In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-i...In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. AIpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase.展开更多
Diabetic neuropathy, the most common form of peripheral neuropathy, presents as different forms of focal or diffuse neuropathy, including the disabling, or potentially life-threatening clinical entities of painful dia...Diabetic neuropathy, the most common form of peripheral neuropathy, presents as different forms of focal or diffuse neuropathy, including the disabling, or potentially life-threatening clinical entities of painful diabetic neuropathy, autonomic neuropathy, and diabetic foot. The pathogenesis of diabetic neuropathy results from the concurrent action of various intersecting factors of nerve damage, such as oxidative stress and mitochondrial dysfunction, inflammation, microangiopathy and ischemia, triggered by hyperglycemia and related biochemical changes. Symptomatic treatment of diabetic neuropathy mainly concerns therapies for neuropathic pain, interventions targeted at the organ systems involved in autonomic neuropathy, and management of diabetic foot. Therapeutic approaches to the pathogenesis of diabetic neuropathy have focused on the different components of the causes of nerve damage, particularly oxidative stress, which has been demonstrated to play a central role. Alpha-lipoic acid, a potent lipophilic free radical scavenger, has been used in treatment of patients with diabetic neuropathy, displaying efficacy on the chief symptoms, including neuropathic pain, and showing that neuropathic deficits may be improved by treatment. Current evidence suggests a possible efficacy of alpha-lipoic acid not only for neuropathic symptoms, but also for reducing the risk factors for diabetic neuropathy.展开更多
Alpha-lipoic acid-loaded lipid nanoparticles(ALA-LNs) were prepared by high pressure homogenization method.The influences of storage conditions such as time and temperature on the physical and chemical storage stabili...Alpha-lipoic acid-loaded lipid nanoparticles(ALA-LNs) were prepared by high pressure homogenization method.The influences of storage conditions such as time and temperature on the physical and chemical storage stability of ALA-LNs were studied in details.The stability was evaluated by particle size and polydispersity index,morphology of ALA-LNs,and capacity of ALA loading.The dilution and pH stability of ALA-LNs suspensions were also studied.After three months storage,the mean size of ALA-LNs at 4 and 40 ℃ was increased by 2.68% and 3.62% compared with the original size,respectively.ALA-LNs stored at 40 ℃ had ellipsoid shape and the mean size was about 152 nm(SD=23.6).The loading capacity of ALA at 40 ℃ was much higher than those stored at other two temperatures.The good dilution and pH stability were also demonstrated.The sample had good fluidity even at 4 ℃.展开更多
Alpha lipoic acid has the ability to react and neutralize reactive oxygen species (ROS) such as superoxide radicals, simple oxygen, hydroxyl radicals, hypochlorous acid and peroxyl radicals. A rapid high-performance l...Alpha lipoic acid has the ability to react and neutralize reactive oxygen species (ROS) such as superoxide radicals, simple oxygen, hydroxyl radicals, hypochlorous acid and peroxyl radicals. A rapid high-performance liquid chromatographic method for determination of lipoic acid in a nutritional supplement was developed. The method involved sample preparation and the mobile phase comprised of 50 mM disodium hydrogen phosphate buffer (pH 2.5 adjusted with 1 M H<sub>3</sub>PO<sub>4</sub>): acetonitrile in the ratio of 50:50. The separation was done using a C18 column (150 mm) and detection was carried out using UV detection at 201 nm. The assay was found to be linear in the range of 1.56 - 50 μg/mL with the correlation coefficient of 0.9997. Method precision was determined while LOD was 0.05 μg/mL and LOQ 0.15 μg/mL. The chromatographic peak LA retention time was 6 min.展开更多
Objective:Relevance of cardiac autonomic neuropathy has not been fully recognized and there is no standardized treatment protocol.Aim:To evaluate the effects of alpha-lipoic acid on the beat-to-beat vectorcardiographi...Objective:Relevance of cardiac autonomic neuropathy has not been fully recognized and there is no standardized treatment protocol.Aim:To evaluate the effects of alpha-lipoic acid on the beat-to-beat vectorcardiographic parameters,namely spatial QRS-T angle,QT dispersion(QTd)and corrected QT interval(QTc)in type 2 diabetes mellitus persons with cardiac autonomic neuropathy.Research designs and methods:Our study involved 33 persons with definite stage of cardiac autonomic neuropathy and diabetes mellitus type 2,which were assigned to each of two groups:one took standard antihyperglycaemic treatment(n=15,control group)and the other(n=18)in addition to standard therapy-600 mg of alpha-lipoic acid daily for three months.The analysis of vectorcardiographic parameters was performed.Results:It was found out that alpha-lipoic acid contributed to decrease of the vectorcardiographic parameters,namely QRS-T angle,QTd and QTc.Conclusions:The positive influences of alpha-lipoic acid suggest the usefulness of its prescription to type 2 diabetes mellitus persons with definite stage of cardiac autonomic neuropathy.The efficacy of alpha-lipoic acid is the result of its direct effect on the parameters of vectorcardiography.展开更多
Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administere...Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administered with Nω-nitro-L-arginine methyl ester(L-NAME).Methods:Male rats were divided into four groups(SHR,SHR+ALA,SHR+L-NAME,SHR+ALA+L-NAME).The respective group of rats was administered with ALA(100 mg/kg/day)from age 4 weeks to 28 weeks and L-NAME(25 mg/kg/day)from age 16 weeks to 28 weeks.SBP was measured every two weeks and twenty four hour urine was collected at 4 weeks,16 weeks and 28 weeks for estimation of protein,creatinine and N-acetyl-e end of 28 weeks,rats were sacrificed and blood and kidneys colα-Dglucosaminidase.At thlected for assessment of blood creatinine,kidney thiobarbituric acid reactive substances,protein carbonyls,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,glutathione S-transferase,glutathione disulfide,glutathione,total antioxidant status and nitric oxide as well as histopathological examination.Results:ALA supplementation significantly reduced SBP of SHR and SHR+L-NAME rats when compared to their respective non-supplemented groups.Renal oxidant status markers including thiobarbituric acid reactive substances and protein carbonyls were significantly reduced on SHR and SHR+L-NAME rats supplemented with ALA at 28 weeks as well as ALA supplementation significantly increased renal antioxidants including superoxide dismutase,catalase,glutathione peroxidase,glutathione S-transferase,glutathione and glutathione/glutathione disulfide ratio at 28 weeks.No significant change in nitric oxide levels was observed between the ALA supplemented and non-supplemented groups.Renal dysfunction was ameliorated on ALA supplementation as evidenced by significant reduction in urine protein levels,N-acetyl-α-D-glucosaminidase activity and significant increase of creatinine clearance in SHR and SHR+L-NAME at 28 weeks.Renal histopathological examination showed that ALA supplementation prevented vascular damage in SHR and ameliorated glomerular damage in SHR+L-NAME at 28 weeks.Conclusions:ALA has hypotensive and renoprotective effects on both SHR and SHR+LNAME,which could be due to its ability to ameliorate oxidative stress in the kidneys.展开更多
Background Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to b...Background Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant α-lipoic acid （α-LA） could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin （STZ） 45 mg/kg. Experimental animals were randomly assigned to 3 groups： normal control （NC）, diabetes （DM） and DM treated with α-LA （α-LA）. The latter group was administered with a-LA （100 mg/kg ip per day）, the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde （MDA）, reduced glutathione （GSH） and the activity of manganese superoxide diamutase （Mn-SOD） in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting Results At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by α-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while α-LA reversed this structural derangement. The index of cardiac function （±dp/dtmax） in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but α-LA delayed deterioration of cardiac function （P 〈0.05）. Conclusions Our findings indicate that the antioxidant α-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of α-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.展开更多
The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving c...The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving carbon neutrality is the utilization of CO_(2) under economic and sustainable conditions.Recently,the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO_(2) into carboxylic acids,which can effectively alleviate CO_(2) emissions and create high-value chemicals.The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO_(2) conversion into carboxylic acids through photo-,electric-,and thermal catalysis.Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level,inspiring the preparation of high-performance catalysts.In addition,theoretical calculations,advanced technologies,and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity.Finally,challenges and prospects are provided for the future development of this field.It is hoped that this review will contribute to a deeper understanding of the conversion of CO_(2) into carboxylic acids and inspire more innovative breakthroughs.展开更多
