Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strateg...Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.展开更多
The radical addition/functional group migration strategy has emerged as a powerful tool for the difunctionalization of unsaturated hydrocarbons,yet the heteroatom-mediated functional group migration remains largely un...The radical addition/functional group migration strategy has emerged as a powerful tool for the difunctionalization of unsaturated hydrocarbons,yet the heteroatom-mediated functional group migration remains largely unexplored.Herein,we report an unprecedented radical difunctionalization of alkynes employing oxime esters as bifunctional reagents through a novel C-centered radical addition/N-centered radical translocation sequence.This innovative transformation paradigm enables efficient alkylamination of alkynes under mild photocatalytic redox conditions.Mechanistic investigations reveal a cascade sequence initiated by single-electron transfer from oxime derivatives,proceeding through radical addition,6-exo-trig cyclization,and subsequent imino group migration.展开更多
The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postn...Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.展开更多
In wave-equation migration and demigration,the cross-correlation imaging/forwarding step implicitly injects an additional copy of the source wavelet,so that the amplitude spectrum of the wavelet is applied redundantly...In wave-equation migration and demigration,the cross-correlation imaging/forwarding step implicitly injects an additional copy of the source wavelet,so that the amplitude spectrum of the wavelet is applied redundantly(effectively imposing a wavelet-spectrum weighting,often akin to an amplitude-squared bias).This redundancy degrades structural fidelity and amplitude balance yet is frequently overlooked.We(i)formalize the mechanism by which cross-correlation duplicates the source-wavelet amplitude effect in both migration and demigration,and(ii)introduce a source-equalized operator that removes the redundancy by deconvolving(or dividing by)the wavelet amplitude spectrum in the imaging condition and its demigration counterpart,while leaving phase/kinematics intact.Using a band-limited Ricker wavelet on a two-layer model and on Marmousi,we show that,if unmanaged,the redundant wavelet spectrum broadens main lobes,introduces ringing,and suppresses vertical resolution in migrated images,and inflates spectrum mismatches between demigrated and observed data even when peak times agree.With our correction,images recover observed-data-consistent bandwidth and sharpened interfaces,and demigrated data also exhibit improved spectrum conformity and reduced amplitude misfit.The results clarify when source amplitudes matter,why cross-correlation makes them redundantly matter,and how a lightweight spectral correction restores physically meaningful amplitude behavior in wave-equation migration/demigration.展开更多
As the primary functional component of a fusion reactor,the fusion blanket pebble bed,composed of numerous particles,is crucial for tritium breeding,neutron multiplication,and radiation shielding.Particles within trit...As the primary functional component of a fusion reactor,the fusion blanket pebble bed,composed of numerous particles,is crucial for tritium breeding,neutron multiplication,and radiation shielding.Particles within tritium-breeding pebble beds are subjected to prolonged neutron irradiation,high thermal loads,and strong magnetic fields in fusion environments.Such conditions render them susceptible to pulverization and fragmentation.The resulting fragments and powders migrate and are deposited into the gas channel,driven by the purge gas.The reduction in the effective flow area of the gas increases the flow resistance,resulting in tritium retention,degraded heat transfer,and other adverse effects.These conditions impair the thermodynamic properties of the pebble beds and hinder the self-maintenance of tritium.Limited information exists on powder migration and clogging mechanisms in fusion blanket pebble beds,particularly under diverse physical conditions.The aim of this study was to use a computational fluid dynamics model coupled with the discrete element method(CFD-DEM)to numerically explore powder migration and clogging in pebble beds.The model considers factors such as breeder orientation,purge velocity,powder size distribution,and friction coefficient.We propose two migration and clogging mechanisms.One involves powder with a large particle size,and the other does not.The results indicate that the powder migration velocity progresses through three stages:rapid decay,linear decay,and stability.Pebble-bed clogging manifests in two forms:extensive superficial clogging and uniform internal clogging.Two fitted curves were used to depict the migration and clogging tendencies.The powder size distribution significantly influenced the powder migration.The breeder orientation,powder size,and friction coefficient affected the distribution of the clogging powders.However,the impact of the purge velocity on powder migration and clogging in pebble beds was limited,and this effect varied significantly with different particle size ratios.Based on the analysis,a formula is proposed to characterize the behavior of the powder in the pebble beds.The results of this study can aid in analyzing and predicting powder dynamics in pebble beds.展开更多
