The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia ...The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.展开更多
BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomy...BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
This article discusses the study by GrubićRotkvićet al on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and heart failure(HF).T2DM and HF a...This article discusses the study by GrubićRotkvićet al on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and heart failure(HF).T2DM and HF are highly comorbid,with a significantly increased prevalence of HF in patients with T2DM.SGLT2i exhibit potential in reducing hospitalization rates for HF and cardiovascular mortality through multiple mechanisms,including improving blood glucose control,promoting urinary sodium excretion,reducing sympathetic nervous system activity,lowering both preload and afterload on the heart,alleviating inflammation and oxidative stress,enhancing endothelial function,improving myocardial energy metabolism,and stabilizing cardiac ion homeostasis.Further research and clinical practice will help optimize the use of SGLT2i in HF patients.展开更多
BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is exp...BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.展开更多
BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly ...BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.展开更多
BACKGROUND Increasing evidence has shown that hippocampal damage serves as a marker of early cognitive decline in patients with type 2 diabetes mellitus(T2DM);however,the association between hippocampal subregion volu...BACKGROUND Increasing evidence has shown that hippocampal damage serves as a marker of early cognitive decline in patients with type 2 diabetes mellitus(T2DM);however,the association between hippocampal subregion volume changes and cognitive decline in different dimensions remains unclear.AIM To investigate changes in hippocampal subregion volumes in patients with T2DM and their relationship with cognitive function impairment.METHODS Sixty patients with T2DM and 32 healthy controls were recruited.All participants underwent a 3.0 T magnetic resonance scan and a series of clinical assessments.Hippocampal subfield volumes were determined using FreeSurfer 7.4.1.A two-sample t-test was used to evaluate group differences.Partial correlation analysis was performed to assess the relationship between hippocampal subregion volumes and cognitive function.aP<0.05 was considered statistically significant.RESULTS Compared with controls,the volume of right hippocampus-amygdala transition area(t=-3.053,P=0.003)in patients with T2DM was significantly reduced,which was negatively correlated with the required time of the Trail Making Test(TMT)-A(r=-0.331,P=0.028)and TMT-B(r=-0.402,P=0.007)and positively correlated with the scores of Symbol Digit Modalities Test(r=0.381,P=0.011),Auditory Verbal Learning Test(AVLT)-N7(r=0.309,P=0.041),and Digital Span Test(r=0.300,P=0.048).The volume of the right molecular layer(t=-2.998,P=0.004)was also significantly reduced,which was positively associated with the scores of AVLT-N7(r=0.311,P=0.045).In addition,the left hippocampal fissure volume(t=3.617,P=0.002)was significantly increased in patients with T2DM.CONCLUSION Declines in cognitive performance,especially memory and executive function,are linked to changes in the volumes of the right hippocampus-amygdala transition area and right molecular layer in patients with T2DM.展开更多
BACKGROUND Cardiorespiratory fitness(CRF)is inversely associated with the risk of cardiovascular disease,which is related to impaired vascular function.However,its relationship with vascular function remains unknown i...BACKGROUND Cardiorespiratory fitness(CRF)is inversely associated with the risk of cardiovascular disease,which is related to impaired vascular function.However,its relationship with vascular function remains unknown in patients with type 2 diabetes.AIM To assess the relationship of CRF with vascular function in type 2 diabetes.METHODS Patients with type 2 diabetes who were aged≥18 years and underwent an incremental and symptom-limited exercise test were included.Vascular function was assessed by the construction of the vascular health index(VHI),which is defined as a composite score of ankle-brachial index,transcutaneous oxygen pressure,pulse wave velocity,and carotid intima-media thickness.Impaired vascular function is defined as a VHI of<8 points.Linear and logistic regression analyses were used to assess the associations.RESULTS We included 343 patients with type 2 diabetes.CRF was positively correlated with VHI(β=0.10,P=0.047),particularly with ankle-brachial index and pulse wave velocity.The odds ratio(OR)of impaired vascular function was 0.44[95%confidence interval(CI):0.20-0.96]for the highest vs the lowest CRF category.For each one metabolic equivalent increase in CRF,the OR of impaired vascular function was 0.73(95%CI:0.57-0.93).CONCLUSION Higher CRF was associated with better vascular function and lower odds of impaired vascular function in patients with type 2 diabetes.展开更多
