Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 377
Filtrar
1.
Hum Cell ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33415691

RESUMO

In this study, we aimed to investigate the role of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) in cardiac remodeling after myocardial infarction (MI) and explore the underlying molecular mechanism. MI model was established by ligation of the left anterior descending coronary artery. C57/BL6J mice were randomly administered with 3.0 mg/kg/day PHPS1 (PHPS1-treated group) or normal saline (model group) by intraperitoneal injection. After 4 weeks of infusion, the effects of PHPS1 on cardiac remodeling were evaluated. Echocardiography results showed that PHPS1 treatment aggravated the MI-induced deterioration of cardiac function, with worse cardiac function parameters. PHPS1 treatment significantly increased the infarcted area, as well as the fibrotic area and the expression of collagen I and collagen III. Western blots and immunofluorescence staining showed that PHPS1 treatment up-regulated the expression of p-GRK2, p-SMAD2/3 and p-ERK1/2, while U0126 reversed the effect of PHPS1. The present study indicated that PHPS1 treatment contributed to myocardial fibrosis and infarction by activating ERK/SMAD signaling pathway, suggesting that SHP-2 may be a promising treatment target for cardiac remodeling after MI.

2.
Anal Chim Acta ; 1146: 41-52, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33461718

RESUMO

Pathogenic infections, particularly caused by Gram-positive bacteria (G+), pose a serious threat to human health, and therefore the fast and accurate discrimination of G+ bacteria from Gram-negative bacteria (G-) and fungi is highly desirable. Organic molecules with facile synthesis, robust photostability, good biocompatibility, and high selectivity toward pathogens are urgently needed in the clinical diagnosis and therapy. To this end, herein we report the synthesis of two naphthalimide-based bioprobes named tetraphenylethylene-naphthalimide (TPE-NIM) and triphenylamine-naphthalimide (TPA-NIM) with aggregation-induced emission (AIE) characteristic. First, the staining capacity of the designed AIEgens toward six kinds of bacteria and two kinds of fungi was evaluated. Both TPE-NIM and TPA-NIM showed a high degree of binding/imaging selectivity for G+ bacteria over G- bacteria and fungi via a wash-free protocol. Second, the two AIEgens had the ability to visualize the biofilms formed by G+ bacteria (Staphylococcus aureus) and can quickly track the G+ bacteria (Staphylococcus aureus) in red blood cell suspensions. Third, we have revealed that electrostatic attraction and hydrophobic interaction both contribute to the selective binding of the AIEgens toward G+ bacteria. In view of the high binding/imaging specificity toward G+ bacteria, low hemolysis rates, and low toxicity toward the bacterial cells, these AIEgens can be applied for the clinical detection of pathogenic infections caused by G+ bacteria and broaden the theranostic applications of AIE materials.

3.
Biotechnol Bioeng ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399214

RESUMO

Microbial production of l-tryptophan (l-trp) has received considerable attention because of its diverse applications in food additives and pharmaceuticals. Overexpression of rate-limiting enzymes and blockage of competing pathways can effectively promote microbial production of l-trp. However, the biosynthetic process remains suboptimal due to imbalanced flux distribution between central carbon and tryptophan metabolism, presenting a major challenge to further improvement of l-trp yield. In this study, we redistributed central carbon metabolism to improve phosphoenolpyruvate (PEP) and erythrose-4-phosphate (E4P) pools in an l-trp producing strain of Escherichia coli for efficient l-trp synthesis. To do this, a phosphoketolase from Bifidobacterium adolescentis was introduced to strengthen E4P formation, and the l-trp titer and yield increased to 10.8 g/L and 0.148 g/g glucose, respectively. Next, the phosphotransferase system was substituted with PEP-independent glucose transport, meditated by a glucose facilitator from Zymomonas mobilis and native glucokinase. This modification improved l-trp yield to 0.164 g/g glucose, concomitant with 58% and 40% decreases of acetate and lactate accumulation, respectively. Then, to channel more central carbon flux to the tryptophan biosynthetic pathway, several metabolic engineering strategies were applied to rewire the PEP-pyruvate-oxaloacetate node. Finally, the constructed strain SX11 produced 41.7 g/L l-trp with an overall yield of 0.227 g/g glucose after 40 h fed-batch fermentation in 5-L bioreactor. This is the highest overall yield of l-trp ever reported from a rationally engineered strain. Our results suggest the flux redistribution of central carbon metabolism to maintain sufficient supply of PEP and E4P is a promising strategy for efficient l-trp biosynthesis, and this strategy would likely also increase the production of other aromatic amino acids and derivatives.

