In order to study the minimization of excess sludge production,the reduction in the excess sludge production in the presence of an inhibitor and uncoupler was studied in this work.The experimental results show that su...In order to study the minimization of excess sludge production,the reduction in the excess sludge production in the presence of an inhibitor and uncoupler was studied in this work.The experimental results show that such an addition could effectively reduce the production of excess sludge.With the energy uncoupling model established in this work,energy uncoupling coefficient(Eu)was used to evaluate the reduction in excess sludge production.The energy uncoupling coefficients in the presence of dinitrophenol(dNP),Zn^(2+),and Cu^(2+)was 0.75,0.46,and 0.18,respectively.The analysis demonstrated that energy spilling occurred in the presence of dNP,and that dNP was an effective uncoupler for reducing the production of excess activated sludge without affecting the microbial respiration activity.展开更多
Chlorfenapyr poisoning is associated with high mortality due to the absence of evidence-based treatment strategies or specific antidotes.[1,2]Chlorfenapyr is a novel N-substituted halogenated pyrrole pro-insecticide.T...Chlorfenapyr poisoning is associated with high mortality due to the absence of evidence-based treatment strategies or specific antidotes.[1,2]Chlorfenapyr is a novel N-substituted halogenated pyrrole pro-insecticide.The active metabolite of tralopyril(a metabolite of chlorfenapyr)can uncouple oxidative phosphorylation and impair adenosine triphosphate(ATP)production.[3]Blood purification techniques,including hemoperfusion(HP),may facilitate tralopyril clearance.[4,5]Here,we present a case of severe chlorfenapyr poisoning that was treated with intensive HP.H owever,during follow-up,we unexpectedly found a ventricular aneurysm in the left ventricle that was not fully explained by coronary artery lesions.展开更多
Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochon...Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells(A10 cells). BAM15 relaxed phenylephrine(PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PEinduced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP,and niclosamide had the comparable IC50 value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide.BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells.BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.展开更多
Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induc...Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca^(2+)]_i, mitochondrial reactive oxygen species(mitoROS), and mitochondrial membrane potential of smooth muscle cells(A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine(PE)-and high K^(+)(KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE-and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE-and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATPchannel activation in smooth muscle cells of arteries.Triclosan treatment increased cytosolic [Ca^(2+)]_i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.展开更多
The gravity-driven membrane bioreactor(MBR)system is promising for decentralized sewage treatment because of its low energy consumption and maintenance requirements.However,the growing sludge not only increases membra...The gravity-driven membrane bioreactor(MBR)system is promising for decentralized sewage treatment because of its low energy consumption and maintenance requirements.However,the growing sludge not only increases membrane fouling,but also augments operational complexities(sludge discharge).We added the metabolic uncoupler 3,3’,4f,5-tetrachlorosalicylanilide(TC$)to the system to deal with the mentioned issues.Based on the results,TCS addition effectively decreased sludge ATP and sludge yield(reduced by 50%).Extracellular polymeric substances(EPS;proteins and polysaccharides)decreased with the addition of TCS and were transformed into dissolved soluble microbial products(SMPs)in the bulk solution,leading to the break of sludge floes into small fragments.Permeability was increased by more than two times,reaching 60-70 L/m2/h bar when 10-30 mg/L TCS were added,because of the reduced suspended sludge and the formation of a thin cake layer with low EPS levels.Resistance analyses confirmed that appropriate dosages of TCS primarily decreased the cake layer and hydraulically reversible resistances.Permeability decreased at high dosage(50 mg/L)due to the release of excess sludge fragments and SMP into the supernatant,with a thin but more compact fouling layer with low bioactivity developing on the membrane surface,causing higher cake layer and pore blocking resistances.Our study provides a fundamental understanding of how a metabolic uncoupler affects the sludge and bio-fouling layers at different dosages,with practical relevance for in situ sludge reduction and membrane fouling alleviation in MBR systems.展开更多
