The Warburg effect,characterized by excessive lactate production,and transcriptional dysregulation are two hallmarks of tumors.However,the precise influence of lactate on epigenetic modifications at a genome-wide leve...The Warburg effect,characterized by excessive lactate production,and transcriptional dysregulation are two hallmarks of tumors.However,the precise influence of lactate on epigenetic modifications at a genome-wide level and its impact on gene transcription in tumor cells remain unclear.In this study,we conducted genome-wide profiling of histone H3 lysine 18 lactylation(H3K18la)in T-cell acute lymphoblastic leukemia(T-ALL).We observed elevated lactate and H3K18la levels in T-ALL cells compared to normal T cells,with H3K18la levels positively associated with cell proliferation.Accordingly,we observed a significant shift in genome-wide H3K18la modifications from T cell immunity in normal T cells to leukemogenesis in T-ALL,correlated with altered gene transcription profiles.We showed that H3K18la primarily functions in active transcriptional regulation and observed clusters of H3K18la modifications resembling super-enhancers.Disrupting H3K18la modification revealed both synergistic and divergent changes between H3K18la and histone H3 lysine 27 acetylation(H3K27ac)modifications.Finally,we found that the high transcription of H3K18la target genes,IGFBP2 and IARS,is associated with inferior prognosis of T-ALL.These findings enhance our understanding of how metabolic disruptions contribute to transcription dysregulation through epigenetic changes in T-ALL,underscoring the interplay of histone modifications in maintaining oncogenic epigenetic stability.展开更多
Effective sealing of wet,dynamic and concealed wounds remains a formidable challenge in clinical practice.Sprayable hydrogel sealants are promising due to their ability to cover a wide area rapidly,but they face limit...Effective sealing of wet,dynamic and concealed wounds remains a formidable challenge in clinical practice.Sprayable hydrogel sealants are promising due to their ability to cover a wide area rapidly,but they face limitations in dynamic and moist environments.To address this issue,we have employed the principle of a homogeneous network to design a sprayable hydrogel sealant with enhanced fatigue resistance and reduced swelling.This network is formed by combining the spherical structure of lysozyme(LZM)with the orthotetrahedral structure of 4-arm-polyethylene glycol(4-arm-PEG).We have achieved exceptional sprayability by controlling the pH of the precursor solution.The homogeneous network,constructed through uniform cross-linking of amino groups in protein and 4-arm-PEG-NHS,provides the hydrogel with outstanding fatigue resistance,low swelling and sustained adhesion.In vitro testing demonstrated that it could endure 2000 cycles of underwater shearing,while in vivo experiments showed adhesion maintenance exceeding 24 h.Furthermore,the hydrogel excelled in sealing leaks and promoting ulcer healing in models including porcine cardiac hemorrhage,lung air leakage and rat oral ulcers,surpassing commonly used clinical materials.Therefore,our research presents an advanced biomaterial strategy with the potential to advance the clinical management of wet,dynamic and concealed wounds.展开更多
The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the t...The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.展开更多
A new online scheduling algorithm is proposed for photovoltaic(PV)systems with battery-assisted energy storage systems(BESS).The stochastic nature of renewable energy sources necessitates the employment of BESS to bal...A new online scheduling algorithm is proposed for photovoltaic(PV)systems with battery-assisted energy storage systems(BESS).The stochastic nature of renewable energy sources necessitates the employment of BESS to balance energy supplies and demands under uncertain weather conditions.The proposed online scheduling algorithm aims at minimizing the overall energy cost by performing actions such as load shifting and peak shaving through carefully scheduled BESS charging/discharging activities.The scheduling algorithm is developed by using deep deterministic policy gradient(DDPG),a deep reinforcement learning(DRL)algorithm that can deal with continuous state and action spaces.One of the main contributions of this work is a new DDPG reward function,which is designed based on the unique behaviors of energy systems.The new reward function can guide the scheduler to learn the appropriate behaviors of load shifting and peak shaving through a balanced process of exploration and exploitation.The new scheduling algorithm is tested through case studies using real world data,and the results indicate that it outperforms existing algorithms such as Deep Q-learning.The online algorithm can efficiently learn the behaviors of optimum non-casual off-line algorithms.展开更多
Nitric oxide(NO)and hydrogen sulfide(H_(2)S)gasotransmitters exhibit potential therapeutic effects in the car-diovascular system.Herein,biomimicking multilayer structures of biological blood vessels,bilayer smalldiame...Nitric oxide(NO)and hydrogen sulfide(H_(2)S)gasotransmitters exhibit potential therapeutic effects in the car-diovascular system.Herein,biomimicking multilayer structures of biological blood vessels,bilayer smalldiameter vascular grafts(SDVGs)with on-demand NO and H_(2)S release capabilities,were designed and fabri-cated.The keratin-based H_(2)S donor(KTC)with good biocompatibility and high stability was first synthesized and then electrospun with poly(L-lactide-co-caprolactone)(PLCL)to be used as the outer layer of grafts.The elec-trospun poly(ε-caprolactone)(PCL)mats were aminolyzed and further chelated with copper(II)ions to construct glutathione peroxidase(GPx)-like structural surfaces for the catalytic generation of NO,which acted as the inner layer of grafts.The on-demand release of NO and H_(2)S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells(HUASMCs).Dual releases of NO and H_(2)S gaso-transmitters could enhance their respective production,resulting in enhanced promotion of HUVECs and inhi-bition of HUASMCs owing to their combined actions.In addition,the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress.In rat abdominal aorta replacement models,the grafts remained patency for 6 months.These grafts were capable of facilitating rapid endothelialization and alleviating neo-intimal hyperplasia without obvious injury,inflammation,or thrombosis.More importantly,the grafts were expected to avoid calcification with the degradation of the grafts.Taken together,these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.展开更多
