Graphene,owing to its inherent chemical inertness,biocompatibility,and mechanical flexibility,has great potential in guiding cell behaviors such as adhesion and differentiation.However,due to the two-dimensional(2D)na...Graphene,owing to its inherent chemical inertness,biocompatibility,and mechanical flexibility,has great potential in guiding cell behaviors such as adhesion and differentiation.However,due to the two-dimensional(2D)nature of graphene,the microfabrication of graphene into micro/nanoscale patterns has been widely adopted for guiding cellular assembly.In this study,we report crumpled graphene,i.e.,monolithically defined graphene with a nanoscale wavy surface texture,as a tissue engineering platform that can efficiently promote aligned C2C12 mouse myoblast cell differentiation.We imparted out-of-plane,nanoscale crumpled morphologies to flat graphene via compressive straininduced deformation.When C2C12 mouse myoblast cells were seeded on the uniaxially crumpled graphene,not only were the alignment and elongation promoted at a single-cell level but also the differentiation and maturation of myotubes were enhanced compared to that on flat graphene.These results demonstrate the utility of the crumpled graphene platform for tissue engineering and regenerative medicine for skeletal muscle tissues.展开更多
Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases.Although there have been several studies related to ultrasonic neuromodulation,th...Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases.Although there have been several studies related to ultrasonic neuromodulation,these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers.In addition,the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown.To determine these mechanisms and accurately modulate neural circuits,researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level.Herein,we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution.The piezoelectric micromachined ultrasonic transducers(pMUTs)with small membranes(submm membranes)generate enough power to stimulate neurons and enable precise modulation of neural circuits.We designed the ultrasound transducer as an array structure to enable localized modulation in the target region.In addition,we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments,such as in vitro cell cultures and brain slices.In this work,we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound.We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.展开更多
Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored str...Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.展开更多
The demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks.Direct intracerebral drug inje...The demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks.Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain,and it expands the utility of drugs by bypassing the blood-brain barrier(BBB).In addition,uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes,pointing to a critical issue still to be overcome.Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications,it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures,which differ from two-dimensionally fabricated shank-type neural probes.Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality.We fabricated a microfluidic interconnection cable(pFIC)and integrated it with a flexible penetrating microelectrode array(FPMA)that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base.We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection.This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities.展开更多
Sterol regulatory element binding protein-2(SREBP-2)is activated by cytokines or pathogen,such as virus or bacteria,but its association with diminished cholesterol levels in COVID-19 patients is unknown.Here,we evalua...Sterol regulatory element binding protein-2(SREBP-2)is activated by cytokines or pathogen,such as virus or bacteria,but its association with diminished cholesterol levels in COVID-19 patients is unknown.Here,we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19.Intriguingly,we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity.We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression,while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients.Using an infectious disease mouse model,inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages.These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.展开更多
基金S.N.gratefully acknowledges support from DTRA(HDTRA1620298),NSF(MRSEC DMR-1720633 and DMR-1708852)KRISS(KRISS–2018–GP2018-0012)+4 种基金ONR(N00014-17-1-2830)NASA ECF(NNX16AR56G)D.K.acknowledges financial support from NRF(2016R1C1B1009689,2019R1H1A1080221,2019R1A2C1090056),MOTIE(20000512)the new faculty research fund of Ajou University,and the Ajou University research fund.Experiments were carried out in part at the Materials Research Laboratory Central Research Facilities,Holonyak Micro and Nanotechnology Laboratory,and the Beckman Institute Imaging Technology Group at the University of Illinois at Urbana-ChampaignThis research was partially supported by the NSF through the University of Illinois at Urbana-Champaign Materials Research Science and Engineering Center DMR-1720633.
文摘Graphene,owing to its inherent chemical inertness,biocompatibility,and mechanical flexibility,has great potential in guiding cell behaviors such as adhesion and differentiation.However,due to the two-dimensional(2D)nature of graphene,the microfabrication of graphene into micro/nanoscale patterns has been widely adopted for guiding cellular assembly.In this study,we report crumpled graphene,i.e.,monolithically defined graphene with a nanoscale wavy surface texture,as a tissue engineering platform that can efficiently promote aligned C2C12 mouse myoblast cell differentiation.We imparted out-of-plane,nanoscale crumpled morphologies to flat graphene via compressive straininduced deformation.When C2C12 mouse myoblast cells were seeded on the uniaxially crumpled graphene,not only were the alignment and elongation promoted at a single-cell level but also the differentiation and maturation of myotubes were enhanced compared to that on flat graphene.These results demonstrate the utility of the crumpled graphene platform for tissue engineering and regenerative medicine for skeletal muscle tissues.
基金This work was supported by the Brain Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(NRF-2017M3C7A1028854)Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Ministry of Science&ICT(NRF-2017M3A9B3061319)This work was also supported by the KIST Institutional Program(2E29200).
文摘Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases.Although there have been several studies related to ultrasonic neuromodulation,these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers.In addition,the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown.To determine these mechanisms and accurately modulate neural circuits,researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level.Herein,we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution.The piezoelectric micromachined ultrasonic transducers(pMUTs)with small membranes(submm membranes)generate enough power to stimulate neurons and enable precise modulation of neural circuits.We designed the ultrasound transducer as an array structure to enable localized modulation in the target region.In addition,we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments,such as in vitro cell cultures and brain slices.In this work,we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound.We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.
基金funded by Korea Institute of Science and Technology Intramural Funding (2E26640,2E30952Republic of Korea)+7 种基金National Research Council of Science & Technology (NST) grant by Korean government (MSIP) (CRC-15-04-KISTRepublic of Korea)Center for Women In Science,Engineering,and Technology (WISET) grant by Korean government (WISET2020-525Republic of Korea)National Research Foundation of Korea (2017R1A2B2003993,2020R1A2C2004610Republic of Korea)UST Young Scientist Research Program through Korea University of Science and Technology (UST) (2017YS03Republic of Korea)。
文摘Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.
基金supported by the Brain Research Program under Grant No.NRF-2018M3C7A1022309 through the National Research Foundation of Korea.
文摘The demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks.Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain,and it expands the utility of drugs by bypassing the blood-brain barrier(BBB).In addition,uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes,pointing to a critical issue still to be overcome.Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications,it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures,which differ from two-dimensionally fabricated shank-type neural probes.Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality.We fabricated a microfluidic interconnection cable(pFIC)and integrated it with a flexible penetrating microelectrode array(FPMA)that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base.We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection.This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities.
基金supported by grants from the National Research Foundation of Korea(NRF)funded by the KRIBB Research Initiative Program(OGM4391913 and KGM5391911)supported by a grant from the National Research Foundation of Korea(NRF)funded by the Korean Government(MSIT)(grant no.2018R1A2A3075013,2019R1C1C1006300,2019R1A4A1028700,2020R1A4A4079817,and 2020R1A2C1004131)+2 种基金the Ministry of Education(NRF-2018R1D1A1B07050422)supported by KIST Institutional Program(2V07950)supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(grant no.HI15C0001).
文摘Sterol regulatory element binding protein-2(SREBP-2)is activated by cytokines or pathogen,such as virus or bacteria,but its association with diminished cholesterol levels in COVID-19 patients is unknown.Here,we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19.Intriguingly,we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity.We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression,while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients.Using an infectious disease mouse model,inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages.These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.
