Two series of novel derivatives of imidazo[4,5-b]pyridine were synthesized. These compounds could be used as side chains of semisynthesised ketolide antibiotics. The side chains have free amine group which can attache...Two series of novel derivatives of imidazo[4,5-b]pyridine were synthesized. These compounds could be used as side chains of semisynthesised ketolide antibiotics. The side chains have free amine group which can attached to ketolide core. Macrolides with this kind of side chains will show obvious activities against erythromycin-resistant strains. The structure of the side chains was confirmed by ^1H, ^13C NMR, MS, HMBC spectra. 2007 Ping Sheng Lei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.展开更多
After type A acute aortic dissection(AAD)repair or modified Bentall procedure,uncontrollable bleeding from the anastomotic sites of the fragile dissected tissues or aortic root area is a critical situation to a cardia...After type A acute aortic dissection(AAD)repair or modified Bentall procedure,uncontrollable bleeding from the anastomotic sites of the fragile dissected tissues or aortic root area is a critical situation to a cardiac surgeon.For postoperative care,lots of blood transfusion with strict monitoring on the patient all night and subsequent reoperation for the bleeding control is usually needed.We managed to make contained local compression of upper half of the heart,from upper part of the right ventricle to just above the innominate vein,using bovine pericardium with closing both sides of transverse sinus in two cases of uncontrolled postoperative bleeding(bleeding from distal anastomotic site in type-A AAD and valve sitting site in modified Bentall procedure).Even though reoperations for the removal of packed gauges were done in both cases 2 days later,postoperative courses at intensive care unit were very smooth with little need for transfusion.This kind of contained local compression trial could be a useful strategy for dealing with the malignant uncontrollable bleeding from the fragile aortic tissue or root area after acute dissection or aortic root repair.展开更多
According to the observation in experiment of stability of the oil film, the assumption of velocity distribution for both the water flow and the oil film is introduced. On the basis of the assumption, Orr-Sommerfeld s...According to the observation in experiment of stability of the oil film, the assumption of velocity distribution for both the water flow and the oil film is introduced. On the basis of the assumption, Orr-Sommerfeld stability equation is applied to develop the method of determining the critical velocity of the oil film, and the criterion for stability of the oil film is obtained. Meanwhile, a formula describing the relation between the thickness of the oil film and the velocity of the water flow is also given and examined by the laboratory experiment.展开更多
The hormone defined serum free conditioned medium (SFCM) of human nasopharyngeal carcinoma epithelioid cell line (CNE1) was assayed by both the 3H-thymidine incorporation test and the soft agar test. It was found that...The hormone defined serum free conditioned medium (SFCM) of human nasopharyngeal carcinoma epithelioid cell line (CNE1) was assayed by both the 3H-thymidine incorporation test and the soft agar test. It was found that the SFCM stimulated the growth of long-term serum-free cultured CNE4 cells in ac-cordence with the fact that the growth rate of long-term serum-free cultured CNE1 cells was directly proportional to the plating density. Alternatively 5% SFCM inhibited the growth of short-term serum-free cultured CNE4 cells by 51% in which the indicator cell remained the responsiveness state of growing in the serum-supplemented medium to the effector of interest. Furthermore, SFCM resulted in the inhibition of anchorage-independent growth of CNE4 cells and A431 cells. Also in soft agar test. SFCM reduced the colony formation of NRK(?),9F cells in the presence of EGF or EGF plus TGF-β. These finding suggested that CNE4 secreted autocrine growth stimulating factor(s) and growth inhibiting factor(s) in the serum-free medium, the latter strongly reverse malignant phenotypes of CNE4 and A431 cells in serum-supplemented surrounding.展开更多