Bacterial cells are widely accepted as nucleation sites for calcium carbonate precipitation in biomineralization based on the Microbially Induced Carbonate Precipitation(MICP)process.For MICP-based insitu biotreatment...Bacterial cells are widely accepted as nucleation sites for calcium carbonate precipitation in biomineralization based on the Microbially Induced Carbonate Precipitation(MICP)process.For MICP-based insitu biotreatment,the firstproblem to be solved is how to introduce and retain the bacterial cells in the soil,which involves the migration and retention of bacterial cells during the biogrouting process.Soil particle size,a key factor in determining pore throat size,can have a significanteffect on the migration and retention of bacterial cells in the soil and therefore on biomineralization.To investigate the effect of particle size on the migration and retention of bacterial cells in sand and its biomineralization,two sets of tests were carried out in this study,including percolation tests and sand column treatment tests.Soil urease activity(definedas urease activity per unit mass of soil)and calcium carbonate content of the biomineralized sand were measured to comprehensively assess the migration and retention of bacterial cells in the sand.The results indicate that sands with a particle size smaller than 0.25 mmwould inhibit the migration of bacteria in the sand,resulting in a nonuniform distribution of precipitated calcium carbonate and a low strength enhancement of biomineralization.On the other hand,sands with a particle size larger than 1.18 mm are unfavorable for retaining bacterial cells in the sand,resulting in low calcium conversion efficiency.Meanwhile,particle size would also affect the formation of effective calcium carbonate through interparticle contact number and interparticle pore size,and thus biomineralization.展开更多
Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration vi...Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.展开更多
【目的】针对几何误差和非几何误差导致远程运动中心(Remote Center of Motion,RCM)机械臂运动过程中产生RCM约束点位置误差,进而存在一定的安全性问题,提出了一种微创手术机器人RCM机械臂广义运动学误差建模与补偿方法。【方法】首先,...【目的】针对几何误差和非几何误差导致远程运动中心(Remote Center of Motion,RCM)机械臂运动过程中产生RCM约束点位置误差,进而存在一定的安全性问题,提出了一种微创手术机器人RCM机械臂广义运动学误差建模与补偿方法。【方法】首先,基于切比雪夫多项式建立表征几何误差和非几何误差引起的关节相关运动学误差的误差模型;然后,通过最小二乘法对误差模型中的多项式系数和运动学参数误差进行辨识;最后,采用关节空间补偿的方法,以降低RCM约束点位置误差。【结果】试验结果表明,补偿后的RCM约束点位置误差由2.7261 mm减小到0.6415 mm,减小了约76.5%。展开更多
Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.How...Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.展开更多
The corrosion of waste canisters in the deep geological disposal facilities(GDFs)for high-level radioactive waste(HLRW)can generate gas,which escapes from the engineered barrier system through the interfaces between t...The corrosion of waste canisters in the deep geological disposal facilities(GDFs)for high-level radioactive waste(HLRW)can generate gas,which escapes from the engineered barrier system through the interfaces between the bentonite buffer blocks and the host rock and those between the bentonite blocks.In this study,a series of water infiltration and gas breakthrough experiments were conducted on granite and on granite-bentonite specimens with smooth and grooved interfaces.On this basis,this study presents new insights and a quantitative assessment of the impact of the interface between clay and host rock on gas transport.As the results show,the water permeability values from water infiltration tests on granite and granite-bentonite samples(10−19-10−20m^(2))are found to be slightly higher than that of bentonite.The gas permeability of the mock-up samples with smooth interfaces is one order of magnitude larger than that of the mock-up with grooved interfaces.The gas results of breakthrough pressures for the granite and the granite-bentonite mock-up samples are significantly lower than that of bentonite.The results highlight the potential existence of preferential gas migration channels between the rock and bentonite buffer that require further considerations in safety assessment.展开更多
Difunctionalization of unsaturated hydrocarbons is a pivotal synthetic strategy enabling the conversion of alkenes and alkynes into high value-added compounds.It allows for the introduction of two functional groups in...Difunctionalization of unsaturated hydrocarbons is a pivotal synthetic strategy enabling the conversion of alkenes and alkynes into high value-added compounds.It allows for the introduction of two functional groups into the unsaturated bond in a single step,facilitating the efficient construction of complex molecular architectures,which has been widely utilized in material chemistry,pharmaceutical and fine chemical synthesis.Recently,significant progress has been made via free radical-mediated difunctionalization due to the extensive application of photocatalysis.However,highly selective difunc-tionalization reactions still remain challenging.The research progress of selective difunctionalization of unsaturated hydro-carbons using a free radical addition/functional group migration strategy over the past decade is summarized,and synthetic strategies and key reaction steps are systematically elaborated.展开更多