Omega-3 polyunsaturated fatty acids(n-3 PUFAs),particularly docosahexaenoic acid(22:6n-3,DHA),play crucial roles in the reproductive health of vertebrates,including humans.Nevertheless,the underlying mechanism related...Omega-3 polyunsaturated fatty acids(n-3 PUFAs),particularly docosahexaenoic acid(22:6n-3,DHA),play crucial roles in the reproductive health of vertebrates,including humans.Nevertheless,the underlying mechanism related to this phenomenon remains largely unknown.In this study,we employed two zebrafish genetic models,i.e.,elovl2^(-/-)mutant as an endogenous DHAdeficient model and fat1(omega-3 desaturase encoding gene)transgenic zebrafish as an endogenous DHA-rich model,to investigate the effects of DHA on oocyte maturation and quality.Results show that the elovl2^(-/-)mutants had much lower fecundity and poorer oocyte quality than the wild-type controls,while the fat1 zebrafish had higher fecundity and better oocyte quality than wildtype controls.DHA deficiency in elovl2^(-/-)embryos led to defects in egg activation,poor microtubule stability,and reduced pregnenolone levels.Further study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1,which encodes the cholesterol side-chain cleavage enzyme,thereby stabilizing microtubule assembly during oogenesis.In turn,the hypothalamic-pituitary-gonadal axis was enhanced by DHA.In conclusion,using two unique genetic models,our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.展开更多
In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic...In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.展开更多
Sweet osmanthus(Osmanthus fragrans) is a having general approval aromatic tree in China that is widely applied to landscaping and gardening. However, the evergreen tree adaptability is limited by many environmental st...Sweet osmanthus(Osmanthus fragrans) is a having general approval aromatic tree in China that is widely applied to landscaping and gardening. However, the evergreen tree adaptability is limited by many environmental stresses. Currently, limited information is available regarding the genetic analysis and functional identification of expansin genes in response to abiotic stress in sweet osmanthus. In this study, a total of 29 expansin genes were identified and divided into four groups by genome-wide analysis from the sweet osmanthus genome. Transcriptome and quantitative Real-time PCR analysis showed that the cell wall-localized protein expansin-like A(OfEXLA1) gene was significantly induced by salt and drought treatment. Histochemical GUS staining of transgenic Arabidopsis lines in which GUS activity was driven with the OfEXLA1 promoter, GUS activity was significantly induced by salt, drought, and exogenous abscisic acid(ABA). In yeast, we found OfEXLA1overexpression significantly improved the population of cells compared with wild-type strains after NaCl and polyethylene glycol(PEG)treatment. Additionally, OfEXLA1 overexpression not only promoted plant growth, but also improved the salt and drought tolerance in Arabidopsis. To gain insight into the role of ABA signaling in the regulation of OfEXLA1 improving abiotic tolerance in sweet osmanthus, four differentially expressed ABA Insensitive 5(ABI5)-like genes(OfABL4, OfABL5, OfABL7, and OfABL8) were identified from transcriptome, and dualluciferase(dual-LUC) and yeast one hybrid(Y1H) assay showed that OfABL4 and OfABL5 might bind to OfEXLA1 promoter to accumulate the OfEXLA1 expression by responding to ABA signaling to improve abiotic tolerance in sweet osmanthus. These results provide the information for understanding the molecular functions of expansin-like A gene and molecular breeding of sweet osmanthus in future.展开更多
Background The benefits of combining benzoic acid and essential oils(BAO)to mitigate intestinal impairment during the weaning process have been well established,while the detailed underlying mechanism has not been ful...Background The benefits of combining benzoic acid and essential oils(BAO)to mitigate intestinal impairment during the weaning process have been well established,while the detailed underlying mechanism has not been fully elucidated.Previous research has primarily focused on the reparative effects of BAO on intestinal injury,while neglecting its potential in enhancing intestinal stress resistance.Methods In this study,we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure.Piglets were pre-supplemented with BAO for 14 d,followed by a challenge with LPS or saline to collect blood and intestinal samples.Results Our findings demonstrated that BAO supplementation led to significant improvements in piglets’final weight,average daily gain,and feed intake/body gain ratio.Additionally,BAO supplementation positively influenced the composition of intestinal microbiota,increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota,Prevotella and Oscillospira.Furthermore,BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge.This was evidenced by elevated levels of T-AOC,SOD,and GSH,as well as decreased levels of MDA,TNF-α,and IL-6 in the plasma.Moreover,piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity,as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts.Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway.Additionally,the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO.Conclusions In summary,our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition,reinforcing the intestinal barrier,and enhancing antioxidative and anti-inflammatory capabilities.These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.展开更多
Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal ...Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.展开更多
α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in var...α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.展开更多