The strength and stiffness contribution of infill masonry is generally ignored in the design, due to the uncertainty in the strength properties of masonry, separation of infill from frame, low tensile strength, brittl...The strength and stiffness contribution of infill masonry is generally ignored in the design, due to the uncertainty in the strength properties of masonry, separation of infill from frame, low tensile strength, brittle characteristics of masonry walls, less out of plane strength and stiffness, etc.. They are considered as nonstructural elements which is reasonable for the frames under gravity loads but it is not true for the frames under seismic loads. Contained masonry as infill in RC (reinforced concrete) frames provides better contact at the interface and a higher out of plane strength and stiffness. Considering the seismic action on the frames which are likely to be subjected to in-plane as well as out of plane shaking, a research work has been carried out by the authors to investigate the seismic performance of RC frames with and without contained masonry infill panels using FE (finite element) computer program (ANSYS-Ver. l 1) and experimentally using the tri-axial shake table to evaluate the methods proposed in IS-1893-2002 to calculate the fundamental natural frequency. The RC frames were designed and detailed as per IS (Indian Standard) specifications such as IS 456-2000, IS 1893-2002 and IS 13920-1993. Based on the experimental and analytical investigations, the contained masonry infill panels significantly affect the seismic load resisting characteristics of the RC frames. The IS 1893-2002 formulation does not predict the values and hence the recommendation needs to be validated with experimental results.展开更多
The anti-corruption battle must go deeper,President Xi Jinping said on January 6,calling for strict governance of the Communist Party of China(CPC)systematically,creatively and effectively.Xi,also General Secretary of...The anti-corruption battle must go deeper,President Xi Jinping said on January 6,calling for strict governance of the Communist Party of China(CPC)systematically,creatively and effectively.Xi,also General Secretary of the CPC Central Committee and Chairman of the Central Military Commission。展开更多
Using the 3-D sono-elasticity method and the simplified nonstructural mass method,the different dynamic modeling methods of the added water for a single-hull structure are first analyzed in this study.Then,the complet...Using the 3-D sono-elasticity method and the simplified nonstructural mass method,the different dynamic modeling methods of the added water for a single-hull structure are first analyzed in this study.Then,the complete internal flow field method and the simplified nonstructural mass method of the contained water between the double hulls of a double-hull structure are investigated.Finally,based on the calculation and analysis under multiple conditions,a reasonable and simplified dynamic modeling method of added water and contained water is obtained.It is indicated that the mass of added water for a single-hull structure is closely related to the mass of total underwater displacement of the structure.With the increase in the analysis frequency,the mass of added water is characterized by first decreasing rapidly and then decreasing gradually and smoothly.The contained water between the double hulls is distributed to the pressure hull and the light shell based on the ratio of the impedances of the double hulls.The results can basically reflect the acoustic radiation characteristics of the double-hull structure.展开更多
Established in 2019,the Shandong Port Group(SPG)comprises four port groups(Qingdao Port,Rizhao Port,Yantai Port,and Bohaiwan Port)and 12 business segments.SPG connects 3,345 kilometers of coastline within Shandong Pro...Established in 2019,the Shandong Port Group(SPG)comprises four port groups(Qingdao Port,Rizhao Port,Yantai Port,and Bohaiwan Port)and 12 business segments.SPG connects 3,345 kilometers of coastline within Shandong Province.Its cargo throughput has consistently ranked first globally for many years,and its container volume growth ranks second globally,forming a port cluster covering the entire industrial chain.展开更多
Alzheimer’s disease(AD)is the most common form of dementia characterized pathologically by the deposition of amyloid plaques and hyperphosphorylated tau containing neurofibrillary tangles.The disease presents clinica...Alzheimer’s disease(AD)is the most common form of dementia characterized pathologically by the deposition of amyloid plaques and hyperphosphorylated tau containing neurofibrillary tangles.The disease presents clinically with progressive memory loss and disruption of cognitive function.Currently,there is no cure for AD;recent advances in the therapeutics aimed at clearing the amyloid protein from the brain have led to potential disease stabilization,however,this does not prevent eventual disease progression(Cummings et al.,2024).展开更多
Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containin...Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.展开更多
