Underground hydrogen storage has gained interest in recent years due to the enormous demand for clean energy.Hydrogen is more diffusive than air,with a smaller density and lower viscosity.These unique properties intro...Underground hydrogen storage has gained interest in recent years due to the enormous demand for clean energy.Hydrogen is more diffusive than air,with a smaller density and lower viscosity.These unique properties introduce distinctive hydrodynamic phenomena in hydrogen storage,one of which is fingering.Fingering could induce the fluid trapped in small clusters of pores,leading to a dramatic decrease in hydrogen saturation and a lower recovery rate.In this study,numerical simulations are performed at the microscopic scale to understand the evolution of hydrogen saturation and the impacts of injection and withdrawal cycles.Two sets of micromodels with different porosity(0.362 and 0.426)and minimum sizes of pore throats(0.362 mm and 0.181 mm)are developed in the numerical model.A parameter analysis is then conducted to understand the influence of injection velocity(in the range of 10^(-2)m/s to 10^(-5)m/s)and porous structure on the fingering pattern,followed by an image analysis to capture the evolution of the fingering pattern.Viscous fingering,capillary fingering,and crossover fingering are observed and identified under different boundary conditions.The fractal dimension,specific area,mean angle,and entropy of fingers are proposed as geometric descriptors to characterize the shape of the fingering pattern.When porosity increases from 0.362 to 0.426,the saturation of hydrogen increases by 26.2%.Narrower pore throats elevate capillary resistance,which hinders fluid invasion.These results underscore the importance of pore structures and the interaction between viscous and capillary forces for hydrogen recovery efficiency.This work illuminates the influence of the pore structures and the fluid properties on the immiscible displacement of hydrogen and can be further extended to optimize the injection strategy of hydrogen in underground hydrogen storage.展开更多
Studying immiscible fluid displacement patterns can provide a better understanding of displacement processes within heterogeneous porous media,thereby helping improving oil recovery and optimizing geological CO_(2) se...Studying immiscible fluid displacement patterns can provide a better understanding of displacement processes within heterogeneous porous media,thereby helping improving oil recovery and optimizing geological CO_(2) sequestration.As the injection rate of water displacing oil increases and the displacement pattern transits from capillary fingering to viscous fingering,there is a broad crossover zone between the two that can adversely affect the oil displacement efficiency.While previous studies have utilized phase diagrams to investigate the influence of the viscosity ratio and wettability of the crossover zone,fewer have studied the impact of rock heterogeneity.In this study,we created pore network models with varying degrees of heterogeneity to simulate water flooding at different injection rates.Our model quantifies capillary and viscous fingering characteristics while investigating porous media heterogeneity's role in the crossover zone.Analysis of simulation results reveals that a higher characteristic front flow rate within the crossover zone leads to earlier breakthrough and reduced displacement efficiency.Increased heterogeneity in the porous media raises injection-site pressure,lowers water saturation,and elevates the characteristic front flow rate,thereby expanding the extent of crossover zone.展开更多
Viscous fingering is one of the main challenges that could reduce areal sweep efficiency during waterflooding in oil reservoirs. A series of waterflooding experiments were carried out in a Hele-Shaw cell at ambient te...Viscous fingering is one of the main challenges that could reduce areal sweep efficiency during waterflooding in oil reservoirs. A series of waterflooding experiments were carried out in a Hele-Shaw cell at ambient temperature during which areal sweep efficiency was estimated and techniques to ease the fingering problem were examined. The onset and propagation of viscous fingers were monitored as a function of both injection rate and injection/production positions. Image processing techniques were utilized to quantitatively investigate the propagation of fingers. The experimental results show that, under specific conditions, increasing the number of finger branches could improve the areal sweep efficiency, whereas growth of a single narrow finger has a negative impact on oil displacement efficiency. According to the obtained results,increasing the injection rate improves the areal sweep efficiency up to a critical rate at which viscous fingers start to grow.The impact of heterogeneity of the medium on distributing the viscous fingers was also investigated by introducing two different arrangements of fractures in the model. The results show that fractures perpendicular to the direction of flow would distribute the displacing water more uniformly, while fractures in the direction of flow would amplify the unfavorable sweep efficiency.展开更多
Fingering phenomena are common occurrence in the natural world.It generally takes place when a less viscous fluid displacesa more viscous fluid typically in porous media.Nowadays,such phenomena have extensively been s...Fingering phenomena are common occurrence in the natural world.It generally takes place when a less viscous fluid displacesa more viscous fluid typically in porous media.Nowadays,such phenomena have extensively been studied due to itsimportance in many industrial fields.In this paper,the effects of surface wettability on finger pattern are studied and simulatednumerically by the Lattice Boltzmann method(LBM).The displacement efficiency is investigated by using two parameters,namely,the breakthrough time and the areal sweep efficiency.The simulation has demonstrated that surface wettability willinfluence the finger pattern no matter the gravity is considered or not,but in the presence of gravity,the finger pattern is muchmore complicated and irregular due to the coexistence and competition of capillary force,viscous force and gravity.展开更多
