Aqueous zinc-ion hybrid capacitors(ZIHCs)are promising electrochemical energy storage systems with advantages of high-energy density,low cost,safety and environmental friendliness.However,application of carbon-based c...Aqueous zinc-ion hybrid capacitors(ZIHCs)are promising electrochemical energy storage systems with advantages of high-energy density,low cost,safety and environmental friendliness.However,application of carbon-based cathodes is limited by their low-energy density due to the lack of active sites.Herein,a chemisorption sites modulating strategy is proposed to construct nitrogen-doped polyimide carbon nanoflowers with abundant oxygen vacancies and carbonyl functionalization via high-temperature calcination and subsequent acid processing.The synergistic effect of oxygen vacancies,carbonyl groups,enhanced surface area and porous structure enables stable zinc-ion storage with high capacity.Remarkably,the carbon materials can circulate 20,000 cycles stably at a current density of 2 A·g^(-1).After 10,000 cycles at a high rate of 3 A·g^(-1),a capacity retention rate of 64%can still be achieved.The as-prepared ZIHCs provide an energy density of 65.61 Wh·kg^(-1)at the power density of 197.82 W·kg^(-1).Current research shows that polyimide-derived carbon material synthesized by acid activation provides a new idea for developing cathodes in aqueous ZIHCs.展开更多
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th...The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.展开更多
The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke ...The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to ...A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
Sulfur-doped iron-cobalt tannate nanorods(S-FeCoTA)derived from metal-organic frameworks(MOFs)as electrocatalysts were synthesized via a one-step hydrothermal method.The optimized S-FeCoTA was interlaced by loose nano...Sulfur-doped iron-cobalt tannate nanorods(S-FeCoTA)derived from metal-organic frameworks(MOFs)as electrocatalysts were synthesized via a one-step hydrothermal method.The optimized S-FeCoTA was interlaced by loose nanorods,which had many voids.The S-FeCoTA catalysts exhibited excellent electrochemical oxygen evolution reaction(OER)performance with a low overpotential of 273 mV at 10 mA·cm^(-2)and a small Tafel slope of 36 mV·dec^(-1)in 1 mol·L^(-1)KOH.The potential remained at 1.48 V(vs RHE)at 10 mA·cm^(-2)under continuous testing for 15 h,implying that S-FeCoTA had good stability.The Faraday efficiency of S-FeCoTA was 94%.The outstanding OER activity of S-FeCoTA is attributed to the synergistic effects among S,Fe,and Co,thus promoting electron transfer,reducing the reaction kinetic barrier,and enhancing the OER performance.展开更多
Fatty acids are the main constituents of vegetable oils.To determine the fatty acid compositions of small trade vegetable oils and some less well studied beneficial vegetable oils,and investigate their relationships w...Fatty acids are the main constituents of vegetable oils.To determine the fatty acid compositions of small trade vegetable oils and some less well studied beneficial vegetable oils,and investigate their relationships with antioxidant activity and oxidative stability,gas chromatography-mass spectrometry was performed to characterize the associated fatty acid profiles.The antioxidant activity of vegetable oils,based on their DPPH-scavenging capacity(expressed as IC_(50) values),was used to assess their impact on human health,and their oxidative stability was characterized by performing lipid oxidation analysis to determine the oxidative induction time of fats and oils.In addition,correlation analyses were performed to examine associations between the fatty acid composition of the oils and DPPH-scavenging capacity and oxidative stability.The results revealed that among the assessed oils,coffee seed oil has the highest saturated fatty acid content(355.10 mg/g),whereas Garddenia jaminoides oil has the highest unsaturated fatty acid content(844.84 mg/g).Coffee seed oil was also found have the lowest DPPH IC_(50) value(2.30 mg/mL)and the longest oxidation induction time(17.09 h).Correlation analysis revealed a significant linear relationship(P<0.05)between oxidative stability and unsaturated fatty acid content,with lower contents tending to be associated with better oxidative stability.The findings of this study provide reference data for the screening of functional edible vegetable oils.展开更多