The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the t...The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.展开更多
Background:Small-diameter vascular grafts have become the focus of attention in tissue engineering.Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery.Ther...Background:Small-diameter vascular grafts have become the focus of attention in tissue engineering.Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery.Therefore,we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine(TMP)to overcome these limitations.Methods:Based on electrospinning and 3D printing,3D-printed electrospun vascular grafts loaded with TMP were fabricated.The inner layer of the graft was composed of electrospun poly(L-lactic-cocaprolactone)(PLCL)nanofibers and the outer layer consisted of 3D printed polycaprolactone(PCL)microfibers.The characterization and mechanical properties were tested.The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated.Additionally,rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety.Results:Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties.In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion.Afterwards,rat abdominal aorta was replaced with 3D-printed electrospun grafts.The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis.Moreover,no obvious aneurysmal dilatation was observed.Conclusions:The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.展开更多
基金supported by the Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province(Grant No.2022ZQNZD011 to Yu Liu)the Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics(Grant No.20dz2260900 to Yu Liu)+3 种基金the National Natural Science Foundation of China(Grant No.31970627 to Yu Liu)the Foundation of National Research Center for Translational Medicine at Shanghai[Grant No.NRCTM(SH)-2019-04 to Shuhong Shen]the Shanghai Municipal Health Commission(Grant No.20234Z0003 to Meng Yin)the Shanghai Science and Technology Development Foundation(Grant No.23Y11907200 to Meng Yin),China.
文摘The Warburg effect,characterized by excessive lactate production,and transcriptional dysregulation are two hallmarks of tumors.However,the precise influence of lactate on epigenetic modifications at a genome-wide level and its impact on gene transcription in tumor cells remain unclear.In this study,we conducted genome-wide profiling of histone H3 lysine 18 lactylation(H3K18la)in T-cell acute lymphoblastic leukemia(T-ALL).We observed elevated lactate and H3K18la levels in T-ALL cells compared to normal T cells,with H3K18la levels positively associated with cell proliferation.Accordingly,we observed a significant shift in genome-wide H3K18la modifications from T cell immunity in normal T cells to leukemogenesis in T-ALL,correlated with altered gene transcription profiles.We showed that H3K18la primarily functions in active transcriptional regulation and observed clusters of H3K18la modifications resembling super-enhancers.Disrupting H3K18la modification revealed both synergistic and divergent changes between H3K18la and histone H3 lysine 27 acetylation(H3K27ac)modifications.Finally,we found that the high transcription of H3K18la target genes,IGFBP2 and IARS,is associated with inferior prognosis of T-ALL.These findings enhance our understanding of how metabolic disruptions contribute to transcription dysregulation through epigenetic changes in T-ALL,underscoring the interplay of histone modifications in maintaining oncogenic epigenetic stability.
基金supported by the National key research and development program(2021YFB3800800)the National Natural Science Foundation of China(31922041,11932012,32171341,82202334)+2 种基金the 111 Project(B14018)Excellence Project of Shanghai Municipal Health Commission(20234Z0003)the Science and Technology Innovation Project and Excellent Academic Leader Project of Shanghai Science and Technology Committee(21S31901500,21XD1421100)are acknowledged.
文摘Effective sealing of wet,dynamic and concealed wounds remains a formidable challenge in clinical practice.Sprayable hydrogel sealants are promising due to their ability to cover a wide area rapidly,but they face limitations in dynamic and moist environments.To address this issue,we have employed the principle of a homogeneous network to design a sprayable hydrogel sealant with enhanced fatigue resistance and reduced swelling.This network is formed by combining the spherical structure of lysozyme(LZM)with the orthotetrahedral structure of 4-arm-polyethylene glycol(4-arm-PEG).We have achieved exceptional sprayability by controlling the pH of the precursor solution.The homogeneous network,constructed through uniform cross-linking of amino groups in protein and 4-arm-PEG-NHS,provides the hydrogel with outstanding fatigue resistance,low swelling and sustained adhesion.In vitro testing demonstrated that it could endure 2000 cycles of underwater shearing,while in vivo experiments showed adhesion maintenance exceeding 24 h.Furthermore,the hydrogel excelled in sealing leaks and promoting ulcer healing in models including porcine cardiac hemorrhage,lung air leakage and rat oral ulcers,surpassing commonly used clinical materials.Therefore,our research presents an advanced biomaterial strategy with the potential to advance the clinical management of wet,dynamic and concealed wounds.