Understanding fingering, as a challenge to stable displacement during the immiscible flow, has become a crucial phenomenon for geological carbon sequestration, enhanced oil recovery, and groundwater protection. Typica...Understanding fingering, as a challenge to stable displacement during the immiscible flow, has become a crucial phenomenon for geological carbon sequestration, enhanced oil recovery, and groundwater protection. Typically governed by gravity, viscous and capillary forces, these factors lead invasive fluids to occupy pore space irregularly and incompletely. Previous studies have demonstrated capillary numbers,describing the viscous and capillary forces, to quantificationally induce evolution of invasion patterns.While the evolution mechanisms of invasive patterns have not been deeply elucidated under the constant capillary number and three variable parameters including velocity, viscosity, and interfacial tension.Our research employs two horizontal visualization systems and a two-phase laminar flow simulation to investigate the tendency of invasive pattern transition by various parameters at the pore scale. We showed that increasing invasive viscosity or reducing interfacial tension in a homogeneous pore space significantly enhanced sweep efficiency, under constant capillary number. Additionally, in the fingering crossover pattern, the region near the inlet was prone to capillary fingering with multi-directional invasion, while the viscous fingering with unidirectional invasion was more susceptible occurred in the region near the outlet. Furthermore, increasing invasive viscosity or decreasing invasive velocity and interfacial tension promoted the extension of viscous fingering from the outlet to the inlet, presenting that the subsequent invasive fluid flows toward the outlet. In the case of invasive trunk along a unidirectional path, the invasive flow increased exponentially closer to the outlet, resulting in a significant decrease in the width of the invasive interface. Our work holds promising applications for optimizing invasive patterns in heterogeneous porous media.展开更多
Viscous fingering in a modified Hele-Shaw cell is numerically investigated. The cell allows periodic variation of depth in the lateral direction. The wavenumber n of the depth perturbation has great influence on finge...Viscous fingering in a modified Hele-Shaw cell is numerically investigated. The cell allows periodic variation of depth in the lateral direction. The wavenumber n of the depth perturbation has great influence on fingering patterns. For n = 1, the fingering pattern due to the interface instability remains the same as that in the conventional Hele- Shaw cell, while the depth variation causes the steady finger to be a little narrower. For n = 2, four different fingering patterns are captured, similar to the available experimental observations in a modified Hele-Shaw cell containing a centered step-like occlusion. It is found that new fingering patterns appear as n further increases, among which, two patterns with spatial oscillation along both edges of the finger are particularly interesting. One is a symmetric oscillatory finger for n = 3, and the other is an asymmetric one for n = 4. The influence of capillary number on fingering patterns is studied for n = 3 and 4. We find that spatial oscillation of the finger nearly ceases at moderate capillary numbers and occurs again as the capillary number increases further. Meanwhile, the wide finger shifts to the narrow one. It is accompanied by a sudden decrease in the finger width which otherwise decreases continuously as the capillary number increases. The wavenumber and the amplitude of depth perturbation have little effect on the finger width.展开更多
We investigate the nonlinear dynamics of amoving interface in aHele-Shaw cell subject to an in-plane applied electric field.We develop a spectrally accurate numerical method for solving a coupled integral equation sys...We investigate the nonlinear dynamics of amoving interface in aHele-Shaw cell subject to an in-plane applied electric field.We develop a spectrally accurate numerical method for solving a coupled integral equation system.Although the stiffness due to the high order spatial derivatives can be removed using a small scale decomposition technique,the long-time simulation is still expensive since the evolving velocity of the interface drops dramatically as the interface expands.We remove this physically imposed stiffness by employing a rescaling scheme,which accelerates the slow dynamics and reduces the computational cost.Our nonlinear results reveal that positive currents restrain finger ramification and promote the overall stabilization of patterns.On the other hand,negative currents make the interface more unstable and lead to the formation of thin tail structures connecting the fingers and a small inner region.When no fluid is injected,and a negative current is utilized,the interface tends to approach the origin and break up into several drops.We investigate the temporal evolution of the smallest distance between the interface and the origin and find that it obeys an algebraic law(t∗−t)b,where t∗is the estimated pinch-off time.展开更多
Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Curre...Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Current therapeutic strategies for T1D are mainly through subcutaneous administration of insulin or islet/pancreas transplantation.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
Objective:Ring finger protein 145(RNF145),an E3 ubiquitin ligase,is significantly upregulated in hepatocellular carcinoma(HCC).However,its role in HCC remains unknown.The study aimed to investigate the functions and u...Objective:Ring finger protein 145(RNF145),an E3 ubiquitin ligase,is significantly upregulated in hepatocellular carcinoma(HCC).However,its role in HCC remains unknown.The study aimed to investigate the functions and underlying mechanisms of RNF145 in HCC.Methods:The role of RNF145 in HCC was investigated using data from The Cancer Genome Atlas(TCGA)and in vitro experimental assays.Its oncogenic functions were assessed using the transwell migration assay and the wound-healing assay.The molecular mechanism was explored through protein immunoprecipitation and western blot analyses.Data from public databases were analyzed to correlate RNF145 expression with clinicopathological features.Univariate and multivariate Cox analyses established RNF145 as an independent prognostic factor.Subsequently,a prognostic nomogram was constructed.Results:RNF145 was upregulated in HCC.The expression level of RNF145 in HCC showed significant correlations with histological grade,pathological stage,and vascular invasion.Functionally,knockdown of RNF145 effectively abolished the migratory and invasive capacities of HCC cells.This pro-metastatic effect is mediated through the RNF145-driven ubiquitination and subsequent degradation of protocadherin 9(PCDH9).Conclusion:Our findings confirm the significant upregulation of RNF145 in HCC and promote metastasis by facilitating PCDH9 ubiquitination and degradation,highlighting its role as a prognostic biomarker and a potential therapeutic target.展开更多
Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways ...Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors.Method:The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing(scRNA-seq)data in middle cerebral artery occlusion reperfusion(MCAO/R).Monocle2 mapped endothelial differentiation paths.Gene set enrichment analysis(GSEA)analyzed endothelial subcluster variations.Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3(Zmiz1-Fzd3)promoter interaction.Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid.Polymerase chain reaction(PCR)and western blotting assessed MCAO/R or Zmiz1 overexpression effects on Fzd3-related mRNA and proteins.A retroviral vector carrying Zmiz1 was injected into the brains of mice to study its effect on Fzd3.Result:Lrg1−/−mice exhibited elevated cell adhesion proteins and decreased microvascular leakage after MCAO/R.CSOmap showed widened astrocyte spacing in thesemice.RSS revealed Zmiz1 overexpression inMCAO/R+Lrg1−/−mice.MCAO/R and pcDNA3-Zmiz1 transfection both enhanced luciferase activity with Fzd3,indicating Zmiz1 binding to Fzd3.Retroviral Zmiz1 injection or knockdown disrupted ischemic brain tight junctions,highlighting Zmiz1’s key role in blood-brain barrier protection,likely through Fzd3 pathway modulation.Conclusion:The findings indicate Lrg1 knockout induces endothelial differentiation by activating Zmiz1,which is crucial for maintaining blood-brain barrier function,possibly via modulating the Fzd3 pathway.展开更多
Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially e...Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.展开更多
Understanding and controlling fracture propagation is one of the most challenging engineering problems,especially in the oil and gas sector,groundwater hydrology,and geothermal energy applications.Predicting fracture ...Understanding and controlling fracture propagation is one of the most challenging engineering problems,especially in the oil and gas sector,groundwater hydrology,and geothermal energy applications.Predicting fracture orientation while possessing a nonlinear material response becomes more complex when the medium is subjected to anisotropic boundary stresses.Furthermore,the fracturing behaviour of geological porous media that exhibit high leak-off potential is not clearly understood.In this context,a novel testing technique is used to simulate in situ conditions in the laboratory and to study the instability characteristics of such geomaterials.The bespoke apparatus designed and developed in this research programme is capable of applying true anisotropic boundary stresses,injecting fluid at a predefined flow rate and viscosity while imaging instability/fracture propagation in a porous medium such as sand and bio-cemented sands.Pressure profiles and fracture propagation are simultaneously recorded during fluid injection into specimens subjected to different boundary stresses.Analysis of the images obtained during the fluid injection process provides information on the evolution of infiltration and fracture area during the injection event.The quantification of pressure and the corresponding fracture signature is,therefore,useful for a comprehensive understanding of the mechanics of fluid-induced fracture propagation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent and aggressive forms of liver cancer,with high morbidity and poor prognosis due to late diagnosis and limited treatment options.Despite advances in ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent and aggressive forms of liver cancer,with high morbidity and poor prognosis due to late diagnosis and limited treatment options.Despite advances in understanding its molecular mechanisms,effective biomarkers for early detection and targeted therapy remain scarce.Zinc finger protein 71(ZNF71),a zinc-finger protein,has been implicated in various cancers,yet its role in HCC remains largely unexplored.This gap in knowledge underscores the need for further investigation into the ZNF71 of potential as a diagnostic or therapeutic target in HCC.AIM To explore the expression levels,clinical relevance,and molecular mechanisms of ZNF71 in the progression of HCC.METHODS The study evaluated ZNF71 expression in 235 HCC specimens and 13 noncancerous liver tissue samples using immunohistochemistry.High-throughput datasets were employed to assess the differential expression of ZNF71 in HCC and its association with clinical and pathological features.The impact of ZNF71 on HCC cell line growth was examined through clustered regularly interspaced short palindromic repeat knockout screens.Co-expressed genes were identified and analyzed for enrichment using LinkedOmics and Sangerbox 3.0,focusing on significant correlations(P<0.01,correlation coefficient≥0.3).Furthermore,the relationship between ZNF71 expression and immune cell infiltration was quantified using TIMER2.0.RESULTS ZNF71 showed higher expression in HCC tissues vs non-tumorous tissues,with a significant statistical difference(P<0.05).Data from the UALCAN platform indicated increased ZNF71 levels across early to mid-stage HCC,correlating with disease severity(P<0.05).High-throughput analysis presented a standardized mean difference in ZNF71 expression of 0.55(95%confidence interval[CI]:0.34-0.75).The efficiency of ZNF71 mRNA was evaluated,yielding an area under the curve of 0.78(95%CI:0.75-0.82),a sensitivity of 0.63(95%CI:0.53-0.72),and a specificity of 0.82(95%CI:0.73-0.89).Diagnostic likelihood ratios were positive at 3.61(95%CI:2.41-5.41)and negative at 0.45(95%CI:0.36-0.56).LinkedOmics analysis identified strong positive correlations of ZNF71 with genes such as ZNF470,ZNF256,and ZNF285.Pathway enrichment analyses highlighted associations with herpes simplex virus type 1 infection,the cell cycle,and DNA replication.Negative correlations involved metabolic pathways,peroxisomes,and fatty acid degradation.TIMER2.0 analysis demonstrated positive correlations of high ZNF71 expression with various immune cell types,including CD4^(+)T cells,B cells,regulatory T cells,monocytes,macrophages,and myeloid dendritic cells.CONCLUSION ZNF71 is significantly upregulated in HCC,correlating with the disease’s clinical and pathological stages.It appears to promote HCC progression through mechanisms involving the cell cycle and metabolism and is associated with immune cell infiltration.These findings suggest that ZNF71 could be a novel target for diagnosing and treating HCC.展开更多
PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different patho...PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most common causes of cancer mortality worldwide.The transcription factor Myc-associated zinc finger protein(MAZ)has been implicated in cancer progression.However,its pre...BACKGROUND Colorectal cancer(CRC)is one of the most common causes of cancer mortality worldwide.The transcription factor Myc-associated zinc finger protein(MAZ)has been implicated in cancer progression.However,its precise function and mecha-nisms in CRC remain unclear.AIM To investigate the role and mechanism of the MAZ/ubiquitin-like with PHD and RING finger domains 1(UHRF1)/esophageal cancer-related gene 4(ECRG4)axis in CRC metastasis.METHODS Western blot,quantitative reverse transcription polymerase chain reaction(PCR)and transwell were performed to evaluate the impact of MAZ knockdown on CRC cell migration and invasion.A xenograft tumor metastasis model was es-tablished by injecting MAZ-deficient CRC cells into nude mice to assess in vivo metastatic potential.Dual-luciferase reporter assay was performed to determine the role of MAZ and its downstream target,UHRF1.Chromatin immunoprecip-itation-quantitative PCR and methylation-specific PCR were used to analyze whether UHRF1 regulated ECRG4 through DNA methylation.RESULTS MAZ was highly upregulated in CRC cells and promoted CRC migration,inva-sion,epithelial-mesenchymal transition(EMT)and metastasis.Mechanistically,MAZ transcriptionally activated UHRF1,which in turn led to DNA methylation of ECRG4.Knockdown of MAZ suppressed CRC migration and invasion was reversed by overexpression of UHRF1.Loss of UHRF1 upregulated ECRG4,inhibited EMT,and reduced cell migration and invasion.However,simultaneous knockdown of ECRG4 partially reversed these effects.CONCLUSION MAZ promotes CRC cell migration,invasion,and EMT by transcriptionally activating UHRF1,which downreg-ulates ECRG4 through DNA methylation.展开更多
Wheat(Triticum aestivum L.)is a highly valued cereal crop produced and consumed globally,particularly in arid or semi-arid regions(Zhou et al.,2020;Mao et al.,2023).However,its production is increasingly threatened by...Wheat(Triticum aestivum L.)is a highly valued cereal crop produced and consumed globally,particularly in arid or semi-arid regions(Zhou et al.,2020;Mao et al.,2023).However,its production is increasingly threatened by the rising incidence of drought events associated with climate change.Arid regions are especially susceptible to these droughts,which are intensifying in both severity and frequency(Eckardt et al.,2023;Mao et al.,2023;Yang and Qin,2023).As of a 2022 report,more than 92%of wheat-producing regions are estimated to experience one or more drought/heatwave events in each growing season.Furthermore,the duration and frequency of these combined stress events have increased by approximately 28%over the past four decades(He et al.,2022).To address this challenge,wheat breeding programs have allocated substantial and research efforts to developing elite,stress tolerant lines.This initiative is large part by rapid innovation in transgenic and genome editing strategies(Hu and Xiong,2014;Gao et al.,2021.展开更多
Finger reimplantation is a pivotal technique in microsurgery,playing an irreplaceable role in restoring the functional integrity of fingers,maintaining the aesthetic appearance of the hand,ensuring the patient’s abil...Finger reimplantation is a pivotal technique in microsurgery,playing an irreplaceable role in restoring the functional integrity of fingers,maintaining the aesthetic appearance of the hand,ensuring the patient’s ability to perform delicate hand operations,and enhancing their social participation and quality of life.This paper reports on the perioperative nursing approach employed in a successful case of replantation involving a single hand with a multi-planar,20-segment amputation of four fingers.By establishing a specialized nursing team,conducting a comprehensive assessment of the patient’s condition,formulating a personalized nursing plan,and implementing precise nursing care,we achieved successful outcomes.After nearly four weeks of meticulous diagnosis,treatment,and nursing,17 segments of the replanted fingers survived,preserving the functional length of the amputated fingers and maximizing the restoration of hand function.This nursing method provides valuable insights and approaches for effectively managing vascular crises following digital replantation,improving the replantation survival rate,and enhancing patient satisfaction.展开更多
[Objectives]To explore the effects of motivational interviewing intervention based on the transtheoretical model(TTM)on psychological resilience and self-management in patients undergoing finger reimplantation after a...[Objectives]To explore the effects of motivational interviewing intervention based on the transtheoretical model(TTM)on psychological resilience and self-management in patients undergoing finger reimplantation after amputation.[Methods]The patients with finger replantation due to fractures admitted from October 2024 to June 2025 were divided into either the control group or the observation group according to the random number table method,with 40 cases in each group.The control group received conventional perioperative care,while the observation group underwent motivational interviewing based on TTM framework on the basis of the control group.The psychological resilience and self-management levels of the two patient groups were then compared following their respective care interventions.[Results]The psychological resilience and self-management scores of the patients were significantly higher than those of the control group after the intervention,with the difference being statistically significant(P<0.05).[Conclusions]Motivational interviewing based on the TTM can effectively improve the psychological resilience and self-management in patients undergoing severed finger reimplantation,while effectively reducing the occurrence of vascular crisis.展开更多
基金supported by the National Key Research and Development Project(Grant No.2023YFE0110900)the National Natural Science Foundation of China(Grant Nos.42320104003,42477168).
