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1.
Proteomics Clin Appl ; : e2100031, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542231

RESUMO

PURPOSE: Disulfiram (DSF) has been proven safe and shows the promising antitumor effect in preclinical studies. However, the precise mechanism of DSF on tumor is rarely reported. This study aims to fully understand the mechanism of action of DSF with a systems perspective in anticancer effects. EXPERIMENTAL DESIGN: SILAC-based quantitative proteomics strategy was used to systematically identify differential expression proteins (DEPs) after DSF treatment in HeLa cells. Bioinformatical analysis (PANTHER, DAVID, and STRING) were performed to characterize biological functions of DEPs. Functional studies were performed to explore underlying mechanisms of DSF in cancer cells. RESULTS: In total, 201 proteins were dysregulated significantly after DSF exposure. Functional studies of hexokinase 2 (HK2), which catalyzed the first irreversible enzymatic step in glucose metabolism, revealed that various phenotypic effects observed after DSF treatment in cancer cells, at least partly, through the regulation of HK2 expression. CONCLUSIONS AND CLINICAL RELEVANCE: By correlating the proteomics data with these functional studies, the current results provided novel insights into the mechanism underlying DSF function in cancer cells. Meanwhile, these provided theoretical basis for the new use of old drugs in clinical therapy.

2.
Mol Pharm ; 18(9): 3544-3552, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34482695

RESUMO

Maternal embryo leucine zipper kinase (MELK) is a serine/threonine kinase and is highly expressed in triple-negative breast cancer (TNBC). This study aimed to develop a 18F-radiolabeled tracer based on the structure of a small-molecule MELK inhibitor OTSSP167 and evaluate its application for PET imaging of MELK expression in TNBC. OTSSP167 was modified with ethylene glycol to adjust its pharmacokinetics and was then radiolabeled with 18F to obtain [18F]F-ET-OTSSP167 at a labeling yield of 7.14 ± 2.19% and a molar activity of 16.23 ± 1.13 MBq/nmol. In vitro binding assays showed differentiated binding affinities of [18F]F-ET-OTSSP167 in different breast cancer cell lines, with high uptake in MDA-MB-231 (mild MELK expression) and low uptake in MCF-7 (negative MELK expression). PET imaging revealed that MDA-MB-231 tumors could be clearly delineated in vivo, while low tracer uptake was observed in MCF-7 tumors. These findings were confirmed by ex vivo biodistribution studies and were consistent with the immunohistochemistry and tissue staining results. Tracer accumulation in MDA-MB-231 tumors was significantly inhibited by excess amounts of OTSSP167, indicating high specificity of the tracer. In summary, [18F]F-ET-OTSSP167, an easily-prepared probe, can be used to visualize MELK positive tumors, demonstrating its promising clinical potential in selecting patients for MELK inhibitor therapy.

3.
Chemosphere ; 287(Pt 1): 132044, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34474391

RESUMO

Bisphenol A (BPA) is a known endocrine disruptor and has been gradually replaced in industrial applications by other bisphenols, such as bisphenol S (BPS). However, whether these analogues are any safer for the central nervous system remains elusive. Here, we investigated behavioral impairments in mice after BPA and BPS exposure from postnatal days 21-49 (P21~P49). Results showed that BPA (0.1 and 1 mg/kg/d) and BPS (1 mg/kg/d) impaired emotion and social interaction of mice, while low dose exposure (0.1 mg/kg/d) induced no observable changes on emotion in mice. The behavioral deficits were accompanied by hyperactivation of the basolateral amygdala (BLA), i.e., dose-dependent increase in neuronal firing rates and local field potential power. In addition, glutamate receptors were up-regulated in the BLA, showing the same activation trend after exposure to different doses of BPA and BPS. Taken together, these findings imply that BPA and BPS cause behavioral impairments in juvenile mice by disrupting local neuronal activation in the BLA. Although BPS exerted less adverse effects on mice than BPA at the low dose, it does not appear to be a safe alternative to BPA in regard to brain function after prolonged high-volume exposure.