This study investigates the impact of different water coupling coefficients on the blasting effect of red sandstone.The analysis is based on the theories of detonation wave and elastic wave,focusing on the variation i...This study investigates the impact of different water coupling coefficients on the blasting effect of red sandstone.The analysis is based on the theories of detonation wave and elastic wave,focusing on the variation in wall pressure of the blasting holes.Using DDNP explosive as the explosive load,blasting tests were conducted on red sandstone specimens with four different water coupling coefficients:1.20,1.33,1.50,and 2.00.The study examines the morphologies of the rock specimens after blasting under these different water coupling coefficients.Additionally,the fractal dimensions of the surface cracks resulting from the blasting were calculated to provide a quantitative evaluation of the extent of rock damage.CT scanning and 3D reconstruction were performed on the post-blasting specimens to visually depict the extent of damage and fractures within the rock.Additionally,the volume fractal dimension and damage degree of the post-blasting specimens are calculated.The findings are then combined with numerical simulation to facilitate auxiliary analysis.The results demonstrate that an increase in the water coupling coefficient leads to a reduction in the peak pressure on the hole wall and the crushing zone,enabling more of the explosion energy to be utilized for crack propagation following the explosion.The specimens exhibited distinct failure patterns,resulting in corresponding changes in fractal dimensions.The simulated pore wall pressure–time curve validated the derived theoretical results,whereas the stress cloud map and explosion energy-time curve demonstrated the buffering effect of the water medium.As the water coupling coefficient increases,the buffering effect of the water medium becomes increasingly prominent.展开更多
The exercise recommendation system is emerging as a promising application in online learning scenarios,providing personalized recommendations to assist students with explicit learning directions.Existing solutions gen...The exercise recommendation system is emerging as a promising application in online learning scenarios,providing personalized recommendations to assist students with explicit learning directions.Existing solutions generally follow a collaborative filtering paradigm,while the implicit connections between students(exercises)have been largely ignored.In this study,we aim to propose an exercise recommendation paradigm that can reveal the latent connections between student-student(exercise-exercise).Specifically,a new framework was proposed,namely personalized exercise recommendation with student and exercise portraits(PERP).It consists of three sequential and interdependent modules:Collaborative student exercise graph(CSEG)construction,joint random walk,and recommendation list optimization.Technically,CSEG is created as a unified heterogeneous graph with students’response behaviors and student(exercise)relationships.Then,a joint random walk to take full advantage of the spectral properties of nearly uncoupled Markov chains is performed on CSEG,which allows for full exploration of both similar exercises that students have finished and connections between students(exercises)with similar portraits.Finally,we propose to optimize the recommendation list to obtain different exercise suggestions.After analyses of two public datasets,the results demonstrated that PERP can satisfy novelty,accuracy,and diversity.展开更多
几乎所有类型的心脏、大血管疾病均可引起心力衰竭（心衰）。心衰时,机体会启动一系列代偿机制,如心脏前负荷增加、心肌肥厚、交感兴奋性增强、RAAS激活等。心肌肥厚以心肌纤维增多为主,能源供体的线粒体也相应增多。解偶联蛋白2（uncou...几乎所有类型的心脏、大血管疾病均可引起心力衰竭（心衰）。心衰时,机体会启动一系列代偿机制,如心脏前负荷增加、心肌肥厚、交感兴奋性增强、RAAS激活等。心肌肥厚以心肌纤维增多为主,能源供体的线粒体也相应增多。解偶联蛋白2（uncoupling protein 2,UCP2）是位于线粒体内膜上的质子转运体,通过将内膜外的H＋转运回线粒体基质,导致氧化磷酸化解偶联。在心衰的发生发展过程中,展开更多
AIM: To detect the expression of mitochondrial uncoupling protein 2 (UCP2) in colon cancer and analyze the relation between UCP2 expression and clinical pathological features of colon cancer.METHODS: Fifteen colon tis...AIM: To detect the expression of mitochondrial uncoupling protein 2 (UCP2) in colon cancer and analyze the relation between UCP2 expression and clinical pathological features of colon cancer.METHODS: Fifteen colon tissue samples and 15 its adjacent tissue samples were obtained from colon cancer patients during surgical interventions. UCP2 expression was detected with immunohistochemical method in 10 normal controls, 10 hyperplastic polyp patients, 20 tubular adenoma patients and 78 colon cancer patients. Patients with rectal cancer were excluded. Quantitative reverse transcription polymerase chain reaction and Western blotting were used to detect UCP2 expressions in colon cancer tissue samples and its adjacent tissue samples. Relation between UCP2 expression and clinical pathological features of colon cancer was also analyzed. RESULTS: The UCP2 mRNA expression level was fourfold higher in colon cancer tissue samples than in its adjacent tissue samples. The UCP2 protein expression level was three-fold higher in colon cancer tissue samples than in its adjacent normal tissue samples. The UCP2 was mainly expressed in cytoplasm. The UCP2 was not expressed in normal colon mucosa. Strong positive staining for UCP2 with a diffuse distribution pattern was identified throughout the mucosa in colon cancer tissue samples with a positive expression rate of 85.9%. The UCP2 expression level was higher in colon cancer tissue samples at clinical stages Ⅲ and Ⅳ than in those at stageⅠ+ Ⅱ. Univariate analysis showed that the high UCP2 expression level was significantly correlated to colon cancer metastasis (hazard ratio = 4.321, confidence interval = 0.035-0.682, P = 0.046). CONCLUSION: UCP2 is highly expressed in human colon cancer tissue and may be involved in colon cancer metastasis.展开更多
