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As global climate change persists, ongoing warming exposes plants, including kiwifruit, to repeated cycles of drought stress and rewatering, necessitating the identification of drought-resistant genotypes for breeding purposes. To better understand the physiological mechanisms underlying drought resistance and recovery in kiwifruit, moderate (40-45% field capacity) and severe (25-30% field capacity) drought stresses were applied, followed by rewatering (80-85% field capacity) to eight kiwifruit rootstocks in this study. We then conducted a multivariate analysis of 20 indices for the assessment of drought resistance and recovery capabilities. Additionally, we identified four principal components, each playing a vital role in coping with diverse water conditions. Three optimal indicator groups were pinpointed, enhancing precision in kiwifruit drought resistance and recovery assessment and simplifying the evaluation system. Finally, MX-1 and HW were identified as representative rootstocks for future research on kiwifruit's responses to moderate and severe drought stresses. This study not only enhances our understanding of the response mechanisms of kiwifruit rootstocks to progressive drought stress and recovery but also provides theoretical guidance for reliable screening of drought-adaptive kiwifruit genotypes.
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Actinidia , Secas , Genótipo , Actinidia/genética , Actinidia/fisiologia , Análise Multivariada , Estresse Fisiológico/genética , Raízes de Plantas/fisiologia , Raízes de Plantas/genética , Água/metabolismo , Frutas/genética , Frutas/fisiologia , Resistência à SecaRESUMO
Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field.
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Encéfalo , Aprendizado Profundo , Imageamento por Ressonância Magnética , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Macaca mulatta , Neuroimagem/métodos , Pan troglodytes/anatomia & histologia , Envelhecimento/fisiologiaRESUMO
BACKGROUND: Soy 11S globulin has high thermal stability, limiting its application in the production of low-temperature gel foods. In this study, the low-frequency magnetic field (LF-MF, 5 mT) treatment (time, 30, 60, 90, and 120 min) was used to improve the solubility, conformation, physicochemical properties, surface characteristics, and gel properties of soy 11S globulin. RESULTS: Compared with the native soy 11S globulin, the sulfhydryl content, emulsifying capacity, gel strength, water-holding capacity, and absolute zeta potential values significantly increased (P < 0.05) after LF-MF treatment. The LF-MF treatment induced the unfolding of the protein structure and the fracture of disulfide bonds. The variations in solubility, foaming properties, viscosity, surface hydrophobicity, and rheological properties were closely related to the conformational changes of soy 11S globulin, with the optimum LF-MF modification time being 90 min. CONCLUSION: LF-MF treatment is an effective method to improve various functional properties of native soy 11S globulin, and this study provides a reference for the development of plant-based proteins in the food industry. © 2024 Society of Chemical Industry.
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Globulinas , Glycine max , Interações Hidrofóbicas e Hidrofílicas , Campos Magnéticos , Reologia , Solubilidade , Proteínas de Soja , Proteínas de Soja/química , Viscosidade , Globulinas/química , Glycine max/química , Conformação ProteicaRESUMO
BACKGROUND: Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. METHODS: This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. RESULTS: Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug-related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. CONCLUSIONS: FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.
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Neurofibroma Plexiforme , Neurofibromatose 1 , Humanos , Adulto , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/patologia , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibroma Plexiforme/patologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
SYHA1813 is a potent multikinase inhibitor that targets vascular endothelial growth factor receptors (VEGFRs)/colony-stimulating factor 1 receptor (CSF1R). This study aimed to evaluate the safety, pharmacokinetics (PK), and antitumor activity of escalating doses of SYHA1813 in patients with recurrent high-grade gliomas (HGGs) or advanced solid tumors. This study adopted a combination of accelerated titration and a 3 + 3 design for dose escalation, with a starting dose of 5 mg once daily. The dose escalation continued at successive dose levels until the maximum tolerated dose (MTD) was determined. A total of 14 patients were enrolled and treated, including 13 with WHO grade III or IV gliomas and 1 with colorectal cancer. Two patients experienced dose-limiting toxicities (grade 4 hypertension and grade 3 mucositis oral) at 30 mg SYHA1813. The MTD was defined as 15 mg once daily. Hypertension (n = 6, 42.9%) was the most frequent treatment-related adverse event. Among evaluable patients (n = 10), 2 (20%) patients achieved partial response, and 7 (70%) had stable disease. The exposure increased with increasing doses within the studied dose range of 5 to 30 mg. Biomarker assessments demonstrated significant reductions in the levels of soluble VEGFR2 (P = .0023) and increases in the levels of VEGFA (P = .0092) and placental growth factor (P = .0484). The toxicities of SYHA1813 were manageable, and encouraging antitumor efficacy was observed in patients with recurrent malignant glioma. This study is registered with the Chinese Clinical Trial Registry ( www.chictr.org.cn/index.aspx ; identifier ChiCTR2100045380).
