Purpose:To investigate how long indocyanine green (ICG) remains in the fundus after vitreoretinal surgery assisted with ICG,and to identify factors that influence the persistence duration.Methods:Fifty five eyes diagn...Purpose:To investigate how long indocyanine green (ICG) remains in the fundus after vitreoretinal surgery assisted with ICG,and to identify factors that influence the persistence duration.Methods:Fifty five eyes diagnosed as idiopathic macular hole (Stage 2 and 3) were randomly divided into five groups.ICG solution at concentrations of 5,2.5,2.5,1.25,and 0.5 mg/ml,employed in cases of Group I to V respectively,was applied to stain the internal limiting membrane(ILM) during the procedure of internal limiting membrane peeling..A prospective study was carried out after pars plana vitrectomy and ILM peeling were performed on 55 eyes with Stage 2,3,or 4 idiopathic macular holes..Infrared fundus pictures were obtained in all patients before and after surgery.Results:High levels of fluorescence from residual ICG (ICG hyperfluorescence) were mainly localized at the posterior pole of the fundus after surgery.In Group Ⅰ,Ⅱ,Ⅲ,Ⅳ and Ⅴ,the duration of persistence of flurorescence from ICG was 8.33±0.87,3.59±0.94,3.75±0.79,2.30±0.48,and 1.29±0.49 months,respectively.Although no significant difference was detected between Group Ⅱ and Group Ⅲ,the general inter-group difference was significant among the five groups in which different ICG concentration was applied.In Group Ⅲ,even though 90% of the macular holes acquired anatomical closure,ICG hyperfluorescence was detected in the macular area.Conclusion:ICG remains in the fundus for a period of months.The persistence duration of fluorescence from ICG is positively correlated with the concentration and the staining time of ICG.Hyaluronan is beneficial in reducing the amount of ICG residue in the macular area.展开更多
Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable fo...Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.展开更多
During the Cambrian, gypsum-bearing evaporites formed in the Sichuan Basin, SW China. These rocks are important for oil and gas sealing, but details of their distribution and origin are not well established. This stud...During the Cambrian, gypsum-bearing evaporites formed in the Sichuan Basin, SW China. These rocks are important for oil and gas sealing, but details of their distribution and origin are not well established. This study examines the regional distribution and origin of the gypsum-bearing evaporites using a comprehensive analysis of drilling data from 34 wells, 5 measured cross-sections in the basin and surrounding area, and 96 maps of area-survey data. Results show that in the stratigraphic succession, the gypsum-bearing evaporites occur mainly in the Lower Cambrian Longwangmiao Formation, the Middle Cambrian Douposi Formation, and the Middle-Upper Cambrian Xixiangchi Group. Geographically, the rocks are found mainly in the southeastern part of the basin, and the distribution of deposits shows an overall SW-NE trend. The sedimentary environments for evaporite formation were evaporative lagoon and inter-platform basin in a platform setting. Gypsum was generated by the underwater concentration of sea water in a strongly evaporative environment. Both an evaporative restricted platform and a mixeddeposition restricted platform model appear to be applicable to the development of gypsum in the Sichuan Basin. The gypsum-bearing evaporites with the best sealing capacity are located mostly in the southeastern part of the basin. These constraints can be applied directly to regional exploration, and have implications for the regional paleogeography and paleoclimate.展开更多
Background: The purpose is to investigate the relationship between full-thickness macular hole(MH) and retinal break(RB) and/or lattice degeneration.Methods: Patients diagnosed as full-thickness MH and referred to Dr....Background: The purpose is to investigate the relationship between full-thickness macular hole(MH) and retinal break(RB) and/or lattice degeneration.Methods: Patients diagnosed as full-thickness MH and referred to Dr. Lin Lu from January 2009 to December 2013 were evaluated. All patients underwent general ophthalmologic examinations, fundus examination and optical coherence tomography(OCT). The RB and/or lattice degeneration were recorded.Results: Totally 183 eyes of 167 patients were included. The sex ratio of men to women was 1:2.88. A total of 17 eyes were pseudophakic and 166 eyes were phakic. RB and/or lattice degeneration were found in 62 eyes(33.88%). The prevalence of RB and/or lattice degeneration was similar between men and women(P=0.344>0.05). There was no statistical difference between the pseudophakic eyes and phakic eyes(P=0.138>0.05). All of the RB and/or lattice degeneration were located near or anterior to the equator. The inferior quadrants and the vertical meridian were af ected more often than the superior quadrants and the horizontal meridian.Conclusions: We identified a high incidence of RB/lattice degeneration in cases of full-thickness MH. Carefully examination of the peripheral retina and prophylactic treatment of RB and/or lattice degeneration are critical.展开更多
In this study,we present novel molecular mechanisms by which FOXO1 functions as a tumor suppressor to prevent the pathogenesis of nasopharyngeal carcinoma(NPC).First,we observed that FOXO1 not only controlled tumor st...In this study,we present novel molecular mechanisms by which FOXO1 functions as a tumor suppressor to prevent the pathogenesis of nasopharyngeal carcinoma(NPC).First,we observed that FOXO1 not only controlled tumor stemness and metastasis,but also sensitized NPC cells to cisplatin(DDP)in vitro and in vivo.Mechanistic studies demonstrated that FOXO1-induced miR-200b expression through the GSK3β/β-catenin/TCF4 network-mediated stimulation of ZEB1,which reduced tumor stemness and the epithelial–mesenchymal transition(EMT)signal.Furthermore,we observed FOXO1 interaction with MYH9 and suppression of MYH9 expression by modulating the PI3K/AKT/c-Myc/P53/miR-133a-3p pathway.Decreased MYH9 expression not only reduced its interactions with GSK3β,but also attenuated TRAF6 expression,which then decreased the ubiquitin-mediated degradation of GSK3βprotein.Increased GSK3βexpression stimulated theβ-catenin/TCF4/ZEB1/miR-200b network,which increased the downstream tumor stemness and EMT signals.Subsequently,we observed that chemically synthesized cinobufotalin(CB)strongly increased FOXO1-induced DDP chemosensitivity by reducing MYH9 expression,and the reduction in MYH9 modulated GSK3β/β-catenin and its downstream tumor stemness and EMT signal in NPC.In clinical samples,the combination of low FOXO1 expression and high MYH9 expression indicated the worst overall survival rates.Our studies demonstrated that CB potently induced FOXO1-mediated DDP sensitivity by antagonizing its binding partner MYH9 to modulate tumor stemness in NPC.展开更多
The advancement of cost-effective and selective electrocatalyst towards CO_(2) to CO conversion is crucial for renewable energy conversion and storage,thus to achieve carbon-neutral cycle in a sustainable manner.In th...The advancement of cost-effective and selective electrocatalyst towards CO_(2) to CO conversion is crucial for renewable energy conversion and storage,thus to achieve carbon-neutral cycle in a sustainable manner.In this communication,we report that CujSb decorated Cu nanowire arrays on Cu foil act as a highly active and selective electrocatalyst for CO_(2) to CO conversion.In CO_(2)-saturated 0.1 M KHCO_(3),it achieves a high Faraday efficiency(FE)of 86.5%for CO,at-0.90 V vs.reversible hydrogen electrode(RHE).The H_(2)/CO ratio is tunable from 0.08:1 to 5.9:1 by adjusting the potential.It is worth noting that HCOO-product was totally suppressed on such catalyst,compared with Sb counterpart.The improving selectivity for CO could be attributed to the bimetallic effect and nanowire arrays structure.展开更多
文摘Purpose:To investigate how long indocyanine green (ICG) remains in the fundus after vitreoretinal surgery assisted with ICG,and to identify factors that influence the persistence duration.Methods:Fifty five eyes diagnosed as idiopathic macular hole (Stage 2 and 3) were randomly divided into five groups.ICG solution at concentrations of 5,2.5,2.5,1.25,and 0.5 mg/ml,employed in cases of Group I to V respectively,was applied to stain the internal limiting membrane(ILM) during the procedure of internal limiting membrane peeling..A prospective study was carried out after pars plana vitrectomy and ILM peeling were performed on 55 eyes with Stage 2,3,or 4 idiopathic macular holes..Infrared fundus pictures were obtained