Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the ser...Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.展开更多
Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Alt...Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.展开更多
Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)an...Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)and two-dimensional carbide and nitride(MXene)with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy.A light-activated virtual sensor array(LAVSA)based on BP/Ti_(3)C_(2)Tx was prepared under photomodulation and further assembled into an instant gas sensing platform(IGSP).In addition,a machine learning(ML)algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD.Due to the synergistic effect of BP and Ti_(3)C_(2)Tx as well as photo excitation,the synthesized heterostructured complexes exhibited higher performance than pristine Ti_(3)C_(2)Tx,with a response value 26%higher than that of pristine Ti_(3)C_(2)Tx.In addition,with the help of a pattern recognition algorithm,LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols,ketones,aldehydes,esters,and acids.Meanwhile,with the assistance of ML,the IGSP achieved 69.2%accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients.In conclusion,an immediate,low-cost,and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD,which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.展开更多
Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder patient...Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder patients.One report showed that global deaths from CVD increased from 12.4 million in 1990 to 19.8 million in 2022,reflecting the global population growth and aging,as well as the impact of metabolic,environmental,and behavioral risks.[1]With the progress of aging population,the burden of CVD in the elderly in China has increased year by year,and factors including multiple complications,organ function decline,and high complication rate have made the interventional treatment of CVD in the elderly one of the difficulties and focuses in the field of cardiology in China.展开更多
Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease...Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.展开更多
Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammat...Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammation and anti-oxidation functions,and improving mitochondrial quality.Chronic diseases as non-communicable diseases are mainly caused by multiple factors,such as physiological decline and dysfunction in the body,and have become a significant challenge on public health worldwide.It is worth noting that chronic diseases such as Alzheimer's disease(AD),Parkinson's disease(PD),muscle atrophy,cardiovascular disease,obesity,and cancer are accompanied by abnormal mitochondrial function.Therefore,targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases.Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria,and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions.In this article,current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized,which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediati...Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.展开更多
Today,with the rapid development of the internet,a large amount of information often accompanies the rapid transmission of disease outbreaks,and increasing numbers of scholars are studying the relationship between inf...Today,with the rapid development of the internet,a large amount of information often accompanies the rapid transmission of disease outbreaks,and increasing numbers of scholars are studying the relationship between information and the disease transmission process using complex networks.In fact,the disease transmission process is very complex.Besides this information,there will often be individual behavioral measures and other factors to consider.Most of the previous research has aimed to establish a two-layer network model to consider the impact of information on the transmission process of disease,rarely divided into information and behavior,respectively.To carry out a more in-depth analysis of the disease transmission process and the intrinsic influencing mechanism,this paper divides information and behavior into two layers and proposes the establishment of a complex network to study the dynamic co-evolution of information diffusion,vaccination behavior,and disease transmission.This is achieved by considering four influential relationships between adjacent layers in multilayer networks.In the information layer,the diffusion process of negative information is described,and the feedback effects of local and global vaccination are considered.In the behavioral layer,an individual's vaccination behavior is described,and the probability of an individual receiving a vaccination is influenced by two factors:the influence of negative information,and the influence of local and global disease severity.In the disease layer,individual susceptibility is considered to be influenced by vaccination behavior.The state transition equations are derived using the micro Markov chain approach(MMCA),and disease prevalence thresholds are obtained.It is demonstrated through simulation experiments that the negative information diffusion is less influenced by local vaccination behavior,and is mainly influenced by global vaccination behavior;vaccination behavior is mainly influenced by local disease conditions,and is less influenced by global disease conditions;the disease transmission threshold increases with the increasing vaccination rate;and the scale of disease transmission increases with the increasing negative information diffusion rate and decreases with the increasing vaccination rate.Finally,it is found that when individual vaccination behavior considers both the influence of negative information and disease,it can increase the disease transmission threshold and reduce the scale of disease transmission.Therefore,we should resist the diffusion of negative information,increase vaccination proportions,and take appropriate protective measures in time.展开更多
