AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.展开更多
Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been wide...Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been widely employed for liposome preparation.Although some studies have explored factors affecting liposomal size in microfluidic processes,most focus on small-sized liposomes,predominantly through experimental data analysis.However,the production of larger liposomes,which are equally significant,remains underexplored.In this work,we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning(ML)model capable of accurately predicting liposomal size.Experimental validation was conducted using a staggered herringbone micromixer(SHM)chip.Our findings reveal that most investigated variables significantly influence liposomal size,often interrelating in complex ways.We evaluated the predictive performance of several widely-used ML algorithms,including ensemble methods,through cross-validation(CV)for both lipo-some size and polydispersity index(PDI).A standalone dataset was experimentally validated to assess the accuracy of the ML predictions,with results indicating that ensemble algorithms provided the most reliable predictions.Specifically,gradient boosting was selected for size prediction,while random forest was employed for PDI prediction.We successfully produced uniform large(600 nm)and small(100 nm)liposomes using the optimised experimental conditions derived from the ML models.In conclusion,this study presents a robust methodology that enables precise control over liposome size distribution,of-fering valuable insights for medicinal research applications.展开更多
The hydrazine oxidation reaction(HzOR)has garnered significant attention as a feasible approach to replace sluggish anodic reactions to save energy.Nevertheless,there are still difficulties in developing highly effici...The hydrazine oxidation reaction(HzOR)has garnered significant attention as a feasible approach to replace sluggish anodic reactions to save energy.Nevertheless,there are still difficulties in developing highly efficient catalysts for the HzOR.Herein,we report amorphous ruthenium nanosheets(a-Ru NSs)with a thickness of approximately 9.6 nm.As a superior bifunctional electrocatalyst,a-Ru NSs exhibited enhanced electrocatalytic performance toward both the HzOR and hydrogen evolution reaction(HER),outperforming benchmark Pt/C catalysts,where the a-Ru NSs achieved a work-ing potential of merely-76 mV and a low overpotential of only 17 mV to attain a current density of 10 mA·cm^(-2) for the HzOR and HER,respectively.Furthermore,a-Ru NSs displayed a low cell voltage of 28 mV at 10 mA·cm^(-2) for overall hy-drazine splitting in a two-electrode electrolyzer.In situ Raman spectra revealed that the a-Ru NSs can efficiently promote N‒N bond cleavage,thereby producing more*NH_(2)and accelerating the progress of the reaction.展开更多
Flexible electronics is gaining prominence in modern technology,particularly in flexible displays,wearable electronics,and biomedical applications.Electrodes,as core components of flexible electronics,demand high cond...Flexible electronics is gaining prominence in modern technology,particularly in flexible displays,wearable electronics,and biomedical applications.Electrodes,as core components of flexible electronics,demand high conductivity,flexibility,and stretchability.However,traditional rigid conductive materials often generate interfacial slip with elastic substrates due to mismatched Young's modulus,adversely affecting device performance.Room-temperature liquid metals(LMs),with their high conductivity and stretchability,have emerged as ideal materials for stable and reliable flexible electronic devices.This review discusses the physical,chemical,and biocompatibility properties of LMs.Additionally,LM-based fabrication strategies including patterning and sintering for flexible electrodes are outlined.Applications in implantable medical devices,wearable electronics,and flexible energy storage are illustrated.Finally,the primary challenges and future research directions in LMs are identified.展开更多
BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This...BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This suggests that sex hormones may play an important role in changing renal function in patients with diabetes.There have been only a few studies on the correlation between sex hormones and DKD,which have contradictory conclusions.AIM To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus(T2DM).METHODS This retrospective cross-sectional study included 356 patients with T2DM.Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices.By adjusting for age,body mass index,systolic blood pressure,diastolic blood pressure,duration of diabetes,use of sodium-glucose cotrasporter-2 inhibitor,use of glucagon-like peptide-1 receptor agonist,hypertension,use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor,diabetic retinopathy,diabetic peripheral vascular disease,triglyceride,uric acid,and hemoglobin A1c,multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio(UACR)and DKD.RESULTS In men,dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors[regression coefficient(β)=-0.691,95%confidence interval(CI):-1.241 to-0.141 for quartile 4 vs quartile 1;P=0.006 for trend].Elevated levels of estradiol were positively associated with DKD[odds ratio(OR)=3.097,95%CI:1.083-8.856 for quartile 4 vs quartile 1;P=0.041 for trend],and higher luteinizing hormone(LH)levels were similarly associated with DKD(OR=4.164,95%CI:1.30-13.330 for quartile 4 vs quartile 1;P=0.048 for trend).In postmenopausal women,LH levels were positively correlated with log-transformed UACR and DKD(β=1.039,95%CI:0.284-1.794 for quartile 4 vs quartile 1;P=0.006 for trend and OR=15.117,95%CI:2.191-104.326 for quartile 4 vs quartile 1;P=0.004 for trend).Follicle-stimulating hormone(FSH)levels were also positively associated with DKD(OR=9.588,95%CI:1.680-54.709 for quartile 4 vs quartile 1;P=0.014 for trend).CONCLUSION In men with T2DM,elevated levels of estradiol and LH levels were positively associated with increased risk of DKD.In postmenopausal women with T2DM,high FSH and LH levels were positively associated with increased risk of DKD.展开更多