in all patients before and after surgery.Results:High levels of fluorescence from residual ICG (ICG hyperfluorescence) were mainly localized at the posterior pole of the fundus after surgery.In Group Ⅰ,Ⅱ,Ⅲ,Ⅳ and Ⅴ,the duration of persistence of flurorescence from ICG was 8.33±0.87,3.59±0.94,3.75±0.79,2.30±0.48,and 1.29±0.49 months,respectively.Although no significant difference was detected between Group Ⅱ and Group Ⅲ,the general inter-group difference was significant among the five groups in which different ICG concentration was applied.In Group Ⅲ,even though 90% of the macular holes acquired anatomical closure,ICG hyperfluorescence was detected in the macular area.Conclusion:ICG remains in the fundus for a period of months.The persistence duration of fluorescence from ICG is positively correlated with the concentration and the staining time of ICG.Hyaluronan is beneficial in reducing the amount of ICG residue in the macular area.
基金supported by the State Key Program of the Natural Science Foundation of China(81830107)the Natural Science Foundation of China(81973349,82304517)+2 种基金the Key R&D Program of Zhejiang(2022C03077)the Fundamental Research Funds for the Central Universities(226-2023-00059)the China Postdoctoral Science Foundation(2023M733130)。
文摘Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.
基金funded by the Major State Basic Research Development Program of China ("973" project, Grant No. 2012CB214803)National Science and Technology Major Project of China (Grant No. 2016ZX05004)
文摘During the Cambrian, gypsum-bearing evaporites formed in the Sichuan Basin, SW China. These rocks are important for oil and gas sealing, but details of their distribution and origin are not well established. This study examines the regional distribution and origin of the gypsum-bearing evaporites using a comprehensive analysis of drilling data from 34 wells, 5 measured cross-sections in the basin and surrounding area, and 96 maps of area-survey data. Results show that in the stratigraphic succession, the gypsum-bearing evaporites occur mainly in the Lower Cambrian Longwangmiao Formation, the Middle Cambrian Douposi Formation, and the Middle-Upper Cambrian Xixiangchi Group. Geographically, the rocks are found mainly in the southeastern part of the basin, and the distribution of deposits shows an overall SW-NE trend. The sedimentary environments for evaporite formation were evaporative lagoon and inter-platform basin in a platform setting. Gypsum was generated by the underwater concentration of sea water in a strongly evaporative environment. Both an evaporative restricted platform and a mixeddeposition restricted platform model appear to be applicable to the development of gypsum in the Sichuan Basin. The gypsum-bearing evaporites with the best sealing capacity are located mostly in the southeastern part of the basin. These constraints can be applied directly to regional exploration, and have implications for the regional paleogeography and paleoclimate.
基金supported by National Nature Science Foundation of China (NO.81170863)
文摘Background: The purpose is to investigate the relationship between full-thickness macular hole(MH) and retinal break(RB) and/or lattice degeneration.Methods: Patients diagnosed as full-thickness MH and referred to Dr. Lin Lu from January 2009 to December 2013 were evaluated. All patients underwent general ophthalmologic examinations, fundus examination and optical coherence tomography(OCT). The RB and/or lattice degeneration were recorded.Results: Totally 183 eyes of 167 patients were included. The sex ratio of men to women was 1:2.88. A total of 17 eyes were pseudophakic and 166 eyes were phakic. RB and/or lattice degeneration were found in 62 eyes(33.88%). The prevalence of RB and/or lattice degeneration was similar between men and women(P=0.344>0.05). There was no statistical difference between the pseudophakic eyes and phakic eyes(P=0.138>0.05). All of the RB and/or lattice degeneration were located near or anterior to the equator. The inferior quadrants and the vertical meridian were af ected more often than the superior quadrants and the horizontal meridian.Conclusions: We identified a high incidence of RB/lattice degeneration in cases of full-thickness MH. Carefully examination of the peripheral retina and prophylactic treatment of RB and/or lattice degeneration are critical.
