在低纹理场景中,基于点特征的同时定位与地图构建(Simultaneous Localization and Mapping,SLAM)算法很难追踪足够多的有效特征点,系统甚至无法正常工作.众所周知,丰富的线段特征存在在人造结构化环境中的地面与墙面交界处.因此,提出一...在低纹理场景中,基于点特征的同时定位与地图构建(Simultaneous Localization and Mapping,SLAM)算法很难追踪足够多的有效特征点,系统甚至无法正常工作.众所周知,丰富的线段特征存在在人造结构化环境中的地面与墙面交界处.因此,提出一种点线特征融合的双目视觉SLAM算法.在特征提取前,引入梯度密度滤波器加速线特征提取和提高线匹配的准确度,在特征点匹配阶段,采用渐进采样一致性(Progressive Sampling Consensus,PROSAC)算法剔除误匹配点,从而提高定位精度.此外,在特征的融合过程中引入加权思想.在构造误差函数时对点线特征权重进行合理分配.最后,通过在公开的数据集上得到的仿真并与一些优秀的算法进行对比,该算法性能优于PL-SLAM和LSD-SLAM算法,证明了算法的有效性和准确性.展开更多
Objectives To evaluate the expression profile of myoD microRNA-29(miR-29)family in L6myoblast differentiated to myotube or L6 myotube treated by glucose and insulin,and to further probe the molecular mechanism of myoD...Objectives To evaluate the expression profile of myoD microRNA-29(miR-29)family in L6myoblast differentiated to myotube or L6 myotube treated by glucose and insulin,and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.Methods The expression of myoD and miR-29 family was detected by using real-time PCR and Western blot analysis.The potential promoter and transcription factors binding sites of miR-29 clusters were predicted by Promoter scan and transcriptional factor search.The promoter sequence of miR-29b1-a and miR-29b2-c cluster was cloned into a luciferase reporter plasmid and the regulatory effect of myoD was analyzed by using dual luciferase reporter assay.Electrophoretic mobility shift assay was further conducted to indicate the binding of myoD on specific sequence.Moreover,overexpression of myoD was achieved by a recombinant adenovirus system(Ad-myoD).L6 cells were infected with Ad-myoD and real-time PCR was conducted to analyze the expression of miR-29b and miR-29c.Results The expression levels of myoD,miR-29a,miR-29b,and miR-29c were increased in L6myoblast differentiated to myotube.The expression of myoD,miR-29b,and miR-29c was up-regulated in L6myotube treated with glucose and insulin,but miR-29a depicted no significant change.Dual luciferase reporter gene assay showed that myoD functioned as a positive regulator of miR-29b2-c expression and myoD could bind to the specific sequence located at the promoter region of miR-29b2-c cluster.Enforced expression of myoD led to a marked increase of miR-29b and miR-29c levels in L6 cells.Conclusion MyoD might act as a crucial regulator of myogenesis and glucose metabolism in muscle through regulating the expression of miR-29b2-c.展开更多
[Objectives] To establish a method for determining the content of chlorogenic acid in Wuli Huichun Wan. [Methods] The content of chlorogenic acid in Wuli Huichun Wan was determined by high performance liquid chromatog...[Objectives] To establish a method for determining the content of chlorogenic acid in Wuli Huichun Wan. [Methods] The content of chlorogenic acid in Wuli Huichun Wan was determined by high performance liquid chromatography( HPLC) combined with Agilent Eclipse Plus C18 column( 4. 6 mm × 250 mm,5 μm),in mobile phase of 0. 4% phosphoric acid solution-acetonitrile( 12∶ 88) at flow rate of1. 0 m L/min,and detection wavelength of 327 nm. [Results] The linearity of chlorogenic acid in the range of 4-48 μg injection was good( r = 1); the average recovery rate was 99. 61% and the RSD was 0. 98%. [Conclusions] The established method is simple and accurate and has high reproducibility,thus can be used as quality control method for Wuli Huichun Wan.展开更多
[Objectives] To identify original plant and traits of Yi medicine Mubaribo( Verbenae herba) and provide effective experimental data for its identification and application.[Methods]The original plant,traits,and microsc...[Objectives] To identify original plant and traits of Yi medicine Mubaribo( Verbenae herba) and provide effective experimental data for its identification and application.[Methods]The original plant,traits,and microscopic identification were used.[Results]Stem was square,the edges of basal leaves usually had rough saw teeth and notches; most cauline leaves were three parted,edges of lobes have uneven saw teeth,both edges had hard hair; spikes were terminal and axillary,thin and delicate; corolla was light purple to blue. Epidermal cells of stem were long polygonal or quasi-rectangular,vertical wall was straight with pores; lower epidermal cells of leaves were vertical to wall and took on wavy bending; pores were infinitive or anisocytic; 3-5 subsidiary cells; 4 glandularscale head cells,stalk single cell,non-glandular single cell; pollen grains were quasi-circular or quasi-triangular,smooth surface,and 3 germination apertures. [Conclusions] Yi medicine Mubaribo has distinctive identifying characteristics in original plant,traits,and microscopic tissues. This study is expected to provide certain reference for identification of original plant and medicine and formulation of quality standard for Yi medicine Mubaribo,and to provide basis for its further research and development.展开更多
Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) has become one major threat to human population health.The RNA-dependent RNA polymerase(RdRp) presents an ideal target of antivirals,whereas nucleoside analo...Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) has become one major threat to human population health.The RNA-dependent RNA polymerase(RdRp) presents an ideal target of antivirals,whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus.Herein,we report that corilagin(RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp,binds directly to RdRp,effectively inhibits the polymerase activity in both cell-free and cell-based assays,fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration(EC50) value of 0.13 μmol/L.Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp.In addition,combination of RAI-S-37 with remdesivir exhibits additive activity against antiSARS-CoV-2 RdRp.Together with the current data available on the safety and pharmacokinetics of corilagin as a medicinal herbal agent,these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.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
The global coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a positive-sense RNA virus.How the host immune system senses and responds to SARS-CoV-2 inf...The global coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a positive-sense RNA virus.How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved.Here,we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway.SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation.cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection.We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion.Furthermore,cytoplasmic chromatin-cGAS-STING pathway,but not MAVS-mediated viral RNA sensing pathway,contributes to interferon and pro-inflammatory gene expression upon cell fusion.Finally,we show that cGAS is required for host antiviral responses against SARS-CoV-2,and a STING-activating compound potently inhibits viral replication.Together,our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection,mediated by cytoplasmic chromatin from the infected cells.Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19.In addition,these findings extend our knowledge in host defense against viral infection by showing that host cells’self-nucleic acids can be employed as a“danger signal”to alarm the immune system.展开更多
基金Supported by the National Nature Science Foundation of China(81100608 and 30901342)
文摘Objectives To evaluate the expression profile of myoD microRNA-29(miR-29)family in L6myoblast differentiated to myotube or L6 myotube treated by glucose and insulin,and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.Methods The expression of myoD and miR-29 family was detected by using real-time PCR and Western blot analysis.The potential promoter and transcription factors binding sites of miR-29 clusters were predicted by Promoter scan and transcriptional factor search.The promoter sequence of miR-29b1-a and miR-29b2-c cluster was cloned into a luciferase reporter plasmid and the regulatory effect of myoD was analyzed by using dual luciferase reporter assay.Electrophoretic mobility shift assay was further conducted to indicate the binding of myoD on specific sequence.Moreover,overexpression of myoD was achieved by a recombinant adenovirus system(Ad-myoD).L6 cells were infected with Ad-myoD and real-time PCR was conducted to analyze the expression of miR-29b and miR-29c.Results The expression levels of myoD,miR-29a,miR-29b,and miR-29c were increased in L6myoblast differentiated to myotube.The expression of myoD,miR-29b,and miR-29c was up-regulated in L6myotube treated with glucose and insulin,but miR-29a depicted no significant change.Dual luciferase reporter gene assay showed that myoD functioned as a positive regulator of miR-29b2-c expression and myoD could bind to the specific sequence located at the promoter region of miR-29b2-c cluster.Enforced expression of myoD led to a marked increase of miR-29b and miR-29c levels in L6 cells.Conclusion MyoD might act as a crucial regulator of myogenesis and glucose metabolism in muscle through regulating the expression of miR-29b2-c.
文摘[Objectives] To establish a method for determining the content of chlorogenic acid in Wuli Huichun Wan. [Methods] The content of chlorogenic acid in Wuli Huichun Wan was determined by high performance liquid chromatography( HPLC) combined with Agilent Eclipse Plus C18 column( 4. 6 mm × 250 mm,5 μm),in mobile phase of 0. 4% phosphoric acid solution-acetonitrile( 12∶ 88) at flow rate of1. 0 m L/min,and detection wavelength of 327 nm. [Results] The linearity of chlorogenic acid in the range of 4-48 μg injection was good( r = 1); the average recovery rate was 99. 61% and the RSD was 0. 98%. [Conclusions] The established method is simple and accurate and has high reproducibility,thus can be used as quality control method for Wuli Huichun Wan.