Mesenchymal stem cells(MSCs),which are mechanosensitive cells,mediate the cells crosstalk in response to mechanical force,thereby playing a crucial role in bone homeostasis.Migrasomes serve as an important mediator fo...Mesenchymal stem cells(MSCs),which are mechanosensitive cells,mediate the cells crosstalk in response to mechanical force,thereby playing a crucial role in bone homeostasis.Migrasomes serve as an important mediator for cellular communication.However,whether the mechanical stimulus regulates the biology and property of migrasomes on bone metabolism remains unknown.This study shows that mechanical stimulus could promote MSCs to synthesize and secrete migrasomes,which could significantly alleviate chronic infectious bone destruction in periodontal tissue by inhibiting osteoclastic differentiation of macrophage and reestablishing local immune microenvironment.Mechanistically,miR-29b-3p is more abundant in migrasomes from mechanical force stimulated MSCs than in control ones.MiR-29b-3p blocks the activation of pyrin domain containing protein 3(NLRP3)and mitochondrial DNA(mtDNA)release by directly targeting on Tet1.Thus,mechanical sensing migrasomes inhibit osteoclast differentiation to alleviate inflammation induced bone destruction.These findings reveal that the mechanical stimulus controls the formation and properties of migrasomes,which provides a new biotechnological strategy for chronic infectious bone destruction intervention.展开更多
According to the No. 14 proclamation issued by Customs Service, as from April 1st 2007, the importation of galena and the lead ore concentrate will enjoy the favorable policy intended for associated gold deposits, i.e...According to the No. 14 proclamation issued by Customs Service, as from April 1st 2007, the importation of galena and the lead ore concentrate will enjoy the favorable policy intended for associated gold deposits, i.e. the value-added tax for gold component in the imported galena and lead ore concentrate is exempted,展开更多
Qingshan officials released that the 300,000- ton/year nickel-contained pig iron plant of the Group in Fu’an,Fujian will be put into produc- tion at the end of this year.Upon completion,4 units of 25,000-walt electri...Qingshan officials released that the 300,000- ton/year nickel-contained pig iron plant of the Group in Fu’an,Fujian will be put into produc- tion at the end of this year.Upon completion,4 units of 25,000-walt electric furnace will展开更多
Biodiversity has always been valued by ecology,Diversity is generally believed to lead to stability,and biodiversity is an important condition for ecosystems to maintain health.So what factors are related to forest ec...Biodiversity has always been valued by ecology,Diversity is generally believed to lead to stability,and biodiversity is an important condition for ecosystems to maintain health.So what factors are related to forest ecosystem biodiversity,and what kind of forest structure affects and determines the size of biodiversity.This study proposes the concept of contained uniformity based on the theory of uniformity,and uses the convergence of contained uniformity to obtain the judgment model of the forest station pattern type.At the same time,it proposes the concept of forest ecosystem distance diversity,and uses the judgment model of the stand pattern type to derive the mathematical definition of forest ecosystem distance diversity.Combining the ecological characteristics of different stand patterns and measurement indicators of forest ecosystem biodiversity,the connection between forest ecosystem distance diversity and biodiversity is derived,and this is used as an indicator to evaluate forest ecosystem biodiversity.Forest ecosystem distance diversity,as an indicator of biodiversity,can not only conduct early assessment and prediction of the biodiversity of immature forests(forests in the early succession or recovery stage),but also provide a quantitative basis for forest structure optimization.Ultimately realize the sustainable development of forestry production and operation and biodiversity protection.展开更多
The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of mol...The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.展开更多
Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restric...Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restrict maize plant growth and development,leading to great yield losses.Leucine-rich repeat receptor-like kinases(LRR-RLKs)function in biotic and abiotic stress responses in the model plant Arabidopsis(Arabidopsis thaliana),but their roles in abiotic stress responses in maize are not entirely understood.In this study,we determine that the LRR-RLK ZmMIK2,a homolog of the Arabidopsis LRR-RK MALE DISCOVERER 1(MDIS1)-INTERACTING RECEPTOR LIKE KINASE 2(MIK2),functions in resistance to both drought and salt stress in maize.Zmmik2 plants exhibit enhanced resistance to both stresses,whereas overexpressing ZmMIK2 confers the opposite phenotypes.Furthermore,we identify C2-DOMAIN-CONTAINING PROTEIN 1(ZmC2DP1),which interacts with the intracellular region of ZmMIK2.Notably,that region of ZmMIK2 mediates the phosphorylation of ZmC2DP1,likely by increasing its stability.Both ZmMIK2 and ZmC2DP1 are mainly expressed in roots.As with ZmMIK2,knockout of ZmC2DP1 enhances resistance to both drought and salt stress.We conclude that ZmMIK2-ZmC2DP1 acts as a negative regulatory module in maize drought-and salt-stress responses.展开更多
The cavity characteristics in liquid-filled containers caused by high-velocity impacts represent an important area of research in hydrodynamic ram phenomena.The dynamic expansion of the cavity induces liquid pressure ...The cavity characteristics in liquid-filled containers caused by high-velocity impacts represent an important area of research in hydrodynamic ram phenomena.The dynamic expansion of the cavity induces liquid pressure variations,potentially causing catastrophic damage to the container.Current studies mainly focus on non-deforming projectiles,such as fragments,with limited exploration of shaped charge jets.In this paper,a uniquely experimental system was designed to record cavity profiles in behind-armor liquid-filled containers subjected to shaped charge jet impacts.The impact process was then numerically reproduced using the explicit simulation program ANSYS LS-DYNA with the Structured Arbitrary Lagrangian-Eulerian(S-ALE)solver.The formation mechanism,along with the dimensional and shape evolution of the cavity was investigated.Additionally,the influence of the impact kinetic energy of the jet on the cavity characteristics was analyzed.The findings reveal that the cavity profile exhibits a conical shape,primarily driven by direct jet impact and inertial effects.The expansion rates of both cavity length and maximum radius increase with jet impact kinetic energy.When the impact kinetic energy is reduced to 28.2 kJ or below,the length-to-diameter ratio of the cavity ultimately stabilizes at approximately 7.展开更多
基金Finacial support of this research by the National Natural Science Foundation of China (No. 30572275) ;Natural Science Foundation of Beijing (No. 7062047) are gratefully acknowledged by the authors.
文摘Two series of novel derivatives of imidazo[4,5-b]pyridine were synthesized. These compounds could be used as side chains of semisynthesised ketolide antibiotics. The side chains have free amine group which can attached to ketolide core. Macrolides with this kind of side chains will show obvious activities against erythromycin-resistant strains. The structure of the side chains was confirmed by ^1H, ^13C NMR, MS, HMBC spectra. 2007 Ping Sheng Lei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
文摘After type A acute aortic dissection(AAD)repair or modified Bentall procedure,uncontrollable bleeding from the anastomotic sites of the fragile dissected tissues or aortic root area is a critical situation to a cardiac surgeon.For postoperative care,lots of blood transfusion with strict monitoring on the patient all night and subsequent reoperation for the bleeding control is usually needed.We managed to make contained local compression of upper half of the heart,from upper part of the right ventricle to just above the innominate vein,using bovine pericardium with closing both sides of transverse sinus in two cases of uncontrolled postoperative bleeding(bleeding from distal anastomotic site in type-A AAD and valve sitting site in modified Bentall procedure).Even though reoperations for the removal of packed gauges were done in both cases 2 days later,postoperative courses at intensive care unit were very smooth with little need for transfusion.This kind of contained local compression trial could be a useful strategy for dealing with the malignant uncontrollable bleeding from the fragile aortic tissue or root area after acute dissection or aortic root repair.
文摘According to the observation in experiment of stability of the oil film, the assumption of velocity distribution for both the water flow and the oil film is introduced. On the basis of the assumption, Orr-Sommerfeld stability equation is applied to develop the method of determining the critical velocity of the oil film, and the criterion for stability of the oil film is obtained. Meanwhile, a formula describing the relation between the thickness of the oil film and the velocity of the water flow is also given and examined by the laboratory experiment.
