Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over ti...Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.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 chemical looping with oxygen uncoupling(CLOU)process,CuO is a promising material due to the high oxygen carrier capacity and exothermic reaction in fuel reactor but limited by the low melting point.The combusti...In the chemical looping with oxygen uncoupling(CLOU)process,CuO is a promising material due to the high oxygen carrier capacity and exothermic reaction in fuel reactor but limited by the low melting point.The combustion rate of carbon is faster than the decoupling rate of oxygen carrier(OC).Hence,high temperature tolerance and rapid oxygen release rate of CuO modified by three different ores were investigated in this study.The kinetics analysis of oxygen decoupling with Cu-based oxygen carriers was also evaluated.Results showed that CuO modified by chrysolite had faster oxygen release rate than that of CuO.Limestone showed obvious positive effect on the oxidization process.The selected OCs could keep stable in at least 20 cycles,for about 1200 min.Shrinking core model(SCM)fitted well for the decoupling process in the temperature range of 1123-1223 K.Reduction rate kinetic information may aid in the development of chemical looping with oxygen uncoupling(CLOU)technologies during reactor design and process modeling.Ternary doped copper oxide with chrysolite and limestone could improve the reactivity of CuO in decoupling and coupling process and also improve the high temperature tolerance.展开更多
AIM: To analyze the expression of uncoupling protein 2(UCP2) in retinal pigment epithelium(RPE) cells at the different human age, further explore the possible new target of RPE cells protection.METHODS: Adult retinal ...AIM: To analyze the expression of uncoupling protein 2(UCP2) in retinal pigment epithelium(RPE) cells at the different human age, further explore the possible new target of RPE cells protection.METHODS: Adult retinal pigment epithelial-19(ARPE-19) cells and the primary RPE cells at the different age(9-20 y,50-55 y, 60-70 y, >70 y) were cultured and harvested. The expression of UCP2 in these cells was detected by reverse transcription-polymerase chain reaction(RT-PCR), Western blot and confocal microscopy.RESULTS: Cells from the donors more than 60 y are larger and more fibroblastic in appearance compared to ARPE-19 cells and those primary cultures obtained from the younger individuals by using phase-contrast micrographs. Results of RT-PCR, Western blot and confocal microscopy all showed that UCP2 was highly expressed in ARPE-19 cells and in the younger primary cultured human RPE cells at the age of 9-20 y and 50-55 y, whereas lower expression of UCP2 was measured in the older primary cultured human RPE cells at the age more than 60 y.CONCLUSION: Expression of UCP2 gene is decreased in aged RPE cells, promoting the lower ability of anti-oxidation in these cells. It is indicated that UCP2 gene might be a new target for protecting the cells from oxidative stress damage.展开更多
Oxygen uncoupling characteristics of a natural manganese ore and a perovskitetype oxide CaMn_(0.5)Ti0_(37)5Fe_(0.125)O_(3)were studied by using a microfluidized bed thermogravimetric analysis(MFBTGA)technology which i...Oxygen uncoupling characteristics of a natural manganese ore and a perovskitetype oxide CaMn_(0.5)Ti0_(37)5Fe_(0.125)O_(3)were studied by using a microfluidized bed thermogravimetric analysis(MFBTGA)technology which is based on a realtime mass measurement of fluidizing particles inside a bubbling bed reactor.The chemical stability,kinetics of the oxygen release and uptake reactions and fluidization property were investigated and the experimental data measured by MFBTGA were compared with the results in a regular TGA instrument(TGA Q500).The regular TGA Q500 results show the reactivity of both the manganese ore and perovskite oxide are stable for multi cycles,and the oxygen uncoupling capacity of the manganese ore is~1.2%(mass)which is~2 times higher than that of the perovskite oxide.However,the experimental results from the MFBTGA indicated that there is a serious agglomeration for the manganese ore.A very important finding is that the reaction rate of oxygen release and oxygen uptake of the perovskite oxide measured by the MFBTGA are~2 and~4 times faster than that of testedby the TGA Q500.We can conclude that MFBTGA is a very useful tool to measure the reactivity stability and kinetics of oxygen carriers in highthroughput analysis instead of the regular TGA.展开更多
BACKGROUND: Uncoupling protein 2(UCP2) has been suggested to inhibit mitochondrial production of reactive oxygen species(ROS) by decreasing the mitochondrial membrane potential. Experimental acute pancreatitis is asso...BACKGROUND: Uncoupling protein 2(UCP2) has been suggested to inhibit mitochondrial production of reactive oxygen species(ROS) by decreasing the mitochondrial membrane potential. Experimental acute pancreatitis is associated with increased UCP2 expression, whereas UCP2 deficiency retards regeneration of aged mice from acute pancreatitis. Here, we have addressed biological and molecular functions of UCP2 in pancreatic stellate cells(PSCs), which are involved in pancreatic wound repair and fibrogenesis.METHODS: PSCs were isolated from 12 months old(aged) UCP2^(-/-) mice and animals of the wild-type(WT) strain C57BL/6. Proliferation and cell death were assessed by employing trypan blue staining and a 5-bromo-2'-deoxyuridine incorporation assay. Intracellular fat droplets were visualized by oil red O staining. Levels of m RNA were determined by RT-PCR, while protein expression