Background Green tea is a popular beverage worldwide and epigallocatechin-3-gallate(EGCG)is the most bioactive polyphenol in green tea.Our study aims to investigate the anti-proliferation and anti-migration effects of...Background Green tea is a popular beverage worldwide and epigallocatechin-3-gallate(EGCG)is the most bioactive polyphenol in green tea.Our study aims to investigate the anti-proliferation and anti-migration effects of EGCG against colorectal-cancer SW480,SW620,and LS411N cells,and elucidate the underlying mechanism.Methods The in vitro anti-proliferation and anti-migration effects of EGCG against colon-cancer cells were evaluated using MTT,scratch-wound-healing,and transwell-migration assays.The effects of EGCG on apoptosis were assessed by Annexin V-FITC/PI double staining and JC-1 staining.Besides,Western blotting was employed to detect the protein-expression level and elucidate the underlying pathways.Real-time qPCR and dual-luciferase reporter assay were adopted to determine the mRNA level and promoter activity.Results Our results demonstrated that treatment with EGCG resulted in significant inhibition of cell proliferation by the induction of apoptosis.EGCG also inhibited SW480 cell migration in a dose-dependent manner as assessed by wound-healing and transwell-migration assays.Western blot confirmed that EGCG induced apoptosis by the activation of Caspase-3 and PARP.In addition,both STAT3 and phosphorylated STAT3(p-STAT3)were downregulated significantly by EGCG in three selected colorectal-cancer cell lines.EGCG treatment also resulted in a significant decrease in Bcl-2,MCL-1,and Vimentin,and an increase in E-cadherin.When STAT3 was inhibited,EGCG showed no obvious effect on cell proliferation and migration.Further investigation by luciferase-reporter-activity assay showed that EGCG suppressed the promoter activity of STAT3 and downregulated the transcription of STAT3.Conclusion Our study presents evidence on the anti-proliferation and anti-migration effects of EGCG against colorectalcancer SW480,SW620,and LS411N cells by downregulating the expression of STAT3 and suggests that EGCG could be an effective and natural supplement for colon-cancer treatment.展开更多
受新加坡国家公园局(National Parks Board of Singapore,NParks)委托,由Henning Larsen事务所和A61建筑事务所共同设计的射靶场自然公园项目,基于它在景观改造、生态再生和遗产保护方面的贡献而获得认可。在日益紧迫的生物多样性危机中...受新加坡国家公园局(National Parks Board of Singapore,NParks)委托,由Henning Larsen事务所和A61建筑事务所共同设计的射靶场自然公园项目,基于它在景观改造、生态再生和遗产保护方面的贡献而获得认可。在日益紧迫的生物多样性危机中,射靶场自然公园守护着新加坡最后的原始森林之一。展开更多
Background:The maturation of the immune system is critical during early life,as it involves the differentiation,maturation,and establishment of immune tolerance of immune cells.This process is influenced not only by g...Background:The maturation of the immune system is critical during early life,as it involves the differentiation,maturation,and establishment of immune tolerance of immune cells.This process is influenced not only by genetic factors but also by en-vironmental factors,particularly the symbiotic microbiota.Bifidobacterium animalis subsp.lactis(BB-12),originally found in dairy products,is widely used in infant for-mula and dietary supplements.However,its role and mechanisms in immune develop-ment during early life remain unclear.Methods:Using GF mice as the experimental model,B.animalis subsp.lactis BB-12 was administered via gavage during early life.In the juvenile stage,changes in T-cell subsets in the spleen,thymus,and gut intraepithelial lymphocytes(IEL)were assessed using spectral flow cytometry.Additionally,targeted metabolomics analysis of trypto-phan metabolism and short-chain fatty acid pathways in colonic tissue was conducted to explore how B.animalis subsp.lactis BB-12 influences the immune system through gut microbiota metabolism.Results:BB-12 effectively modulates the gut immune microenvironment,leading to beneficial changes in T-cell subsets in key immune tissues such as the spleen,thymus,and gut IELs.Metabolomics analysis further supports these findings by showing that BB-12 intervention greatly increased the production of tryptophan derivatives and acetic acid in the colon of GF mice.Conclusion:The findings provide theoretical evidence for the role of B.animalis subsp.lactis in immune system development and support its application in dietary supple-ments,suggesting potential as a component for infant immune health and in prevent-ing immune-related diseases.展开更多