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Glioma , Hipertensão , Neoplasias , Humanos , Feminino , Fator A de Crescimento do Endotélio Vascular , Fator de Crescimento Placentário/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Glioma/tratamento farmacológico , Receptores de Fator Estimulador de Colônias , Dose Máxima TolerávelRESUMO
To study the use of partial or total potassium bicarbonate (PBC) to replace sodium tripolyphosphate (STPP) on reduced-phosphate silver carp batters, all the batters were composed of silver carp surimi, pork back fat, ice water, spices, sugar, and sodium chloride. Therein, the sample of T1 contained 4 g/kg STPP; T2 contained 1 g/kg PBC, 3 g/kg STPP; T3 contained 2 g/kg PBC, 2 g/kg STPP; T4 contained 3 g/kg PBC, 1 g/kg STPP; T5 contained 4 g/kg PBC, and they were all produced using a bowl chopper. The changes in pH, whiteness, water- and oil-holding capacity, gel and rheological properties, as well as protein conformation were investigated. The pH, cooking yield, water- and oil-holding capacity, texture properties, and the G' values at 90 °C of the reduced-phosphate silver carp batters with PBC significantly increased (p < 0.05) compared to the sample without PBC. Due to the increasing pH and enhanced ion strength, more ß-sheet and ß-turns structures were formed. Furthermore, by increasing PBC, the pH significantly increased (p < 0.05) and the cooked silver carp batters became darkened. Meanwhile, more CO2 was generated, which destroyed the gel structure, leading the water- and oil-holding capacity, texture properties, and G' values at 90 °C to be increased and then decreased. Overall, using PBC partial as a substitute of STPP enables reduced-phosphate silver carp batter to have better gel characteristics and water-holding capacity by increasing its pH and changing its rheology characteristic and protein conformation.
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Carpas , Água , Animais , Água/química , Fosfatos , ReologiaRESUMO
Recently, an increasing number of studies have highlighted the role of the cerebellum in language processing. However, the role of neural reorganization within the cerebellum as well as within the cerebrocerebellar system caused by poststroke aphasia remains unknown. To solve this problem, in the present study, we investigated regional alterations of the cerebellum as well as the functional reorganization of the cerebrocerebellar circuit by combining structural and resting-state functional magnetic resonance imaging (fMRI) techniques. Twenty patients diagnosed with aphasia following left-hemispheric stroke and 20 age-matched healthy controls (HCs) were recruited in this study. The Western Aphasia Battery (WAB) test was used to assess the participants' language ability. Gray matter volume, spontaneous brain activity, functional connectivity, and effective connectivity were examined in each participant. We discovered that gray matter volumes in right cerebellar lobule VI and right Crus I were significantly lower in the patient group, and the brain activity within these regions was significantly correlated with WAB scores. We also discovered decreased functional connectivity within the crossed cerebrocerebellar circuit, which was significantly correlated with WAB scores. Moreover, altered information flow between the cerebellum and the contralateral cerebrum was found. Together, our findings provide evidence for regional alterations within the cerebellum and the reorganization of the cerebrocerebellar system following poststroke aphasia and highlight the important role of the cerebellum in language processing within aphasic individuals after stroke.