BACKGROUND Increased blood urea nitrogen(BUN)levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes(T2D),potentially playing a role in the development o...BACKGROUND Increased blood urea nitrogen(BUN)levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes(T2D),potentially playing a role in the development of diabetic complications,including diabetic peripheral neuropathy.AIM To examine the relationship between BUN levels and peripheral nerve function in patients with T2D.METHODS This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured.Electromyography was used to assess peripheral motor and sensory nerve function in all patients,and overall composite Z-scores were subsequently calculated for nerve latency,amplitude,and conduction velocity(NCV)across the median,ulnar,common peroneal,posterior tibial,superficial peroneal,and sural nerves.RESULTS Across the quartiles of BUN levels,the overall composite Z-score for latency(F=38.996,P for trend<0.001)showed a significant increasing trend,whereas the overall composite Z-scores for amplitude(F=50.972,P for trend<0.001)and NCV(F=30.636,P for trend<0.001)exhibited a significant decreasing trend.Moreover,the BUN levels were closely correlated with the latency,amplitude,and NCV of each peripheral nerve.Furthermore,multivariate linear regression analysis revealed that elevated BUN levels were linked to a higher overall composite Z-score for latency(β=0.166,t=3.864,P<0.001)and lower overall composite Z-scores for amplitude(β=-0.184,t=-4.577,P<0.001)and NCV(β=-0.117,t=-2.787,P=0.006)independent of the estimated glomerular filtration rate and other clinical covariates.Additionally,when the analysis was restricted to sensory or motor nerves,elevated BUN levels remained associated with sensory or motor peripheral nerve dysfunction.CONCLUSION Increased BUN levels were independently associated with compromised peripheral nerve function in patients with T2D.展开更多
BACKGROUND Previous studies have shown that individuals with type 1 diabetes(T1D)frequently present with reduced fecal elastase levels,suggesting exocrine pancreatic insufficiency.However,the underlying determinants a...BACKGROUND Previous studies have shown that individuals with type 1 diabetes(T1D)frequently present with reduced fecal elastase levels,suggesting exocrine pancreatic insufficiency.However,the underlying determinants and the longitudinal trajectory of these changes remain poorly understood.AIM To evaluate longitudinal changes in fecal elastase among individuals with T1D,identify associated factors,and determine clinical implications.METHODS Pancreatic exocrine function was evaluated in a cohort of patients with T1D by measuring fecal elastase concentrations(FECs).After a mean follow-up of 8.5±0.5 years,participants were recontacted,and a second stool sample was obtained.At both time points,detailed medical histories were collected,including information on diabetes progression,metabolic control,complications,gastrointestinal symptoms,and nutritional status.The study was approved by the institutional ethics committee,and written informed consent was obtained from all participants.RESULTS A total of 106 individuals with T1D(mean age=46.2 years;50%male)were enrolled.At baseline,the median FEC was 239.5μg/g,with 44 participants(41.5%)demonstrating abnormally low levels(<200μg/g).Reduced fecal elastase was significantly associated with male sex,diabetes-related complications,particularly retinopathy,and higher glycated hemoglobin levels.No significant differences in gastrointestinal symptoms,body mass index,nor most serum nutritional markers were observed between individuals with normal vs reduced fecal elastase levels.Sixty-six participants completed follow-up.Their median fecal elastase was 171.5μg/g,with 59.1%presenting levels below 200μg/g.Paired analysis showed a non-significant decline in FEC s over time.No clinical nor metabolic variables predicted longitudinal changes in FEC independently.CONCLUSION Fecal elastase levels are frequently reduced in individuals with T1D and may show a gradual decline over time.The clinical impact of these changes appears to be limited.展开更多
Background The co-existence of Type 2 diabetes mellitus(T2DM)and hypertension presents a significant clinical challenge due to their synergistic detrimental effects on cardiovascular outcomes.Conventional combination ...Background The co-existence of Type 2 diabetes mellitus(T2DM)and hypertension presents a significant clinical challenge due to their synergistic detrimental effects on cardiovascular outcomes.Conventional combination therapies often fall short in comprehensively addressing the intertwined pathophysiologies,particularly vascular endothelial dysfunction.This study aimed to evaluate the efficacy of a novel regimen combining sitagliptin-metformin with nifedipine in managing blood pressure,blood glucose,and vascular function in this high-risk population.Methods 150 patients with T2DM and hypertension were randomly assigned to either the control group(n=75)treated with metformin and nifedipine,or the experimental group(n=75)treated with sitagliptin-metformin compound preparation combined with nifedipine.Changes in blood pressure,blood glucose levels,flow-mediated dilation(FMD)and nitroglycerin-mediated dilation(NMD)of the brachial artery,and serum levels of biomarkers[nitric oxide(NO),endothelin-1(ET-1)]were compared before and after treatment.The