AIMTo investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). METHODSA retrospective an...AIMTo investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). METHODSA retrospective analysis of our OLT Database (2006-2015) was performed. Baseline haematological indices and intraoperative blood transfusion requirements, as a combination of cell salvage return and estimation of 300 mls/unit of allogenic blood, was noted as a surrogate for intraoperative bleeding. Two groups: Excessive transfusion (> 1200 mL returned) and No excessive transfusion ( RESULTSOf 322 OLT patients, 77 were excluded due to fulminant disease; redo transplant or baseline haemoglobin (Hb) of P ≤ 0.001), platelet count (P = 0.005), clauss fibrinogen (P = 0.004) and heparinase MA (P = 0.001) were all statistically significantly different. Univariate logistic regression with a cut-off of platelets 9</sup>/L as the predictor and Haemorrhage as the outcome showed an odds ratio of 1.393 (95%CI: 0.758-2.563; P = 0.286). Review of receiver operating characteristic curves showed an area under the curve (AUC) for platelet count of 0.604 (95%CI: 0.534-0.675; P = 0.005) as compared with AUC for fibrinogen level, 0.678 (95%CI: 0.612-0.744; P ≤ 0.001). A multivariate logistic regression shows United Kingdom model for End Stage Liver Disease (P = 0.006), Hb (P = 0.022) and Fibrinogen (P = 0.026) to be statistically significant, whereas Platelet count was not statistically significant. CONCLUSIONPlatelet count alone does not predict excessive transfusion. Additional investigations, e.g., clauss fibrinogen and viscoelastic tests, provide more robust assessment of bleeding-risk in thrombocytopenia and cirrhosis.展开更多
To investigate the additional clinical impact of hepatic ischaemia reperfusion injury (HIRI) on patients sustaining acute kidney injury (AKI) following liver transplantation. METHODSThis was a single-centre retrospect...To investigate the additional clinical impact of hepatic ischaemia reperfusion injury (HIRI) on patients sustaining acute kidney injury (AKI) following liver transplantation. METHODSThis was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation (OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT (> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration (CVVHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase (AST) within 24 h post-OLT was used as a surrogate marker for HIRI and severity was classified as minor (< 1000 IU/L), moderate (1000-5000 IU/L) or severe (> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications (AKI and HIRI) alone and then as a combined outcome. RESULTSOut of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF and 70% sustained moderate or severe HIRI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively (P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIRI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIRI had a longer median time to extubation (P < 0.001) and intensive care length of stay (P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIRI was 89%, compared to 100% in the groups with either or neither complication (P = 0.049). CONCLUSIONHIRI has an important role in the development of AKI post-OLT and has a negative impact on patient outcomes, especially when occurring alongside AKI.展开更多
Liver transplantation(LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusionfree transplantat...Liver transplantation(LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusionfree transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical "piggyback" techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management(PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. Variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT.展开更多
Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despit...Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.展开更多
Background: The impact of perioperative intravenous fluid administration on surgical outcomes has been documented in literature, but not specifically studied in the context of hepato-pancreato-biliary(HPB) surgery. Th...Background: The impact of perioperative intravenous fluid administration on surgical outcomes has been documented in literature, but not specifically studied in the context of hepato-pancreato-biliary(HPB) surgery. This study aimed to investigate the impact of postoperative intravenous fluid administration on intensive care unit(ICU), in this subgroup of patients. Methods: A single-center retrospective cohort of 241 HPB patients was assessed, focusing on intravenous fluid administration in ICU, during the first 24 h. Intravenous fluid variables were compared to hospital stay and postoperative complications. Data were assessed using Spearman's