文摘Underground hydrogen storage has gained interest in recent years due to the enormous demand for clean energy.Hydrogen is more diffusive than air,with a smaller density and lower viscosity.These unique properties introduce distinctive hydrodynamic phenomena in hydrogen storage,one of which is fingering.Fingering could induce the fluid trapped in small clusters of pores,leading to a dramatic decrease in hydrogen saturation and a lower recovery rate.In this study,numerical simulations are performed at the microscopic scale to understand the evolution of hydrogen saturation and the impacts of injection and withdrawal cycles.Two sets of micromodels with different porosity(0.362 and 0.426)and minimum sizes of pore throats(0.362 mm and 0.181 mm)are developed in the numerical model.A parameter analysis is then conducted to understand the influence of injection velocity(in the range of 10^(-2)m/s to 10^(-5)m/s)and porous structure on the fingering pattern,followed by an image analysis to capture the evolution of the fingering pattern.Viscous fingering,capillary fingering,and crossover fingering are observed and identified under different boundary conditions.The fractal dimension,specific area,mean angle,and entropy of fingers are proposed as geometric descriptors to characterize the shape of the fingering pattern.When porosity increases from 0.362 to 0.426,the saturation of hydrogen increases by 26.2%.Narrower pore throats elevate capillary resistance,which hinders fluid invasion.These results underscore the importance of pore structures and the interaction between viscous and capillary forces for hydrogen recovery efficiency.This work illuminates the influence of the pore structures and the fluid properties on the immiscible displacement of hydrogen and can be further extended to optimize the injection strategy of hydrogen in underground hydrogen storage.
基金supported by the Research and Innovation Fund for Graduate Students of Southwest Petroleum University(No.2022KYCX027)supported by the National Natural Science Foundation for Youth Grant(No.41902157).
文摘Studying immiscible fluid displacement patterns can provide a better understanding of displacement processes within heterogeneous porous media,thereby helping improving oil recovery and optimizing geological CO_(2) sequestration.As the injection rate of water displacing oil increases and the displacement pattern transits from capillary fingering to viscous fingering,there is a broad crossover zone between the two that can adversely affect the oil displacement efficiency.While previous studies have utilized phase diagrams to investigate the influence of the viscosity ratio and wettability of the crossover zone,fewer have studied the impact of rock heterogeneity.In this study,we created pore network models with varying degrees of heterogeneity to simulate water flooding at different injection rates.Our model quantifies capillary and viscous fingering characteristics while investigating porous media heterogeneity's role in the crossover zone.Analysis of simulation results reveals that a higher characteristic front flow rate within the crossover zone leads to earlier breakthrough and reduced displacement efficiency.Increased heterogeneity in the porous media raises injection-site pressure,lowers water saturation,and elevates the characteristic front flow rate,thereby expanding the extent of crossover zone.
基金Shiraz University Enhanced Oil Recovery(EOR)Research Center for the support
文摘Viscous fingering is one of the main challenges that could reduce areal sweep efficiency during waterflooding in oil reservoirs. A series of waterflooding experiments were carried out in a Hele-Shaw cell at ambient temperature during which areal sweep efficiency was estimated and techniques to ease the fingering problem were examined. The onset and propagation of viscous fingers were monitored as a function of both injection rate and injection/production positions. Image processing techniques were utilized to quantitatively investigate the propagation of fingers. The experimental results show that, under specific conditions, increasing the number of finger branches could improve the areal sweep efficiency, whereas growth of a single narrow finger has a negative impact on oil displacement efficiency. According to the obtained results,increasing the injection rate improves the areal sweep efficiency up to a critical rate at which viscous fingers start to grow.The impact of heterogeneity of the medium on distributing the viscous fingers was also investigated by introducing two different arrangements of fractures in the model. The results show that fractures perpendicular to the direction of flow would distribute the displacing water more uniformly, while fractures in the direction of flow would amplify the unfavorable sweep efficiency.
基金supported by the NSFC sponsored project under grant(50976017)(50736001)
文摘Fingering phenomena are common occurrence in the natural world.It generally takes place when a less viscous fluid displacesa more viscous fluid typically in porous media.Nowadays,such phenomena have extensively been studied due to itsimportance in many industrial fields.In this paper,the effects of surface wettability on finger pattern are studied and simulatednumerically by the Lattice Boltzmann method(LBM).The displacement efficiency is investigated by using two parameters,namely,the breakthrough time and the areal sweep efficiency.The simulation has demonstrated that surface wettability willinfluence the finger pattern no matter the gravity is considered or not,but in the presence of gravity,the finger pattern is muchmore complicated and irregular due to the coexistence and competition of capillary force,viscous force and gravity.
基金supported by the National Natural Science Foundation of China Joint Fund Project (Grant/Award Number: U20B6003)National Natural Science Foundation of China (Grant/Award Number: 52304054)。
文摘Understanding fingering, as a challenge to stable displacement during the immiscible flow, has become a crucial phenomenon for geological carbon sequestration, enhanced oil recovery, and groundwater protection. Typically governed by gravity, viscous and capillary forces, these factors lead invasive fluids to occupy pore space irregularly and incompletely. Previous studies have demonstrated capillary numbers,describing the viscous and capillary forces, to quantificationally induce evolution of invasion patterns.While the evolution mechanisms of invasive patterns have not been deeply elucidated under the constant capillary number and three variable parameters including velocity, viscosity, and interfacial tension.Our research employs two horizontal visualization systems and a two-phase laminar flow simulation to investigate the tendency of invasive pattern transition by various parameters at the pore scale. We showed that increasing invasive viscosity or reducing interfacial tension in a homogeneous pore space significantly enhanced sweep efficiency, under constant capillary number. Additionally, in the fingering crossover pattern, the region near the inlet was prone to capillary fingering with multi-directional invasion, while the viscous fingering with unidirectional invasion was more susceptible occurred in the region near the outlet. Furthermore, increasing invasive viscosity or decreasing invasive velocity and interfacial tension promoted the extension of viscous fingering from the outlet to the inlet, presenting that the subsequent invasive fluid flows toward the outlet. In the case of invasive trunk along a unidirectional path, the invasive flow increased exponentially closer to the outlet, resulting in a significant decrease in the width of the invasive interface. Our work holds promising applications for optimizing invasive patterns in heterogeneous porous media.