Mineral fulvic acid(MFA)was used as an eco-friendly pyrite depressant to recover chalcopyrite by flotation with the use of the butyl xanthate as a collector.Flotation experiments showed that MFA produced a stronger in...Mineral fulvic acid(MFA)was used as an eco-friendly pyrite depressant to recover chalcopyrite by flotation with the use of the butyl xanthate as a collector.Flotation experiments showed that MFA produced a stronger inhibition effect on pyrite than on chalcopyrite.The separation of chalcopyrite from pyrite was realized by introducing 150 mg/L MFA at a pulp pH of approximately 8.0.The copper grade,copper recovery,and separation efficiency were 28.03%,84.79%,and 71.66%,respectively.Surface adsorption tests,zeta potential determinations,and localized electrochemical impedance spectroscopy tests showed that more MFA adsorbed on pyrite than on chalcopyrite,which weakened the subsequent interactions between pyrite and the collector.Atomic force microscope imaging further confirmed the adsorption of MFA on pyrite,and X-ray photoelectron spectroscopy results indicated that hydrophilic Fe-based species on the pyrite surfaces increased after exposure of pyrite to MFA,thereby decreasing the floatability of pyrite.展开更多
The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase ge...The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase gene family member OsCHI3 participates in rice responses to drought stress through the regulation of flavonoid biosynthesis.Overexpression of OsCHI3 increased the tolerance of rice to drought stress.In contrast,CRISPR/Cas9-mediated deletion of OsCHI3 reduced the drought tolerance of rice,an effect that is reversed by exogenous ABA treatment.Transcriptomic and physiological biochemical analyses indicated that flavonoids regulated by OsCHI3 not only scavenge reactive oxygen species(ROS)but also increase drought tolerance in rice by stimulating ABA biosynthesis through the regulation of OsNCED1 and OsABA8ox3 expression.These findings demonstrate that OsCHI3 increases drought stress tolerance in rice by activating the antioxidant defense system and the ABA metabolic pathway,providing new clues for drought-resistant rice breeding research.展开更多
Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic ...Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.展开更多
Pyrrolizidine alkaloids(PAs)and their N-oxides(PANOs)are phytotoxins produced by various plant species and have been emerged as environmental pollutants.The sorption/desorption behaviors of PAs/PANOs in soil are cruci...Pyrrolizidine alkaloids(PAs)and their N-oxides(PANOs)are phytotoxins produced by various plant species and have been emerged as environmental pollutants.The sorption/desorption behaviors of PAs/PANOs in soil are crucial due to the horizontal transfer of these natural products from PA-producing plants to soil and subsequently absorbed by plant roots.This study firstly investigated the sorption/desorption behaviors of PAs/PANOs in tea plantation soils with distinct characteristics.Sorption amounts for seneciphylline(Sp)and seneciphylline-N-oxide(SpNO)in three acidic soils ranged from 2.9 to 5.9μg/g and 1.7 to 2.8μg/g,respectively.Desorption percentages for Sp and SpNO were from 22.2%to 30.5%and 36.1%to 43.9%.In the mixed PAs/PANOs systems,stronger sorption of PAs over PANOs was occurred in tested soils.Additionally,the Freundlich models more precisely described the sorption/desorption isotherms.Cation exchange capacity,sand content and total nitrogen were identified as major influencing factors by linear regression models.Overall,the soils exhibiting higher sorption capacities for compounds with greater hydrophobicity.PANOs were more likely to migrate within soils and be absorbed by tea plants.It contributes to the understanding of environmental fate of PAs/PANOs in tea plantations and provides basic data and clues for the development of PAs/PANOs reduction technology.展开更多