Pine wood nematode infection is a devastating disease.Unmanned aerial vehicle(UAV)remote sensing enables timely and precise monitoring.However,UAV aerial images are challenged by small target size and complex sur-face...Pine wood nematode infection is a devastating disease.Unmanned aerial vehicle(UAV)remote sensing enables timely and precise monitoring.However,UAV aerial images are challenged by small target size and complex sur-face backgrounds which hinder their effectiveness in moni-toring.To address these challenges,based on the analysis and optimization of UAV remote sensing images,this study developed a spatio-temporal multi-scale fusion algorithm for disease detection.The multi-head,self-attention mechanism is incorporated to address the issue of excessive features generated by complex surface backgrounds in UAV images.This enables adaptive feature control to suppress redundant information and boost the model’s feature extraction capa-bilities.The SPD-Conv module was introduced to address the problem of loss of small target feature information dur-ing feature extraction,enhancing the preservation of key features.Additionally,the gather-and-distribute mechanism was implemented to augment the model’s multi-scale feature fusion capacity,preventing the loss of local details during fusion and enriching small target feature information.This study established a dataset of pine wood nematode disease in the Huangshan area using DJI(DJ-Innovations)UAVs.The results show that the accuracy of the proposed model with spatio-temporal multi-scale fusion reached 78.5%,6.6%higher than that of the benchmark model.Building upon the timeliness and flexibility of UAV remote sensing,the pro-posed model effectively addressed the challenges of detect-ing small and medium-size targets in complex backgrounds,thereby enhancing the detection efficiency for pine wood nematode disease.This facilitates early preemptive preser-vation of diseased trees,augments the overall monitoring proficiency of pine wood nematode diseases,and supplies technical aid for proficient monitoring.展开更多
While the interaction between information and disease in static networks has been extensively investigated,many studies have ignored the characteristics of network evolution.In this study,we construct a new two-layer ...While the interaction between information and disease in static networks has been extensively investigated,many studies have ignored the characteristics of network evolution.In this study,we construct a new two-layer coupling model to explore the interactions between information and disease.The upper layer describes the diffusion of disease-related information,and the lower layer represents the disease transmission.We then use power-law distributions to examine the influence of asymmetric activity levels on dynamic propagation,revealing a mapping relationship characterizing the interconnected propagation of information and diseases among partial nodes within the network.Subsequently,we derive the disease outbreak threshold by using the microscopic Markov-chain approach(MMCA).Finally,we perform extensive Monte Carlo(MC)numerical simulations to verify the accuracy of our theoretical results.Our findings indicate that the activity levels of individuals in the disease transmission layer have a more significant influence on disease transmission compared with the individual activity levels in the information diffusion layer.Moreover,reducing the damping factor can delay disease outbreaks and suppress disease transmission,while improving individual quarantine measures can contribute positively to disease control.This study provides valuable insights into policymakers for developing outbreak prevention and control strategies.展开更多
Nowadays,inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid,thiopurine,and immunomodulator treatments.Patients with active disease,that do not respond to corticosteroid and/or thiopur...Nowadays,inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid,thiopurine,and immunomodulator treatments.Patients with active disease,that do not respond to corticosteroid and/or thiopurine treatment,can switch to the usage of the chimeric monoclonal antibody infliximab(IFX).However,to date,no treatment appeared to be conclusive in lowering the incidence of IBD relapses.With the aim to increase the effectiveness of IFX treatment,we combined it with an adjuvant purple corn supplementation enriched in anthocyanins.IBD-patients were enrolled before they underwent to the IFX-infusion,and they were allocated in 2 different study arms.Patients in the intervention-arm followed a dietary supplementation with purple corn water-soluble extract,whereas control patients had a daily consumption of red fruit tea.16S rDNA gene-sequencing and high-resolution mass-spectrometry metabo-lipidomics analyses were conducted on stool and sera samples,respectively.As a result,the experimental intervention mainly affected the serum metabolome of IBD-patients by decreasing the concentration of specific lipids.Focusing on IBD patient annotated taxa,a significant decrease in Lactobacillus and Bifi dobacterium relative abundances was found.As far as it concerns the ulcerative colitis patient subset,the experimental intervention led to a decrease in Alistipes and Erysipelotrichaceae UCG-003 genus abundances and a concomitant Parabacteroides increase.On the contrary,after treatment,Crohn’s disease patients did not exhibit metataxonomics differences at the genus level.At the end of the treatment that led to a reshaped microbiota community,the gathered data paves the way for the usage of a specifically designed probiotic supplementation as a valuable strategy for IBD-patients under IFX infusion.展开更多
