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Pretreatment of lignocellulose yields a complex sugar mixture that potentially can be converted into bioethanol and other chemicals by engineered yeast. One approach to overcome competition between sugars for uptake and metabolism is the use of a consortium of specialist strains capable of efficient conversion of single sugars. Here, we show that maltose inhibits cell growth of a xylose-fermenting specialist strain IMX730.1 that is unable to utilize glucose because of the deletion of all hexokinase genes. The growth inhibition cannot be attributed to a competition between maltose and xylose for uptake. The inhibition is enhanced in a strain lacking maltase enzymes (dMalX2) and completely eliminated when all maltose transporters are deleted. High-level accumulation of maltose in the dMalX2 strain is accompanied by a hypotonic-like transcriptional response, while cells are rescued from maltose-induced cell death by the inclusion of an extracellular osmolyte such as sorbitol. These data suggest that maltose-induced cell death is due to high levels of maltose uptake causing hypotonic-like stress conditions and can be prevented through engineering of the maltose transporters. Transporter engineering should be included in the development of stable microbial consortia for the efficient conversion of lignocellulosic feedstocks.
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Maltose , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Maltose/metabolismo , Viabilidade Microbiana , Deleção de Genes , Sorbitol/metabolismo , Sorbitol/farmacologia , Xilose/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Glucose/metabolismoRESUMO
Etoposide-induced 2.4 (EI24) exerts tumor suppressor activity through participating in cell apoptosis, autophagy, and inflammation. However, its role in renal diseases has not been elucidated. This study showed that the EI24 level decreased gradually in the kidneys of mice with unilateral ureteral obstruction (UUO) and in another fibrosis model induced by diabetic kidney disease. The overexpression of EI24 was used to investigate the possible role both in vivo and in vitro. The overexpression 1 day after UUO through tail vein injection alleviated the progression of renal interstitial fibrosis (RIF). EI24 inhibited epithelial-mesenchymal transition, excessive deposition of the extracellular matrix, and activation of fibroblasts. Furthermore, administration of EI24-overexpressing plasmids restrained the phosphorylation of nuclear factor-κB (NF-κB) and c-Jun kinase (JNK) through regulating the proteasome-dependent degradation of TRAF2, and then, inhibited the expression of downstream inflammation-associated cytokines (interleukin-6, tumor necrosis factor-α, and monocyte chemotactic protein-1) and infiltration of macrophages and neutrophils in mouse kidney after UUO. In conclusion, the data indicated that EI24, a novel anti-fibrosis regulator, was important in the progression of RIF.
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Proteínas Reguladoras de Apoptose/metabolismo , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal , Proteínas Nucleares/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Fibrose/genética , Masculino , Camundongos , Proteínas Nucleares/genética , Obstrução Ureteral/genética , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologiaRESUMO
OBJECTIVES: This study aimed to assess the factors influencing bone erosion (BE) in patients with gout using dual-energy gemstone spectral imaging computer tomography. METHODS: We compared the clinical data, laboratory indices, and tissue urate levels at the monosodium urate (MSU) bone interface measured by dual-energy gemstone spectral imaging computed tomography of 87 gout patients with (n = 41) and without (n = 46) BE. Logistic regression analysis was used to investigate the risk factors associated with BE. RESULTS: In total, 47.1% of patients with gout had BE. The disease duration, serum uric acid, tissue urate levels, and the presence of tophi were significantly higher (p < .05) in gout patients with BE than in those without BE. Longer disease duration (odds ratio = 1.11, 95% confidence interval: 1.00-1.24, p < .05) and increased tissue urate levels (odds ratio = 1.01, 95% confidence interval: 1.00-1.02, p < .05) were independently associated with BE. Tissue urate levels at the MSU-bone interface were correlated with the presence of tophi (r = 0.62, p < .001), BE (r = 0.51, p < .001), renal calculus (r = 0.24, p = .03), and serum uric acid levels (r = 0.23, p = .03). CONCLUSIONS: This study found that longer disease duration and elevated tissue urate concentrations at the MSU-bone interface were associated with BE in patients with gout.
