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Magnesium ion batteries (MIBs) are expected to be the promising candidates in the post-lithium-ion era with high safety, low cost and almost dendrite-free nature. However, the sluggish diffusion kinetics and strong solvation capability of the strongly polarized Mg2+ are seriously limiting the specific capacity and lifespan of MIBs. In this work, catalytic desolvation is introduced into MIBs for the first time by modifying vanadium pentoxide (V2O5) with molybdenum disulfide quantum dots (MQDs), and it is demonstrated via density function theory (DFT) calculations that MQDs can effectively lower the desolvation energy barrier of Mg2+, and therefore catalyze the dissociation of Mg2+-1,2-Dimethoxyethane (Mg2+-DME) bonds and release free electrolyte cations, finally contributing to a fast diffusion kinetics within the cathode. Meanwhile, the local interlayer expansion can also increase the layer spacing of V2O5 and speed up the magnesiation/demagnesiation kinetics. Benefiting from the structural configuration, MIBs exhibit superb reversible capacity (≈300 mAh g-1 at 50 mA g-1) and unparalleled cycling stability (15 000 cycles at 2 A g-1 with a capacity of ≈70 mAh g-1). This approach based on catalytic reactions to regulate the desolvation behavior of the whole interface provides a new idea and reference for the development of high-performance MIBs.
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Coumarin is a natural product known for its diverse biological activities. While its antifungal properties in agricultural chemistry have been extensively studied, there is limited research on its antibacterial potential. In this study, we developed several novel coumarin derivatives by combining coumarin with pyridinium salt through molecular hybridization and chemical synthesis. Our findings reveal that most of these derivatives exhibit promising antibacterial activity. Among them, derivative A25 has been identified as the most effective compound based on three-dimensional quantitative structure-activity relationships. It demonstrates significant in vitro and in vivo activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc), and Xanthomonas campestris pv. citri (Xac), outperforming the commercially available thiediazole copper. Initial investigations into its mechanism of action suggest that A25 disrupts the cell membranes of Xoc and Xoo, thereby inhibiting bacterial growth. Additionally, A25 enhances the activity of defense enzymes in rice and modulates the expression of proteins related to the pyruvate metabolism pathway. This dual action contributes to rice's resistance against bacterial infestation. We anticipate that this study will serve as a foundation for the development of coumarin-based bactericides.
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Antibacterianos , Cumarinas , Pruebas de Sensibilidad Microbiana , Oryza , Xanthomonas , Cumarinas/farmacología , Cumarinas/síntesis química , Cumarinas/química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Xanthomonas/efectos de los fármacos , Oryza/microbiología , Compuestos de Piridinio/farmacología , Compuestos de Piridinio/química , Compuestos de Piridinio/síntesis química , Xanthomonas campestris/efectos de los fármacos , Diseño de Fármacos , Sales (Química)/farmacología , Sales (Química)/química , Relación Estructura-ActividadRESUMEN
BACKGROUND: Cancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment (TME), play crucial roles in tumor stemness. It has been shown in various cancer studies that stanniocalcin-1 (STC1) is secreted by CAFs, however, its function in HCC is still not clear. METHODS: The serum concentration and intracellular expression level of STC1 were quantified by ELISA and western blotting, respectively. The role of CAF-derived STC1 in HCC stemness was investigated by sphere formation, sorafenib resistance, colony formation, and transwell migration and invasion assays in vitro and in an orthotopic liver xenograft model in vivo. An HCC tissue microarray containing 72 samples was used to evaluate the expression of STC1 and Notch1 in HCC tissues. Coimmunoprecipitation (CoIP) and dual-luciferase reporter assays were performed to further explore the underlying mechanisms. ELISAs were used to measure the serum concentration of STC1 in HCC patients. RESULTS: We demonstrated that CAFs were the main source of STC1 in HCC and that CAF-derived STC1 promoted