Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissue...Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.展开更多
Objective:To explore the relationship between bitter taste and bitter flavor(efficacy),their character-istics were analyzed at the target and pharmacodynamic points.Methods:Compounds with bitter receptor activity were...Objective:To explore the relationship between bitter taste and bitter flavor(efficacy),their character-istics were analyzed at the target and pharmacodynamic points.Methods:Compounds with bitter receptor activity were obtained by high-throughput screening models of the human bitter taste receptors(hTAS2Rs),which were used to analyze bitter taste.The efficacy of anti-asthma medications was used as an example to research bitter flavor(efficacy).The pharmacological effects of bitter taste and bitter flavor(efficacy)were classified according to the functional modules.The coverage for the same targets or pharmacological effects in the overall protein interaction network(PIN)of bitter taste and bitter flavor(efficacy)was analyzed to reveal their relationship.The effect of the compound polydatin with anti-asthma activation on hTAS2R14 was studied to verify the reliability of the aforementioned idea.Results:A total of 121 Chinese materia medica(CMM)compounds that activate hTAS2R10,hTAS2R14,and hTAS2R49 were obtained.The analysis results indicated that 108 same targets for bitter taste and bitter flavor(efficacy)were obtained,accounting for 13.9%in the PIN of bitter taste and 72.5%in the PIN of bitter flavor(efficacy).The pharmacological effects shared by bitter taste and bitter flavor(efficacy)accounted for 79%of the PIN of bitter taste and 81%of the PIN of bitter flavor(efficacy).The activating effect of the anti-asthma compound polydatin on hTAS2R14 was dose-dependent with EC 50 of 4.3 m M.Conclusion:In this study,the relationship between bitter taste and bitter flavor(efficacy)has been demonstrated from the target and pharmacodynamic points,which are based on hTAS2Rs and anti-asthma effect.Bitter taste and bitter flavor(efficacy)exhibited a high correlation.This study provides a theoretical and scientific basis for the hypothesis that“the property theory of CMM is the clinical pharmacodynamics of CMM.”展开更多
Currently,the video captioning models based on an encoder-decoder mainly rely on a single video input source.The contents of video captioning are limited since few studies employed external corpus information to guide...Currently,the video captioning models based on an encoder-decoder mainly rely on a single video input source.The contents of video captioning are limited since few studies employed external corpus information to guide the generation of video captioning,which is not conducive to the accurate descrip-tion and understanding of video content.To address this issue,a novel video captioning method guided by a sentence retrieval generation network(ED-SRG)is proposed in this paper.First,a ResNeXt network model,an efficient convolutional network for online video understanding(ECO)model,and a long short-term memory(LSTM)network model are integrated to construct an encoder-decoder,which is utilized to extract the 2D features,3D features,and object features of video data respectively.These features are decoded to generate textual sentences that conform to video content for sentence retrieval.Then,a sentence-transformer network model is employed to retrieve different sentences in an external corpus that are semantically similar to the above textual sentences.The candidate sentences are screened out through similarity measurement.Finally,a novel GPT-2 network model is constructed based on GPT-2 network structure.The model introduces a designed random selector to randomly select predicted words with a high probability in the corpus,which is used to guide and generate textual sentences that are more in line with human natural language expressions.The proposed method in this paper is compared with several existing works by experiments.The results show that the indicators BLEU-4,CIDEr,ROUGE_L,and METEOR are improved by 3.1%,1.3%,0.3%,and 1.5%on a public dataset MSVD and 1.3%,0.5%,0.2%,1.9%on a public dataset MSR-VTT respectively.It can be seen that the proposed method in this paper can generate video captioning with richer semantics than several state-of-the-art approaches.展开更多
基金Shanghai Science and Technology Commission“R&D Public Service Platform and Institutional Capacity Improvement Project”,Grant/Award Number:21DZ2291300National Science and Technology Major Project,Grant/Award Number:2017ZX10304402-001-006 and 2017ZX10304402-001-012Start-on Funding from Shanghai Public Health Clinical Center,Grant/Award Number:KY-GW-2019-11,KYGW-2019-19 and KY-GW-2021-39。
文摘Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.