4.
Hypertension ; : HYPERTENSIONAHA12117574, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488435

RESUMO

Plasma circulating extracellular vesicles (EVs) have been utilized as a potential therapeutic strategy to treat ischemic disease through intramyocardial injection (efficient but invasive) or tail vein injection (noninvasive but low cardiac retention). An effective and noninvasive delivery of EVs for future clinical use is necessary. The large animal (canine) model was complemented with a murine ischemia-reperfusion injury (IRI) model, as well as H9 human embryonic stem cell-induced cardiomyocytes or neonatal rat cardiomyocytes to investigate the effective delivery method and the role of plasma EVs in the IRI model. We further determine the crucial molecule within EVs that confers the cardioprotective role in vivo and in vitro and investigate the efficiency of CHP (cardiac homing peptide)-linked EVs in alleviating IRI. D-SPECT imaging showed that percutaneous intracoronary delivery of EVs reduced infarct extent in dogs. CHP-EVs further reduced IRI-induced cardiomyocyte apoptosis in mice and neonatal rat cardiomyocytes. Mechanistically, administration of EVs by percutaneous intracoronary delivery (in dog) and myocardial injection (in mice) just before reperfusion reduced infarct size of IRI by increasing miR-486 levels. miR-486-deleted EVs exacerbated oxygen-glucose deprivation/reoxygenation-induced human embryonic stem cell-induced cardiomyocytes and neonatal rat cardiomyocyte apoptosis. EV-miR-486 inhibited the PTEN (phosphatase and tensin homolog deleted on chromosome ten) expression and then promoted AKT (protein kinase B) activation in human embryonic stem cell-induced cardiomyocytes and neonatal rat cardiomyocytes. In conclusion, plasma-derived EVs convey miR-486 to the myocardium and attenuated IRI-induced infarction and cardiomyocyte apoptosis. CHP strategy was effective to improve cardiac retention of EVs in mice (in vivo) and dogs (ex vivo).

5.
Brief Bioinform ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34368837

RESUMO

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here, we propose a novel framework, named AIMEE, integrating AI model and enzymological experiments, to identify inhibitors against 3CL protease of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value <3 µM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to the domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and was proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and for expanding the boundaries of drug discovery. The code and data are available at https://github.com/SIAT-code/AIMEE.

6.
Diabetes Metab J ; 45(4): 526-538, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34352988

RESUMO

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most serious complications of type 2 diabetes mellitus (T2DM). DPN increases the risk of ulcers, foot infections, and noninvasive amputations, ultimately leading to long-term disability. METHODS: Seven hundred patients with T2DM were investigated from 2013 to 2017 in the Sanlin community by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 681 patients (19 missing) were investigated using a questionnaire, physical examination, biochemical index test, and follow-up Toronto clinical scoring system (TCSS) test. Patients with a TCSS score ≥6 points were diagnosed with DPN. After removing missing values, 612 patients were divided into groups in a 3:1 ratio for external validation. Using different Lasso analyses (misclassification error, mean squared error, -2log-likelihood, and area under curve) and a logistic regression analysis of the training set, models A, B, C, and D were established. The receiver operating characteristic (ROC) curve, calibration plot, dynamic component analysis (DCA) measurements, net classification improvement (NRI) and integrated discrimination improvement (IDI) were used to validate discrimination and clinical practicality of the model. RESULTS: Through data analysis, model A (containing four factors), model B (containing five factors), model C (containing seven factors), and model D (containing seven factors) were built. After calibration, ROC curve, DCA, NRI and IDI, models C and D exhibited better accuracy and greater predictive power. CONCLUSION: Four prediction models were established to assist with the early screening of DPN in patients with T2DM. The influencing factors in model C and D are more important factors for patients with T2DM diagnosed with DPN.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34300033