Caffeine intake during pregnancy is common,while its effect on gut microbiota composition of offspring and the relationship with susceptibility to adult diseases remains unclear.This study aimed to confirm the effects...Caffeine intake during pregnancy is common,while its effect on gut microbiota composition of offspring and the relationship with susceptibility to adult diseases remains unclear.This study aimed to confirm the effects of prenatal caffeine exposure(PCE)on the gut microbiota composition and its metabolites in female offspring rats,and to further elucidate its underlying mechanism and intervention targets in adult non-alcoholic fatty disease(NAFLD).The results showed that the gut microbiota of PCE female offspring at multiple time points from infancy to adolescence were significantly changed with depletion of butyric acid-producing bacteria,leading to a decrease in butyric acid in adulthood.It was also found that PCE female offspring rats were sensitive to NAFLD induced by a postnatal high-fat diet(HFD),which is mainly related to the enhancement of hepatic triglyceride synthesis function.Through mechanism exploration,we found that HFD further reduced the fecal and serum butyric acid levels in the PCE female offspring,which was significantly negatively correlated with hepatic SREBP-1c/FASN mRNA expression and triglyceride level.In vivo and in vitro experiments confirmed that sodium butyrate(NaB)supplementation could reduce hepatic lipid accumulation through MCT1/GPR109A-AMPK,thereby effectively decreasing the susceptibility to NAFLD in the PCE female offspring rats.展开更多
Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,di...Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.展开更多
The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based inte...The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.展开更多
Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieve...Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes(DEGs)between the non-alcoholic steatohepatitis(NASH)group and the healthy group using the'limma'package in R software and weighted gene co-expression network analysis.Gene ontology,kyoto encyclopedia of genes and genomes pathway,and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs.Ferroptosis-and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures,respectively.A combined signature for cuproptosis-and ferroptosis-related genes,called CRF,was constructed using the STRING database.Hub genes were identified by overlapping DEGs,WGCNA-derived key genes,and combined signature CRF genes,and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction.A nomogram of NASH diagnostic model was established utilizing the'rms'package in R software based on the hub genes,and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis.In addition,immune cell infiltration in NASH versus healthy controls was examined using the CIBERSORT algorithm.The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis.Results Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group.WGCNA highlighted 8 significant modules and 11,095 pivotal genes,of which 330 genes constituted CRF.Intersection analysis identified IL6,IL1B,JUN,NR4A1,and PTGS2 as hub genes.The hub genes were all downregulated in the NASH group,and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction.Receiver operating characteristic curve analysis confirmed the diagnostic efficacy of these hub genes with areas under the curve of 0.985,0.941,1.000,0.967,and 0.985,respectively.Immune infiltration assessment revealed that gamma delta T cells,M1 macrophages,M2 macrophages,and resting mast cells were predominantly implicated.Conclusion Our investigation underscores the significant association of cuproptosis-and ferroptosis-related genes,specifically IL6,IL1B,JUN,NR4A1,and PTGS2,with NASH.These findings offer novel insights into the pathogenesis of NASH,potentially guiding future diagnostic and therapeutic strategies.展开更多
Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients w...Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients worldwide.The neuropathology of AD is perplexing and there is a scarcity of disease-modifying treatments.Currently,early diagnosis of AD has been made possible with the discovery of biological markers associated with pathology,providing strong support for the improvement of the disease status.The search for inhibitors of AD markers from dietary supplements(DSs)has become a major hot topic.Especially with the widespread use of DSs,DSs containing polyphenols,alkaloids,terpenes,polysaccharides and other bioactive components can prevent AD by reducing Aβdeposition,inhibiting tau protein hyperphosphorylation,reconstructing synaptic dysfunction,weakening cholinesterase activity,regulating mitochondrial oxidative stress,neuronal inflammation and apoptosis.This review summarizes the anti-AD effects of the main DSs and their bioactive constituents,as well as the potential molecular mechanisms covers from 2017 to 2023.Additionally,we discussed the opportunities and challenges faced by DSs in the process of AD prevention and treatment,aiming to further provide new perspectives for functional food development.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the main cause of chronic liver disease worldwide.Bupleurum is widely used in the treatment of non-alcoholic fatty liver,and saikosaponin D(SSD)is one of the main active comp...Non-alcoholic fatty liver disease(NAFLD)is the main cause of chronic liver disease worldwide.Bupleurum is widely used in the treatment of non-alcoholic fatty liver,and saikosaponin D(SSD)is one of the main active components of Bupleurum.The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on“gut-liver axis”.Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice,improved insulin sensitivity,and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase(AST)and alanine aminotransferase(ALT).Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor(Fxr),small heterodimer partner(Shp),recombinant fibroblast growth factor 15(Fgf15)and apical sodium dependent bile acid transporter(Asbt)in the intestine,suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling.SSD can significantly reduce the gut microbiota associated with bile salt hydrolase(BSH)expression,such as Clostridium.Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids,thereby inhibiting the intestinal FXR.These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.展开更多
The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A com...The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.展开更多
Potentilla anserina L.(PA)belongs to the Rosaceae family,is a common edible plant in the Qinghai-Tibet Plateau areas of China.This study elucidates the mechanism upon which crude polysaccharide of PA(PAP)on fat accumu...Potentilla anserina L.(PA)belongs to the Rosaceae family,is a common edible plant in the Qinghai-Tibet Plateau areas of China.This study elucidates the mechanism upon which crude polysaccharide of PA(PAP)on fat accumulation in HepG2 cells stimulated by oleic acid(OA)and high fat high sugar induced mice.The result revealed that PAP inhibited lipid accumulation in obese mice and ameliorated the degree of damage in OA-induced HepG2 cells.Specifically,compared to the control group,the TG and TC levels were decreased in cells and mice serum,the aspartate transaminase and alamine aminotransferase contents were declined in liver of obese mice by PAP treatment.The expressions of adipogenic genes of SREBP-1c,C/EBPα,PPARγ,and FAS were inhibited after PAP treatment.Moreover,PAP increased the mRNA levels of CPT-1 and PPARα,which were involved in fatty acid oxidation.The present results indicated the PAP could alleviate the damage of liver associated with obesity and PAP treatment might provide a dietary therapeutic option for the treatment of hyperlipidemia.展开更多
BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to ex...BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.展开更多
基金supported by the China Postdoctoral Science Foundation(2021M693870,2022M711395)the National Natural Science Foundation of China(32000426,31971335)Department of Education of Liaoning Province(1911520092).
文摘Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.
基金supported by the National Natural Science Foundation of China(52173143 and 82371108)Natural Science Foundation of Henan Province(232300421176)Basic Science Key Project of Henan Eye Hospital(20JCZD002 and 23JCZD003).
文摘Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.
基金supported by the National Natural Science Foundation of China(22278241)the National Key R&D Program of China(2018YFA0901700)+1 种基金a grant from the Institute Guo Qiang,Tsinghua University(2021GQG1016)Department of Chemical Engineering-iBHE Joint Cooperation Fund.
文摘Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)and two-dimensional carbide and nitride(MXene)with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy.A light-activated virtual sensor array(LAVSA)based on BP/Ti_(3)C_(2)Tx was prepared under photomodulation and further assembled into an instant gas sensing platform(IGSP).In addition,a machine learning(ML)algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD.Due to the synergistic effect of BP and Ti_(3)C_(2)Tx as well as photo excitation,the synthesized heterostructured complexes exhibited higher performance than pristine Ti_(3)C_(2)Tx,with a response value 26%higher than that of pristine Ti_(3)C_(2)Tx.In addition,with the help of a pattern recognition algorithm,LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols,ketones,aldehydes,esters,and acids.Meanwhile,with the assistance of ML,the IGSP achieved 69.2%accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients.In conclusion,an immediate,low-cost,and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD,which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.
文摘Cardiovascular diseases(CVD)are the leading cause of death in the world and one of the most common diseases in the elderly,with high prevalence and poor prognosis,which seriously affect the health of the elder patients.One report showed that global deaths from CVD increased from 12.4 million in 1990 to 19.8 million in 2022,reflecting the global population growth and aging,as well as the impact of metabolic,environmental,and behavioral risks.[1]With the progress of aging population,the burden of CVD in the elderly in China has increased year by year,and factors including multiple complications,organ function decline,and high complication rate have made the interventional treatment of CVD in the elderly one of the difficulties and focuses in the field of cardiology in China.
基金This study was supported by the National Natural Science Foundation of China(82003529,72125009)the National Key Research and Development Program of the Ministry of Science and Technology of China(2019YFC2005000)+4 种基金the Chinese Scientific and Technical Innovation Project 2030(2018AAA0102100)the National High Level Hospital Clinical Research Funding(“Star of Outlook”Scientific Research Project of Peking University First Hospital,2022XW06)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-046)the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the PKU-Baidu Fund(2020BD004,2020BD005 and 2020BD032).