5.
Angiology ; : 3319720984592, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33401931

RESUMO

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = -0.702, P < .001), CACS (r = -0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = -0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.

6.
Environ Sci Pollut Res Int ; 28(2): 1889-1900, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32860603

RESUMO

In January 2012, a serious accident polluted the Longjiang River with high concentrations of cadmium (Cd) and other concomitant metals and metalloids in the water. After emergency treatment (i.e., the addition of coagulants), these metals and metalloids were transferred from the water into the sediment through precipitation of the flocculent materials produced. In this study, the long-term distribution of six metals and metalloids in the sediment of the Longjiang River was investigated and their ecological risks were assessed. Approximately 1 year after the accident (i.e., late 2012), the average Cd content in the sediment of the affected sites decreased to 25.6 ± 19.5 mg/kg, which was 8 times higher than that of 3.16 ± 3.18 mg/kg in the upstream reference sites. In 2016 and 2017, the average Cd content in the sediment of the affected sites further decreased to 4.91 ± 2.23 and 6.27 ± 4.27 mg/kg, respectively. Compared with late 2012, the amounts of Zn, Pb, and Cu obviously decreased in 2016 and 2017, whereas there were no obvious differences in the As and Hg amounts during 3 years considered. Among metals and metalloids, the average contribution of Cd to the potential ecological risk index (RI) was 90%, 69%, and 70% in the affected areas in 2012, 2016, and 2017, respectively, suggesting that Cd was the most important factor affecting the ecological risk of metals in the Longjiang River. It should be noted that the average contribution of Hg to RI in the affected areas increased from 8% in 2012 to 25% and 23% in 2016 and 2017, respectively. The sequence of contribution of six elements was Cd > Hg > As>Pb > Cu ≈ Zn. A high ecological risk of metals and metalloids was found in the sediments of two reservoirs, probably owing to the barrier effect of the dam. This study will be useful for the environmental management of rivers affected by accidental pollution of metals and metalloids.


Assuntos
Metaloides , Metais Pesados , Poluentes Químicos da Água , Acidentes , China , Monitoramento Ambiental , Sedimentos Geológicos , Metaloides/análise , Metais Pesados/análise , Medição de Risco , Rios , Poluentes Químicos da Água/análise
7.
Life Sci ; 265: 118751, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189823

RESUMO

AIMS: To address the roles of SHP2 in regulating angiotensin II (Ang II) induced abdominal aortic aneurysm (AAA) and the potential molecular mechanisms. MAIN METHODS: AAA model was established in apolipoprotein E-deficient (apoE-/-) mice infused with Ang II. Suprarenal aortic luminal diameters were ultrasonically measured to determine the presentation of AAA in mice. The inflammatory and immunosuppressive factors in serum were detected by ELISA. AAA lesion size, positive macrophages and elastic laminae degradation were examined by histological analysis. Myeloid-derived suppressor cells (MDSCs) were measured by flow cytometry after magnetic bead sorting. Bioinformatics analysis was applied to screen the crucial genes related the progression of AAA. KEY FINDINGS: Treatment with PHPS1 (SHP2 inhibitor) significantly decreased the vascular diameter of AAA. Histological analysis showed that PHPS1 obviously reduced the Masson positive area, macrophages positive area, as well as the damage rate of elastic laminae. Moreover, PHPS1 suppressed the expression of INF-γ, TNF-α and MMPs, as well as elevated IL-10 and arginase-1 expression. Additionally, PHPS1 enhanced the expression of granulocytic MDSCs (G-MDSCs). By consulting with bioinformatics, STAT3 was selected. In G-MDSCs, PHPS1 stimulation obviously increased the phosphorylation level of STAT3, as well as elevated the protein expression of C/EBPß and arginase-1. However, the above phenomena can be blocked after Stattic (STAT3 inhibitor) treatment. SIGNIFICANCE: SHP2 may affect the AAA progression by interfering with expansion and function of MDSCs to regulate the body immunity, which might afford a novel direction for the treatment of patients with AAA.