RESUMO

OBJECTIVE: Interpersonal theories of suicide suggest that the Interpersonal Needs Questionnaire (INQ) can be used to measure suicidal ideation, but few studies have focused on migrant people, a group with a high prevalence of suicidal ideation. The aim of this study was to validate the psychometric properties of the INQ-15 and its prediction of suicidal ideation among migrant industrial workers in China. METHOD: A stratified multi-stage sample of 2023 industrial workers was recruited from 16 factories in Shenzhen, China. There were 1805 nonlocal workers, which we defined as migrant workers with a mean age of 32.50 ± 8.43 years old who were 67.3% male. The structure of the Chinese version of the INQ-15 and its correlation and predictive utility for suicidal ideation were examined through factor analysis, the Item Response Theory, the M2 test, logistic regression, and receiver operating characteristic (ROC) analysis. RESULTS: Different from studies among various samples in which a two-factor solution is identified, results within this sample indicated three factors: perceived burdensomeness, thwarted belongingness, and social isolation. The model fit statistics of three-factor INQ were 0.075 for RMSEA, 0.945 for CFI, 0.932 for TLI, and 0.067 for SRMR. The model standard estimated factor loadings ranged from 0.366 to 0.869. The summed scores of INQ and perceived burdensomeness predicted suicidal ideation after controlling for sociodemographic characteristics such as age, gender, and income with AUC of 0.733 (95% CI: 0.712/0.754) and 0.786 (95% CI: 0.766/0.804). In the meantime, the comparison of the predictive ability between INQ total scores and PB scores was significant with p < 0.05. CONCLUSION: The INQ has good psychometric properties and can be used to assess how migrant workers living in the Shenzhen perceive meeting interpersonal psychological needs and shows good predictive ability of suicidal ideation. Perceived burdensomeness appears to play a role in suicide and may be a point of intervention, yet the notable deviation from previous findings and the relative weakness of two of the other factors warrant further study.


Assuntos
Ideação Suicida , Migrantes , Adulto , China , Feminino , Humanos , Relações Interpessoais , Masculino , Teoria Psicológica , Psicometria , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-34241652

RESUMO

PURPOSE: To describe the uptake of 68Gallium-labelled fibroblast activation protein inhibitor (68Ga-FAPI) in the bones and joints for better understanding of the role of 68Ga-FAPI PET in benign and malignant bone lesions and joint diseases. METHODS: All 129 68Ga-FAPI PET/MR or PET/CT scans from June 1, 2020, to February 20, 2021, performed at our PET center were retrospectively reviewed. Foci of elevated 68Ga-FAPI uptake in the bones and joints were identified. All lesions were divided into malignant and benign diseases. Benign lesions included osteofibrous dysplasia, periodontitis, degenerative bone diseases, arthritis, and other inflammatory or trauma-related abnormalities. The number, locations, and SUVmax of all lesions were recorded and analyzed. The detectability of 68Ga-FAPI PET and 18F-FDG PET in patients who had two scans was also compared. RESULTS: Elevated uptake of 68Ga-FAPI in/around the bones and joints was found in 82 cases (63.57%). A total of 295 lesions were identified, including 94 (31.9%) malignant lesions (all were metastases) and 201 (68.1%) benign lesions. The benign lesions consisted of 13 osteofibrous dysplasia, 48 degenerative bone disease, 33 periodontitis, 56 arthritis, and 51 other inflammatory or trauma-related abnormalities. The spine, shoulder joint, alveolar ridge, and pelvis were the most commonly involved locations. Bone metastases were mainly distributed in the spine, pelvis, and ribs. Among benign diseases, periodontitis and arthritis are site-specific. The mean SUVmax of bone metastases was significantly higher than that of benign diseases (7.14 ± 4.33 vs. 3.57 ± 1.60, p < 0.001), but overlap existed. The differences in SUVmax among subgroups of benign diseases were statistically significant (p < 0.001), with much higher uptake in periodontitis (4.45 ± 1.17). 68Ga-FAPI PET identified much more lesions than 18F-FDG PET (104 vs. 48) with higher uptake value. CONCLUSION: 68Ga-FAPI accumulated in both bone metastases and some benign diseases of the bones and joints. Although the uptake of 68Ga-FAPI was often higher in bone metastases, this finding cannot be used to distinguish between benign and malignant lesions. 68Ga-FAPI PET also has the potential to locate and evaluate the extent of both malignant tumor and benign diseases in bones and joints. TRIAL REGISTRATION: NCT04554719, NCT04605939. Registered September 8, 2020 and October 25, 2020-retrospectively registered, http://clinicaltrails.gov/show/NCT04554719 ; http://clinicaltrails.gov/show/NCT04605939.