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Afasia , Cérebro , Afasia/diagnóstico por imagem , Afasia/etiologia , Cerebelo/diagnóstico por imagem , Córtex Cerebral , Humanos , Imageamento por Ressonância MagnéticaRESUMO
To study the effects of an ultrasound (0, 30, and 60 min) and sodium bicarbonate (0% and 0.2%) combination on the reduced-salt pork myofibrillar protein, the changes in pH, turbidity, aggregation, and conformation were investigated. After the ultrasound-assisted sodium bicarbonate treatment, the pH increased by 0.80 units, the absolute value of Zeta potential, hydrophobic force, and active sulfhydryl group significantly increased (p < 0.05), and the turbidity and particle size significantly decreased (p < 0.05). Meanwhile, the fluorescence intensity decreased from 894 to 623, and the fluorescence peak showed a significant redshift, which indicated that the ultrasound-assisted sodium bicarbonate treatment exposed the non-polarity of the microenvironment in which the fluorescence emission group was located, leading to the microenvironment and protein structure of myofibrillar tryptophan being changed. Overall, an ultrasound-assisted sodium bicarbonate treatment could significantly improve pork myofibrillar protein solubility and change the protein structure under a reduced-salt environment.
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Carne de Porco , Carne Vermelha , Animais , Suínos , Bicarbonato de Sódio/farmacologia , Proteínas , Solubilidade , Interações Hidrofóbicas e Hidrofílicas , Cloreto de Sódio , Cloreto de Sódio na DietaRESUMO
The changes in the gel and rheological properties and water-holding capacity of PSE meat myofibrillar proteins with different amounts of sodium bicarbonate (SC, 0−0.6/100 g) were studied. Compared to the PSE meat myofibrillar proteins with 0/100 g SC, the texture properties and cooking yield significantly increased (p < 0.05) with increasing SC; meanwhile, adding SC caused the gel color to darken. All samples had similar curves with three phases, and the storage modulus (G') values significantly increased with the increasing SC. The thermal stability of the PSE meat myofibrillar proteins was enhanced, and the G' value at 80 °C increased with the increasing SC. Because water was bound more tightly to the protein matrix, the initial relaxation times of T21 and T22 shortened, the peak ratio of P21 significantly increased (p < 0.05), and the P22 significantly decreased (p < 0.05), which implied that the mobility of the water was reduced. Overall, SC could improve the thermal stability of the PSE meat myofibrillar proteins and increase the water-holding capacity and textural properties of the cooked PSE meat myofibrillar protein gels.
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Proteínas de Carne , Bicarbonato de Sódio , Água , Culinária , Reologia , GéisRESUMO
BACKGROUND: Systemic cardiac hypoperfusion is a well-acknowledged contributor to ischemic leukoencephalopathy. However, it has remained elusive how atherosclerosis-mediated cardiac remodelling modifies cerebral perfusion homeostasis as well as neuroimaging burden in cerebral small vessel disease (CSVD) development. METHODS: This retrospective study identified 103 arteriosclerotic CSVD (aCSVD) patients (CSVD burdenlow 0 ~ 1, n = 61 and CSVD burdenhigh 2 ~ 4, n = 42) from Sep. 2017 to Dec. 2019 who underwent transthoracic echocardiography(n = 81), structural magnetic resonance imaging and arterial spin labelling (ASL). Total CSVD burden was graded according to the ordinal "small vessel disease" rating score (0-4). We investigated the univariate and multivariate linear regression of mean deep regional cerebral blood flow (CBF) as well as logistic regression analysis of CSVD burdenhigh. RESULTS: Right atrial diameter (B coefficient, - 0.289; 95% CI, - 0.578 to - 0.001; P = 0.049) and left ventricular ejection fraction (B coefficient, 32.555; 95% CI, 7.399 to 57.711; P = 0.012) were independently associated with deep regional CBF in aCSVD patients. Binary logistic regression analysis demonstrated decreased deep regional CBF (OR 0.894; 95% CI 0.811-0.985; P = 0.024) was independently associated with higher CSVD burden after adjusted for clinical confounders. Multivariate receiver operating characteristics curve integrating clinical risk factors, mean deep CBF and echocardiographic parameters showed predictive significance for CSVD burdenhigh diagnosis (area under curve = 84.25, 95% CI 74.86-93.65%, P < 0.0001). CONCLUSION: The interrelationship of "cardiac -deep regional CBF-neuroimaging burden" reinforces the importance and prognostic significance of echocardiographic and cerebral hemodynamic assessment in CSVD early-warning.