was analyzed by immunoblotting and immunofluorescence analysis. Intracellular ROS levels were measured with 2', 7'-dichlorofluorescin diacetate. Expression of senescence-associated β-galactosidase(SA β-Gal) was used as a surrogate marker of cellular senescence.RESULTS: PSCs derived from UCP2^(-/-) mice proliferated at a lower rate than cells from WT mice. In agreement with this observation, the UCP2 inhibitor genipin displayed dosedependent inhibitory effects on WT PSC growth. Interestingly, ROS levels in PSCs did not differ between the two strains, and PSCs derived from UCP2^(-/-) mice did not senesce faster than those from corresponding WT cells. PSCs from UCP2^(-/-) mice and WT animals were also indistinguishable with respect to the activation-dependent loss of intracellular fat droplets, expression of the activation marker α-smooth muscle actin, type I collagen and the autocrine/paracrine mediators interleukin-6 and transforming growth factor-β1.CONCLUSIONS: A reduced proliferative capacity of PSC from aged UCP2^(-/-) mice may contribute to the retarded regeneration after acute pancreatitis. Apart from their slower growth, PSC of UCP2^(-/-) mice displayed no functional abnormalities. The antifibrotic potential of UCP2 inhibitors deserves further attention.展开更多
Objective: Determine the role of uncoupling protein 2 (UCP2) in the myocardial apoptosis of diabetic mellitus(DM). Methods: DM animal models were induced by streptozotocinon (STZ) on UCP2 knock-out mice (UCP2KO) and w...Objective: Determine the role of uncoupling protein 2 (UCP2) in the myocardial apoptosis of diabetic mellitus(DM). Methods: DM animal models were induced by streptozotocinon (STZ) on UCP2 knock-out mice (UCP2KO) and wild-type mice (WT), which were reared for 7 and 28 days after successful modeling, respectively. The expressions of relative protein for myocardial apoptosis, pro-caspase-9, were investigated using western blot. However, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to explain apoptosis at the DNA level. Results: Image analysis showed that the expression of pro-caspase-9 protein levels increased slightly in UCP-/- + DM-7-day group comparing with DM-7-day group (P > 0.05). The expression of pro-caspase-9 protein levels increased significantly (P < 0.05)in UCP-/- + DM-28-day group comparing with DM-28-day group. TUNEL analysis indicated that UCP2 reduced the number of apoptotic myocytes in the DM-28-day group by 70% in comparison to DM-7-day group by 30% (P < 0.05). Conclusion UCP2 may be one of the most important factors that contribute to the myocardial apoptosis of DM.展开更多
Uncoupling protein 1 (UCP1) expressed by the brown adipose tissue (BAT) in the mitochondrial crista acts as a homeostatic thermogenerator of eutherians. The evaluation of UCP1 expression in the BAT offers significant ...Uncoupling protein 1 (UCP1) expressed by the brown adipose tissue (BAT) in the mitochondrial crista acts as a homeostatic thermogenerator of eutherians. The evaluation of UCP1 expression in the BAT offers significant scientific insight, especially in studies targeting limited areas such as the periarterial and pericardial regions of small experimental mammals. However, the negligible amount of this adipose tissue would render the general quantitative evaluation of the protein unreliable because of lipid contamination and low protein concentration. To address this problem, we quantitatively evaluated UCP1 expression in the mitochondrion of the mouse interscapular BAT using immunoelectron microscopy and immunohistochemical studies using a combination of primary and secondary antibodies in scheme A (rabbit anti-UCP1 IgG/gold particle-conjugated goat anti-rabbit IgG), B (rabbit IgG/gold particle-conjugated goat anti-rabbit IgG), C (rabbit anti-UCP1 IgG/gold particle-unconjugated goat anti-rabbit IgG), and D (rabbit IgG/gold particle-unconjugated goat anti-rabbit IgG). Scheme A shows the immunopositive reaction of obvious gold particles in the mitochondrial area, whereas other procedures revealed less distinctive reactions. The distinctive gold particle immunoreaction comprised electrical high-density spots with a mean diameter of >5 nm. However, in scheme B, the electrical high-density spots were scattered outside the mitochondrion and were significantly smaller than 4 nm;schemes C and D demonstrated few immunoreactions. Logistic regression analysis between schemes A and B showed that the threshold diameter of the electrical high-density spots measuring >5 nm indicated a true positive immunoreaction to anti-UCP1 antibody specifically in the mitochondrial area. Minor statistical difference was observed in the primary anti-UCP1 antibody between polyclonal IgG and monoclonal antibodies. Therefore, immunoelectron microscopy might be useful for evaluating negligible protein expression in some limited areas, such as UCP1 expression in the BAT of small experimental animals.展开更多