9.
Cancers (Basel) ; 13(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298651

RESUMO

We explored the clinical value of 18F-FDG PET/MR in a head-to-head comparison with PET/CT in loco-regional recurrent and metastatic cervical lymph nodes of differentiated thyroid carcinoma (DTC) patients after comprehensive treatment. 18F-FDG PET/CT and neck PET/MR scans that were performed in DTC patients with suspected recurrence or cervical lymph node metastasis after comprehensive treatment were retrospectively analyzed. Detection rates, diagnostic efficacy, image conspicuity, and measured parameters were compared between 18F-FDG PET/CT and PET/MR. The gold standard was histopathological diagnosis or clinical and imaging follow-up results for more than 6 months. Among the 37 patients enrolled, no suspicious signs of tumor were found in 10 patients, 24 patients had lymph node metastasis, and 3 patients had both recurrence and lymph node metastases. A total of 130 lesions were analyzed, including 3 malignant and 6 benign thyroid nodules, as well as 74 malignant and 47 benign cervical lymph nodes. Compared with PET/CT, PET/MR presented better detection rates (91.5% vs. 80.8%), image conspicuity (2.74 ± 0.60 vs. 1.9 ± 0.50, p < 0.001, especially in complex level II), and sensitivity (80.5% vs. 61.0%). SUVmax differed in benign and malignant lymph nodes in both imaging modalities (p < 0.05). For the same lesion, the SUVmax, SUVmean, and diameters measured by PET/MR and PET/CT were consistent and had significant correlation. In conclusion, compared with 18F-FDG PET/CT, PET/MR was more accurate in determining recurrent and metastatic lesions, both from a patient-based and from a lesion-based perspective. Adding local PET/MR after whole-body PET/CT may be recommended to provide more precise diagnostic information and scope of surgical resection without additional ionizing radiation. Further scaling-up prospective studies and economic benefit analysis are expected.

10.
Hum Mol Genet ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34169321

RESUMO

Motile cilia and flagellar defects can result in primary ciliary dyskinesia (PCD), which is a multisystemic genetic disorder that affects roughly 1:10000 individuals. The nexin-dynein regulatory complex (N-DRC) links neighboring doublet microtubules within flagella, serving as a central regulatory hub for motility in Chlamydomonas. Herein, we identified two homozygous DRC1 variants in human patients that were associated with multiple morphological abnormalities of the sperm flagella (MMAF) and male infertility. Drc1-/-, Drc1R554X/R554X, and Drc1W244X/W244X mice on the C57BL/6 background suffered from prepubertal mortality. However, when the ICR background was introduced, some of these mice were able to survive and recapitulate the MMAF phenotypes detected in human patients. By analyzing these animals, we determined that DRC1 is an essential regulator of N-DRC assembly in cilia and flagella. When DRC1 is absent, this results in the shortening of cilia and consequent impairment of their motility. Damage associated with DRC1 deficiency in sperm flagella was more pronounced than in cilia, as manifested by complete axoneme structural disorder in addition to the loss of the DRC structure. Together, these findings suggest that DRC1 is required for the structural stability of flagella but not cilia, emphasizing the key role of this protein in mammalian species.

11.
Genomics ; 113(4): 2769-2779, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34147634

RESUMO

This study aimed to investigate the transcriptome profiles of liver and kidney in pregnant sheep under a nutritional restriction. Twenty Hu sheep were segregated into control group (CON) and severe feed restriction (FR) group. Results showed that the concentration of insulin decreased, whereas glucagon, epinephrine, and norepinephrine increased in the FR group. Histological morphology showed no apparent difference in terms of fat deposition in the kidney. In addition, FR significantly decreased the hepatic gene expression of gluconeogenic genes. However, in the kidney, the relative mRNA expression levels of gluconeogenic genes and glucose transporter 1 were observed to increase while the mRNA expression of sodium-glucose co-transporter 1 were decreased by FR. The differentially expressed genes in the liver were associated with fatty acid metabolism and inflammation. In the kidney, FR mainly activated the gluconeogenesis improving negative energy balance. These results provide a better understanding of the consequences of starvation during pregnancy.

12.
Bioresour Technol ; 336: 125317, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34087730

RESUMO

In this study, an integrated investigation to the microbial activities, extracellular polymeric substance (EPS), microbial community and function of anammox granular sludge (AnGS) was performed.Results showed that AnGS at 0.5-1.0 mm had the highest average specific anammox activity (SAA) of 345.9 mg NH4+-N·gVSS-1·d-1, but AnGS at 1.0-1.5 mm with higher SAA might lead to better nitrogen removal efficiency. The content of slime EPS and SAA achieved positively correlation with R2 of 98.11%, while protein/polysaccharide ratio of slime EPS and sludge volume index achieved negatively correlation with R2 of 99.13%. Cadidatus Broccadia and Denitratisoma were positive correlations and most abundant in AnGS 0.5-1.0 mm of 20% and AnGS 1.0-1.5 mm of 37%, respectively. AnGS at 0.5-1.0 mm exhibited higher energy metabolism which mostly contributed to produce protein. The study provides new insights into the mechanisms of AnGS about 1 mm playing more important role in nitrogen removal performance.