文摘The hormone defined serum free conditioned medium (SFCM) of human nasopharyngeal carcinoma epithelioid cell line (CNE1) was assayed by both the 3H-thymidine incorporation test and the soft agar test. It was found that the SFCM stimulated the growth of long-term serum-free cultured CNE4 cells in ac-cordence with the fact that the growth rate of long-term serum-free cultured CNE1 cells was directly proportional to the plating density. Alternatively 5% SFCM inhibited the growth of short-term serum-free cultured CNE4 cells by 51% in which the indicator cell remained the responsiveness state of growing in the serum-supplemented medium to the effector of interest. Furthermore, SFCM resulted in the inhibition of anchorage-independent growth of CNE4 cells and A431 cells. Also in soft agar test. SFCM reduced the colony formation of NRK(?),9F cells in the presence of EGF or EGF plus TGF-β. These finding suggested that CNE4 secreted autocrine growth stimulating factor(s) and growth inhibiting factor(s) in the serum-free medium, the latter strongly reverse malignant phenotypes of CNE4 and A431 cells in serum-supplemented surrounding.
文摘The strength and stiffness contribution of infill masonry is generally ignored in the design, due to the uncertainty in the strength properties of masonry, separation of infill from frame, low tensile strength, brittle characteristics of masonry walls, less out of plane strength and stiffness, etc.. They are considered as nonstructural elements which is reasonable for the frames under gravity loads but it is not true for the frames under seismic loads. Contained masonry as infill in RC (reinforced concrete) frames provides better contact at the interface and a higher out of plane strength and stiffness. Considering the seismic action on the frames which are likely to be subjected to in-plane as well as out of plane shaking, a research work has been carried out by the authors to investigate the seismic performance of RC frames with and without contained masonry infill panels using FE (finite element) computer program (ANSYS-Ver. l 1) and experimentally using the tri-axial shake table to evaluate the methods proposed in IS-1893-2002 to calculate the fundamental natural frequency. The RC frames were designed and detailed as per IS (Indian Standard) specifications such as IS 456-2000, IS 1893-2002 and IS 13920-1993. Based on the experimental and analytical investigations, the contained masonry infill panels significantly affect the seismic load resisting characteristics of the RC frames. The IS 1893-2002 formulation does not predict the values and hence the recommendation needs to be validated with experimental results.
文摘The anti-corruption battle must go deeper,President Xi Jinping said on January 6,calling for strict governance of the Communist Party of China(CPC)systematically,creatively and effectively.Xi,also General Secretary of the CPC Central Committee and Chairman of the Central Military Commission。
基金supported by the National Natural Science Foundation of China(Grant No.51909246)supported by the Nature Science Foundation of Jiangsu Province of China(Grant No.BK20220044).
文摘Using the 3-D sono-elasticity method and the simplified nonstructural mass method,the different dynamic modeling methods of the added water for a single-hull structure are first analyzed in this study.Then,the complete internal flow field method and the simplified nonstructural mass method of the contained water between the double hulls of a double-hull structure are investigated.Finally,based on the calculation and analysis under multiple conditions,a reasonable and simplified dynamic modeling method of added water and contained water is obtained.It is indicated that the mass of added water for a single-hull structure is closely related to the mass of total underwater displacement of the structure.With the increase in the analysis frequency,the mass of added water is characterized by first decreasing rapidly and then decreasing gradually and smoothly.The contained water between the double hulls is distributed to the pressure hull and the light shell based on the ratio of the impedances of the double hulls.The results can basically reflect the acoustic radiation characteristics of the double-hull structure.
文摘Established in 2019,the Shandong Port Group(SPG)comprises four port groups(Qingdao Port,Rizhao Port,Yantai Port,and Bohaiwan Port)and 12 business segments.SPG connects 3,345 kilometers of coastline within Shandong Province.Its cargo throughput has consistently ranked first globally for many years,and its container volume growth ranks second globally,forming a port cluster covering the entire industrial chain.