This study aims to explore the unconscious motivations underlying migration in Niger, with an emphasis on understanding the phenomenon of pathological travel. Its aim is to identify the unconscious factors of patholog...This study aims to explore the unconscious motivations underlying migration in Niger, with an emphasis on understanding the phenomenon of pathological travel. Its aim is to identify the unconscious factors of pathological travel among migrants. Pathological travel, as discussed in the scientific literature on psychopathology, is characterised by movements initiated under the influence of delusions, hallucinations or other serious psychiatric disorders. The aim of this research is to contribute to our understanding of how these unconscious factors influence migration decisions. Using a retrospective analysis of five cases, this study examines the psychological and psychiatric dimensions of migration, particularly among patients referred to the psychiatry department of the Niamey National Hospital between 2017 and 2018. The five cases analysed, representing 12% of a cohort of 40 migrant patients, suffered from chronic psychotic disorders, including schizophrenia and chronic hallucinatory psychosis. By means of diagnostic interviews and categorical sorting, three main unconscious motivations were identified: the delusional state with themes of filiation and persecution, the hallucinations that dictated the travel behaviour, and the dissociative states manifested by depersonalisation and derealisation. It also emerges from this analysis that pathological travel often involves prolonged journeys on foot and without purpose. Thus, untreated mental illness plays a significant role in shaping and influencing individual and social behaviour. The results of this study have important implications for public health and migration policy. They highlight the need to integrate health assessments into migration management systems, particularly in regions serving as transit hubs for migrants. The research also highlights the need for culturally sensitive psychiatric interventions to address the interaction between pre-existing mental disorders and migration. This study contributes to a better understanding of the psychological dimensions of migration by highlighting the importance of addressing mental health as an integral part of humanitarian action. The knowledge gained paves the way for future research to explore this understudied aspect of migration on a broader scale.展开更多
文摘Breast cancer(BRCA)is characterized by high heterogeneity,with aggressive subtypes frequently showing poor prognosis and resistance to conventional therapies,making the discovery of new therapeutic targets and strategies imperative.Although elevated expression of discs large homolog 3(DLG3)has been reported in BRCA,its functional role in disease progression remains unclear.We performed bioinformatic analyses of clinical datasets to evaluate the prognostic significance of DLG3 expression in BRCA patients.In vitro gain-and loss-of-function experiments were conducted to assess the impact of DLG3 on BRCA cell proliferation,migration,and colony formation.Transcriptomic profiling,coupled with pharmacological inhibition,was employed to identify and validate downstream signaling pathways.Additionally,we extended our validation to an in vivo model to assess the role of DLG3 in tumor progression.We found that elevated DLG3 levels correlated with poor prognosis in breast cancer patients.Functionally,DLG3 overexpression significantly promoted cell proliferation and migration in estrogen receptor-positive MCF7 and triple-negative MDA-MB-231 breast cancer cells,whereas its knockdown suppressed these effects.Transcriptomic analyses revealed that DLG3 activates signal transducer and activator of transcription 3(STAT3)signaling,a finding further corroborated by Western blot.Critically,treatment with the STAT3 inhibitor Stattic attenuated DLG3-driven proliferation and migration,supporting a DLG3-STAT3 oncogenic axis.Furthermore,in vivo studies validated the role of DLG3 in promoting tumor growth and its correlation with elevated STAT3 signaling,consistent with our in vitro findings.Our findings establish DLG3 as a novel driver of breast cancer progression that directly activates STAT3 signaling.DLG3 thus represents both a potential prognostic biomarker and a promising therapeutic target for aggressive breast cancer subtypes,including triple-negative breast cancer.