Assuntos
Nitrogênio , Esgotos , Reatores Biológicos , Desnitrificação , Matriz Extracelular de Substâncias Poliméricas , Oxirredução
13.
Genes Genomics ; 43(7): 829-835, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33932219

RESUMO

BACKGROUND: 2,4-Dinitrophenol (2,4-DNP) is an important organic environmental pollutant that is highly toxic to all forms of living organisms. A gram-positive strain (designated XM24D) was isolated from 2,4-DNP-contaminated soil by an enrichment technique. OBJECTIVE: The study was designed to analyze the ability of XM24D to degrade 2,4-DNP and its analogs and to reveal the degradation pathways of these aromatic compounds. METHODS: The degradation ability of XM24D was tested by a growth experiment. 2,4-DNP and its analog degradation pathways were predicted by genome and comparative transcriptome sequencing. RESULTS: Growth profiles showed that XM24D was able to utilize 2,4-DNP as the sole source of carbon, nitrogen and energy. Analogs of 2,4-DNP, including 4-nitrophenol (PNP) and 2-chloro-4-nitrophenol (2C4NP), can also be degraded by XM24D. Genome analysis showed that the XM24D genome contains two chromosomes with a combined size of 9.08 Mb and an average GC content of 67.07 %. Average nucleotide identity analysis indicated that Rhodococcus imtechensis RKJ300 is the most closely related strain to XM24D. Comparative transcriptome analysis revealed that the 2,4-DNP/PNP/2C4NP degradation pathway in XM24D is highly similar in sequence and organization to the 2,4-DNP degradation pathway in Rhodococcus opacus HL PM-1, the PNP degradation pathway in Rhodococcus opacus SAO101 and the 2C4NP degradation pathway in Rhodococcus imtechensis RKJ300. These results suggested that 2,4-DNP/PNP/2C4NP was degraded via the 2,4-dinitrocyclohexanone/4-nitrocatechol/hydroxyquinol pathway in XM24D. CONCLUSIONS: Genomic and transcriptomic information on XM24D provides a valuable reference for further investigating the evolutionary characteristics of nitrophenol degradation pathways in microorganisms.

14.
Aging (Albany NY) ; 13(7): 10749-10769, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33848981

RESUMO

Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration in vitro. We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic ß-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions in vivo, suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression.


Assuntos
Proteínas Hedgehog/genética , MicroRNAs/genética , Proteínas Repressoras/genética , Neoplasias Gástricas/genética , Via de Sinalização Wnt/fisiologia , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
15.
Eur J Nucl Med Mol Imaging ; 48(11): 3469-3481, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33829415

RESUMO

PURPOSE: To construct multivariate radiomics models using hybrid 18F-FDG PET/MRI for distinguishing between Parkinson's disease (PD) and multiple system atrophy (MSA). METHODS: Ninety patients (60 with PD and 30 with MSA) were randomized to training and test sets in a 7:3 ratio. All patients underwent 18F-fluorodeoxyglucose (18F-FDG) PET/MRI to simultaneously obtain metabolic images (18F-FDG), structural MRI images (T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) and T2-weighted fluid-attenuated inversion recovery (T2/FLAIR)) and functional MRI images (susceptibility-weighted imaging (SWI) and apparent diffusion coefficient). Using PET and five MRI sequences, we extracted 1172 radiomics features from the putamina and caudate nuclei. The radiomics signatures were constructed with the least absolute shrinkage and selection operator algorithm in the training set, with progressive optimization through single-sequence and double-sequence radiomics models. Multivariable logistic regression analysis was used to develop a clinical-radiomics model, combining the optimal multi-sequence radiomics signature with clinical characteristics and SUV values. The diagnostic performance of the models was assessed by receiver operating characteristic and decision curve analysis (DCA). RESULTS: The radiomics signatures showed favourable diagnostic efficacy. The optimal model comprised structural (T1WI), functional (SWI) and metabolic (18F-FDG) sequences (RadscoreFDG_T1WI_SWI) with the area under curves (AUCs) of the training and test sets of 0.971 and 0.957, respectively. The integrated model, incorporating RadscoreFDG_T1WI_SWI, three clinical symptoms (disease duration, dysarthria and autonomic failure) and SUVmax, demonstrated satisfactory calibration and discrimination in the training and test sets (0.993 and 0.994, respectively). DCA indicated the highest clinical benefit of the clinical-radiomics integrated model. CONCLUSIONS: The radiomics signature with metabolic, structural and functional information provided by hybrid 18F-FDG PET/MRI may achieve promising diagnostic efficacy for distinguishing between PD and MSA. The clinical-radiomics integrated model performed best.

