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Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.
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Mediastinite , Quinolinas , Feminino , Animais , Ratos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distribuição Tecidual , Mediastinite/diagnóstico por imagem , Mediastinite/tratamento farmacológico , Radioisótopos de Gálio , Fluordesoxiglucose F18RESUMO
We evaluated the efficiency of using a 308-nm excimer laser with either tacrolimus, pimecrolimus, or halometasone for the treatment of childhood vitiligo. Patients who received combined treatments had significantly higher rates of repigmentation in comparison with individuals who underwent excimer laser alone therapy. Moreover, patients who received treatment with excimer laser and halometasone had significantly higher rates of repigmentation, even higher than individuals who were treated with tacrolimus combined or pimecrolimus combined. This regimen was more effective on the face, neck, and limbs. We conclude that the use of a combined excimer laser and halometasone cream has a greater therapeutic effect than laser alone.
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Betametasona/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Lasers de Excimer/uso terapêutico , Tacrolimo/análogos & derivados , Tacrolimo/administração & dosagem , Vitiligo/terapia , Administração Tópica , Betametasona/administração & dosagem , Criança , Terapia Combinada , Humanos , Estudos Prospectivos , Pigmentação da Pele/efeitos dos fármacos , Resultado do TratamentoAssuntos
Lasers de Excimer/uso terapêutico , Terapia com Luz de Baixa Intensidade , Vitiligo/radioterapia , Adulto , Povo Asiático , Betametasona/análogos & derivados , Betametasona/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Terapia Combinada , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pigmentação da Pele , Tacrolimo/uso terapêutico , Vitiligo/tratamento farmacológicoRESUMO
Phthalate esters (PE), a significant class of organic compounds used in industry, can contaminate humans and animals by entering water and food chains. Recent studies demonstrate the influence of PE on the development and progression of heart diseases, particularly in obese people. Di-isobutyl phthalate (DIBP) was administered orally to normal and diet-induced obese mice in this research to assess cardiovascular risk. The modifications in the microbial composition and metabolites were examined using RNA sequencing and mass spectrometry analysis. Based on the findings, lean group rodents were less susceptible to DIBP exposure than fat mice because of their cardiovascular systems. Histopathology examinations of mice fed a high-fat diet revealed lesions and plagues that suggested a cardiovascular risk. In the chronic DIBP microbial remodeling metagenomics Faecalibaculum rodentium was the predominant genera in obese mice. According to metabolomics data, arachidonic acid (AA) metabolism changes caused by DIBP were linked to unfavorable cardiovascular events. Our research offers new understandings of the cardiovascular damage caused by DIBP exposure in obese people and raises the possibility that arachidonic acid metabolism could be used as a regulator of the gut microbiota to avert related diseases.
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Solar-driven interfacial evaporation (SDIE) has attracted great attention by offering a zero-carbon-emission solution for clean water production. The manipulation of the surface structure of the evaporator markedly promotes the enhancement of light capture and the improvement of evaporation performance. Herein, inspired by seedless lotus pod, a flexible pristine polypyrrole (PPy) membrane with macro/micro-bubble and nanotube asymmetric structure is fabricated through template-assisted interfacial polymerization. The macro- and micro-hierarchical structure of the open bubbles enable multiple reflections inner and among the bubble cavities for enhanced light trapping and omnidirectional photothermal conversion. In addition, the multilevel structure (macro/micro/nano) of the asymmetric PPy (PPy-A) membrane induces water evaporation in the form of clusters, leading to a reduction of water evaporation enthalpy. The PPy-A membranes achieve a full-spectrum light absorption of 96.3% and high evaporation rate of 2.03 kg m-2 h-1 under 1 sun. Long-term stable desalination is also verified with PPy-A membranes by applying one-way water channel. This study demonstrates the feasibility of pristine PPy membranes in SDIE applications, providing guidelines for modulation of the evaporator topologies toward high-efficient solar evaporation.