incidence of adverse reactions during treatment was also monitored.Results After treatment,both groups showed significant reductions in blood pressure,blood glucose parameters,and ET-1 levels compared to baseline.The experimental group demonstrated significantly lower values in these assessments at the same time points than control group(P<0.05).Conversely,FMD,NMD,and NO levels increased significantly in both groups after treatment,with experimental group showing significantly higher values than control group(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The combination of sitagliptinmetformin compound preparation and nifedipine significantly enhanced blood pressure control and blood glucose control and exerted a positive regulatory effect on vascular endothelial function in patients with T2DM and hypertension,demonstrating high clinical value for widespread application.展开更多
The present study investigated the potential therapeutic potential of Ficus carica polysaccharides(FCPS)in type 2 diabetic mellitus(T2DM)mice,focusing on elucidating the underlying molecular mechanisms.Network pharmac...The present study investigated the potential therapeutic potential of Ficus carica polysaccharides(FCPS)in type 2 diabetic mellitus(T2DM)mice,focusing on elucidating the underlying molecular mechanisms.Network pharmacology analysis identified 37 shared targets between FCPS and T2DM,including perixisome proliferator activated receptor alpha(PPARα),highlighting the significance of PPAR signaling pathways in FCPS-mediated T2DM treatment.The results demonstrated that FCPS treatment significantly reduced markers of glucose and lipid metabolism(fasting blood glucose(FBG),nonestesterified fatty acid(NEFA),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)),inflammatory cytokines(tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1beta(IL-1β),monocyte chemoattractant protein-1(MCP-1)),and liver damage(glutamic pyruvic transaminase(GPT)and glutamic oxaloacetic transaminase(GOT))in T2DM mice.Additionally,FCPS ameliorated hepatic lipid droplet accumulation,fatty degeneration,and hepatocyte structural abnormalities.Western blot analysis confirmed FCPS-induced upregulation of key proteins in the IRS-1/AKT/PPARαsignaling pathway,(insulin receptor substrate 1(IRS-1),phosphatidyqinositol-3 kinase(PI3K),phospho-protein kinase B(p-AKT),glucose transporter 2(GLUT2),phospho-glycogen synthase kinase 3 beta(p-GSK-3β),phospho-adenosine 5′-monophosphate-activated protein kinase alpha(p-AMPKα),peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α),PPARα,peroxisome proliferator-activated receptor gamma(PPARγ))and downregulation of GSK-3β,sterol regulatory element binding protein 1c(SREBP-1c),fatty acid synthase(FAS),and 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR).16S r RNA sequencing results revealed FCPS's ability to modulate gut microbiota dysbiosis in T2DM mice by promoting beneficial bacteria(e.g.,Lactobacillus_reuteri,Candidatus_Saccharimonas)and suppressing opportunistic pathogens(e.g.,Proteobacteria,Gammaproteobacteria,Escherichia-Shigella).These findings collectively suggest that FCPS has a marked effectiveness in improving glucose and lipid metabolism,decreasing inflammatory responses,as well as modulating the gut microbiota in T2DM mice via the gut-hepatic axis,demonstrating its potential as a functional food for diabetes prevention and management.展开更多
This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitu...This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.展开更多
BACKGROUND Radial head fractures constitute approximately one-third of all elbow fractures,significantly impacting the young and active population.While open reduction and internal fixation is the preferred treatment ...BACKGROUND Radial head fractures constitute approximately one-third of all elbow fractures,significantly impacting the young and active population.While open reduction and internal fixation is the preferred treatment for displaced fractures,its high complication rate in comminuted fractures has led to the increasing use of radial head arthroplasty(RHA).RHA provides improved functional outcomes with fewer complications,yet its long-term efficacy remains a topic of debate.AIM To evaluate the functional outcomes of patients undergoing RHA with a modular metallic prosthesis for comminuted Mason type III and IV radial head fractures.METHODS A prospective and retrospective hospital-based study was conducted at Dayanand Medical College and Hospital,Ludhiana over 32 months(January 2021-August 2023).A total of 26 patients with Mason type III and IV fractures were included,with six retrospective and 20 prospective cases.Functional outcomes were assessed using the Mayo Elbow Performance Score(MEPS),elbow range of motion,pain via Visual Analog Scale,and activities of daily living at immediate postoperative,three-month,and six-month follow-ups.RESULTS MEPS at 6 months follow up for 4 cases(15.38%)had good scores,and 22 cases(84.62%)had excellent scores,with a mean±SD of 97.31±6.67.Comparisons showed significant improvement from immediate post-operative to 3 months(P<0.0001),from immediate post-operative to 6 months(P<0.0001),and between 3 months and 6 months(P<0.0001).None of the patients had elbow instability after radial head replacement and 22 cases(84.62%)had no complications,while 3 cases(11.54%)had a stiff elbow,and 1 case(3.85%)had heterotopic ossification.CONCLUSION RHA is an effective treatment for comminuted radial head fractures,providing stable elbow function with minimal complications.展开更多
Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization o...Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.展开更多
This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared ...This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared spectroscopy,X-ray diffraction,high-performance anion-exchange chromatography,and differential scanning calorimetry.Significant differences were observed in their morphological,physicochemical,and functional properties.PMS had a smaller particle size(13.68 μm),irregular polygonal shape,A-type,lower water absorption(62.67 %),and higher oil absorption(51.17 %).In contrast,SGS exhibited larger particles(31.75 μm),a nearly spherical shape,B-type,higher crystallinity(50.66 %),and greater amylose content(21.54 %),with superior thermal stability,shear resistance,and gelatinization enthalpy.SGS also contained higher resistant starch(83.28 %) and longer average chain length(20.58 %),but showed lower solubility,swelling power,light transmittance,and freeze-thaw stability.The physicochemical properties differences in crystal pattern and particle morphology between PMS and SGS lead to distinct behaviors during in vitro digestion and fermentation.These findings highlight the potential of medicinal plant starches in functional ingredients and industrial processes.展开更多
Limitations regarding phosphorus(P)are widespread in ecosystems.Understanding the impacts of the wetland types on microbially mediated soil P availability and cycling is essential for the effective management of wetla...Limitations regarding phosphorus(P)are widespread in ecosystems.Understanding the impacts of the wetland types on microbially mediated soil P availability and cycling is essential for the effective management of wetlands.In this study,the Beidagang wetland,Baodi paddy field,and Dahuangpu wetland in Tianjin,China were chosen as representatives of the coastal wetland(B),constructed wetland(R),and swampy wetland(W),respectively.Sequential P extraction and metagenomics approaches were adopted to explore the soil P fraction and microbially regulated P cycle.Proteobacteria were the predominant microbes-related soil P cycle.IMPA,gph,rsbU_P,ugpQ,and glpK genes were dominant in organic P(Po)mineralization,while gcd,ppa,and ppx genes were dominant in inorganic P(Pi)solubilization.The salinity,NO_(3)^(-)-N concentration,the ratio of total carbon to total nitrogen(TC/TN),total carbon(TC),and the ratio of soil organic carbon to total P(SOC/TP)were the co-drivers of microbially mediated P cycle processes.Microbial network complexity-relate P cycle was the lowest in the coastal wetland.Salinity and NO_(3)^(-)-N exhibited a significant negative relation to the abundance of most genes-relate Pi solubilization and a remarkable positive correlation with the abundance of many genes-relate Po mineralization.These findings demonstrated that Po mineralization tended to occur in habitats with high salinity and nutrient imbalances,whereas the dissolution of Pi was prone to occur in low-salinity environments with relatively balanced soil nutrients.This study improves understanding of how salinity and soil nutrients jointly shape microbial-regulated soil P cycle in different types of wetlands.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,su...BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.展开更多
In this paper,we construct new examples of hyperbolic metasurfaces in CP^(3) and CP^(4),and discusses the existence of solutions for a class of Fermat type functional equations.
基金supported by the National Natural Science Foundation of China,Nos.82071387(to HT),81971172(to YW)the Natural Science Foundation of Zhejiang Province,China,No.LY22H090012(to HT)the Basic Research Project of Wenzhou City,China,No.Y20220923(to MZ)。
文摘The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
基金Supported by the University of Louisville-China Pediatric Research Exchange Program(Cai L,Tan Y,Huang J,and Keller B,no salary support)University of Louisville Executive Vice President for Research and Innovation Internal Grant(Huang J and Cai L)University of Louisville School of Medicine Basic Grant(Huang J and Cai L).
文摘BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
文摘This article discusses the study by GrubićRotkvićet al on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and heart failure(HF).T2DM and HF are highly comorbid,with a significantly increased prevalence of HF in patients with T2DM.SGLT2i exhibit potential in reducing hospitalization rates for HF and cardiovascular mortality through multiple mechanisms,including improving blood glucose control,promoting urinary sodium excretion,reducing sympathetic nervous system activity,lowering both preload and afterload on the heart,alleviating inflammation and oxidative stress,enhancing endothelial function,improving myocardial energy metabolism,and stabilizing cardiac ion homeostasis.Further research and clinical practice will help optimize the use of SGLT2i in HF patients.