correlation test for bivariate correlations and logistic regression for multivariate analysis. Results: The median volume of intravenous fluid administered in the first 24 h postoperatively was 4380 mL, of which 2200 mL was crystalloid, 1500 mL colloid and 680 mL "other" fluid. Patients with one or more complications had a higher median total intravenous fluid input(4790 vs. 4300 mL), higher colloid volume(20 0 0 vs. 150 0 mL), lower urine output(1595 vs. 1900 mL) and greater overall fluid balance( + 3040 vs. + 2553 mL) than those without complications. There were correlations between total intravenous fluid volume administered( r = 0.278, P < 0.001), intravenous colloid input( r = 0.278, P < 0.001), urine output( r =-0.295, P < 0.001), positive fluid balance( r = 0.344, P < 0.001) and length of hospital stay. Logistic regression model was constructed to predict the occurrence of one or more complications; total intravenous fluid volume and overall fluid balance were both independent significant predictors(OR = 2.463, P = 0.007; OR = 1.001, P = 0.011; respectively). Conclusions: Administration of high volumes of intravenous fluids in the first 24 hours post-HPB surgery, along with higher positive fluid balance is associated with a higher rate of complications and longer hospital stay. Moreover, lower urine output is associated with longer hospital stay. Whether these are the cause of complications or the result of them remains unclear.展开更多
From the silence of a monastery where he voluntarily enclosed himself for many years, the enlightened mind of Ettore Majorana produced a new mathematics and a new physics which foster a historic leap in human knowledg...From the silence of a monastery where he voluntarily enclosed himself for many years, the enlightened mind of Ettore Majorana produced a new mathematics and a new physics which foster a historic leap in human knowledge. Here we quote his theory and some salient aspects of the construction of a machine, realized by Rolando Pelizza, which have demonstrated how exact and real the hypotheses of Ettore were. The world now has magnificent and new possibilities： it can annihilate matter, produce infinite energy at practically no cost, transmute matter and transfer it to other dimensions. But this knowledge, which we call Third Millennium Physics, will not immediately be available to humanity and first it is necessary to go through a process of gradually acquiring consciousness and change in human attitudes.展开更多
Volcanic eruptions release large amounts of ash clouds and gas aerosols into the atmosphere,which can be simulated by air quality prediction models.However,the performance of these models remains unsatisfactory,even t...Volcanic eruptions release large amounts of ash clouds and gas aerosols into the atmosphere,which can be simulated by air quality prediction models.However,the performance of these models remains unsatisfactory,even though both relevant physics and chemistry are considered.Hence,exploring the approaches for improvement such as inclusion of data assimilation is significative.In this study,we depict the modeling of the volcanic ash dispersion from the Hunga Tonga–Hunga Ha’apai underwater volcano,which erupted in a series of large explosions in late December 2021 and early January 2022.On 15 January 2022,a particularly significant explosion sent a massive ash cloud high into the atmosphere.We used the inline Weather Research and Forecasting model coupled with chemistry(WRF-Chem)and incorporated meteorological data assimilation within the Flux Adjusting Surface Data Assimilation System(FASDAS).We compared three forecast scenarios:one with only meteorology and no chemistry(OMET),one with gas and aerosol chemistry and no assimilation(NODA),and one with both chemistry and assimilation(FASDAS).We found that FASDAS resulted in lower planetary boundary layer height(PBLH),downward surface shortwave flux,and 2-m temperature by up to 800 m,200 W m^(−2),and 6℃ on the land portion,respectively,while the opposite was observed near the eruption site.We validated the model against the observations and the results showed that FASDAS significantly enhanced the model performance in retrieving meteorological variables.However,the simulations also revealed significant biases in the concentration of volcanic ash around the ash clouds.Data from the Copernicus TROPOspheric Monitoring Instrument Sentinel-5 Precursor(TROPOMI-S5P)showed a westward trend of the total SO2 emissions.This work demonstrates the significant contribution of data assimilation to the results of operational air quality predictions during violent volcanic eruption events.展开更多