基金Supported by Postgraduate Innovation Type of Scientific Research Item of Southwest Minzu University(CX2016SZ046)National Science and Technology Project of the Ministry of Science and Technology in the 13th Five-Year Plan Period(2015BAC05B02)Key Technology R&D Program of Sichuan Province,China(2015SZ0062)
文摘[Objectives] To identify original plant and traits of Yi medicine Mubaribo( Verbenae herba) and provide effective experimental data for its identification and application.[Methods]The original plant,traits,and microscopic identification were used.[Results]Stem was square,the edges of basal leaves usually had rough saw teeth and notches; most cauline leaves were three parted,edges of lobes have uneven saw teeth,both edges had hard hair; spikes were terminal and axillary,thin and delicate; corolla was light purple to blue. Epidermal cells of stem were long polygonal or quasi-rectangular,vertical wall was straight with pores; lower epidermal cells of leaves were vertical to wall and took on wavy bending; pores were infinitive or anisocytic; 3-5 subsidiary cells; 4 glandularscale head cells,stalk single cell,non-glandular single cell; pollen grains were quasi-circular or quasi-triangular,smooth surface,and 3 germination apertures. [Conclusions] Yi medicine Mubaribo has distinctive identifying characteristics in original plant,traits,and microscopic tissues. This study is expected to provide certain reference for identification of original plant and medicine and formulation of quality standard for Yi medicine Mubaribo,and to provide basis for its further research and development.
基金supported by the National MegaProject for Infectious Disease (2018ZX10301408, China)the National Mega-Project for Significant New Drug Discovery (2018ZX09711003-002-002, China)+3 种基金the National Natural Science Foundation of China (81802019 and 81902075)the Beijing Natural Science Foundation (7184228, China)CAMS Innovation Fund for Medical Sciences (2018-I2M-3-004 and 2020-I2M-2010, China)the Peking Union Medical College Youth Fund (3332016063 and 3332018096, China)。
文摘Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) has become one major threat to human population health.The RNA-dependent RNA polymerase(RdRp) presents an ideal target of antivirals,whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus.Herein,we report that corilagin(RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp,binds directly to RdRp,effectively inhibits the polymerase activity in both cell-free and cell-based assays,fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration(EC50) value of 0.13 μmol/L.Computation modeling predicts that RAI-S-37 lands at the palm domain of RdRp and prevents conformational changes required for nucleotide incorporation by RdRp.In addition,combination of RAI-S-37 with remdesivir exhibits additive activity against antiSARS-CoV-2 RdRp.Together with the current data available on the safety and pharmacokinetics of corilagin as a medicinal herbal agent,these results demonstrate the potential of being developed into one of the much-needed SARS-CoV-2 therapeutics.
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.
基金This work was supported by grants from National Key R&D Program of China(2020YFA0707600 to Z.Z.,2020YFA0707800 to W.Wei.)the National Natural Science Foundation of China(81930063,31870893,and 81971948 to J.W.,Z.Z.,and X.L.)+3 种基金the National Major Sciences&Technology Project for Control and Prevention of Major Infectious Diseases in China(2018ZX10301401 to Z.Z.and X.L.)the Beijing Municipal Science&Technology Commission(Z181100001318009)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2016-I2M-1-014,2016-I2M-1-005 to J.W.and X.L.)the Beijing Advanced Innovation Center for Genomics(ICG)at Peking University,and the Peking-Tsinghua Center for Life Sciences.
文摘The global coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a positive-sense RNA virus.How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved.Here,we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway.SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation.cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection.We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion.Furthermore,cytoplasmic chromatin-cGAS-STING pathway,but not MAVS-mediated viral RNA sensing pathway,contributes to interferon and pro-inflammatory gene expression upon cell fusion.Finally,we show that cGAS is required for host antiviral responses against SARS-CoV-2,and a STING-activating compound potently inhibits viral replication.Together,our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection,mediated by cytoplasmic chromatin from the infected cells.Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19.In addition,these findings extend our knowledge in host defense against viral infection by showing that host cells’self-nucleic acids can be employed as a“danger signal”to alarm the immune system.
