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Abiotic stress is an important factor affecting turf establishment and limiting the sustainability of the turf industry. To alleviate the effects of combined cold and drought stress in cold- and drought-prone regions, it is essential to select and introduce turfgrass germplasms that are suitable for these conditions for successful turf establishment. Thus, we evaluated the effects of combined extreme cold and drought stress on the morphological, plant leaf functional, photosynthetic, and physiological and biochemical traits of 16 wild annual bluegrass (Poa annua) germplasms. We found that there were significant differences (P < 0.05) among different provenances, combined cold and drought stress, and the main interaction factors. Combined cold and drought stress altered the morphological characteristics of the 16 germplasms to varying degrees. Furthermore, combined cold and drought stress significantly reduced the net photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (Tr), instantaneous water use efficiency (WUE), chlorophyll content, chlorophyll fluorescence parameters, accumulated intercellular CO2 concentration (Ci), and relative electrical conductivity (REC) and malondialdehyde (MDA), proline (Pro), soluble protein (SP), soluble sugar (SS), superoxide anion (O2.-), hydrogen peroxide (H2O2), and hydroxyl radical (·OH) and other active oxygen, and increased the superoxide dismutase activity (SOD), peroxidase activity (POD), catalase activity (CAT), ascorbate peroxidase activity (APX) and glutathione reductase (GR) activities. Comprehensive evaluation using principal component analysis (PCA), membership function analysis, and clustered heatmaps indicated that the 'HZ' germplasm had stronger combined cold and drought tolerance, whereas the 'ZQ' germplasm was more sensitive to combined cold and drought, which was roughly consistent with the order of morphological damage symptoms. Therefore, it is recommended to use the 'HZ' germplasm for planting projects in cold- and drought-prone areas, while the 'ZQ' germplasm is more suitable for use under warmer and non-water-deficient conditions.
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Frío Extremo , Poaceae , Poaceae/metabolismo , Sequías , Peróxido de Hidrógeno/metabolismo , Estaciones del Año , Fotosíntesis , Clorofila/metabolismo , Antioxidantes/metabolismo , Estrés FisiológicoRESUMEN
Microbial deodorization is a novel strategy for reducing odor in livestock and poultry feces. Herein, 12 strains of ammonia (NH3) and 15 hydrogen sulfide (H2S) removing bacteria were obtained with a removal efficiency of 65.20-79.80% and 34.90-79.70%, respectively. A novel bacteria deodorant named MIX (Bacillus zhangzhouensis, Bacillus altitudinis, and Acinetobacter pittii at a ratio of 1:1:2) were obtained. MIX can shorten the temperature rising stage by 2 days and prolong the thermophilic stage by 4 days. The ability of MIX to remove NH3, H2S, and volatile fatty acids (VFAs) and the underlying removal mechanism were analyzed during pig feces fermentation. MIX can significantly reduce the concentrations of NH3 and H2S by 41.82% and 66.35% and increase the concentrations of NO3--N and SO42- by 7.80% and 8.83% (P < 0.05), respectively, on the 25th day. Moreover, the concentrations of acetic, propionate, iso-valerate, and valerate were significantly reduced. The dominant bacteria communities at the phylum level were Firmicutes, Proteobacteria, Bacteroidetes, and Spirochaetes. B. zhangzhouensis and B. altitudinis could convert NH4+-N to NO3--N, and A. pittii could transfer H2S to SO42-. This study revealed that bacteria deodorant can reduce the concentrations of NH3, H2S, and VFAs in pig feces and increase those of NH4+, NO3-, and SO42- and has excellent potential in deodorizing livestock and poultry feces composting.