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Human phenomics is defined as the comprehensive collection of observable phenotypes and characteristics influenced by a complex interplay among factors at multiple scales. These factors include genes, epigenetics at the microscopic level, organs, microbiome at the mesoscopic level, and diet and environmental exposures at the macroscopic level. "Phenomic imaging" utilizes various imaging techniques to visualize and measure anatomical structures, biological functions, metabolic processes, and biochemical activities across different scales, both in vivo and ex vivo. Unlike conventional medical imaging focused on disease diagnosis, phenomic imaging captures both normal and abnormal traits, facilitating detailed correlations between macro- and micro-phenotypes. This approach plays a crucial role in deciphering phenomes. This review provides an overview of different phenomic imaging modalities and their applications in human phenomics. Additionally, it explores the associations between phenomic imaging and other omics disciplines, including genomics, transcriptomics, proteomics, immunomics, and metabolomics. By integrating phenomic imaging with other omics data, such as genomics and metabolomics, a comprehensive understanding of biological systems can be achieved. This integration paves the way for the development of new therapeutic approaches and diagnostic tools.
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Imaging-derived phenotypes (IDPs) have been increasingly used in population-based cohort studies in recent years. As widely reported, magnetic resonance imaging (MRI) is an important imaging modality for assessing the anatomical structure and function of the brain with high resolution and excellent soft-tissue contrast. The purpose of this article was to describe the imaging protocol of the brain MRI in the China Phenobank Project (CHPP). Each participant underwent a 30-min brain MRI scan as part of a 2-h whole-body imaging protocol in CHPP. The brain imaging sequences included T1-magnetization that prepared rapid gradient echo, T2 fluid-attenuated inversion-recovery, magnetic resonance angiography, diffusion MRI, and resting-state functional MRI. The detailed descriptions of image acquisition, interpretation, and post-processing were provided in this article. The measured IDPs included volumes of brain subregions, cerebral vessel geometrical parameters, microstructural tracts, and function connectivity metrics.
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Invasion and metastasis of melanoma are a series of complicated biological events regulated by multiple factors. The coregulation of many molecules involved in the development and progression of melanoma contributes to invasion and migration. mGluR1 is a metabotropic glutamate receptor that is overexpressed in melanocytes and is sufficient to induce melanoma. In our study, we found that mGluR1 was obviously increased in melanoma. Furthermore, we found that miR-129-5p could directly target and regulate mGluR1 mRNA, which was significantly reduced in A375 cells. Overexpression of miR-129-5p inhibited cell migration, invasion and clonal formation. lncRNA-AC130710 directly targeted and suppressed miR-129-5p in A375 cells. Downregulation of lncRNA-AC130710 suppressed the levels of mGluR1 mRNA by promoting miR-129-5p expression and further inhibiting migration, invasion and colony formation in A375 cells, which was associated with the activation of the PKCα-MAPK signaling pathway. Taken together, our study showed that the lncRNA-AC130710/miR-129-5p/mGluR1 axis plays an important role in the invasion and metastasis of melanoma.
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Polypyrrole has been extensively explored for Cr(VI) removal from wastewater towing to the advantages of superior performance, low cost, facile synthesis, and high environmental stability. However, the unsatisfactory adsorption capacity and complicated process of adsorbent separation from aqueous solutions remain a huge challenge, limiting its practical application. Herein, a flexible PPy membrane with bayberry-like vesicle structures (PPy-B) was prepared via template-assisted interfacial polymerization. It was found that sodium sulfosalicylate not only improved the flexibility and strength of the PPy-B membrane for easy-handling but also participated in the polymerization of PPy as a dopant to improve the specific surface area and doping level for increasing adsorption sites. Benefiting from these, the easy-handling PPy-B membrane exhibited a high adsorption capacity (586.90-682.50 mg/g at 298-318 K), a high reusability (five adsorption-desorption cycles), and a high ultimate adsorption capacity after adsorption-desorption cycles until membrane failure (1174.86 mg/g at 298 K). The proposed mechanisms of the enhanced Cr(VI) removal involve electrostatic adsorption, reduction, and ion exchange. This flexible PPy membrane therefore shows attractive advantages in wastewater treatment.