The juvenile-to-adult phase change with first flowering as the indicator plays a crucial role in the lifecycle of fruit trees. However, the molecular mechanisms underlying phase change in fruit trees remain largely un...The juvenile-to-adult phase change with first flowering as the indicator plays a crucial role in the lifecycle of fruit trees. However, the molecular mechanisms underlying phase change in fruit trees remain largely unknown. Shikimic acid (ShA) pathway is a main metabolic pathway closely related to the synthesis of hormones and many important secondary metabolites participating in plant phase change. So,whether ShA regulates phase change in plants is worth clarifying. Here, the distinct morphological characteristics and the underlying mechanisms of phase change in jujube (Ziziphus jujuba Mill.), an important fruit tree native to China with nutritious fruit and outstanding tolerance abiotic stresses, were clarified. A combined transcriptome and metabolome analysis found that ShA is positively involved in jujube(Yuhong’×Xing 16’) phase change. The genes in the upstream of ShA synthesis pathway (ZjDAHPS, ZjDHQS and ZjSDH), the contents of ShA and the downstream secondary metabolites like phenols were significantly upregulated in the phase change period. Further, the treatment of spraying exogenous ShA verified that ShA at a very low concentration (60 mg·L^(-1)) can substantially speed up the phase change and flowering of jujube and other tested plants including Arabidopsis, tomato and wheat. The exogenous ShA (60 mg·L^(-1)) treatment in jujube seedlings could increase the accumulation of endogenous ShA, enhance leaf photosynthesis and the synthesis of phenols especially flavonoids and phenolic acids, and promote the expression of genes (ZjCOs, ZjNFYs and ZjPHYs) involved in flowering pathway. Basing on above results, we put forward a propose for the underlying mechanism of ShA regulating phase change, and a hypothesis that ShA could be considered a phytohormone-like substance because it is endogenous, ubiquitous, movable and highly efficient at very low concentrations. This study highlights the critical role of ShA in plant phase change and its phytohormone-like properties.展开更多
AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples...AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.展开更多
Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability o...Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.展开更多
The poor stability of RuO_(2)electrocatalysts has been the primary obstacles for their practical application in polymer electrolyte membrane electrolyzers.To dramatically enhance the durability of RuO_(2)to construct ...The poor stability of RuO_(2)electrocatalysts has been the primary obstacles for their practical application in polymer electrolyte membrane electrolyzers.To dramatically enhance the durability of RuO_(2)to construct activity-stability trade-off model is full of significance but challenging.Herein,a single atom Zn stabilized RuO_(2)with enriched oxygen vacancies(SA Zn-RuO_(2))is developed as a promising alternative to iridium oxide for acidic oxygen evolution reaction(OER).Compared with commercial RuO_(2),the enhanced Ru–O bond strength of SA Zn-RuO_(2)by forming Zn-O-Ru local structure motif is favorable to stabilize surface Ru,while the electrons transferred from Zn single atoms to adjacent Ru atoms protects the Ru active sites from overoxidation.Simultaneously,the optimized surrounding electronic structure of Ru sites in SA ZnRuO_(2)decreases the adsorption energies of OER intermediates to reduce the reaction barrier.As a result,the representative SA Zn-RuO_(2)exhibits a low overpotential of 210 mV to achieve 10 mA cm^(-2)and a greatly enhanced durability than commercial RuO_(2).This work provides a promising dual-engineering strategy by coupling single atom doping and vacancy for the tradeoff of high activity and catalytic stability toward acidic OER.展开更多
The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed ...The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.展开更多
Free amino acid(FAA)is the important component of vinegar that infl uences quality perception and consumer acceptance.FAA is one of the major metabolites produced by microorganisms;however,the microbial metabolic netw...Free amino acid(FAA)is the important component of vinegar that infl uences quality perception and consumer acceptance.FAA is one of the major metabolites produced by microorganisms;however,the microbial metabolic network on FAA biosynthesis remains unclear.Through metagenomic analysis,this work aimed to elucidate the roles of microbes in FAA biosynthesis during Monascus rice vinegar fermentation.Taxonomic profiles from functional analyses showed 14 dominant genera with high contributions to the metabolism pathways.The metabolic network for FAA biosynthesis was then constructed,and the microbial distribution in different metabolic pathways was illuminated.The results revealed that 5 functional genera were closely involved in FAA biosynthesis.This study illuminated the metabolic roles of microorganisms in FAA biosynthesis and provided crucial insights into the functional attributes of microbiota in vinegar fermentation.展开更多
基金supported by Science Research Project from the Education Department of Liaoning Province,No.L2010271
文摘In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. AIpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase.