基金Project supported by the National Natural Science Foundation of China(No.11232011)the 111 Project of China(No.B07033)
文摘Viscous fingering in a modified Hele-Shaw cell is numerically investigated. The cell allows periodic variation of depth in the lateral direction. The wavenumber n of the depth perturbation has great influence on fingering patterns. For n = 1, the fingering pattern due to the interface instability remains the same as that in the conventional Hele- Shaw cell, while the depth variation causes the steady finger to be a little narrower. For n = 2, four different fingering patterns are captured, similar to the available experimental observations in a modified Hele-Shaw cell containing a centered step-like occlusion. It is found that new fingering patterns appear as n further increases, among which, two patterns with spatial oscillation along both edges of the finger are particularly interesting. One is a symmetric oscillatory finger for n = 3, and the other is an asymmetric one for n = 4. The influence of capillary number on fingering patterns is studied for n = 3 and 4. We find that spatial oscillation of the finger nearly ceases at moderate capillary numbers and occurs again as the capillary number increases further. Meanwhile, the wide finger shifts to the narrow one. It is accompanied by a sudden decrease in the finger width which otherwise decreases continuously as the capillary number increases. The wavenumber and the amplitude of depth perturbation have little effect on the finger width.
基金the National Science Foundation,Division of Mathematical Sciences(NSF-DMS)grants DMS-1714973,1719960,1763272(J.L.)DMS-1720420(S.L.).J.L.thanks the support from the Simons Foundation(594598QN)for a NSF-Simons Center for Multiscale Cell Fate Research.J.L.also thanks the National Institutes of Health for partial support through grants 1U54CA217378-01A1 for a National Center in Cancer Systems Biology at UC Irvine and P30CA062203 for the Chao Family Comprehensive Cancer Center at UC Irvine.
文摘We investigate the nonlinear dynamics of amoving interface in aHele-Shaw cell subject to an in-plane applied electric field.We develop a spectrally accurate numerical method for solving a coupled integral equation system.Although the stiffness due to the high order spatial derivatives can be removed using a small scale decomposition technique,the long-time simulation is still expensive since the evolving velocity of the interface drops dramatically as the interface expands.We remove this physically imposed stiffness by employing a rescaling scheme,which accelerates the slow dynamics and reduces the computational cost.Our nonlinear results reveal that positive currents restrain finger ramification and promote the overall stabilization of patterns.On the other hand,negative currents make the interface more unstable and lead to the formation of thin tail structures connecting the fingers and a small inner region.When no fluid is injected,and a negative current is utilized,the interface tends to approach the origin and break up into several drops.We investigate the temporal evolution of the smallest distance between the interface and the origin and find that it obeys an algebraic law(t∗−t)b,where t∗is the estimated pinch-off time.
基金supported by the National Natural Science Foundation of China(32325024,32400981,32222024,32271224,32471228,and 82270891)the National Key Research and Development Program of China(2023YFA1800400)+3 种基金the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(23SG22)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0507300)the ECNU public platform for Innovation(011)the instruments sharing platform of School of Life Sciences.
文摘Type 1 diabetes(T1D)is defined by autoimmune-mediated destruction of the insulin-producing pancreatic β-cells.Impaired insulin secretion due to β-cell apoptosis and islet massloss is the main feature of T1D[1].Current therapeutic strategies for T1D are mainly through subcutaneous administration of insulin or islet/pancreas transplantation.
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 Guangdong Basic and Applied Basic Research Foundation(2024A1515012800)Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province(CXPJJH125001-2540).
文摘Objective:Ring finger protein 145(RNF145),an E3 ubiquitin ligase,is significantly upregulated in hepatocellular carcinoma(HCC).However,its role in HCC remains unknown.The study aimed to investigate the functions and underlying mechanisms of RNF145 in HCC.Methods:The role of RNF145 in HCC was investigated using data from The Cancer Genome Atlas(TCGA)and in vitro experimental assays.Its oncogenic functions were assessed using the transwell migration assay and the wound-healing assay.The molecular mechanism was explored through protein immunoprecipitation and western blot analyses.Data from public databases were analyzed to correlate RNF145 expression with clinicopathological features.Univariate and multivariate Cox analyses established RNF145 as an independent prognostic factor.Subsequently,a prognostic nomogram was constructed.Results:RNF145 was upregulated in HCC.The expression level of RNF145 in HCC showed significant correlations with histological grade,pathological stage,and vascular invasion.Functionally,knockdown of RNF145 effectively abolished the migratory and invasive capacities of HCC cells.This pro-metastatic effect is mediated through the RNF145-driven ubiquitination and subsequent degradation of protocadherin 9(PCDH9).Conclusion:Our findings confirm the significant upregulation of RNF145 in HCC and promote metastasis by facilitating PCDH9 ubiquitination and degradation,highlighting its role as a prognostic biomarker and a potential therapeutic target.
基金supported by the Foundation Project:National Natural Science.Foundation of China(Nos.:82460249,82100417,81760094)The Foundation of Jiangxi Provincial Department of Science and Technology Outstanding Youth Fund Project(20212BAB206022,20242BAB23080).
