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This experiment was conducted to investigate the impacts of dietary selenium yeast (SeY) on the growth performance, fish body composition, metabolic ability, antioxidant capability, immunity and inflammatory responses in juvenile black carp (Mylopharyngodn piceus). The base diet was supplemented with 0.00, 0.30 and 0.60 g/kg SeY (0.04, 0.59 and 1.15 mg/kg of selenium) to form three isonitrogenous and isoenergetic diets for juvenile black carp with a 60-day. Adequate dietary SeY (0.30 and 0.60 g/kg) could significantly increase the weight gain (WG), special growth rate (SGR) compared to the SeY deficient groups (0.00 g/kg) (P < 0.05). Meanwhile, 0.30 and 0.60 g/kg SeY elevated the mRNA levels of selenoprotein T2 (SEPT2), selenoprotein H (SEPH), selenoprotein S (SEPS) and selenoprotein M (SEPM) in the liver and intestine compared with the SeY deficient groups (P < 0.05). Adequate dietary SeY could promote glucose catabolism and utilization through activating glucose transport (GLUT2), glycolysis (GCK, HK, PFK, PK, PDH), tricarboxylic acid cycle (ICDH and MDH), glycogen synthesis (LG, GCS and GBE) and IRS/PI3K/AKT signal pathway molecules (IRS2b, PI3Kc and AKT1) compared with the SeY deficient groups (P < 0.05). Similarly, adequate dietary SeY could improve lipid transport and triglycerides (TG) synthesis through increasing transcription amounts of CD36, GK, DGAT, ACC and FAS in the fish liver compared with the SeY deficient groups (P < 0.05). In addition, adequate SeY could markedly elevate activities of antioxidant enzymes (T-SOD, CAT, GR, GPX) and contents of T-AOC and GSH, while increased transcription amounts of Nrf2, Cu/Zn-SOD, CAT, and GPX in fish liver and intestine (P < 0.05). However, adequate SeY notably decreased contents of MDA, and the mRNA transcription levels of Keap1 in the intestine compared with the SeY deficient groups (P < 0.05). Adequate SeY markedly increased amounts or levels of the immune factors (ALP, ACP, LZM, C3, C4 and IgM) and the transcription levels of innate immune-related functional genes in the liver and intestine (LZM, C3 and C9) compared to the SeY deficient groups (P < 0.05). Moreover, adequate SeY could notably reduce levels of IL-8, IL-1ß, and IFN-γ and elevate TGF-1ß levels in fish intestine (P < 0.05). The transcription levels of MAPK13, MAPK14 and NF-κB p65 were notably reduced in fish intestine treated with 0.30 and 0.60 g/kg SeY (P < 0.05). In conclusion, these results suggested that 0.30 and 0.60 g/kg SeY could not only improve growth performance, increase Se, glucose and lipid metabolic abilities, enhance antioxidant capabilities and immune responses, but also alleviate inflammation, thereby supplying useful reference for producing artificial feeds in black carp.
Assuntos
Carpas , Selênio , Animais , Antioxidantes/metabolismo , Carpas/genética , Carpas/metabolismo , Selênio/metabolismo , Saccharomyces cerevisiae/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Imunidade Inata , Fosfatidilinositol 3-Quinases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Suplementos Nutricionais , Dieta/veterinária , RNA Mensageiro , Glucose , Selenoproteínas/metabolismo , Lipídeos , Superóxido Dismutase/metabolismo , Ração Animal/análise , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismoRESUMO
Herein, we described the first synthesis of the pentasaccharide and decasaccharide of the A.â baumannii ATCC 17961 O-antigen for developing a synthetic carbohydrate-based vaccine against A.â baumannii infection. The efficient synthesis of the rare sugar 2,3-diacetamido-glucuronate was achieved using our recently introduced organocatalytic glycosylation method. We found, for the first time, that long-range levulinoyl group participation via a hydrogen bond can result in a significantly improved ß-selectivity in glycosylations. This solves the stereoselectivity problem of highly branched galactose acceptors. The proposed mechanism was supported by control experiments and DFT computations. Benefiting from the long-range levulinoyl group participation strategy, the pentasaccharide donor and acceptor were obtained via an efficient [2+1+2] one-pot glycosylation method and were used for the target decasaccharide synthesis.