Quinoid structures are considered to be conducive to the charge transport of organic molecules,but this hypothesis is rarely proven at single-molecule level.Herein,as a proof of concept,the single-molecule conductance...Quinoid structures are considered to be conducive to the charge transport of organic molecules,but this hypothesis is rarely proven at single-molecule level.Herein,as a proof of concept,the single-molecule conductance of two furan-based isomers,3,3'-bis(4-(methylthio)phenyl)-2,2'-bifuran(2,2'-SMPBF)and 4,4'-bis(4-(methylthio)phenyl)-3,3'-bifuran(3,3'-SMPBF),is investigated by the scanning tunneling microscopy break junction(STM-BJ)technique and theoretical simulation.2,2'-SMPBF prefers to adopt a nearly planar conformation with intact alternating single and double bonds extended via2,2'-bifuran moiety and therefore exhibits goodπ-conjugation and a prominent quinoid structure.However,theπ-conjugation of 3,3'-SMPBF is interrupted due to ineffective cross-conjugation in the 3,3'-bifuran moiety,leading to the absence of a quinoid structure.2,2'-SMPBF displays switchable multiple conductances induced by the interconversion between folded and unfolded conformations and an abnormal rebound of conductance along with the increases of electrode displacement,which is demonstrated to be caused by the quinoid structure in a nearly planar conformation during the stretching process.However,3,3'-SMPBF without a quinoid structure in unfolded conformation exhibits extremely low conductance that cannot be captured in STM-BJ measurements.These results reveal the significant contribution of quinoid structure to molecular charge transport and provide valuable information on the structure-transport relationship for the design of efficient organic semiconductors.展开更多
We present new data on the^(63)Cu(γ,n)cross-section studied using a quasi-monochromatic and energy-tunableγbeam produced at the Shanghai Laser Electron Gamma Source to resolve the long-standing discrepancy between e...We present new data on the^(63)Cu(γ,n)cross-section studied using a quasi-monochromatic and energy-tunableγbeam produced at the Shanghai Laser Electron Gamma Source to resolve the long-standing discrepancy between existing measurements and evaluations of this cross-section.Using an unfolding iteration method,^(63)Cu(γ,n)data were obtained with an uncertainty of less than 4%,and the inconsistencies between the available experimental data were discussed.Theγ-ray strength function of^(63)Cu(γ,n)was successfully extracted as an experimental constraint.We further calculated the cross-section of the radiative neutron capture reaction^(62)Cu(n,γ)using the TALYS code.Our calculation method enables the extraction of(n,γ)cross-sections for unstable nuclides.展开更多
There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative...There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative changes of lipids in specific brain regions associated with depressive disorder are far from elucidated.In the present study,lipid profiling characteristics of whole brain sections are systematically determined by using matrix-assisted laser desorption ionization-mass spectrometry imaging(MALDI-MSI)-combined with histomorphological analysis in rats with depressive-like behavior induced by multiple early life stress(mELS)and unstressed control.Lipid dyshomeostasis and different degrees of metabolic disturbance occur in the eight paired representative brain sections from micro-region and molecular level.More specifically,17 lipid molecules show the severe dyshomeostasis between intergroup(control and depressed rats)or intra-group(multiple emotion-regulation-related brain regions).Quite specially,phosphatidylcholine(PC)(39:6)expression in section 7 is significantly upregulated only in the amygdala of depressed rat relative to control rat,by contrast,up-regulated phosphatidylglycerol(PG)(34:2)in section 2 emerges in the medial prefrontal cortex,insular cortex,and nucleus accumbens simultaneously.Linking spatial distribution to quantitative variation of lipids from the whole brain sections contributes the uncovering of new insights in causal mechanism of lipid dyshomeostasis in depression investigation and related targeting interventions.展开更多
Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October ...Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.展开更多
基金supported by grants from Shenzhen Longhua District Science and Technology Innovation Breau[201801 to K.W.L.]Shenzhen Municipal Science and Technology program of China[JCYJ20160425100840929 to K.W.L.]the Natural Science Foundation of Guangdong province[2019A1515011009 to H.C.G.].