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Desodorantes , Sulfuro de Hidrógeno , Porcinos , Animales , Fermentación , Heces , Amoníaco , Bacterias , Ácidos Grasos Volátiles , ValeratosRESUMEN
Rhizome growth and development is regulated by phytohormone. However, endogenous phytohormones affect rhizome initiation, and sustained growth in perennial grass species remains elusive. In this study, we investigated the morphological characteristics and the content of indole-3-acetic acid (IAA), zeatin (ZT), gibberellic acid (GA3), and abscisic acid (ABA) in the rhizomes of two different Kentucky bluegrass. Using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), we performed metabolite analysis of two different rhizomes. In our study, the multi-rhizome Kentucky bluegrass material 'Yuzhong' had an average of 1113 rhizomes, while the few-rhizome material 'Anding' had an average of 347 rhizomes. The diameter of rhizome and length of rhizome internode in 'Yuzhong' were 1.68-fold and 1.33-fold higher than that of the 'Anding', respectively. The rhizome dry weight of 'Yuzhong' was 75.06 g, while the 'Anding' was 20.79 g. 'Yuzhong' had a higher ZT content (5.50 µg·g-1), which is 2.4-fold that of 'Anding' (2.27 µg·g-1). In contrast, the IAA, ABA, and GA3 content of rhizome were markedly higher in 'Anding' than 'Yuzhong'. Correlation analysis revealed significant correlations between ZT and ZT/ABA with the number of rhizomes, diameter of rhizome, and length of rhizome internode, whereas IAA, ABA, GA3, and IAA/ZT were opposite. In the metabolic profiles, we identified 163 differentially expressed metabolites (DEMs) (60 upregulated and 103 downregulated) in positive ion mode and 75 DEMs (36 upregulated and 39 downregulated) in negative ion mode. Histidine metabolism and ABC transporters pathways were the most significantly enriched in the positive and negative ion mode, respectively, both of which are involved in the synthesis and transport of cytokinin. These results indicate that cytokinin is crucial for rhizome development and promotes rhizome germination and growth of Kentucky bluegrass.
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BACKGROUND: Rhizome is vital for carbon and nitrogen metabolism of the whole plant. However, the effect of carbon and nitrogen in the rhizome on rhizome expansion remains unclear. RESULTS: Three wild Kentucky bluegrass (Poa pratensis L.) germplasms with different rhizome expansion capacity (strong expansion capacity, 'YZ'; medium expansion capacity, 'WY'; and weak expansion capacity, 'AD') were planted in the field and the rhizomes number, tiller number, rhizome dry weight, physiological indicators and enzyme activity associated carbon and nitrogen metabolisms were measured. Liquid chromatography coupled to mass spectrometry (LC-MS) was utilized to analyze the metabolomic of the rhizomes. The results showed that the rhizome and tiller numbers of the YZ were 3.26 and 2.69-fold of that of the AD, respectively. The aboveground dry weight of the YZ was the greatest among all three germplasms. Contents of soluble sugar, starch, sucrose, NO3--N, and free amino acid were significantly higher in rhizomes of the YZ than those of the WY and AD (P < 0.05). The activities of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and sucrose phosphate synthase (SPS) of the YZ were the highest among all three germplasm, with values of 17.73 A·g- 1 h- 1, 5.96 µmol·g- 1 min- 1, and 11.35 mg·g- 1 h- 1, respectively. Metabolomics analyses revealed that a total of 28 differentially expressed metabolites (DEMs) were up-regulated, and 25 DEMs were down-regulated in both comparison groups (AD vs. YZ group and WY vs. YZ group). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that metabolites related to histidine metabolism, tyrosine metabolism, tryptophan metabolism, and phenylalanine metabolism were associated with rhizomes carbon and nitrogen metabolism. CONCLUSIONS: Overall, the results suggest that soluble sugar, starch, sucrose, NO3--N, and free amino acid in rhizome are important to and promote rhizome expansion in Kentucky bluegrass, while tryptamine, 3-methylhistidine, 3-indoleacetonitrile, indole, and histamine may be key metabolites in promoting carbon and nitrogen metabolism of rhizome.
