Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinicalapplications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural pro...Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinicalapplications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, withtheir mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability andlongevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation;however, theprotective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels duringimplantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimeticneuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array.This customizable system achieves distributed and minimally invasive implantation across brain regions. Mostimportantly, the system’s nonvisual monitoring capability provides an early warning detection for intracranial softtissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstratesexceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperativeand chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential forfuture applications in neuroscience and brain-machine interfaces.展开更多
Taking advantage of the dispersive Fourier transformation technique, the decaying evolution processes of doublepulse mode-locking in a single-walled carbon-nanotube-based Er-doped fiber laser are observed in detail fo...Taking advantage of the dispersive Fourier transformation technique, the decaying evolution processes of doublepulse mode-locking in a single-walled carbon-nanotube-based Er-doped fiber laser are observed in detail for the first time to our knowledge. The decaying dynamics of the double-pulse mode-locking state is analyzed in the spectral and temporal domains. We reveal that the two pulses in one cluster disappear either simultaneously or one by one during the decaying processes of double-pulse mode-locking states. In addition, the spectral evolution patterns of the special double-pulse states(i.e., bound states) are extremely distinct at different decline rates of the pump power.展开更多
Engineered functional neural interfaces (fNIs) serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimula...Engineered functional neural interfaces (fNIs) serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms, fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.展开更多
The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits,which provides a promising approach for the study of p...The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits,which provides a promising approach for the study of progressive neurophysiological phenomena.Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance.However,lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness.Herein,we report a hybrid probe(Silk-Optrode)consisting of a silk protein optical fiber and multiple flexible microelectrode arrays.The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals.Silk plays an important role due to its high transparency,excellent biocompatibility,and mechanical controllability.Through the hydration of the silk optical fiber,the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue.The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses,surpassing previous work of a similar type.Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions.展开更多
Gold nanoclusters(Au NCs)are promising luminescent nanomaterials due to their outstanding optical properties.However,their relatively low quantum yields and environment-dependent photoluminescence properties have limi...Gold nanoclusters(Au NCs)are promising luminescent nanomaterials due to their outstanding optical properties.However,their relatively low quantum yields and environment-dependent photoluminescence properties have limited their biological applications.To address these problems,we developed a novel strategy to prepare chitosan oligosaccharide lactate(Chi)-functionalized Au NCs(Au NCs@Chi),which exhibited emission with enhanced quantum yield and elongated emission lifetime as compared to the Au NCs,as well as exhibited environment-independent photoluminescence properties.In addition,utilizing the free amino groups of Chi onto Au NCs@Chi,we designed a FRET-based sensing platform for the detection of hydrogen sulfide(H_(2)S).The Au NCs and the specific H_(2)S-sensitive merocyanine compound were respectively employed as an energy donor and acceptor in the platform.The addition of H_(2)S induced changes in the emission profile and luminescence lifetime of the platform with high sensitivity and selectivity.Utilization of the platform was demonstrated to detect exogenous and endogenous H_(2)S in vitro and in vivo through wavelength-ratiometric and time-resolved luminescence imaging(TLI).Compared to previously reported luminescent molecules,the platform was less affected by experimental conditions and showed minimized autofluorescence interference and improved accuracy of detection.展开更多
Background:Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration.However,the expression and function of Mc4r in the mouse limb and digit has not been fully invest...Background:Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration.However,the expression and function of Mc4r in the mouse limb and digit has not been fully investigated.Our previous work showed that Mc4r−/−mice fail to regenerate the digit,but whether activation of MC4R signaling could rescue digit regeneration,or stimulate proximal digit regeneration is not clear.Results:We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice.We found that Mc4r-GFP is mainly expressed in the limb nerves,and in the limb muscles that are undergoing secondary myogenesis.Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix.We also examined the effect ofα-MSH on mouse digit regeneration.We found that administration ofα-MSH in the Mc4r+/−mice rescue the delayed regeneration of distal digit tip.α-MSH could rescue distal digit regeneration in denervated hindlimbs.In addition,α-MSH could stimulate regeneration of the proximally amputated digit,which is non-regenerative.Conclusions:Mc4r expression in the mouse limb and digit is closely related to nerve tissues,andα-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.展开更多
基金This work was partially supported by the National Key R&D Program of China(Grant Nos.2019YFA0905200,2021ZD0201600,2021YFC2501500,2021YFF1200700,2022ZD0209300,2022ZD0212300,2022YFF0706500)National Natural Science Foundation of China(Grant No.61974154)+8 种基金Key Research Program of Frontier Sciences,CAS(Grant No.ZDBS-LYJSC024)Shanghai Pilot Program for Basic Research—Chinese Academy of Science,Shanghai Branch(Grant No.JCYJ-SHFY-2022-01)Shanghai Municipal Science and Technology Major Project(Grant No.2021SHZDZX)CAS Pioneer Hundred Talents Program,Shanghai Pujiang Program(Grant Nos.19PJ1410900,21PJ1415100)the Science and Technology Commission Foundation of Shanghai(No.21JM0010200)Shanghai Rising-Star Program(Grant No.22QA1410900)the Innovative Research Team of High-level Local Universities in Shanghai,the Jiangxi Province 03 Special Project and 5G Project(Grant No.20212ABC03W07)Fund for Central Government in Guidance of Local Science and Technology Development(Grant No.20201ZDE04013)Special Fund for Science and Technology Innovation Strategy of Guangdong Province(Grant Nos.2021B0909060002,2021B0909050004).