Energy uncoupling is often used for sludge reduction because it is easy to operate and does not require a significant amount of extra equipments(i.e.no additional tank required).However,over time the supernatant extra...Energy uncoupling is often used for sludge reduction because it is easy to operate and does not require a significant amount of extra equipments(i.e.no additional tank required).However,over time the supernatant extracted using this method can deteriorate,ultimately requiring further treatment.The purpose of this study was to determine the effect of using a low-pressure ultrafiltration membrane process for sludge water recovery after the sludge had undergone an energy uncoupling treatment(using 3,3’,4’,5-tetrachlorosalicylanilide(TCS)).Energy uncoupling was found to break apart sludge floe by reducing extracellular polymeric substances(EPS)and adenosine triphosphate(ATP)content.Analysis of supernatant indicated that when energy uncoupling and membrane filtration were coapplied and the TCS dosage was below 30 mg/L,there was no significant deterioration in organic component removal.However,ammonia and phosphate concentrations were found to increase as the concentration of TCS added increased.Additionally,due to low sludge concentrations and EPS contents,addition of 30-60 mg/L TCS during sludge reduction increased the permeate flux(two times higher than the control)and decreased the hydraulic reversible and cake layer resistances.In contrast,high dosage of TCS aggravated membrane fouling by forming compact fouling layers.In general,this study found that the co-application of energy uncoupling and membrane filtration processes represents an effective alternative method for simultaneous sludge reduction and sludge supernatant recovery.展开更多
This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson’s disease(PD).Mitochondria provide cellular energy in the...This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson’s disease(PD).Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation,but as an integral part of this process,superoxides and other reactive oxygen species are also produced.Excessive free radical production contributes to oxidative stress.Cells have evolved to handle such stress via various endogenous anti-oxidant proteins.One such family of proteins is the mitochondrial uncoupling proteins(UCPs),which are anion carriers located in the mitochondrial inner membrane.There are five known homologues(UCP1 to 5),of which UCP4 and 5 are predominantly expressed in neural cells.In a series of previous publications,we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium(MPP+;toxic metabolite of MPTP)and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential,and reducing oxidative stress.We also showed how their expression can be influenced by nuclear factor kappa-B(NF-B)signaling pathway specifically in UCP4.Furthermore,we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin(hormone produced by adipocytes)acting via UCP2 against MPP+-induced toxicity.There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD.Their expression,which can be induced,may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.展开更多
The 3’-terminal flanking region of porcine uncoupling protein 3 (UCP3) was cloned, the sequence data revealed 15 nucleotide substitutions among Landrace and three Chinese native pig breeds named Neijiang, Minpig and ...The 3’-terminal flanking region of porcine uncoupling protein 3 (UCP3) was cloned, the sequence data revealed 15 nucleotide substitutions among Landrace and three Chinese native pig breeds named Neijiang, Minpig and Erhualian. The continuous 9 polymorphic sites were checked by PCR-RFLP, the results indicated that Erhualian had extraordinary gene frequency, presented most significant difference by x2 test compared with Landrace, Largewhite, Neijiang and Minpig respectively, significant level compared with Meishan; and Meishan also had significant difference compared with Landrace and Minpig respectively. These results can be concluded that Taihu pigs have special genetic characteristics among pig breeds.展开更多
Objective To investigate the involvement of sirtuin 1(SIRT1)-uncoupling protein 2(UCP2) pathway in the development of non-alcoholic fatty liver disease and whether berberine exerts its effects by regulating this pathw...Objective To investigate the involvement of sirtuin 1(SIRT1)-uncoupling protein 2(UCP2) pathway in the development of non-alcoholic fatty liver disease and whether berberine exerts its effects by regulating this pathway. Methods Male SD rats were divided into three groups: normal control group, high-fat diet group, and berberine supplement group. The rats in the normal control group were given normal diet while the rats in the other two groups were fed with high-fat diet. Rats in the berberine supplement group were concurrently given berberine(100 mg/kg body weight) once daily. After 16 weeks, the levels of serum, liver lipids, and serum aminotransferase were measured using an automatic biochemical analyzer. Superoxide dismutase(SOD) activity and malondialdehyde(MDA) content in the liver were measured using commercial kits. Histopathological changes of liver tissues were observed by hematoxylin and eosin(HE) staining and Oil Red O staining. The hepatic m RNA and protein levels of SIRT1 and UCP2 were assayed by reverse transcription polymerase chain reaction(RT-PCR) or Western blotting. Results Berberine supplement could significantly decrease the serum and liver lipid contents in rats fed with high-fat diet. Meanwhile, SOD level was significantly elevated, but MDA level was reduced in the liver. The results of HE and Oil Red O staining showed that the hepatic steatosis was alleviated in berberine supplement group. Furthermore, berberine induced an increase in SIRT1 expression but a decrease in UCP2 expression. Conclusion The regulation of hepatic SIRT1-UCP2 pathway may be an important mechanism by which berberine exerts the beneficial effects in NAFLD rats.展开更多
Uncoupling protein (UCP) is a proton translocator, which is located exclusively in the mitochondrial inner membrane of brown adipose tissue (BAT).It facilitates proton translocation across the membrane,resulting in th...Uncoupling protein (UCP) is a proton translocator, which is located exclusively in the mitochondrial inner membrane of brown adipose tissue (BAT).It facilitates proton translocation across the membrane,resulting in the dissipation展开更多
