BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is curre...BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB.Levels of copper ion,lactate,glucose,heat shock protein-70(HSP-70),and dihydrolipoamide dehydrogenase(DLAT)were determined.A diabetic rat model was established and CPB was performed.The rats were assessed for the development of CPB-AKI,and for the association of AKI with cuproptosis by detecting copper levels,iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.RESULTS CPB resulted in elevations of copper,lactate,HSP-70 and DLAT in blood and urine in both diabetic and nondiabetic patients.CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats.Cuproptosis-related proteins also appeared to be significantly reduced.CONCLUSION CPB-AKI is associated with cuproptosis.Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.展开更多
Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics,including viscoelasticity and liquid crystal(LC)state.Thus,integrating osteoid-like features into 3D printing...Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics,including viscoelasticity and liquid crystal(LC)state.Thus,integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair.Despite extensive research on viscoelasticity,the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials.Moreover,the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood.Here,we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink.By utilizing these LC scaffolds as 3D research models,we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation,while viscoelasticity operates via mechanotransduction pathways.Additionally,our investigation revealed a synergistic effect between LC state and viscoelasticity,amplifying cellprotein interactions and osteogenic mechanotransduction processes.Furthermore,the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing.Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis,offering valuable insights for the biomimetic design of bone repair scaffolds.展开更多
Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical im...Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a mag- netoreceptor with remote magnetic stimulation. The noninvasive activation of neurons was achieved by neuronal expression of an exogenous magnetoreceptor, an iron-sulfur cluster assembly protein 1 （Iscal）. In HEK-293 cells and cultured hippocampal neurons expressing this magnetoreceptor, application of an external magnetic field resulted in membrane depolarization and calcium influx in a reproducible and reversible manner, as indicated by the ultrasensitive fluorescent calcium indicator GCaMP6s.Moreover, the magnetogenetic control of neuronal activity might be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for the external magnetic field applied. The activation of this magnetoreceptor can depolarize neurons and elicit trains of action potentials, which can be triggered repetitively with a remote magnetic field in whole-cell patch-clamp recording. In transgenic Caenorhabditis elegans expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4- specific neurons, application of the external magnetic field triggered muscle contraction and withdrawal behavior of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons, respectively. The advantages of magnetogenetics over optogenetics are its exclusive non-invasive, deep penetration, long-term continuous dosing, unlimited accessibility, spatial uniformity and relative safety. Like optogenetics that has gone through decade-long improvements, magnetogenetics, with continuous modification and maturation, will reshape the current landscape of neuromodulation toolboxes and will have a broad range of applications to basic and translational neuroscience as well as other biological sciences. We envision a new age of magnetogenetics is coming.展开更多
基金Supported by the Natural Science Foundation of Heilongjiang Province,No.LH2022H035the First Affiliated Hospital of Harbin Medical University Foundation,No.2024JQ14.
文摘BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB.Levels of copper ion,lactate,glucose,heat shock protein-70(HSP-70),and dihydrolipoamide dehydrogenase(DLAT)were determined.A diabetic rat model was established and CPB was performed.The rats were assessed for the development of CPB-AKI,and for the association of AKI with cuproptosis by detecting copper levels,iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.RESULTS CPB resulted in elevations of copper,lactate,HSP-70 and DLAT in blood and urine in both diabetic and nondiabetic patients.CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats.Cuproptosis-related proteins also appeared to be significantly reduced.CONCLUSION CPB-AKI is associated with cuproptosis.Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.
基金supported by the National Natural Science Foundation of China(31771047)Guangdong Provincial Natural Science Foundation of China(2022A1515010592and 2023A1515010107)+2 种基金Guangdong Provincial Key Areas R&D Programs(2022B1111080007)the Key Areas Research and Development Program of Guangzhou(202103030003)the Outstanding Innovative Talents Cultivation Funded Programs for Doctoral Students of Jinan University(2023CXB013).
文摘Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics,including viscoelasticity and liquid crystal(LC)state.Thus,integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair.Despite extensive research on viscoelasticity,the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials.Moreover,the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood.Here,we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink.By utilizing these LC scaffolds as 3D research models,we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation,while viscoelasticity operates via mechanotransduction pathways.Additionally,our investigation revealed a synergistic effect between LC state and viscoelasticity,amplifying cellprotein interactions and osteogenic mechanotransduction processes.Furthermore,the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing.Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis,offering valuable insights for the biomimetic design of bone repair scaffolds.
基金supported by Tsinghua-Peking Center for Life SciencesIDG/Mc Govern Foundationthe National Natural Science Foundation of China
文摘Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a mag- netoreceptor with remote magnetic stimulation. The noninvasive activation of neurons was achieved by neuronal expression of an exogenous magnetoreceptor, an iron-sulfur cluster assembly protein 1 （Iscal）. In HEK-293 cells and cultured hippocampal neurons expressing this magnetoreceptor, application of an external magnetic field resulted in membrane depolarization and calcium influx in a reproducible and reversible manner, as indicated by the ultrasensitive fluorescent calcium indicator GCaMP6s.Moreover, the magnetogenetic control of neuronal activity might be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for the external magnetic field applied. The activation of this magnetoreceptor can depolarize neurons and elicit trains of action potentials, which can be triggered repetitively with a remote magnetic field in whole-cell patch-clamp recording. In transgenic Caenorhabditis elegans expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4- specific neurons, application of the external magnetic field triggered muscle contraction and withdrawal behavior of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons, respectively. The advantages of magnetogenetics over optogenetics are its exclusive non-invasive, deep penetration, long-term continuous dosing, unlimited accessibility, spatial uniformity and relative safety. Like optogenetics that has gone through decade-long improvements, magnetogenetics, with continuous modification and maturation, will reshape the current landscape of neuromodulation toolboxes and will have a broad range of applications to basic and translational neuroscience as well as other biological sciences. We envision a new age of magnetogenetics is coming.