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Poa , Rizoma , Rizoma/metabolismo , Poa/metabolismo , Carbono/metabolismo , Kentucky , Nitrógeno/metabolismo , Sacarosa/metabolismo , Aminoácidos/metabolismo , Almidón/metabolismoRESUMEN
The herb A. squarrosum is reputed to possess medicinal properties for humans, and has the potential to be a feed resource for livestock. We hypothesized that this herb would improve the meat quality of lambs. To test this hypothesis, 24 Tan ewe-lambs (27.7 ± 0.45 kg) were offered diets containing 0 (CON), 100 (AS100), 200 (AS200) and 300 (AS300) g A. squarrosum/kg DM, and average daily gain, carcass traits, blood metabolites, meat quality and fatty acid profiles were determined. Drip loss % and cooking loss % decreased with the AS100 and AS200 diets (P < 0.05). Dietary A. squarrosum reduced muscle fiber area and diameter and increased density of the meat (P < 0.05), which indicated that the meat was more tender. The concentrations of C10:0 and C18:1n-9 t were 1ower and of C17:0 and C18:3n-3 were greater in the AS200 and AS300 treatments than CON (P < 0.05). Our results suggest that feeding lambs up to 200 g/kg DM of A. squarrosum can increase the water-holding capacity and L* value of meat without compromising growth. Further research is needed to determine the optimal level.
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Ácidos Grasos , Oveja Doméstica , Femenino , Ovinos , Animales , Humanos , Ácidos Grasos/metabolismo , Oveja Doméstica/metabolismo , Dieta/veterinaria , Carne/análisis , Músculo Esquelético/metabolismo , Alimentación Animal/análisisRESUMEN
Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ²=9.99, P<0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ²=4.85 and 5.58, both P<0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ²=9.65 and 7.82,both P<0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.
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Niño , Femenino , Masculino , Recién Nacido , Humanos , Lactante , Bloqueadores de los Canales de Sodio/efectos adversos , Oxcarbazepina , Lacosamida , Estudios Retrospectivos , Epilepsias Parciales/tratamiento farmacológico , Convulsiones , Sodio , Anticonvulsivantes/efectos adversosRESUMEN
ObjectiveTo investigate inhibitory effect of extracts from Veronica peregrina (EVP) on the osteoclastic bone metastasis induced by breast cancer cells. MethodBone metastasis model was established by injection of MDA-MB-231 cells, a human breast cancer cell line, into the left ventricle of BALB/c nude mice. The expression of human cytokeratin-19 (Ck-19) gene in mouse bone marrow was determined by nested polymerase chain reaction(PCR) to assess the bone metastasis of MDA-MB-231 cells. To assess the effects of EVP on the activation of bone marrow macrophages (BMMs), we counted the multinuclear cells and measured the secretion of Cathepsin K. Western blot was adopted to assess the effects of EVP on receptor activator of nuclear factor-κB (RANK), Runt-related transcription factor 2 ( Runx2 ), phosphorylated Runx2 (p-Runx2), and matrix metalloproteinase-9 (MMP-9) in BMMs. Gelatin zymography was employed to determine the activities of matrix metalloproteinases (MMPs). ResultCompared with that in the blank group, Ck-19 expression was down-regulated in EVP groups (P<0.05). The multinucleated cells increased when the BMMs were induced by soluble receptor activator of nuclear factor-κB ligand (sRANKL), which was inhibited by EVP (P<0.05). The level of cathepsin K in the supernatant of sRANKL group increased compared with that of the blank group, while EVP groups had lower cathepsin K levels than sRANKL group (P<0.05). Compared with the blank group, the sRANKL group showed up-regulated RANK expression, Runx2 phosphorylation, and MMP-9 expression (P<0.05), while the expression levels of RANK, p-Runx2, and MMP-9 were down-regulated when the cells were incubated with EVP (P<0.05). Furthermore, exposure of BMMs to sRANKL resulted in an increase in gelatin hydrolyzation compared with the blank group (P<0.01), which, however, was reversed in EVP groups (P<0.05). ConclusionEVP significantly inhibits bone marrow metastasis of MDA-MB-231 cells, which may be associated with the suppression of osteoclast activation by inhibiting Runx2 phosphorylation.