Objective To study the effects of 1,25-dihydroxyvitamin D3on high-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells.Methods The HK-2 cells with different culture m...Objective To study the effects of 1,25-dihydroxyvitamin D3on high-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells.Methods The HK-2 cells with different culture media were divided into normal glucose group (NG group,5.5 mmol/L D-glucose) ;high glucose group (HG group,30 mmol/L D-glucose) ;mannitol group (MG group,5.5 mmol/L D-glucose+24.5 mmol/L manni-展开更多
Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is...Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.展开更多
COVID-19 patients often experience dyspnea due to several factors. The underlying unique pathophysiology of dyspnea in COVID-19 is not yet fully understood, but it is believed to be related to a combination of respira...COVID-19 patients often experience dyspnea due to several factors. The underlying unique pathophysiology of dyspnea in COVID-19 is not yet fully understood, but it is believed to be related to a combination of respiratory, cardiovascular, and neuromuscular factors. Hypoxemia is considered one of the key symptoms of COVID-19. This affects the respiratory drive, which determines the rate, depth, and pattern of breathing. The relationship between increased ventilatory neural drive and abnormal gas exchange, particularly in the context of ventilation/perfusion (V/Q) mismatches and chemosensitivity, has gained significant attention following the COVID-19 pandemic. The ACE2 receptors allow viral entry into the lungs, leading to the loss of surfactant, hypoxic vasoconstriction, and intrapulmonary shunting that may result in a V/Q mismatch. Additionally, acidosis, hypercapnia, elevated 2,3-diphosphogly-cerate levels and fever may shift the oxygen diffusion curve rightward, lowering arterial oxygen saturation levels and triggering ventilatory responses. This paper examines how physio pathological factors such as altered gas diffusion, chemosensory feedback, V/Q ratios, altered compliance, arterial blood gases, and respiratory muscle dysfunction in these patients affect ventilatory drive. A review of the published literature was also conducted to determine the mechanism of dyspnea. To ensure appropriate gas exchange, individuals need to augment their minute ventilation (VE) when physiological dead space is elevated. This serves as a compensatory mechanism to counteract the effects of compromised gas exchange and keep adequate oxygenation throughout the body. The respiratory centers may experience dysregulation due to the impact of the virus on the respiratory system, which could affect the rhythm-generating and pattern-generating signals that are vital for regulating the respiratory rate and depth of breathing effort. The cerebral cortex, in conjunction with the brain stem centers, plays a crucial role in regulating ventilation during prolonged hypoxemia. This interaction between these two components may help elucidate the conscious respiratory sensation (or dyspnea) experienced by patients. It is hypothesized that neuroventilatory decoupling acts as a mechanism to prevent sensory signals from translating into mechanical or ventilatory responses. This decoupling phenomenon is believed to have a notable impact on the intensity of breathlessness. By understanding the relationship between increased ventilatory neural drive and abnormal gas exchange, particularly in the context of ventilation/perfusion (V/Q) mismatches and altered chemosensitivity, healthcare professionals can develop strategies to optimize respiratory support for COVID-19 patients.展开更多
In nature,there are widely distributed bi-modulus materials with different deformation characteristics under compressive and tensile stress states,such as concrete,rock and ceramics.Due to the lack of constitutive mod...In nature,there are widely distributed bi-modulus materials with different deformation characteristics under compressive and tensile stress states,such as concrete,rock and ceramics.Due to the lack of constitutive model that could reasonably consider the bi-modulus property of materials,and the lack of simple and reliable measurement methods for the tensile elastic parameters of materials,scientists and engineers always neglect the effect of the bi-modulus property of materials in engineering design and numerical simulation.To solve this problem,this study utilizes the uncoupled strain-driven constitutive model proposed by Latorre and Montáns(2020)to systematically study the distributions and magnitudes of stresses and strains of bi-modulus materials in the three-point bending test through the numerical method.Furthermore,a new method to synchronously measure the tensile and compressive elastic moduli of materials through the four-point bending test is proposed.The numerical results show that the bi-modulus property of materials has a significant effect on the stress,strain and displacement in the specimen utilized in the three-point and four-point bending tests.Meanwhile,the results from the numerical tests,in which the elastic constitutive model proposed by Latorre and Montáns(2020)is utilized,also indicate that the newly proposed measurement method has a good reliability.Although the new measurement method proposed in this study can synchronously and effectively measure the tensile and compressive elastic moduli,it cannot measure the tensile and compressive Poisson’s ratios.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
基金supported by a grant from the Bundesminis-terium für Bildung und Forschung (01ZX1903A)。
文摘Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms.