文摘Background Green tea is a popular beverage worldwide and epigallocatechin-3-gallate(EGCG)is the most bioactive polyphenol in green tea.Our study aims to investigate the anti-proliferation and anti-migration effects of EGCG against colorectal-cancer SW480,SW620,and LS411N cells,and elucidate the underlying mechanism.Methods The in vitro anti-proliferation and anti-migration effects of EGCG against colon-cancer cells were evaluated using MTT,scratch-wound-healing,and transwell-migration assays.The effects of EGCG on apoptosis were assessed by Annexin V-FITC/PI double staining and JC-1 staining.Besides,Western blotting was employed to detect the protein-expression level and elucidate the underlying pathways.Real-time qPCR and dual-luciferase reporter assay were adopted to determine the mRNA level and promoter activity.Results Our results demonstrated that treatment with EGCG resulted in significant inhibition of cell proliferation by the induction of apoptosis.EGCG also inhibited SW480 cell migration in a dose-dependent manner as assessed by wound-healing and transwell-migration assays.Western blot confirmed that EGCG induced apoptosis by the activation of Caspase-3 and PARP.In addition,both STAT3 and phosphorylated STAT3(p-STAT3)were downregulated significantly by EGCG in three selected colorectal-cancer cell lines.EGCG treatment also resulted in a significant decrease in Bcl-2,MCL-1,and Vimentin,and an increase in E-cadherin.When STAT3 was inhibited,EGCG showed no obvious effect on cell proliferation and migration.Further investigation by luciferase-reporter-activity assay showed that EGCG suppressed the promoter activity of STAT3 and downregulated the transcription of STAT3.Conclusion Our study presents evidence on the anti-proliferation and anti-migration effects of EGCG against colorectalcancer SW480,SW620,and LS411N cells by downregulating the expression of STAT3 and suggests that EGCG could be an effective and natural supplement for colon-cancer treatment.
文摘受新加坡国家公园局(National Parks Board of Singapore,NParks)委托,由Henning Larsen事务所和A61建筑事务所共同设计的射靶场自然公园项目,基于它在景观改造、生态再生和遗产保护方面的贡献而获得认可。在日益紧迫的生物多样性危机中,射靶场自然公园守护着新加坡最后的原始森林之一。
基金supported by the National Key R&D Programs of China(2022YFF0710701,2022YFF0710702)Guangzhou Key Research and Development Program(202206010157)+2 种基金Guangzhou Joint Fund for Key Laboratory(202201020381)Medical Joint Fund of Jinan University(YXJC202204)Open Research Project of the Key Laboratory of Viral Pathogenesis and Infection Prevention and Control of the Ministry of Education(2023VPPC-R02).
文摘Background:The maturation of the immune system is critical during early life,as it involves the differentiation,maturation,and establishment of immune tolerance of immune cells.This process is influenced not only by genetic factors but also by en-vironmental factors,particularly the symbiotic microbiota.Bifidobacterium animalis subsp.lactis(BB-12),originally found in dairy products,is widely used in infant for-mula and dietary supplements.However,its role and mechanisms in immune develop-ment during early life remain unclear.Methods:Using GF mice as the experimental model,B.animalis subsp.lactis BB-12 was administered via gavage during early life.In the juvenile stage,changes in T-cell subsets in the spleen,thymus,and gut intraepithelial lymphocytes(IEL)were assessed using spectral flow cytometry.Additionally,targeted metabolomics analysis of trypto-phan metabolism and short-chain fatty acid pathways in colonic tissue was conducted to explore how B.animalis subsp.lactis BB-12 influences the immune system through gut microbiota metabolism.Results:BB-12 effectively modulates the gut immune microenvironment,leading to beneficial changes in T-cell subsets in key immune tissues such as the spleen,thymus,and gut IELs.Metabolomics analysis further supports these findings by showing that BB-12 intervention greatly increased the production of tryptophan derivatives and acetic acid in the colon of GF mice.Conclusion:The findings provide theoretical evidence for the role of B.animalis subsp.lactis in immune system development and support its application in dietary supple-ments,suggesting potential as a component for infant immune health and in prevent-ing immune-related diseases.
