Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting trea...Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment efficiency.It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer.Herein,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal barrier.We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties.Of these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to LSMs.Furthermore,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in vivo.These findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.展开更多
The Niangzhong diabase dikes,dated at 138.1±0.4 Ma,are located within the outcrop area of the Comei large igneous province(LIP).These diabase samples can be divided into two groups:samples in Group 1 show varying...The Niangzhong diabase dikes,dated at 138.1±0.4 Ma,are located within the outcrop area of the Comei large igneous province(LIP).These diabase samples can be divided into two groups:samples in Group 1 show varying MgO(1.50 wt.%-10.25 wt.%)and TiO_(2)(0.85 wt.%-4.63 wt.%)contents,and enriched initial isotope compositions(^(87)Sr/^(86)Sr(t)=0.7056-0.7112,ε_(Nd)(t)=-0.3-+3.8),with OIB-like REEs and trace elements patterns,resulting from low degree melting of garnet-bearing lherzolite mantle sources;in contrast,samples in Group 2 show limited MgO(4.14 wt.%-7.75 wt.%)and TiO_(2)(0.98 wt.%-1.69 wt.%)contents,and depleted initial isotope compositions(^(87)Sr/^(86)Sr(t)=0.7075-0.7112,ε_(Nd)(t)=+5.5-+6.2),with N-MORB-like REEs and trace elements patterns,resulting from relatively high degree melting of spinel-bearing lherzolite mantle source.Combined with the published representative data about Comei LIP,we summarize that the source components for Comei LIP products include OIB end-member,enriched OIB end-member,and N-MORB end-member,respectively.Melts modeling suggests that magmas in the Comei LIP evolve in a relatively high oxygen fugacity condition,which influenced their fractionation sequences and led to systematic changes of TiO_(2)contents,Ti/Y and Ti/Ti*ratios.From the spatial and temporal distribution of above three end-member samples,deep process of Kerguelen plume during the Comei LIP formation can be interpreted as the interaction among the Kerguelen plume,the overlying lithospheric mantle,and the upwelling asthenosphere.The magmatism of Comei LIP began at~140 Ma and then lasted and peaked at~132 Ma with the progressively lithospheric thinning of eastern Gondwana upon the impact of Kerguelen plume.展开更多
The soybean E1 gene is a major regulator that plays an important role in flowering time and maturity.However,it remains unclear how cultivars carrying the dominant E1 allele adapt to the higher latitudinal areas of no...The soybean E1 gene is a major regulator that plays an important role in flowering time and maturity.However,it remains unclear how cultivars carrying the dominant E1 allele adapt to the higher latitudinal areas of northern China.We mapped the novel quantitative trait locus QNE1(QTL near E1) for flowering time to the region proximal to E1 on chromosome 6 in two mapping populations.Positional cloning revealed Glyma.06G204300,encoding a TCP-type transcription factor,as a strong candidate gene for QNE1.Association analysis further confirmed that functional single nucleotide polymorphisms(SNPs) at nucleotides 686 and 1,063 in the coding region of Glyma.06G204300 were significantly associated with flowering time.The protein encoded by the candidate gene is localized primarily to the nucleus.Furthermore,soybean and Brassica napus plants overexpressing Glyma.06G204300 exhibited early flowering.We conclude that despite their similar effects on flowering time,QNE1 and E4 may control flowering time through different regulatory mechanisms,based on expression studies and weighted gene co-expression network analysis of flowering time-related genes.Deciphering the molecular basis of QNE1 control of flowering time enriches our knowledge of flowering gene networks in soybean and will facilitate breeding soybean cultivars with broader latitudinal adaptation.展开更多
Background The Midasin AAA(ATPase associated with various activities)ATPase 1(MDN1)gene,a member of the AAA protein family,plays a crucial role in ribosome maturation.MDN1 is expressed in the human brain throughout li...Background The Midasin AAA(ATPase associated with various activities)ATPase 1(MDN1)gene,a member of the AAA protein family,plays a crucial role in ribosome maturation.MDN1 is expressed in the human brain throughout life,especially during early development and adulthood.However,MDN1 variants have not been previously reported in patients with epilepsy.This study aims to explore the association between MDN1 variants and epilepsy.Methods Trios-based whole-exome sequencing was performed in a cohort of patients with epilepsy susceptibility from the China Epilepsy Gene 1.0 Project.The excess,damaging efects,and molecular subregional implications of variants,as well as the spatio-temporal expression of MDN1,were analyzed to validate the gene-disease association.Results Compound heterozygous variants in MDN1 were identifed in fve unrelated patients with febrile seizures or secondary epilepsy.Three patients presented with febrile seizures/epilepsy with febrile seizures plus,while two patients developed epilepsy secondary to brain damage(fve or seven years after).These variants were either absent or present at low frequencies in the control group,and exhibited statistically signifcant higher frequencies in the case group compared to controls.All the missense variants were predicted to be damaging by at least one in silico tool.In each pair of compound heterozygous variants,one allele was located in the AAA2-AAA3 domains,while the other allele was located in the linker domain or its vicinity.In contrast,most of the variants from the asymptomatic control group were located outside the AAA domains,suggesting a molecular subregional implication of the MDN1 variants.Conclusions MDN1 is potentially a susceptibility gene for epilepsy.展开更多
基金the financial support from the National Natural Science Foundation of China(Nos.82003678,82222066,82025032)Chinese Pharmacopoeia Commission(No.2021Y30)。