Background Meat originating from the spent hen is an important source of poultry meat production;however,multiple factors cause the decline in the meat quality of spent hens.Chinese herbs have been widely used as medi...Background Meat originating from the spent hen is an important source of poultry meat production;however,multiple factors cause the decline in the meat quality of spent hens.Chinese herbs have been widely used as medi-cine for a long time to prevent diseases and as nutrient supplements to improve the product quality.This experi-ment explored the effects of adding 1.0%Chinese herbal formula(CHF,including 0.30%Leonurus japonicus Houtt.,0.20%Salvia miltiorrhiza Bge.,0.25%Ligustrum lucidum Ait.,and 0.25%Taraxacum mongolicum Hand.-Mazz.)for 120 d to the spent hens’diet through metabolomics,network pharmacology,and microbiome strategies.Results The results indicated that CHF supplementation improved the meat quality by reducing drip loss(P<0.05),b*value(P=0.058),and shear force(P=0.099)and increasing cooked meat percentage(P=0.054)and dry matter(P<0.05)of breast muscle.The addition of CHF improved the nutritional value of breast muscle by increasing(P<0.05)the content of C18:2n-6,n-6/n-3 polyunsaturated fatty acids(PUFA),total PUFA,PUFA-to-saturated fatty acids(SFA)ratio,and hypocholesterolemic-to-hypercholesterolemic ratio,and tending to increase serine content(P=0.069).The targeted metabolomics analysis revealed that the biosynthesis of SFA,linoleic acid metabolism,fatty acid degradation,fatty acid elongation,and fatty acid biosynthesis pathways were enriched by CHF supplementation.Furthermore,the network pharmacology analysis indicated that CHF was closely associated with oxidative stress and lipid metabo-lism.The CHF supplementation increased the glutathione peroxidase level(P<0.05)and upregulated gene expres-sion related to the Nrf2 pathway(including HO-1,P<0.05;Nrf2,P=0.098;CAT,P=0.060;GPX1,P=0.063;and SOD2,P=0.052)and lipid metabolism(including PPARγ,P<0.05;SREBP1,P=0.059;and CPT1A,P=0.058).Additionally,CHF supplementation increased Firmicutes and decreased Bacteroidetes,Spirochaetes,and Synergistetes abundances(P<0.05),which may contribute to better meat quality.Conclusions Our results suggest that CHF supplementation improved the quality and nutritional value of meat,which will provide a theoretical basis for the utilization of CHF as a feed additive in spent hens’diets.展开更多
The persistent stability of ruthenium dioxide(RuO_(2))in acidic oxygen evolution reactions(OER)is compromised by the involvement of lattice oxygen(LO)and metal dissolution during the OER process.Heteroatom doping has ...The persistent stability of ruthenium dioxide(RuO_(2))in acidic oxygen evolution reactions(OER)is compromised by the involvement of lattice oxygen(LO)and metal dissolution during the OER process.Heteroatom doping has been recognized as a viable strategy to foster the stability of RuO_(2)for acidic OER applications.This study presented an ion that does not readily gain or lose electrons,Ba^(2+),into RuO_(2)(Ba-RuO_(2))nanosheet(NS)catalyst that increased the number of exposed active sites,achieving a current density of 10 mA/cm^(2)with an overpotential of only 229 mV and sustaining this output for over 250 h.According to density functional theory(DFT)and X-ray absorption spectroscopy,Ba doping resulted in a longer Ru-O bond length,which in turn diminished the covalency of the bond.This alteration curtailed the involvement of LO and the dissolution of ruthenium(Ru),thereby markedly improving the durability of the catalyst over extended periods.Additionally,attenuated total reflectance-surface enhanced infrared absorption spectroscopy analysis substantiated that the OER mechanism shifted from a LO-mediated pathway to an adsorbate evolution pathway due to Ba doping,thereby circumventing Ru over-oxidation and further enhancing the stability of RuO_(2).Furthermore,DFT findings uncovered that Ba doping optimizes the adsorption energy of intermediates,thus enhancing the OER activity in acidic environments.This study offers a potent strategy to guide future developments on Ru-based oxide catalysts'stability in an acidic environment.展开更多
Stroke,a major cerebrovascular disease,has high morbidity and mortality.Effective methods to reduce the risk and improve the prognosis are lacking.Currently,uric acid(UA)is associated with the pathological mechanism,p...Stroke,a major cerebrovascular disease,has high morbidity and mortality.Effective methods to reduce the risk and improve the prognosis are lacking.Currently,uric acid(UA)is associated with the pathological mechanism,prognosis,and therapy of stroke.UA plays pro/anti-oxidative and pro-inflammatory roles in vivo.The specific role of UA in stroke,which may have both neuroprotective and damaging effects,remains unclear.There is a U-shaped association between serum uric acid(SUA)levels and ischemic stroke(IS).UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke(AIS).Urate-lowering therapy(ULT)plays a protective role in IS with hyperuricemia or gout.SUA levels are associated with the cerebrovascular injury mechanism,risk,and outcomes of hemorrhagic stroke.In this review,we summarize the current research on the role of UA in stroke,providing potential targets for its prediction and treatment.展开更多
Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,ma...Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.展开更多
Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clost...Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.展开更多
基金supported by the National Natural Science Foundation of China(Nos.52272211 and 52072145)the Funding of Jilin Province Development and Reform Commission(Nos.2024C018-11 and 2020C026-2)+3 种基金the Scientific and Technological Developing Project of Jilin Province(Nos.20230508046RC,20240602023RC,YDZJ202101ZYTS185 and YDZJ202201ZYTS372)Jilin Talent Development Funding(No.2021Y027)the Funds for Special Projects of the Central Government in Guidance of Local Science and Technology Development(No.202002017JC)the Research Program on Science and Technology from the Education Department of Jilin Province(Nos.JJKH20220439KJ and JJKH20210550KJ).
文摘Aqueous zinc-ion hybrid capacitors(ZIHCs)are promising electrochemical energy storage systems with advantages of high-energy density,low cost,safety and environmental friendliness.However,application of carbon-based cathodes is limited by their low-energy density due to the lack of active sites.Herein,a chemisorption sites modulating strategy is proposed to construct nitrogen-doped polyimide carbon nanoflowers with abundant oxygen vacancies and carbonyl functionalization via high-temperature calcination and subsequent acid processing.The synergistic effect of oxygen vacancies,carbonyl groups,enhanced surface area and porous structure enables stable zinc-ion storage with high capacity.Remarkably,the carbon materials can circulate 20,000 cycles stably at a current density of 2 A·g^(-1).After 10,000 cycles at a high rate of 3 A·g^(-1),a capacity retention rate of 64%can still be achieved.The as-prepared ZIHCs provide an energy density of 65.61 Wh·kg^(-1)at the power density of 197.82 W·kg^(-1).Current research shows that polyimide-derived carbon material synthesized by acid activation provides a new idea for developing cathodes in aqueous ZIHCs.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
基金supported by MICIU(grant number PID2021-128133NB-100/AEI/FEDER10.13039/501100011033 to JMHG)by the National Institutes of Health(grant number R01 NS083858 to SAK)+1 种基金the Intramural Grants Program IGPP00057(to SAK)VIC enjoys a FPU contract from the Comunidad de Madrid(PIPF-2022/SAL-GL-25948)。
文摘The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金supported by the Army Laboratory Animal Foundation of China,No.SYDW[2020]22(to TC)the Shaanxi Provincial Key R&D Plan General Project of China,No.2022SF-236(to YM)the National Natural Science Foundation of China,No.82202070(to TC)。
文摘A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain unclear.Therefore,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity.After 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic cells.To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension.The results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly upregulated.In addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated weightlessness.These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
文摘Sulfur-doped iron-cobalt tannate nanorods(S-FeCoTA)derived from metal-organic frameworks(MOFs)as electrocatalysts were synthesized via a one-step hydrothermal method.The optimized S-FeCoTA was interlaced by loose nanorods,which had many voids.The S-FeCoTA catalysts exhibited excellent electrochemical oxygen evolution reaction(OER)performance with a low overpotential of 273 mV at 10 mA·cm^(-2)and a small Tafel slope of 36 mV·dec^(-1)in 1 mol·L^(-1)KOH.The potential remained at 1.48 V(vs RHE)at 10 mA·cm^(-2)under continuous testing for 15 h,implying that S-FeCoTA had good stability.The Faraday efficiency of S-FeCoTA was 94%.The outstanding OER activity of S-FeCoTA is attributed to the synergistic effects among S,Fe,and Co,thus promoting electron transfer,reducing the reaction kinetic barrier,and enhancing the OER performance.
