Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarge...Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.展开更多
The Rpd3 histone deacetylase complex is a multiple-subunit complex that mediates the regulation of chromatin accessibility and gene expression.Sin3,the largest subunit of Rpd3 complex,is conserved in a broad range of ...The Rpd3 histone deacetylase complex is a multiple-subunit complex that mediates the regulation of chromatin accessibility and gene expression.Sin3,the largest subunit of Rpd3 complex,is conserved in a broad range of eukaryotes.Despite being a molecular scaffold for complex assembly,the functional sites and mechanism of action of Sin3 remain unexplored.In this study,we functionally characterized a glutamate residue(E810)in Fg Sin3,the ortholog of yeast Sin3 in Fusarium graminearum(known as wheat scab fungus).Our findings indicate that E810 was important for the functions of Fg Sin3 in regulating vegetative growth,sexual reproduction,wheat infection,and DON biosynthesis.Furthermore,the E810K missense mutation restored the reduced H4 acetylation caused by the deletion of FNG1,the ortholog of the human inhibitor of growth(ING1)gene in F.graminearum.Correspondingly,the defects of the fng1 mutant were also partially rescued by the E810K mutation in Fg Sin3.Sequence alignment and evolutionary analysis revealed that E810 residue is well-conserved in fungi,animals,and plants.Based on Alphafold2 structure modeling,E810 localized on the Fg Rpd3–Fg Sin3 interface for the formation of a hydrogen bond with Fg Rpd3.Mutation of E810 disrupts the hydrogen bond and likely affects the Fg Rpd3–Fg Sin3 interaction.Taken together,E810 of Fg Sin3 is functionally associated with Fng1 in the regulation of H4 acetylation and related biological processes,probably by affecting the assembly of the Rpd3 complex.展开更多
The Kunene Complex(KC)represents a very large Mesoproterozoic igneous body,mainly composed of anorthosites and gabbroic rocks that extends from SW Angola to NW Namibia(outcropping 18,000 km^(2),NE-SW trend,and ca.350 ...The Kunene Complex(KC)represents a very large Mesoproterozoic igneous body,mainly composed of anorthosites and gabbroic rocks that extends from SW Angola to NW Namibia(outcropping 18,000 km^(2),NE-SW trend,and ca.350 km long and up to 50 km wide).Little is known about its structure at depth.Here,we use recently acquired aerogeophysical data to accurately determine its hidden extent and to unravel its morphology at depth.These data have been interpreted and modelled to investigate the unexposed KC boundaries,reconstructing the upper crustal structure(between 0 and 15 km depth)overlain by the thin sedimentary cover of the Kalahari Basin.The modelling reveals that the KC was emplaced in the upper crust and extends in depth up to ca.5 km,showing a lobular geometry and following a large NE-SW to NNE-SSW linear trend,presumably inherited from older Paleoproterozoic structures.The lateral continuation of the KC to the east(between 50 and 125 km)beneath the Kalahari Cenozoic sediments suggests an overall size three times the outcropping dimension(about 53,500 km^(2)).This affirmation clearly reinforces the economic potential of this massif,related to the prospecting of raw materials and certain types of economic mineralization(Fe-Ti oxides,metallic sulphides or platinum group minerals).Up to 11 lobes have been isolated with dimensions ranging from 135.5 to 37.3 km in length and 81.9 to 20.7 km in width according to remanent bodies revealed by TMI mapping.A total volume of 65,184 km3 was calculated only for the magnetically remanent bodies of the KC.A long-lasting complex contractional regime,where large strike-slip fault systems were involved,occurred in three kinematic pulses potentially related to a change of velocity or convergence angle acting on previous Paleoproterozoic inherited sutures.The coalescent magmatic pulses can be recognized by means of magnetic anomalies,age of the bodies as well as the lineations inferred in this work:(i)Emplacement of the eastern mafic bodies and granites in a stage of significant lateral extension in a transtensional context between 1500 Ma and 1420 Ma;(ii)Migration of the mantle derived magmas westwards with deformation in a complex contractional setting with shearing structures involving western KC bodies and basement from 1415 Ma to 1340 Ma;(iii)NNW-SSE extensional structures are relocated westwards,involving mantle magmas,negative flower structures and depression that led to the formation of late Mesoproterozoic basins from 1325 Ma to 1170 Ma.Additionally,we detect several first and second order structures to place the structuring of the KC in a craton-scale context in relation to the crustal structures detected in NW Namibia.展开更多
OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic tar...OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.展开更多
Lishiite,(Ca_(2)□)Sr_(3)(CO_(3))_(5),is a new mineral species from Shaxiongdong,Hubei Province,China.It mainly occours as conchoidal crystals and with combination of hexagonal prism and pyramid and is associated with...Lishiite,(Ca_(2)□)Sr_(3)(CO_(3))_(5),is a new mineral species from Shaxiongdong,Hubei Province,China.It mainly occours as conchoidal crystals and with combination of hexagonal prism and pyramid and is associated with calcite,K-feldspar,albite,aegirine,apatite,and ancylite-(Ce)(?)and strontianite etc.Lishiite is brittle with conchiform fracture and has a Mohs hardness of approximately 4 and none cleavages were observed.The Vickers microhardness(VHN10)is 197.42 kg/mm^(2)(range:166.88 kg/mm^(2) to 214.58 kg/mm^(2)),and the calculated density of lishiite is 3.696 g/cm3.Hand specimen of lishiite are yellow-brown.The empirical chemical formula of the lishiite is ^(A)(Ca_(1.18)Sr_(0.25)Na_(0.19□1.38))_(Σ3.00)^( B)[Sr_(2.17)(Ce_(0.42)La_(0.24)Nd_(0.09)Eu_(0.01))_(Σ0.76) Ba_(0.07)]_(Σ3.00)(C_(5.05)O_(15)).As a member of the burbankite group,the general formula of lishiite follows the general formula A_(3)B_(3)(CO_(3))_(5),where A=Na,Ca,or and B=Sr,Ba,REE,or Ca.Its crystal structure is hexagonal(space group P6_(3)mc)with unit cell parameters a=10.4898(5)Å,c=6.4167(5)Å,and V=611.47(6)Å^(3),characterized by layers of AO_(8) and BO_(10) polyhedra connected to[CO_(3)]^(3−)groups.The discovery of lishiite provides new insights into the evolutionary history of rare earth element(REE)carbonate deposit formation.展开更多
To investigate the long-term stability of deep rocks,a three-dimensional(3D)time-dependent model that accounts for excavation-induced damage and complex stress state is developed.This model comprises three main compon...To investigate the long-term stability of deep rocks,a three-dimensional(3D)time-dependent model that accounts for excavation-induced damage and complex stress state is developed.This model comprises three main components:a 3D viscoplastic isotropic constitutive relation that considers excavation damage and complex stress state,a quantitative relationship between critical irreversible deformation and complex stress state,and evolution characteristics of strength parameters.The proposed model is implemented in a self-developed numerical code,i.e.CASRock.The reliability of the model is validated through experiments.It is indicated that the time-dependent fracturing potential index(xTFPI)at a given time during the attenuation creep stage shows a negative correlation with the extent of excavationinduced damage.The time-dependent fracturing process of rock demonstrates a distinct interval effect of the intermediate principal stress,thereby highlighting the 3D stress-dependent characteristic of the model.Finally,the influence of excavation-induced damage and intermediate principal stress on the time-dependent fracturing characteristics of the surrounding rocks around the tunnel is discussed.展开更多
Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive disorders.In this study,we investigated the cardioprotective effects and...Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive disorders.In this study,we investigated the cardioprotective effects and mechanisms of the essential oil,the main active ingredient of Cymbopogon citratus,on isoproterenol(ISO)-induced cardiomyocyte hypertrophy.Methods:The compositions of Cymbopogon citratus essential oil(CCEO)were determined by gas chromatography-mass spectrometry.Cardiomyocytes were pretreated with 16.9µg/L CCEO for 1 h followed by 10µmol/L ISO for 24 h.Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated.Subsequently,transcriptome sequencing(RNA-seq)and target verification were used to further explore the underlying mechanism.Results:Our results showed that the CCEO mainly included citronellal(45.66%),geraniol(23.32%),and citronellol(10.37%).CCEO inhibited ISO-induced increases in cell surface area and protein content,as well as the upregulation of fetal gene expression.Moreover,CCEO inhibited ISO-induced NLRP3 inflammasome expression,as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3,ASC,CASP1,GSDMD,and IL-1β,as well as reduced protein levels of NLRP3,ASC,pro-caspase-1,caspase-1(p20),GSDMD-FL,GSDMD-N,and pro-IL-1β.The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes.Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1,Sdhd,mt-Cytb,Uqcrq,and mt-Atp6 but had no obvious effects on mt-Col expression.Conclusion:CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.展开更多
Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NC...Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NCAPD3 on HCC cells and the potential underlying mechanisms.Methods NCAPD3 expression in HCC tumors and adjacent noncancerous tissues was quantified via quantitative PCR.Patients were divided into high-and low-expression groups on the basis of NCAPD3 levels,and associations with clinical parameters were assessed.The effects of NCAPD3 knockdown and the phosphatidylinositol-3-kinase(PI3K)agonist Y-P 740 on cell functions were examined via cell proliferation,Transwell migration,and invasion assays.Differentially expressed genes following NCAPD3 knockdown in SMMC-7721 cells were identified via mRNA sequencing.Western blotting was performed to measure NCAPD3,AKT serine/threonine kinase 1(AKT1),and phosphorylated AKT1 levels.Results NCAPD3 mRNA expression was notably upregulated in HCC tissues as compared with that in adjacent noncancer tissues.A positive correlation was observed between NCAPD3 expression and both lymphatic and distant metastases in patients with HCC.NCAPD3 knockdown reduced the proliferation and metastasis of SMMC-7721 and Huh-7 cells.mRNA sequencing revealed 140 downregulated genes and 125 upregulated genes.Further validation experiments confirmed that NCAPD3 modulated the PI3K-AKT signalling pathway and that the PI3K agonist Y-P 740 counteracted the effects of NCAPD3 knockdown.Conclusions Elevated NCAPD3 expression was strongly correlated with HCC metastasis.NCAPD3 inhibition impedes HCC cell growth and metastatic potential by suppressing the PI3K–AKT signalling pathway.展开更多
In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)pro...In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.展开更多
文摘Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.
基金supported by the grants from the National Natural Science Foundation of China(32102181)the Shaanxi Science Fund for Distinguished Young Scholars,China(2022JC-14)。
文摘The Rpd3 histone deacetylase complex is a multiple-subunit complex that mediates the regulation of chromatin accessibility and gene expression.Sin3,the largest subunit of Rpd3 complex,is conserved in a broad range of eukaryotes.Despite being a molecular scaffold for complex assembly,the functional sites and mechanism of action of Sin3 remain unexplored.In this study,we functionally characterized a glutamate residue(E810)in Fg Sin3,the ortholog of yeast Sin3 in Fusarium graminearum(known as wheat scab fungus).Our findings indicate that E810 was important for the functions of Fg Sin3 in regulating vegetative growth,sexual reproduction,wheat infection,and DON biosynthesis.Furthermore,the E810K missense mutation restored the reduced H4 acetylation caused by the deletion of FNG1,the ortholog of the human inhibitor of growth(ING1)gene in F.graminearum.Correspondingly,the defects of the fng1 mutant were also partially rescued by the E810K mutation in Fg Sin3.Sequence alignment and evolutionary analysis revealed that E810 residue is well-conserved in fungi,animals,and plants.Based on Alphafold2 structure modeling,E810 localized on the Fg Rpd3–Fg Sin3 interface for the formation of a hydrogen bond with Fg Rpd3.Mutation of E810 disrupts the hydrogen bond and likely affects the Fg Rpd3–Fg Sin3 interaction.Taken together,E810 of Fg Sin3 is functionally associated with Fng1 in the regulation of H4 acetylation and related biological processes,probably by affecting the assembly of the Rpd3 complex.