An analytical method is presented, which enables the non-uniform velocity and pressure distributions at the impeller inlet of a pump to be accurately computed. The analyses are based on the potential flow theory and t...An analytical method is presented, which enables the non-uniform velocity and pressure distributions at the impeller inlet of a pump to be accurately computed. The analyses are based on the potential flow theory and the geometrical similarity of the streamline distribution along the leading edge of the impeller blades. The method is thus called streamline similarity method（SSM）. The obtained geometrical form of the flow distribution is then simply described by the geometrical variable G（s） and the first structural constant G_Ⅰ. As clearly demonstrated and also validated by experiments, both the flow velocity and the pressure distributions at the impeller inlet are usually highly non-uniform. This knowledge is indispensible for impeller blade designs to fulfill the shockless inlet flow condition. By introducing the second structural constant G_Ⅱ, the paper also presents the simple and accurate computation of the shock loss, which occurs at the impeller inlet. The introduction of two structural constants contributes immensely to the enhancement of the computational accuracies. As further indicated, all computations presented in this paper can also be well applied to the non-uniform exit flow out of an impeller of the Francis turbine for accurately computing the related mean values.展开更多
Autophagy is a cellular self-eating process essential for stress response and maintainingtissue homeostasis by lysosomal degradation of unwanted or damaged proteins and organelles.Here, we show that cells with defecti...Autophagy is a cellular self-eating process essential for stress response and maintainingtissue homeostasis by lysosomal degradation of unwanted or damaged proteins and organelles.Here, we show that cells with defective mitochondria induce autophagy to promotecell survival through activating the AMPK pathway. Loss of mitochondrial complex III proteincytochrome b activates the AMPK signaling and induced autophagy. Inhibiting mitochondria energeticsby mitochondria-targeted agents activates the AMPK signaling and induced autophagy.Genetic inhibition of AMPK inhibits autophagy induction in cells with defective mitochondria,while genetic inhibition of autophagy has no effect on AMPK activation. Mitochondria dysfunctionhas no effect of DNA repair of UV-induced DNA damage. However, mitochondria dysfunctionsensitizes cells to apoptosis induced by UV radiation. Genetic inhibition of autophagy orAMPK sensitized cells to apoptosis in cells with defective mitochondria. Our results demonstratethat AMPK and autophagy senses mitochondria dysfunction and serves as a mechanismfor survival. Our findings may provide new insights into the interplay between mitochondriafunction and autophagy process in maintaining tissue homeostasis, and suggest that this interactionmay play important roles in diseases such as cancer and neurodegeneration.展开更多
文摘AIMTo investigate the relationship between baseline platelet count, clauss fibrinogen, maximum amplitude (MA) on thromboelastography, and blood loss in orthotopic liver transplantation (OLT). METHODSA retrospective analysis of our OLT Database (2006-2015) was performed. Baseline haematological indices and intraoperative blood transfusion requirements, as a combination of cell salvage return and estimation of 300 mls/unit of allogenic blood, was noted as a surrogate for intraoperative bleeding. Two groups: Excessive transfusion (> 1200 mL returned) and No excessive transfusion ( RESULTSOf 322 OLT patients, 77 were excluded due to fulminant disease; redo transplant or baseline haemoglobin (Hb) of P ≤ 0.001), platelet count (P = 0.005), clauss fibrinogen (P = 0.004) and heparinase MA (P = 0.001) were all statistically significantly different. Univariate logistic regression with a cut-off of platelets 9</sup>/L as the predictor and Haemorrhage as the outcome showed an odds ratio of 1.393 (95%CI: 0.758-2.563; P = 0.286). Review of receiver operating characteristic curves showed an area under the curve (AUC) for platelet count of 0.604 (95%CI: 0.534-0.675; P = 0.005) as compared with AUC for fibrinogen level, 0.678 (95%CI: 0.612-0.744; P ≤ 0.001). A multivariate logistic regression shows United Kingdom model for End Stage Liver Disease (P = 0.006), Hb (P = 0.022) and Fibrinogen (P = 0.026) to be statistically significant, whereas Platelet count was not statistically significant. CONCLUSIONPlatelet count alone does not predict excessive transfusion. Additional investigations, e.g., clauss fibrinogen and viscoelastic tests, provide more robust assessment of bleeding-risk in thrombocytopenia and cirrhosis.
