobrecarga de Ferro/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologiaRESUMO
OBJECTIVES: Glioblastoma (GBM) and brain metastases (BMs) are the two most common malignant brain tumors in adults. Magnetic resonance imaging (MRI) is a commonly used method for screening and evaluating the prognosis of brain tumors, but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited. In recent years, deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system. This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases (SBMs), and to further explore the impact of multimodality data fusion on classification tasks. METHODS: Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed. First, structural T1-weight, T1C-weight, and T2-weight were selected as 3 inputs to the entire model, regions of interest (ROIs) were manually delineated on the registered three modal MR images, and multimodality radiomics features were obtained, dimensions were reduced using a random forest (RF)-based feature selection method, and the importance of each feature was further analyzed. Secondly, we used the method of contrast disentangled to find the shared features and complementary features between different modal features. Finally, the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. RESULTS: The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs. Furthermore, compared with single-modal data, the multimodal fusion models using machine learning algorithms such as support vector machine (SVM), Logistic regression, RF, adaptive boosting (AdaBoost), and gradient boosting decision tree (GBDT) achieved significant improvements, with area under the curve (AUC) values of 0.974, 0.978, 0.943, 0.938, and 0.947, respectively; our comparative disentangled multi-modal MR fusion method performs well, and the results of AUC, accuracy (ACC), sensitivity (SEN) and specificity(SPE) in the test set were 0.985, 0.984, 0.900, and 0.990, respectively. Compared with other multi-modal fusion methods, AUC, ACC, and SEN in this study all achieved the best performance. In the ablation experiment to verify the effects of each module component in this study, AUC, ACC, and SEN increased by 1.6%, 10.9% and 15.0%, respectively after 3 loss functions were used simultaneously. CONCLUSIONS: A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.
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Neoplasias Encefálicas , Aprendizado Profundo , Glioblastoma , Adulto , Humanos , Glioblastoma/diagnóstico por imagem , Estudos Retrospectivos , Algoritmos , Neoplasias Encefálicas/diagnóstico por imagemRESUMO
Radiation-induced intestinal injury (RIII) is a common complication after radiation therapy in patients with pelvic, abdominal, or retroperitoneal tumours. Recently, in the model of DSS (Dextran Sulfate Sodium Salt) -induced intestinal inflammatory injury, it has been found in the study that transgenic mice expressing hVDR in IEC (Intestinal Epithelial Cell) manifest highly anti-injury properties in colitis, suggesting that activated VDR in the epithelial cells of intestine may inhibit colitis by protecting the mucosal epithelial barrier. In this study, we investigated the effect of the expression and regulation of VDR on the protection of RIII, and the radiosensitivity in vitro experiments, and explored the initial mechanism of VDR in regulating radiosensitivity of IEC. As a result, we found that the expression of VDR in intestinal tissues and cells in mice can be induced by ionizing radiation. VDR agonists are able to prolong the average survival time of mice after radiation and reduce the radiation-induced intestinal injury. For lack of vitamin D, the radiosensitivity of intestinal epithelial cells in mice increased, which can be reduced by VDR activation. Ensuing VDR activation, the radiation-induced intestinal stem cells damage is decreased, and the regeneration and differentiation of intestinal stem cells is promoted as well. Finally, on the basis of sequencing analysis, we validated and found that VDR may target the HIF/PDK1 pathway to mitigate RIII. We concluded that agonism or upregulation of VDR expression attenuates radiation-induced intestinal damage in mice and promotes the repair of epithelial damage in intestinal stem cells.
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Colite , Receptores de Calcitriol , Animais , Camundongos , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Lesões Experimentais por RadiaçãoRESUMO
Emerging evidence has indicated that cognitive impairment is an underrecognized feature of multiple system atrophy (MSA). Mild cognitive impairment (MCI) is related to a high risk of dementia. However, the mechanism underlying MCI in MSA remains controversial. In this study, we conducted the amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) analyses to detect the characteristics of local neural activity and corresponding network alterations in MSA patients with MCI (MSA-MCI). We enrolled 80 probable MSA patients classified as cognitively normal (MSA-NC, n = 36) and MSA-MCI (n = 44) and 40 healthy controls. Compared with MSA-NC, MSA-MCI exhibited decreased ALFF in the right dorsal lateral prefrontal cortex (RDLPFC) and increased ALFF in the right cerebellar lobule IX and lobule IV-V. In the secondary FC analyses, decreased FC in the left inferior parietal lobe (IPL) was observed when we set the RDLPFC as the seed region. Decreased FC in the bilateral cuneus, left precuneus, and left IPL and increased FC in the right middle temporal gyrus were shown when we set the right cerebellar lobule IX as the seed region. Furthermore, FC of DLPFC-IPL and cerebello-cerebral circuit, as well as ALFF alterations, were significantly correlated with Montreal Cognitive Assessment scores in MSA patients. We also employed whole-brain voxel-based morphometry analysis, but no gray matter atrophy was detected between the patient subgroups. Our findings indicate that altered spontaneous activity in the DLPFC and the cerebellum and disrupted DLPFC-IPL, cerebello-cerebral networks are possible biomarkers of early cognitive decline in MSA patients.