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Carboidratos , Antígenos O , Antígenos O/química , Carboidratos/química , Oligossacarídeos/química , Glicosilação , GalactoseRESUMO
In the present study, the full-length cDNA sequences of leptin (LEP) and its receptor (LEPR) from turbot Scophthalmus maximus were cloned. The cDNA of tLEP was 1126 bp in length encoding 157 amino acids. The amino acid sequence shared low identity with human LEP (18.8 %), but the three-dimensional structures of these two LEPs were strongly conserved. The deduced 1173-amino acid sequence of tLEPR was 28 % identical to human LEPR, and 82 % too range-spotted grouper LEPR, containing all functionally important domains conserved in vertebrate LEPR. Tissue distribution analysis showed that tLEP was abundantly expressed in brain, eyes and liver. The highest level of tLEPR mRNA was found in liver and kidney. After a 9-week feeding trial using diets with different ratios of carbohydrate-lipid (1:6, 1:2, 2:1 and 14:1), it was found that the increase in dietary carbohydrate-to-lipid ratios from 1:6 to 2:1 did not significantly influence tLEP and tLEPR expression in turbot liver (P > 0.05). The hepatic tLEP expression was significantly elevated in treatment with 14:1 dietary carbohydrate-to-lipid ratio (P < 0.05). The hepatic tLEPR mRNA level in group with 14:1 dietary carbohydrate-to-lipid ratio was significantly lower than that in 1:6 group (P < 0.05), but had no significant difference with the other two groups (P > 0.05). These results revealed the important relationship between dietary carbohydrate-to-lipid ratio and LEP expression in turbot.
Assuntos
Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Proteínas de Peixes/genética , Linguados/genética , Leptina/genética , Receptores para Leptina/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , DNA Complementar/genética , Expressão Gênica , Fígado/metabolismo , Filogenia , RNA Mensageiro/metabolismoRESUMO
Glucokinase (GK) and fructose-1,6-bisphosphatase (FBPase) play crucial role in glucose metabolism. In the present study, the cDNA encoding GK and FBPase was cloned from the liver of turbot Scophthalmus maximus by rapid amplification of cDNA end technique. Effects of dietary glucose and dextrin on the activities and gene expressions of these two enzymes were also studied. Results showed that the full length of GK cDNA was 2226 bp, consisting of an open reading frame (ORF) of 1434 bp. The full-length cDNA coding FBPase was 1314 bp with a 1014 bp ORF encoding 337 amino acids. Analyses of gene expression of GK and FBPase were conducted in gill, liver, the whole intestine, the whole kidney, heart, the dorsal white muscle and brain. The highest expression of GK was found in liver, followed by muscle. The expression of FBPase was found higher in liver than heart and gill. Both hepatic GK activity and mRNA expression were highly induced in turbot after being fed with dietary carbohydrates (p < 0.05). However, the GK activity and mRNA expression in the group with dietary glucose did not significantly differ from those in the group with dietary dextrin (p > 0.05). Compared with the control group, there were no significant differences in FBPase activity and mRNA expression in the glucose as well as dextrin group (p > 0.05). The increased hepatic GK activity and gene expression indicated that the first step of glycolysis was activated in turbot by dietary carbohydrates.
Assuntos
Dextrinas/farmacologia , Dieta/veterinária , Linguados/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Fígado/enzimologia , Análise de Variância , Animais , Clonagem Molecular , Primers do DNA/genética , Frutose-Bifosfatase/metabolismo , Glucoquinase/metabolismo , Fígado/efeitos dos fármacos , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Cyclopropanes are among the most important structural units in natural products, pharmaceuticals, and agrochemicals. Herein, we report a manganese-catalyzed cyclopropanation of allylic alcohols with sulfones as carbene alternative precursors via a borrowing hydrogen strategy under mild conditions. Various allylic alcohols and arylmethyl trifluoromethyl sulfones work efficiently in this borrowing hydrogen transformation and thereby deliver the corresponding cyclopropylmethanol products in 58% to 99% yields. Importantly, a major benefit of this transformation is that the versatile free alcohol moiety is retained in the resultant products, which can undergo a wide range of downstream transformations to provide access to a series of functional molecules. Mechanistic studies support a sequential reaction mechanism that involves catalytic dehydrogenation, Michael addition, cyclization, and catalytic hydrogenation.