基金supported by the subsidiary programme“Ayudas Extraordinarias Menciones Excelencia Severo Ochoa”of the CN IGME-CSIC(project AECEX2021,grant 15903)the University of Minnesota and National Science Foundation(award NSF-EAR 2153786)+1 种基金the Portuguese Foundation for Science and Technology(FCT)support,Geosciences Center project UIDB/00073/2020(doi:10.54499/UIDB/00073/2020)University of Coimbra and and GeoBioTec project UIDB/04035/2020(doi:10.54499/UIDB/04035/2020),Nova School of Science and Technology.
文摘The Kunene Complex(KC)represents a very large Mesoproterozoic igneous body,mainly composed of anorthosites and gabbroic rocks that extends from SW Angola to NW Namibia(outcropping 18,000 km^(2),NE-SW trend,and ca.350 km long and up to 50 km wide).Little is known about its structure at depth.Here,we use recently acquired aerogeophysical data to accurately determine its hidden extent and to unravel its morphology at depth.These data have been interpreted and modelled to investigate the unexposed KC boundaries,reconstructing the upper crustal structure(between 0 and 15 km depth)overlain by the thin sedimentary cover of the Kalahari Basin.The modelling reveals that the KC was emplaced in the upper crust and extends in depth up to ca.5 km,showing a lobular geometry and following a large NE-SW to NNE-SSW linear trend,presumably inherited from older Paleoproterozoic structures.The lateral continuation of the KC to the east(between 50 and 125 km)beneath the Kalahari Cenozoic sediments suggests an overall size three times the outcropping dimension(about 53,500 km^(2)).This affirmation clearly reinforces the economic potential of this massif,related to the prospecting of raw materials and certain types of economic mineralization(Fe-Ti oxides,metallic sulphides or platinum group minerals).Up to 11 lobes have been isolated with dimensions ranging from 135.5 to 37.3 km in length and 81.9 to 20.7 km in width according to remanent bodies revealed by TMI mapping.A total volume of 65,184 km3 was calculated only for the magnetically remanent bodies of the KC.A long-lasting complex contractional regime,where large strike-slip fault systems were involved,occurred in three kinematic pulses potentially related to a change of velocity or convergence angle acting on previous Paleoproterozoic inherited sutures.The coalescent magmatic pulses can be recognized by means of magnetic anomalies,age of the bodies as well as the lineations inferred in this work:(i)Emplacement of the eastern mafic bodies and granites in a stage of significant lateral extension in a transtensional context between 1500 Ma and 1420 Ma;(ii)Migration of the mantle derived magmas westwards with deformation in a complex contractional setting with shearing structures involving western KC bodies and basement from 1415 Ma to 1340 Ma;(iii)NNW-SSE extensional structures are relocated westwards,involving mantle magmas,negative flower structures and depression that led to the formation of late Mesoproterozoic basins from 1325 Ma to 1170 Ma.Additionally,we detect several first and second order structures to place the structuring of the KC in a craton-scale context in relation to the crustal structures detected in NW Namibia.
基金Supported by Guangzhou Science and Technology Bureau Research Fund:the Mechanism of Action of Huangqi Guizhi Decoction on Precancerous Lesions in Cag Rats was Studied based on the Phosphatidylinositol 3-Kinase-Protein Kinase B-Mechanistic Target of Rapamycin Complex 2 Pathway(No.202102080643)Guangzhou Traditional Chinese Medicine and Integrative Medicine Research Project:Observation on the Therapeutic Effect of Wenyang Jianpi Ointment on Chronic Atrophic Gastritis of Spleen and Stomach Weakness Type and Study on its Regulatory Effect on Transforming Growth Factor Beta 3(No.20222A010079)Panyu District Science and Technology Project:the Mechanism by which the Modified Huangqi Guizhi Decoction Regulates the Transforming Growth Factor-β3 Signaling Pathway to Improve Precancerous Lesions in Rats with Chronic Atrophic Gastritis(No.2020-Z04-025)。
文摘OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.