文摘Diabetic neuropathy, the most common form of peripheral neuropathy, presents as different forms of focal or diffuse neuropathy, including the disabling, or potentially life-threatening clinical entities of painful diabetic neuropathy, autonomic neuropathy, and diabetic foot. The pathogenesis of diabetic neuropathy results from the concurrent action of various intersecting factors of nerve damage, such as oxidative stress and mitochondrial dysfunction, inflammation, microangiopathy and ischemia, triggered by hyperglycemia and related biochemical changes. Symptomatic treatment of diabetic neuropathy mainly concerns therapies for neuropathic pain, interventions targeted at the organ systems involved in autonomic neuropathy, and management of diabetic foot. Therapeutic approaches to the pathogenesis of diabetic neuropathy have focused on the different components of the causes of nerve damage, particularly oxidative stress, which has been demonstrated to play a central role. Alpha-lipoic acid, a potent lipophilic free radical scavenger, has been used in treatment of patients with diabetic neuropathy, displaying efficacy on the chief symptoms, including neuropathic pain, and showing that neuropathic deficits may be improved by treatment. Current evidence suggests a possible efficacy of alpha-lipoic acid not only for neuropathic symptoms, but also for reducing the risk factors for diabetic neuropathy.
基金Supported by International Scientific Cooperation Project of China (No.2008DFB50060)Suzhou Innovation Funds of High-Tech Enterprise (No.SG0958)
文摘Alpha-lipoic acid-loaded lipid nanoparticles(ALA-LNs) were prepared by high pressure homogenization method.The influences of storage conditions such as time and temperature on the physical and chemical storage stability of ALA-LNs were studied in details.The stability was evaluated by particle size and polydispersity index,morphology of ALA-LNs,and capacity of ALA loading.The dilution and pH stability of ALA-LNs suspensions were also studied.After three months storage,the mean size of ALA-LNs at 4 and 40 ℃ was increased by 2.68% and 3.62% compared with the original size,respectively.ALA-LNs stored at 40 ℃ had ellipsoid shape and the mean size was about 152 nm(SD=23.6).The loading capacity of ALA at 40 ℃ was much higher than those stored at other two temperatures.The good dilution and pH stability were also demonstrated.The sample had good fluidity even at 4 ℃.
文摘Alpha lipoic acid has the ability to react and neutralize reactive oxygen species (ROS) such as superoxide radicals, simple oxygen, hydroxyl radicals, hypochlorous acid and peroxyl radicals. A rapid high-performance liquid chromatographic method for determination of lipoic acid in a nutritional supplement was developed. The method involved sample preparation and the mobile phase comprised of 50 mM disodium hydrogen phosphate buffer (pH 2.5 adjusted with 1 M H<sub>3</sub>PO<sub>4</sub>): acetonitrile in the ratio of 50:50. The separation was done using a C18 column (150 mm) and detection was carried out using UV detection at 201 nm. The assay was found to be linear in the range of 1.56 - 50 μg/mL with the correlation coefficient of 0.9997. Method precision was determined while LOD was 0.05 μg/mL and LOQ 0.15 μg/mL. The chromatographic peak LA retention time was 6 min.
文摘Objective:Relevance of cardiac autonomic neuropathy has not been fully recognized and there is no standardized treatment protocol.Aim:To evaluate the effects of alpha-lipoic acid on the beat-to-beat vectorcardiographic parameters,namely spatial QRS-T angle,QT dispersion(QTd)and corrected QT interval(QTc)in type 2 diabetes mellitus persons with cardiac autonomic neuropathy.Research designs and methods:Our study involved 33 persons with definite stage of cardiac autonomic neuropathy and diabetes mellitus type 2,which were assigned to each of two groups:one took standard antihyperglycaemic treatment(n=15,control group)and the other(n=18)in addition to standard therapy-600 mg of alpha-lipoic acid daily for three months.The analysis of vectorcardiographic parameters was performed.Results:It was found out that alpha-lipoic acid contributed to decrease of the vectorcardiographic parameters,namely QRS-T angle,QTd and QTc.Conclusions:The positive influences of alpha-lipoic acid suggest the usefulness of its prescription to type 2 diabetes mellitus persons with definite stage of cardiac autonomic neuropathy.The efficacy of alpha-lipoic acid is the result of its direct effect on the parameters of vectorcardiography.
基金supported by Short Term Research Grant Scheme(304/PPSP/6131496)provided by Universiti Sains Malaysia.