基金financially supported by the National Natural Science Foundation of China(Nos.U23A20594,22375066 and 21788102)Guang Dong Basic and Applied Basic Research Foundation(No.2023B1515040003)。
文摘Quinoid structures are considered to be conducive to the charge transport of organic molecules,but this hypothesis is rarely proven at single-molecule level.Herein,as a proof of concept,the single-molecule conductance of two furan-based isomers,3,3'-bis(4-(methylthio)phenyl)-2,2'-bifuran(2,2'-SMPBF)and 4,4'-bis(4-(methylthio)phenyl)-3,3'-bifuran(3,3'-SMPBF),is investigated by the scanning tunneling microscopy break junction(STM-BJ)technique and theoretical simulation.2,2'-SMPBF prefers to adopt a nearly planar conformation with intact alternating single and double bonds extended via2,2'-bifuran moiety and therefore exhibits goodπ-conjugation and a prominent quinoid structure.However,theπ-conjugation of 3,3'-SMPBF is interrupted due to ineffective cross-conjugation in the 3,3'-bifuran moiety,leading to the absence of a quinoid structure.2,2'-SMPBF displays switchable multiple conductances induced by the interconversion between folded and unfolded conformations and an abnormal rebound of conductance along with the increases of electrode displacement,which is demonstrated to be caused by the quinoid structure in a nearly planar conformation during the stretching process.However,3,3'-SMPBF without a quinoid structure in unfolded conformation exhibits extremely low conductance that cannot be captured in STM-BJ measurements.These results reveal the significant contribution of quinoid structure to molecular charge transport and provide valuable information on the structure-transport relationship for the design of efficient organic semiconductors.
基金supported by the National Key Research and Development Program(Nos.2023YFA1606901 and 2022YFA1602400)National Natural Science Foundation of China(Nos.U2230133,12275338,and 12388102)Open Fund of the CIAE Key Laboratory of Nuclear Data(No.JCKY2022201C152).
文摘We present new data on the^(63)Cu(γ,n)cross-section studied using a quasi-monochromatic and energy-tunableγbeam produced at the Shanghai Laser Electron Gamma Source to resolve the long-standing discrepancy between existing measurements and evaluations of this cross-section.Using an unfolding iteration method,^(63)Cu(γ,n)data were obtained with an uncertainty of less than 4%,and the inconsistencies between the available experimental data were discussed.Theγ-ray strength function of^(63)Cu(γ,n)was successfully extracted as an experimental constraint.We further calculated the cross-section of the radiative neutron capture reaction^(62)Cu(n,γ)using the TALYS code.Our calculation method enables the extraction of(n,γ)cross-sections for unstable nuclides.
基金supported by the China Science and Technology Innovation 2030-Major Project(Nos.2022ZD0211701,2021ZD0200700)the National Natural Science Foundation of China(Nos.82130042,81830040,22176195,82127801)+3 种基金Shenzhen Science and Technology Serial Funds(Nos.GJHZ20210705141400002,KCXFZ20211020164543006,JCYJ20220818101615033,ZDSYS20220606100606014,KQTD 20221101093608028)the National Key R&D Program of China(No.2022YFF0705003)Guangdong Province Zhu Jiang Talents Plan(No.2021QN02Y028)the Guangdong Science and Technology Department(No.2021B1212030004)。
文摘There is growing evidence that lipid metabolism instability in depressive disorder may be a core early pathological event associated with numerous pathogenesis hypotheses.However,spatial distributions and quantitative changes of lipids in specific brain regions associated with depressive disorder are far from elucidated.In the present study,lipid profiling characteristics of whole brain sections are systematically determined by using matrix-assisted laser desorption ionization-mass spectrometry imaging(MALDI-MSI)-combined with histomorphological analysis in rats with depressive-like behavior induced by multiple early life stress(mELS)and unstressed control.Lipid dyshomeostasis and different degrees of metabolic disturbance occur in the eight paired representative brain sections from micro-region and molecular level.More specifically,17 lipid molecules show the severe dyshomeostasis between intergroup(control and depressed rats)or intra-group(multiple emotion-regulation-related brain regions).Quite specially,phosphatidylcholine(PC)(39:6)expression in section 7 is significantly upregulated only in the amygdala of depressed rat relative to control rat,by contrast,up-regulated phosphatidylglycerol(PG)(34:2)in section 2 emerges in the medial prefrontal cortex,insular cortex,and nucleus accumbens simultaneously.Linking spatial distribution to quantitative variation of lipids from the whole brain sections contributes the uncovering of new insights in causal mechanism of lipid dyshomeostasis in depression investigation and related targeting interventions.
文摘Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.
