[Objectives]This study was conducted to improve the quality of frozen silver carp surimi products.[Methods]Huangzhou radish powder and silver carp surimi were used as raw materials to analyze the effects of different ...[Objectives]This study was conducted to improve the quality of frozen silver carp surimi products.[Methods]Huangzhou radish powder and silver carp surimi were used as raw materials to analyze the effects of different amounts(1%,2%,3%,4%,5%)of Huangzhou radish powder on the water-holding capacity,cooking loss rate,whiteness value,TPA,gel strength and sensory quality of surimi products.[Results]When the addition amount of Huangzhou radish powder was 1%,water-holding capacity,hardness,chewiness and the gel strength of the surimi product reached their maximum values,which were 86.86%,3470.36 g,2628.50 g and 707.48 g·mm,respectively.Meanwhile,the cooking loss rate was reduced to a minimum value(13.66%),and the sensory quality reached the best.The whiteness of surimi products showed a decreasing trend with the increase of the addition amount of Huangzhou radish powder.However,the whiteness of the surimi product was not significantly affected when the addition amount of Huangzhou radish powder was 1%.Therefore,when the addition amount of Huangzhou radish powder was 1%,the quality of surimi products could be improved.[Conclusions]This study provides a new idea for the development and utilization of Huangzhou radish.展开更多
Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation(AST).However,it remains largely unknown how Lkb1 deficiency dynamically regulates...Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation(AST).However,it remains largely unknown how Lkb1 deficiency dynamically regulates AST.Using the classical AST mouse model(Kras LSL-G12D/+;Lkb1flox/flox,KL),we here comprehensively analyze the temporal transcriptomic dynamics of lung tumors at different stages by dynamic network biomarker(DNB)and identify the tipping point at which the Wnt signaling is abruptly suppressed by the excessive accumulation of reactive oxygen species(ROS)through its downstream effector FOXO3A.Bidirectional genetic perturbation of the Wnt pathway using two different Ctnnb1 conditional knockout mouse strains confirms its essential role in the negative regulation of AST.Importantly,pharmacological activation of the Wnt pathway before but not after the tipping point inhibits squamous transdifferentiation,highlighting the irreversibility of AST after crossing the tipping point.Through comparative transcriptomic analyses of mouse and human tumors,we find that the lineage-specific transcription factors(TFs)of adenocarcinoma and squamous cell carcinoma form a“Yin-Yang”counteracting network.Interestingly,inactivation of the Wnt pathway preferentially suppresses the adenomatous lineage TF network and thus disrupts the“Yin-Yang”homeostasis to lean towards the squamous lineage,whereas ectopic expression of NKX2-1,an adenomatous lineage TF,significantly dampens such phenotypic transition accelerated by the Wnt pathway inactivation.The negative correlation between the Wnt pathway and AST is further observed in a large cohort of human lung adenosquamous carcinoma.Collectively,our study identifies the tipping point of AST and highlights an essential role of the ROS-Wnt axis in dynamically orchestrating the homeostasis between adeno-and squamous-specific TF networks at the AST tipping point.展开更多
Small cell lung cancer(SCLC)is a recalcitrant cancer featured with high metastasis capability.We previously found that TAZ acts as a crucial molecular switch in orchestrating SCLC phenotypic transition and metastasis(...Small cell lung cancer(SCLC)is a recalcitrant cancer featured with high metastasis capability.We previously found that TAZ acts as a crucial molecular switch in orchestrating SCLC phenotypic transition and metastasis(Jin et al.,2022).However,the downstream mechanisms by which TAZ regulates SCLC malignant progression remain elusive.展开更多
Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy.However,the relation between the...Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy.However,the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear.Through comprehensive bioinformatic analyses,we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy.Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant.Mechanistically,activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance.Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors.Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance,which holds important clinical implications for improving SCLC treatment.展开更多