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This study aimed to investigate the effect of swine manure composting with microbial inoculation (MI) and without MI (CK) on heavy metal (Cr, Cd, and Pb) fractions, humic substance (HS), and metabolism pathway. The results showed that MI could passivate the heavy metal Cr and reduce the proportion of exchangeable (EXC) fraction of Cd, but it does not affect the EXC fraction of Pb. Compared to CK, HS, humic acid (HA), and fulvic acid (FA) were significantly increased with MI at the maturity stage. The propagation of Proteobacteria (day 4) and Firmicutes (days 12 and 24) was strengthened with MI. Canonical correlation analysis found that HA and Firmicutes were positively correlated with heavy metal (Cr, Cd, and Pb) residual (RES) fraction, and FA was positively correlated with Proteobacteria. Moreover, MI can significantly increase amino acid metabolism and carbohydrate metabolism by day 4, enhance the metabolism of enzyme families and glycan biosynthesis by day 12, and improve membrane transport. Overall, MI could facilitates the increase in HA and FA content and transfer of heavy metal (Cr, Cd, and Pb) fractions, it particularly helps increase the RES fraction.
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Compostaje , Metales Pesados , Animales , Sustancias Húmicas/análisis , Estiércol , Metales Pesados/análisis , Suelo , PorcinosRESUMEN
Objective:To investigate the inhibitory effects of Danshen injection against ovarian cancer cell proliferation induced by the interaction between platelets and cancer cells. Method:The induction of platelets on SKOV3 growth <italic>in vitro</italic> and the inhibitory effect of Danshen injection at 12,24,and 48 g·L<sup>-1</sup> were observed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell colony formation assays. The content of transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>) in the platelet-tumor cell interaction system and platelet supernatant and the effect of Danshen injection on TGF-<italic>β</italic><sub>1 </sub>secretion were detected by enzyme-linked immunosorbent assay (ELISA). The influences of tumor cell culture supernatant on platelet aggregation and secretion and the inhibitory effect of Danshen injection were determined by microplate assay and ELISA. The effects of Danshen injection on platelet nuclear factor kappa B (NF-<italic>κ</italic>B) signaling pathway were assayed by Western Blot. Result:Compared with the blank group, the platelet induction group exhibited significantly elevated absorbance at <italic>A</italic><sub>570 </sub>(<italic>P</italic><0.01), while the absorbance at <italic>A</italic><sub>570</sub> in the platelet + Danshen injection group was significantly lower than that in the platelet induction group (<italic>P</italic><0.01). The comparison with the Danshen injection group revealed that the cell proliferation inhibitory rate in the platelet + Danshen injection group at the same dose was more significant (<italic>P</italic><0.01). The number of colonies in the platelet induction group was obviously increased in contrast to that in the blank group(<italic>P</italic><0.05), while the number of colonies in the platelet + Danshen injection group was significantly lower than that in the platelet induction group(<italic>P</italic><0.05,<italic>P</italic><0.01). As demonstrated by comparison with the blank group, TGF-<italic>β</italic><sub>1 </sub>content in the supernatant of the platelet induction group rose remarkably(<italic>P</italic><0.01), whereas that in the platelet + Danshen injection group declined(<italic>P</italic><0.01). Compared with the Danshen injection (24 g·L<sup>-1</sup>) group, the platelet + Danshen injection group displayed more obvious inhibition(<italic>P</italic><0.01). Compared with the blank group, Danshen injection significantly reduced the TGF-<italic>β</italic><sub>1 </sub>content in platelet supernatant(<italic>P</italic><0.05,<italic>P</italic><0.01). There was no significant change in the content of TGF-<italic>β</italic><sub>1 </sub>in SKOV3 supernatant treated with Danshen injection. The platelet aggregation, thromboxane A<sub>2</sub>(TXB<sub>2</sub>), and serotonin (5-HT) secretion in the SKOV3 cell supernatant induction group were significantly increased as compared with those in the blank group (<italic>P</italic><0.01), while such indexes in the cell supernatant induction + Danshen injection group were obviously decreased (<italic>P</italic><0.01). Compared with the Danshen injection (24 g·L<sup>-1</sup>) group, the cell supernatant induction + Danshen injection group displayed more obvious inhibition at the same dose(<italic>P</italic><0.01). Compared with the blank group, the platelet induction group exhibited obviously up-regulated phosphorylated TGF-<italic>β</italic>-activated kinase-1 (TAK-1) and NF-<italic>κ</italic>B, but down-regulated phosphorylated inhibitory protein of NF-<italic>κ</italic>B (I<italic>κ</italic>B)(<italic>P</italic><0.01), which however were significantly reversed in the platelet + Danshen injection group<bold>(</bold><italic>P</italic><0.01). Conclusion:Danshen injection affect the proliferation of SKOV3 cells by inhibiting their interaction with platelets, which may be related to the inhibited secretion of TGF-<italic>β</italic><sub>1</sub>.