8.
Br J Pharmacol ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300142

RESUMO

BACKGROUND AND PURPOSE: Macrophage infiltration into lungs is one of hallmarks of pulmonary hypertension (PH). Glycolysis is the main metabolic pathway for macrophage activation. However, the effect of macrophage glycolysis on the development of PH remains unknown. We investigated the effect of PFKFB3, a critical glycolytic regulator that mediates macrophage glycolysis, on PH development. EXPERIMENTAL APPROACH: Lung tissues from PH patients were examined by immunostaining with macrophage markers. PH was induced in Wistar rats with SU5416/hypoxia and in mice with hypoxia. Lungs and macrophages were isolated for analysis by RT-PCR, Western blot, flow cytometry and immunostaining. KEY RESULTS: The expression of glycolytic molecules was increased in circulating peripheral blood mononuclear cells (PBMCs) and lung macrophages of PH patients; these results were recapitulated in lung macrophages of SU5416/hypoxia (Su/Hx)-induced PH rats and hypoxia-induced PH mice. PH was ameliorated in myeloid-specific Pfkfb3-deficienct mice (Pfkfb3ΔMϕ ) or mice treated with the PFKFB3 inhibitor 3PO compared with their controls. Alveolar macrophages of PH Pfkfb3ΔMϕ mice produced lower levels of growth factors and pro-inflammatory cytokines than those of control mice. Circulating myeloid cells and lung myeloid cells are much fewer in PH Pfkfb3ΔMϕ mice than controls. Mechanistically, overexpression of Hif1a or Hif2a in bone marrow-derived macrophages (BMDMs) cultured with bone marrow of Pfkfb3ΔMϕ mice rescued the decreased expression of the pro-inflammatory cytokines and growth factors. CONCLUSIONS AND IMPLICATIONS: Myeloid Pfkfb3 deficiency protects mice from PH, thereby suggesting that myeloid PFKFB3 is one of the important targets in the therapeutic effect of PFKFB3 inhibition in PH treatment.

9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(12): 1368-1370, 2020 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-33306824

RESUMO

OBJECTIVE: To detect pathological variants of the SLC12A3 gene in a Chinese pedigree affected with Gitelman syndrome (GS). METHODS: Clinical data and peripheral blood samples of the proband and his family members were collected. All exons of the SLC12A3 gene were amplified by PCR and subjected to Sanger sequencing. RESULTS: Sanger sequencing has revealed that the proband has carried a c.486_489 delTACG (p.Ile162Met fs*8) deletion and a heterozygous c.2890C>T (p.Arg964Trp) missense variant in the SLC12A3 gene. Neither variant was reported previously and was not found among healthy controls. CONCLUSION: The c.486_489delTACG (p.Ile162Met fs*8) and c.2890C>T (p.Arg964Trp) variants of the SLC12A3 gene probably underlay the GS in the proband. Above discovery has enriched the variant spectrum of GS.


Assuntos
Síndrome de Gitelman , China , Síndrome de Gitelman/genética , Heterozigoto , Humanos , Mutação/genética , Linhagem , Membro 3 da Família 12 de Carreador de Soluto/genética
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1233-1235, 2020 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-33179227

RESUMO

OBJECTIVE: To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Clinical data and peripheral blood samples of the pedigrees were collected. All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing. Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls. RESULTS: For pedigree 1, Sanger sequencing has identified a heterozygous missense variant c.3002G>C (p.Asp968His) in exon 11 of the ADAR1 gene in the proband and his father. For pedigree 2, a novel nonsense variant c.3145C>T (p.Gln1049Ter) was identified in exon 12 of the ADAR1 gene in the proband and his son, which were previously unreported and absent among the healthy controls. CONCLUSION: The c.3002G>C (p.Asp968His) and c.3145C>T (p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.