16.
Adv Mater ; : e2005910, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33852764

RESUMO

Two of the key questions to be addressed are whether and how one can turn cocoon silk into fascinating materials with different electronic and optical functions so as to fabricate the flexible devices. In this review, a comprehensive overview of the unique strategy of mesoscopic functionalization starting from silk fibroin (SF) materials to the fabrication of various meso flexible SF devices is presented. Notably, SF materials with novel and enhanced properties can be achieved by mesoscopically reconstructing the hierarchical structures of SF materials. This is based on rerouting the refolding process of SF molecules by meso-nucleation templating. As-acquired functionalized SF materials can be applied to fabricate bio-compatible/degradable flexible/implantable meso-optical/electronic devices of various types. Consequently, functionalized SF can be fabricated into optical elements, that is, nonlinear photonic and fluorescent components, and make it possible to construct silk meso-electronics with high-performance. These advances enable the applications of SF-material based devices in the areas of physical and biochemical sensing, meso-memristors, transistors, brain electrodes, and energy generation/storage, applicable to on-skin long-term monitoring of human physiological conditions, and in-body sensing, information processing, and storage.

17.
J Am Chem Soc ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848155

RESUMO

A two-dimensional polymer (2DP) single crystal (T-2DP) with submillimeter size was synthesized by single-crystal to single-crystal transformation based on photochemical [2 + 2]-cycloaddition. A successful conversion from monomer to polymer was achieved in the single-crystal state. The structure information with an atomic resolution of both the monomer and 2DP was given through single-crystal X-ray diffraction. By simply treated with trifluoroacetic acid (TFA) under mild conditions, an unprecedented efficiency of exfoliation was achieved. The triazine core in T-2DP could be protonated by TFA, which resulted in a solution-like sample with >60% of monolayers. The size of the exfoliated monolayer reaches to several hundreds of µm2. This is another precious example of 2DP single crystal with nearly perfect structure and large enough size. The successful preparation of the highly desirable 2DP "solution" for a long time containing large sized and large amount of 2DP monolayers may open up new prospects for the basic properties study and the applications of 2DPs.

18.
J Nucl Med ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863819

RESUMO

We sought to evaluate the performance of 68Ga-DOTA-FAPI-04 (68Ga-FAPI) PET/MR for the diagnosis of primary tumor and metastatic lesions in patients with gastric carcinomas and to compare the results with those of 18F-FDG PET/CT. Methods: Twenty patients with histologically proven gastric carcinomas were recruited, and each patient underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/MR. A visual scoring system was established to compare the detectability of primary tumors and metastases in different organs/regions (the peritoneum, abdominal lymph nodes, supradiaphragmatic lymph nodes, liver, ovary, bone, and other tissues). The original maximum standardized uptake value (SUVmax) and normalized SUVmax (calculated by dividing a lesion's original SUVmax with the mean SUV of the descending aorta) of selected lesions on both 18F-FDG PET/CT and 68Ga-FAPI PET/MR were measured. Original/normalized SUVmax-FAPI and SUVmax-FDG were compared for patient-based (including a single lesion with the highest activity uptake in each organ/region) and lesion-based (including all lesions [≤ 5] or the 5 lesions with highest activity [> 5]) analyses, respectively. Results: The 20 recruited patients (median age: 56.0 y; range: 29-70 y) included 9 men and 11 women, 14 patients for initial staging and 6 for recurrence detection. 68Ga-FAPI PET was superior to 18F-FDG PET for primary tumor detection (100.00% [14/14] vs 71.43% [10/14], P = 0.034), and the former had higher tracer uptake levels (P < 0.05). 68Ga-FAPI PET was superior to 18F-FDG PET in both patient-based and lesion-based evaluation except for the metastatic lesions in supradiaphragmatic lymph nodes and ovaries. Additionally, multiple sequences of MR images were beneficial for the interpretation of hepatic metastases in 3 patients, uterine and rectal metastases in 1 patient, ovarian lesions in 7 patients, and osseous metastases in 2 patients. Conclusion: 68Ga-FAPI PET/MR outperformed 18F-FDG PET/CT in visualizing the primary and most metastatic lesions of gastric cancer, and might be a promising method with the potential of replacing 18F-FDG PET/CT.