基金This study was supported by the national nature science fund of China(81772872,81572643,81872198)the Science and Technology Project of Guangdong Province(No.2016A020215233,20140212,2014A020212342)+5 种基金the People’s Livelihood Science and Technology grant of Guangzhou Municipal Science and Technology Project(No.201803010023)the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine(No.20193010)the Guangzhou Science and Technology Plan(No.201804010023,201707010425)the Nature Science Fund of Guangdong Province(2016A030313526,2017A030313701)the Supporting Plan for Special Talents in Guangdong Province(No.2016TQ03R466)the Seeding Program of Shenzhen Hospital of Southern Medical University,and the Guangdong Medical Science and Technology Research Fund Project(No.A2016610).
文摘In this study,we present novel molecular mechanisms by which FOXO1 functions as a tumor suppressor to prevent the pathogenesis of nasopharyngeal carcinoma(NPC).First,we observed that FOXO1 not only controlled tumor stemness and metastasis,but also sensitized NPC cells to cisplatin(DDP)in vitro and in vivo.Mechanistic studies demonstrated that FOXO1-induced miR-200b expression through the GSK3β/β-catenin/TCF4 network-mediated stimulation of ZEB1,which reduced tumor stemness and the epithelial–mesenchymal transition(EMT)signal.Furthermore,we observed FOXO1 interaction with MYH9 and suppression of MYH9 expression by modulating the PI3K/AKT/c-Myc/P53/miR-133a-3p pathway.Decreased MYH9 expression not only reduced its interactions with GSK3β,but also attenuated TRAF6 expression,which then decreased the ubiquitin-mediated degradation of GSK3βprotein.Increased GSK3βexpression stimulated theβ-catenin/TCF4/ZEB1/miR-200b network,which increased the downstream tumor stemness and EMT signals.Subsequently,we observed that chemically synthesized cinobufotalin(CB)strongly increased FOXO1-induced DDP chemosensitivity by reducing MYH9 expression,and the reduction in MYH9 modulated GSK3β/β-catenin and its downstream tumor stemness and EMT signal in NPC.In clinical samples,the combination of low FOXO1 expression and high MYH9 expression indicated the worst overall survival rates.Our studies demonstrated that CB potently induced FOXO1-mediated DDP sensitivity by antagonizing its binding partner MYH9 to modulate tumor stemness in NPC.
基金supported by the National Natural Science Foundation of China(No.22072015)the Foundation of Sichuan Department of Science and Technology(No.2017FZ0079).
文摘The advancement of cost-effective and selective electrocatalyst towards CO_(2) to CO conversion is crucial for renewable energy conversion and storage,thus to achieve carbon-neutral cycle in a sustainable manner.In this communication,we report that CujSb decorated Cu nanowire arrays on Cu foil act as a highly active and selective electrocatalyst for CO_(2) to CO conversion.In CO_(2)-saturated 0.1 M KHCO_(3),it achieves a high Faraday efficiency(FE)of 86.5%for CO,at-0.90 V vs.reversible hydrogen electrode(RHE).The H_(2)/CO ratio is tunable from 0.08:1 to 5.9:1 by adjusting the potential.It is worth noting that HCOO-product was totally suppressed on such catalyst,compared with Sb counterpart.The improving selectivity for CO could be attributed to the bimetallic effect and nanowire arrays structure.