HCC stemness through activation of the Notch signaling pathway. In HCC patients, the expression of STC1 was positively correlated with Notch1 expression and poor prognosis. The co-IP assay showed that STC1 directly bound to Notch1 receptors to activate the Notch signaling pathway, thereby promoting the stemness of HCC cells. Our data further demonstrated that STC1 was a direct transcriptional target of CSL in HCC cells. Furthermore, ELISA revealed that the serum STC1 concentration was higher in patients with advanced liver cancer than in patients with early liver cancer. CONCLUSIONS: CAF-derived STC1 promoted HCC stemness via the Notch1 signaling pathway. STC1 might serve as a potential biomarker for the prognostic assessment of HCC, and the stromal-tumor amplifying STC1-Notch1 feedforward signal could constitute an effective therapeutic target for HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias de los Tejidos Blandos , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Glicoproteínas/metabolismo , Línea Celular Tumoral , Microambiente Tumoral , Receptor Notch1RESUMEN
The present study aimed to investigate the application of a multilayer quartz sand substrate horizontal subsurface flow constructed wetland (HSFCW) for campus sewage treatment. It aimed to assess the pollutant removal efficiency and anti-clogging performance under the suggested maximum organic loading rate (250 g/m2/d). The results of the multilayer HSFCW (CW6) were compared to the mololayer HSFCW (CW1) for the removal of the chemical oxygen demand (COD), solid accumulation, and microbial communities. During operation, the combination conditions of high hydraulic loading rate (HLR) with low COD concentration were better for COD removal under a high organic loading rate (OLR) of 200-300 g/m2/d. The maximum removal rate reached 80.4% in CW6 under high HLR, which was 13.8% higher than that in CW1, showing better adsorption and biodegradation ability of organic matter. Impressive clogging resistance capacity was found in CW6 due to the lower contents of the insoluble organic matter (IOM) that are prone to clogging, indicating full degradation of organic matters, particularly IOM, in CW6 under high HLR. Less abundance of unclassified Chitinophagaceae (under low HLR), Pedobacter and Saccharibacteria_genera_incertae_sedis (under high HLR) in CW6, which contributed to aerobic membrane fouling, helped to prevent clogging. Moreover, Brevundimonas, Cloacibacterium, Citrobacter, Luteimonas contributed to IOM degradation, thus further enhancing the anti-clogging performance. In view of the better clogging resistance performance, the application of CW6 operated under high HLR and low COD concentrations was recommended to achieve economical, efficient, and steady COD removal for domestic sewage treatment in long-term operation.
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Arena , Eliminación de Residuos Líquidos , Eliminación de Residuos Líquidos/métodos , Aguas del Alcantarillado , Cuarzo , Carbono , Humedales , NitrógenoRESUMEN
Introduction: The aim of the study was to detect the saliva chemokine (C-X-C motif) ligand 13 (CXCL13), macrophage migration inhibitory factor (MIF), and interleukin 35 (IL-35) levels in patients with primary Sjögren's syndrome (pSS) and pSS-associated interstitial lung disease (pSS-ILD), and to explore the relationship between CXCL13, MIF, IL-35 levels, and disease severity. Material and methods: ESSDAI score was used to evaluate the disease activity of pSS patients, and the levels of CXCL13, MIF and IL-35 in saliva of subjects were detected and analyzed, and the relationship between CXCL13, MIF, IL-35 and the occurrence of pSS was evaluated. Pearson's correlation coefficient was used to analyze the correlation between CXCL13, MIF, IL-35 and ESSDAI score. ROC curve analysis was conducted to assess the diagnostic value of CXCL13, MIF, IL-35 and their combined application in pSS. Results: The levels of CXCL13, MIF, and IL-35 in saliva were positively correlated with ESSDAI score. Saliva CXCL13 and IL-35 are risk factors for the development of pSS into pSS-ILD. The ROC curve shows that the combination of saliva CXCL13, MIF and IL-35 has the highest diagnostic efficiency for pSS-ILD. Conclusions: CXCL13, MIF and IL-35 are related to the activity of pSS, and the combined diagnosis of these three indexes is expected to be an important method to predict the occurrence and development of pSS.