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Objective To analyze the patterns of lymph nodes metastasis (LNM) in supraglottic laryngeal squamous cell carcinomas (SLSCC) patients with different tumor differentiation. Methods We retrospectively investigated the clinicopathological data of patients diagnosed as SLSCC. The LNM patterns were analyzed by different tumor differentiation degrees. Results A total of 79 patients were included and divided into poorly differentiated group (n=20), middle differentiated group (n=52) and well differentiated group (n=7). There were 38 patients in N0 stage, 8 patients in N1 stage, 28 patients in N2 stage and 5 patients in N3 stage; 36 patients with LNM in level Ⅱ, 21 patients with LNM in level Ⅲ, 7 patients with LNM in level Ⅳ and no patients with LNM in level Ⅴ or Ⅵ. Conclusion SLSCC patients can benefit from bilateral neck dissection, and the patients with poor or moderate differentiation can benefit from neck dissection (levelsⅡ-Ⅳ), while the patients with well differentiation dissection may be more appropriate for neck dissection (levels Ⅱ-Ⅲ).
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Oral administration of nanoparticles is extremely limited due to the two processes of mucus permeation and epithelial absorption, which requires completely opposite surface properties of the nanocarriers. To tackle the contradiction, we developed a rational strategy to modify the surface of mesoporous carbon nanoparticles with chitosan concealed by a hydrophilic N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) layer. Probucol (PB) with the low poor permeability and solubility was loaded in optimal nanocarriers to realize the high loading efficacy and controlled release. The pHPMA polymer is a hydrophilic "mucus-inert" material, which could be dissociable from the surface of nanoparticles in the mucus, thus promoting their mucus permeation and causing exposure of chitosan in transepithelial transport. The swelling effect of chitosan under acidic conditions allowed regulation of PB release behavior. In conclusion, the mucus-permeable nanocarrier could effectively overcome multiple gastrointestinal absorption barriers and the oral bioavailability of PB-loaded HCMCN was 2.76-fold that of commercial preparation.
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Carbono/química , Portadores de Fármacos/química , Nanopartículas/química , Polímeros/química , Probucol/química , Probucol/farmacocinética , Adhesividad , Administración Oral , Animales , Disponibilidad Biológica , Portadores de Fármacos/toxicidad , Interacciones Hidrofóbicas e Hidrofílicas , Masculino , Ensayo de Materiales , Ratones , Membrana Mucosa/química , Porosidad , Probucol/administración & dosificaciónRESUMEN
This study determined the physicochemical changes and bacterial community succession in the pig manure composting process with microbial inoculant. Microbial inoculant could prolong the thermophilic stage by 2â¯days and increased the germination index (GI). Analysis with 16S rDNA showed that the Chao1 and Shannon indices increased at the thermophilic stage in the treatment (T), while those of the control (C) decreased. Microbial inoculant increased the relative abundance of Flavobacterium and Solibacillus in 4-12 and 12-24â¯days, respectively. Acinetobacter was reduced at 4-12â¯days. The key physicochemical factors affecting microbial successions were revealed by canonical correspondence analysis (CCA) and correlation analysis. Linear discriminant analysis (LDA) effect size (LEfse) analysis showed that there were 78 biomarkers, while in piles T and C, there were 35 and 43 biomarkers, respectively. These results indicated the addition of microbial inoculant improved the maturity and fertility, as well as significantly regulating the microbial community structure.
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Compostaje , Microbiota , Animales , Bacterias , Estiércol , Suelo , Porcinos , Zea maysRESUMEN
Central nervous system injury leads to irreversible neuronal loss and glial scar formation, which ultimately results in persistent neurological dysfunction. Regenerative medicine suggests that replenishing missing neurons may be an ideal approach to repair the damage. Recent researches showed that many mature cells could be transdifferentiated into functional neurons by reprogramming. Therefore, reprogramming endogenous glia in situ to produce functional neurons shows great potential and unique advantage for repairing neuronal damage and treating neurodegenerative diseases. The present review summarized the current research progress on in situ transdifferentiation in the central nervous system, focusing on the cell types, characteristics and research progress of glial cells that could be transdifferentiated in situ, in order to provide theoretical basis for the development of new therapeutic strategies of neuronal injury and further clinical application.