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financial support by the Fundamental Research Funds for the Central Universities(xjh012019019)the National Natural Science Foundation of China(51606087)。
文摘In the chemical looping with oxygen uncoupling(CLOU)process,CuO is a promising material due to the high oxygen carrier capacity and exothermic reaction in fuel reactor but limited by the low melting point.The combustion rate of carbon is faster than the decoupling rate of oxygen carrier(OC).Hence,high temperature tolerance and rapid oxygen release rate of CuO modified by three different ores were investigated in this study.The kinetics analysis of oxygen decoupling with Cu-based oxygen carriers was also evaluated.Results showed that CuO modified by chrysolite had faster oxygen release rate than that of CuO.Limestone showed obvious positive effect on the oxidization process.The selected OCs could keep stable in at least 20 cycles,for about 1200 min.Shrinking core model(SCM)fitted well for the decoupling process in the temperature range of 1123-1223 K.Reduction rate kinetic information may aid in the development of chemical looping with oxygen uncoupling(CLOU)technologies during reactor design and process modeling.Ternary doped copper oxide with chrysolite and limestone could improve the reactivity of CuO in decoupling and coupling process and also improve the high temperature tolerance.
基金Supported by the National Natural Science Foundation of China(No.81100665 No.81770929)
文摘AIM: To analyze the expression of uncoupling protein 2(UCP2) in retinal pigment epithelium(RPE) cells at the different human age, further explore the possible new target of RPE cells protection.METHODS: Adult retinal pigment epithelial-19(ARPE-19) cells and the primary RPE cells at the different age(9-20 y,50-55 y, 60-70 y, >70 y) were cultured and harvested. The expression of UCP2 in these cells was detected by reverse transcription-polymerase chain reaction(RT-PCR), Western blot and confocal microscopy.RESULTS: Cells from the donors more than 60 y are larger and more fibroblastic in appearance compared to ARPE-19 cells and those primary cultures obtained from the younger individuals by using phase-contrast micrographs. Results of RT-PCR, Western blot and confocal microscopy all showed that UCP2 was highly expressed in ARPE-19 cells and in the younger primary cultured human RPE cells at the age of 9-20 y and 50-55 y, whereas lower expression of UCP2 was measured in the older primary cultured human RPE cells at the age more than 60 y.CONCLUSION: Expression of UCP2 gene is decreased in aged RPE cells, promoting the lower ability of anti-oxidation in these cells. It is indicated that UCP2 gene might be a new target for protecting the cells from oxidative stress damage.
基金The research has received funding from the National Natural Science Foundation of China(51976102)the National Key Research and Development Plan of China(2016YFB0600802-A and No.2017YFE0112500).
文摘Oxygen uncoupling characteristics of a natural manganese ore and a perovskitetype oxide CaMn_(0.5)Ti0_(37)5Fe_(0.125)O_(3)were studied by using a microfluidized bed thermogravimetric analysis(MFBTGA)technology which is based on a realtime mass measurement of fluidizing particles inside a bubbling bed reactor.The chemical stability,kinetics of the oxygen release and uptake reactions and fluidization property were investigated and the experimental data measured by MFBTGA were compared with the results in a regular TGA instrument(TGA Q500).The regular TGA Q500 results show the reactivity of both the manganese ore and perovskite oxide are stable for multi cycles,and the oxygen uncoupling capacity of the manganese ore is~1.2%(mass)which is~2 times higher than that of the perovskite oxide.However,the experimental results from the MFBTGA indicated that there is a serious agglomeration for the manganese ore.A very important finding is that the reaction rate of oxygen release and oxygen uptake of the perovskite oxide measured by the MFBTGA are~2 and~4 times faster than that of testedby the TGA Q500.We can conclude that MFBTGA is a very useful tool to measure the reactivity stability and kinetics of oxygen carriers in highthroughput analysis instead of the regular TGA.