文摘Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administered with Nω-nitro-L-arginine methyl ester(L-NAME).Methods:Male rats were divided into four groups(SHR,SHR+ALA,SHR+L-NAME,SHR+ALA+L-NAME).The respective group of rats was administered with ALA(100 mg/kg/day)from age 4 weeks to 28 weeks and L-NAME(25 mg/kg/day)from age 16 weeks to 28 weeks.SBP was measured every two weeks and twenty four hour urine was collected at 4 weeks,16 weeks and 28 weeks for estimation of protein,creatinine and N-acetyl-e end of 28 weeks,rats were sacrificed and blood and kidneys colα-Dglucosaminidase.At thlected for assessment of blood creatinine,kidney thiobarbituric acid reactive substances,protein carbonyls,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,glutathione S-transferase,glutathione disulfide,glutathione,total antioxidant status and nitric oxide as well as histopathological examination.Results:ALA supplementation significantly reduced SBP of SHR and SHR+L-NAME rats when compared to their respective non-supplemented groups.Renal oxidant status markers including thiobarbituric acid reactive substances and protein carbonyls were significantly reduced on SHR and SHR+L-NAME rats supplemented with ALA at 28 weeks as well as ALA supplementation significantly increased renal antioxidants including superoxide dismutase,catalase,glutathione peroxidase,glutathione S-transferase,glutathione and glutathione/glutathione disulfide ratio at 28 weeks.No significant change in nitric oxide levels was observed between the ALA supplemented and non-supplemented groups.Renal dysfunction was ameliorated on ALA supplementation as evidenced by significant reduction in urine protein levels,N-acetyl-α-D-glucosaminidase activity and significant increase of creatinine clearance in SHR and SHR+L-NAME at 28 weeks.Renal histopathological examination showed that ALA supplementation prevented vascular damage in SHR and ameliorated glomerular damage in SHR+L-NAME at 28 weeks.Conclusions:ALA has hypotensive and renoprotective effects on both SHR and SHR+LNAME,which could be due to its ability to ameliorate oxidative stress in the kidneys.
文摘Background Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant α-lipoic acid （α-LA） could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin （STZ） 45 mg/kg. Experimental animals were randomly assigned to 3 groups： normal control （NC）, diabetes （DM） and DM treated with α-LA （α-LA）. The latter group was administered with a-LA （100 mg/kg ip per day）, the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde （MDA）, reduced glutathione （GSH） and the activity of manganese superoxide diamutase （Mn-SOD） in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting Results At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by α-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while α-LA reversed this structural derangement. The index of cardiac function （±dp/dtmax） in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but α-LA delayed deterioration of cardiac function （P 〈0.05）. Conclusions Our findings indicate that the antioxidant α-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of α-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.
基金financial support from the King Abdullah University of Science and Technology(KAUST).
文摘The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving carbon neutrality is the utilization of CO_(2) under economic and sustainable conditions.Recently,the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO_(2) into carboxylic acids,which can effectively alleviate CO_(2) emissions and create high-value chemicals.The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO_(2) conversion into carboxylic acids through photo-,electric-,and thermal catalysis.Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level,inspiring the preparation of high-performance catalysts.In addition,theoretical calculations,advanced technologies,and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity.Finally,challenges and prospects are provided for the future development of this field.It is hoped that this review will contribute to a deeper understanding of the conversion of CO_(2) into carboxylic acids and inspire more innovative breakthroughs.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Precision Seed Design and Breeding,XDA24010108)National Natural Science Foundation of China(31972780&31721005)+1 种基金National Key R&D Program of China(2018YFA0801000)State Key Laboratory of Freshwater Ecology and Biotechnology(2019FBZ05)。
文摘Omega-3 polyunsaturated fatty acids(n-3 PUFAs),particularly docosahexaenoic acid(22:6n-3,DHA),play crucial roles in the reproductive health of vertebrates,including humans.Nevertheless,the underlying mechanism related to this phenomenon remains largely unknown.In this study,we employed two zebrafish genetic models,i.e.,elovl2^(-/-)mutant as an endogenous DHAdeficient model and fat1(omega-3 desaturase encoding gene)transgenic zebrafish as an endogenous DHA-rich model,to investigate the effects of DHA on oocyte maturation and quality.Results show that the elovl2^(-/-)mutants had much lower fecundity and poorer oocyte quality than the wild-type controls,while the fat1 zebrafish had higher fecundity and better oocyte quality than wildtype controls.DHA deficiency in elovl2^(-/-)embryos led to defects in egg activation,poor microtubule stability,and reduced pregnenolone levels.Further study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1,which encodes the cholesterol side-chain cleavage enzyme,thereby stabilizing microtubule assembly during oogenesis.In turn,the hypothalamic-pituitary-gonadal axis was enhanced by DHA.In conclusion,using two unique genetic models,our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.