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Humanos , Transdiferenciación Celular , Reprogramación Celular , Sistema Nervioso Central , Biología Celular , Enfermedades Neurodegenerativas , Neuroglía , Biología Celular , Neuronas , Biología CelularRESUMEN
In this paper, an experimental study of silicon-based avalanche photodiode (Si-APD) with millisecond pulse laser irradiation was carried out, and the C-V curve of Si-APD was obtained by using a semiconductor analyzer. Based on the single-side abrupt junction character of n+p, combined with the corresponding theoretical derivation, the doping concentration varying with the axial depth of damaged Si-APD was obtained by inverse computation. The lattice dislocation and junction reduction were the fundamental causes of the reduced doping concentration. The research results provide a new method for the study of the internal doping concentration for detectors with millisecond pulse laser damage.
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In this manuscript, the effect of the particle size of polymer-functionalized mesoporous carbon (MPP) nanoparticles on enhancing oral absorption of a water-insoluble drug is first investigated. The insoluble drug, fenofibrate (Fen), was selected as the model drug loaded in the MPP nanoparticles. MPP nanoparticles with different particle sizes were designed for improving the oral bioavailability of drugs, in which the branched polyethyleneimine (PEI) and polyacrylic acid (PAA) were modified on the surfaces of mesoporous carbon nanoparticles (MCNs) with amide bonds. In addition, PEI-functionalized carbon quantum dots (PCA) and radioisotope 125I were applied to label the MPP nanoparticles to trace in the vivo process. According to the data, the MPP nanoparticles could markedly improve the dissolution rate and oral bioavailability of Fen. Interestingly, the MPP nanoparticle size had a notable effect on Fen oral absorption, and intermediate sized MPP nanoparticles were expected to be more ideal oral drug carriers. The nanoparticles were safe and easily excreted. These findings present the prospect of MPP nanoparticles for oral application, and guides the rational design of an oral delivery system with respect to particle size.
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Carbono , Portadores de Fármacos , Absorción por la Mucosa Oral/efectos de los fármacos , Polietileneimina , Puntos Cuánticos/química , Animales , Células CACO-2 , Carbono/química , Carbono/farmacocinética , Carbono/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Humanos , Masculino , Polietileneimina/química , Polietileneimina/farmacología , Porosidad , Ratas , Ratas Sprague-DawleyRESUMEN
Objective: To study the effect of sumoylation on the structure, stability and activity of human thymine DNA glycosylase (TDG). Methods: Expression and purification systems were established for obtaining SUMO-1-TDG protein with high purity which can be used for crystal screening and activity detection. Structure of SUMO-1-TDG was solved after crystal screening, diffraction data collection and structure analysis. The change of TDG stability led by sumoylation was detected through a protein thermal shift assay. In addition, an activity assay was applied to investigate the effect of sumoylation on the activity of TDG. Results: A high-resolution structure of SUMO-1-TDG which could clearly describe the interaction between TDG and SUMO-1 was solved. The melting temperature (Tm) value of SUMO-1-TDG increased by about 16℃ and the catalytic activity increased by 9.70%, comparing with TDG protein. Conclusion: SUMO-1 binds to TDG to modify the intermolecular interaction of amino acids near the binding site, and further participates in the regulation of the stability and catalytic activity of TDG protein.
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Objective·To study the effect of sumoylation on the structure,stability and activity of human thymine DNA glycosylase (TDG).Methods·Expression and purification systems were established for obtaining SUMO-1-TDG protein with high purity which can be used for crystal screening and activity detection.Structure of SUMO-1-TDG was solved after crystal screening,diffraction data collection and structure analysis.The change of TDG stability led by sumoylation was detected through a protein thermal shift assay.In addition,an activity assay was applied to investigate the effect of sumoylation on the activity of TDG.Results·A high-resolution structure of SUMO-1-TDG which could clearly describe the interaction between TDG and SUMO-1 was solved.The melting temperature ? value of SUMO-1-TDG increased by about 16 ℃ and the catalytic activity increased by 9.70%,comparing with TDG protein.Conclusion·SUMO-1 binds to TDG to modify the intermolecular interaction of amino acids near the binding site,and further participates in the regulation of the stability and catalytic activity of TDG protein.