文摘BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.
基金Medical Ethics Committee of the Nanxishan Hospital of Guangxi Zhuang Autonomous Region(Approval No.NXSYY-2024-209).
文摘BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.
基金Supported by the Bethune Charitable Foundation,No.Z04JKM2022E035the Liyang City's 2023 Annual research and development Plan Follows Nanjing Project,No.LC2024001.
文摘BACKGROUND Increasing evidence has shown that hippocampal damage serves as a marker of early cognitive decline in patients with type 2 diabetes mellitus(T2DM);however,the association between hippocampal subregion volume changes and cognitive decline in different dimensions remains unclear.AIM To investigate changes in hippocampal subregion volumes in patients with T2DM and their relationship with cognitive function impairment.METHODS Sixty patients with T2DM and 32 healthy controls were recruited.All participants underwent a 3.0 T magnetic resonance scan and a series of clinical assessments.Hippocampal subfield volumes were determined using FreeSurfer 7.4.1.A two-sample t-test was used to evaluate group differences.Partial correlation analysis was performed to assess the relationship between hippocampal subregion volumes and cognitive function.aP<0.05 was considered statistically significant.RESULTS Compared with controls,the volume of right hippocampus-amygdala transition area(t=-3.053,P=0.003)in patients with T2DM was significantly reduced,which was negatively correlated with the required time of the Trail Making Test(TMT)-A(r=-0.331,P=0.028)and TMT-B(r=-0.402,P=0.007)and positively correlated with the scores of Symbol Digit Modalities Test(r=0.381,P=0.011),Auditory Verbal Learning Test(AVLT)-N7(r=0.309,P=0.041),and Digital Span Test(r=0.300,P=0.048).The volume of the right molecular layer(t=-2.998,P=0.004)was also significantly reduced,which was positively associated with the scores of AVLT-N7(r=0.311,P=0.045).In addition,the left hippocampal fissure volume(t=3.617,P=0.002)was significantly increased in patients with T2DM.CONCLUSION Declines in cognitive performance,especially memory and executive function,are linked to changes in the volumes of the right hippocampus-amygdala transition area and right molecular layer in patients with T2DM.
基金Supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2024ZD0523303the Funding for Pairing Support to Jiangsu High-Level Hospitals-Zhongda Hospital,No.ZDLYG19the Key Research and Development Program in Jiangsu Province,No.BE2022828.
文摘BACKGROUND Cardiorespiratory fitness(CRF)is inversely associated with the risk of cardiovascular disease,which is related to impaired vascular function.However,its relationship with vascular function remains unknown in patients with type 2 diabetes.AIM To assess the relationship of CRF with vascular function in type 2 diabetes.METHODS Patients with type 2 diabetes who were aged≥18 years and underwent an incremental and symptom-limited exercise test were included.Vascular function was assessed by the construction of the vascular health index(VHI),which is defined as a composite score of ankle-brachial index,transcutaneous oxygen pressure,pulse wave velocity,and carotid intima-media thickness.Impaired vascular function is defined as a VHI of<8 points.Linear and logistic regression analyses were used to assess the associations.RESULTS We included 343 patients with type 2 diabetes.CRF was positively correlated with VHI(β=0.10,P=0.047),particularly with ankle-brachial index and pulse wave velocity.The odds ratio(OR)of impaired vascular function was 0.44[95%confidence interval(CI):0.20-0.96]for the highest vs the lowest CRF category.For each one metabolic equivalent increase in CRF,the OR of impaired vascular function was 0.73(95%CI:0.57-0.93).CONCLUSION Higher CRF was associated with better vascular function and lower odds of impaired vascular function in patients with type 2 diabetes.