文摘Background:Climate change profoundly shapes the population health at the global scale.However,there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease(CKD).Methods:In the present study,we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018.Standard time-series regression models and random-effects Meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span,respectively.Results:A total of 768,129 hospitalizations for CKD was recorded during the study period.The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD,especially in sub-tropical cities.With a 1℃ increase in daily mean temperature,the cumulative relative risks(RR)over lag 0-7 d were 1.008[95% confidence interval(CI)1.003-1.012]for nationwide.The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%.Stronger associations were observed among younger patients and those with obstructive nephropathy.Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days(RR=1.116,95%CI 1.069-1.166)above the effect of daily mean temperature.Conclusions:Short-term heat exposure may increase the risk of hospitalization for CKD.Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.
基金supported by the National Natural Science Foundation of China(No.32071176)the 14th Five-Year-Plan Advantageous and Characteristic Disciplines(Groups)of Colleges and Universities in Hubei Province for Exercise and Brain Science from Hubei Provincial Department of Education+1 种基金the Chutian Scholar ProgramInnovative Start-Up Foundation from Wuhan Sports University to Ning Chen。
文摘Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammation and anti-oxidation functions,and improving mitochondrial quality.Chronic diseases as non-communicable diseases are mainly caused by multiple factors,such as physiological decline and dysfunction in the body,and have become a significant challenge on public health worldwide.It is worth noting that chronic diseases such as Alzheimer's disease(AD),Parkinson's disease(PD),muscle atrophy,cardiovascular disease,obesity,and cancer are accompanied by abnormal mitochondrial function.Therefore,targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases.Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria,and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions.In this article,current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized,which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.
基金financially supported by the National Natural Science Foundation of China(82074131,81774170,82260926)the Guangdong Basic and Applied Basic Research Foundation(2018B030306012,2022A1515220179,2021A1515011667)+2 种基金the Outstanding Youth Development Scheme project of Southern Medical University(G621299870)the Young Elite Scientists Sponsorship Program by CACM(2021-QNRC2-B28)the China Postdoctoral Science Foundation(2022M721532).
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 72174121 and 71774111)the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learningthe Natural Science Foundation of Shanghai (Grant No. 21ZR1444100)
文摘Today,with the rapid development of the internet,a large amount of information often accompanies the rapid transmission of disease outbreaks,and increasing numbers of scholars are studying the relationship between information and the disease transmission process using complex networks.In fact,the disease transmission process is very complex.Besides this information,there will often be individual behavioral measures and other factors to consider.Most of the previous research has aimed to establish a two-layer network model to consider the impact of information on the transmission process of disease,rarely divided into information and behavior,respectively.To carry out a more in-depth analysis of the disease transmission process and the intrinsic influencing mechanism,this paper divides information and behavior into two layers and proposes the establishment of a complex network to study the dynamic co-evolution of information diffusion,vaccination behavior,and disease transmission.This is achieved by considering four influential relationships between adjacent layers in multilayer networks.In the information layer,the diffusion process of negative information is described,and the feedback effects of local and global vaccination are considered.In the behavioral layer,an individual's vaccination behavior is described,and the probability of an individual receiving a vaccination is influenced by two factors:the influence of negative information,and the influence of local and global disease severity.In the disease layer,individual susceptibility is considered to be influenced by vaccination behavior.The state transition equations are derived using the micro Markov chain approach(MMCA),and disease prevalence thresholds are obtained.It is demonstrated through simulation experiments that the negative information diffusion is less influenced by local vaccination behavior,and is mainly influenced by global vaccination behavior;vaccination behavior is mainly influenced by local disease conditions,and is less influenced by global disease conditions;the disease transmission threshold increases with the increasing vaccination rate;and the scale of disease transmission increases with the increasing negative information diffusion rate and decreases with the increasing vaccination rate.Finally,it is found that when individual vaccination behavior considers both the influence of negative information and disease,it can increase the disease transmission threshold and reduce the scale of disease transmission.Therefore,we should resist the diffusion of negative information,increase vaccination proportions,and take appropriate protective measures in time.