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Artrite Gotosa , Gota , Osso e Ossos , Gota/complicações , Gota/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X/métodos , Ácido ÚricoRESUMO
Aflatoxin B1 (AFB1) causes oxidative stress and hepatocyte apoptosis through its epoxidized metabolite AFBO, which is catalyzed by CYP450 enzymes. Ferulic acid (FA) is a phenolic acid commonly found in plants and is known for its antioxidant capacity. However, the role of FA in AFB1-induced liver injury is still elusive. In this study, rats were exposed to AFB1 and simultaneously treated with FA for 30 days. The results showed that I) FA alleviated the histopathological changes induced by AFB1, inhibited the elevation of serological indexes induced by AFB1, and reduced the production of AFBO in liver. II) AFB1-induced increase in CYP450 expression was significantly reduced by FA. The molecular docking results of FA and CYP2A6 showed high fitness score and interaction. III) FA obviously inhibited the production of MDA, and significantly activated the Nrf2/GST pathway and antioxidant enzymes (SOD and GST). IV) AFB1-induced hepatocyte apoptosis, the high expression of p53, bax, cyt-c, caspase-9, caspase-3, and the low expression of bcl-2 were all restored by FA. It has been suggested from these results that FA proved effective against AFB1-induced liver damage in rats via inhibiting CYP450 enzyme, promoting antioxidant pathway Nrf2/GST, activating antioxidant enzymes (SOD and GST), and regulating the mitochondrial pathway.
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Objective To evaluate lateral pterygoid muscle(LPM)contraction in the patients with temporomandibular disorders(TMD)based on 3D-T2 weighted imaging(3D-T2WI).Multiplanar reconstruction(MPR)was employed to measure the length of LPM in the images taken in closed-and open-mouth positions. Methods Seventeen TMD patients [age of(29.82±10.70)years,males/females=8/9] and 13 normal volunteers [control,age of(23.54±3.31)years,males/females=6/7] received 3D-T2WI of the temporomandibular joints in closed-and open-mouth positions from November 2019 to April 2020 in Department of Radiology,Hainan Hospital of Chinese PLA General Hospital.According to the position of the discs,the subjects were classified into the following groups:TMD with disc displacement without reduction(TMD-DDwoR),TMD with disc displacement with reduction(TMD-DDwR),TMD without disc displacement(TMDwoDD),and normal control without disc displacement(NCwoDD).MPR was employed to measure the maximal length of the superior belly of LPM.One-way analysis of variance,receiver operating characteristic curve,and permutation test were employed for the statistical analyses. Results The contraction of LPM was significantly shorter in TMD-DDwoR group [(3.36±1.96)mm] than in TMDwoDD group [(7.90±3.95)mm],NCwoDD group [(8.77±3.13)mm](F=12.891,P=0.000),and TMD-DDwR group[(7.12±3.69)mm](χ2=5.314,P=0.031). Conclusion This study confirmed that the contraction of LPM decreased in patients with TMD-DDwoR,which provided imaging evidence for the study of disc displacement mechanism in TMD patients.