Overall 5-years survival of pancreatic cancer patients is nearly 5%,making this cancer type one of the most lethal neoplasia.Furthermore,the incidence rate of pancreatic cancer has a growing trend that determines a co...Overall 5-years survival of pancreatic cancer patients is nearly 5%,making this cancer type one of the most lethal neoplasia.Furthermore,the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology.The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis,early metastasis of tumor,and resistance to almost all tested cytotoxic drugs.In this respect,the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer.Some studies have shown that the mitochondrial uncoupling protein 2(UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues.In addition,recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming,including aerobic glycolysis stimulation,promotion of cancer progression.These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer.In this editorial,recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.展开更多
In the present paper, the spectrums of off-diagonal infinite-dimensional Hamiltonian operators are studied. At first, we prove that the spectrum, the continuous-spectrum, and the union of the point-spectrum and residu...In the present paper, the spectrums of off-diagonal infinite-dimensional Hamiltonian operators are studied. At first, we prove that the spectrum, the continuous-spectrum, and the union of the point-spectrum and residual- spectrum of the operators are symmetric with respect to real axis and imaginary axis. Then for the purpose of reducing the dimension of the studied problems, the spectrums of the operators are expressed by the spectrums of the product of two self-adjoint operators in state spac,3. At last, the above-mentioned results are applied to plane elasticity problems, which shows the practicability of the results.展开更多
AIM To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and en...AIM To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11. Body weight, stool consistency and rectal bleeding were recorded daily, and these composed the disease activity index (DAI) score for the assessment of disease severity. After cervical dislocation was performed on day 14, the length of the colon in each mouse was measured, and colonic tissue was collected for further study, which included the following: haematoxylin and eosin staining, UCP2 and miR-133a detection by immunohistochemical staining, western blot and quantitative real-time PCR, measurement of apoptosis by TUNEL assay, and the assessment of inflammation (TNF-alpha, IL-1 beta, IL-6 and MCP1), oxidative stress (H2O2 and MDA) and metabolic parameters (ATP) by ELISA and colorimetric methods. RESULTS An animal model of IBD was successfully established, as shown by an increased DAI score, shortened colon length and specific pathologic changes, along with significantly increased UCP2 and decreased miR-133a levels. Compared with the DSS group, the severity of IBD was alleviated in the UCP2 and the miR-133a groups after successful UCP2 knockdown and miR-133a overexpression. The extent of apoptosis, as well as the levels of TNF-alpha, IL-1 beta, MDA and ATP, were significantly increased in both the UCP2 and miR-133a groups compared with the DSS group. CONCLUSION The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD.展开更多
Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups,...Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride （LCT） respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue （IBAT） mass, expressions of mRNA and protein of beta 3-adrenergic receptors （β3-AR）, uncoupling protein-1 （UCP1）, hormone sensitive lipase （HSL）, protein kinase A （PKA）, and adipose triglyceride lipase （ATGL） in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group （P〈O.05） after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group （P〈O.05）. Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group （P〈O.05）. Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.展开更多
Reactive oxygen species（ROS） are free radicals thought to mediate the neurotoxic effects of several neurodegenerative disorders.In the central nervous system,ROS can also trigger a phenotypic switch in both astrocyt...Reactive oxygen species（ROS） are free radicals thought to mediate the neurotoxic effects of several neurodegenerative disorders.In the central nervous system,ROS can also trigger a phenotypic switch in both astrocytes and microglia that further aggravates neurodegeneration,termed reactive gliosis.Negative regulators of ROS,such as mitochondrial uncoupling protein 2（UCP2） are neuroprotective factors that decrease neuron loss in models of stroke,epilepsy,and parkinsonism.However,it is unclear whether UCP2 acts purely to prevent ROS production,or also to prevent gliosis.In this review article,we discuss published evidence supporting the hypothesis that UCP2 is a neuroprotective factor both through its direct effects in decreasing mitochondrial ROS and through its effects in astrocytes and microglia.A major effect of UCP2 activation in glia is a change in the spectrum of secreted cytokines towards a more anti-inflammatory spectrum.There are multiple mechanisms that can control the level or activity of UCP2,including a variety of metabolites and micro RNAs.Understanding these mechanisms will be key to exploitingthe protective effects of UCP2 in therapies for multiple neurodegenerative conditions.展开更多
Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha(PPAR-a), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the dis...Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha(PPAR-a), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-a and PPAR-c was assessed in the nodose ganglion(NG) and the nucleus of the solitary tract(NTS). Hypertension induced by drinking high fructose(HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-a and PPAR-c were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-a, the mitochondrial uncoupling protein 2(UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats.These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.展开更多