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Objective: Recent studies have shown that gene alternative splicing (AS) and long noncoding RNAs (lncRNAs) are involved in diabetes mellitus (DM) and its complications. Currently, myo-inositol (MI) is considered as effective for the treatment of insulin resistance and lipid metabolism disorders in diabetes patients. We hope to better explore the potential roles of gene AS and lncRNAs in liver glucose and lipid metabolism in diabetes, as well as the effects of myo-inositol treatment, through transcriptome analysis. Methods: This study analysed glucose and lipid metabolism-related biochemical indicators and liver HE staining in four groups of mice: the control group (Ctrl group), the diabetes group (DM group), the myo-inositol treatment group (MI group), and the metformin treatment group (Met group). The changes in relevant gene-regulated alternative splicing events (RASEs) and lncRNAs were analysed by RNA sequencing of liver tissue, and coexpression analysis and functional enrichment analysis were used to predict the possible lncRNAs and RASEs involved in liver glucose and lipid metabolism. Result: Metformin and myo-inositol alleviated insulin resistance, lipid metabolism disorders, and hepatic steatosis in diabetic mice. Transcriptome sequencing analysis revealed differential splicing events of genes related to lipid metabolism and differentially expressed lncRNAs (DElncRNAs). Six different lncRNAs and their potentially interacting splicing events were predicted. Conclusion: The present study revealed novel changes in RASEs and lncRNAs in the livers of diabetic mice following treatment with myo-inositol, which may shed light on the potential mechanisms by which myo-inositol delays and treats the progression of hepatic glucose and lipid metabolism in diabetes.
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Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration-time curve (AUC0-12h) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.
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Atropina , Disponibilidade Biológica , Preparações de Ação Retardada , Estabilidade de Medicamentos , Soluções Oftálmicas , Poliestirenos , Animais , Coelhos , Preparações de Ação Retardada/farmacocinética , Poliestirenos/química , Poliestirenos/farmacocinética , Soluções Oftálmicas/farmacocinética , Soluções Oftálmicas/administração & dosagem , Atropina/farmacocinética , Atropina/administração & dosagem , Atropina/química , Masculino , Derivados da Hipromelose/química , Lágrimas/metabolismo , Liberação Controlada de Fármacos , Humor Aquoso/metabolismo , Polissacarídeos Bacterianos/química , Administração OftálmicaRESUMO
Based on SPOT-VGT images and meteorological data, this paper applied an integrated method to investigate the vegetation dynamic and its response to climate factors during 1998-2008 in Northeast China Transect, one of 15 ecological transects listed in the International Geosphere-Biosphere Programme. The main findings are as follows: (1) The NDVI time series presented nonlinear patterns that vary with timescales. The series fluctuated greatly at the smallest timescale (20 days), showing no salient trend, whereas a trend manifested itself more and more with the increase of time scale and finally stabilized at the 320-day scale. Little difference was found between vegetation types about the NDVI periodicity, as they occurred on either a 280-day or a 290-day cycle. (2) NDVI exhibited a significant correlation with temperature, precipitation, and sunshine hours. Overall, the correlation between NDVI and temperature was the highest, followed by precipitation, sunshine hours, and relative humidity. For different vegetation types, the correlations between NDVI and climate variables diversified, increasing from desert steppe to typical steppe, meadow steppe, and forest. (3) The periodicity of temperature and precipitation occurred in either a 280-day or 290-day cycle, which was approximately coincident with that of NDVI. This further supported the significant relationship between NDVI and these two climate factors. (4) At all the time scales under examination, NDVI and temperature and precipitation are significantly, positively correlated, especially at the 160-day scale, which can be regarded as the most suitable time scale for investigating the responses of vegetation dynamics to climate factors at most stations.
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Clima , Monitoramento Ambiental/métodos , Plantas , Biodiversidade , China , Ecologia , Chuva , TemperaturaRESUMO
Citrus reticulata "Chachi" (CRC) leaves contain abundant flavonoids, indicating that they possess good nutritional/pharmacological research and development potential. This study aims to explore chemical antioxidant quality markers based on the spectrum-effect relationship and quality control strategy of CRC leaves. The ultrahigh performance liquid chromatography (UPLC) system was used to establish chromatographic fingerprints of Citrus reticulata "Chachi" leaves. Simultaneously, they were evaluated by using similarity analysis (SA), hierarchical cluster analysis (HCA), and principal component analysis (PCA). Afterwards, the DPPH assay was adopted to study the antioxidant effects. The spectrum-effect relationship between UPLC fingerprints and DPPH radical-scavenging activities was studied with grey relational analysis (GRA). Analysis results indicated that there were twenty-one common peaks of fourteen batches of CRC leaves which were from different regions of Guangdong province, and their similarities ranged from 0.648 to 0.997. HCA results showed that fourteen batches of samples of CRC leaves could be divided into six classes at Euclidean distance of 5. The results from GRA showed that tangeretin and hesperidin were the main flavonoids responsible for the antioxidant activity in CRC leaves. In conclusion, this research established a chromatographic analysis method suitable for CRC leaves and demonstrated that chromatographic fingerprints analysis combined with the antioxidant activity could be used to evaluate the material basis of CRC leaves and may provide a reference to establish a quality standard.