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Myrica , Poluentes Químicos da Água , Adsorção , Cromo/química , Cinética , Polímeros/química , Pirróis/química , Água/química , Poluentes Químicos da Água/químicaRESUMO
Widely grown in the Northern Hemisphere, the genus Aquilegia (columbine) is a model system in adaptive radiation research. While morphological variations between species have been associated with environmental factors, such as pollinators, how genetic and epigenetic factors are involved in the rapid divergence in this genus remains under investigated. In this study, we surveyed the genomes and DNA methylomes of ten Aquilegia species, representative of the Asian, European and North American lineages. Our analyses of the phylogeny and population structure revealed high genetic and DNA methylomic divergence across these three lineages. By multi-level genome-wide scanning, we identified candidate genes exhibiting lineage-specific genetic or epigenetic variation patterns that were signatures of inter-specific divergence. We demonstrated that these species-specific genetic variations and epigenetic variabilities are partially independent and are both functionally related to various biological processes vital to adaptation, including stress tolerance, cell reproduction and DNA repair. Our study provides an exploratory overview of how genetic and epigenetic signatures are associated with the diversification of the Aquilegia species.
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Aquilegia , Aquilegia/genética , Epigênese Genética , Epigenômica , Filogenia , Especificidade da EspécieRESUMO
Myocardial infarction (MI) is one of the fatal diseases in humans. Its incidence is constantly increasing annually all over the world. The problem is accompanied by the limited regenerative capacity of cardiomyocytes, yielding fibrous scar tissue formation. The propagation of electrical impulses in such tissue is severely hampered, negatively influencing the normal heart pumping function. Thus, reconstruction of the internal cardiac electrical connection is currently a major concern of myocardial repair. Conductive biomaterials with or without cell loading were extensively investigated to address this problem. This article introduces a detailed overview of the recent progress in conductive biomaterials and fabrication methods of conductive scaffolds for cardiac repair. After that, the advances in myocardial tissue construction in vitro by the restoration of intercellular communication and simulation of the dynamic electrophysiological environment are systematically reviewed. Furthermore, the latest trend in the study of cardiac repair in vivo using various conductive patches is summarized. Finally, we discuss the achievements and shortcomings of the existing conductive biomaterials and the properties of an ideal conductive patch for myocardial repair. We hope this review will help readers understand the importance and usefulness of conductive biomaterials in cardiac repair and inspire researchers to design and develop new conductive patches to meet the clinical requirements. STATEMENT OF SIGNIFICANCE: After myocardial infarction, the infarcted myocardial area is gradually replaced by heterogeneous fibrous tissue with inferior conduction properties, resulting in arrhythmia and heart remodeling. Conductive biomaterials have been extensively adopted to solve the problem. Summarizing the relevant literature, this review presents an overview of the types and fabrication methods of conductive biomaterials, and focally discusses the recent advances in myocardial tissue construction in vitro and myocardial repair in vivo, which is rarely covered in previous reviews. As well, the deficiencies of the existing conductive patches and their construction strategies for myocardial repair are discussed as well as the improving directions. Confidently, the readers of this review would appreciate advantages and current limitations of conductive biomaterials/patches in cardiac repair.