基金supported by the Shaanxi Provincial Natural Science Basic Research Plan(2025JC-YBMS-114)the National Key Research and Development Program of China(2024YFB3212500)+1 种基金the Xi’an Jiaotong University(7121192002)the Fundamental Research Funds for the Central Universities(xzy022024023)。
文摘The radical addition/functional group migration strategy has emerged as a powerful tool for the difunctionalization of unsaturated hydrocarbons,yet the heteroatom-mediated functional group migration remains largely unexplored.Herein,we report an unprecedented radical difunctionalization of alkynes employing oxime esters as bifunctional reagents through a novel C-centered radical addition/N-centered radical translocation sequence.This innovative transformation paradigm enables efficient alkylamination of alkynes under mild photocatalytic redox conditions.Mechanistic investigations reveal a cascade sequence initiated by single-electron transfer from oxime derivatives,proceeding through radical addition,6-exo-trig cyclization,and subsequent imino group migration.
文摘The published article titled“MicroRNA-133b Inhibits Proliferation,Cellular Migration,and Invasion via Targeting LASP1 in Hepatocarcinoma Cells”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1269–1282.
基金supported by NIH grants,Nos.R01NS125074,R01AG083164,R01NS107365,and R21NS127177(to YL),1F31NS129204-01A1(to KW)and Albert Ryan Fellowship(to KW).
文摘Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo.
基金supported by the National Natural Science Foundation of China(42430303)Strategy Priority Research Program(Category B)of the Chinese Academy of Sciences(XDB0710000)+2 种基金National Natural Science Foundation of China(42288201)the National Key R&D Program of China(2023YFF0803203)the IGGCAS start-up funding(Grant No.E251510101).
文摘In wave-equation migration and demigration,the cross-correlation imaging/forwarding step implicitly injects an additional copy of the source wavelet,so that the amplitude spectrum of the wavelet is applied redundantly(effectively imposing a wavelet-spectrum weighting,often akin to an amplitude-squared bias).This redundancy degrades structural fidelity and amplitude balance yet is frequently overlooked.We(i)formalize the mechanism by which cross-correlation duplicates the source-wavelet amplitude effect in both migration and demigration,and(ii)introduce a source-equalized operator that removes the redundancy by deconvolving(or dividing by)the wavelet amplitude spectrum in the imaging condition and its demigration counterpart,while leaving phase/kinematics intact.Using a band-limited Ricker wavelet on a two-layer model and on Marmousi,we show that,if unmanaged,the redundant wavelet spectrum broadens main lobes,introduces ringing,and suppresses vertical resolution in migrated images,and inflates spectrum mismatches between demigrated and observed data even when peak times agree.With our correction,images recover observed-data-consistent bandwidth and sharpened interfaces,and demigrated data also exhibit improved spectrum conformity and reduced amplitude misfit.The results clarify when source amplitudes matter,why cross-correlation makes them redundantly matter,and how a lightweight spectral correction restores physically meaningful amplitude behavior in wave-equation migration/demigration.
文摘As the primary functional component of a fusion reactor,the fusion blanket pebble bed,composed of numerous particles,is crucial for tritium breeding,neutron multiplication,and radiation shielding.Particles within tritium-breeding pebble beds are subjected to prolonged neutron irradiation,high thermal loads,and strong magnetic fields in fusion environments.Such conditions render them susceptible to pulverization and fragmentation.The resulting fragments and powders migrate and are deposited into the gas channel,driven by the purge gas.The reduction in the effective flow area of the gas increases the flow resistance,resulting in tritium retention,degraded heat transfer,and other adverse effects.These conditions impair the thermodynamic properties of the pebble beds and hinder the self-maintenance of tritium.Limited information exists on powder migration and clogging mechanisms in fusion blanket pebble beds,particularly under diverse physical conditions.The aim of this study was to use a computational fluid dynamics model coupled with the discrete element method(CFD-DEM)to numerically explore powder migration and clogging in pebble beds.The model considers factors such as breeder orientation,purge velocity,powder size distribution,and friction coefficient.We propose two migration and clogging mechanisms.One involves powder with a large particle size,and the other does not.The results indicate that the powder migration velocity progresses through three stages:rapid decay,linear decay,and stability.Pebble-bed clogging manifests in two forms:extensive superficial clogging and uniform internal clogging.Two fitted curves were used to depict the migration and clogging tendencies.The powder size distribution significantly influenced the powder migration.The breeder orientation,powder size,and friction coefficient affected the distribution of the clogging powders.However,the impact of the purge velocity on powder migration and clogging in pebble beds was limited,and this effect varied significantly with different particle size ratios.Based on the analysis,a formula is proposed to characterize the behavior of the powder in the pebble beds.The results of this study can aid in analyzing and predicting powder dynamics in pebble beds.