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Luxações Articulares , Transtornos da Articulação Temporomandibular , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Contração Muscular , Músculos Pterigoides/diagnóstico por imagem , Disco da Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Adulto JovemRESUMO
Diabetic nephropathy (DN) is a serious microvascular complication of diabetes mellitus.The main pathological features of DN include glomerular sclerosis and renal tubular interstitial fibrosis, which results in epithelial mesenchymal transition (EMT) and excessive extracellular matrix (ECM) deposition.Transforming growth factor-ß1(TGF-ß1) is a critical factor that regulates the manifestation of renal fibrosis.Smad2 and Smad3 are the main downstream of the TGF-ß1 pathway. Ski-related novel protein N(SnoN) is a negative regulator of TGF-ß1, and inhibits the activation of the TGF-ß1/Smad2/3 signalling pathway. In this study, the expression of Smad2 and Smad3 proteins, SnoN mRNA, SnoN proteins, and the ubiquitination levels of SnoN were determined in DN rats and renal tubular epithelial cells(NRK52E cells). Knockdown and overexpression of Smad2 or Smad3 in NRK52E cells were used to investigate the specific roles of Smad2 and Smad3 in the development of high glucose-induced renal tubular fibrosis, with a specific focus on their effect on the regulation of SnoN expression. Our study demonstrated that Smad3 could inhibit SnoN expression and increase ECM deposition in NRK52E cells, to promote high glucose-induced renal tubular fibrosis. In contrast, Smad2 could induce SnoN expression and reduce ECM deposition, to inhibit high glucose-induced fibrosis. The underlying mechanism involves regulation of SnoN expression. These findings provide a novel mechanism to understanding the significant role of the TGF-ß1/ Smad2/3 pathway in DN.
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Glucose/toxicidade , Túbulos Renais/patologia , Proteínas do Tecido Nervoso/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular , Matriz Extracelular/metabolismo , Fibrose , Masculino , Proteínas do Tecido Nervoso/genética , Ratos Sprague-Dawley , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Unveiling the mechanisms that drive the pathological phenotypes of diabetic nephropathy (DN) could help develop new effective therapeutics for this ailment. Transforming growth factor-ß1 (TGF-ß1)/Smad3 signaling is aberrantly induced in DN, leading to elevated microRNA-21 (miR-21) expression and tissue fibrosis. Ski-related novel protein (SnoN) negatively regulates the TGF-ß pathway, but the relationship between SnoN and miR-21 has not been described in the context of DN. In this study, this association was investigated in vivo (streptozotocin-induced rat model of diabetes) and in vitro (NRK-52E model system under high glucose conditions). In both model systems, we observed reduced amounts of the SnoN protein and elevated miR-21 amounts, indicative of an inverse relationship. These changes in SnoN and miR-21 amounts were accompanied by reduced E-cadherin and elevated α-smooth muscle actin and collagen III levels, consistent with epithelial to mesenchymal transition (EMT). In vitro overexpression of SnoN in NRK-52E cells downregulated miR-21 at the transcriptional and posttranscriptional levels and repressed EMT and extracellular matrix (ECM) deposition. In contrast, knockdown of SnoN resulted in miR-21 upregulation, particularly at the transcriptional level. We further demonstrated that overexpression and inhibition of miR-21 promoted and suppressed EMT and ECM deposition, respectively, without affecting SnoN levels. Our results indicated that SnoN suppresses the development of DN as well as renal fibrosis by downregulating miR-21, and therefore represents a novel and promising therapeutic target for DN.
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Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/prevenção & controle , Rim/metabolismo , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Linhagem Celular , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal , Fibrose , Regulação da Expressão Gênica , Rim/patologia , Masculino , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Smad3/metabolismo , Estreptozocina , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta1/genéticaRESUMO
3-Methyl-1-butanol (3MB) is a promising biofuel that can be produced from 2-ketoisocaproate via the common L-leucine biosynthesis pathway. Corynebacterium glutamicum was chosen as a host bacterium because of its strong resistance to isobutanol. In the current study, several strategies were designed to overproduce 3MB in C. glutamicum through a non-fermentation pathway. The engineered C. glutamicum mutant was obtained by silencing the pyruvate dehydrogenase gene complex (aceE) and deleting the lactic dehydrogenase gene (ldh), followed by mutagenesis with diethyl sulfate (DES) and selection with Fmoc-3-4-thiazolyl-L-alanine (FTA). The mutant could produce 659 mg/L of 3MB after 12 h of incubation. To facilitate carbon flux to 3MB biosynthesis, the engineered recombinant was also constructed without branched-chain acid aminotransferase (ilvE) activity by deleting the ilvE gene. This recombinant could produce 697 mg/L of 3MB after 12 h of incubation.