文摘The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.
基金supported in part by the U.S National Science Foundation(NSF)(No.ECCS-1711087)NSF Center for Infrastructure Trustworthiness in Energy Systems(CITES).
文摘A new online scheduling algorithm is proposed for photovoltaic(PV)systems with battery-assisted energy storage systems(BESS).The stochastic nature of renewable energy sources necessitates the employment of BESS to balance energy supplies and demands under uncertain weather conditions.The proposed online scheduling algorithm aims at minimizing the overall energy cost by performing actions such as load shifting and peak shaving through carefully scheduled BESS charging/discharging activities.The scheduling algorithm is developed by using deep deterministic policy gradient(DDPG),a deep reinforcement learning(DRL)algorithm that can deal with continuous state and action spaces.One of the main contributions of this work is a new DDPG reward function,which is designed based on the unique behaviors of energy systems.The new reward function can guide the scheduler to learn the appropriate behaviors of load shifting and peak shaving through a balanced process of exploration and exploitation.The new scheduling algorithm is tested through case studies using real world data,and the results indicate that it outperforms existing algorithms such as Deep Q-learning.The online algorithm can efficiently learn the behaviors of optimum non-casual off-line algorithms.
基金supported by the National Natural Science Fund of China(81873923)Jiangsu Higher Education Institutions(19KJA310001 and PAPD)Jiangsu Collaborative Innovation Center of Biomedical Functional Materials.
文摘Nitric oxide(NO)and hydrogen sulfide(H_(2)S)gasotransmitters exhibit potential therapeutic effects in the car-diovascular system.Herein,biomimicking multilayer structures of biological blood vessels,bilayer smalldiameter vascular grafts(SDVGs)with on-demand NO and H_(2)S release capabilities,were designed and fabri-cated.The keratin-based H_(2)S donor(KTC)with good biocompatibility and high stability was first synthesized and then electrospun with poly(L-lactide-co-caprolactone)(PLCL)to be used as the outer layer of grafts.The elec-trospun poly(ε-caprolactone)(PCL)mats were aminolyzed and further chelated with copper(II)ions to construct glutathione peroxidase(GPx)-like structural surfaces for the catalytic generation of NO,which acted as the inner layer of grafts.The on-demand release of NO and H_(2)S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells(HUASMCs).Dual releases of NO and H_(2)S gaso-transmitters could enhance their respective production,resulting in enhanced promotion of HUVECs and inhi-bition of HUASMCs owing to their combined actions.In addition,the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress.In rat abdominal aorta replacement models,the grafts remained patency for 6 months.These grafts were capable of facilitating rapid endothelialization and alleviating neo-intimal hyperplasia without obvious injury,inflammation,or thrombosis.More importantly,the grafts were expected to avoid calcification with the degradation of the grafts.Taken together,these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.
文摘The authors regret to inform that four images/graphs in Fig.3 and 6 lacked order annotations of A/B/C/D.And the order annotations of cell viability of HUVECs and HUASMCs are opposite in Fig.6.The correct form of the two figures are as below.The authors apologize for any inconvenience caused and state that this does not change the discussion and the scientific conclusions of the article.
基金supported by the Science and Technology Commission of Shanghai Municipality,China(Nos.20S31900900,20DZ2254900)the Sino German Science Foundation Research Exchange Center,China(M-0263)+3 种基金China Education Association for International Exchange(2022181)supported by the General Project of SHDC(SHDC22021213)Fundamental Research Funds for the Central Universities(No.2232023D-10).This project was also supported by Researchers Supporting Project Number(RSP2024R65)King Saud University,Riyadh,Saudi Arabia.
文摘Background:Small-diameter vascular grafts have become the focus of attention in tissue engineering.Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery.Therefore,we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine(TMP)to overcome these limitations.Methods:Based on electrospinning and 3D printing,3D-printed electrospun vascular grafts loaded with TMP were fabricated.The inner layer of the graft was composed of electrospun poly(L-lactic-cocaprolactone)(PLCL)nanofibers and the outer layer consisted of 3D printed polycaprolactone(PCL)microfibers.The characterization and mechanical properties were tested.The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated.Additionally,rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety.Results:Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties.In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion.Afterwards,rat abdominal aorta was replaced with 3D-printed electrospun grafts.The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis.Moreover,no obvious aneurysmal dilatation was observed.Conclusions:The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.