Objective:To explore the effects of acupuncture on the expression of uncoupling protein 1（UCP1）gene of brown adipose tissue （BAT）in obese rats.Methods:The expression of UCP1gene ofBAT was determined with RT-PCR te...Objective:To explore the effects of acupuncture on the expression of uncoupling protein 1（UCP1）gene of brown adipose tissue （BAT）in obese rats.Methods:The expression of UCP1gene ofBAT was determined with RT-PCR technique.The changes of body weight,Lee’s index,body fat,andthe expression of UCP1gene of BAT in obese rats were observed before and after acupuncture.Results:The body weight,Lee’s indeX,body fat in obese rats were all markedly higher than those in normal rats,but the expression of UCP1gene of BAT in obese rats was all lower than that in normal rats.There werenegative correlation between the Obesity index and the expression of UCP1gent in BAT.After acupunc-ture the marked effect of weight loss was achieved while the expression of UCP1gene of BAT Obviously in-creased in obese rats.Conclusion:The abnormal reduction for expression of UCP1gene of BAT might bean important cause for the obesity.To promote the expression of UCP1in obese organism might be an im-portant cellular and mole展开更多
AIM:To confirm the hypothesis that polymorphisms of the uncoupling protein 3(UCP3)gene are associated with the occurrence of nonalcoholic fatty liver disease(NAFLD).METHODS:A total of 250 NAFLD patients(147 malesand 1...AIM:To confirm the hypothesis that polymorphisms of the uncoupling protein 3(UCP3)gene are associated with the occurrence of nonalcoholic fatty liver disease(NAFLD).METHODS:A total of 250 NAFLD patients(147 malesand 103 females)and 200 healthy individuals who served as controls(control,109 males and 91 females),aged between 6 and 16 years were enrolled in this study.The four non-synonymous single nucleotide polymorphisms(SNPs)in the UCP3 gene polymorphisms of rs1726745,rs3781907,rs11235972 and rs1800849,were genotyped using MassArray.Body mass index(BMI),waist and hip circumference,blood pressure(BP),fasting blood glucose(FBG),insulin and lipid profiles were measured and B-ultrasound examination was performed in all subjects.RESULTS:NAFLD patients showed risk factors for metabolic syndrome:elevated BMI,waist-to-hip ratio,BP,FBG,homeostasis model assessment-estimated insulin resistance,total triglyceride,total cholesterol and low-density lipoprotein-cholesterol,while decreased high-density lipoprotein-cholesterol level compared with the control group.The GG genotype distributions of rs11235972 in the NAFLD group differed significantly from that in the control group.We found that waist circumference between CC(58.76±6.45 cm)and CT+TT(57.00±5.59 cm),and hip circumference between CC(71.28±7.84 cm)and CT+TT genotypes(69.06±7.75 cm)were significantly different with and without rs1800849 variation(P<0.05).CONCLUSION:A higher prevalence of rs11235972 GG genotype was observed in the NAFLD group compared with the control group.No differences were observed for the other SNPs.However,there was a significant difference in body height in addition to waist and hip circumference between the CC(mutant type group)and CT+TT group with and without rs1800849 variation.展开更多
AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1(GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2 were analyzed in human NCI-H716 cells,...AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1(GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2 were analyzed in human NCI-H716 cells,which serve as a model for enteroendocrine L-cells,by quantitative reverse transcription-polymerase chain reaction and Western blotting before and after treatment with oleic acid.Localization of UCP2 and GLP-1 in NCI-H716 cells was assessed by immunofluorescence labeling.NCI-H716 cells were transiently transfected with a small interfering RNA(siRNA) that targets UCP2(siUCP2) or with a nonspecific siRNA using Lipofectamine 2000.The concentrations of bioactive GLP-1 in the medium were measured by enzyme linked immunosorbent assay.RESULTS:Both GLP-1 and UCP2 granules were expressed mainly in the cytoplasm of NCI-H716 cells.NCI-H716 cells that secreted GLP-1 also expressed UCP2.Time-course experiments revealed that release of GLP-1 from NCI-H716 cells into the medium reached a maximum at 120 min and remained stable until at least 180 min after treatment with oleic acid(the level of GLP-1 increased about 2.3-fold as compared with the level of GLP-1 in the control cells,P < 0.05).In an experiment to determine dose dependence,stimulation of NCI-H716 cells with ≤ 8 mmol oleic acid led to a concentration-dependent release of GLP-1 into the medium;10 mmol oleic acid diminished the release of GLP-1.Furthermore,GLP-1 secretion induced by oleic acid from NCI-H716 cells that were transfected with siUCP2 decreased to 41.8%,as compared with NCI-H716 cells that were transfected with a non-specific siRNA(P < 0.01).CONCLUSION:UCP2 affected GLP-1 secretion induced by oleic acid.UCP2 plays an important role in L-cell secretion that is induced by free fatty acids.展开更多
基金This work was supported by the Key Technologies Research and Development Program of the Tenth Five-Year Plan of Anhui Province(Grant No.04013029)the Research Foundation of Hefei University of Technology(Grant No.050801F).