基金supported by a grant from the Bundesministerium für Bildung und Forschung(0315892A,GERONTOSYS program)
文摘BACKGROUND: Uncoupling protein 2(UCP2) has been suggested to inhibit mitochondrial production of reactive oxygen species(ROS) by decreasing the mitochondrial membrane potential. Experimental acute pancreatitis is associated with increased UCP2 expression, whereas UCP2 deficiency retards regeneration of aged mice from acute pancreatitis. Here, we have addressed biological and molecular functions of UCP2 in pancreatic stellate cells(PSCs), which are involved in pancreatic wound repair and fibrogenesis.METHODS: PSCs were isolated from 12 months old(aged) UCP2^(-/-) mice and animals of the wild-type(WT) strain C57BL/6. Proliferation and cell death were assessed by employing trypan blue staining and a 5-bromo-2'-deoxyuridine incorporation assay. Intracellular fat droplets were visualized by oil red O staining. Levels of m RNA were determined by RT-PCR, while protein expression was analyzed by immunoblotting and immunofluorescence analysis. Intracellular ROS levels were measured with 2', 7'-dichlorofluorescin diacetate. Expression of senescence-associated β-galactosidase(SA β-Gal) was used as a surrogate marker of cellular senescence.RESULTS: PSCs derived from UCP2^(-/-) mice proliferated at a lower rate than cells from WT mice. In agreement with this observation, the UCP2 inhibitor genipin displayed dosedependent inhibitory effects on WT PSC growth. Interestingly, ROS levels in PSCs did not differ between the two strains, and PSCs derived from UCP2^(-/-) mice did not senesce faster than those from corresponding WT cells. PSCs from UCP2^(-/-) mice and WT animals were also indistinguishable with respect to the activation-dependent loss of intracellular fat droplets, expression of the activation marker α-smooth muscle actin, type I collagen and the autocrine/paracrine mediators interleukin-6 and transforming growth factor-β1.CONCLUSIONS: A reduced proliferative capacity of PSC from aged UCP2^(-/-) mice may contribute to the retarded regeneration after acute pancreatitis. Apart from their slower growth, PSC of UCP2^(-/-) mice displayed no functional abnormalities. The antifibrotic potential of UCP2 inhibitors deserves further attention.
文摘Objective: Determine the role of uncoupling protein 2 (UCP2) in the myocardial apoptosis of diabetic mellitus(DM). Methods: DM animal models were induced by streptozotocinon (STZ) on UCP2 knock-out mice (UCP2KO) and wild-type mice (WT), which were reared for 7 and 28 days after successful modeling, respectively. The expressions of relative protein for myocardial apoptosis, pro-caspase-9, were investigated using western blot. However, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to explain apoptosis at the DNA level. Results: Image analysis showed that the expression of pro-caspase-9 protein levels increased slightly in UCP-/- + DM-7-day group comparing with DM-7-day group (P > 0.05). The expression of pro-caspase-9 protein levels increased significantly (P < 0.05)in UCP-/- + DM-28-day group comparing with DM-28-day group. TUNEL analysis indicated that UCP2 reduced the number of apoptotic myocytes in the DM-28-day group by 70% in comparison to DM-7-day group by 30% (P < 0.05). Conclusion UCP2 may be one of the most important factors that contribute to the myocardial apoptosis of DM.
文摘Uncoupling protein 1 (UCP1) expressed by the brown adipose tissue (BAT) in the mitochondrial crista acts as a homeostatic thermogenerator of eutherians. The evaluation of UCP1 expression in the BAT offers significant scientific insight, especially in studies targeting limited areas such as the periarterial and pericardial regions of small experimental mammals. However, the negligible amount of this adipose tissue would render the general quantitative evaluation of the protein unreliable because of lipid contamination and low protein concentration. To address this problem, we quantitatively evaluated UCP1 expression in the mitochondrion of the mouse interscapular BAT using immunoelectron microscopy and immunohistochemical studies using a combination of primary and secondary antibodies in scheme A (rabbit anti-UCP1 IgG/gold particle-conjugated goat anti-rabbit IgG), B (rabbit IgG/gold particle-conjugated goat anti-rabbit IgG), C (rabbit anti-UCP1 IgG/gold particle-unconjugated goat anti-rabbit IgG), and D (rabbit IgG/gold particle-unconjugated goat anti-rabbit IgG). Scheme A shows the immunopositive reaction of obvious gold particles in the mitochondrial area, whereas other procedures revealed less distinctive reactions. The distinctive gold particle immunoreaction comprised electrical high-density spots with a mean diameter of >5 nm. However, in scheme B, the electrical high-density spots were scattered outside the mitochondrion and were significantly smaller than 4 nm;schemes C and D demonstrated few immunoreactions. Logistic regression analysis between schemes A and B showed that the threshold diameter of the electrical high-density spots measuring >5 nm indicated a true positive immunoreaction to anti-UCP1 antibody specifically in the mitochondrial area. Minor statistical difference was observed in the primary anti-UCP1 antibody between polyclonal IgG and monoclonal antibodies. Therefore, immunoelectron microscopy might be useful for evaluating negligible protein expression in some limited areas, such as UCP1 expression in the BAT of small experimental animals.
基金This work was jointly supported by the National Natural Science Foundation of China(No.51608150)Open Project of State Key Laboratory of Urban Water Resource and Environment,Harbin Institute of Technology(No.ES201810-02)+2 种基金Natural Science Foundation of Heilongjiang Province(No.E2017042)China Postdoctoral Science Foundation Grant(Nos.2018T110303 and 2017M610210)Heilongjiang Province Postdoctoral Science Foundation Grant(LBH-TZ14 and LBHZ16070).