文摘Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment efficiency.It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer.Herein,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal barrier.We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties.Of these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to LSMs.Furthermore,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in vivo.These findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research(No.2019QZKK0702)the National Natural Science Foundation of China(Nos.92055202,41873023,42102059)+3 种基金the China Geological Survey(No.DD20190057)the National Key Research and Development Project of China(No.2016YFC0600304)the Basic Scientific Research Fund of Key Laboratory of Deep-Earth Dynamics of Ministry of Natural Resources(Nos.J1901-1,J190110)the National Foundation from China Scholarship Council。
文摘The Niangzhong diabase dikes,dated at 138.1±0.4 Ma,are located within the outcrop area of the Comei large igneous province(LIP).These diabase samples can be divided into two groups:samples in Group 1 show varying MgO(1.50 wt.%-10.25 wt.%)and TiO_(2)(0.85 wt.%-4.63 wt.%)contents,and enriched initial isotope compositions(^(87)Sr/^(86)Sr(t)=0.7056-0.7112,ε_(Nd)(t)=-0.3-+3.8),with OIB-like REEs and trace elements patterns,resulting from low degree melting of garnet-bearing lherzolite mantle sources;in contrast,samples in Group 2 show limited MgO(4.14 wt.%-7.75 wt.%)and TiO_(2)(0.98 wt.%-1.69 wt.%)contents,and depleted initial isotope compositions(^(87)Sr/^(86)Sr(t)=0.7075-0.7112,ε_(Nd)(t)=+5.5-+6.2),with N-MORB-like REEs and trace elements patterns,resulting from relatively high degree melting of spinel-bearing lherzolite mantle source.Combined with the published representative data about Comei LIP,we summarize that the source components for Comei LIP products include OIB end-member,enriched OIB end-member,and N-MORB end-member,respectively.Melts modeling suggests that magmas in the Comei LIP evolve in a relatively high oxygen fugacity condition,which influenced their fractionation sequences and led to systematic changes of TiO_(2)contents,Ti/Y and Ti/Ti*ratios.From the spatial and temporal distribution of above three end-member samples,deep process of Kerguelen plume during the Comei LIP formation can be interpreted as the interaction among the Kerguelen plume,the overlying lithospheric mantle,and the upwelling asthenosphere.The magmatism of Comei LIP began at~140 Ma and then lasted and peaked at~132 Ma with the progressively lithospheric thinning of eastern Gondwana upon the impact of Kerguelen plume.
基金supported by the Strategic Priority Research Program(XDA24010105-4,XDA28070000)the Key Deployment Projects(ZDRW-ZS-2019-2)of the Chinese Academy of Sciences+1 种基金the National Natural Science Foundation of China(U21A20215,31771818,31771869)the Young Scientists Group Project(2022QNXZ05)of Northeast Institute of Geography and Agroecology,Chinese Academy of Sciences。
文摘The soybean E1 gene is a major regulator that plays an important role in flowering time and maturity.However,it remains unclear how cultivars carrying the dominant E1 allele adapt to the higher latitudinal areas of northern China.We mapped the novel quantitative trait locus QNE1(QTL near E1) for flowering time to the region proximal to E1 on chromosome 6 in two mapping populations.Positional cloning revealed Glyma.06G204300,encoding a TCP-type transcription factor,as a strong candidate gene for QNE1.Association analysis further confirmed that functional single nucleotide polymorphisms(SNPs) at nucleotides 686 and 1,063 in the coding region of Glyma.06G204300 were significantly associated with flowering time.The protein encoded by the candidate gene is localized primarily to the nucleus.Furthermore,soybean and Brassica napus plants overexpressing Glyma.06G204300 exhibited early flowering.We conclude that despite their similar effects on flowering time,QNE1 and E4 may control flowering time through different regulatory mechanisms,based on expression studies and weighted gene co-expression network analysis of flowering time-related genes.Deciphering the molecular basis of QNE1 control of flowering time enriches our knowledge of flowering gene networks in soybean and will facilitate breeding soybean cultivars with broader latitudinal adaptation.
基金funded by Medical Joint Fund of Jinan University(No.YXJC2022010)Dongguan Science and Technology Bureau 2023(No.20231800905272)+3 种基金The City School(institute)Enterprise Joint Funding Project of Guangzhou Science and Technology Bureau(No.2025A03J4094)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515010218)Science and Technology Projects in Guangzhou(No.2023A03J1026)Fundamental Research Funds for the Central Universities(No.21623405).
文摘Background The Midasin AAA(ATPase associated with various activities)ATPase 1(MDN1)gene,a member of the AAA protein family,plays a crucial role in ribosome maturation.MDN1 is expressed in the human brain throughout life,especially during early development and adulthood.However,MDN1 variants have not been previously reported in patients with epilepsy.This study aims to explore the association between MDN1 variants and epilepsy.Methods Trios-based whole-exome sequencing was performed in a cohort of patients with epilepsy susceptibility from the China Epilepsy Gene 1.0 Project.The excess,damaging efects,and molecular subregional implications of variants,as well as the spatio-temporal expression of MDN1,were analyzed to validate the gene-disease association.Results Compound heterozygous variants in MDN1 were identifed in fve unrelated patients with febrile seizures or secondary epilepsy.Three patients presented with febrile seizures/epilepsy with febrile seizures plus,while two patients developed epilepsy secondary to brain damage(fve or seven years after).These variants were either absent or present at low frequencies in the control group,and exhibited statistically signifcant higher frequencies in the case group compared to controls.All the missense variants were predicted to be damaging by at least one in silico tool.In each pair of compound heterozygous variants,one allele was located in the AAA2-AAA3 domains,while the other allele was located in the linker domain or its vicinity.In contrast,most of the variants from the asymptomatic control group were located outside the AAA domains,suggesting a molecular subregional implication of the MDN1 variants.Conclusions MDN1 is potentially a susceptibility gene for epilepsy.