文摘Objective:Leucine-rich alpha-2 glycoprotein 1(Lrg1)could regulate diverse cells in cerebral ischemiareperfusion.Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors.Method:The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing(scRNA-seq)data in middle cerebral artery occlusion reperfusion(MCAO/R).Monocle2 mapped endothelial differentiation paths.Gene set enrichment analysis(GSEA)analyzed endothelial subcluster variations.Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3(Zmiz1-Fzd3)promoter interaction.Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid.Polymerase chain reaction(PCR)and western blotting assessed MCAO/R or Zmiz1 overexpression effects on Fzd3-related mRNA and proteins.A retroviral vector carrying Zmiz1 was injected into the brains of mice to study its effect on Fzd3.Result:Lrg1−/−mice exhibited elevated cell adhesion proteins and decreased microvascular leakage after MCAO/R.CSOmap showed widened astrocyte spacing in thesemice.RSS revealed Zmiz1 overexpression inMCAO/R+Lrg1−/−mice.MCAO/R and pcDNA3-Zmiz1 transfection both enhanced luciferase activity with Fzd3,indicating Zmiz1 binding to Fzd3.Retroviral Zmiz1 injection or knockdown disrupted ischemic brain tight junctions,highlighting Zmiz1’s key role in blood-brain barrier protection,likely through Fzd3 pathway modulation.Conclusion:The findings indicate Lrg1 knockout induces endothelial differentiation by activating Zmiz1,which is crucial for maintaining blood-brain barrier function,possibly via modulating the Fzd3 pathway.
基金supported by the National Natural Science Foundation of China(No.81702296).
文摘Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.
基金supported and funded by the British Petroleum-International Centre for Advanced Materials(BP-ICAM)on project ICAM-39(Water Injection in Soft Sand Reservoirs)the University of Cambridge,UK.Their support is gratefully acknowledged.
文摘Understanding and controlling fracture propagation is one of the most challenging engineering problems,especially in the oil and gas sector,groundwater hydrology,and geothermal energy applications.Predicting fracture orientation while possessing a nonlinear material response becomes more complex when the medium is subjected to anisotropic boundary stresses.Furthermore,the fracturing behaviour of geological porous media that exhibit high leak-off potential is not clearly understood.In this context,a novel testing technique is used to simulate in situ conditions in the laboratory and to study the instability characteristics of such geomaterials.The bespoke apparatus designed and developed in this research programme is capable of applying true anisotropic boundary stresses,injecting fluid at a predefined flow rate and viscosity while imaging instability/fracture propagation in a porous medium such as sand and bio-cemented sands.Pressure profiles and fracture propagation are simultaneously recorded during fluid injection into specimens subjected to different boundary stresses.Analysis of the images obtained during the fluid injection process provides information on the evolution of infiltration and fracture area during the injection event.The quantification of pressure and the corresponding fracture signature is,therefore,useful for a comprehensive understanding of the mechanics of fluid-induced fracture propagation.
基金Supported by Joint Project on Regional High Incidence Diseases Research of Guangxi Natural Science Foundation,No.2024GXNSFAA010057 and No.2024GXNSFAA010085Natural Science Foundation of Guangxi,China,No.2022GXNSFBA035657+2 种基金Guangxi Zhuang Autonomous Region Health Commission Self-Financed Scientific Research Project,No.Z20210764Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project,No.GXZYA20230270 and No.GXZYA20240305Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University(2022).
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent and aggressive forms of liver cancer,with high morbidity and poor prognosis due to late diagnosis and limited treatment options.Despite advances in understanding its molecular mechanisms,effective biomarkers for early detection and targeted therapy remain scarce.Zinc finger protein 71(ZNF71),a zinc-finger protein,has been implicated in various cancers,yet its role in HCC remains largely unexplored.This gap in knowledge underscores the need for further investigation into the ZNF71 of potential as a diagnostic or therapeutic target in HCC.AIM To explore the expression levels,clinical relevance,and molecular mechanisms of ZNF71 in the progression of HCC.METHODS The study evaluated ZNF71 expression in 235 HCC specimens and 13 noncancerous liver tissue samples using immunohistochemistry.High-throughput datasets were employed to assess the differential expression of ZNF71 in HCC and its association with clinical and pathological features.The impact of ZNF71 on HCC cell line growth was examined through clustered regularly interspaced short palindromic repeat knockout screens.Co-expressed genes were identified and analyzed for enrichment using LinkedOmics and Sangerbox 3.0,focusing on significant correlations(P<0.01,correlation coefficient≥0.3).Furthermore,the relationship between ZNF71 expression and immune cell infiltration was quantified using TIMER2.0.RESULTS ZNF71 showed higher expression in HCC tissues vs non-tumorous tissues,with a significant statistical difference(P<0.05).Data from the UALCAN platform indicated increased ZNF71 levels across early to mid-stage HCC,correlating with disease severity(P<0.05).High-throughput analysis presented a standardized mean difference in ZNF71 expression of 0.55(95%confidence interval[CI]:0.34-0.75).The efficiency of ZNF71 mRNA was evaluated,yielding an area under the curve of 0.78(95%CI:0.75-0.82),a sensitivity of 0.63(95%CI:0.53-0.72),and a specificity of 0.82(95%CI:0.73-0.89).Diagnostic likelihood ratios were positive at 3.61(95%CI:2.41-5.41)and negative at 0.45(95%CI:0.36-0.56).LinkedOmics analysis identified strong positive correlations of ZNF71 with genes such as ZNF470,ZNF256,and ZNF285.Pathway enrichment analyses highlighted associations with herpes simplex virus type 1 infection,the cell cycle,and DNA replication.Negative correlations involved metabolic pathways,peroxisomes,and fatty acid degradation.TIMER2.0 analysis demonstrated positive correlations of high ZNF71 expression with various immune cell types,including CD4^(+)T cells,B cells,regulatory T cells,monocytes,macrophages,and myeloid dendritic cells.CONCLUSION ZNF71 is significantly upregulated in HCC,correlating with the disease’s clinical and pathological stages.It appears to promote HCC progression through mechanisms involving the cell cycle and metabolism and is associated with immune cell infiltration.These findings suggest that ZNF71 could be a novel target for diagnosing and treating HCC.