基金Supported by the Social Development Projects of Nantong,No.MS12019019,No.HS2022004 and No.MS2023083the Medical Research Project of the Jiangsu Health Commission,No.Z2022058the National Natural Science Foundation of China,No.32101027。
文摘BACKGROUND Increased blood urea nitrogen(BUN)levels have been demonstrated to be associated with broader metabolic disturbances and the incidence of type 2 diabetes(T2D),potentially playing a role in the development of diabetic complications,including diabetic peripheral neuropathy.AIM To examine the relationship between BUN levels and peripheral nerve function in patients with T2D.METHODS This observational study involved the systematic recruitment of 585 patients with T2D for whom BUN levels and estimated glomerular filtration rate were measured.Electromyography was used to assess peripheral motor and sensory nerve function in all patients,and overall composite Z-scores were subsequently calculated for nerve latency,amplitude,and conduction velocity(NCV)across the median,ulnar,common peroneal,posterior tibial,superficial peroneal,and sural nerves.RESULTS Across the quartiles of BUN levels,the overall composite Z-score for latency(F=38.996,P for trend<0.001)showed a significant increasing trend,whereas the overall composite Z-scores for amplitude(F=50.972,P for trend<0.001)and NCV(F=30.636,P for trend<0.001)exhibited a significant decreasing trend.Moreover,the BUN levels were closely correlated with the latency,amplitude,and NCV of each peripheral nerve.Furthermore,multivariate linear regression analysis revealed that elevated BUN levels were linked to a higher overall composite Z-score for latency(β=0.166,t=3.864,P<0.001)and lower overall composite Z-scores for amplitude(β=-0.184,t=-4.577,P<0.001)and NCV(β=-0.117,t=-2.787,P=0.006)independent of the estimated glomerular filtration rate and other clinical covariates.Additionally,when the analysis was restricted to sensory or motor nerves,elevated BUN levels remained associated with sensory or motor peripheral nerve dysfunction.CONCLUSION Increased BUN levels were independently associated with compromised peripheral nerve function in patients with T2D.
文摘BACKGROUND Previous studies have shown that individuals with type 1 diabetes(T1D)frequently present with reduced fecal elastase levels,suggesting exocrine pancreatic insufficiency.However,the underlying determinants and the longitudinal trajectory of these changes remain poorly understood.AIM To evaluate longitudinal changes in fecal elastase among individuals with T1D,identify associated factors,and determine clinical implications.METHODS Pancreatic exocrine function was evaluated in a cohort of patients with T1D by measuring fecal elastase concentrations(FECs).After a mean follow-up of 8.5±0.5 years,participants were recontacted,and a second stool sample was obtained.At both time points,detailed medical histories were collected,including information on diabetes progression,metabolic control,complications,gastrointestinal symptoms,and nutritional status.The study was approved by the institutional ethics committee,and written informed consent was obtained from all participants.RESULTS A total of 106 individuals with T1D(mean age=46.2 years;50%male)were enrolled.At baseline,the median FEC was 239.5μg/g,with 44 participants(41.5%)demonstrating abnormally low levels(<200μg/g).Reduced fecal elastase was significantly associated with male sex,diabetes-related complications,particularly retinopathy,and higher glycated hemoglobin levels.No significant differences in gastrointestinal symptoms,body mass index,nor most serum nutritional markers were observed between individuals with normal vs reduced fecal elastase levels.Sixty-six participants completed follow-up.Their median fecal elastase was 171.5μg/g,with 59.1%presenting levels below 200μg/g.Paired analysis showed a non-significant decline in FEC s over time.No clinical nor metabolic variables predicted longitudinal changes in FEC independently.CONCLUSION Fecal elastase levels are frequently reduced in individuals with T1D and may show a gradual decline over time.The clinical impact of these changes appears to be limited.
文摘Background The co-existence of Type 2 diabetes mellitus(T2DM)and hypertension presents a significant clinical challenge due to their synergistic detrimental effects on cardiovascular outcomes.Conventional combination therapies often fall short in comprehensively addressing the intertwined pathophysiologies,particularly vascular endothelial dysfunction.This study aimed to evaluate the efficacy of a novel regimen combining sitagliptin-metformin with nifedipine in managing blood pressure,blood glucose,and vascular function in this high-risk population.Methods 150 patients with T2DM and hypertension were randomly assigned to either the control group(n=75)treated with metformin and nifedipine,or the experimental group(n=75)treated with sitagliptin-metformin compound preparation combined with nifedipine.Changes in blood pressure,blood glucose levels,flow-mediated dilation(FMD)and nitroglycerin-mediated dilation(NMD)of the brachial artery,and serum levels of biomarkers[nitric oxide(NO),endothelin-1(ET-1)]were compared before and after treatment.The incidence of adverse reactions during treatment was also monitored.Results After treatment,both groups showed significant reductions in blood pressure,blood glucose parameters,and ET-1 levels compared to baseline.The experimental group demonstrated significantly lower values in these assessments at the same time points than control group(P<0.05).Conversely,FMD,NMD,and NO levels increased significantly in both groups after treatment,with experimental group showing significantly higher values than control group(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The combination of sitagliptinmetformin compound preparation and nifedipine significantly enhanced blood pressure control and blood glucose control and exerted a positive regulatory effect on vascular endothelial function in patients with T2DM and hypertension,demonstrating high clinical value for widespread application.