基金The Guangdong Basic and Applied Basic Research Foundation(2022A1515010730)National Natural Science Foundation of China(32001647)+2 种基金National Natural Science Foundation of China(31972022)Financial and moral assistance supported by the Guangdong Basic and Applied Basic Research Foundation(2019A1515011996)111 Project(B17018)。
文摘In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.
基金supported by the National Natural Science Foundation of China (Grant Nos.31902057 and 32072615)Zhejiang Provincial Natural Science Foundation of China (Grant No.LQ19C160012)the key research and development program of Zhejiang Province (Grant No.2021C02071)。
文摘Sweet osmanthus(Osmanthus fragrans) is a having general approval aromatic tree in China that is widely applied to landscaping and gardening. However, the evergreen tree adaptability is limited by many environmental stresses. Currently, limited information is available regarding the genetic analysis and functional identification of expansin genes in response to abiotic stress in sweet osmanthus. In this study, a total of 29 expansin genes were identified and divided into four groups by genome-wide analysis from the sweet osmanthus genome. Transcriptome and quantitative Real-time PCR analysis showed that the cell wall-localized protein expansin-like A(OfEXLA1) gene was significantly induced by salt and drought treatment. Histochemical GUS staining of transgenic Arabidopsis lines in which GUS activity was driven with the OfEXLA1 promoter, GUS activity was significantly induced by salt, drought, and exogenous abscisic acid(ABA). In yeast, we found OfEXLA1overexpression significantly improved the population of cells compared with wild-type strains after NaCl and polyethylene glycol(PEG)treatment. Additionally, OfEXLA1 overexpression not only promoted plant growth, but also improved the salt and drought tolerance in Arabidopsis. To gain insight into the role of ABA signaling in the regulation of OfEXLA1 improving abiotic tolerance in sweet osmanthus, four differentially expressed ABA Insensitive 5(ABI5)-like genes(OfABL4, OfABL5, OfABL7, and OfABL8) were identified from transcriptome, and dualluciferase(dual-LUC) and yeast one hybrid(Y1H) assay showed that OfABL4 and OfABL5 might bind to OfEXLA1 promoter to accumulate the OfEXLA1 expression by responding to ABA signaling to improve abiotic tolerance in sweet osmanthus. These results provide the information for understanding the molecular functions of expansin-like A gene and molecular breeding of sweet osmanthus in future.
基金supported by the National Key Research and Development Program(2021YFD1300400)Natural Science Foundation of Guangdong Province(2021A1515010944)Science and Technology Projects in Guangzhou(202201011730).
文摘Background The benefits of combining benzoic acid and essential oils(BAO)to mitigate intestinal impairment during the weaning process have been well established,while the detailed underlying mechanism has not been fully elucidated.Previous research has primarily focused on the reparative effects of BAO on intestinal injury,while neglecting its potential in enhancing intestinal stress resistance.Methods In this study,we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure.Piglets were pre-supplemented with BAO for 14 d,followed by a challenge with LPS or saline to collect blood and intestinal samples.Results Our findings demonstrated that BAO supplementation led to significant improvements in piglets’final weight,average daily gain,and feed intake/body gain ratio.Additionally,BAO supplementation positively influenced the composition of intestinal microbiota,increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota,Prevotella and Oscillospira.Furthermore,BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge.This was evidenced by elevated levels of T-AOC,SOD,and GSH,as well as decreased levels of MDA,TNF-α,and IL-6 in the plasma.Moreover,piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity,as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts.Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway.Additionally,the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO.Conclusions In summary,our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition,reinforcing the intestinal barrier,and enhancing antioxidative and anti-inflammatory capabilities.These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.
基金supported by Fujian Provincial Natural Science(2020J01122587)National Natural Science Foundation of China(82103355,82102255,and 82222901)+1 种基金RGC Theme-based Research Scheme(T12-703/19-R)Research grants Council-General Research Fund(14117422 and 14117123)。
文摘Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.
基金supported by the General Research Fund of Hong Kong (14105820)。
文摘α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.