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Objective To observe any curative effect of applying comprehensive pulmonary rehabilitation in moderate and severe cases of chronic obstructive pulmonary disease (COPD).Methods A total of 135 persons hospitalized with moderate or severe COPD were randomly divided into a rehabilitation group of 75 and acontrol group of 60.Both groups were given routine treatment,while the rehabilitation group was additionally provided with a comprehensive pulmonary rehabilitation regimen,including health education,exercise training,respiratory function training,respiratory muscle training,psychological support and nutritional intervention for six months.Before and after the treatment,both groups were evaluated using their walking distance within 6 minutes (6MWD),an anhelation index,a COPD assessment test (CAT),the Beck anxiety and depression scale,a nutritional assessment and indexes of pulmonary function and blood gases.Results After the intervention the average 6 MWD,anhelation index,CAT score,Beck anxiety and depression scores,forced expiratory volume,forced vital capacity and PaO2 of the rehabilitation group were all significantly better than before the treatment and better than those of the control group.Conclusion For moderate and severe COPD patients,comprehensive pulmonary rehabilitation effectively strengthens their moving ability,pulmonary function and arterial partial pressure of oxygen,while relieving anhelation,anxiety and depression.
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The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates. Their structures were confirmed by ESI-HRMS, ¹H-NMR, and 13C-NMR spectroscopic analyses. Two conjugates (26 and 42) showed strong cytotoxicity to MDCK cells in the CellTiter-Glo assay at a concentration of 100 µM. However, they showed no significant cytotoxicity to HL-60, Hela, and A549 cell lines in MTT assay under the concentration of 10 µM (except compound 42 showed weak cytotoxicity to HL-60 cell line (10 µM, ~53%)). Compounds 20, 28, 36, and 44 displayed weak potency to influenza A/WSN/33 (H1N1) virus (100 µM, ~20-30%), and no significant anti-influenza activity was found for the other conjugates. The data suggested that both the C-5 acetylamide and C-9 hydroxy of sialic acid were important for its binding with hemagglutinin during viral entry into host cells, while C-4 and C-2 hydroxy were not critical for the binding process and could be replaced with hydrophobic moieties. The research presented herein had significant implications for the design of novel antiviral inhibitors based on a sialic acid scaffold.
Asunto(s)
Antivirales/síntesis química , Antivirales/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Ácido N-Acetilneuramínico/química , Triterpenos/síntesis química , Triterpenos/farmacología , Animales , Antivirales/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Línea Celular Tumoral , Perros , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Humanos , Células de Riñón Canino Madin Darby , Espectroscopía de Protones por Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Triterpenos/químicaRESUMEN
In recent years, spherical nanoparticles has been studied extensively on biomedical applications including bioimaging and biosensing, diagnostics and theranostics, but the effect of the shape of nanoparticles has received little attention. In the present study, we designed three different shaped fluorescent mesoporous silica nanoparticles (MSNs), long rod nanoparticles (NLR), short rod nanoparticles (NSR), and spherical nanoparticles (NS) to systematically examine their behavior in vivo after oral administration. The results of the ex vivo optical imaging study in mice indicated that rod nanoparticles had a longer residence time in the gastrointestinal compared with spherical nanoparticles. The in vivo biodistribution showed that all the orally administered MSNs were mainly taken up by the liver, and kidney. NLR had a great capacity to overcoming rapid clearance by the RES and exhibited a longer circulation in the blood than NSR and NS. During renal excretion, the spherical nanoparticles were cleared faster than rod nanoparticles. In addition, it was also found that MSNs can be degraded in vivo and NSR were degraded faster than NLR and NS probably owing to their higher specific surface area. The pharmacokinetic results demonstrated that nifedipine(NI)-loaded NLR had a higher bioavailability than NI-loaded NSR and NS.