文摘In order to study the minimization of excess sludge production,the reduction in the excess sludge production in the presence of an inhibitor and uncoupler was studied in this work.The experimental results show that such an addition could effectively reduce the production of excess sludge.With the energy uncoupling model established in this work,energy uncoupling coefficient(Eu)was used to evaluate the reduction in excess sludge production.The energy uncoupling coefficients in the presence of dinitrophenol(dNP),Zn^(2+),and Cu^(2+)was 0.75,0.46,and 0.18,respectively.The analysis demonstrated that energy spilling occurred in the presence of dNP,and that dNP was an effective uncoupler for reducing the production of excess activated sludge without affecting the microbial respiration activity.
基金supported by the National Key Research and Development Program of China(2023YFC3603100 and 2023YFC3603105)"Leading Goose"R&D Program of Zhejiang(2022C03076-4).
文摘Chlorfenapyr poisoning is associated with high mortality due to the absence of evidence-based treatment strategies or specific antidotes.[1,2]Chlorfenapyr is a novel N-substituted halogenated pyrrole pro-insecticide.The active metabolite of tralopyril(a metabolite of chlorfenapyr)can uncouple oxidative phosphorylation and impair adenosine triphosphate(ATP)production.[3]Blood purification techniques,including hemoperfusion(HP),may facilitate tralopyril clearance.[4,5]Here,we present a case of severe chlorfenapyr poisoning that was treated with intensive HP.H owever,during follow-up,we unexpectedly found a ventricular aneurysm in the left ventricle that was not fully explained by coronary artery lesions.
基金supported by the National Natural Science Foundation of China (Nos. 91739102 and 81773725)
文摘Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells(A10 cells). BAM15 relaxed phenylephrine(PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PEinduced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP,and niclosamide had the comparable IC50 value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide.BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells.BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.
基金supported by the National Natural Science Foundation of China(Grant Nos.81373406 and 81421063)
文摘Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca^(2+)]_i, mitochondrial reactive oxygen species(mitoROS), and mitochondrial membrane potential of smooth muscle cells(A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine(PE)-and high K^(+)(KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE-and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE-and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATPchannel activation in smooth muscle cells of arteries.Triclosan treatment increased cytosolic [Ca^(2+)]_i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.
基金This work was jointly supported by the National Natural Science Foundation of China(Grant No.51608150)the Open Project of State Key Laboratory of Urban Water Resource and Environment,Harbin Institute of Technology(No.ES201810-02)+3 种基金the Natural Science Foundation of Heilongjiang Province(No.E2017042)the Natural Science Foundation of Harbin(No.2017RAQXJ206)special support from the China Postdoctoral Fund(No.2018T110303)special support from the Heilongjiang Postdoctoral Found(No.LBH-TZ14).
文摘The gravity-driven membrane bioreactor(MBR)system is promising for decentralized sewage treatment because of its low energy consumption and maintenance requirements.However,the growing sludge not only increases membrane fouling,but also augments operational complexities(sludge discharge).We added the metabolic uncoupler 3,3’,4f,5-tetrachlorosalicylanilide(TC$)to the system to deal with the mentioned issues.Based on the results,TCS addition effectively decreased sludge ATP and sludge yield(reduced by 50%).Extracellular polymeric substances(EPS;proteins and polysaccharides)decreased with the addition of TCS and were transformed into dissolved soluble microbial products(SMPs)in the bulk solution,leading to the break of sludge floes into small fragments.Permeability was increased by more than two times,reaching 60-70 L/m2/h bar when 10-30 mg/L TCS were added,because of the reduced suspended sludge and the formation of a thin cake layer with low EPS levels.Resistance analyses confirmed that appropriate dosages of TCS primarily decreased the cake layer and hydraulically reversible resistances.Permeability decreased at high dosage(50 mg/L)due to the release of excess sludge fragments and SMP into the supernatant,with a thin but more compact fouling layer with low bioactivity developing on the membrane surface,causing higher cake layer and pore blocking resistances.Our study provides a fundamental understanding of how a metabolic uncoupler affects the sludge and bio-fouling layers at different dosages,with practical relevance for in situ sludge reduction and membrane fouling alleviation in MBR systems.
基金National Key Research and Development Program of China(2021YFC2902103)National Natural Science Foundation of China(51934001)Fundamental Research Funds for the Central Universities(2023JCCXLJ02).