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Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , Engenharia Genética , Mutação , Pentanóis/metabolismo , Cromossomos Bacterianos , Genes Bacterianos , Cetona Oxirredutases/genéticaRESUMO
Objective To investigate the difference in texture features on diffusion weighted imaging (DWI) images between breast benign and malignant tumors.Methods Patients including 56 with mass-like breast cancer, 16 with breast fibroadenoma, and 4 with intraductal papilloma of breast treated in the Hainan Hospital of Chinese PLA General Hospital were retrospectively enrolled in this study, and allocated to the benign group (20 patients) and the malignant group (56 patients) according to the post-surgically pathological results. Texture analysis was performed on axial DWI images, and five characteristic parameters including Angular Second Moment (ASM), Contrast, Correlation, Inverse Difference Moment (IDM), and Entropy were calculated. Independent sample t-test and Mann-Whitney U test were performed for intergroup comparison. Regression model was established by using Binary Logistic regression analysis, and receiver operating characteristic curve (ROC) analysis was carried out to evaluate the diagnostic efficiency.Results The texture features ASM, Contrast, Correlation and Entropy showed significant differences between the benign and malignant breast tumor groups (PASM=0.014, Pcontrast=0.019, Pcorrelation=0.010, Pentropy=0.007). The area under the ROC curve was 0.685, 0.681, 0.754, and 0.683 respectively for the positive texture variables mentioned above, and that for the combined variables (ASM, Contrast, and Entropy) was 0.802 in the model of Logistic regression. Binary Logistic regression analysis demonstrated that ASM, Contrast and Entropy were considered as the specific imaging variables for the differential diagnosis of breast benign and malignant tumors.Conclusions The texture analysis of DWI may be a simple and effective tool in the differential diagnosis between breast benign and malignant tumors.
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Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Fibroadenoma/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
DNA transduction across aqueous solutions has been reported previously. In this study, we examined a few key factors affecting DNA transduction rate in an extremely low frequency electromagnetic field. These include: the chemical composition of the aqueous solutions, the type of experimental vessel, the dilution step, and the origin of the DNA fragments. The results indicate that partially introducing essential ingredients for DNA amplification (i.e. dNTPs and PCR buffer) to the aqueous solution enhanced the transduction rate greatly, and transduction vessels made of hydrophilic quartz yielded more favorable results than vessels made of hydrophobic plastic. In addition, performing a serial dilution to the transduction solution more than doubled the transduction rate compared to that without the dilution step. For the DNA fragments used in this study, there was one with a pathogenic origin and two with non-pathogenic origins. However, all three fragments achieved DNA transduction regardless of the difference in their origins. The experimental setup for eliminating the false positives caused by both biological and potentially physical contamination is also described.
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DNA/genética , Campos Eletromagnéticos , Sequência de Bases , Cinética , Reação em Cadeia da Polimerase , Água/químicaRESUMO
OBJECTIVE: To screen for MYOC gene variants among sporadic patients with primary open angle glaucoma (POAG). METHODS: For 398 patients with POAG, Sanger sequencing was applied to detect potential variants of the MYOC gene. RESULTS: Eight patients (2.0%) were found to harbor variations of the MYOC gene. These included five types of variants, among which c.667C>T (p.Pro223Ser) and c.1138G>T (p.Asp380Tyr) were novel. c.382C>T (p.Arg128Trp), c.1109C>T(p.Pro370Leu) and c.1130C>A (p.Thr377Lys) were previously associated with POAG. Alignment of amino acid sequences of MYOC proteins of various species revealed that the two novel variants have occurred at highly conserved positions. c.1138G>T was predicted to be possible pathogenic by Bioinformatic analysis. CONCLUSION: Two novel variants of the MYOC gene were detected among sporadic POAG patients, which enriched its variant spectrum.