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Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular , Volume Sistólico/fisiologia , Idoso , Doenças de Pequenos Vasos Cerebrais/etiologia , Doenças de Pequenos Vasos Cerebrais/patologia , Feminino , Átrios do Coração/patologia , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Estudos Retrospectivos , Fatores de Risco , Função Ventricular EsquerdaRESUMO
Functional multipotency renders human umbilical cord mesenchymal stem cell (hUC-MSC) a promising candidate for the treatment of spinal cord injury (SCI). However, its safety and efficacy have not been fully understood for clinical translation. In this study, we performed cellular, kinematic, physiological, and anatomical analyses, either in vitro or in vivo, to comprehensively evaluate the safety and efficacy associated with subarachnoid transplantation of hUC-MSCs in rats with subacute incomplete SCI. Concerning safety, hUC-MSCs were shown to have normal morphology, excellent viability, steady proliferation, typical biomarkers, stable karyotype in vitro, and no tumorigenicity both in vitro and in vivo. Following subarachnoid transplantation of hUC-MSCs in the subject rodents, the biodistribution of hUC-MSCs was restricted to the spinal cord, and no toxicity to immune system or organ function was observed. Body weight, organ weight, and the ratio of the latter upon the former between stem cell-transplanted rats and placebo-injected rats revealed no statistical differences. Regarding efficacy, hUC-MSCs could differentiate into osteoblasts, chondrocytes, adipocytes and neural progenitor cells in vitro. While in vivo studies revealed that subarachnoid transplantation of stem cells resulted in significant improvement in locomotion, earlier automatic micturition recovery and reduced lesion size, which correlated with increased regeneration of tracking fiber and reduced parenchymal inflammation. In vivo luminescence imaging showed that a few of the transplanted luciferase-labeled hUC-MSCs tended to migrate towards the lesion epicenter. Shortened latency and enhanced amplitude were also observed in both motor and sensory evoked potentials, indicating improved signal conduction in the damaged site. Immunofluorescent staining confirmed that a few of the administrated hUC-MSCs integrated into the spinal cord parenchyma and differentiated into astrocytes and oligodendrocytes, but not neurons. Moreover, decreased astrogliosis, increased remyelination, and neuron regeneration could be observed. To the best of our knowledge, this preclinical study provides detailed safety and efficacy evidence regarding intrathecal transplantation of hUC-MSCs in treating SCI for the first time and thus, supports its initiation in the following clinical trial.
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Células-Tronco Mesenquimais/citologia , Células-Tronco Neurais/citologia , Neurônios/patologia , Traumatismos da Medula Espinal/patologia , Cordão Umbilical/citologia , Astrócitos/patologia , Diferenciação Celular/fisiologia , Células Cultivadas , Condrócitos/patologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
The effects of high pressure (100-500 MPa) and heated (80 °C, 25 min) combinations on gel properties, rheological characteristic and water distribution of pork batters were investigated. Compared to the only-heat, the cooking yield, a* value, hardness, cohesiveness, and chewiness of cooked pork batters treated less than 300 MPa were significantly increased (P < 0.05), meanwhile, the b* value was significantly decreased (P < 0.05). Opposite, the color and cooking yield were not significant different (P > 0.05) when over 300 MPa, except the L* value. At 300 MPa, the cooking yield, hardness, chewiness, and G' value at 80 °C of pork batter were the highest. The initial relaxation time of T21 was decreased significantly (P < 0.05), and the peak ration of P21 was increased significantly (P < 0.05) when treated at 200 and 300 MPa, that indicated the water was bound tightly and the ratio of immobilized water was increased. Overall, 300 MPa treatment and thermal combinations could improve the gel properties of pork batters.