基金supported by the Open Project Fund of Key Laboratory of Xinjiang Uygur Autonomous Region(2021D04019)the Natural Science Foundation of Xinjiang Uygur Autonomous Region(2024D01C57)+1 种基金the National Natural Science Foundation of China(32460188)the Key Research and Development Program in Xinjiang Uygur Autonomous Region to Weilan Wang(2024B02025 and 2024B02025-2)。
文摘The present study investigated the potential therapeutic potential of Ficus carica polysaccharides(FCPS)in type 2 diabetic mellitus(T2DM)mice,focusing on elucidating the underlying molecular mechanisms.Network pharmacology analysis identified 37 shared targets between FCPS and T2DM,including perixisome proliferator activated receptor alpha(PPARα),highlighting the significance of PPAR signaling pathways in FCPS-mediated T2DM treatment.The results demonstrated that FCPS treatment significantly reduced markers of glucose and lipid metabolism(fasting blood glucose(FBG),nonestesterified fatty acid(NEFA),triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)),inflammatory cytokines(tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1beta(IL-1β),monocyte chemoattractant protein-1(MCP-1)),and liver damage(glutamic pyruvic transaminase(GPT)and glutamic oxaloacetic transaminase(GOT))in T2DM mice.Additionally,FCPS ameliorated hepatic lipid droplet accumulation,fatty degeneration,and hepatocyte structural abnormalities.Western blot analysis confirmed FCPS-induced upregulation of key proteins in the IRS-1/AKT/PPARαsignaling pathway,(insulin receptor substrate 1(IRS-1),phosphatidyqinositol-3 kinase(PI3K),phospho-protein kinase B(p-AKT),glucose transporter 2(GLUT2),phospho-glycogen synthase kinase 3 beta(p-GSK-3β),phospho-adenosine 5′-monophosphate-activated protein kinase alpha(p-AMPKα),peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α),PPARα,peroxisome proliferator-activated receptor gamma(PPARγ))and downregulation of GSK-3β,sterol regulatory element binding protein 1c(SREBP-1c),fatty acid synthase(FAS),and 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR).16S r RNA sequencing results revealed FCPS's ability to modulate gut microbiota dysbiosis in T2DM mice by promoting beneficial bacteria(e.g.,Lactobacillus_reuteri,Candidatus_Saccharimonas)and suppressing opportunistic pathogens(e.g.,Proteobacteria,Gammaproteobacteria,Escherichia-Shigella).These findings collectively suggest that FCPS has a marked effectiveness in improving glucose and lipid metabolism,decreasing inflammatory responses,as well as modulating the gut microbiota in T2DM mice via the gut-hepatic axis,demonstrating its potential as a functional food for diabetes prevention and management.
基金Supported by Fujian Provincial Science and Technology Innovation Joint Fund Project,No.2024Y9555Youth Research Project of the Science and Technology Plan of Fujian Provincial Health Commission,No.2024QNB005+1 种基金Fujian Provincial Natural Science Foundation Project,No.2024J011124Fujian Provincial Medical Project for Creating Dual High-Quality Development(High Level and High Standard),No.ETK2025004.
文摘This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.
文摘BACKGROUND Radial head fractures constitute approximately one-third of all elbow fractures,significantly impacting the young and active population.While open reduction and internal fixation is the preferred treatment for displaced fractures,its high complication rate in comminuted fractures has led to the increasing use of radial head arthroplasty(RHA).RHA provides improved functional outcomes with fewer complications,yet its long-term efficacy remains a topic of debate.AIM To evaluate the functional outcomes of patients undergoing RHA with a modular metallic prosthesis for comminuted Mason type III and IV radial head fractures.METHODS A prospective and retrospective hospital-based study was conducted at Dayanand Medical College and Hospital,Ludhiana over 32 months(January 2021-August 2023).A total of 26 patients with Mason type III and IV fractures were included,with six retrospective and 20 prospective cases.Functional outcomes were assessed using the Mayo Elbow Performance Score(MEPS),elbow range of motion,pain via Visual Analog Scale,and activities of daily living at immediate postoperative,three-month,and six-month follow-ups.RESULTS MEPS at 6 months follow up for 4 cases(15.38%)had good scores,and 22 cases(84.62%)had excellent scores,with a mean±SD of 97.31±6.67.Comparisons showed significant improvement from immediate post-operative to 3 months(P<0.0001),from immediate post-operative to 6 months(P<0.0001),and between 3 months and 6 months(P<0.0001).None of the patients had elbow instability after radial head replacement and 22 cases(84.62%)had no complications,while 3 cases(11.54%)had a stiff elbow,and 1 case(3.85%)had heterotopic ossification.CONCLUSION RHA is an effective treatment for comminuted radial head fractures,providing stable elbow function with minimal complications.