Adult lung is a highly quiescent organ,with extremely low cell turnover frequency.However,emerging evidences support the occurrence of repair and regeneration in pulmonary epithelia in response to various injuries.Lun...Adult lung is a highly quiescent organ,with extremely low cell turnover frequency.However,emerging evidences support the occurrence of repair and regeneration in pulmonary epithelia in response to various injuries.Lung regeneration mainly depends on the proliferation of regionally distributed pulmonary stem cells that re-enter the cell cycle.Genetic lineage-tracing approaches help to track the lung epithelial differentiation and/or de-differentiation path,and single-cell transcriptomic technique reveals the essential molecular signaling involved in lung regeneration.Dysregulation of the molecular signaling that balances quiescence and self-renewal leads to the transformation of lung stem cells,and thus promotes lung cancer development.Interestingly,different subtypes of lung cancer share common cells of origin and the pathological transition among various subtypes is responsible for drug resistance in the clinic.In this review,we summarize the recent understanding of lung stem cells in regeneration and tumorigenesis as well as related molecular mechanisms,with the hope to provide helpful insights for clinical treatments of respiratory diseases.展开更多
Small cell lung cancer(SCLC)is the most aggressive lung cancer with high heterogeneity.Mouse SCLC cells derived from the Rb1L/L/Trp53L/L(RP)autochthonous mouse model grew as adhesion or suspension in cell culture,and ...Small cell lung cancer(SCLC)is the most aggressive lung cancer with high heterogeneity.Mouse SCLC cells derived from the Rb1L/L/Trp53L/L(RP)autochthonous mouse model grew as adhesion or suspension in cell culture,and the adhesion cells are defined as non-neuroendocrine(non-NE)SCLC cells.Here,we uncover the heterogenous subpopulations within the non-NE cells and referred to them as mesenchymallike(Mes)and epithelial-like(Epi)SCLC cells.The Mes cells have increased capability to form colonies in soft agar and harbored stronger metastatic capability in vivo when compared with the Epi cells.Gene Set Enrichment Analysis reveals that the transforming growth factor(TGF)-βsignaling is enriched in the Mes cells.Importantly,inhibition of the TGF-βsignaling through ectopic expression of dominant-negative Tgfbr2(Tgfbr2-DN)or treatment with Tgfbr1 inhibitor SD-208 consistently abrogates tumor metastasis in nude mouse allograft assays.Moreover,genetic deletion of Tgfbr2 or Smad4,the key components of the TGF-βsignaling pathway,dramatically attenuates SCLC metastasis in the RP autochthonous mouse model.Collectively,our results uncover the high heterogeneity in non-NE SCLC cells and highlight an important role of TGF-βsignaling in promoting SCLC metastasis.展开更多
基金Supported by Scientific Research Program Guiding Project of the Education Department of Hubei Province(B2020166)Special Projects of the Central Government Guiding Local Science and Technology Development(2018ZYYD019)。
文摘[Objectives]This study was conducted to improve the quality of frozen silver carp surimi products.[Methods]Huangzhou radish powder and silver carp surimi were used as raw materials to analyze the effects of different amounts(1%,2%,3%,4%,5%)of Huangzhou radish powder on the water-holding capacity,cooking loss rate,whiteness value,TPA,gel strength and sensory quality of surimi products.[Results]When the addition amount of Huangzhou radish powder was 1%,water-holding capacity,hardness,chewiness and the gel strength of the surimi product reached their maximum values,which were 86.86%,3470.36 g,2628.50 g and 707.48 g·mm,respectively.Meanwhile,the cooking loss rate was reduced to a minimum value(13.66%),and the sensory quality reached the best.The whiteness of surimi products showed a decreasing trend with the increase of the addition amount of Huangzhou radish powder.However,the whiteness of the surimi product was not significantly affected when the addition amount of Huangzhou radish powder was 1%.Therefore,when the addition amount of Huangzhou radish powder was 1%,the quality of surimi products could be improved.[Conclusions]This study provides a new idea for the development and utilization of Huangzhou radish.