基金This study was supported by the National Natural Science Foundation of China(81430094).
文摘Objective:To explore the relationship between bitter taste and bitter flavor(efficacy),their character-istics were analyzed at the target and pharmacodynamic points.Methods:Compounds with bitter receptor activity were obtained by high-throughput screening models of the human bitter taste receptors(hTAS2Rs),which were used to analyze bitter taste.The efficacy of anti-asthma medications was used as an example to research bitter flavor(efficacy).The pharmacological effects of bitter taste and bitter flavor(efficacy)were classified according to the functional modules.The coverage for the same targets or pharmacological effects in the overall protein interaction network(PIN)of bitter taste and bitter flavor(efficacy)was analyzed to reveal their relationship.The effect of the compound polydatin with anti-asthma activation on hTAS2R14 was studied to verify the reliability of the aforementioned idea.Results:A total of 121 Chinese materia medica(CMM)compounds that activate hTAS2R10,hTAS2R14,and hTAS2R49 were obtained.The analysis results indicated that 108 same targets for bitter taste and bitter flavor(efficacy)were obtained,accounting for 13.9%in the PIN of bitter taste and 72.5%in the PIN of bitter flavor(efficacy).The pharmacological effects shared by bitter taste and bitter flavor(efficacy)accounted for 79%of the PIN of bitter taste and 81%of the PIN of bitter flavor(efficacy).The activating effect of the anti-asthma compound polydatin on hTAS2R14 was dose-dependent with EC 50 of 4.3 m M.Conclusion:In this study,the relationship between bitter taste and bitter flavor(efficacy)has been demonstrated from the target and pharmacodynamic points,which are based on hTAS2Rs and anti-asthma effect.Bitter taste and bitter flavor(efficacy)exhibited a high correlation.This study provides a theoretical and scientific basis for the hypothesis that“the property theory of CMM is the clinical pharmacodynamics of CMM.”
基金supported in part by the National Natural Science Foundation of China under Grants 62273272 and 61873277in part by the Chinese Postdoctoral Science Foundation under Grant 2020M673446+1 种基金in part by the Key Research and Development Program of Shaanxi Province under Grant 2023-YBGY-243in part by the Youth Innovation Team of Shaanxi Universities.
文摘Currently,the video captioning models based on an encoder-decoder mainly rely on a single video input source.The contents of video captioning are limited since few studies employed external corpus information to guide the generation of video captioning,which is not conducive to the accurate descrip-tion and understanding of video content.To address this issue,a novel video captioning method guided by a sentence retrieval generation network(ED-SRG)is proposed in this paper.First,a ResNeXt network model,an efficient convolutional network for online video understanding(ECO)model,and a long short-term memory(LSTM)network model are integrated to construct an encoder-decoder,which is utilized to extract the 2D features,3D features,and object features of video data respectively.These features are decoded to generate textual sentences that conform to video content for sentence retrieval.Then,a sentence-transformer network model is employed to retrieve different sentences in an external corpus that are semantically similar to the above textual sentences.The candidate sentences are screened out through similarity measurement.Finally,a novel GPT-2 network model is constructed based on GPT-2 network structure.The model introduces a designed random selector to randomly select predicted words with a high probability in the corpus,which is used to guide and generate textual sentences that are more in line with human natural language expressions.The proposed method in this paper is compared with several existing works by experiments.The results show that the indicators BLEU-4,CIDEr,ROUGE_L,and METEOR are improved by 3.1%,1.3%,0.3%,and 1.5%on a public dataset MSVD and 1.3%,0.5%,0.2%,1.9%on a public dataset MSR-VTT respectively.It can be seen that the proposed method in this paper can generate video captioning with richer semantics than several state-of-the-art approaches.