文摘This study investigates the impact of different water coupling coefficients on the blasting effect of red sandstone.The analysis is based on the theories of detonation wave and elastic wave,focusing on the variation in wall pressure of the blasting holes.Using DDNP explosive as the explosive load,blasting tests were conducted on red sandstone specimens with four different water coupling coefficients:1.20,1.33,1.50,and 2.00.The study examines the morphologies of the rock specimens after blasting under these different water coupling coefficients.Additionally,the fractal dimensions of the surface cracks resulting from the blasting were calculated to provide a quantitative evaluation of the extent of rock damage.CT scanning and 3D reconstruction were performed on the post-blasting specimens to visually depict the extent of damage and fractures within the rock.Additionally,the volume fractal dimension and damage degree of the post-blasting specimens are calculated.The findings are then combined with numerical simulation to facilitate auxiliary analysis.The results demonstrate that an increase in the water coupling coefficient leads to a reduction in the peak pressure on the hole wall and the crushing zone,enabling more of the explosion energy to be utilized for crack propagation following the explosion.The specimens exhibited distinct failure patterns,resulting in corresponding changes in fractal dimensions.The simulated pore wall pressure–time curve validated the derived theoretical results,whereas the stress cloud map and explosion energy-time curve demonstrated the buffering effect of the water medium.As the water coupling coefficient increases,the buffering effect of the water medium becomes increasingly prominent.
基金supported by the Industrial Support Project of Gansu Colleges under Grant No.2022CYZC-11Gansu Natural Science Foundation Project under Grant No.21JR7RA114+1 种基金National Natural Science Foundation of China under Grants No.622760736,No.1762078,and No.61363058Northwest Normal University Teachers Research Capacity Promotion Plan under Grant No.NWNU-LKQN2019-2.
文摘The exercise recommendation system is emerging as a promising application in online learning scenarios,providing personalized recommendations to assist students with explicit learning directions.Existing solutions generally follow a collaborative filtering paradigm,while the implicit connections between students(exercises)have been largely ignored.In this study,we aim to propose an exercise recommendation paradigm that can reveal the latent connections between student-student(exercise-exercise).Specifically,a new framework was proposed,namely personalized exercise recommendation with student and exercise portraits(PERP).It consists of three sequential and interdependent modules:Collaborative student exercise graph(CSEG)construction,joint random walk,and recommendation list optimization.Technically,CSEG is created as a unified heterogeneous graph with students’response behaviors and student(exercise)relationships.Then,a joint random walk to take full advantage of the spectral properties of nearly uncoupled Markov chains is performed on CSEG,which allows for full exploration of both similar exercises that students have finished and connections between students(exercises)with similar portraits.Finally,we propose to optimize the recommendation list to obtain different exercise suggestions.After analyses of two public datasets,the results demonstrated that PERP can satisfy novelty,accuracy,and diversity.
文摘几乎所有类型的心脏、大血管疾病均可引起心力衰竭（心衰）。心衰时,机体会启动一系列代偿机制,如心脏前负荷增加、心肌肥厚、交感兴奋性增强、RAAS激活等。心肌肥厚以心肌纤维增多为主,能源供体的线粒体也相应增多。解偶联蛋白2（uncoupling protein 2,UCP2）是位于线粒体内膜上的质子转运体,通过将内膜外的H＋转运回线粒体基质,导致氧化磷酸化解偶联。在心衰的发生发展过程中,
基金Supported by Scientific Research Fund from Jiangsu Province,No.BK2006243National Natural Science Foundation of China,No.30771039
文摘AIM: To detect the expression of mitochondrial uncoupling protein 2 (UCP2) in colon cancer and analyze the relation between UCP2 expression and clinical pathological features of colon cancer.METHODS: Fifteen colon tissue samples and 15 its adjacent tissue samples were obtained from colon cancer patients during surgical interventions. UCP2 expression was detected with immunohistochemical method in 10 normal controls, 10 hyperplastic polyp patients, 20 tubular adenoma patients and 78 colon cancer patients. Patients with rectal cancer were excluded. Quantitative reverse transcription polymerase chain reaction and Western blotting were used to detect UCP2 expressions in colon cancer tissue samples and its adjacent tissue samples. Relation between UCP2 expression and clinical pathological features of colon cancer was also analyzed. RESULTS: The UCP2 mRNA expression level was fourfold higher in colon cancer tissue samples than in its adjacent tissue samples. The UCP2 protein expression level was three-fold higher in colon cancer tissue samples than in its adjacent normal tissue samples. The UCP2 was mainly expressed in cytoplasm. The UCP2 was not expressed in normal colon mucosa. Strong positive staining for UCP2 with a diffuse distribution pattern was identified throughout the mucosa in colon cancer tissue samples with a positive expression rate of 85.9%. The UCP2 expression level was higher in colon cancer tissue samples at clinical stages Ⅲ and Ⅳ than in those at stageⅠ+ Ⅱ. Univariate analysis showed that the high UCP2 expression level was significantly correlated to colon cancer metastasis (hazard ratio = 4.321, confidence interval = 0.035-0.682, P = 0.046). CONCLUSION: UCP2 is highly expressed in human colon cancer tissue and may be involved in colon cancer metastasis.