基金funded by The National Natural Science Foundation of China(32271865)The Fundamental Research Funds for Central Universities(2572023CT16)the Fundamental Research Funds for Natural Science Foundation of Heilongjiang for Distinguished Young Scientists(JQ2023F002).
文摘Pine wood nematode infection is a devastating disease.Unmanned aerial vehicle(UAV)remote sensing enables timely and precise monitoring.However,UAV aerial images are challenged by small target size and complex sur-face backgrounds which hinder their effectiveness in moni-toring.To address these challenges,based on the analysis and optimization of UAV remote sensing images,this study developed a spatio-temporal multi-scale fusion algorithm for disease detection.The multi-head,self-attention mechanism is incorporated to address the issue of excessive features generated by complex surface backgrounds in UAV images.This enables adaptive feature control to suppress redundant information and boost the model’s feature extraction capa-bilities.The SPD-Conv module was introduced to address the problem of loss of small target feature information dur-ing feature extraction,enhancing the preservation of key features.Additionally,the gather-and-distribute mechanism was implemented to augment the model’s multi-scale feature fusion capacity,preventing the loss of local details during fusion and enriching small target feature information.This study established a dataset of pine wood nematode disease in the Huangshan area using DJI(DJ-Innovations)UAVs.The results show that the accuracy of the proposed model with spatio-temporal multi-scale fusion reached 78.5%,6.6%higher than that of the benchmark model.Building upon the timeliness and flexibility of UAV remote sensing,the pro-posed model effectively addressed the challenges of detect-ing small and medium-size targets in complex backgrounds,thereby enhancing the detection efficiency for pine wood nematode disease.This facilitates early preemptive preser-vation of diseased trees,augments the overall monitoring proficiency of pine wood nematode diseases,and supplies technical aid for proficient monitoring.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 72174121 and 71774111)the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learningthe Project for the Natural Science Foundation of Shanghai, China (Grant No. 21ZR1444100)
文摘While the interaction between information and disease in static networks has been extensively investigated,many studies have ignored the characteristics of network evolution.In this study,we construct a new two-layer coupling model to explore the interactions between information and disease.The upper layer describes the diffusion of disease-related information,and the lower layer represents the disease transmission.We then use power-law distributions to examine the influence of asymmetric activity levels on dynamic propagation,revealing a mapping relationship characterizing the interconnected propagation of information and diseases among partial nodes within the network.Subsequently,we derive the disease outbreak threshold by using the microscopic Markov-chain approach(MMCA).Finally,we perform extensive Monte Carlo(MC)numerical simulations to verify the accuracy of our theoretical results.Our findings indicate that the activity levels of individuals in the disease transmission layer have a more significant influence on disease transmission compared with the individual activity levels in the information diffusion layer.Moreover,reducing the damping factor can delay disease outbreaks and suppress disease transmission,while improving individual quarantine measures can contribute positively to disease control.This study provides valuable insights into policymakers for developing outbreak prevention and control strategies.
基金supported by the grant from Italian Ministry of Health Ricerca Corrente 2023 IRCCS“S.de Bellis”by the Apulia Region grant SiCURA“Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA”(KC3U5Y1).
文摘Nowadays,inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid,thiopurine,and immunomodulator treatments.Patients with active disease,that do not respond to corticosteroid and/or thiopurine treatment,can switch to the usage of the chimeric monoclonal antibody infliximab(IFX).However,to date,no treatment appeared to be conclusive in lowering the incidence of IBD relapses.With the aim to increase the effectiveness of IFX treatment,we combined it with an adjuvant purple corn supplementation enriched in anthocyanins.IBD-patients were enrolled before they underwent to the IFX-infusion,and they were allocated in 2 different study arms.Patients in the intervention-arm followed a dietary supplementation with purple corn water-soluble extract,whereas control patients had a daily consumption of red fruit tea.16S rDNA gene-sequencing and high-resolution mass-spectrometry metabo-lipidomics analyses were conducted on stool and sera samples,respectively.As a result,the experimental intervention mainly affected the serum metabolome of IBD-patients by decreasing the concentration of specific lipids.Focusing on IBD patient annotated taxa,a significant decrease in Lactobacillus and Bifi dobacterium relative abundances was found.As far as it concerns the ulcerative colitis patient subset,the experimental intervention led to a decrease in Alistipes and Erysipelotrichaceae UCG-003 genus abundances and a concomitant Parabacteroides increase.On the contrary,after treatment,Crohn’s disease patients did not exhibit metataxonomics differences at the genus level.At the end of the treatment that led to a reshaped microbiota community,the gathered data paves the way for the usage of a specifically designed probiotic supplementation as a valuable strategy for IBD-patients under IFX infusion.