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Proteínas do Citoesqueleto/genética , Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Humanos , MutaçãoRESUMO
OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) rs547984, rs540782, rs693421 and rs2499601 of Zona Pellucida Glycoprotein 4 (ZP4) gene with primary open-angle glaucoma (POAG) among ethnic Han Chinese from Sichuan Province. METHODS: A dye terminator-based SNaPshot method was used to genotype 336 patients with POAG and 768 healthy controls. RESULTS: No significant difference was detected in allelic frequencies of rs547984, rs540782, rs693421 and rs2499601 between the two groups (P>0.05). Haplotypic analysis showed a significant difference in G-G-A-G haplotype formed by the 4 SNPs between the POAG and the control groups (P<0.05). CONCLUSION: ZP4 gene SNPs rs547984, rs540782, rs693421, rs2499601 are not associated with POAG among ethnic Hans from Sichuan.
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Povo Asiático/genética , Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Glicoproteínas da Zona Pelúcida/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , China/etnologia , Feminino , Glaucoma de Ângulo Aberto/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The diagnostic criteria of splenic hemangioma is the delayed filling enhancement pattern on the dynamic contrast CT imaging or magnetic resonance (MR) T1-weighted image,which requires long examination time and thus decreases the MR scanning efficiency. Contrast-enhanced T2 fluid-attenuated inversion recovery (FLAIR) imaging is a new MR imaging technique that can be used to evaluate the intrinsic characteristics of hemangioma. However,few literature has discribed its role in diagnosing splenic hemangioma. In this article we reported one case of splenic hemangioma diagnosed by contrast-enhanced T2 FLAIR imaging,which reduced the MR scanning time and provided valuable experience for the diagnosis of splenic hemangioma.
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Meios de Contraste , Hemangioma/diagnóstico por imagem , Aumento da Imagem , Imageamento por Ressonância Magnética , Humanos , Baço/diagnóstico por imagem , Baço/patologiaRESUMO
KEY MESSAGE: We report a transcriptome assembly and expression profiles from RNA-Seq data and identify genes responsible for culm gall formation in Zizania latifolia induced by Ustilago esculenta. The smut fungus Ustilago esculenta can induce culm gall in Zizania latifolia, which is used as a vegetable in Asian countries. However, the underlying molecular mechanism of culm gall formation is still unclear. To characterize the processes underlying this host-fungus association, we performed transcriptomic and expression profiling analyses of culms from Z. latifolia infected by the fungus U. esculenta. Transcriptomic analysis detected U. esculenta induced differential expression of 19,033 and 17,669 genes in Jiaobai (JB) and Huijiao (HJ) type of gall, respectively. Additionally, to detect the potential gall inducing genes, expression profiles of infected culms collected at -7, 1 and 10 DAS of culm gall development were analyzed. Compared to control, we detected 8089 genes (4389 up-regulated, 3700 down-regulated) and 5251 genes (3121 up-regulated, 2130 down-regulated) were differentially expressed in JB and HJ, respectively. And we identified 376 host and 187 fungal candidate genes that showed stage-specific expression pattern, which are possibly responsible for gall formation at the initial and later phases, respectively. Our results indicated that cytokinins play more prominent roles in regulating gall formation than do auxins. Together, our work provides general implications for the understanding of gene regulatory networks for culm gall development in Z. latifolia, and potential targets for genetic manipulation to improve the future yield of this crop.