基金supported by Telethon Italy award GGP15225(to RC and GM)Italian Ministry of Health award RF-2016-02362950(to RC and CZ)+1 种基金the CJD Foundation USA(to RC)the Associazione Italiana Encefalopatie da Prioni(AIEnP)(to RC).
文摘PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.
基金Supported by Hangzhou Medical and Health Science and Technology Plan,No.B20210014.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most common causes of cancer mortality worldwide.The transcription factor Myc-associated zinc finger protein(MAZ)has been implicated in cancer progression.However,its precise function and mecha-nisms in CRC remain unclear.AIM To investigate the role and mechanism of the MAZ/ubiquitin-like with PHD and RING finger domains 1(UHRF1)/esophageal cancer-related gene 4(ECRG4)axis in CRC metastasis.METHODS Western blot,quantitative reverse transcription polymerase chain reaction(PCR)and transwell were performed to evaluate the impact of MAZ knockdown on CRC cell migration and invasion.A xenograft tumor metastasis model was es-tablished by injecting MAZ-deficient CRC cells into nude mice to assess in vivo metastatic potential.Dual-luciferase reporter assay was performed to determine the role of MAZ and its downstream target,UHRF1.Chromatin immunoprecip-itation-quantitative PCR and methylation-specific PCR were used to analyze whether UHRF1 regulated ECRG4 through DNA methylation.RESULTS MAZ was highly upregulated in CRC cells and promoted CRC migration,inva-sion,epithelial-mesenchymal transition(EMT)and metastasis.Mechanistically,MAZ transcriptionally activated UHRF1,which in turn led to DNA methylation of ECRG4.Knockdown of MAZ suppressed CRC migration and invasion was reversed by overexpression of UHRF1.Loss of UHRF1 upregulated ECRG4,inhibited EMT,and reduced cell migration and invasion.However,simultaneous knockdown of ECRG4 partially reversed these effects.CONCLUSION MAZ promotes CRC cell migration,invasion,and EMT by transcriptionally activating UHRF1,which downreg-ulates ECRG4 through DNA methylation.
基金supported by grants from the Major Project on Agricultural Bio-breeding of China(2023ZD04026)National Natural Science Foundation of China(31872866 and 32372124)+2 种基金China Postdoctoral Science Foundation(2022M721101)National Natural Science Foundation of Hunan(2023JJ40132)Natural Science Foundation of Chongqing(CSTB2023NSCQ-MSX0542).
文摘Wheat(Triticum aestivum L.)is a highly valued cereal crop produced and consumed globally,particularly in arid or semi-arid regions(Zhou et al.,2020;Mao et al.,2023).However,its production is increasingly threatened by the rising incidence of drought events associated with climate change.Arid regions are especially susceptible to these droughts,which are intensifying in both severity and frequency(Eckardt et al.,2023;Mao et al.,2023;Yang and Qin,2023).As of a 2022 report,more than 92%of wheat-producing regions are estimated to experience one or more drought/heatwave events in each growing season.Furthermore,the duration and frequency of these combined stress events have increased by approximately 28%over the past four decades(He et al.,2022).To address this challenge,wheat breeding programs have allocated substantial and research efforts to developing elite,stress tolerant lines.This initiative is large part by rapid innovation in transgenic and genome editing strategies(Hu and Xiong,2014;Gao et al.,2021.
文摘Finger reimplantation is a pivotal technique in microsurgery,playing an irreplaceable role in restoring the functional integrity of fingers,maintaining the aesthetic appearance of the hand,ensuring the patient’s ability to perform delicate hand operations,and enhancing their social participation and quality of life.This paper reports on the perioperative nursing approach employed in a successful case of replantation involving a single hand with a multi-planar,20-segment amputation of four fingers.By establishing a specialized nursing team,conducting a comprehensive assessment of the patient’s condition,formulating a personalized nursing plan,and implementing precise nursing care,we achieved successful outcomes.After nearly four weeks of meticulous diagnosis,treatment,and nursing,17 segments of the replanted fingers survived,preserving the functional length of the amputated fingers and maximizing the restoration of hand function.This nursing method provides valuable insights and approaches for effectively managing vascular crises following digital replantation,improving the replantation survival rate,and enhancing patient satisfaction.
基金Supported by 2023 Shiyan Taihe Hospital Fund Project(2023JJXM024).
文摘[Objectives]To explore the effects of motivational interviewing intervention based on the transtheoretical model(TTM)on psychological resilience and self-management in patients undergoing finger reimplantation after amputation.[Methods]The patients with finger replantation due to fractures admitted from October 2024 to June 2025 were divided into either the control group or the observation group according to the random number table method,with 40 cases in each group.The control group received conventional perioperative care,while the observation group underwent motivational interviewing based on TTM framework on the basis of the control group.The psychological resilience and self-management levels of the two patient groups were then compared following their respective care interventions.[Results]The psychological resilience and self-management scores of the patients were significantly higher than those of the control group after the intervention,with the difference being statistically significant(P<0.05).[Conclusions]Motivational interviewing based on the TTM can effectively improve the psychological resilience and self-management in patients undergoing severed finger reimplantation,while effectively reducing the occurrence of vascular crisis.