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Intermolecular carbophosphination reaction of alkynes or alkenes with unreactive C-P bonds remains an elusive challenge. Herein, we used a Ni-Al bimetallic catalyst to realize an intermolecular carbophosphination reaction of alkynes with 5-membered phosphole oxides, providing a series of 7-membered phosphepines in up to 94 % yield.
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NEW FINDINGS: What is the central question of this study? What is the protective benefit of n-3 polyunsaturated fatty acids (PUFAs) on liver fibrosis and what are the relevant signalling pathways in a transgenic mouse model overexpressing the mfat-1 enzyme? What is the main finding and its importance? n-3 PUFA elevation strongly prevented carbon tetrachloride (CCl4 )-induced hepatic damage and inhibited the activation of hepatic stellate cells. n-3 PUFAs suppressed CCl4 -induced activation of mTOR, elevated Bcl-2 expression, and reduced Bax level, suggesting that n-3 PUFAs can render strong protective effects against liver fibrosis and point to the potential of mfat-1 gene therapy as a treatment modality. ABSTRACT: Liver fibrosis is a reversible wound healing response with excessive accumulation of extracellular matrix proteins. It is a globally prevalent disease with ultimately severe pathological consequences. However, very few current clinical therapeutic options are available. Nutritional addition of n-3 polyunsaturated fatty acids (PUFAs) can delay and lessen the development of liver fibrosis. Herein, this study examined the protective benefit of n-3 PUFAs on liver fibrosis and the relevant signalling pathways using a transgenic mouse model overexpressing the mfat-1 enzyme that converts n-6 to n-3 PUFAs. Male C57BL/6 wild-type and mfat-1 transgenic mice were administered carbon tetrachloride (CCl4 ) or control corn oil by intraperitoneal injection. Blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were subsequently measured. CCl4 -induced hepatic damage and fibrosis were assessed using haematoxylin-eosin and Masson's trichrome staining. Western blot assays were used to detect and quantify fibrosis-related proteins and mechanistic target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) signalling components. The direct effect of docosahexaenoic acid (DHA) on primary hepatic stellate cells (HSCs) was also investigated in a co-culture experiment. n-3 PUFAs, as a result of mfat-1 activity, had a strong protective effect on liver fibrosis. The elevation of ALT and AST induced by CCl4 was significantly lessened in the mfat-1 mice. Histological determination revealed the protective effects of n-3 PUFAs on liver inflammation and collagen deposition. Co-incubation with DHA reduced the expression of profibrogenic factors in the primary HSCs. Moreover, mfat-1 transgenic mice showed significant reduction of proteins that are involved in mTOR and Bcl-2/Bax signalling pathways. Collectively, these results suggest that n-3 PUFA elevation strongly prevents CCl4 -induced hepatic damage by directly inhibiting the activation of HSCs and regulating the basal activity of the mTOR and Bcl-2/Bax signalling pathways. Gene therapy applying mfat-1 and elevating n-3 PUFAs represents a promising treatment strategy to prevent liver fibrosis.