基金supported by the project China Geological Survey(DD202501026090)the National Key Research and Development Program of China(2024YFC2910102).
文摘Lishiite,(Ca_(2)□)Sr_(3)(CO_(3))_(5),is a new mineral species from Shaxiongdong,Hubei Province,China.It mainly occours as conchoidal crystals and with combination of hexagonal prism and pyramid and is associated with calcite,K-feldspar,albite,aegirine,apatite,and ancylite-(Ce)(?)and strontianite etc.Lishiite is brittle with conchiform fracture and has a Mohs hardness of approximately 4 and none cleavages were observed.The Vickers microhardness(VHN10)is 197.42 kg/mm^(2)(range:166.88 kg/mm^(2) to 214.58 kg/mm^(2)),and the calculated density of lishiite is 3.696 g/cm3.Hand specimen of lishiite are yellow-brown.The empirical chemical formula of the lishiite is ^(A)(Ca_(1.18)Sr_(0.25)Na_(0.19□1.38))_(Σ3.00)^( B)[Sr_(2.17)(Ce_(0.42)La_(0.24)Nd_(0.09)Eu_(0.01))_(Σ0.76) Ba_(0.07)]_(Σ3.00)(C_(5.05)O_(15)).As a member of the burbankite group,the general formula of lishiite follows the general formula A_(3)B_(3)(CO_(3))_(5),where A=Na,Ca,or and B=Sr,Ba,REE,or Ca.Its crystal structure is hexagonal(space group P6_(3)mc)with unit cell parameters a=10.4898(5)Å,c=6.4167(5)Å,and V=611.47(6)Å^(3),characterized by layers of AO_(8) and BO_(10) polyhedra connected to[CO_(3)]^(3−)groups.The discovery of lishiite provides new insights into the evolutionary history of rare earth element(REE)carbonate deposit formation.
基金supported by the National Natural Science Foundation of China(Grant No.52125903)the China Postdoctoral Science Foundation(Grant No.2023M730367)the Fundamental Research Funds for Central Public Welfare Research Institutes of China(Grant No.CKSF2023323/YT).
文摘To investigate the long-term stability of deep rocks,a three-dimensional(3D)time-dependent model that accounts for excavation-induced damage and complex stress state is developed.This model comprises three main components:a 3D viscoplastic isotropic constitutive relation that considers excavation damage and complex stress state,a quantitative relationship between critical irreversible deformation and complex stress state,and evolution characteristics of strength parameters.The proposed model is implemented in a self-developed numerical code,i.e.CASRock.The reliability of the model is validated through experiments.It is indicated that the time-dependent fracturing potential index(xTFPI)at a given time during the attenuation creep stage shows a negative correlation with the extent of excavationinduced damage.The time-dependent fracturing process of rock demonstrates a distinct interval effect of the intermediate principal stress,thereby highlighting the 3D stress-dependent characteristic of the model.Finally,the influence of excavation-induced damage and intermediate principal stress on the time-dependent fracturing characteristics of the surrounding rocks around the tunnel is discussed.
基金supported by grants from the National Natural Science Foundation of China(Nos.81960732 and 82060733)the Natural Science Foundation of Jiangxi Province(No.20224BAB206111)+2 种基金the Science and Technology Plan of Jiangxi Provincial Health Commission(No.202311141)the Open Project of Jiangxi Provincial Key Laboratory of Drug Design and Evaluation(No.JKLDE-KF-2101)the Open Project of Key Laboratory of Modern Preparation of TCM,Ministry of Education,Jiangxi University of Chinese Medicine(No.TCM-201911).