19.
Front Immunol ; 12: 625957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767697

RESUMO

Endotoxin-induced lung injury is one of the major causes of death induced by endotoxemia, however, few effective therapeutic options exist. Hydrogen inhalation has recently been shown to be an effective treatment for inflammatory lung injury, but the underlying mechanism is unknown. In the current study we aim to investigate how hydrogen attenuates endotoxin-induced lung injury and provide reference values for the clinical application of hydrogen. LPS was used to establish an endotoxin-induced lung injury mouse model. The survival rate and pulmonary pathologic changes were evaluated. THP-1 and HUVECC cells were cultured in vitro. The thioredoxin 1 (Trx1) inhibitor was used to evaluate the anti-inflammatory effects of hydrogen. Hydrogen significantly improved the survival rate of mice, reduced pulmonary edema and hemorrhage, infiltration of neutrophils, and IL-6 secretion. Inhalation of hydrogen decreased tissue factor (TF) expression and MMP-9 activity, while Trx1 expression was increased in the lungs and serum of endotoxemia mice. LPS-stimulated THP-1 and HUVEC-C cells in vitro and showed that hydrogen decreases TF expression and MMP-9 activity, which were abolished by the Trx1 inhibitor, PX12. Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity via activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/farmacologia , Hidrogênio/farmacologia , Pulmão/efeitos dos fármacos , Tiorredoxinas/metabolismo , Tromboplastina/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Técnicas de Cocultura , Modelos Animais de Doenças , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos ICR , Infiltração de Neutrófilos/efeitos dos fármacos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/metabolismo , Edema Pulmonar/patologia , Edema Pulmonar/prevenção & controle , Transdução de Sinais , Células THP-1
20.
Cell Biol Int ; 45(6): 1296-1305, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33739578

RESUMO

The prognosis of advanced colorectal cancer (CRC) is currently still very poor, which suggests that the biological mechanisms of CRC oncogenesis are not fully understood. This study was conducted to explore the regulatory effect of SOX-17 on the expression of microRNA (miR)-302b-3p, and the involvement of SOX-17 in the invasion and apoptosis of CRC cells. The expression of SOX-17 and miR-302a,b,c,d-3p in colorectal cancer and normal colon epithelial cell lines was measured by real-time polymerase chain reaction and/or western blot. The regulatory effects of SOX-17 on miR-302b-3p gene in HT29 and LoVo cells were tested using the ChiP assay. The biological activities of SOX-17 and miR-302b-3p were evaluated by invasion and apoptosis assay. Results showed that transfection of SOX-17 small interfering RNA (siSOX-17) significantly increased, whereas transfection of SOX-17 overexpression vector (oeSOX-17) significantly decreased, miR-302b expression in HT29 and LoVo cells. Cotransfection of oeSOX-17 and miR-302b-3p inhibitor (INmiR-302b) significantly blocked the effects of SOX-17 in HT29 and LoVo cells. ChIP experiments showed that SOX-17 bonded to the miR-302b-3p promoter in HT29 and LoVo cells. Transfection of oeSOX-17 and miR-302b-3p mimics (MImiR-302b) significantly decreased, whereas transfection of siSOX-17 and INmiR-302b significantly increased, the invasion of HT29 and LoVo cells. In contrast, transfection of oeSOX-17 and MImiR-302b significantly increased, while transfection of siSOX-17 and INmiR-302b significantly decreased, apoptosis in HT29 and LoVo cells. Cotransfection of oeSOX-17 and INmiR-302b significantly blocked the effects of oeSOX-17 on cell invasion and apoptosis in HT29 and LoVo cells. These results suggested that SOX-17 can bind to the promoter of miR-302b-3p gene to regulate its expression, while both SOX-17 and miR-302b regulate the invasion and apoptosis in colorectal cancer cells.

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