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Tetracloruro de Carbono , Ácidos Grasos Omega-3 , Animales , Tetracloruro de Carbono/efectos adversos , Tetracloruro de Carbono/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/prevención & control , Masculino , Ratones , Ratones Endogámicos C57BL , Serina-Treonina Quinasas TOR/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Based on the role of ATG7 in the initiation of autophagy, autophagy can be divided into ATG7-dependent selective autophagy and ATG7-independent alternative autophagy. However, the detailed roles of two different types of autophagy in antitumor therapy have not been fully elucidated so far. Here, we for the first time demonstrated an investigational inducer, w09, could induce both selective autophagy and alternative autophagy in NSCLC, but the phenotypes of these two kinds of autophagy are differentï¼(1) w09-induced selective autophagy mainly promoted cell apoptosis, while w09-triggered alternative autophagy markedly induced autophagic cell death in NSCLCï¼(2) w09-induced ATG7 dependent autophagy mainly promoted the accumulation of SQSTM1/p62, while w09-triggered ATG7 independent autophagy markedly accelerated the degradation of SQSTM1/p62. These above results were further confirmed by knockout ATG7 gene in A549 cells or restoration of ATG7 function in H1650 cells. Deletion of ATG7 gene markedly attenuated the effect of w09-induced autophagy or apoptosis on A549 cells, while restoration of functional ATG7 markedly enhanced the effect of w09-induced autophagy and apoptosis on H1650 cells. Mechanistically, we further revealed that w09 induced two different types of autophagy through inhibiting PI3K/AKT/mTOR signaling pathway. Notably, compared with A549WT xenograft model, the in vivo antitumor effect of w09 or Taxel on the ATG7-deficient A549 xenograft model was significantly attenuated. Therefore, a special attention must be paid to distinguish which kinds of autophagy have been induced by autophagy inducers with antitumor agents by targeting PI3K/AKT/mTOR signaling pathway.
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Antineoplásicos/uso terapéutico , Proteína 7 Relacionada con la Autofagia/genética , Autofagia , Neoplasias Pulmonares/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The inducible nitric oxide synthase (iNOS) is associated with more aggressive solid tumors, including hepatocellular carcinoma (HCC). Notch signaling in cancer stem cells promotes cancer progression and requires Notch cleavage by ADAM (a disintegrin and metalloprotease) proteases. We hypothesized that iNOS/NO promotes Notch1 activation through TACE/ADAM17 activation in liver cancer stem cells (LCSCs), leading to a more aggressive cancer phenotype. Expression of the stem cell markers CD24 and CD133 in the tumors of patients with HCC was associated with greater iNOS expression and worse outcomes. The expression of iNOS in CD24+CD133+ LCSCs, but not CD24-CD133- LCSCs, promoted Notch1 signaling and stemness characteristics in vitro and in vivo, as well as accelerating HCC initiation and tumor formation in the mouse xenograft tumor model. iNOS/NO led to Notch1 signaling through a pathway involving the soluble guanylyl cyclase/cGMP/PKG-dependent activation of TACE/ADAM17 and up-regulation of iRhom2 in LCSCs. In patients with HCC, higher TACE/ADAM17 expression and Notch1 activation correlated with poor prognosis. These findings link iNOS to Notch1 signaling in CD24+CD133+ LCSCs through the activation of TACE/ADAM17 and identify a mechanism for how iNOS contributes to progression of CD24+CD133+ HCC.
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Antígeno AC133/metabolismo , Proteína ADAM17/metabolismo , Antígeno CD24/metabolismo , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Receptores Notch/metabolismo , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Células Madre Neoplásicas/patología , Fenotipo , Transducción de Señal/fisiología , Regulación hacia Arriba/fisiologíaRESUMEN
A carbamoyl fluoride-enabled enantioselective Ni-catalyzed carbocarbamoylation of unactivated alkenes was developed, providing a broad range of chiral γ-lactams bearing an all-carbon quaternary center in 45-96% yield and 38-97% ee.