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Materiais Biocompatíveis , Engenharia Tecidual , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Condutividade Elétrica , Humanos , Miocárdio , Miócitos Cardíacos/fisiologia , Engenharia Tecidual/métodosRESUMO
OBJECTIVE: To evaluate the effects of recombinant adenovirus encoding human apM1 gene on proliferation and nitric oxide synthase (NOS) activity in human umbilical vein endothelial cells (HUVECs). METHODS: Protein expression of apM1 in cell culture supernatant of HUVECs transfected with human Ad-apM1 was detected by double antibody sandwich ELISA. The effect of human adiponectin on cell proliferation was assessed by MTT assay. The total NOS and iNOS expressions were measured by chromatometre. RESULTS: Human adiponectin protein level and total NOS and eNOS expressions were significant increased and iNOS expression significantly reduced in culture supernatant of HUVECs infected with Ad-apM1 compared to that in control HUVECs. The recombinant adenovirus had no influence on HUVECs growth as determined by MTT assay. CONCLUSIONS: Human Ad-apM1 can be effectively expressed in HUVECs and do not influence HUVECs growth. Increased total NOS and eNOS expressions and decreased iNOS expression in HUVECs transfected with Ad-apM1 gene suggest a potential role of Ad-apM1 gene transfer for the prevention and treatment of arteriosclerosis.
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Adenoviridae/genética , Proliferação de Células , Células Endoteliais/metabolismo , Óxido Nítrico Sintase/metabolismo , Adiponectina/genética , Células Cultivadas , Células Endoteliais/citologia , Endotélio Vascular/citologia , Expressão Gênica , Técnicas de Transferência de Genes , Humanos , Veias Umbilicais/citologiaRESUMO
Adiponectin plays an important role in atherosclerosis, but its relationship with the early initiation of atherosclerosis in diabetes mellitus is still not completely understood. In this study, we defined the role of adiponectin early in the process of atherosclerosis in hyperglycemic rats. Recombinant adenovirus expressing the full-length apM1 cDNA gene (Ad-APN) was constructed and successfully transfected into hyperglycemic rats characterized by the presentation of early atherosclerosis. The levels of sICAM-1 and C-reactive protein (CRP) in serum as well as the expression of VCAM-1, ICAM-1 and MCP-1 in aortic tissue were evaluated. Serum adiponectin was significantly increased in Ad-APN-treated rats compared with Ad-ßgal-treated rats. The levels of sICAM-1 and CRP in serum were dramatically reduced by 22 and 21%, respectively, in Ad-APN-treated rats. Additionally, in aortic tissue, significantly reduced mRNA levels of VCAM-1, ICAM-1 and MCP-1 were observed after Ad-APN transfection. These results suggest that, in hyperglycemic rats, adiponectin plays an inhibitory role in the early development of atherosclerosis. In conclusion, the protective effect of adiponectin is associated with the reduced activity of various inflammation-related factors.
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AIM: To investigate the effect and mechanism of ascorbic acid on podocyte, last barrier of glomerular filtration, in diabetic rats. METHODS: Diabetic rats induced by streptozotocin injection intraperitoneally were treated by ascorbic acid for 5 weeks. The levels of blood glucose (BG), HbA1c, urinary albumin excretion rate (UAER) and superoxide diamutase (SOD), catalase (CAT) and malondialdehyde (MDA) in renal cortex were measured. The podocyte ultrastructure was observed while the expression of desmin protein, a marker of podocyte injury, was examined. RESULTS: Compared with control group, BG and HbA1c were increased markedly in diabetic group. The activities of SOD and CAT were decreased and the concentrations of MDA were increased significantly in diabetic renal cortex. There were the increased proteinic expression of desmin, foot process effacement in podocytes and UAER markedly in diabetic rats. Compared with diabetic rats, foot process effacement and the changes of UAER were ameliorated markedly while the activities of SOD were increased, the levels of MDA and proteinic expression of desmin were decreased markedly although BG, HbA1c and the activities of CAT were no significant difference in the diabetic rats by ascorbic acid treatment. CONCLUSION: The findings suggest that there are marked injury in podocyte, last barrier of glomerular filtration, in diabetic rats and administration of ascorbic acid can protect podocyte by increasing antioxidative capacity and ameliorating the renal oxidative stress.