基金partially supported by the National Natural Science Foundation of China (Grant No.31772285)the National Key R&D Program Project Funding (Grant No.2018YFD1000607)Foundation for 100 Innovative Talents of Hebei Province(Grant No.SLRC2019031)。
文摘The juvenile-to-adult phase change with first flowering as the indicator plays a crucial role in the lifecycle of fruit trees. However, the molecular mechanisms underlying phase change in fruit trees remain largely unknown. Shikimic acid (ShA) pathway is a main metabolic pathway closely related to the synthesis of hormones and many important secondary metabolites participating in plant phase change. So,whether ShA regulates phase change in plants is worth clarifying. Here, the distinct morphological characteristics and the underlying mechanisms of phase change in jujube (Ziziphus jujuba Mill.), an important fruit tree native to China with nutritious fruit and outstanding tolerance abiotic stresses, were clarified. A combined transcriptome and metabolome analysis found that ShA is positively involved in jujube(Yuhong’×Xing 16’) phase change. The genes in the upstream of ShA synthesis pathway (ZjDAHPS, ZjDHQS and ZjSDH), the contents of ShA and the downstream secondary metabolites like phenols were significantly upregulated in the phase change period. Further, the treatment of spraying exogenous ShA verified that ShA at a very low concentration (60 mg·L^(-1)) can substantially speed up the phase change and flowering of jujube and other tested plants including Arabidopsis, tomato and wheat. The exogenous ShA (60 mg·L^(-1)) treatment in jujube seedlings could increase the accumulation of endogenous ShA, enhance leaf photosynthesis and the synthesis of phenols especially flavonoids and phenolic acids, and promote the expression of genes (ZjCOs, ZjNFYs and ZjPHYs) involved in flowering pathway. Basing on above results, we put forward a propose for the underlying mechanism of ShA regulating phase change, and a hypothesis that ShA could be considered a phytohormone-like substance because it is endogenous, ubiquitous, movable and highly efficient at very low concentrations. This study highlights the critical role of ShA in plant phase change and its phytohormone-like properties.
文摘AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.
基金supported by fund from the National Natural Science Foundation of China(32172322)。
文摘Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.
基金supported by the Taishan Scholar Program of Shandong Province,China (tsqn202211162)the National Natural Science Foundation of China (22102079)the Natural Science Foundation of Shandong Province of China (ZR2021YQ10,ZR2022QB163)。
文摘The poor stability of RuO_(2)electrocatalysts has been the primary obstacles for their practical application in polymer electrolyte membrane electrolyzers.To dramatically enhance the durability of RuO_(2)to construct activity-stability trade-off model is full of significance but challenging.Herein,a single atom Zn stabilized RuO_(2)with enriched oxygen vacancies(SA Zn-RuO_(2))is developed as a promising alternative to iridium oxide for acidic oxygen evolution reaction(OER).Compared with commercial RuO_(2),the enhanced Ru–O bond strength of SA Zn-RuO_(2)by forming Zn-O-Ru local structure motif is favorable to stabilize surface Ru,while the electrons transferred from Zn single atoms to adjacent Ru atoms protects the Ru active sites from overoxidation.Simultaneously,the optimized surrounding electronic structure of Ru sites in SA ZnRuO_(2)decreases the adsorption energies of OER intermediates to reduce the reaction barrier.As a result,the representative SA Zn-RuO_(2)exhibits a low overpotential of 210 mV to achieve 10 mA cm^(-2)and a greatly enhanced durability than commercial RuO_(2).This work provides a promising dual-engineering strategy by coupling single atom doping and vacancy for the tradeoff of high activity and catalytic stability toward acidic OER.
基金supported by National Natural Science Foundation of China(Nos.31871861 and 31501548)The Apicultural Industry Technology System(NCYTI-43-KXJ17)The Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2015-IAR)。
文摘The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.
基金The authors are grateful for the financial support from National Natural Science Foundation of China(32001728).
文摘Free amino acid(FAA)is the important component of vinegar that infl uences quality perception and consumer acceptance.FAA is one of the major metabolites produced by microorganisms;however,the microbial metabolic network on FAA biosynthesis remains unclear.Through metagenomic analysis,this work aimed to elucidate the roles of microbes in FAA biosynthesis during Monascus rice vinegar fermentation.Taxonomic profiles from functional analyses showed 14 dominant genera with high contributions to the metabolism pathways.The metabolic network for FAA biosynthesis was then constructed,and the microbial distribution in different metabolic pathways was illuminated.The results revealed that 5 functional genera were closely involved in FAA biosynthesis.This study illuminated the metabolic roles of microorganisms in FAA biosynthesis and provided crucial insights into the functional attributes of microbiota in vinegar fermentation.
