In a recent study,a research group from Taiyuan University of Technology published their findings in the journal Opto-Electronic Science with a title"Simultaneously realizing thermal and electromagnetic cloaking ...In a recent study,a research group from Taiyuan University of Technology published their findings in the journal Opto-Electronic Science with a title"Simultaneously realizing thermal and electromagnetic cloaking by multi-physical null medium."This work introduces a structure that can control simultaneously both electromagnetic waves and heat flow.For the first time,a single structure capable of cloaking both electromagnetic waves and heat flow was experimentally demonstrated.This research offers new solutions for the simultaneous control of electromagnetic waves and heat flow,and advances the hybrid design of electromagnetic compatibility and thermal management,which may have important potentials in e.g.medical applications.展开更多
Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma(HCC)in individuals infected with the hepatitis virus.However,the molecular pathways leading to its bioactivation ...Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma(HCC)in individuals infected with the hepatitis virus.However,the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined.Here,we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1(AFB1)targets.Among the most significant hits was the aryl hydrocarbon receptor(AHR),a ligand-binding transcription factor regulating cell metabolism,differentiation,and immunity.展开更多
Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-021-00713-1 z published online 9 August 2021 After online publication of the article^(1),the authors noticed one inadvertent mistak...Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-021-00713-1 z published online 9 August 2021 After online publication of the article^(1),the authors noticed one inadvertent mistake occurred during the production process in Fig.7 that needs to be corrected.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.展开更多
Laboratory research and pharmacoepidemiology provide support for metformin as a potential antitumor agent.However,the lack of a clear understanding of the indications of metformin limits its efficacy.Here,we performed...Laboratory research and pharmacoepidemiology provide support for metformin as a potential antitumor agent.However,the lack of a clear understanding of the indications of metformin limits its efficacy.Here,we performed a genome-wide CRISPR knockout negative screen to identify potential targets that might synergize with metformin.Next-generation sequencing of pooled genomic DNAs isolated from surviving cells after 18 days of metformin treatment(T18)compared to those of the untreated cells at day 0(T0)yielded candidate genes.Knockdown of a group of cyclin-dependent kinases(CDKs),including CDK1,CDK4,and CDK6,confirmed the results of the screen.Combination treatment of the CDKs inhibitor abemaciclib with metformin profoundly inhibited tumor viability in vitro and in vivo.Although cell cycle parameters were not further altered under the combination treatment,investigation of the metabolome revealed significant changes in cell metabolism,especially with regard to fatty acid oxidation,the tricarboxylic acid cycle and aspartate metabolism.Such changes appeared to be mediated through inhibition of the mTOR pathway.Collectively,our study suggests that the combination of CDKs inhibitor with metformin could be recognized as a potential therapy in future clinical applications.展开更多
Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, w...Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.展开更多
Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling t...Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction.Here,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response.RNF138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic cells.Furthermore,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)domain.More importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling.Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth.Overall,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.展开更多
基金National Key Research and Development Program of China(No.2022YFB2804100)‘Pioneer and Leading Goose’R&D Program of Zhejiang(Nos.2023C03002,2022C03051 and 2023C03135)+2 种基金National Natural Science Foundation of China(No.91233208)Ningbo Science and Technology Project(Nos.2023Z179,2023Z122 and 2020Z077)Special Development Fund of Shanghai Zhangjiang Science City.
文摘In a recent study,a research group from Taiyuan University of Technology published their findings in the journal Opto-Electronic Science with a title"Simultaneously realizing thermal and electromagnetic cloaking by multi-physical null medium."This work introduces a structure that can control simultaneously both electromagnetic waves and heat flow.For the first time,a single structure capable of cloaking both electromagnetic waves and heat flow was experimentally demonstrated.This research offers new solutions for the simultaneous control of electromagnetic waves and heat flow,and advances the hybrid design of electromagnetic compatibility and thermal management,which may have important potentials in e.g.medical applications.
基金This work was supported by the National Key R&D Program of China(2018YFC1312100)the National Natural Science Foundation Fund(81772490)+1 种基金the National Key R&D Program of China(2020YFQ002705)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(Grants 2016-I2M-1-001,2017-I2M-3-004,and 2019-I2M-1-003).
文摘Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma(HCC)in individuals infected with the hepatitis virus.However,the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined.Here,we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1(AFB1)targets.Among the most significant hits was the aryl hydrocarbon receptor(AHR),a ligand-binding transcription factor regulating cell metabolism,differentiation,and immunity.
文摘Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-021-00713-1 z published online 9 August 2021 After online publication of the article^(1),the authors noticed one inadvertent mistake occurred during the production process in Fig.7 that needs to be corrected.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.
基金supported by the National Natural Science Foundation Fund(81472559,81772490)the National Key R&D Program of China(2020YFC2002705,2018YFC0115204)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(Grants 2016-I2M-1-001,2017-I2M-3-004,and 2019-I2M-1-003).
文摘Laboratory research and pharmacoepidemiology provide support for metformin as a potential antitumor agent.However,the lack of a clear understanding of the indications of metformin limits its efficacy.Here,we performed a genome-wide CRISPR knockout negative screen to identify potential targets that might synergize with metformin.Next-generation sequencing of pooled genomic DNAs isolated from surviving cells after 18 days of metformin treatment(T18)compared to those of the untreated cells at day 0(T0)yielded candidate genes.Knockdown of a group of cyclin-dependent kinases(CDKs),including CDK1,CDK4,and CDK6,confirmed the results of the screen.Combination treatment of the CDKs inhibitor abemaciclib with metformin profoundly inhibited tumor viability in vitro and in vivo.Although cell cycle parameters were not further altered under the combination treatment,investigation of the metabolome revealed significant changes in cell metabolism,especially with regard to fatty acid oxidation,the tricarboxylic acid cycle and aspartate metabolism.Such changes appeared to be mediated through inhibition of the mTOR pathway.Collectively,our study suggests that the combination of CDKs inhibitor with metformin could be recognized as a potential therapy in future clinical applications.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(81788101,31870163,and 32100104)the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-022)+6 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB29010102)CAS Southest Asia Biodiversity Research Institute(151C53KYSB20210023)Beijing Natural Science Foundation(L192007)National Pathogen Resource Center,and State Key Laboratory Special Fund(2060204)Y.B.is supported by the NSFC Outstanding Young Scholars(31822055)Youth Innovation Promotion Association of the CAS(2017122 and Y2021034)Overseas Expertise Introduction Center for Discipline Innovation(“111 Center”)(BP0820029).
文摘Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-066,2017-I2M-4-002 to H.Z.,2021-I2M-1-019 to W.S.,2021-1-I2M-014 to C.Z.L.)the National Natural Science Foundation of China(81972311,82141127 and 81672461 to H.Z.,81672472,and 31970794 to W.S.,81570780 to C.Z.L.,32000586 to K.L.)+4 种基金the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310026 to H.Z.)Sanming Project of Medicine in Shenzhen(SZSM202011010 to H.Z.)the National Key Research and Development Program of China(2018YFC1003500 to W.S.)the State Key Laboratory Special fund from the Ministry of Science(2060204 to W.S.)the State Key Project on Infection Diseases of China(2017ZX10201021-007-003 to H.Z.).
文摘Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction.Here,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response.RNF138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic cells.Furthermore,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)domain.More importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling.Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth.Overall,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.