基金We thank Drs.Tyler Jacks,Ronald A.DePinho,Kwok-kin Wong,and Lijian Hui for the generous gift of various mouse strains.We also thank Ruiqi Wang,Rui Liu,Pei Chen,Chao Zheng,and Jifan Shi for helpful discussion.This work was supported by the National Basic Research Program of China(Nos.2017YFA0505500 to H.J.and L.C.,2020YFA0803300 to H.J.)the National Natural Science Foundation of China(Nos.91731314,82030083,31621003,81872312,82011540007 to H.J.,12131020,31930022,12026608 to L.C.,82273093 to Z.F.,81871875,82173340 to L.H.,81802279 to H.H.,81902326 to X.W.,81402371 to Y.J.)+7 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Nos.XDB19020201 to H.J.,XDB38040400 to L.C.)Basic Frontier Scientific Research Program of Chinese Academy of Science(No.ZDBS-LY-SM006 to H.J.)International Cooperation Project of Chinese Academy of Sciences(No.153D31KYSB20190035 to H.J.)the Science and Technology Commission of Shanghai Municipality(No.21ZR1470300 to L.H.)the Youth Innovation Promotion Association CAS(No.Y919S31371 to X.W.)Special Fund for Science and Technology Innovation Strategy of Guangdong Province(Nos.2021B0909050004,2021B0909060002 to L.C.)Major Key Project of PCL(No.PCL2021A12 to L.C.)JST Moonshot R&D Project(No.JPMJMS2021 to L.C.).
文摘Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation(AST).However,it remains largely unknown how Lkb1 deficiency dynamically regulates AST.Using the classical AST mouse model(Kras LSL-G12D/+;Lkb1flox/flox,KL),we here comprehensively analyze the temporal transcriptomic dynamics of lung tumors at different stages by dynamic network biomarker(DNB)and identify the tipping point at which the Wnt signaling is abruptly suppressed by the excessive accumulation of reactive oxygen species(ROS)through its downstream effector FOXO3A.Bidirectional genetic perturbation of the Wnt pathway using two different Ctnnb1 conditional knockout mouse strains confirms its essential role in the negative regulation of AST.Importantly,pharmacological activation of the Wnt pathway before but not after the tipping point inhibits squamous transdifferentiation,highlighting the irreversibility of AST after crossing the tipping point.Through comparative transcriptomic analyses of mouse and human tumors,we find that the lineage-specific transcription factors(TFs)of adenocarcinoma and squamous cell carcinoma form a“Yin-Yang”counteracting network.Interestingly,inactivation of the Wnt pathway preferentially suppresses the adenomatous lineage TF network and thus disrupts the“Yin-Yang”homeostasis to lean towards the squamous lineage,whereas ectopic expression of NKX2-1,an adenomatous lineage TF,significantly dampens such phenotypic transition accelerated by the Wnt pathway inactivation.The negative correlation between the Wnt pathway and AST is further observed in a large cohort of human lung adenosquamous carcinoma.Collectively,our study identifies the tipping point of AST and highlights an essential role of the ROS-Wnt axis in dynamically orchestrating the homeostasis between adeno-and squamous-specific TF networks at the AST tipping point.
基金supported by the National Key Research and Development Program of China(grants 2022YFA1103900,2020YFA0803300 to H.J.2022YFA1004800 to L.C.)+7 种基金the National Natural Science Foundation of China(grants 82341002,32293192,82030083 to H.J.82273400 to Y.J.82303039 to Z.Q.32071271 to Y.Z.T2350003,T2341007,12131020,31930022 to L.C.)the Innovative Research Team of High-level Local Universities in Shanghai(SSMU-ZLCX20180500 to H.J.)Science and Technology Commission of Shanghai Municipality(23JS1401300 to L.C.)the Japan Science and Technology Agency Moonshot R&D(JPMJMS2021 to L.C.)。
文摘Small cell lung cancer(SCLC)is a recalcitrant cancer featured with high metastasis capability.We previously found that TAZ acts as a crucial molecular switch in orchestrating SCLC phenotypic transition and metastasis(Jin et al.,2022).However,the downstream mechanisms by which TAZ regulates SCLC malignant progression remain elusive.