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The objective of this study was to evaluate relationship with aggregation, secondary structures and gel properties of pork myofibrillar protein with different sodium chloride (1%, 2% and 3%). When the sodium chloride increased from 1 to 3%, the active sulfhydryl, surface hydrophobicity, hardness and cooking yield of myofibrillar protein were increased significantly (p < 0.05), the particle size, total sulfhydryl and Zeta potential were decreased significantly (p < 0.05), these meant the aggregations of pork myofibrillar protein were decreased. The changes of proteins aggregation induced the strongest intensity band of Amide I shifted up from 1660 cm-1 to 1661 cm-1, meanwhile, the ß-sheet structure content was increased significantly (p < 0.05) with the sodium chloride increased. From the above, the lower proteins aggregation and higher ß-sheet structure content could improve the water holding capacity and texture of pork myofibrillar protein gel.
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OBJECTIVES: To characterize the genetic environment of the carbapenem resistance determinant in Proteus vulgaris of swine origin. METHODS: The carbapenem-resistant P. vulgaris strain BC22 was isolated from a faecal swab from a diseased pig with diarrhoea in Sichuan Province of China in 2018. The presence of carbapenemase genes was screened by PCR. WGS and bioinformatics analysis were performed to analyse the genetic environment of the carbapenem resistance determinant. RESULTS: P. vulgaris strain BC22 was found to harbour the carbapenemase gene blaNDM-1. WGS data revealed that blaNDM-1 was located in a truncated ISAba125 composite transposon. The carbapenem resistance gene blaNDM-1 and 20 other resistance genes, including the multiresistance gene cfr and the bifunctional aminoglycoside/quinolone resistance gene aac(6')-lb-cr, were located in a novel SXT/R391 integrative and conjugative element (ICE). This new SXT/R391 ICE of 148.7 kb was chromosomally located, and could be transferred to Escherichia coli. CONCLUSIONS: Here, we report a carbapenemase gene, blaNDM-1, integrated into an SXT/R391 ICE. Our study highlights that this SXT/R391 ICE may facilitate the dissemination of clinically important resistance genes such as blaNDM-1, cfr and aac(6')-lb-cr.
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Proteus vulgaris , beta-Lactamases , Animais , Proteínas de Bactérias/genética , China , Conjugação Genética , Suínos , beta-Lactamases/genéticaRESUMO
To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/uso terapêutico , Liraglutida/uso terapêutico , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fosfato de Sitagliptina/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Modelos Lineares , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prognóstico , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To explore the effect of BRAF inhibitor on epithelioid glioblastoma (Ep-GBM) with BRAFV600E mutation. METHODS: A patient of Ep-GBM with BRAFV600E mutation underwent BRAF inhibition therapy. The rationale behind combined BRAF and MEK inhibition in Ep-GBM was reviewed. RESULTS: Vemurafenib can initially inhibit the progression of Ep-GBM with BRAFV600E mutation. However, the tumor may become resistant to vemurafenib and then progress. CONCLUSIONS: BRAF inhibition therapy can inhibit the progression of Ep-GBM with BRAFV600E mutation, but the subsequent resistance development leads to a poor outcome.
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Glioblastoma , Proteínas Proto-Oncogênicas B-raf , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Vemurafenib/uso terapêuticoRESUMO
PURPOSE: Visibility of deep medullary veins (DMVs) seen at SWI is predictive of poor prognosis in ischemic stroke. Few attentions have been paid to DMVs in atherosclerotic cerebral small vessel disease (aCSVD) which is attributed to long-term imbalanced microhemodynamics. We conducted this retrospective study to explore the association between DMVs profiles and aCSVD risk factors, neuroimaging markers. METHODS: Two hundred and two patients identified as aCSVD from January 2017 to March 2019 were included in the study. Their demographic, clinical, laboratory, and neuroimaging data were reviewed. The quantity and morphology of DMVs were assessed with a 5-grade (range 0~4) visual rating scale. Total CSVD burden was calculated with an ordinal "SVD score" (range 0~4). Spearman rank correlation and multivariable logistic regression analysis were performed to determine the association between DMV scale and CSVD markers. RESULTS: DMV scale showed strong positive correlation with CSVD burden (rs = 0.629, P < 0.001). Age (OR 1.078, 95% CI 1.015-1.145, P = 0.015) and hypertension (OR 2.629, 95% CI 1.024-6.749, P = 0.045) were two demographic risk factors for high DMV scale. Among CSVD neuroimaging markers, periventricular WMH (OR 2.925, 95% CI 1.464-5.845, P = 0.002), deep WMH (OR 2.872, 95% CI 1.174-7.022, P = 0.021), lacunae (OR 1.961, 95% CI 1.181-3.254, P = 0.009), and cerebral atrophy (OR 2.046, 95% CI 1.079-3.880, P = 0.028) were associated with high DMV scale after adjusting for clinical and metabolic confounders. CONCLUSION: Multifactorial association between DMV scale and epidemiological, radiological contributors of aCSVD suggests DMV's involved pathomechanism may participate in aCSVD development. Attach importance to DMV radiological profile in aCSVD will provide more neuroimaging information for diagnosis and prognosis.