Assuntos
Adenosina Desaminase/genética , Transtornos da Pigmentação/congênito , Proteínas de Ligação a RNA/genética , Humanos , Mutação , Linhagem , Transtornos da Pigmentação/genética
11.
Molecules ; 25(22)2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33218007

RESUMO

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a-5v) exerted neuroprotective effects on ß-amyloid (Aß)-induced PC12 cells as a potential approach for the treatment of Alzheimer's disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aß25-35-induced PC12 cells at 5 µg/mL. We found that compound 5c was non-neurotoxic at 30 µg/mL and significantly increased the viability of Aß25-35-induced PC12 cells at 1.25, 2.5 and 5 µg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3ß) and decreased the expression of nuclear factor-κB (NF-κB) in Aß25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aß25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3ß/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.

12.
Anal Chem ; 92(23): 15679-15684, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33174733

RESUMO

Tumor microenvironment turn-on nanoprobes that could specifically detect the occurrence of diseases possess great potential in early diagnosis. Here, a GSH activated nanoprobe was designed for fluorescence and 19F magnetic resonance (MR) dual-modal turn-on imaging of tumors. Specifically, fluorescence AgInS2 quantum dots (QDs for fluorescence imaging) were co-encapsulated with perfluoro-15-crown-5-ether (P19FCE for19F MRI) by amphiphilic polymers and further coated with in situ formed manganese dioxide (MnO2) nanoshells, which served as efficient fluorescence and 19F MR quenchers due to energy transfer and paramagnetic relaxation effects, respectively. The over-expressed GSH in tumors would decompose the MnO2 nanoshells, resulting in remarkable enhancement of both fluorescence and 19F MRI signals of the nanoprobes, accordingly lighting up the tumor site.

13.
Nanoscale ; 12(46): 23578-23585, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33225340

RESUMO

Although nanozymes overcome a series of shortcomings of natural enzymes, their wide applications are hampered due to their limited varieties. In this work, we propose a coenzyme-dependent nanozyme, a synergistic composite comprising zeolitic imidazolate frameworks encapsulated with polyethylenimine (PEI) and functionalized with a flavin mononucleotide (PEI/ZIF-FMN). The flavin mononucleotide (FMN) plays the role of a prosthetic group, and the positively charged NH2 groups in PEI readily provide the binding affinity to nicotinamide adenine dinucleotide (NADH), which facilitates the electron transfer from NADH to FMN and terminal electron acceptors (such as O2) with a greatly enhanced (80 times) catalytic performance. The integrated nanoparticle-coenzyme composite works as an NADH oxidase mimic and couples with dehydrogenases for the tandem enzymatic reaction. PEI/ZIF-FMN also mediated the electron transfer from NADH to cytochrome c (Cyt c), thereby exhibiting Cyt c reductase-like activity.

14.
BMC Genomics ; 21(1): 715, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066732

RESUMO

BACKGROUND: As global warming continues, heat stress (HS) is becoming an increasingly significant factor limiting plant growth and reproduction, especially for cool-season grass species. The objective of this study was to determine the transcriptional regulatory network of Cleistogenes songorica under HS via transcriptome profiling, identify of gene families and comparative analysis across major Poaceae species. RESULTS: Physiological analysis revealed significantly decreased leaf relative water content (RWC) but increased proline (Pro) content in C. songorica under 24 h of HS. Transcriptome profiling indicated that 16,028 and 14,645 genes were differentially expressed in the shoots and roots of C. songorica under HS, respectively. Two subgenomes of C. songorica provide equal contribution under HS on the basis of the distribution and expression of differentially expressed genes (DEGs). Furthermore, 216 DEGs were identified as key evolutionarily conserved genes involved in the response to HS in C. songorica via comparative analysis with genes of four Poaceae species; these genes were involved in the 'response to heat' and 'heat acclimation'. Notably, most of the conserved DEGs belonged to the heat-shock protein (HSP) superfamily. Similar results were also obtained from co-expression analysis. Interestingly, hub-genes of co-expression analysis were found to overlap with conserved genes, especially heat-shock protein (HSP). In C. songorica, 84 HSP and 32 heat-shock transcription factor (HSF) genes were identified in the allotetraploid C. songorica genome, and might have undergone purifying selection during evolutionary history based on syntenic and phylogenetic analysis. By analysing the expression patterns of the CsHSPs and CsHSFs, we found that the transcript abundance of 72.7% of the CsHSP genes and of 62.5% of the CsHSF genes changed under heat stress in both the shoots and roots. Finally, a core regulatory network of HS was constructed on the basis of the CsHSP, CsHSF and other responsive genes in C. songorica. CONCLUSIONS: Regulatory network and key genes were comprehensively analysed and identified in C. songorica under HS. This study improves our knowledge of thermotolerance mechanisms in native grasses, and also provides candidate genes for potential applications in the genetic improvement of grasses.