文摘Energy uncoupling is often used for sludge reduction because it is easy to operate and does not require a significant amount of extra equipments(i.e.no additional tank required).However,over time the supernatant extracted using this method can deteriorate,ultimately requiring further treatment.The purpose of this study was to determine the effect of using a low-pressure ultrafiltration membrane process for sludge water recovery after the sludge had undergone an energy uncoupling treatment(using 3,3’,4’,5-tetrachlorosalicylanilide(TCS)).Energy uncoupling was found to break apart sludge floe by reducing extracellular polymeric substances(EPS)and adenosine triphosphate(ATP)content.Analysis of supernatant indicated that when energy uncoupling and membrane filtration were coapplied and the TCS dosage was below 30 mg/L,there was no significant deterioration in organic component removal.However,ammonia and phosphate concentrations were found to increase as the concentration of TCS added increased.Additionally,due to low sludge concentrations and EPS contents,addition of 30-60 mg/L TCS during sludge reduction increased the permeate flux(two times higher than the control)and decreased the hydraulic reversible and cake layer resistances.In contrast,high dosage of TCS aggravated membrane fouling by forming compact fouling layers.In general,this study found that the co-application of energy uncoupling and membrane filtration processes represents an effective alternative method for simultaneous sludge reduction and sludge supernatant recovery.
基金This project is financially supported by the Henry G Leong Professorship in Neurology(SLH),the Donation Fund for Neurology Research(SLH),and Seed Funding for Basic Research,University of Hong Kong(PWLH)PWL Ho is supported by a Research Assistant ProfessorshipJWM Ho and HF Liu are supported by Postdoctoral Fellowships from the University of Hong Kong.
文摘This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson’s disease(PD).Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation,but as an integral part of this process,superoxides and other reactive oxygen species are also produced.Excessive free radical production contributes to oxidative stress.Cells have evolved to handle such stress via various endogenous anti-oxidant proteins.One such family of proteins is the mitochondrial uncoupling proteins(UCPs),which are anion carriers located in the mitochondrial inner membrane.There are five known homologues(UCP1 to 5),of which UCP4 and 5 are predominantly expressed in neural cells.In a series of previous publications,we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium(MPP+;toxic metabolite of MPTP)and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential,and reducing oxidative stress.We also showed how their expression can be influenced by nuclear factor kappa-B(NF-B)signaling pathway specifically in UCP4.Furthermore,we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin(hormone produced by adipocytes)acting via UCP2 against MPP+-induced toxicity.There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD.Their expression,which can be induced,may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 30000119) the National High Technology Research Development Program of China (Grant No. 2001AA213121).
文摘The 3’-terminal flanking region of porcine uncoupling protein 3 (UCP3) was cloned, the sequence data revealed 15 nucleotide substitutions among Landrace and three Chinese native pig breeds named Neijiang, Minpig and Erhualian. The continuous 9 polymorphic sites were checked by PCR-RFLP, the results indicated that Erhualian had extraordinary gene frequency, presented most significant difference by x2 test compared with Landrace, Largewhite, Neijiang and Minpig respectively, significant level compared with Meishan; and Meishan also had significant difference compared with Landrace and Minpig respectively. These results can be concluded that Taihu pigs have special genetic characteristics among pig breeds.
基金National Natural Science Foundation of China(No.81273617 and 81302878)Traditional Chinese Medicine Bureau of Guangdong Province(No.20152112)
文摘Objective To investigate the involvement of sirtuin 1(SIRT1)-uncoupling protein 2(UCP2) pathway in the development of non-alcoholic fatty liver disease and whether berberine exerts its effects by regulating this pathway. Methods Male SD rats were divided into three groups: normal control group, high-fat diet group, and berberine supplement group. The rats in the normal control group were given normal diet while the rats in the other two groups were fed with high-fat diet. Rats in the berberine supplement group were concurrently given berberine(100 mg/kg body weight) once daily. After 16 weeks, the levels of serum, liver lipids, and serum aminotransferase were measured using an automatic biochemical analyzer. Superoxide dismutase(SOD) activity and malondialdehyde(MDA) content in the liver were measured using commercial kits. Histopathological changes of liver tissues were observed by hematoxylin and eosin(HE) staining and Oil Red O staining. The hepatic m RNA and protein levels of SIRT1 and UCP2 were assayed by reverse transcription polymerase chain reaction(RT-PCR) or Western blotting. Results Berberine supplement could significantly decrease the serum and liver lipid contents in rats fed with high-fat diet. Meanwhile, SOD level was significantly elevated, but MDA level was reduced in the liver. The results of HE and Oil Red O staining showed that the hepatic steatosis was alleviated in berberine supplement group. Furthermore, berberine induced an increase in SIRT1 expression but a decrease in UCP2 expression. Conclusion The regulation of hepatic SIRT1-UCP2 pathway may be an important mechanism by which berberine exerts the beneficial effects in NAFLD rats.