文摘Fatty acids are the main constituents of vegetable oils.To determine the fatty acid compositions of small trade vegetable oils and some less well studied beneficial vegetable oils,and investigate their relationships with antioxidant activity and oxidative stability,gas chromatography-mass spectrometry was performed to characterize the associated fatty acid profiles.The antioxidant activity of vegetable oils,based on their DPPH-scavenging capacity(expressed as IC_(50) values),was used to assess their impact on human health,and their oxidative stability was characterized by performing lipid oxidation analysis to determine the oxidative induction time of fats and oils.In addition,correlation analyses were performed to examine associations between the fatty acid composition of the oils and DPPH-scavenging capacity and oxidative stability.The results revealed that among the assessed oils,coffee seed oil has the highest saturated fatty acid content(355.10 mg/g),whereas Garddenia jaminoides oil has the highest unsaturated fatty acid content(844.84 mg/g).Coffee seed oil was also found have the lowest DPPH IC_(50) value(2.30 mg/mL)and the longest oxidation induction time(17.09 h).Correlation analysis revealed a significant linear relationship(P<0.05)between oxidative stability and unsaturated fatty acid content,with lower contents tending to be associated with better oxidative stability.The findings of this study provide reference data for the screening of functional edible vegetable oils.
基金supported by Fundamental Research Projects of Yunnan Province,China(Nos.202101BE070001-009,202301AU070189).
文摘Mineral fulvic acid(MFA)was used as an eco-friendly pyrite depressant to recover chalcopyrite by flotation with the use of the butyl xanthate as a collector.Flotation experiments showed that MFA produced a stronger inhibition effect on pyrite than on chalcopyrite.The separation of chalcopyrite from pyrite was realized by introducing 150 mg/L MFA at a pulp pH of approximately 8.0.The copper grade,copper recovery,and separation efficiency were 28.03%,84.79%,and 71.66%,respectively.Surface adsorption tests,zeta potential determinations,and localized electrochemical impedance spectroscopy tests showed that more MFA adsorbed on pyrite than on chalcopyrite,which weakened the subsequent interactions between pyrite and the collector.Atomic force microscope imaging further confirmed the adsorption of MFA on pyrite,and X-ray photoelectron spectroscopy results indicated that hydrophilic Fe-based species on the pyrite surfaces increased after exposure of pyrite to MFA,thereby decreasing the floatability of pyrite.
基金supported by Science and Technology Innovation Program of Hunan province(2024NK1010,2023NK1010,2023ZJ1080)the National Natural Science Foundation of China(U21A20208).
文摘The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase gene family member OsCHI3 participates in rice responses to drought stress through the regulation of flavonoid biosynthesis.Overexpression of OsCHI3 increased the tolerance of rice to drought stress.In contrast,CRISPR/Cas9-mediated deletion of OsCHI3 reduced the drought tolerance of rice,an effect that is reversed by exogenous ABA treatment.Transcriptomic and physiological biochemical analyses indicated that flavonoids regulated by OsCHI3 not only scavenge reactive oxygen species(ROS)but also increase drought tolerance in rice by stimulating ABA biosynthesis through the regulation of OsNCED1 and OsABA8ox3 expression.These findings demonstrate that OsCHI3 increases drought stress tolerance in rice by activating the antioxidant defense system and the ABA metabolic pathway,providing new clues for drought-resistant rice breeding research.