基金Supported by grants from Associazione Italiana Ricerca Cancro,Milan,ItalyFondazione Cari Pa Ro,Padova,ItalyMinistero dell’Istruzione,dell’Universitàe della Ricerca,Rome,Italy
文摘Overall 5-years survival of pancreatic cancer patients is nearly 5%,making this cancer type one of the most lethal neoplasia.Furthermore,the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology.The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis,early metastasis of tumor,and resistance to almost all tested cytotoxic drugs.In this respect,the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer.Some studies have shown that the mitochondrial uncoupling protein 2(UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues.In addition,recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming,including aerobic glycolysis stimulation,promotion of cancer progression.These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer.In this editorial,recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.
基金supported by the National Natural Science Foundation of China under Grant No.10562002the Specialized Research Fund for the Doctoral Program of Higher Education of China under Grant No.20070126002+1 种基金the Natural Science Foundation of Inner Mongolia under Grant No.200508010103the Inner Mongolia University Scientific Research Starting Foundation for Talented Scholars under Grant No.207066
文摘In the present paper, the spectrums of off-diagonal infinite-dimensional Hamiltonian operators are studied. At first, we prove that the spectrum, the continuous-spectrum, and the union of the point-spectrum and residual- spectrum of the operators are symmetric with respect to real axis and imaginary axis. Then for the purpose of reducing the dimension of the studied problems, the spectrums of the operators are expressed by the spectrums of the product of two self-adjoint operators in state spac,3. At last, the above-mentioned results are applied to plane elasticity problems, which shows the practicability of the results.
基金National Natural Science Foundation of China,No.81370008 and No.81000169Natural Science Foundation of Zhejiang Province,No.R2110159,No.LY15H030006 and No.LY16H030003
文摘AIM To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11. Body weight, stool consistency and rectal bleeding were recorded daily, and these composed the disease activity index (DAI) score for the assessment of disease severity. After cervical dislocation was performed on day 14, the length of the colon in each mouse was measured, and colonic tissue was collected for further study, which included the following: haematoxylin and eosin staining, UCP2 and miR-133a detection by immunohistochemical staining, western blot and quantitative real-time PCR, measurement of apoptosis by TUNEL assay, and the assessment of inflammation (TNF-alpha, IL-1 beta, IL-6 and MCP1), oxidative stress (H2O2 and MDA) and metabolic parameters (ATP) by ELISA and colorimetric methods. RESULTS An animal model of IBD was successfully established, as shown by an increased DAI score, shortened colon length and specific pathologic changes, along with significantly increased UCP2 and decreased miR-133a levels. Compared with the DSS group, the severity of IBD was alleviated in the UCP2 and the miR-133a groups after successful UCP2 knockdown and miR-133a overexpression. The extent of apoptosis, as well as the levels of TNF-alpha, IL-1 beta, MDA and ATP, were significantly increased in both the UCP2 and miR-133a groups compared with the DSS group. CONCLUSION The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD.
基金supported by the National Natural Science Foundation of China(No.81172667 and No.81202203)
文摘Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride （LCT） respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue （IBAT） mass, expressions of mRNA and protein of beta 3-adrenergic receptors （β3-AR）, uncoupling protein-1 （UCP1）, hormone sensitive lipase （HSL）, protein kinase A （PKA）, and adipose triglyceride lipase （ATGL） in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group （P〈O.05） after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group （P〈O.05）. Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group （P〈O.05）. Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.
文摘Reactive oxygen species（ROS） are free radicals thought to mediate the neurotoxic effects of several neurodegenerative disorders.In the central nervous system,ROS can also trigger a phenotypic switch in both astrocytes and microglia that further aggravates neurodegeneration,termed reactive gliosis.Negative regulators of ROS,such as mitochondrial uncoupling protein 2（UCP2） are neuroprotective factors that decrease neuron loss in models of stroke,epilepsy,and parkinsonism.However,it is unclear whether UCP2 acts purely to prevent ROS production,or also to prevent gliosis.In this review article,we discuss published evidence supporting the hypothesis that UCP2 is a neuroprotective factor both through its direct effects in decreasing mitochondrial ROS and through its effects in astrocytes and microglia.A major effect of UCP2 activation in glia is a change in the spectrum of secreted cytokines towards a more anti-inflammatory spectrum.There are multiple mechanisms that can control the level or activity of UCP2,including a variety of metabolites and micro RNAs.Understanding these mechanisms will be key to exploitingthe protective effects of UCP2 in therapies for multiple neurodegenerative conditions.