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Nonaqueous rechargeable lithium-oxygen batteries (LOBs) are one of the most promising candidates for future electric vehicles and wearable/flexible electronics. However, their development is severely hindered by the sluggish kinetics of the ORR and OER during the discharge and charge processes. Here, we employ MOF-assisted spatial confinement and ionic substitution strategies to synthesize Ru single atoms riveted with nitrogen-doped porous carbon (Ru SAs-NC) as the electrocatalytic material. By using the optimized Ru0.3 SAs-NC as electrocatalyst in the oxygen-breathing electrodes, the developed LOB can deliver the lowest overpotential of only 0.55 V at 0.02 mA cm-2. Moreover, in-situ DEMS results quantify that the e-/O2 ratio of LOBs in a full cycle is only 2.14, indicating a superior electrocatalytic performance in LOB applications. Theoretical calculations reveal that the Ru-N4 serves as the driving force center, and the amount of this configuration can significantly affect the internal affinity of intermediate species. The rate-limiting step of the ORR on the catalyst surface is the occurrence of 2e- reactions to generate Li2O2, while that of the OER pathway is the oxidation of Li2O2. This work broadens the field of vision for the design of single-site high-efficiency catalysts with maximum atomic utilization efficiency for LOBs.
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OBJECTIVES: To evaluate the population pharmacokinetics of cefoperazone in children and establish an evidence-based dosing regimen using a developmental pharmacokinetic-pharmacodynamic approach in order to optimize cefoperazone treatment. METHODS: A model-based, open-label, opportunistic-sampling pharmacokinetic study was conducted in China. Blood samples from 99 cefoperazone-treated children were collected and quantified by HPLC/MS. NONMEM software was used for population pharmacokinetic-pharmacodynamic analysis. This study was registered at ClinicalTrials.gov (NCT03113344). RESULTS: A two-compartment model with first-order elimination agreed well with the experimental data. Covariate analysis showed that current body weight had a significant effect on the pharmacokinetics of cefoperazone. Monte Carlo simulation showed that for bacteria for which cefoperazone has an MIC of 0.5 mg/L, 78.1% of hypothetical children treated with '40 mg/kg/day, q8h, IV drip 3 h' would reach the pharmacodynamic target. For bacteria for which cefoperazone has an MIC of 8 mg/L, 88.4% of hypothetical children treated with 80 mg/kg/day (continuous infusion) would reach the treatment goal. A 160 mg/kg/day (continuous infusion) regimen can cover bacteria for which cefoperazone has an MIC of 16 mg/L. Nevertheless, even if using the maximum reported dose of 160 mg/kg/day (continuous infusion), the ratio of hypothetical children reaching the treatment target was only 9.9% for bacteria for which cefoperazone has an MIC of 32 mg/L. CONCLUSIONS: For cefoperazone, population pharmacokinetics were evaluated in children and an appropriate dosing regimen was developed based on developmental pharmacokinetics-pharmacodynamics. The dose indicated in the instructions (20-160 mg/kg/day) can basically cover the clinically common bacteria for which cefoperazone has an MIC of ≤16 mg/L. However, for bacteria for which the MIC is >16 mg/L, cefoperazone is not a preferred choice.
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Antibacterianos , Cefoperazona , Antibacterianos/uso terapéutico , Niño , China , Cromatografía Líquida de Alta Presión , Humanos , Pruebas de Sensibilidad Microbiana , Método de MontecarloRESUMEN
BACKGROUND: The optimal sampling techniques for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remain unclear and have not been standardized. The aim of this study was to compare the wet-suction and dry-suction techniques for sampling solid lesions in the pancreas, mediastinum, and abdomen. METHODS: This was a multicenter, crossover, randomized controlled trial with randomized order of sampling techniques. The 296 consecutive patients underwent EUS-FNA with 22G needles and were randomized in a ratio of 1:1 into two separate groups that received the dry-suction and wet-suction techniques in a different order. The primary outcome was to compare the histological diagnostic accuracy of dry suction and wet suction for malignancy. The secondary outcomes were to compare the cytological diagnostic accuracy and specimen quality. RESULTS: Among the 269 patients with pancreatic (nâ=â161) and non-pancreatic (nâ=â108) lesions analyzed, the wet-suction technique had a significantly better histological diagnostic accuracy (84.9â% [95â% confidence interval (CI) 79.9â%â-â89.0â%] vs. 73.2â% [95â%CI 67.1â%â-â78.7â%]; Pâ=â0.001), higher specimen adequacy (94.8â% vs. 78.8â%; Pâ<â0.001), and less blood contamination (Pâ<â0.001) than the dry-suction technique. In addition, sampling non-pancreatic lesions with two passes of wet suction provided a histological diagnostic accuracy of 91.6â%. CONCLUSIONS: The wet-suction technique in EUS-FNA generates better histological diagnostic accuracy and specimen quality than the dry-suction technique. Furthermore, sampling non-pancreatic lesions with two passes of EUS-FNA with wet suction may provide a definitive histological diagnosis when rapid on-site evaluation is not routinely available.