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Herein, we report a new glycosylation system for the highly efficient and stereoselective formation of glycosidic bonds using glycosyl N-phenyl trifluoroacetimidate (PTFAI) donors and a charged thiourea hydrogen-bond-donor catalyst. The glycosylation protocol features broad substrate scope, controllable stereoselectivity, good to excellent yields and exceptionally mild catalysis conditions. Benefitting from the mild reaction conditions, this new hydrogen bond-mediated glycosylation system in combination with a hydrogen bond-mediated aglycon delivery system provides a reliable method for the synthesis of challenging phenolic glycosides. In addition, a chemoselective glycosylation procedure was developed using different imidate donors (trichloroacetimidates, N-phenyl trifluoroacetimidates, N-4-nitrophenyl trifluoroacetimidates, benzoxazolyl imidates and 6-nitro-benzothiazolyl imidates) and it was applied for a trisaccharide synthesis through a novel one-pot single catalyst strategy.
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Amyloid ß (Aß) peptides have long been viewed as a potential target for Alzheimer's disease (AD). Aggregation of Aß peptides in the brain tissue is believed to be an exclusively pathological process. Therefore, blocking the initial stages of Aß peptide aggregation with small molecules could hold considerable promise as the starting point for the development of new therapies for AD. Recent rapid progresses in our understanding of toxic amyloid assembly provide a fresh impetus for this interesting approach. Here, we discuss the problems, challenges and new concepts in targeting Aß peptides.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Sistemas de Liberação de Medicamentos , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Animais , Desenho de Fármacos , HumanosRESUMO
The variation of the rate of cyclic electron transport around Photosystem I (PS I) during photosynthetic induction was investigated by illuminating dark-adapted spinach leaf discs with red + far-red actinic light for a varied duration, followed by abruptly turning off the light. The post-illumination re-reduction kinetics of P700+, the oxidized form of the photoactive chlorophyll of the reaction centre of PS I (normalized to the total P700 content), was well described by the sum of three negative exponential terms. The analysis gave a light-induced total electron flux from which the linear electron flux through PS II and PS I could be subtracted, yielding a cyclic electron flux. Our results show that the cyclic electron flux was small in the very early phase of photosynthetic induction, rose to a maximum at about 30 s of illumination, and declined subsequently to <10% of the total electron flux in the steady state. Further, this cyclic electron flow, largely responsible for the fast and intermediate exponential decays, was sensitive to 3-(3,4-dichlorophenyl)-1,1-dimethyl urea, suggesting an important role of redox poising of the cyclic components for optimal function. Significantly, our results demonstrate that analysis of the post-illumination re-reduction kinetics of P700+ allows the quantification of the cyclic electron flux in intact leaves by a relatively straightforward method.
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Fotossíntese/fisiologia , Complexo de Proteína do Fotossistema I/metabolismo , Folhas de Planta/metabolismo , Spinacia oleracea/metabolismo , Clorofila/metabolismo , Transporte de Elétrons/fisiologiaRESUMO
There exist limitations in the detection of exogenous oligosaccharides due to their polydisperse and diversiform nature, and particularly the interference of endogenous glycosaminoglycans (GAGs). Herein, a surface plasmon resonance (SPR) assay for detecting acidic oligosaccharide sugar chain (AOSC), an anti-Alzheimer's drug candidate, in cerebrospinal fluid (CSF) was developed based on a carbohydrate antigen-antibody interaction. Rabbits were treated with AOSC intravenously and orally at 40 or 200 mg x kg(-1), respectively. CSF samples were collected at given time points for quantitative determination of AOSC concentrations in the CSF using an SPR-based competitive inhibition assay, and the existence of AOSC in the CSF was indicated as a blood-brain barrier (BBB) accessibility index. AOSC concentration as low as 50 ppb (0.05 microg x ml(-1)) was detected in the CSF, with its peak value approaching 2.091 and 3.316 microg x ml(-1) following intravenous and oral administration, respectively. This is the first time the capacity of AOSC to pass through the BBB has been confirmed using SPR-based competitive inhibition immunoassay. Importantly, the accessibility of AOSC to the BBB indicates AOSC has potential therapeutic value for treating neurodegenerative diseases, particular Alzheimer's disease.