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Caules de Planta/crescimento & desenvolvimento , Caules de Planta/genética , Poaceae/genética , Poaceae/microbiologia , Análise de Sequência de RNA/métodos , Ustilago/fisiologia , Vias Biossintéticas/genética , Citocininas/biossíntese , Regulação para Baixo/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Genes Fúngicos , Interações Hospedeiro-Patógeno/genética , Ácidos Indolacéticos/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Caules de Planta/microbiologia , Tumores de Planta/microbiologia , Poaceae/crescimento & desenvolvimento , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Transcriptoma/genética , Regulação para Cima/genéticaRESUMO
Objective To investigate the difference of texture on conventional T2-weighted image (T2WI) between hepatic cyst and hepatic hemangioma. Methods All the subjects included 156 patients with hepatic cyst [A group:100 cases with equi or low signal on diffusion weighted imaging (DWI);B group:56 cases with high signal on DWI] and 100 patients with hemangioma (C group). Conventional magnetic resonance imaging T2WI,DWI and dynamic contrast enhancement were performed on all the patients,and the texture analysis was applied with the images of T2WI,and the texture parameters included angular second moment,contrast,correlation,inverse difference moment,and entropy. Independent sample t-test and Aspin-Welch test were performed for the comparisons among groups. Results All the texture parameters showed significant difference among groups [(A+B) group vs. C group:ρ angular second moment=0.000,ρcontrast=0.000,ρcorrelation=0.000,Pinverse difference moment=0.822,ρentropy=0.000;A group vs. C group:ρangular second moment=0.000,ρcontrast=0.000,ρcorrelation=0.000,ρinverse difference moment=0.092,ρentropy=0.000;B group vs. C group:ρangular second moment=0.000,ρcontrast=0.000,ρcorrelation=0.000,ρinverse difference moment=0.046,ρentropy=0.009],and receiver operating characteristic curve analysis demonstrated that contrast and correlation had high differential diagnostic values between hepatic cyst and hemangioma. Conclusion Hepatic cyst and hemangioma present evident different texture characteristics,and the texture analysis may be considered as a simple and effective tool in the differential diagnosis between hepatic cyst and hemangioma based on the images of T2WI.
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Cistos/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Humanos , Fígado/patologiaRESUMO
In this study, differences between two strains of inbred mice in aspects of neutrophil function, namely Rac1 expression, chemotaxis, nicotinamide adenine dinucleotide phosphate oxidase activity and formation of neutrophil extracellular traps (NETs), were determined. Neutrophils from CBA/CaH mice exhibited weaker Rac1 expression and a slower chemotactic gradient than BALB/c mice. Furthermore, PMA- or fMLP-stimulated neutrophils from CBA/CaH mice generated much less superoxide and NETs than similarly stimulated neutrophils from BALB/c mice. These findings suggest that neutrophils from BALB/c mice are functionally more efficient than those from CBA/CaH mice.
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Camundongos/classificação , Camundongos/fisiologia , Neutrófilos/imunologia , Animais , Quimiotaxia , Armadilhas Extracelulares/metabolismo , Perfilação da Expressão Gênica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , NADPH Oxidases/análise , Neuropeptídeos/biossíntese , Neuropeptídeos/genética , Neutrófilos/enzimologia , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Especificidade da Espécie , Superóxidos/metabolismo , Proteínas rac1 de Ligação ao GTP/biossíntese , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
A maternal high-fat (HF) diet during pregnancy and lactation can result in adverse metabolic and reproductive outcomes in female offspring independent of postnatal diet. Interventions during critical windows of developmental plasticity may prevent developmental programming in offspring. The effects of maternal supplementation with the anti-inflammatory lipid conjugated linoleic acid (CLA) on early-onset puberty, metabolic dysfunction, and estrous cycle dysfunction was assessed. Sprague-Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA). Diets were fed ad libitum for 10 days prior to time mating and throughout gestation and lactation. Offspring plasma/tissues were taken at Day 24 (prepubertal) or Day 150 (adult). Puberty was assessed from Day 26 and estrous cycle from Day 128. Female offspring from HF mothers had lower birth weights but by Postnatal Day 24 had exhibited catch-up growth concomitant with increased fat mass, hyperleptinemia, and dyslipidemia. Maternal CLA supplementation reversed these effects. Early-onset puberty was only observed in HF offspring; this was reversed in HFCLA offspring. In adulthood, despite no evidence of glucose intolerance or altered insulin sensitivity, HF offspring displayed increased fat mass, dyslipidemia, disrupted estrous cyclicity. and hyperleptinemia; this was reversed by maternal CLA supplementation. Data presented in this study demonstrate the importance of diet in women of reproductive age and during pregnancy on reproductive and metabolic parameters in their offspring and that supplementation with CLA during critical windows of development may represent a therapeutic strategy in the prevention of early-life programming of metabolic and reproductive dysfunction.