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Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pancreáticas , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Humanos , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Succión/métodosRESUMEN
BACKGROUND: For spring-type Chinese cabbage production, premature bolting refers to the excessive elongation of dwarf stems before harvesting. Although quantitative trait loci (QTL) mapping for bolting-related traits have been studied extensively, the main flower stalk length (MFSL) have been rarely investigated. Two inbred lines, 06-247 and He102, have significant differences in the MFSL. In this study, these two materials were selected as parental lines for the construction of a recombinant inbred line (RIL) mapping population. High-density mapping of QTL for the MFSL was performed based on the deep resequencing of parental lines and specific locus-amplified fragment sequencing (SLAF-Seq) of individual recombination inbred lines. RESULTS: An F7 population consisting of 150 lines was developed. Deep resequencing of parental lines produced 21.08 gigabases, whereas SLAF-Seq produced an average of 428.35 million bases for each progeny. The total aligned data from the parental lines identified 1,082,885 high-quality single nucleotide polymorphisms (SNPs) between parental lines. Out of these, 5392 SNP markers with a segregation type of aa×bb and average integrity of > 99% were suitable for the genetic linkage map construction. The final map contained 10 linkage groups (LGs) was 1687.82 cM in length with an average distance of 0.32 cM between adjacent markers. Based on the high-density map, nine QTLs for MFSL were found to be distributed on seven chromosomes, and two major-effect QTLs were identified for the first time. The physical distance between adjacent markers of two major-effect QTLs was 44.37 kbp and 121.91 kbp, respectively. Approximately 2056 and 6769 SNP markers within confidence intervals were identified according to the results of parental line resequencing, which involved 24 and 199 mutant genes. CONCLUSIONS: The linkage map constructed in this study has the highest density in Chinese cabbage to date. Two major-effect QTLs for MFSL in Chinese cabbage were also identified. Among these, a novel QTL associated with bolting mapped on LG A04 was identified based on MFSL. The results of this study provide an important platform for gene/QTL mapping and marker-assisted selection (MAS) breeding for bolting-resistant Chinese cabbage.
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Brassica rapa/genética , Sitios de Carácter Cuantitativo , Brassica rapa/anatomía & histología , Mapeo Cromosómico , Ligamiento Genético , Técnicas de Genotipaje , Secuenciación de Nucleótidos de Alto Rendimiento , Fenotipo , Tallos de la Planta/anatomía & histología , Polimorfismo de Nucleótido SimpleRESUMEN
The role and regulators of extracellular vesicle (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF-1) is a transcription factor that plays an important role in liver IR and regulates certain guanosine triphosphatases. However, the relationships among IRF-1, Rab27a, and EV secretion are largely unknown. Here, we show induction of IRF-1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers. Interferon γ stimulation, IRF-1 transduction, or IR promoted Rab27a expression and EV secretion. Meanwhile, silencing of IRF-1 decreased Rab27a expression and EV secretion. Rab27a silencing decreased EV secretion and liver IR injury. Ten putative IRF-1 binding motifs in the 1,692-bp Rab27a promoter region were identified. Chromatin immunoprecipitation and electrophoretic mobility shift assay verified five functional IRF-1 binding motifs, which were confirmed by a Rab27a promoter luciferase assay. IR-induced EVs contained higher oxidized phospholipids (OxPL). OxPLs on the EV surface activated neutrophils through the toll-like receptor 4 pathway. OxPL-neutralizing E06 antibody blocked the effect of EVs and decreased liver IR injury. CONCLUSION: These findings provide a novel mechanism by which IRF-1 regulates Rab27a transcription and EV secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. (Hepatology 2018;67:1056-1070).