文摘Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinicalapplications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, withtheir mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability andlongevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation;however, theprotective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels duringimplantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimeticneuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array.This customizable system achieves distributed and minimally invasive implantation across brain regions. Mostimportantly, the system’s nonvisual monitoring capability provides an early warning detection for intracranial softtissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstratesexceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperativeand chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential forfuture applications in neuroscience and brain-machine interfaces.
基金National Natural Science Foundation of China(NSFC)(61223007)
文摘Taking advantage of the dispersive Fourier transformation technique, the decaying evolution processes of doublepulse mode-locking in a single-walled carbon-nanotube-based Er-doped fiber laser are observed in detail for the first time to our knowledge. The decaying dynamics of the double-pulse mode-locking state is analyzed in the spectral and temporal domains. We reveal that the two pulses in one cluster disappear either simultaneously or one by one during the decaying processes of double-pulse mode-locking states. In addition, the spectral evolution patterns of the special double-pulse states(i.e., bound states) are extremely distinct at different decline rates of the pump power.
文摘Engineered functional neural interfaces (fNIs) serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms, fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.
基金partially supported by the National Key R&D Program of China(Grant Nos.2019YFA0905200,2021ZD0201600,2021YFC2501500,2021YFF1200700,2022ZD0209300,2022ZD0212300)National Natural Science Foundation of China(Grant No.61974154)+8 种基金Key Research Program of Frontier Sciences,CAS(Grant No.ZDBSLY-JSC024)Shanghai Pilot Program for Basic Research—Chinese Academy of Science,Shanghai Branch(Grant No.JCYJ-SHFY-2022-01)Shanghai Municipal Science and Technology Major Project(Grant No.2021SHZDZX)CAS Pioneer Hundred Talents Program,Shanghai Pujiang Program(Grant Nos.19PJ1410900,21PJ1415100)the Science and Technology Commission Foundation of Shanghai(No.21JM0010200)Shanghai Rising-Star Program(Grant No.22QA1410900)the Innovative Research Team of High-level Local Universities in Shanghai,the Jiangxi Province 03 Special Project and 5G Project(Grant No.20212ABC03W07)Fund for Central Government in Guidance of Local Science and Technology Development(Grant No.20201ZDE04013)Special Fund for Science and Technology Innovation Strategy of Guangdong Province(Grant Nos.2021B0909060002,2021B0909050004)。
文摘The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits,which provides a promising approach for the study of progressive neurophysiological phenomena.Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance.However,lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness.Herein,we report a hybrid probe(Silk-Optrode)consisting of a silk protein optical fiber and multiple flexible microelectrode arrays.The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals.Silk plays an important role due to its high transparency,excellent biocompatibility,and mechanical controllability.Through the hydration of the silk optical fiber,the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue.The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses,surpassing previous work of a similar type.Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions.
基金supported by the National Program for Support of Top-Notch Young Professionalsthe Synergetic Innovation Center for Organic Electronics and Information Displaysthe Priority Academic Program Development of Jiangsu Higher Education Institutions(YX03001).
文摘Gold nanoclusters(Au NCs)are promising luminescent nanomaterials due to their outstanding optical properties.However,their relatively low quantum yields and environment-dependent photoluminescence properties have limited their biological applications.To address these problems,we developed a novel strategy to prepare chitosan oligosaccharide lactate(Chi)-functionalized Au NCs(Au NCs@Chi),which exhibited emission with enhanced quantum yield and elongated emission lifetime as compared to the Au NCs,as well as exhibited environment-independent photoluminescence properties.In addition,utilizing the free amino groups of Chi onto Au NCs@Chi,we designed a FRET-based sensing platform for the detection of hydrogen sulfide(H_(2)S).The Au NCs and the specific H_(2)S-sensitive merocyanine compound were respectively employed as an energy donor and acceptor in the platform.The addition of H_(2)S induced changes in the emission profile and luminescence lifetime of the platform with high sensitivity and selectivity.Utilization of the platform was demonstrated to detect exogenous and endogenous H_(2)S in vitro and in vivo through wavelength-ratiometric and time-resolved luminescence imaging(TLI).Compared to previously reported luminescent molecules,the platform was less affected by experimental conditions and showed minimized autofluorescence interference and improved accuracy of detection.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.31771283&31771608)the National Institute of Health(R01HD084440).
文摘Background:Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration.However,the expression and function of Mc4r in the mouse limb and digit has not been fully investigated.Our previous work showed that Mc4r−/−mice fail to regenerate the digit,but whether activation of MC4R signaling could rescue digit regeneration,or stimulate proximal digit regeneration is not clear.Results:We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice.We found that Mc4r-GFP is mainly expressed in the limb nerves,and in the limb muscles that are undergoing secondary myogenesis.Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix.We also examined the effect ofα-MSH on mouse digit regeneration.We found that administration ofα-MSH in the Mc4r+/−mice rescue the delayed regeneration of distal digit tip.α-MSH could rescue distal digit regeneration in denervated hindlimbs.In addition,α-MSH could stimulate regeneration of the proximally amputated digit,which is non-regenerative.Conclusions:Mc4r expression in the mouse limb and digit is closely related to nerve tissues,andα-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.