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Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Veias Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Substância Branca/irrigação sanguínea , Substância Branca/diagnóstico por imagem , Idoso , Biomarcadores , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Neuroimagem/normas , Estudos RetrospectivosRESUMO
As the COVID-19 pandemic is intensifying globally, more and more people are pinning their hopes on the development of vaccines. At present, there are many research teams who have adopted different vaccine technology routes to develop 2019-nCoV vaccines. This article reviews and analyzes the current development and research status of 2019-nCoV vaccines in different routes, and explores their possible development in the future.
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Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/uso terapêutico , Betacoronavirus , COVID-19 , Vacinas contra COVID-19 , Humanos , SARS-CoV-2RESUMO
Krüppel-like factors (KLFs) are zinc-finger transcriptional factors that regulate target gene expression. Recent studies have shown that KLFs play essential roles in cancer development, whereas the function of KLF7 in glioma remains unclear. In this study, we showed that KLF7 was up-regulated in glioma tissues and its expression was inversely correlated with the patients' survival. Functional experiments demonstrated that KLF7 promoted the proliferation, migration and tumorigenesis of glioma cells. Mechanistically, KLF7 transcriptionally activated argininosuccinate lyase (ASL), which was observed highly expressed in glioma tissues. The biosynthesis of polyamine, a urea cycle metabolite, was enhanced by KLF7 in glioma cells. In addition, ASL contributed to the growth of glioma cells triggered by KLF7. Our findings demonstrate KLF7 as an oncogene and link KLF7 to ASL-mediated polyamine metabolism in glioma.
Assuntos
Argininossuccinato Liase/genética , Neoplasias Encefálicas/genética , Glioma/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Poliaminas/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Ativação TranscricionalRESUMO
BACKGROUND: Proliferating cell nuclear antigen (PCNA), a conserved trimeric ring complex, is loaded onto replication fork through a hetero-pentameric AAA+ ATPase complex termed replication factor C (RFC) to maintain genome stability. Although architectures of PCNA-RFC complex in yeast have been revealed, the functions of PCNA and protein-protein interactions of PCNA-RFC complex in higher plants are not very clear. Here, essential regions mediating interactions between PCNA and RFC subunits in Arabidopsis and rice were investigated via yeast-two-hybrid method and bimolecular fluorescence complementation techniques. RESULTS: We observed that OsPCNA could interact with all OsRFC subunits, while protein-protein interactions only exist between Arabidopsis RFC2/3/4/5 and AtPCNA1/2. The truncated analyses indicated that the C-terminal of Arabidopsis RFC2/3/4/5 and rice RFC1/2 is essential for binding PCNA while the region of rice RFC3/4/5 mediating interaction with PCNA distributed both at the N- and C-terminal. On the other hand, we found that the C- and N-terminal of Arabidopsis and rice PCNA contribute equally to PCNA-PCNA interaction, and the interdomain connecting loop (IDCL) domain and C-terminal of PCNAs are indispensable for interacting RFC subunits. CONCLUSIONS: These results indicated that Arabidopsis and rice PCNAs are highly conserved in sequence, structure and pattern of interacting with other PCNA monomer. Nevertheless, there are also significant differences between the Arabidopsis and rice RFC subunits in binding PCNA. Taken together, our results could be helpful for revealing the biological functions of plant RFC-PCNA complex.