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Disfunção Cognitiva , Atrofia de Múltiplos Sistemas , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Córtex Cerebral , Imageamento por Ressonância MagnéticaRESUMO
Besides the well-documented ophthalmic manifestations, thyroid-associated ophthalmopathy (TAO) is believed to be related to emotional and psychological abnormalities. Given the previous neuroimaging evidence, we hypothesized that TAO patients would have altered neurovascular coupling associated with clinical-psychiatric disturbances. This study was to investigate neurovascular coupling changes in TAO by combining resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) techniques. Amplitude of low-frequency fluctuation (ALFF) was calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL in 37 TAO patients and 21 healthy controls (HCs). Global neurovascular coupling was assessed by across-voxel CBF-ALFF correlation, and regional neurovascular coupling was evaluated by CBF/ALFF ratio. Auxiliary analyses were performed using fractional ALFF (fALFF) and regional homogeneity (ReHo) as rs-fMRI measures. Compared with HCs, TAO patients showed significantly reduced global CBF-ALFF coupling. Moreover, TAO patients exhibited decreased CBF/ALFF ratio in the left lingual gyrus (LG)/fusiform gyrus (FFG), and increased CBF/ALFF ratio in the bilateral precuneus (PCu). In TAOs, CBF/ALFF ratio in the left LG/FFG was positively correlated with visual acuity, while CBF/ALFF ratio in the bilateral PCu was negatively correlated with Montreal Cognitive Assessment score. The auxiliary analyses showed trends of reduced global neurovascular coupling (i.e., CBF-fALFF correlation and CBF-ReHo correlation), as well as significant altered regional neurovascular coupling (i.e., CBF/fALFF ratio and CBF/ReHo ratio) in several brain regions. These findings indicated that TAO patients had altered neurovascular coupling in the visual and higher-order cognitive cortices. The neurovascular decoupling might be a possible neuropathological mechanism of TAO.
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Oftalmopatia de Graves , Acoplamento Neurovascular , Humanos , Acoplamento Neurovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Marcadores de Spin , DescansoRESUMO
In this study, eight nonconserved residues with exposed surfaces and flexible conformations of the homotetrameric PGUS (ß-glucuronidase from Aspergillus oryzae Li-3) were identified. Single-point mutation into cysteine enabled the thiol-maleimide reaction and site-specific protein assembly using a two-arm polyethylene glycol (PEG)-maleimide crosslinker (Mal2 ). The Mal2 (1k) (with 1 kDa PEG spacer)-crosslinked PGUS assemblies showed low crosslinking efficiency and unimproved thermostability except for G194C-Mal2 (1k). To improve the crosslinking efficiency, a lengthened crosslinker Mal2 (2k) (with 2 kDa PEG spacer) was used to produce PGUS assembly and a highly improved thermostability was achieved with a half-life of 47.2-169.2 min at 70°C, which is 1.04-3.74 times that of wild type PGUS. It is found that the thermostability of PGUS assembly was closely associated with the formation of inter-tetramer assembly and intratetramer crosslinking, rather than the PEGylation of the enzyme. Therefore, the four-arm PEG-maleimide crosslinker Mal4 (2k) (with 2 kDa PEG spacer) was employed to simultaneously increase the inter-tetramer assembly and intratetramer crosslinking, and the resulting PGUS assemblies showed further improved thermostabilities compared with Mal2 (2k)-crosslinked assemblies. Finally, the application of PGUS assemblies with significantly improved thermostability to the bioconversion of GL proved that the PGUS assembly is a strong catalyst for glycyrrhizin (GL) hydrolysis in industrial applications.
Assuntos
Glucuronidase , Ácido Glicirrízico , Glucuronidase/química , Ácido Glicirrízico/metabolismo , Hidrólise , Catálise , Maleimidas , PolietilenoglicóisRESUMO
RATIONALE: Gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) is widely used for compound-specific carbon isotopic analysis. However, current isotopic analysis systems utilize the GC IsoLink combustion reactor, and independent reduction furnaces are not implemented. Therefore, whether this limitation in furnace use affects the precision of compound-specific carbon isotopic analysis needs to be evaluated. METHODS: We attempted to add a separate reduction furnace to the GC IsoLink interface and compared the δ13 C values of n-alkanes (including C and H elements), fatty acid methyl ester (including C, H, and O elements), caffeine (USGS61 and USGS62, including C, H, O, and N elements), and 9-ethylcarbazole (including C, H, and N elements) before and after the addition of the reduction furnace using the GC IsoLink combustion reactor. RESULTS: For n-alkanes and fatty acid methyl esters, the δ13 C differences between the measured values and their standard values were basically falling within 0.5 whether or not an independent reduction furnace was added. However, for the nitrogen-containing compounds (caffeine and 9-ethylcarbazole), the δ13 C differences between the measured values and their standard values were much larger without an independent reduction furnace (1.0-3.71 for USGS61, 1.78-2.19 for USGS62, and 0.39-1.13 for 9-ethylcarbazole) than with a reduction furnace (-0.31-0.68 for USGS61, -0.44-0.06 for USGS62, and -0.04-0.25 for 9-ethylcarbazole). CONCLUSIONS: The addition of an independent reduction furnace had no significant effect on the δ13 C of n-alkanes and fatty acid methyl esters, but it had a significant effect on the δ13 C of nitrogen-containing compounds. It is suggested that GC IsoLink needs an independent reduction furnace to effectively eliminate the interference of NOx on CO2 isotopic determination to improve the accuracy of δ13 C for nitrogen-containing compounds.