文摘Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.
基金supported by the earmarked fund for the Modern Agro-Industry Technology Research System (No.CARS-19)the Innovative Research Team in Chinese Academy of Agricultural Sciences (No.CAAS ASTIP-2014-TRICAAS).
文摘Pyrrolizidine alkaloids(PAs)and their N-oxides(PANOs)are phytotoxins produced by various plant species and have been emerged as environmental pollutants.The sorption/desorption behaviors of PAs/PANOs in soil are crucial due to the horizontal transfer of these natural products from PA-producing plants to soil and subsequently absorbed by plant roots.This study firstly investigated the sorption/desorption behaviors of PAs/PANOs in tea plantation soils with distinct characteristics.Sorption amounts for seneciphylline(Sp)and seneciphylline-N-oxide(SpNO)in three acidic soils ranged from 2.9 to 5.9μg/g and 1.7 to 2.8μg/g,respectively.Desorption percentages for Sp and SpNO were from 22.2%to 30.5%and 36.1%to 43.9%.In the mixed PAs/PANOs systems,stronger sorption of PAs over PANOs was occurred in tested soils.Additionally,the Freundlich models more precisely described the sorption/desorption isotherms.Cation exchange capacity,sand content and total nitrogen were identified as major influencing factors by linear regression models.Overall,the soils exhibiting higher sorption capacities for compounds with greater hydrophobicity.PANOs were more likely to migrate within soils and be absorbed by tea plants.It contributes to the understanding of environmental fate of PAs/PANOs in tea plantations and provides basic data and clues for the development of PAs/PANOs reduction technology.
基金supported by the National Key Research and Development Project(2022YFC3400700)the City-School Cooperation Project of the Fuyang Science and Technology Special Fund undertaken by Fuyang Normal University(SXHZ2020007)+1 种基金the Basic Research Program of Shenzhen Municipal Government(JCYJ20200109114242138)the Special Commissioner for Rural Science and Technology of Guangdong Province(KTP20210345).
文摘Background Meat originating from the spent hen is an important source of poultry meat production;however,multiple factors cause the decline in the meat quality of spent hens.Chinese herbs have been widely used as medi-cine for a long time to prevent diseases and as nutrient supplements to improve the product quality.This experi-ment explored the effects of adding 1.0%Chinese herbal formula(CHF,including 0.30%Leonurus japonicus Houtt.,0.20%Salvia miltiorrhiza Bge.,0.25%Ligustrum lucidum Ait.,and 0.25%Taraxacum mongolicum Hand.-Mazz.)for 120 d to the spent hens’diet through metabolomics,network pharmacology,and microbiome strategies.Results The results indicated that CHF supplementation improved the meat quality by reducing drip loss(P<0.05),b*value(P=0.058),and shear force(P=0.099)and increasing cooked meat percentage(P=0.054)and dry matter(P<0.05)of breast muscle.The addition of CHF improved the nutritional value of breast muscle by increasing(P<0.05)the content of C18:2n-6,n-6/n-3 polyunsaturated fatty acids(PUFA),total PUFA,PUFA-to-saturated fatty acids(SFA)ratio,and hypocholesterolemic-to-hypercholesterolemic ratio,and tending to increase serine content(P=0.069).The targeted metabolomics analysis revealed that the biosynthesis of SFA,linoleic acid metabolism,fatty acid degradation,fatty acid elongation,and fatty acid biosynthesis pathways were enriched by CHF supplementation.Furthermore,the network pharmacology analysis indicated that CHF was closely associated with oxidative stress and lipid metabo-lism.The CHF supplementation increased the glutathione peroxidase level(P<0.05)and upregulated gene expres-sion related to the Nrf2 pathway(including HO-1,P<0.05;Nrf2,P=0.098;CAT,P=0.060;GPX1,P=0.063;and SOD2,P=0.052)and lipid metabolism(including PPARγ,P<0.05;SREBP1,P=0.059;and CPT1A,P=0.058).Additionally,CHF supplementation increased Firmicutes and decreased Bacteroidetes,Spirochaetes,and Synergistetes abundances(P<0.05),which may contribute to better meat quality.Conclusions Our results suggest that CHF supplementation improved the quality and nutritional value of meat,which will provide a theoretical basis for the utilization of CHF as a feed additive in spent hens’diets.