基金Project supported by the National Natural Science Foundation of China.
文摘Uncoupling protein (UCP) is a proton translocator, which is located exclusively in the mitochondrial inner membrane of brown adipose tissue (BAT).It facilitates proton translocation across the membrane,resulting in the dissipation
文摘Objective To study the effects of 1,25-dihydroxyvitamin D3on high-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells.Methods The HK-2 cells with different culture media were divided into normal glucose group (NG group,5.5 mmol/L D-glucose) ;high glucose group (HG group,30 mmol/L D-glucose) ;mannitol group (MG group,5.5 mmol/L D-glucose+24.5 mmol/L manni-
基金supported by the National Natural Science Foundation of China[31872674]the Jilin Talent Development Foundation Grant[20200301018RQ]the Fundamental Research Funds for the Central Universities[CGZH202206].
文摘Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.
文摘COVID-19 patients often experience dyspnea due to several factors. The underlying unique pathophysiology of dyspnea in COVID-19 is not yet fully understood, but it is believed to be related to a combination of respiratory, cardiovascular, and neuromuscular factors. Hypoxemia is considered one of the key symptoms of COVID-19. This affects the respiratory drive, which determines the rate, depth, and pattern of breathing. The relationship between increased ventilatory neural drive and abnormal gas exchange, particularly in the context of ventilation/perfusion (V/Q) mismatches and chemosensitivity, has gained significant attention following the COVID-19 pandemic. The ACE2 receptors allow viral entry into the lungs, leading to the loss of surfactant, hypoxic vasoconstriction, and intrapulmonary shunting that may result in a V/Q mismatch. Additionally, acidosis, hypercapnia, elevated 2,3-diphosphogly-cerate levels and fever may shift the oxygen diffusion curve rightward, lowering arterial oxygen saturation levels and triggering ventilatory responses. This paper examines how physio pathological factors such as altered gas diffusion, chemosensory feedback, V/Q ratios, altered compliance, arterial blood gases, and respiratory muscle dysfunction in these patients affect ventilatory drive. A review of the published literature was also conducted to determine the mechanism of dyspnea. To ensure appropriate gas exchange, individuals need to augment their minute ventilation (VE) when physiological dead space is elevated. This serves as a compensatory mechanism to counteract the effects of compromised gas exchange and keep adequate oxygenation throughout the body. The respiratory centers may experience dysregulation due to the impact of the virus on the respiratory system, which could affect the rhythm-generating and pattern-generating signals that are vital for regulating the respiratory rate and depth of breathing effort. The cerebral cortex, in conjunction with the brain stem centers, plays a crucial role in regulating ventilation during prolonged hypoxemia. This interaction between these two components may help elucidate the conscious respiratory sensation (or dyspnea) experienced by patients. It is hypothesized that neuroventilatory decoupling acts as a mechanism to prevent sensory signals from translating into mechanical or ventilatory responses. This decoupling phenomenon is believed to have a notable impact on the intensity of breathlessness. By understanding the relationship between increased ventilatory neural drive and abnormal gas exchange, particularly in the context of ventilation/perfusion (V/Q) mismatches and altered chemosensitivity, healthcare professionals can develop strategies to optimize respiratory support for COVID-19 patients.
基金funding support from the National Key Research and Development Program of China(Grant No.2022YFC3102402)as well as from the National Natural Science Foundation of China(Grant No.51879257).
文摘In nature,there are widely distributed bi-modulus materials with different deformation characteristics under compressive and tensile stress states,such as concrete,rock and ceramics.Due to the lack of constitutive model that could reasonably consider the bi-modulus property of materials,and the lack of simple and reliable measurement methods for the tensile elastic parameters of materials,scientists and engineers always neglect the effect of the bi-modulus property of materials in engineering design and numerical simulation.To solve this problem,this study utilizes the uncoupled strain-driven constitutive model proposed by Latorre and Montáns(2020)to systematically study the distributions and magnitudes of stresses and strains of bi-modulus materials in the three-point bending test through the numerical method.Furthermore,a new method to synchronously measure the tensile and compressive elastic moduli of materials through the four-point bending test is proposed.The numerical results show that the bi-modulus property of materials has a significant effect on the stress,strain and displacement in the specimen utilized in the three-point and four-point bending tests.Meanwhile,the results from the numerical tests,in which the elastic constitutive model proposed by Latorre and Montáns(2020)is utilized,also indicate that the newly proposed measurement method has a good reliability.Although the new measurement method proposed in this study can synchronously and effectively measure the tensile and compressive elastic moduli,it cannot measure the tensile and compressive Poisson’s ratios.
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,