基金funded by Wellcome 4ward North(Ref:216340/Z/19/Z)ARUK Yorkshire Network Centre Small Grant Scheme,ARUK Preparatory Clinical Fellowship scheme(Ref:ARUK-PCRF2016A-1)+3 种基金Academy of Medical Sciences Starter Grants for Clinical Lecturers Scheme(Ref:SGL028\1097),Parkinson’s UK(Ref:F1301)Michael J Fox Foundation(Ref:005021),Australian Research Council(CE200100012)European Union Seventh Framework Programme(Ref:FP7/2007-2013)under grant agreement no.601055the NIHR Sheffield Biomedical Research Centre award(NIHR 203321)(to SMB).
文摘Alzheimer’s disease(AD)is the most common form of dementia characterized pathologically by the deposition of amyloid plaques and hyperphosphorylated tau containing neurofibrillary tangles.The disease presents clinically with progressive memory loss and disruption of cognitive function.Currently,there is no cure for AD;recent advances in the therapeutics aimed at clearing the amyloid protein from the brain have led to potential disease stabilization,however,this does not prevent eventual disease progression(Cummings et al.,2024).
基金supported by the Jilin Province Health Science and Technology Ability Improvement Project(2023JL057).
文摘Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.
基金supported by the National Key Research and Development Program of China(No.2022YFA1105800(R.L.Y.))Clinical Medicine Plus X-Young Scholars Project of Peking University(No.2025PKULCXQ015(R.L.Y.))+2 种基金Research Foundation of Peking University School and Hospital of Stomatology(No.PKUSS20230103)the Fundamental Research Funds for the Central Universities-Peking University Clinical Scientist Training Program(No.L232107(R.L.Y.))Beijing Municipal Natural Science Foundation-Haidian Original Innovation Joint Fund(Nos.L222001(Xiaomo Liu)and L232107(Jie Shi)).
文摘Mesenchymal stem cells(MSCs),which are mechanosensitive cells,mediate the cells crosstalk in response to mechanical force,thereby playing a crucial role in bone homeostasis.Migrasomes serve as an important mediator for cellular communication.However,whether the mechanical stimulus regulates the biology and property of migrasomes on bone metabolism remains unknown.This study shows that mechanical stimulus could promote MSCs to synthesize and secrete migrasomes,which could significantly alleviate chronic infectious bone destruction in periodontal tissue by inhibiting osteoclastic differentiation of macrophage and reestablishing local immune microenvironment.Mechanistically,miR-29b-3p is more abundant in migrasomes from mechanical force stimulated MSCs than in control ones.MiR-29b-3p blocks the activation of pyrin domain containing protein 3(NLRP3)and mitochondrial DNA(mtDNA)release by directly targeting on Tet1.Thus,mechanical sensing migrasomes inhibit osteoclast differentiation to alleviate inflammation induced bone destruction.These findings reveal that the mechanical stimulus controls the formation and properties of migrasomes,which provides a new biotechnological strategy for chronic infectious bone destruction intervention.
文摘According to the No. 14 proclamation issued by Customs Service, as from April 1st 2007, the importation of galena and the lead ore concentrate will enjoy the favorable policy intended for associated gold deposits, i.e. the value-added tax for gold component in the imported galena and lead ore concentrate is exempted,
文摘Qingshan officials released that the 300,000- ton/year nickel-contained pig iron plant of the Group in Fu’an,Fujian will be put into produc- tion at the end of this year.Upon completion,4 units of 25,000-walt electric furnace will
基金funded by Research on Intelligent Control System of Variable Fertilization of Deep Application Liquid Fertilizer(GXKS2022GKY003)the Key Laboratory of Smart Agriculture Technology,Guangxi Science and Technology Normal University(GXKSKYPT2024008)+1 种基金Key Laboratory of Detection Technology for Sugarcane and Peanut Leaf Spot Disease,Guangxi Science and Technology Normal University(GXKSKYPT2025008)Research on the Application of Uniformity Theory and 3D Virtual Forest Phase in Harbin Normal University’s Science and Technology Innovation Climbing Program Funding Project(XKB202415)。
文摘Biodiversity has always been valued by ecology,Diversity is generally believed to lead to stability,and biodiversity is an important condition for ecosystems to maintain health.So what factors are related to forest ecosystem biodiversity,and what kind of forest structure affects and determines the size of biodiversity.This study proposes the concept of contained uniformity based on the theory of uniformity,and uses the convergence of contained uniformity to obtain the judgment model of the forest station pattern type.At the same time,it proposes the concept of forest ecosystem distance diversity,and uses the judgment model of the stand pattern type to derive the mathematical definition of forest ecosystem distance diversity.Combining the ecological characteristics of different stand patterns and measurement indicators of forest ecosystem biodiversity,the connection between forest ecosystem distance diversity and biodiversity is derived,and this is used as an indicator to evaluate forest ecosystem biodiversity.Forest ecosystem distance diversity,as an indicator of biodiversity,can not only conduct early assessment and prediction of the biodiversity of immature forests(forests in the early succession or recovery stage),but also provide a quantitative basis for forest structure optimization.Ultimately realize the sustainable development of forestry production and operation and biodiversity protection.