文摘Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive disorders.In this study,we investigated the cardioprotective effects and mechanisms of the essential oil,the main active ingredient of Cymbopogon citratus,on isoproterenol(ISO)-induced cardiomyocyte hypertrophy.Methods:The compositions of Cymbopogon citratus essential oil(CCEO)were determined by gas chromatography-mass spectrometry.Cardiomyocytes were pretreated with 16.9µg/L CCEO for 1 h followed by 10µmol/L ISO for 24 h.Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated.Subsequently,transcriptome sequencing(RNA-seq)and target verification were used to further explore the underlying mechanism.Results:Our results showed that the CCEO mainly included citronellal(45.66%),geraniol(23.32%),and citronellol(10.37%).CCEO inhibited ISO-induced increases in cell surface area and protein content,as well as the upregulation of fetal gene expression.Moreover,CCEO inhibited ISO-induced NLRP3 inflammasome expression,as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3,ASC,CASP1,GSDMD,and IL-1β,as well as reduced protein levels of NLRP3,ASC,pro-caspase-1,caspase-1(p20),GSDMD-FL,GSDMD-N,and pro-IL-1β.The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes.Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1,Sdhd,mt-Cytb,Uqcrq,and mt-Atp6 but had no obvious effects on mt-Col expression.Conclusion:CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.
基金supported by grants from Guangxi Nanning Qingxiu District Key Research and Development Program of Science and Technology Plan(no.2020050)Guangxi Medical and Health Appropriate Technology Development,Promotion and Application Project(no.S2021097)+1 种基金Guangxi Key Research and Development Program(no.AB22080064)Guangxi Natural Science Foundation(no.2017GXNSFAA198126).
文摘Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NCAPD3 on HCC cells and the potential underlying mechanisms.Methods NCAPD3 expression in HCC tumors and adjacent noncancerous tissues was quantified via quantitative PCR.Patients were divided into high-and low-expression groups on the basis of NCAPD3 levels,and associations with clinical parameters were assessed.The effects of NCAPD3 knockdown and the phosphatidylinositol-3-kinase(PI3K)agonist Y-P 740 on cell functions were examined via cell proliferation,Transwell migration,and invasion assays.Differentially expressed genes following NCAPD3 knockdown in SMMC-7721 cells were identified via mRNA sequencing.Western blotting was performed to measure NCAPD3,AKT serine/threonine kinase 1(AKT1),and phosphorylated AKT1 levels.Results NCAPD3 mRNA expression was notably upregulated in HCC tissues as compared with that in adjacent noncancer tissues.A positive correlation was observed between NCAPD3 expression and both lymphatic and distant metastases in patients with HCC.NCAPD3 knockdown reduced the proliferation and metastasis of SMMC-7721 and Huh-7 cells.mRNA sequencing revealed 140 downregulated genes and 125 upregulated genes.Further validation experiments confirmed that NCAPD3 modulated the PI3K-AKT signalling pathway and that the PI3K agonist Y-P 740 counteracted the effects of NCAPD3 knockdown.Conclusions Elevated NCAPD3 expression was strongly correlated with HCC metastasis.NCAPD3 inhibition impedes HCC cell growth and metastatic potential by suppressing the PI3K–AKT signalling pathway.
基金Supported by Italian Association for Cancer Research(AIRC),No.21956Italian Ministry of Health-5×1000 funds 2023.
文摘In this editorial,we comment on the article by Zhang et al recently published in the World Journal of Gastroenterology.The manuscript elucidates significant novel mechanisms underlying hepatocellular carcinoma(HCC)progression.HCC is currently considered one of the major causes of global cancer-associated deaths,underscoring the critical need for novel therapeutic targets.Growing evidence underlines the role of the lipid raft protein flotillin-1(FLOT1)in cancer,whose dysregulation drives tumor cell growth and survival.However,the regulatory role of FLOT1 on Golgi apparatus function in HCC is unknown.In this study,Zhang et al elucidated a pivotal mechanism by which FLOT1 promotes HCC progression through activation of transcription factor E3-mediated Golgi stress response.The study reveals that FLOT1 inhibits the mechanistic target of rapamycin complexes 1 and 2 by ubiquitination,facilitating transcription factor E3 dephosphorylation,nuclear translocation,and subsequent upregulation of Golgi stress-associated genes,thereby leading to enhanced HCC cell growth and invasive capacity.These findings obtained in vitro/in vivo highlight the interplay between FLOT1 and Golgi homeostasis in HCC.Targeting FLOT1 may offer a new strategy for the treatment of HCC.