文摘To investigate the additional clinical impact of hepatic ischaemia reperfusion injury (HIRI) on patients sustaining acute kidney injury (AKI) following liver transplantation. METHODSThis was a single-centre retrospective study of consecutive adult patients undergoing orthotopic liver transplantation (OLT) between January 2013 and June 2014. Early AKI was identified by measuring serum creatinine at 24 h post OLT (> 1.5 × baseline) or by the use of continuous veno-venous haemofiltration (CVVHF) during the early post-operative period. Patients with and without AKI were compared to identify risk factors associated with this complication. Peak serum aspartate aminotransferase (AST) within 24 h post-OLT was used as a surrogate marker for HIRI and severity was classified as minor (< 1000 IU/L), moderate (1000-5000 IU/L) or severe (> 5000 IU/L). The impact on time to extubation, intensive care length of stay, incidence of chronic renal failure and 90-d mortality were examined firstly for each of the two complications (AKI and HIRI) alone and then as a combined outcome. RESULTSOut of the 116 patients included in the study, 50% developed AKI, 24% required CVVHF and 70% sustained moderate or severe HIRI. Median peak AST levels were 1248 IU/L and 2059 IU/L in the No AKI and AKI groups respectively (P = 0.0003). Furthermore, peak serum AST was the only consistent predictor of AKI on multivariate analysis P = 0.02. AKI and HIRI were individually associated with a longer time to extubation, increased length of intensive care unit stay and reduced survival. However, the patients who sustained both AKI and moderate or severe HIRI had a longer median time to extubation (P < 0.001) and intensive care length of stay (P = 0.001) than those with either complication alone. Ninety-day survival in the group sustaining both AKI and moderate or severe HIRI was 89%, compared to 100% in the groups with either or neither complication (P = 0.049). CONCLUSIONHIRI has an important role in the development of AKI post-OLT and has a negative impact on patient outcomes, especially when occurring alongside AKI.
文摘Liver transplantation(LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusionfree transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical "piggyback" techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management(PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. Variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT.
基金Supported by the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme
文摘Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.
文摘Background: The impact of perioperative intravenous fluid administration on surgical outcomes has been documented in literature, but not specifically studied in the context of hepato-pancreato-biliary(HPB) surgery. This study aimed to investigate the impact of postoperative intravenous fluid administration on intensive care unit(ICU), in this subgroup of patients. Methods: A single-center retrospective cohort of 241 HPB patients was assessed, focusing on intravenous fluid administration in ICU, during the first 24 h. Intravenous fluid variables were compared to hospital stay and postoperative complications. Data were assessed using Spearman's correlation test for bivariate correlations and logistic regression for multivariate analysis. Results: The median volume of intravenous fluid administered in the first 24 h postoperatively was 4380 mL, of which 2200 mL was crystalloid, 1500 mL colloid and 680 mL "other" fluid. Patients with one or more complications had a higher median total intravenous fluid input(4790 vs. 4300 mL), higher colloid volume(20 0 0 vs. 150 0 mL), lower urine output(1595 vs. 1900 mL) and greater overall fluid balance( + 3040 vs. + 2553 mL) than those without complications. There were correlations between total intravenous fluid volume administered( r = 0.278, P < 0.001), intravenous colloid input( r = 0.278, P < 0.001), urine output( r =-0.295, P < 0.001), positive fluid balance( r = 0.344, P < 0.001) and length of hospital stay. Logistic regression model was constructed to predict the occurrence of one or more complications; total intravenous fluid volume and overall fluid balance were both independent significant predictors(OR = 2.463, P = 0.007; OR = 1.001, P = 0.011; respectively). Conclusions: Administration of high volumes of intravenous fluids in the first 24 hours post-HPB surgery, along with higher positive fluid balance is associated with a higher rate of complications and longer hospital stay. Moreover, lower urine output is associated with longer hospital stay. Whether these are the cause of complications or the result of them remains unclear.
文摘From the silence of a monastery where he voluntarily enclosed himself for many years, the enlightened mind of Ettore Majorana produced a new mathematics and a new physics which foster a historic leap in human knowledge. Here we quote his theory and some salient aspects of the construction of a machine, realized by Rolando Pelizza, which have demonstrated how exact and real the hypotheses of Ettore were. The world now has magnificent and new possibilities： it can annihilate matter, produce infinite energy at practically no cost, transmute matter and transfer it to other dimensions. But this knowledge, which we call Third Millennium Physics, will not immediately be available to humanity and first it is necessary to go through a process of gradually acquiring consciousness and change in human attitudes.
基金Supported by the Research Supporting Project(PNURSP2024R503)of Princess Nourah Bint Abdulrahman University,Saudi Arabia.