基金National Natural Science Foundation of China(Nos.21921003 and 22201293)the National Key R&D Program of China(No.2023YFC3503400)for financial support。
文摘The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.
基金supported by the National Key Research and Development Program of China(2021YFD1200703 and 2022YFF1001602)the National Science Foundation of China(32272024 and 32171940)+2 种基金the Pinduoduo-China Agricultural University Research Fund(PC2023B01001)the Chinese Universities Scientific Fund(2022TC142)the 2115 Talent Development Program of China Agricultural University。
文摘Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restrict maize plant growth and development,leading to great yield losses.Leucine-rich repeat receptor-like kinases(LRR-RLKs)function in biotic and abiotic stress responses in the model plant Arabidopsis(Arabidopsis thaliana),but their roles in abiotic stress responses in maize are not entirely understood.In this study,we determine that the LRR-RLK ZmMIK2,a homolog of the Arabidopsis LRR-RK MALE DISCOVERER 1(MDIS1)-INTERACTING RECEPTOR LIKE KINASE 2(MIK2),functions in resistance to both drought and salt stress in maize.Zmmik2 plants exhibit enhanced resistance to both stresses,whereas overexpressing ZmMIK2 confers the opposite phenotypes.Furthermore,we identify C2-DOMAIN-CONTAINING PROTEIN 1(ZmC2DP1),which interacts with the intracellular region of ZmMIK2.Notably,that region of ZmMIK2 mediates the phosphorylation of ZmC2DP1,likely by increasing its stability.Both ZmMIK2 and ZmC2DP1 are mainly expressed in roots.As with ZmMIK2,knockout of ZmC2DP1 enhances resistance to both drought and salt stress.We conclude that ZmMIK2-ZmC2DP1 acts as a negative regulatory module in maize drought-and salt-stress responses.
基金financial support from the National Natural Science Foundation of China(Grant No.11572159).
文摘The cavity characteristics in liquid-filled containers caused by high-velocity impacts represent an important area of research in hydrodynamic ram phenomena.The dynamic expansion of the cavity induces liquid pressure variations,potentially causing catastrophic damage to the container.Current studies mainly focus on non-deforming projectiles,such as fragments,with limited exploration of shaped charge jets.In this paper,a uniquely experimental system was designed to record cavity profiles in behind-armor liquid-filled containers subjected to shaped charge jet impacts.The impact process was then numerically reproduced using the explicit simulation program ANSYS LS-DYNA with the Structured Arbitrary Lagrangian-Eulerian(S-ALE)solver.The formation mechanism,along with the dimensional and shape evolution of the cavity was investigated.Additionally,the influence of the impact kinetic energy of the jet on the cavity characteristics was analyzed.The findings reveal that the cavity profile exhibits a conical shape,primarily driven by direct jet impact and inertial effects.The expansion rates of both cavity length and maximum radius increase with jet impact kinetic energy.When the impact kinetic energy is reduced to 28.2 kJ or below,the length-to-diameter ratio of the cavity ultimately stabilizes at approximately 7.