基金support by the National Natural Science Foundation of China(NSFC)(Grant Nos.52178319,42477160,52338007).
文摘Bacterial cells are widely accepted as nucleation sites for calcium carbonate precipitation in biomineralization based on the Microbially Induced Carbonate Precipitation(MICP)process.For MICP-based insitu biotreatment,the firstproblem to be solved is how to introduce and retain the bacterial cells in the soil,which involves the migration and retention of bacterial cells during the biogrouting process.Soil particle size,a key factor in determining pore throat size,can have a significanteffect on the migration and retention of bacterial cells in the soil and therefore on biomineralization.To investigate the effect of particle size on the migration and retention of bacterial cells in sand and its biomineralization,two sets of tests were carried out in this study,including percolation tests and sand column treatment tests.Soil urease activity(definedas urease activity per unit mass of soil)and calcium carbonate content of the biomineralized sand were measured to comprehensively assess the migration and retention of bacterial cells in the sand.The results indicate that sands with a particle size smaller than 0.25 mmwould inhibit the migration of bacteria in the sand,resulting in a nonuniform distribution of precipitated calcium carbonate and a low strength enhancement of biomineralization.On the other hand,sands with a particle size larger than 1.18 mm are unfavorable for retaining bacterial cells in the sand,resulting in low calcium conversion efficiency.Meanwhile,particle size would also affect the formation of effective calcium carbonate through interparticle contact number and interparticle pore size,and thus biomineralization.
基金supported by the National Natural Science Foundation of China,No.81571211(to FL)the Natural Science Foundation of Shanghai,No.22ZR1476800(to CH)。
文摘Peripheral nerve defect repair is a complex process that involves multiple cell types;perineurial cells play a pivotal role.Hair follicle neural crest stem cells promote perineurial cell proliferation and migration via paracrine signaling;however,their clinical applications are limited by potential risks such as tumorigenesis and xenogeneic immune rejection,which are similar to the risks associated with other stem cell transplantations.The present study therefore focuses on small extracellular vesicles derived from hair follicle neural crest stem cells,which preserve the bioactive properties of the parent cells while avoiding the transplantation-associated risks.In vitro,small extracellular vesicles derived from hair follicle neural crest stem cells significantly enhanced the proliferation,migration,tube formation,and barrier function of perineurial cells,and subsequently upregulated the expression of tight junction proteins.Furthermore,in a rat model of sciatic nerve defects bridged with silicon tubes,treatment with small extracellular vesicles derived from hair follicle neural crest stem cells resulted in higher tight junction protein expression in perineurial cells,thus facilitating neural tissue regeneration.At 10 weeks post-surgery,rats treated with small extracellular vesicles derived from hair follicle neural crest stem cells exhibited improved nerve function recovery and reduced muscle atrophy.Transcriptomic and micro RNA analyses revealed that small extracellular vesicles derived from hair follicle neural crest stem cells deliver mi R-21-5p,which inhibits mothers against decapentaplegic homolog 7 expression,thereby activating the transforming growth factor-β/mothers against decapentaplegic homolog signaling pathway and upregulating hyaluronan synthase 2 expression,and further enhancing tight junction protein expression.Together,our findings indicate that small extracellular vesicles derived from hair follicle neural crest stem cells promote the proliferation,migration,and tight junction protein formation of perineurial cells.These results provide new insights into peripheral nerve regeneration from the perspective of perineurial cells,and present a novel approach for the clinical treatment of peripheral nerve defects.