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Hiperlipidemias/prevenção & controle , Lactação/fisiologia , Ácidos Linoleicos Conjugados/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Maturidade Sexual/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Suplementos Nutricionais , Feminino , Hiperlipidemias/metabolismo , Leptina/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Mitochondrial DNA depletion syndrome (MDS), characterized by succinate-CoA ligase deficiency and loss of mitochondrial DNA (mtDNA), is caused by specific variants in nuclear genes responsible for mtDNA maintenance. SUCLA2-related mitochondrial DNA depletion syndrome, type 5 (MTDPS-5), presents as a rare, severe early progressive encephalomyopathy. This report investigates a new family exhibiting clinical manifestations of MTDPS-5 and elucidates the genetic basis of this disorder. In two affected siblings, a novel maternally inherited nonsense variant [c.1234C>T (p.Arg412*)] in the SUCLA2 gene and a unique paternally inherited indel variant (g.48569263-48571020del1758insATGA) were identified. Additionally, the siblings exhibited blood mtDNA content lower than 33% compared to age-matched controls. These findings underscore the importance of assessing SUCLA2 variants in patients with severe early progressive encephalomyopathy, even in the absence of methylmalonic aciduria or mtDNA loss, thereby broaden the mutational spectrum of this gene.
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Rapid and effective consumption of D-xylose by Saccharomyces cerevisiae is essential for cost-efficient cellulosic bioethanol production. Hence, heterologous D-xylose metabolic pathways have been introduced into S. cerevisiae. An effective solution is based on a xylose isomerase in combination with the overexpression of the xylulose kinase (Xks1) and all genes of the non-oxidative branch of the pentose phosphate pathway. Although this strain is capable of consuming D-xylose, growth inhibition occurs at higher D-xylose concentrations, even abolishing growth completely at 8% D-xylose. The decreased growth rates are accompanied by significantly decreased ATP levels. A key ATP-utilizing step in D-xylose metabolism is the phosphorylation of D-xylulose by Xks1. Replacement of the constitutive promoter of XKS1 by the galactose tunable promoter Pgal10 allowed the controlled expression of this gene over a broad range. By decreasing the expression levels of XKS1, growth at high D-xylose concentrations could be restored concomitantly with increased ATP levels and high rates of xylose metabolism. These data show that in fermentations with high D-xylose concentrations, too high levels of Xks1 cause a major drain on the cellular ATP levels thereby reducing the growth rate, ultimately causing substrate accelerated death. Hence, expression levels of XKS1 in S. cerevisiae needs to be tailored for the specific growth conditions and robust D-xylose metabolism.
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Eco-friendly biomass carbon dots (CDs) with blue fluorescence emission were rapidly synthesized by a microwave method. Based on the inner filter effect (IFE) between oxytetracycline (OTC) and CDs, the fluorescence of CDs could be selectively quenched by OTC. Therefore, a simple and time-saving fluorescence sensing system for the detection of OTC was established. Under optimal experimental conditions, the concentration of OTC showed a good linear relationship with fluorescence quenching values (ΔF) in the range of 4.0-100.0 µmol L-1, a corresponding correlation coefficient (r) of 0.9975, and a detection limit of 0.12 µmol L-1. The method has the advantages of low cost, time-saving, and green synthesis that could be used for the determination of OTC. Moreover, possessing high sensitivity and specificity, this fluorescence sensing method was successfully applied for detecting OTC in milk, indicating its potential applications in food safety.