文摘Volcanic eruptions release large amounts of ash clouds and gas aerosols into the atmosphere,which can be simulated by air quality prediction models.However,the performance of these models remains unsatisfactory,even though both relevant physics and chemistry are considered.Hence,exploring the approaches for improvement such as inclusion of data assimilation is significative.In this study,we depict the modeling of the volcanic ash dispersion from the Hunga Tonga–Hunga Ha’apai underwater volcano,which erupted in a series of large explosions in late December 2021 and early January 2022.On 15 January 2022,a particularly significant explosion sent a massive ash cloud high into the atmosphere.We used the inline Weather Research and Forecasting model coupled with chemistry(WRF-Chem)and incorporated meteorological data assimilation within the Flux Adjusting Surface Data Assimilation System(FASDAS).We compared three forecast scenarios:one with only meteorology and no chemistry(OMET),one with gas and aerosol chemistry and no assimilation(NODA),and one with both chemistry and assimilation(FASDAS).We found that FASDAS resulted in lower planetary boundary layer height(PBLH),downward surface shortwave flux,and 2-m temperature by up to 800 m,200 W m^(−2),and 6℃ on the land portion,respectively,while the opposite was observed near the eruption site.We validated the model against the observations and the results showed that FASDAS significantly enhanced the model performance in retrieving meteorological variables.However,the simulations also revealed significant biases in the concentration of volcanic ash around the ash clouds.Data from the Copernicus TROPOspheric Monitoring Instrument Sentinel-5 Precursor(TROPOMI-S5P)showed a westward trend of the total SO2 emissions.This work demonstrates the significant contribution of data assimilation to the results of operational air quality predictions during violent volcanic eruption events.
文摘An analytical method is presented, which enables the non-uniform velocity and pressure distributions at the impeller inlet of a pump to be accurately computed. The analyses are based on the potential flow theory and the geometrical similarity of the streamline distribution along the leading edge of the impeller blades. The method is thus called streamline similarity method（SSM）. The obtained geometrical form of the flow distribution is then simply described by the geometrical variable G（s） and the first structural constant G_Ⅰ. As clearly demonstrated and also validated by experiments, both the flow velocity and the pressure distributions at the impeller inlet are usually highly non-uniform. This knowledge is indispensible for impeller blade designs to fulfill the shockless inlet flow condition. By introducing the second structural constant G_Ⅱ, the paper also presents the simple and accurate computation of the shock loss, which occurs at the impeller inlet. The introduction of two structural constants contributes immensely to the enhancement of the computational accuracies. As further indicated, all computations presented in this paper can also be well applied to the non-uniform exit flow out of an impeller of the Francis turbine for accurately computing the related mean values.
基金This work was supported by the NIH/NIEHS grant ES024373 and ES016936(YYH)the American Cancer Society(ACS)grant RSG-13-078-01(YYH)+1 种基金the University of Chicago Cancer Research Center(P30 CA014599),the CTSA(UL1 TR000430)the University of Chicago Friends of Dermatology Endowment Fund.
文摘Autophagy is a cellular self-eating process essential for stress response and maintainingtissue homeostasis by lysosomal degradation of unwanted or damaged proteins and organelles.Here, we show that cells with defective mitochondria induce autophagy to promotecell survival through activating the AMPK pathway. Loss of mitochondrial complex III proteincytochrome b activates the AMPK signaling and induced autophagy. Inhibiting mitochondria energeticsby mitochondria-targeted agents activates the AMPK signaling and induced autophagy.Genetic inhibition of AMPK inhibits autophagy induction in cells with defective mitochondria,while genetic inhibition of autophagy has no effect on AMPK activation. Mitochondria dysfunctionhas no effect of DNA repair of UV-induced DNA damage. However, mitochondria dysfunctionsensitizes cells to apoptosis induced by UV radiation. Genetic inhibition of autophagy orAMPK sensitized cells to apoptosis in cells with defective mitochondria. Our results demonstratethat AMPK and autophagy senses mitochondria dysfunction and serves as a mechanismfor survival. Our findings may provide new insights into the interplay between mitochondriafunction and autophagy process in maintaining tissue homeostasis, and suggest that this interactionmay play important roles in diseases such as cancer and neurodegeneration.