基金supported by the National Key Research and Development Program of China(2022YFD1800904)the National Natural Science Foundation of China(31972650 and 32102673)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_0780)the China Postdoctoral Science Foundation(2020M682297)。
文摘Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.
基金supported by the National Natural Science Foundation of China (No.82174074)。
文摘This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared spectroscopy,X-ray diffraction,high-performance anion-exchange chromatography,and differential scanning calorimetry.Significant differences were observed in their morphological,physicochemical,and functional properties.PMS had a smaller particle size(13.68 μm),irregular polygonal shape,A-type,lower water absorption(62.67 %),and higher oil absorption(51.17 %).In contrast,SGS exhibited larger particles(31.75 μm),a nearly spherical shape,B-type,higher crystallinity(50.66 %),and greater amylose content(21.54 %),with superior thermal stability,shear resistance,and gelatinization enthalpy.SGS also contained higher resistant starch(83.28 %) and longer average chain length(20.58 %),but showed lower solubility,swelling power,light transmittance,and freeze-thaw stability.The physicochemical properties differences in crystal pattern and particle morphology between PMS and SGS lead to distinct behaviors during in vitro digestion and fermentation.These findings highlight the potential of medicinal plant starches in functional ingredients and industrial processes.
基金supported by the National Natural Science Foundation of China(Nos.32271777,31500365,31770499,and 42303014)Tianjin Natural Science Foundation(Nos.12JCYBJC19700 and 18JCYBJC96500)+1 种基金Tianjin Science and Technology Support Program(Nos.23YFZCSN00100,15ZCZDSF00410,and 23YFZCSN00210)the Special Investigation of Technological Basic Resources(No.2021FY101002)。
文摘Limitations regarding phosphorus(P)are widespread in ecosystems.Understanding the impacts of the wetland types on microbially mediated soil P availability and cycling is essential for the effective management of wetlands.In this study,the Beidagang wetland,Baodi paddy field,and Dahuangpu wetland in Tianjin,China were chosen as representatives of the coastal wetland(B),constructed wetland(R),and swampy wetland(W),respectively.Sequential P extraction and metagenomics approaches were adopted to explore the soil P fraction and microbially regulated P cycle.Proteobacteria were the predominant microbes-related soil P cycle.IMPA,gph,rsbU_P,ugpQ,and glpK genes were dominant in organic P(Po)mineralization,while gcd,ppa,and ppx genes were dominant in inorganic P(Pi)solubilization.The salinity,NO_(3)^(-)-N concentration,the ratio of total carbon to total nitrogen(TC/TN),total carbon(TC),and the ratio of soil organic carbon to total P(SOC/TP)were the co-drivers of microbially mediated P cycle processes.Microbial network complexity-relate P cycle was the lowest in the coastal wetland.Salinity and NO_(3)^(-)-N exhibited a significant negative relation to the abundance of most genes-relate Pi solubilization and a remarkable positive correlation with the abundance of many genes-relate Po mineralization.These findings demonstrated that Po mineralization tended to occur in habitats with high salinity and nutrient imbalances,whereas the dissolution of Pi was prone to occur in low-salinity environments with relatively balanced soil nutrients.This study improves understanding of how salinity and soil nutrients jointly shape microbial-regulated soil P cycle in different types of wetlands.
基金Supported by National Natural Science Foundation of China,No.82000792General Project of Chongqing Natural Science Foundation,No.CSTB2023NSCQ-MSX0246 and No.CSTB2022NSCQ-MSX1271+1 种基金Research Project of the State Administration of Traditional Chinese Medicine on Collaborative Chronic Disease Management of Traditional Chinese Medicine and Western Medicine,No.CXZH2024087Science and Health Joint Project of Dazu District Science and Technology Bureau,No.DZKJ2024JSYJ-KWXM1002.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.
基金Supported by the National Natural Foundation of China(Grant No.12361028)the Foundation of Education Department of Jiangxi(Grant Nos.GJJ212305 and GJJ2202228)。
文摘In this paper,we construct new examples of hyperbolic metasurfaces in CP^(3) and CP^(4),and discusses the existence of solutions for a class of Fermat type functional equations.