Localized manipulation of light interference and phase through surface microstructures provides new viable technologies for applications such as anti-counterfeiting,camouflage,high-density optical storage and display....Localized manipulation of light interference and phase through surface microstructures provides new viable technologies for applications such as anti-counterfeiting,camouflage,high-density optical storage and display.However,the single-color rendering mechanism and the material’s intrinsic properties,such as hydrophilicity,low hardness and low melting point,limit the range of applications.In this paper,we propose a structural color based on ultrathin ZrO_(2)thin films,which presents a visible full-spectrum color display.The structural color coating has ultrahigh flame retardancy,super UV resistance,super surface hardness and resistance to acid and alkali corrosion.The use of two different color development mechanisms realizes the hiding of the quick response(QR)code in visible light.The modified film exhibits superhydrophobic properties,unique anti-icing and self-cleaning properties,and shows the material’s potential for camouflage,anti-counterfeiting,military,marine and aerospace applications.展开更多
The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KC...The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.展开更多
基金Supported by grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
基金supported by the National Key Research and Development Plan of the Ministry of Science and Technology,China(Grant No.:2022YFE0125300)the National Natural Science Foundation of China(Grant No:81690262)+2 种基金the National Science and Technology Major Project,China(Grant No.:2017ZX09201004-021)the Open Project of National facility for Translational Medicine(Shanghai),China(Grant No.:TMSK-2021-104)Shanghai Jiao Tong University STAR Grant,China(Grant Nos.:YG2022ZD024 and YG2022QN111).
文摘Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been widely employed for liposome preparation.Although some studies have explored factors affecting liposomal size in microfluidic processes,most focus on small-sized liposomes,predominantly through experimental data analysis.However,the production of larger liposomes,which are equally significant,remains underexplored.In this work,we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning(ML)model capable of accurately predicting liposomal size.Experimental validation was conducted using a staggered herringbone micromixer(SHM)chip.Our findings reveal that most investigated variables significantly influence liposomal size,often interrelating in complex ways.We evaluated the predictive performance of several widely-used ML algorithms,including ensemble methods,through cross-validation(CV)for both lipo-some size and polydispersity index(PDI).A standalone dataset was experimentally validated to assess the accuracy of the ML predictions,with results indicating that ensemble algorithms provided the most reliable predictions.Specifically,gradient boosting was selected for size prediction,while random forest was employed for PDI prediction.We successfully produced uniform large(600 nm)and small(100 nm)liposomes using the optimised experimental conditions derived from the ML models.In conclusion,this study presents a robust methodology that enables precise control over liposome size distribution,of-fering valuable insights for medicinal research applications.
基金supported by the National Key R&D Program of China(2018YFA0702001)National Natural Science Foundation of China(22371268,22301287)+3 种基金Fundamental Research Funds for the Central Universities(WK2060000016)Anhui Provincial Natural Science Foundation(2208085J09,2208085QB33)Collaborative Innovation Program of Hefei Science Center,CAS(2022HSC-CIP020)Youth Innovation Promotion Association of the Chinese Academy of Science(2018494)and USTC Tang Scholar.
文摘The hydrazine oxidation reaction(HzOR)has garnered significant attention as a feasible approach to replace sluggish anodic reactions to save energy.Nevertheless,there are still difficulties in developing highly efficient catalysts for the HzOR.Herein,we report amorphous ruthenium nanosheets(a-Ru NSs)with a thickness of approximately 9.6 nm.As a superior bifunctional electrocatalyst,a-Ru NSs exhibited enhanced electrocatalytic performance toward both the HzOR and hydrogen evolution reaction(HER),outperforming benchmark Pt/C catalysts,where the a-Ru NSs achieved a work-ing potential of merely-76 mV and a low overpotential of only 17 mV to attain a current density of 10 mA·cm^(-2) for the HzOR and HER,respectively.Furthermore,a-Ru NSs displayed a low cell voltage of 28 mV at 10 mA·cm^(-2) for overall hy-drazine splitting in a two-electrode electrolyzer.In situ Raman spectra revealed that the a-Ru NSs can efficiently promote N‒N bond cleavage,thereby producing more*NH_(2)and accelerating the progress of the reaction.