文摘【目的】针对几何误差和非几何误差导致远程运动中心(Remote Center of Motion,RCM)机械臂运动过程中产生RCM约束点位置误差,进而存在一定的安全性问题,提出了一种微创手术机器人RCM机械臂广义运动学误差建模与补偿方法。【方法】首先,基于切比雪夫多项式建立表征几何误差和非几何误差引起的关节相关运动学误差的误差模型;然后,通过最小二乘法对误差模型中的多项式系数和运动学参数误差进行辨识;最后,采用关节空间补偿的方法,以降低RCM约束点位置误差。【结果】试验结果表明,补偿后的RCM约束点位置误差由2.7261 mm减小到0.6415 mm,减小了约76.5%。
文摘Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.
基金The Royal Society,UK,Grant/Award Number:IEC\NSFC\211366Fundamental Research Funds for the Central Universities(China University of Mining and Technology),Grant/Award Number:2023ZDPY11National Natural Science Foundation of China,Grant/Award Numbers:51809263,52174133。
文摘The corrosion of waste canisters in the deep geological disposal facilities(GDFs)for high-level radioactive waste(HLRW)can generate gas,which escapes from the engineered barrier system through the interfaces between the bentonite buffer blocks and the host rock and those between the bentonite blocks.In this study,a series of water infiltration and gas breakthrough experiments were conducted on granite and on granite-bentonite specimens with smooth and grooved interfaces.On this basis,this study presents new insights and a quantitative assessment of the impact of the interface between clay and host rock on gas transport.As the results show,the water permeability values from water infiltration tests on granite and granite-bentonite samples(10−19-10−20m^(2))are found to be slightly higher than that of bentonite.The gas permeability of the mock-up samples with smooth interfaces is one order of magnitude larger than that of the mock-up with grooved interfaces.The gas results of breakthrough pressures for the granite and the granite-bentonite mock-up samples are significantly lower than that of bentonite.The results highlight the potential existence of preferential gas migration channels between the rock and bentonite buffer that require further considerations in safety assessment.
文摘Difunctionalization of unsaturated hydrocarbons is a pivotal synthetic strategy enabling the conversion of alkenes and alkynes into high value-added compounds.It allows for the introduction of two functional groups into the unsaturated bond in a single step,facilitating the efficient construction of complex molecular architectures,which has been widely utilized in material chemistry,pharmaceutical and fine chemical synthesis.Recently,significant progress has been made via free radical-mediated difunctionalization due to the extensive application of photocatalysis.However,highly selective difunc-tionalization reactions still remain challenging.The research progress of selective difunctionalization of unsaturated hydro-carbons using a free radical addition/functional group migration strategy over the past decade is summarized,and synthetic strategies and key reaction steps are systematically elaborated.
文摘This study aims to explore the unconscious motivations underlying migration in Niger, with an emphasis on understanding the phenomenon of pathological travel. Its aim is to identify the unconscious factors of pathological travel among migrants. Pathological travel, as discussed in the scientific literature on psychopathology, is characterised by movements initiated under the influence of delusions, hallucinations or other serious psychiatric disorders. The aim of this research is to contribute to our understanding of how these unconscious factors influence migration decisions. Using a retrospective analysis of five cases, this study examines the psychological and psychiatric dimensions of migration, particularly among patients referred to the psychiatry department of the Niamey National Hospital between 2017 and 2018. The five cases analysed, representing 12% of a cohort of 40 migrant patients, suffered from chronic psychotic disorders, including schizophrenia and chronic hallucinatory psychosis. By means of diagnostic interviews and categorical sorting, three main unconscious motivations were identified: the delusional state with themes of filiation and persecution, the hallucinations that dictated the travel behaviour, and the dissociative states manifested by depersonalisation and derealisation. It also emerges from this analysis that pathological travel often involves prolonged journeys on foot and without purpose. Thus, untreated mental illness plays a significant role in shaping and influencing individual and social behaviour. The results of this study have important implications for public health and migration policy. They highlight the need to integrate health assessments into migration management systems, particularly in regions serving as transit hubs for migrants. The research also highlights the need for culturally sensitive psychiatric interventions to address the interaction between pre-existing mental disorders and migration. This study contributes to a better understanding of the psychological dimensions of migration by highlighting the importance of addressing mental health as an integral part of humanitarian action. The knowledge gained paves the way for future research to explore this understudied aspect of migration on a broader scale.