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Vesículas Extracelulares/metabolismo , Factor 1 Regulador del Interferón/metabolismo , Hígado/patología , Daño por Reperfusión/metabolismo , Proteínas rab27 de Unión a GTP/metabolismo , Animales , Técnicas de Cultivo de Célula , Regulación de la Expresión Génica , Hepatocitos/metabolismo , Humanos , Hígado/metabolismo , Trasplante de Hígado , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
BACKGROUND: Tumour-derived exosomes (TEXs) have a potential for application in cancer vaccines. Whether TEXs after induction by interferon regulatory factor 1 (IRF-1) are capable of enhancing the antitumour response remains to be determined. METHODS: Exosomes released by tumour cells infected with IRF-1-expressing adenovirus (IRF-1-Exo) or treated with interferon-γ (IFN-Exo) were isolated via ultracentrifugation. The IRF-1 target proteins IL-15Rα and MHC class I (MHC-I) were analysed by western blot. Exosomes along with CpG adjuvant were injected into tumour models to assess the antitumour effects. Tumours were harvested for immunofluorescence staining. Splenocytes from tumour-bearing mice were co-cultured with tumour cells. The IFNγ-positive and granzyme B-positive CD8α+ splenocyte cells were quantified by flow cytometry. RESULTS: The IRF-1-Exo or IFN-Exo displayed increased IL-15Rα and MHC-I expression. Injection of IRF-1-Exo or IFN-Exo combined with CpG had improved antitumour effects in mice. This effect may be a result of increased infiltration of tumours by CD4+ and CD8α+ T cells. Antibody-mediated depletion of CD4+ or CD8+ T cells abrogated the antitumour effects. Splenocytes isolated from CpG+IRF-1-Exo-injected Hepa 1-6 tumour mice had increased IFNγ-positive and granzyme B-positive CD8+ cells after co-culturing with Hepa 1-6 cells as compared with MC38 cells. CONCLUSIONS: The IRF-1 priming of TEXs enhances antitumour immune response.
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Exosomas/trasplante , Antígenos de Histocompatibilidad Clase I/metabolismo , Factor 1 Regulador del Interferón/genética , Neoplasias/tratamiento farmacológico , Oligodesoxirribonucleótidos/administración & dosificación , Receptores de Interleucina-15/metabolismo , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Línea Celular Tumoral , Dependovirus/genética , Quimioterapia Combinada , Exosomas/efectos de los fármacos , Exosomas/genética , Humanos , Factor 1 Regulador del Interferón/metabolismo , Interferón gamma/farmacología , Ratones , Trasplante de Neoplasias , Neoplasias/inmunología , Neoplasias/metabolismo , Oligodesoxirribonucleótidos/farmacologíaRESUMEN
Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.