基金supported by the National Key Research and Development Program of China(No.2021YFA1401100)the National Natural Science Foundation of China(Nos.61825403 and 61921005)
文摘Flexible electronics is gaining prominence in modern technology,particularly in flexible displays,wearable electronics,and biomedical applications.Electrodes,as core components of flexible electronics,demand high conductivity,flexibility,and stretchability.However,traditional rigid conductive materials often generate interfacial slip with elastic substrates due to mismatched Young's modulus,adversely affecting device performance.Room-temperature liquid metals(LMs),with their high conductivity and stretchability,have emerged as ideal materials for stable and reliable flexible electronic devices.This review discusses the physical,chemical,and biocompatibility properties of LMs.Additionally,LM-based fabrication strategies including patterning and sintering for flexible electrodes are outlined.Applications in implantable medical devices,wearable electronics,and flexible energy storage are illustrated.Finally,the primary challenges and future research directions in LMs are identified.
基金Supported by the National Natural Science Foundation of China,No.82270942.
文摘BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This suggests that sex hormones may play an important role in changing renal function in patients with diabetes.There have been only a few studies on the correlation between sex hormones and DKD,which have contradictory conclusions.AIM To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus(T2DM).METHODS This retrospective cross-sectional study included 356 patients with T2DM.Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices.By adjusting for age,body mass index,systolic blood pressure,diastolic blood pressure,duration of diabetes,use of sodium-glucose cotrasporter-2 inhibitor,use of glucagon-like peptide-1 receptor agonist,hypertension,use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor,diabetic retinopathy,diabetic peripheral vascular disease,triglyceride,uric acid,and hemoglobin A1c,multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio(UACR)and DKD.RESULTS In men,dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors[regression coefficient(β)=-0.691,95%confidence interval(CI):-1.241 to-0.141 for quartile 4 vs quartile 1;P=0.006 for trend].Elevated levels of estradiol were positively associated with DKD[odds ratio(OR)=3.097,95%CI:1.083-8.856 for quartile 4 vs quartile 1;P=0.041 for trend],and higher luteinizing hormone(LH)levels were similarly associated with DKD(OR=4.164,95%CI:1.30-13.330 for quartile 4 vs quartile 1;P=0.048 for trend).In postmenopausal women,LH levels were positively correlated with log-transformed UACR and DKD(β=1.039,95%CI:0.284-1.794 for quartile 4 vs quartile 1;P=0.006 for trend and OR=15.117,95%CI:2.191-104.326 for quartile 4 vs quartile 1;P=0.004 for trend).Follicle-stimulating hormone(FSH)levels were also positively associated with DKD(OR=9.588,95%CI:1.680-54.709 for quartile 4 vs quartile 1;P=0.014 for trend).CONCLUSION In men with T2DM,elevated levels of estradiol and LH levels were positively associated with increased risk of DKD.In postmenopausal women with T2DM,high FSH and LH levels were positively associated with increased risk of DKD.
基金supported by the National Key Research and Development Program of China(No.2021YFA1401100)the National Natural Science Foundation of China(Nos.61825403 and 61921005).
文摘Localized manipulation of light interference and phase through surface microstructures provides new viable technologies for applications such as anti-counterfeiting,camouflage,high-density optical storage and display.However,the single-color rendering mechanism and the material’s intrinsic properties,such as hydrophilicity,low hardness and low melting point,limit the range of applications.In this paper,we propose a structural color based on ultrathin ZrO_(2)thin films,which presents a visible full-spectrum color display.The structural color coating has ultrahigh flame retardancy,super UV resistance,super surface hardness and resistance to acid and alkali corrosion.The use of two different color development mechanisms realizes the hiding of the quick response(QR)code in visible light.The modified film exhibits superhydrophobic properties,unique anti-icing and self-cleaning properties,and shows the material’s potential for camouflage,anti-counterfeiting,military,marine and aerospace applications.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273458 to Jinfei Chen)the Start-up Fund for the Recruited Talents of the First Affiliated Hospital of Wenzhou Medical University(Grant No.2021QD025 to Jinfei Chen)。
文摘The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.