基金funded by the National Natural Science Foundation of China (82030111, U23A20407)the National Key Research and Development Program of China (2020YFA0803900)+2 种基金the Major Technological Innovation Projects of Hubei Province (2019ACA140)Hubei Province's Outstanding Medical Academic Leader programthe Basic and Clinical Medical Research Joint Fund of Zhongnan Hospital, Wuhan University (ZNLH202208)
文摘Caffeine intake during pregnancy is common,while its effect on gut microbiota composition of offspring and the relationship with susceptibility to adult diseases remains unclear.This study aimed to confirm the effects of prenatal caffeine exposure(PCE)on the gut microbiota composition and its metabolites in female offspring rats,and to further elucidate its underlying mechanism and intervention targets in adult non-alcoholic fatty disease(NAFLD).The results showed that the gut microbiota of PCE female offspring at multiple time points from infancy to adolescence were significantly changed with depletion of butyric acid-producing bacteria,leading to a decrease in butyric acid in adulthood.It was also found that PCE female offspring rats were sensitive to NAFLD induced by a postnatal high-fat diet(HFD),which is mainly related to the enhancement of hepatic triglyceride synthesis function.Through mechanism exploration,we found that HFD further reduced the fecal and serum butyric acid levels in the PCE female offspring,which was significantly negatively correlated with hepatic SREBP-1c/FASN mRNA expression and triglyceride level.In vivo and in vitro experiments confirmed that sodium butyrate(NaB)supplementation could reduce hepatic lipid accumulation through MCT1/GPR109A-AMPK,thereby effectively decreasing the susceptibility to NAFLD in the PCE female offspring rats.
基金financially supported by National Natural Science Foundation of China(32171035)the major fund project of Ningbo Science and Technology Bureau(2019B10034)+4 种基金Opened-end Fund of Key Laboratory(KFJJ-202101,ZPKLP202202)Public Project of Ningbo(202002N3167)Project of Yinzhou(2022AS025)Ningbo Rehabilitation Hospital(2022KY02)sponsored by a K.C.Wong Magna Fund in Ningbo University。
文摘Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.
基金supported by the National Natural Science Foundation of China(31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.
文摘Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes(DEGs)between the non-alcoholic steatohepatitis(NASH)group and the healthy group using the'limma'package in R software and weighted gene co-expression network analysis.Gene ontology,kyoto encyclopedia of genes and genomes pathway,and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs.Ferroptosis-and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures,respectively.A combined signature for cuproptosis-and ferroptosis-related genes,called CRF,was constructed using the STRING database.Hub genes were identified by overlapping DEGs,WGCNA-derived key genes,and combined signature CRF genes,and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction.A nomogram of NASH diagnostic model was established utilizing the'rms'package in R software based on the hub genes,and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis.In addition,immune cell infiltration in NASH versus healthy controls was examined using the CIBERSORT algorithm.The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis.Results Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group.WGCNA highlighted 8 significant modules and 11,095 pivotal genes,of which 330 genes constituted CRF.Intersection analysis identified IL6,IL1B,JUN,NR4A1,and PTGS2 as hub genes.The hub genes were all downregulated in the NASH group,and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction.Receiver operating characteristic curve analysis confirmed the diagnostic efficacy of these hub genes with areas under the curve of 0.985,0.941,1.000,0.967,and 0.985,respectively.Immune infiltration assessment revealed that gamma delta T cells,M1 macrophages,M2 macrophages,and resting mast cells were predominantly implicated.Conclusion Our investigation underscores the significant association of cuproptosis-and ferroptosis-related genes,specifically IL6,IL1B,JUN,NR4A1,and PTGS2,with NASH.These findings offer novel insights into the pathogenesis of NASH,potentially guiding future diagnostic and therapeutic strategies.