基金supported by Young Project of Education Department in Guizhou Province(No.2022099)the Natural Science Special of Guizhou University(No.X202220 Special Post A)the National Natural Science Foundation of China(Grant No.22208071)。
文摘The persistent stability of ruthenium dioxide(RuO_(2))in acidic oxygen evolution reactions(OER)is compromised by the involvement of lattice oxygen(LO)and metal dissolution during the OER process.Heteroatom doping has been recognized as a viable strategy to foster the stability of RuO_(2)for acidic OER applications.This study presented an ion that does not readily gain or lose electrons,Ba^(2+),into RuO_(2)(Ba-RuO_(2))nanosheet(NS)catalyst that increased the number of exposed active sites,achieving a current density of 10 mA/cm^(2)with an overpotential of only 229 mV and sustaining this output for over 250 h.According to density functional theory(DFT)and X-ray absorption spectroscopy,Ba doping resulted in a longer Ru-O bond length,which in turn diminished the covalency of the bond.This alteration curtailed the involvement of LO and the dissolution of ruthenium(Ru),thereby markedly improving the durability of the catalyst over extended periods.Additionally,attenuated total reflectance-surface enhanced infrared absorption spectroscopy analysis substantiated that the OER mechanism shifted from a LO-mediated pathway to an adsorbate evolution pathway due to Ba doping,thereby circumventing Ru over-oxidation and further enhancing the stability of RuO_(2).Furthermore,DFT findings uncovered that Ba doping optimizes the adsorption energy of intermediates,thus enhancing the OER activity in acidic environments.This study offers a potent strategy to guide future developments on Ru-based oxide catalysts'stability in an acidic environment.
基金supported by the National Natural Science Foundation of China(82371300)Zhejiang Provincial Natural Science Foundation of China(LY23H090014)Zhejiang Province Traditional Chinese Medicine Science and Technology Project(2024ZL1215).
文摘Stroke,a major cerebrovascular disease,has high morbidity and mortality.Effective methods to reduce the risk and improve the prognosis are lacking.Currently,uric acid(UA)is associated with the pathological mechanism,prognosis,and therapy of stroke.UA plays pro/anti-oxidative and pro-inflammatory roles in vivo.The specific role of UA in stroke,which may have both neuroprotective and damaging effects,remains unclear.There is a U-shaped association between serum uric acid(SUA)levels and ischemic stroke(IS).UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke(AIS).Urate-lowering therapy(ULT)plays a protective role in IS with hyperuricemia or gout.SUA levels are associated with the cerebrovascular injury mechanism,risk,and outcomes of hemorrhagic stroke.In this review,we summarize the current research on the role of UA in stroke,providing potential targets for its prediction and treatment.
基金supported by National Key R&D Program of China(2023YFD1301200)China Agriculture Research Systems(CARS-40-K11)+2 种基金Beijing Agriculture Innovation Consortium(BAIC06-2024-G05)Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(NCTIP-XD/C08)The Chinese Academy of Agricultural Science and Technology Innovation Project(ASTIP-IAS-12)。
文摘Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.
基金supported by China Agriculture Research System Program(Project No.CARS-41-G04)。
文摘Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.