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Genes de Plantas , Respuesta al Choque Térmico/genética , Raphanus/genética , Redes Reguladoras de GenesRESUMEN
MAIN CONCLUSION: Differential abundance protein species (DAPS) involved in reducing damage and enhancing thermotolerance in radish were firstly identified. Proteomic analysis and omics association analysis revealed a HS-responsive regulatory network in radish. Heat stress (HS) is a major destructive factor influencing radish production and supply in summer, for radish is a cool season vegetable crop being susceptible to high temperature. In this study, the proteome changes of radish taproots under 40 °C treatment at 0 h (Control), 12 h (Heat12) and 24 h (Heat24) were analyzed using iTRAQ (Isobaric Tag for Relative and Absolute Quantification) approach. In total, 2258 DAPS representing 1542 differentially accumulated uniprotein species which respond to HS were identified. A total of 604, 910 and 744 DAPS was detected in comparison of Control vs. Heat12, Control vs. Heat24, and Heat12 vs. Heat24, respectively. Gene ontology and pathway analysis showed that annexin, ubiquitin-conjugating enzyme, ATP synthase, heat shock protein (HSP) and other stress-related proteins were predominately enriched in signal transduction, stress and defense pathways, photosynthesis and energy metabolic pathways, working cooperatively to reduce stress-induced damage in radish. Based on iTRAQ combined with the transcriptomics analysis, a schematic model of a sequential HS-responsive regulatory network was proposed. The initial sensing of HS occurred at the plasma membrane, and then key components of stress signal transduction triggered heat-responsive genes in the plant protective metabolism to re-establish homeostasis and enhance thermotolerance. These results provide new insights into characteristics of HS-responsive DAPS and facilitate dissecting the molecular mechanisms underlying heat tolerance in radish and other root crops.
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Respuesta al Choque Térmico , Raíces de Plantas/metabolismo , Raphanus/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Respuesta al Choque Térmico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/genética , Proteómica , Raphanus/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrometría de Masas en TándemRESUMEN
Highly optimized nickel cobalt mixed oxide has been derived from zeolite imidazole frameworks. While the pure cobalt oxide gives only 178.7 F g-1 as the specific capacitance at a current density of 1 A g-1 , the optimized Ni:Co 1:1 has given an extremely high and unprecedented specific capacitance of 1931 F g-1 at a current density of 1 A g-1 , with a capacitance retention of 69.5% after 5000 cycles in a three electrode test. This optimized Ni:Co 1:1 mixed oxide is further used to make a composite of nickel cobalt mixed oxide/graphene 3D hydrogel for enhancing the electrochemical performance by virtue of a continuous and porous graphene conductive network. The electrode made from GNi:Co 1:1 successfully achieves an even higher specific capacitance of 2870.8 F g-1 at 1 A g-1 and also shows a significant improvement in the cyclic stability with 81% capacitance retention after 5000 cycles. An asymmetric supercapacitor is also assembled using a pure graphene 3D hydrogel as the negative electrode and the GNi:Co 1:1 as the positive electrode. With a potential window of 1.5 V and binder free electrodes, the capacitor gives a high specific energy density of 50.2 Wh kg-1 at a high power density of 750 W kg-1 .
RESUMEN
BACKGROUND: Malaria control and elimination are challenged by diversity and complexity of the determinants on the international border in the Great Mekong Sub-region. Hekou, a Chinese county on the China-Vietnam border, was used to document Chinese experiences and lessons for malaria control and elimination. METHODS: The design was an ecological study. Malaria burden before 1951 and procedures of 64 years (1952-2015) from malaria hyperendemicity to elimination are described. Single and bilinear regression analysis was utilized to analyse the relationship between the annual malaria incidence (AMI) and gross domestic product (GDP), urbanization rate, and banana planting area (BPA). RESULTS: There was a huge malaria burden before 1951. AMI was reduced from 358.62 per 1000 person-years in 1953 to 5.69 per 1000 person-years in 1960. A system of primary health services, comprising three levels of county township hospitals and village health stations maintained malaria control and surveillance activities in changing political and social-economic settings. However, potential under-reported of malaria and market-oriented healthcare led to a malaria epidemic in 1987. Strong political commitment reoriented malaria from a control to an elimination programme. High coverage of malaria intervention and population access to intervention was crucial for malaria control and elimination; meanwhile, AMI was closely associated with socio-economic development, correlation coefficients (R) -0.6845 (95% CI -0.7978, -0.6845) for national GDP, -0.7014 (-0.8093, -0.7014) for national urbanization rate and -0.5563 (-0.7147, -0.3437) for BPA. CONCLUSIONS: Multifactor, including political commitment, effective interventions, social and economic development and changing ecological environment, and the complicated interactions between these factors contribute to malaria elimination in Hekou County.