基金financially supported by the National Key R&D Program of China(2022YFF1100301)Yunnan Revitalization Talents Support Plan-Young Talent Project(YNWRQNBJ-2018-357)。
文摘Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients worldwide.The neuropathology of AD is perplexing and there is a scarcity of disease-modifying treatments.Currently,early diagnosis of AD has been made possible with the discovery of biological markers associated with pathology,providing strong support for the improvement of the disease status.The search for inhibitors of AD markers from dietary supplements(DSs)has become a major hot topic.Especially with the widespread use of DSs,DSs containing polyphenols,alkaloids,terpenes,polysaccharides and other bioactive components can prevent AD by reducing Aβdeposition,inhibiting tau protein hyperphosphorylation,reconstructing synaptic dysfunction,weakening cholinesterase activity,regulating mitochondrial oxidative stress,neuronal inflammation and apoptosis.This review summarizes the anti-AD effects of the main DSs and their bioactive constituents,as well as the potential molecular mechanisms covers from 2017 to 2023.Additionally,we discussed the opportunities and challenges faced by DSs in the process of AD prevention and treatment,aiming to further provide new perspectives for functional food development.
基金supported by National Natural Science Foundation of China (82222071, 82273990, 82104253)the opening project of State Key Laboratory of Natural Medicines (SKLNMKF202208)
文摘Non-alcoholic fatty liver disease(NAFLD)is the main cause of chronic liver disease worldwide.Bupleurum is widely used in the treatment of non-alcoholic fatty liver,and saikosaponin D(SSD)is one of the main active components of Bupleurum.The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on“gut-liver axis”.Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice,improved insulin sensitivity,and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase(AST)and alanine aminotransferase(ALT).Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor(Fxr),small heterodimer partner(Shp),recombinant fibroblast growth factor 15(Fgf15)and apical sodium dependent bile acid transporter(Asbt)in the intestine,suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling.SSD can significantly reduce the gut microbiota associated with bile salt hydrolase(BSH)expression,such as Clostridium.Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids,thereby inhibiting the intestinal FXR.These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.
基金supported by National Natural Science Foundation of China(NSFC:82073538 and 81773433)by the 2018 Chinese Nutrition Society(CNS)Nutrition Research Foundation-DSM Research Fund(CNS-DSM2018A30)。
文摘The associations of individual amino acid with non-alcoholic fatty liver disease(NAFLD)risk remained unclear.The present study aimed to investigate the associations between the two in the Chinese elderly.Methods:A community-based health check-up program was conducted in Qingdao,China.NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation.The dietary intakes of amino acids were investigated with 3-day,24-h dietary records and calculated by Nutrition Calculator software.Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk.Results:400 NAFLD subjects were identified,and 400 participants were randomly selected as controls and matched by gender and age(±3 years)Dose-response analysis showed that 1000 mg increment of aromatic amino acids(AAAs)was associated with reduced 16%risk of NAFLD.Dietary increments of 750 mg/d threonine,950 mg/d valine,or 1700 mg/d lysine were associated with a 20%reduction in the NAFLD risk(all P for linearity<0.05).Conclusion:The present study demonstrated that the dietary increases in milk,eggs and deep-sea fish,which are rich in the amino acids,might contribute to protecting against NAFLD in the elderly.
基金supported by the Natural Science Foundation of Tibet Autonomous Region(XZ202201ZR0012G)Quality Evaluation and Efficient Utilization of Effective Components of Potentilla anserine Resources in Tibet(XZ202201ZD0001N).
文摘Potentilla anserina L.(PA)belongs to the Rosaceae family,is a common edible plant in the Qinghai-Tibet Plateau areas of China.This study elucidates the mechanism upon which crude polysaccharide of PA(PAP)on fat accumulation in HepG2 cells stimulated by oleic acid(OA)and high fat high sugar induced mice.The result revealed that PAP inhibited lipid accumulation in obese mice and ameliorated the degree of damage in OA-induced HepG2 cells.Specifically,compared to the control group,the TG and TC levels were decreased in cells and mice serum,the aspartate transaminase and alamine aminotransferase contents were declined in liver of obese mice by PAP treatment.The expressions of adipogenic genes of SREBP-1c,C/EBPα,PPARγ,and FAS were inhibited after PAP treatment.Moreover,PAP increased the mRNA levels of CPT-1 and PPARα,which were involved in fatty acid oxidation.The present results indicated the PAP could alleviate the damage of liver associated with obesity and PAP treatment might provide a dietary therapeutic option for the treatment of hyperlipidemia.
文摘BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.
