Response features of mitral cells in the olfactory bulb were examined using principal component analysis to determine whether they contain information about odorant stimuli.Using microwire electrode array to record fr...Response features of mitral cells in the olfactory bulb were examined using principal component analysis to determine whether they contain information about odorant stimuli.Using microwire electrode array to record from the olfactory bulb in freely breathing anesthetized rats,we recorded responses of different mitral cells to saturated vapor of anisole(1 M),carvone(1 M),isobutanol(1 M),citral(1 M)and isoamyl actate(1 M).The responses of single mitral cells to the same odorant varied over time.The response profiles showed similarity during certain amount of period,which indicated that the response was not only depended on odor itself but also associated with context.Furthermore,the responses of single mitral cell to different odorants were observed with difference in firing rate.In order to recognize different odorant stimuli,we apply four cells as a sensing group for classification using principal component analysis.Features of each cell’s response describing both temporal and frequency characteristics were selected.The results showed that five different single molecular odorants can be distinguished from each other.These data suggest that action potentials of mitral cells may play a role in odor coding.展开更多
Smell that exists in the natural environment is composed of numerous odor molecules(Bushdid et al.,2014).The mammalian olfactory system can accurately identify environmental olfactory cues,including those related to f...Smell that exists in the natural environment is composed of numerous odor molecules(Bushdid et al.,2014).The mammalian olfactory system can accurately identify environmental olfactory cues,including those related to food selection,recognition of conspecifics/predators,and emotional responses.展开更多
Non-small cell lung cancer(NSCLC)is a leading cause of cancer mortality worldwide.Although epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)have dramatically improved the life expectancy of patien...Non-small cell lung cancer(NSCLC)is a leading cause of cancer mortality worldwide.Although epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)have dramatically improved the life expectancy of patients with NSCLC,concerns about TKI-induced cardiotoxicities have increased.AC0010,a novel third-generation TKI,was developed to overcome drug resistance induced by EGFR-T790M mutation.However,the cardiotoxicity of AC0010 remains unclear.To evaluate the efficacy and cardiotoxicity of AC0010,we designed a novel multifunctional biosensor by integrating microelectrodes(MEs)and interdigital electrodes(IDEs)to comprehensively evaluate cell viability,electrophysiological activity,and morphological changes(beating of cardiomyocytes).The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative,label-free,noninvasive,and real-time manner.AC0010 was found to significantly inhibit NCI-H1975(EGFR-L858R/T790M mutation),while weak inhibition was found for A549(wild-type EGFR).Negligible inhibition was found in the viabilities of HFF-1(normal fibroblasts)and cardiomyocytes.With the multifunctional biosensor,we found that 10μM AC0010 significantly affected the extracellular field potential(EFP)and mechanical beating of cardiomyocytes.The amplitude of EFP continuously decreased after AC0010 treatment,while the interval decreased first and then increased.We analyzed the change in the systole time(ST)and diastole time(DT)within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment.This result probably indicated that the relaxation of cardiomyocytes was insufficient,which may further aggravate the dysfunction.Here,we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations(10μM).This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated.In addition,novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.展开更多
Mammalian olfactory systems have extraordinary ability to sense and identify various trace odorants.Taking advantages of cell culture and micro-fabrication technologies,olfactory cell-or tissue-based biosensor represe...Mammalian olfactory systems have extraordinary ability to sense and identify various trace odorants.Taking advantages of cell culture and micro-fabrication technologies,olfactory cell-or tissue-based biosensor represent a promising platform for in vitro odorant detection.However,in vitro conditions lead to shortened cell/tissue survivals,and the working life of neuron chips is short.The purpose of this study is to develop an in vivo recording and analyzing method for long-term and repeatable detection of odor stimulation.In this study,we implanted penetrating micro-wire array electrode into the olfactory bulb of conscious rats to obtain odor-evoked electrophysiological activities.Then,we investigated the response of ensembles of mitral/tufted cells to stimulation with carvone at a number of concentrations in time and frequency domains.The stable,repeatable odorant responses from up to 16 neural regions could be obtained for at least 3 weeks.Further,we explored the concentration detection sensitivity limitation of developed method,and found the detection low limit of carvone was below10-10mol/L.The result demonstrates that the concentration range of in vivo odorant detection method is much wider than in vitro method.展开更多
基金This research is supported by the National Natural Science Foundation of China(Grant 60725102).