15.
Medicine (Baltimore) ; 99(37): e22229, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925800

RESUMO

BACKGROUND: Since the outbreak of COVID-19, the number of COVID-19 patients has been on the rise. With the improvement of diagnosis and treatment level in various countries, more and more patients have recovered. Baduanjin exercise is a traditional Chinese health care method with a long history, easy-to-learn, and remarkable effect. It is not subject to the constraints of the field and can be practiced at any time. It can be used as an alternative therapy for COVID-19 rehabilitation patients. At present, there are no relevant articles for systematic review. METHODS: We will retrieve a randomized controlled trial of Baduanjin exercise for COVID-19 from the beginning to July 2020. The following databases are areas of concern: Published randomized Cochrane Central Register of Controlled Trials (Central), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan-fang Database-controlled trials in Chinese and English related to Baduanjin exercise and COVID-19 were included. The main result was the effect of Baduanjin exercise on the quality of life in patients recovering from COVID-19. Secondary results to accompany symptoms (such as muscle pain, cough, sputum, runny nose, sore throat, chest tightness, shortness of breath, difficulty breathing, fatigue, headache, nausea, vomiting, anorexia, diarrhea), disappearance rate, 2 consecutive (not on the same day) COVID-19 negative rate of nucleic acid test results, the quality of life improved, improve CT images, the average hospitalization time, severe form of common clinical cure rate and mortality. RESULTS: The results of this study will provide researchers in the field of COVID-19 with a current synthesis of high-quality evidence. CONCLUSION: The conclusion of this study will provide evidence for judging whether Baduanjin exercise is an effective intervention for the quality of life of rehabilitative patients. PROSPERO REGISTRATION NUMBER: CRD42020199443.


Assuntos
Infecções por Coronavirus , Terapia por Exercício/métodos , Pandemias , Pneumonia Viral , Qualidade de Vida , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Infecções por Coronavirus/reabilitação , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Pneumonia Viral/reabilitação , Recuperação de Função Fisiológica , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
16.
Angew Chem Int Ed Engl ; 59(52): 23564-23568, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-32896066

RESUMO

A single-step method for isolation of specific cells based on multiple surface markers will have unique advantages because of its scalability, efficacy, and mildness. Herein, we developed multi-aptamer-mediated proximity ligation method on live cell membranes that leverages a multi-receptor co-recognition design for enhanced specificity, as well as a robust in situ signal amplification design for improved sensitivity of cell isolation. We demonstrated the promising efficacy of our method on differentiating tumor cell subtypes in both cell mixtures and clinical samples. Owing to its simple and fast operation with excellent cell isolation sensitivity and accuracy, this approach will have broad applications in biological science, biomedical engineering, and personalized medicine.

17.
Commun Biol ; 3(1): 494, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895472

RESUMO

Most marine algae preferentially assimilate CO2 via the Calvin-Benson Cycle (C3) and catalyze HCO3- dehydration via carbonic anhydrase (CA) as a CO2-compensatory mechanism, but certain species utilize the Hatch-Slack Cycle (C4) to enhance photosynthesis. The occurrence and importance of the C4 pathway remains uncertain, however. Here, we demonstrate that carbon fixation in Ulva prolifera, a species responsible for massive green tides, involves a combination of C3 and C4 pathways, and a CA-supported HCO3- mechanism. Analysis of CA and key C3 and C4 enzymes, and subsequent analysis of δ13C photosynthetic products showed that the species assimilates CO2 predominately via the C3 pathway, uses HCO3- via the CA mechanism at low CO2 levels, and takes advantage of high irradiance using the C4 pathway. This active and multi-faceted carbon acquisition strategy is advantageous for the formation of massive blooms, as thick floating mats are subject to intense surface irradiance and CO2 limitation.