基金supported by the National Natural Science Foundation of China(82030083 to H.J.,81871875 to L.H.)the National Basic Research Program of China(2017YFA0505501 to H.J.+8 种基金2020YFA0803300 to H.J.)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19020201 to H.J.)the National Natural Science Foundation of China(81872312 to H.J.,82011540007 to H.J.,31621003 to H.J.,81402371 to Y.J.,81802279 to H.H.,81902326 to X.W.,81602443 to X.L.)the Basic Frontier Scientific Research Program of Chinese Academy of Science(ZDBSLY-SM006 to H.J.)the International Cooperation Project of Chinese Academy of Sciences(153D31KYSB20190035 to H.J.)the Youth Innovation Promotion Association CAS(Y919S31371 to X.W.)the Natural Science Foundation of Hunan Province,China(2019JJ50550 to X.L.)Clinical Medical Technology Innovation Guide Project of Hunan(2020SK51827 to X.L.)Project of Scientific Research Plan of Hunan Provincial Health Commission(202103100127 to X.L.)。
文摘Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy.However,the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear.Through comprehensive bioinformatic analyses,we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy.Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant.Mechanistically,activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance.Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors.Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance,which holds important clinical implications for improving SCLC treatment.
基金supported by the National Natural Science Foundation of China(81402371 to Y.J.,82030083 to H.J.,91731314 H.J.,81872312 to H.J.,82011540007 to H.J.,31621003 to H.J.)the National Basic Research Program of China(2017YFA0505501 to H.J.+3 种基金2020YFA0803300 to H.J.)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19020201 to H.J.)the Basic Frontier Scientific Research Program of Chinese Academy of Science(ZDBS-LY-SM006 to H.J.)the International Cooperation Project of Chinese Academy of Sciences(153D31KYSB20190035 to H.J.)。
文摘Adult lung is a highly quiescent organ,with extremely low cell turnover frequency.However,emerging evidences support the occurrence of repair and regeneration in pulmonary epithelia in response to various injuries.Lung regeneration mainly depends on the proliferation of regionally distributed pulmonary stem cells that re-enter the cell cycle.Genetic lineage-tracing approaches help to track the lung epithelial differentiation and/or de-differentiation path,and single-cell transcriptomic technique reveals the essential molecular signaling involved in lung regeneration.Dysregulation of the molecular signaling that balances quiescence and self-renewal leads to the transformation of lung stem cells,and thus promotes lung cancer development.Interestingly,different subtypes of lung cancer share common cells of origin and the pathological transition among various subtypes is responsible for drug resistance in the clinic.In this review,we summarize the recent understanding of lung stem cells in regeneration and tumorigenesis as well as related molecular mechanisms,with the hope to provide helpful insights for clinical treatments of respiratory diseases.
基金supported by the National Natural Science Foundation of China(82030083 to H.J.,81871875 to L.H.)the National Basic Research Program of China(2017YFA0505501 to H.J.+4 种基金2020YFA0803300 to H.J.)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19020201 to H.J.)the National Natural Science Foundation of China(81872312 to H.J.,82011540007 to H.J.,31621003 to H.J.,81402371 to Y.J.)the Basic Frontier Scientific Research Program of Chinese Academy of Science(ZDBS-LY-SM006 to H.J.)the International Cooperation Project of Chinese Academy of Sciences(153D31KYSB20190035 to H.J.)。
文摘Small cell lung cancer(SCLC)is the most aggressive lung cancer with high heterogeneity.Mouse SCLC cells derived from the Rb1L/L/Trp53L/L(RP)autochthonous mouse model grew as adhesion or suspension in cell culture,and the adhesion cells are defined as non-neuroendocrine(non-NE)SCLC cells.Here,we uncover the heterogenous subpopulations within the non-NE cells and referred to them as mesenchymallike(Mes)and epithelial-like(Epi)SCLC cells.The Mes cells have increased capability to form colonies in soft agar and harbored stronger metastatic capability in vivo when compared with the Epi cells.Gene Set Enrichment Analysis reveals that the transforming growth factor(TGF)-βsignaling is enriched in the Mes cells.Importantly,inhibition of the TGF-βsignaling through ectopic expression of dominant-negative Tgfbr2(Tgfbr2-DN)or treatment with Tgfbr1 inhibitor SD-208 consistently abrogates tumor metastasis in nude mouse allograft assays.Moreover,genetic deletion of Tgfbr2 or Smad4,the key components of the TGF-βsignaling pathway,dramatically attenuates SCLC metastasis in the RP autochthonous mouse model.Collectively,our results uncover the high heterogeneity in non-NE SCLC cells and highlight an important role of TGF-βsignaling in promoting SCLC metastasis.