文摘Response features of mitral cells in the olfactory bulb were examined using principal component analysis to determine whether they contain information about odorant stimuli.Using microwire electrode array to record from the olfactory bulb in freely breathing anesthetized rats,we recorded responses of different mitral cells to saturated vapor of anisole(1 M),carvone(1 M),isobutanol(1 M),citral(1 M)and isoamyl actate(1 M).The responses of single mitral cells to the same odorant varied over time.The response profiles showed similarity during certain amount of period,which indicated that the response was not only depended on odor itself but also associated with context.Furthermore,the responses of single mitral cell to different odorants were observed with difference in firing rate.In order to recognize different odorant stimuli,we apply four cells as a sensing group for classification using principal component analysis.Features of each cell’s response describing both temporal and frequency characteristics were selected.The results showed that five different single molecular odorants can be distinguished from each other.These data suggest that action potentials of mitral cells may play a role in odor coding.
基金supported by the Zhejiang Provincial Natural Science Foundation of China (Nos.LY21C100001 and LBY21H180001)the National Natural Science Foundation of China (Nos.62271443 and 32250008).
文摘Smell that exists in the natural environment is composed of numerous odor molecules(Bushdid et al.,2014).The mammalian olfactory system can accurately identify environmental olfactory cues,including those related to food selection,recognition of conspecifics/predators,and emotional responses.
基金This study was supported by the National Natural Science Foundation of China(Grant no.62120106004)the China Postdoctoral Science Foundation(Grant no.2022M712783,BX2021265,2021M702859).
文摘Non-small cell lung cancer(NSCLC)is a leading cause of cancer mortality worldwide.Although epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)have dramatically improved the life expectancy of patients with NSCLC,concerns about TKI-induced cardiotoxicities have increased.AC0010,a novel third-generation TKI,was developed to overcome drug resistance induced by EGFR-T790M mutation.However,the cardiotoxicity of AC0010 remains unclear.To evaluate the efficacy and cardiotoxicity of AC0010,we designed a novel multifunctional biosensor by integrating microelectrodes(MEs)and interdigital electrodes(IDEs)to comprehensively evaluate cell viability,electrophysiological activity,and morphological changes(beating of cardiomyocytes).The multifunctional biosensor can monitor AC0010-induced NSCLC inhibition and cardiotoxicity in a quantitative,label-free,noninvasive,and real-time manner.AC0010 was found to significantly inhibit NCI-H1975(EGFR-L858R/T790M mutation),while weak inhibition was found for A549(wild-type EGFR).Negligible inhibition was found in the viabilities of HFF-1(normal fibroblasts)and cardiomyocytes.With the multifunctional biosensor,we found that 10μM AC0010 significantly affected the extracellular field potential(EFP)and mechanical beating of cardiomyocytes.The amplitude of EFP continuously decreased after AC0010 treatment,while the interval decreased first and then increased.We analyzed the change in the systole time(ST)and diastole time(DT)within a beating interval and found that the DT and DT/beating interval rate decreased within 1 h after AC0010 treatment.This result probably indicated that the relaxation of cardiomyocytes was insufficient,which may further aggravate the dysfunction.Here,we found that AC0010 significantly inhibited EGFR-mutant NSCLC cells and impaired cardiomyocyte function at low concentrations(10μM).This is the first study in which the risk of AC0010-induced cardiotoxicity was evaluated.In addition,novel multifunctional biosensors can comprehensively evaluate the antitumor efficacy and cardiotoxicity of drugs and candidate compounds.
基金supported by the National Key Basic Research Program of China(2009CB320303)the National Natural Science Foundation of China(81027003,60725102)
文摘Mammalian olfactory systems have extraordinary ability to sense and identify various trace odorants.Taking advantages of cell culture and micro-fabrication technologies,olfactory cell-or tissue-based biosensor represent a promising platform for in vitro odorant detection.However,in vitro conditions lead to shortened cell/tissue survivals,and the working life of neuron chips is short.The purpose of this study is to develop an in vivo recording and analyzing method for long-term and repeatable detection of odor stimulation.In this study,we implanted penetrating micro-wire array electrode into the olfactory bulb of conscious rats to obtain odor-evoked electrophysiological activities.Then,we investigated the response of ensembles of mitral/tufted cells to stimulation with carvone at a number of concentrations in time and frequency domains.The stable,repeatable odorant responses from up to 16 neural regions could be obtained for at least 3 weeks.Further,we explored the concentration detection sensitivity limitation of developed method,and found the detection low limit of carvone was below10-10mol/L.The result demonstrates that the concentration range of in vivo odorant detection method is much wider than in vitro method.