基金supported by the National Natural Science Foundation of China(81573431 and 81773731)
文摘Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha(PPAR-a), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-a and PPAR-c was assessed in the nodose ganglion(NG) and the nucleus of the solitary tract(NTS). Hypertension induced by drinking high fructose(HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-a and PPAR-c were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-a, the mitochondrial uncoupling protein 2(UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats.These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
基金The item is supported by the National Nature Science Foundation(No.39970923)
文摘Objective:To explore the effects of acupuncture on the expression of uncoupling protein 1（UCP1）gene of brown adipose tissue （BAT）in obese rats.Methods:The expression of UCP1gene ofBAT was determined with RT-PCR technique.The changes of body weight,Lee’s index,body fat,andthe expression of UCP1gene of BAT in obese rats were observed before and after acupuncture.Results:The body weight,Lee’s indeX,body fat in obese rats were all markedly higher than those in normal rats,but the expression of UCP1gene of BAT in obese rats was all lower than that in normal rats.There werenegative correlation between the Obesity index and the expression of UCP1gent in BAT.After acupunc-ture the marked effect of weight loss was achieved while the expression of UCP1gene of BAT Obviously in-creased in obese rats.Conclusion:The abnormal reduction for expression of UCP1gene of BAT might bean important cause for the obesity.To promote the expression of UCP1in obese organism might be an im-portant cellular and mole
基金Supported by Zhejiang Provincial Natural Science Foundation of ChinaNo.Y2090137+8 种基金the National Key Technology R and D Program of ChinaNo.2012BAI02B03the Fundamental Research Funds for the Central UniversitiesMinistry of EducationChinaNo.2011KYJD008National Natural Science Foundation of ChinaNo.J20121252No.81200460
文摘AIM:To confirm the hypothesis that polymorphisms of the uncoupling protein 3(UCP3)gene are associated with the occurrence of nonalcoholic fatty liver disease(NAFLD).METHODS:A total of 250 NAFLD patients(147 malesand 103 females)and 200 healthy individuals who served as controls(control,109 males and 91 females),aged between 6 and 16 years were enrolled in this study.The four non-synonymous single nucleotide polymorphisms(SNPs)in the UCP3 gene polymorphisms of rs1726745,rs3781907,rs11235972 and rs1800849,were genotyped using MassArray.Body mass index(BMI),waist and hip circumference,blood pressure(BP),fasting blood glucose(FBG),insulin and lipid profiles were measured and B-ultrasound examination was performed in all subjects.RESULTS:NAFLD patients showed risk factors for metabolic syndrome:elevated BMI,waist-to-hip ratio,BP,FBG,homeostasis model assessment-estimated insulin resistance,total triglyceride,total cholesterol and low-density lipoprotein-cholesterol,while decreased high-density lipoprotein-cholesterol level compared with the control group.The GG genotype distributions of rs11235972 in the NAFLD group differed significantly from that in the control group.We found that waist circumference between CC(58.76±6.45 cm)and CT+TT(57.00±5.59 cm),and hip circumference between CC(71.28±7.84 cm)and CT+TT genotypes(69.06±7.75 cm)were significantly different with and without rs1800849 variation(P<0.05).CONCLUSION:A higher prevalence of rs11235972 GG genotype was observed in the NAFLD group compared with the control group.No differences were observed for the other SNPs.However,there was a significant difference in body height in addition to waist and hip circumference between the CC(mutant type group)and CT+TT group with and without rs1800849 variation.
基金Supported by Grant from the National Natural Science Foundation of China,No. 30771039
文摘AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1(GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2 were analyzed in human NCI-H716 cells,which serve as a model for enteroendocrine L-cells,by quantitative reverse transcription-polymerase chain reaction and Western blotting before and after treatment with oleic acid.Localization of UCP2 and GLP-1 in NCI-H716 cells was assessed by immunofluorescence labeling.NCI-H716 cells were transiently transfected with a small interfering RNA(siRNA) that targets UCP2(siUCP2) or with a nonspecific siRNA using Lipofectamine 2000.The concentrations of bioactive GLP-1 in the medium were measured by enzyme linked immunosorbent assay.RESULTS:Both GLP-1 and UCP2 granules were expressed mainly in the cytoplasm of NCI-H716 cells.NCI-H716 cells that secreted GLP-1 also expressed UCP2.Time-course experiments revealed that release of GLP-1 from NCI-H716 cells into the medium reached a maximum at 120 min and remained stable until at least 180 min after treatment with oleic acid(the level of GLP-1 increased about 2.3-fold as compared with the level of GLP-1 in the control cells,P < 0.05).In an experiment to determine dose dependence,stimulation of NCI-H716 cells with ≤ 8 mmol oleic acid led to a concentration-dependent release of GLP-1 into the medium;10 mmol oleic acid diminished the release of GLP-1.Furthermore,GLP-1 secretion induced by oleic acid from NCI-H716 cells that were transfected with siUCP2 decreased to 41.8%,as compared with NCI-H716 cells that were transfected with a non-specific siRNA(P < 0.01).CONCLUSION:UCP2 affected GLP-1 secretion induced by oleic acid.UCP2 plays an important role in L-cell secretion that is induced by free fatty acids.