18.
Med Sci Monit ; 26: e924393, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32920588

RESUMO

BACKGROUND Myasthenia gravis (MG) is an autoimmune neurological disorder of neuromuscular junctions. In this study we established experimental autoimmune myasthenia gravis (EAMG) rat models to investigate the effects of AEB-071 (AEB), which is a specific inhibitor of protein kinase C that prevents T lymphocyte activation. MATERIAL AND METHODS We utilized animals divided into 4 groups: (1) control rats, (2) EAMG, (3) AEB-071+EAMG, and (4) AZP+EAMG. Drug treatment was continued for 10 days. Ten weeks after immunization we measured body weights, assessed mortality rates, and used Lennon scores to evaluate EAMG grades. We also assessed the proportions of Treg, Th1, Th2, Th17, and lymphocytes using flow cytometry. RESULTS In the absence of drug treatment, we found a significant decline in body weights in the EAMG group in comparison to control rats, and EAMG group rats also had higher Lennon scores (P<0.05). Interestingly, we found that AEB-071 restored the body weight of EAMG rats and the decreased mortality rate compared to AZP treatment. Although a decrease in the number of Treg cells was observed, the proportion of Th lymphocytes was significantly increased in the EAMG group, and AEB-071 treatment decreased the proportion of Th lymphocytes. CONCLUSIONS We concluded that AEB-071 treatment imparts beneficial effects in EAMG rat models by reducing mortality rate and restoring Th lymphocyte balance, and thus may be an attractive candidate for use in MG treatment.

19.
Metab Eng ; 62: 198-206, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32961297

RESUMO

L-valine is an essential amino acid and an important amino acid in the food and feed industry. The relatively low titer and low fermentation yield currently limit the large-scale application of L-valine. Here, we constructed a chromosomally engineered Escherichia coli to efficiently produce L-valine. First, the synthetic pathway of L-valine was enhanced by heterologous introduction of a feedback-resistant acetolactate acid synthase from Bacillus subtilis and overexpression of other two enzymes in the L-valine synthetic pathway. For efficient efflux of L-valine, an exporter from Corynebacterium glutamicum was subsequently introduced. Next, the precursor pyruvate pool was increased by knockout of GTP pyrophosphokinase and introduction of a ppGpp 3'-pyrophosphohydrolase mutant to facilitate the glucose uptake process. Finally, in order to improve the redox cofactor balance, acetohydroxy acid isomeroreductase was replaced by a NADH-preferring mutant, and branched-chain amino acid aminotransferase was replaced by leucine dehydrogenase from Bacillus subtilis. Redox cofactor balance enabled the strain to synthesize L-valine under oxygen-limiting condition, significantly increasing the yield in the presence of glucose. Two-stage fed-batch fermentation of the final strain in a 5 L bioreactor produced 84 g/L L-valine with a yield and productivity of 0.41 g/g glucose and 2.33 g/L/h, respectively. To the best of our knowledge, this is the highest L-valine titer and yield ever reported in E. coli. The systems metabolic engineering strategy described here will be useful for future engineering of E. coli strains for the industrial production of L-valine and related products.

20.
IEEE Trans Cybern ; PP2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32780711

RESUMO

This technical correspondence studies the consensus problem for second-order multiagent systems under network topologies with a directed spanning tree. Consensus analysis for systems with the distributed delayed proportional-integral (PI)-type controller is given. Crossing directions of the characteristic roots can be identified by a sufficient condition. If the rightward crossing condition holds, the delay margin can be obtained to guarantee that the systems reach consensus if and only if the time delay is less than the critical value. Otherwise, it is possible that the systems switch from consensus to nonconsensus and back to the consensus as the delay increases. Simulation examples are provided to demonstrate the theoretical analysis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA