The addition of high-content crumb rubber(HCCR)in asphalt can effectively address waste tire pollution and provide sustainable environmental and economic advantages.However,the practical application of conventional ru...The addition of high-content crumb rubber(HCCR)in asphalt can effectively address waste tire pollution and provide sustainable environmental and economic advantages.However,the practical application of conventional rubberized binders is significantly limited by high viscosity and poor storage stability.To address these issues,researchers have pretreated crumb rubber(CR)with oil,but high-temperature performance remains insufficient.Therefore,this study aimed to optimize the viscosity,storage stability,and rheological properties of high-content crumb rubber-modified asphalt(HCCRMA)by varying the pretreatment levels of CR and incorporating various additives,including styrene-butadiene-styrene(SBS),deoiled asphalt(DA),or recycled low-density polyethylene(RLDPE).In addition,CR was pretreated with waste cooking oil(WCO)at various ratios,pre-swelling temperatures,and times.The results show that DA exhibits excellent storage stability and lower viscosity compared with other modifiers in HCCRMA,and the 4%RLDPE with pretreated HCCR has the greatest high-temperature rutting resistance.The inclusion of RLDPE increases the stiffness and elasticity of the modified asphalt,which results in greater high-temperature performance.Additionally,the fluorescence microscopy(FM)test confirms that SBS exhibits better dispersion than other modifiers and forms a more homogeneous phase separation in the HCCRMA.All in all,this research achieved an optimal balance of storage stability and rheological properties in asphalt modified with pretreated HCCR and 6%SBS,which provides a valuable reference for performance improvement of HCCR-modified binders.展开更多
Flubendiamide is a commonly used pesticide with low water solubility and a high organic carbon sorption constant,causing it to adhere to soil particles and negatively impact soil ecosystems.First,chili plant stems,typ...Flubendiamide is a commonly used pesticide with low water solubility and a high organic carbon sorption constant,causing it to adhere to soil particles and negatively impact soil ecosystems.First,chili plant stems,typically discarded after the harvest season,represent an abundant local biomass resource with significant potential for utilization,and were converted into biochar through pyrolysis.Here,we describe the synthesis of biochar modified with iron and chitosan to increase the diversity of functions and surface functional groups of biochar.The resulting chitosan-modified magnetic biochar(CMBC)presents a full range of functional groups of chitosan and iron oxide as shown by Fourier-transform infrared spectroscopy.The correlation between flubendiamide concentration and the dose of biochar on adsorption was explored.The flubendiamide adsorption efficiency of CMBC(1%mass ratio of soil)reached 68.03%in 90 min.The highest adsorption capacity achieved was 0.95 mg·g^(−1).The flubendiamide adsorption mechanism by CMBC can be described with a pseudo-second-order kinetic model.The experiment data closely fit a Freundlich isotherm model(R^(2)=0.998),and the low residual sum of squares values demonstrate the high model applicability.In this study,we present a comprehensive overview of pesticides,alongside kinetic and isotherm model studies of flubendiamide adsorption by CMBC.We emphasize the potential of modified biochar to enhance environmental remediation applications.展开更多
Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this com...Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.展开更多
Coiled tube heat exchangers are widely preferred in shell structures due to their superior heat transfer performance,driven by favorable flow characteristics.This study investigates the effect of modifying coil and sh...Coiled tube heat exchangers are widely preferred in shell structures due to their superior heat transfer performance,driven by favorable flow characteristics.This study investigates the effect of modifying coil and shell configurations on heat transfer efficiency.Two key enhancements were examined:adding fins to the outer coil surface and integrating longitudinal slots within a hollowed shell.These modifications promote turbulence and extend heat transfer duration,thereby improving performance.However,they also introduce challenges,including increased pressure loss andmanufacturing complexity.Numerical simulationswere conducted usingANSYS Fluent 2024R1 under identical boundary conditions.With a fixed cold-side flow rate of 3 L/min,the input temperatures for the hot and cold fluids were 333.15 and 291.65 K,respectively.The hot-side flow rate varied between 2 and 6 L/min.Simulation outcomes were reported for the objectives of the study that included the improvement in heat exchangers’heat transfer enhancement.As it was indicated in the study outcomes,the average heat transfer rate increased by 15.56%,the overall heat transfer coefficient enhanced by about 29.51%,and the convective heat transfer coefficient improved by about 75.96%compared to the conventional shell-and-coil tube heat exchanger model.However,the modified technique resulted in a significant pressure drop.展开更多
Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being s...Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.展开更多
Owing to their global search capabilities and gradient-free operation,metaheuristic algorithms are widely applied to a wide range of optimization problems.However,their computational demands become prohibitive when ta...Owing to their global search capabilities and gradient-free operation,metaheuristic algorithms are widely applied to a wide range of optimization problems.However,their computational demands become prohibitive when tackling high-dimensional optimization challenges.To effectively address these challenges,this study introduces cooperative metaheuristics integrating dynamic dimension reduction(DR).Building upon particle swarm optimization(PSO)and differential evolution(DE),the proposed cooperative methods C-PSO and C-DE are developed.In the proposed methods,the modified principal components analysis(PCA)is utilized to reduce the dimension of design variables,thereby decreasing computational costs.The dynamic DR strategy implements periodic execution of modified PCA after a fixed number of iterations,resulting in the important dimensions being dynamically identified.Compared with the static one,the dynamic DR strategy can achieve precise identification of important dimensions,thereby enabling accelerated convergence toward optimal solutions.Furthermore,the influence of cumulative contribution rate thresholds on optimization problems with different dimensions is investigated.Metaheuristic algorithms(PSO,DE)and cooperative metaheuristics(C-PSO,C-DE)are examined by 15 benchmark functions and two engineering design problems(speed reducer and composite pressure vessel).Comparative results demonstrate that the cooperative methods achieve significantly superior performance compared to standard methods in both solution accuracy and computational efficiency.Compared to standard metaheuristic algorithms,cooperative metaheuristics achieve a reduction in computational cost of at least 40%.The cooperative metaheuristics can be effectively used to tackle both high-dimensional unconstrained and constrained optimization problems.展开更多
Accurate and real-time traffic-sign detection is a cornerstone of Advanced Driver-Assistance Systems(ADAS)and autonomous vehicles.However,existing one-stage detectors miss distant signs,and two-stage pipelines are imp...Accurate and real-time traffic-sign detection is a cornerstone of Advanced Driver-Assistance Systems(ADAS)and autonomous vehicles.However,existing one-stage detectors miss distant signs,and two-stage pipelines are impractical for embedded deployment.To address this issue,we present YOLO-SMM,a lightweight two-stage framework.This framework is designed to augment the YOLOv8 baseline with three targeted modules.(1)SlimNeck replaces PAN/FPN with a CSP-OSA/GSConv fusion block,reducing parameters and FLOPs without compromising multi-scale detail.(2)The MCA model introduces row-and column-aware weights to selectively amplify small sign regions in cluttered scenes.(3)MPDIoU augments CIoU loss with a corner-distance term,supplying stable gradients for sub-20-pixel boxes and tightening localization.An evaluation of YOLO-SMMon the German Traffic Sign Recognition Benchmark(GTSRB)revealed that it attained 96.3% mAP50 and 93.1% mAP50-90 at a rate of 90.6 frames per second(FPS).This represents an improvement of+1.0% over previous performance benchmarks.Them APat 64×64 resolution was found to be 50% of the maximum attainable value,with an FPS of+8.3 when compared to YOLOv8.This result indicates superior performance in terms of accuracy and speed compared to YOLOv7,YOLOv5,RetinaNet,EfficientDet,and Faster R-CNN,all of which were operated under equivalent conditions.展开更多
Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
Accelerated aging tests are widely used to rapidly evaluate the durability of materials,of which thermal-oxidative aging is the most common approach.To quantitatively predict the effects of multiple coupled factors,th...Accelerated aging tests are widely used to rapidly evaluate the durability of materials,of which thermal-oxidative aging is the most common approach.To quantitatively predict the effects of multiple coupled factors,this study takes polyamide66 reinforced with glass fiber(PA66-GF)as a model system and proposed a high-precision paradigm for coupled thermal-oxidative aging.By integrating Arrhenius-type reaction kinetics with oxygen diffusion,a predictive formula that holistically captures the nonlinear synergistic effects of multiple factors was developed,thereby overcoming the limitations of traditional single-variable models.A systematic evaluation of the stepwise improved formulas through nonlinear fitting showed that the coefficient of determination(R^(2))increased from 0.223 to 0.803,elucidating the fundamental reason why conventional approaches fail in quantitative prediction.These formulae were further embedded as physical constraints into a physics-informed neural network(PINN),which further enhanced the predictive performance,with the proposed formula achieving a peak R^(2)of 0.946.The results highlight that robust data fitting alone is insufficient;the decisive factor for the success of PINN lies in whether the embedded formula faithfully reflects the underlying physical mechanisms.When applied to polyamide 6 reinforced with glass fiber(PA6-GF),the Formula-constrained PINN maintained a high level of accuracy(R^(2)=0.916),demonstrating its strong cross-system generalizability.In summary,this work establishes a robust hybrid physics-machine learning framework that combines high accuracy with transferability for predicting the thermal-oxidative aging behavior of composite material systems.展开更多
Floquet engineering provides a powerful and flexible method for modifying the band structures of quantum materials.While circularly polarized light has been shown to convert curved nodal lines in three-dimensional sem...Floquet engineering provides a powerful and flexible method for modifying the band structures of quantum materials.While circularly polarized light has been shown to convert curved nodal lines in three-dimensional semimetals into Weyl points,such a transformation is forbidden for an isolated straight nodal line.In this work,we uncover a dramatic shift in this paradigm when multiple straight nodal lines intersect.We observe that circularly polarized light not only gaps them into Weyl points but also induces unprecedented surface-state Fermi arcs that extend across the entire surface Brillouin zone and form a linked topological structure.These findings advance our fundamental understanding of light-driven transitions in topological semimetals and unveil a unique Weyl semimetal phase defined by linked Fermi arcs.We discuss potential exotic phenomena arising from this phase,applications of our predictions to spin-split antiferromagnets,and the extension of this Weyl semimetal phase to classical systems.展开更多
The South Aral Seabed is an extreme dryland ecosystem undergoing rapid transformation yet remains misrepresented or absent in global land cover datasets.Conventional vegetation indices,specifically the Normalized Diff...The South Aral Seabed is an extreme dryland ecosystem undergoing rapid transformation yet remains misrepresented or absent in global land cover datasets.Conventional vegetation indices,specifically the Normalized Difference Vegetation Index(NDVI),perform poorly in such environments due to their limited ability to distinguish sparse vegetation from highly reflective saline and sandy soils.This study evaluated the effectiveness of the Modified Soil Adjusted Vegetation Index(MSAVI)for improving land cover classification in the South Aral Seabed and conducted a decadal analysis of land cover change between 2013 and 2023 using Landsat 8 imagery(30 m resolution).A spectral index-based classification framework was developed,combining MSAVI with the Normalized Difference Water Index(NDWI)and Salinity Index 1(SI1)to reduce spectral confusion between vegetation,saline soils,and surface water.The MSAVI-based classification achieved an overall accuracy of 77.96%(Kappa coefficient=0.71),supported by 313 field-collected validation points from 2023.While the multi-index approach enabled finer discrimination of ecologically important classes,particularly separating salt pans from solonchak soils,it resulted in a lower overall accuracy(73.80%),highlighting a trade-off between class separability and classification performance.Land cover change analysis revealed a highly dynamic landscape,with 52.96%of the study area transitioning between classes over the decade.Transformed areas(16,893 km2)exceeded stable zones(15,004 km2),driven primarily by rapid desiccation and salinization.Solonchak soils increased at an annual rate of 5.58%,while surface water bodies declined by 4.83%per year.Concurrently,sparse or distressed vegetation increased by 1.43%annually,reflecting ongoing afforestation efforts.This study provides the first MSAVI-based and medium-resolution land cover baseline for the South Aral Seabed and demonstrates that soil-adjusted vegetation indices are essential for reliable dryland classification where conventional indices fail.The proposed spectral index framework offers a replicable methodology applicable to other global drylands facing similar land degradation and restoration challenges.展开更多
Accurate parameter extraction of photovoltaic(PV)models plays a critical role in enabling precise performance prediction,optimal system sizing,and effective operational control under diverse environmental conditions.W...Accurate parameter extraction of photovoltaic(PV)models plays a critical role in enabling precise performance prediction,optimal system sizing,and effective operational control under diverse environmental conditions.While a wide range of metaheuristic optimisation techniques have been applied to this problem,many existing methods are hindered by slow convergence rates,susceptibility to premature stagnation,and reduced accuracy when applied to complex multi-diode PV configurations.These limitations can lead to suboptimal modelling,reducing the efficiency of PV system design and operation.In this work,we propose an enhanced hybrid optimisation approach,the modified Spider Wasp Optimization(mSWO)with Opposition-Based Learning algorithm,which integrates the exploration and exploitation capabilities of the Spider Wasp Optimization(SWO)metaheuristic with the diversityenhancing mechanism of Opposition-Based Learning(OBL).The hybridisation is designed to dynamically expand the search space coverage,avoid premature convergence,and improve both convergence speed and precision in highdimensional optimisation tasks.The mSWO algorithm is applied to three well-established PV configurations:the single diode model(SDM),the double diode model(DDM),and the triple diode model(TDM).Real experimental current-voltage(I-V)datasets from a commercial PV module under standard test conditions(STC)are used for evaluation.Comparative analysis is conducted against eighteen advanced metaheuristic algorithms,including BSDE,RLGBO,GWOCS,MFO,EO,TSA,and SCA.Performance metrics include minimum,mean,and maximum root mean square error(RMSE),standard deviation(SD),and convergence behaviour over 30 independent runs.The results reveal that mSWO consistently delivers superior accuracy and robustness across all PV models,achieving the lowest RMSE values of 0.000986022(SDM),0.000982884(DDM),and 0.000982529(TDM),with minimal SD values,indicating remarkable repeatability.Convergence analyses further show that mSWO reaches optimal solutions more rapidly and with fewer oscillations than all competing methods,with the performance gap widening as model complexity increases.These findings demonstrate that mSWO provides a scalable,computationally efficient,and highly reliable framework for PV parameter extraction.Its adaptability to models of growing complexity suggests strong potential for broader applications in renewable energy systems,including performance monitoring,fault detection,and intelligent control,thereby contributing to the optimisation of next-generation solar energy solutions.展开更多
The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cel...The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.展开更多
Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to ...Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to acquired resistance to BRAF(B-Raf proto-oncogene,serine/threonine kinase)inhibitors in melanoma.This present study aims to elucidate how to overcome the resistance of the eIF4Fi in BRAFV600E mutant melanoma cells and explore the underlying mechanisms.Methods:Melanoma A375(vemurafenib[VEM]-sensitive)and A375R(VEM-resistant)cells were exposed to eIF4Fi RocA at varying doses and durations in vitro.We investigated the impact of RocA on the activity of ERK1/2,AKT serine/threonine kinase 1(AKT1),eIF4E,and enhancer of zeste homolog 2(EZH2).We then examined the impact of RocA on pro-apoptotic BH3-only proteins and proliferative proteins.We subsequently determined the effect of combined eIF4Fi,AKT1 inhibitor,EZH2 inhibitor or VEM on tumor growth in vitro and in vivo.Results:RocA inhibited proliferation and induced apoptosis in A375 cells,but inhibited proliferation in A375R cells.RocA rapidly reactivated ERK1/2 at 3 h and returned to baseline levels at 48 h.However,eIF4E and AKT1 activation began at 12 h and peaked at 48 h.ERK1/2 positively regulated EZH2 and EZH2-dependent expression of c-Fos and EGR1,while AKT1 negatively regulated c-Myc,c-Jun,and BMF,but positively regulated eIF4E.RocA downregulated ERK1/2(or EZH2,AKT1,and eIF4E)independent bcl-2 and Mcl-1 expression.AKT1i enhanced RocA-induced cell apoptosis,while EZH2i reduced RocA-induced cell proliferation.Combined CR-1-31-B,EZH2i,and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo.Conclusion:The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways,resulting in resistance to both eIF4Fi and VEM.Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.展开更多
With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a c...With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.展开更多
As a crucial human activity,dam construction can profoundly impact the surface hydrology patterns.The Three Gorges Reservoir(TGR),as one of the largest hydraulic engineering projects in the world,has gained continuous...As a crucial human activity,dam construction can profoundly impact the surface hydrology patterns.The Three Gorges Reservoir(TGR),as one of the largest hydraulic engineering projects in the world,has gained continuous attention for its eco-hydrological effects.However,further investigation is necessary to understand the runoff and social impacts of the TGR on the Upper Yangtze River.This study first employed a modified SWAT model to simulate runoff,compared scenarios with and without the TGR,and finally evaluated water supply and demand in the Upper Yangtze River.The results showed a significant increasing trend in the surface water area of the Upper Yangtze River from 2000-2020.The modified SWAT model performs well in simulating the runoff,with Nash-Sutcliffe Efficiency and Percent Bias improved by 0.04-0.30 and 2-31.90,respectively.Scenario simulation results revealed that the TGR reduced seasonal differences in runoff.During the flood season,the runoff volume at the Yichang Station in the scenario with the TGR is lower than in the scenario without the TGR,peaking at 4500 m3/s.Conversely,in the dry season,the runoff volume of the scenario with TGR is higher,with a maximum increase of 1500 m3/s.The region exhibiting the greatest runoff variations is the Yangtze River's main stem in the Three Gorges Reservoir region.Besides,the TGR notably alleviated the water supply-demand imbalance in Chongqing during the winter and spring seasons,with a maximum increase of 0.16 in the supplydemand index.This study can contribute significantly to understanding the natural and social impacts of the TGR from the perspective of hydrological and scenario simulation.展开更多
Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying m...Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.展开更多
Steel slag(SS)accumulates unavoidably due to its complex and unstable composition,high production volumes,and limited value-added resource utilization.Single or multiple interface modifiers were proposed to enhance th...Steel slag(SS)accumulates unavoidably due to its complex and unstable composition,high production volumes,and limited value-added resource utilization.Single or multiple interface modifiers were proposed to enhance the properties of SS through high-speed dispersion,transforming its inherent hydrophilic and oleophobic characteristics into hydrophily and lipophilicity.The modification effects were innovatively assessed by observing the color changes of modified steel slag solutions following the dissolution-settlement equilibrium constant.This approach avoided human-induced errors and improved estimated accuracy in conformance with conventional methods such as oil absorption value,activation index,sedimentation volume,and lipophilicity.The hydrolysis of 3-aminopropyltriethoxysilane(KH)generated–Si(OH)_(3)structure to form hydrogen or covalent bonds with active substances(OH groups)from SS.Concurrently,SS underwent encapsulation via Si–O–Si structure resulting from the dehydration of–Si(OH)_(3).The stearic acid coupling agent(SA),aluminate coupling agent(AC),and titanate coupling agent(TN)underwent chemical reactions with Ca(OH)_(2),Al(OH)_(3),and CaCO_(3)in SS.The acidic SA primarily created stable chemical bonds and acted as a supplement due to its package,reducing surface activity and hydrophilicity while enhancing lipophilicity.Specifically,the optimal modification effect was obtained at 3 wt.%SA.Consequently,3 wt.%SA was established as the benchmark for multiple modifiers and the most effective combination was 3 wt.%SA and 3 wt.%AC.Compared with a single interface modifier,SA corroded the SS surface to provide numerous active sites for further modification by KH,AC,or TN,resulting in a more densely packed structure.In addition,more organic groups on SS prevent the proximity of other particles from agglomerating to achieve dispersion and a synergistic modification,laying a theoretical foundation of SS in a new pathway for organic composite materials.展开更多
基金supported by the Transportation Science and Technology Program of Henan Province(grant number:2023-4-2)the Key Research and Development Program of Ningxia Science and Technology Department(grant number:2022BEG02008)+2 种基金China Communications Construction Group Co.,Ltd.Science and Technology R&D Project(grant number:2021KJW02)the Research and Development Program of Henan Transportation Investment Group Co.,Ltd.(grant number:HNJT2025-1-9)the Postdoctoral Fellowship Program of CPSF(grand number:GZC20251139).
文摘The addition of high-content crumb rubber(HCCR)in asphalt can effectively address waste tire pollution and provide sustainable environmental and economic advantages.However,the practical application of conventional rubberized binders is significantly limited by high viscosity and poor storage stability.To address these issues,researchers have pretreated crumb rubber(CR)with oil,but high-temperature performance remains insufficient.Therefore,this study aimed to optimize the viscosity,storage stability,and rheological properties of high-content crumb rubber-modified asphalt(HCCRMA)by varying the pretreatment levels of CR and incorporating various additives,including styrene-butadiene-styrene(SBS),deoiled asphalt(DA),or recycled low-density polyethylene(RLDPE).In addition,CR was pretreated with waste cooking oil(WCO)at various ratios,pre-swelling temperatures,and times.The results show that DA exhibits excellent storage stability and lower viscosity compared with other modifiers in HCCRMA,and the 4%RLDPE with pretreated HCCR has the greatest high-temperature rutting resistance.The inclusion of RLDPE increases the stiffness and elasticity of the modified asphalt,which results in greater high-temperature performance.Additionally,the fluorescence microscopy(FM)test confirms that SBS exhibits better dispersion than other modifiers and forms a more homogeneous phase separation in the HCCRMA.All in all,this research achieved an optimal balance of storage stability and rheological properties in asphalt modified with pretreated HCCR and 6%SBS,which provides a valuable reference for performance improvement of HCCR-modified binders.
基金supported by research funds of Jeonbuk National University in 2024 and partly supported by the National Research Foundation of Korea(NRF-2019R1A2C1006441)from the Ministry of Education.
文摘Flubendiamide is a commonly used pesticide with low water solubility and a high organic carbon sorption constant,causing it to adhere to soil particles and negatively impact soil ecosystems.First,chili plant stems,typically discarded after the harvest season,represent an abundant local biomass resource with significant potential for utilization,and were converted into biochar through pyrolysis.Here,we describe the synthesis of biochar modified with iron and chitosan to increase the diversity of functions and surface functional groups of biochar.The resulting chitosan-modified magnetic biochar(CMBC)presents a full range of functional groups of chitosan and iron oxide as shown by Fourier-transform infrared spectroscopy.The correlation between flubendiamide concentration and the dose of biochar on adsorption was explored.The flubendiamide adsorption efficiency of CMBC(1%mass ratio of soil)reached 68.03%in 90 min.The highest adsorption capacity achieved was 0.95 mg·g^(−1).The flubendiamide adsorption mechanism by CMBC can be described with a pseudo-second-order kinetic model.The experiment data closely fit a Freundlich isotherm model(R^(2)=0.998),and the low residual sum of squares values demonstrate the high model applicability.In this study,we present a comprehensive overview of pesticides,alongside kinetic and isotherm model studies of flubendiamide adsorption by CMBC.We emphasize the potential of modified biochar to enhance environmental remediation applications.
基金Institutional Research Grant,MD Anderson Cancer CenterUPWARDS Training Program(Undergraduate Students Working Towards Research in Science),Grant/Award Number:1R25CA240137-01A1the CPRIT Research Training Award CPRIT Training Program,Grant/Award Number:RP210028。
文摘Background:The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease.Transgenic approaches hold promise in addressing this complex problem.One such model,the Oncopig,has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation.However,the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.Methods:Herein,we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and re-placed in the tissue.The study consisted of 3 animals in 3 cohorts(total of 9 animals)that were evaluated at 14,21,and 28 days.CT imaging,immunohistochemistry,multiplex immunofluorescence,and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation.Results:The tumors were hypovascular on CT and predominantly composed of CD45+cells with a strong lymphohistiocytic component,with no carcinomas identified.Ki-67 staining showed proliferation of CD45+immune cells but no neoplastic component.To provide further insight,the results are evaluated in the context of tumor growth kinetics.Conclusion:While progress has been made in generating targetable lesions,achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.
文摘Coiled tube heat exchangers are widely preferred in shell structures due to their superior heat transfer performance,driven by favorable flow characteristics.This study investigates the effect of modifying coil and shell configurations on heat transfer efficiency.Two key enhancements were examined:adding fins to the outer coil surface and integrating longitudinal slots within a hollowed shell.These modifications promote turbulence and extend heat transfer duration,thereby improving performance.However,they also introduce challenges,including increased pressure loss andmanufacturing complexity.Numerical simulationswere conducted usingANSYS Fluent 2024R1 under identical boundary conditions.With a fixed cold-side flow rate of 3 L/min,the input temperatures for the hot and cold fluids were 333.15 and 291.65 K,respectively.The hot-side flow rate varied between 2 and 6 L/min.Simulation outcomes were reported for the objectives of the study that included the improvement in heat exchangers’heat transfer enhancement.As it was indicated in the study outcomes,the average heat transfer rate increased by 15.56%,the overall heat transfer coefficient enhanced by about 29.51%,and the convective heat transfer coefficient improved by about 75.96%compared to the conventional shell-and-coil tube heat exchanger model.However,the modified technique resulted in a significant pressure drop.
基金supported by the Natural Science Foundation of Heilongjiang Province,China (YQ2022C040)。
文摘Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.
基金funded by National Natural Science Foundation of China(Nos.12402142,11832013 and 11572134)Natural Science Foundation of Hubei Province(No.2024AFB235)+1 种基金Hubei Provincial Department of Education Science and Technology Research Project(No.Q20221714)the Opening Foundation of Hubei Key Laboratory of Digital Textile Equipment(Nos.DTL2023019 and DTL2022012).
文摘Owing to their global search capabilities and gradient-free operation,metaheuristic algorithms are widely applied to a wide range of optimization problems.However,their computational demands become prohibitive when tackling high-dimensional optimization challenges.To effectively address these challenges,this study introduces cooperative metaheuristics integrating dynamic dimension reduction(DR).Building upon particle swarm optimization(PSO)and differential evolution(DE),the proposed cooperative methods C-PSO and C-DE are developed.In the proposed methods,the modified principal components analysis(PCA)is utilized to reduce the dimension of design variables,thereby decreasing computational costs.The dynamic DR strategy implements periodic execution of modified PCA after a fixed number of iterations,resulting in the important dimensions being dynamically identified.Compared with the static one,the dynamic DR strategy can achieve precise identification of important dimensions,thereby enabling accelerated convergence toward optimal solutions.Furthermore,the influence of cumulative contribution rate thresholds on optimization problems with different dimensions is investigated.Metaheuristic algorithms(PSO,DE)and cooperative metaheuristics(C-PSO,C-DE)are examined by 15 benchmark functions and two engineering design problems(speed reducer and composite pressure vessel).Comparative results demonstrate that the cooperative methods achieve significantly superior performance compared to standard methods in both solution accuracy and computational efficiency.Compared to standard metaheuristic algorithms,cooperative metaheuristics achieve a reduction in computational cost of at least 40%.The cooperative metaheuristics can be effectively used to tackle both high-dimensional unconstrained and constrained optimization problems.
基金supported by University of Malaya and Ministry of High Education-Malaysia via Fundamental Research Grant Scheme No.FRGS/1/2023/TK10/UM/02/3.
文摘Accurate and real-time traffic-sign detection is a cornerstone of Advanced Driver-Assistance Systems(ADAS)and autonomous vehicles.However,existing one-stage detectors miss distant signs,and two-stage pipelines are impractical for embedded deployment.To address this issue,we present YOLO-SMM,a lightweight two-stage framework.This framework is designed to augment the YOLOv8 baseline with three targeted modules.(1)SlimNeck replaces PAN/FPN with a CSP-OSA/GSConv fusion block,reducing parameters and FLOPs without compromising multi-scale detail.(2)The MCA model introduces row-and column-aware weights to selectively amplify small sign regions in cluttered scenes.(3)MPDIoU augments CIoU loss with a corner-distance term,supplying stable gradients for sub-20-pixel boxes and tightening localization.An evaluation of YOLO-SMMon the German Traffic Sign Recognition Benchmark(GTSRB)revealed that it attained 96.3% mAP50 and 93.1% mAP50-90 at a rate of 90.6 frames per second(FPS).This represents an improvement of+1.0% over previous performance benchmarks.Them APat 64×64 resolution was found to be 50% of the maximum attainable value,with an FPS of+8.3 when compared to YOLOv8.This result indicates superior performance in terms of accuracy and speed compared to YOLOv7,YOLOv5,RetinaNet,EfficientDet,and Faster R-CNN,all of which were operated under equivalent conditions.
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
基金financially supported by the National Natural Science Foundation of China(No.22473032)。
文摘Accelerated aging tests are widely used to rapidly evaluate the durability of materials,of which thermal-oxidative aging is the most common approach.To quantitatively predict the effects of multiple coupled factors,this study takes polyamide66 reinforced with glass fiber(PA66-GF)as a model system and proposed a high-precision paradigm for coupled thermal-oxidative aging.By integrating Arrhenius-type reaction kinetics with oxygen diffusion,a predictive formula that holistically captures the nonlinear synergistic effects of multiple factors was developed,thereby overcoming the limitations of traditional single-variable models.A systematic evaluation of the stepwise improved formulas through nonlinear fitting showed that the coefficient of determination(R^(2))increased from 0.223 to 0.803,elucidating the fundamental reason why conventional approaches fail in quantitative prediction.These formulae were further embedded as physical constraints into a physics-informed neural network(PINN),which further enhanced the predictive performance,with the proposed formula achieving a peak R^(2)of 0.946.The results highlight that robust data fitting alone is insufficient;the decisive factor for the success of PINN lies in whether the embedded formula faithfully reflects the underlying physical mechanisms.When applied to polyamide 6 reinforced with glass fiber(PA6-GF),the Formula-constrained PINN maintained a high level of accuracy(R^(2)=0.916),demonstrating its strong cross-system generalizability.In summary,this work establishes a robust hybrid physics-machine learning framework that combines high accuracy with transferability for predicting the thermal-oxidative aging behavior of composite material systems.
基金supported by the National Natural Science Foundation of China (Grant No.12174455)Guangdong Basic and Applied Basic Research Foundation (Grant No.2023B1515040023)。
文摘Floquet engineering provides a powerful and flexible method for modifying the band structures of quantum materials.While circularly polarized light has been shown to convert curved nodal lines in three-dimensional semimetals into Weyl points,such a transformation is forbidden for an isolated straight nodal line.In this work,we uncover a dramatic shift in this paradigm when multiple straight nodal lines intersect.We observe that circularly polarized light not only gaps them into Weyl points but also induces unprecedented surface-state Fermi arcs that extend across the entire surface Brillouin zone and form a linked topological structure.These findings advance our fundamental understanding of light-driven transitions in topological semimetals and unveil a unique Weyl semimetal phase defined by linked Fermi arcs.We discuss potential exotic phenomena arising from this phase,applications of our predictions to spin-split antiferromagnets,and the extension of this Weyl semimetal phase to classical systems.
基金supported by the United Kingdom(UK)Darwin Initiative(28-003).
文摘The South Aral Seabed is an extreme dryland ecosystem undergoing rapid transformation yet remains misrepresented or absent in global land cover datasets.Conventional vegetation indices,specifically the Normalized Difference Vegetation Index(NDVI),perform poorly in such environments due to their limited ability to distinguish sparse vegetation from highly reflective saline and sandy soils.This study evaluated the effectiveness of the Modified Soil Adjusted Vegetation Index(MSAVI)for improving land cover classification in the South Aral Seabed and conducted a decadal analysis of land cover change between 2013 and 2023 using Landsat 8 imagery(30 m resolution).A spectral index-based classification framework was developed,combining MSAVI with the Normalized Difference Water Index(NDWI)and Salinity Index 1(SI1)to reduce spectral confusion between vegetation,saline soils,and surface water.The MSAVI-based classification achieved an overall accuracy of 77.96%(Kappa coefficient=0.71),supported by 313 field-collected validation points from 2023.While the multi-index approach enabled finer discrimination of ecologically important classes,particularly separating salt pans from solonchak soils,it resulted in a lower overall accuracy(73.80%),highlighting a trade-off between class separability and classification performance.Land cover change analysis revealed a highly dynamic landscape,with 52.96%of the study area transitioning between classes over the decade.Transformed areas(16,893 km2)exceeded stable zones(15,004 km2),driven primarily by rapid desiccation and salinization.Solonchak soils increased at an annual rate of 5.58%,while surface water bodies declined by 4.83%per year.Concurrently,sparse or distressed vegetation increased by 1.43%annually,reflecting ongoing afforestation efforts.This study provides the first MSAVI-based and medium-resolution land cover baseline for the South Aral Seabed and demonstrates that soil-adjusted vegetation indices are essential for reliable dryland classification where conventional indices fail.The proposed spectral index framework offers a replicable methodology applicable to other global drylands facing similar land degradation and restoration challenges.
基金funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2025R442)Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Accurate parameter extraction of photovoltaic(PV)models plays a critical role in enabling precise performance prediction,optimal system sizing,and effective operational control under diverse environmental conditions.While a wide range of metaheuristic optimisation techniques have been applied to this problem,many existing methods are hindered by slow convergence rates,susceptibility to premature stagnation,and reduced accuracy when applied to complex multi-diode PV configurations.These limitations can lead to suboptimal modelling,reducing the efficiency of PV system design and operation.In this work,we propose an enhanced hybrid optimisation approach,the modified Spider Wasp Optimization(mSWO)with Opposition-Based Learning algorithm,which integrates the exploration and exploitation capabilities of the Spider Wasp Optimization(SWO)metaheuristic with the diversityenhancing mechanism of Opposition-Based Learning(OBL).The hybridisation is designed to dynamically expand the search space coverage,avoid premature convergence,and improve both convergence speed and precision in highdimensional optimisation tasks.The mSWO algorithm is applied to three well-established PV configurations:the single diode model(SDM),the double diode model(DDM),and the triple diode model(TDM).Real experimental current-voltage(I-V)datasets from a commercial PV module under standard test conditions(STC)are used for evaluation.Comparative analysis is conducted against eighteen advanced metaheuristic algorithms,including BSDE,RLGBO,GWOCS,MFO,EO,TSA,and SCA.Performance metrics include minimum,mean,and maximum root mean square error(RMSE),standard deviation(SD),and convergence behaviour over 30 independent runs.The results reveal that mSWO consistently delivers superior accuracy and robustness across all PV models,achieving the lowest RMSE values of 0.000986022(SDM),0.000982884(DDM),and 0.000982529(TDM),with minimal SD values,indicating remarkable repeatability.Convergence analyses further show that mSWO reaches optimal solutions more rapidly and with fewer oscillations than all competing methods,with the performance gap widening as model complexity increases.These findings demonstrate that mSWO provides a scalable,computationally efficient,and highly reliable framework for PV parameter extraction.Its adaptability to models of growing complexity suggests strong potential for broader applications in renewable energy systems,including performance monitoring,fault detection,and intelligent control,thereby contributing to the optimisation of next-generation solar energy solutions.
基金supported by Grant 3195 from Paralyzed Veterans of America Research Foundation (to BRK)
文摘The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.
文摘Objectives:The eukaryotic initiation factor 4F(eIF4F)translation initiation complex inhibitors(eIF4Fi)were recently found to hyperactivate extracellular signal-regulated kinases 1/2(ERK1/2)signals,which contribute to acquired resistance to BRAF(B-Raf proto-oncogene,serine/threonine kinase)inhibitors in melanoma.This present study aims to elucidate how to overcome the resistance of the eIF4Fi in BRAFV600E mutant melanoma cells and explore the underlying mechanisms.Methods:Melanoma A375(vemurafenib[VEM]-sensitive)and A375R(VEM-resistant)cells were exposed to eIF4Fi RocA at varying doses and durations in vitro.We investigated the impact of RocA on the activity of ERK1/2,AKT serine/threonine kinase 1(AKT1),eIF4E,and enhancer of zeste homolog 2(EZH2).We then examined the impact of RocA on pro-apoptotic BH3-only proteins and proliferative proteins.We subsequently determined the effect of combined eIF4Fi,AKT1 inhibitor,EZH2 inhibitor or VEM on tumor growth in vitro and in vivo.Results:RocA inhibited proliferation and induced apoptosis in A375 cells,but inhibited proliferation in A375R cells.RocA rapidly reactivated ERK1/2 at 3 h and returned to baseline levels at 48 h.However,eIF4E and AKT1 activation began at 12 h and peaked at 48 h.ERK1/2 positively regulated EZH2 and EZH2-dependent expression of c-Fos and EGR1,while AKT1 negatively regulated c-Myc,c-Jun,and BMF,but positively regulated eIF4E.RocA downregulated ERK1/2(or EZH2,AKT1,and eIF4E)independent bcl-2 and Mcl-1 expression.AKT1i enhanced RocA-induced cell apoptosis,while EZH2i reduced RocA-induced cell proliferation.Combined CR-1-31-B,EZH2i,and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo.Conclusion:The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways,resulting in resistance to both eIF4Fi and VEM.Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.
基金the Experimental Technology Research Project of Zhejiang University(SYB202138)National Natural Science Foundation of China(32000195)。
文摘With the approval of more and more genetically modified(GM)crops in our country,GM safety management has become more important.Transgenic detection is a major approach for transgenic safety management.Nevertheless,a convenient and visual technique with low equipment requirements and high sensitivity for the field detection of GM plants is still lacking.On the basis of the existing recombinase polymerase amplification(RPA)technique,we developed a multiplex RPA(multi-RPA)method that can simultaneously detect three transgenic elements,including the cauliflower mosaic virus 35S gene(CaMV35S)promoter,neomycin phosphotransferaseⅡgene(NptⅡ)and hygromycin B phosphotransferase gene(Hyg),thus improving the detection rate.Moreover,we coupled this multi-RPA technique with the CRISPR/Cas12a reporter system,which enabled the detection results to be clearly observed by naked eyes under ultraviolet(UV)light(254 nm;which could be achieved by a portable UV flashlight),therefore establishing a multi-RPA visual detection technique.Compared with the traditional test strip detection method,this multi-RPA-CRISPR/Cas12a technique has the higher specificity,higher sensitivity,wider application range and lower cost.Compared with other polymerase chain reaction(PCR)techniques,it also has the advantages of low equipment requirements and visualization,making it a potentially feasible method for the field detection of GM plants.
基金supported by the National Natural Science Foundation of China(Nos.41975044,42371354,41801021,42101385)Open Fund of Hubei Luojia Laboratory(No.2201000043)the Fundamental Research Funds for National Universities,China University of Geosciences,Wuhan。
文摘As a crucial human activity,dam construction can profoundly impact the surface hydrology patterns.The Three Gorges Reservoir(TGR),as one of the largest hydraulic engineering projects in the world,has gained continuous attention for its eco-hydrological effects.However,further investigation is necessary to understand the runoff and social impacts of the TGR on the Upper Yangtze River.This study first employed a modified SWAT model to simulate runoff,compared scenarios with and without the TGR,and finally evaluated water supply and demand in the Upper Yangtze River.The results showed a significant increasing trend in the surface water area of the Upper Yangtze River from 2000-2020.The modified SWAT model performs well in simulating the runoff,with Nash-Sutcliffe Efficiency and Percent Bias improved by 0.04-0.30 and 2-31.90,respectively.Scenario simulation results revealed that the TGR reduced seasonal differences in runoff.During the flood season,the runoff volume at the Yichang Station in the scenario with the TGR is lower than in the scenario without the TGR,peaking at 4500 m3/s.Conversely,in the dry season,the runoff volume of the scenario with TGR is higher,with a maximum increase of 1500 m3/s.The region exhibiting the greatest runoff variations is the Yangtze River's main stem in the Three Gorges Reservoir region.Besides,the TGR notably alleviated the water supply-demand imbalance in Chongqing during the winter and spring seasons,with a maximum increase of 0.16 in the supplydemand index.This study can contribute significantly to understanding the natural and social impacts of the TGR from the perspective of hydrological and scenario simulation.
文摘Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.
基金supported by the National Natural Science Foundation of China(U23A20605)Anhui Graduate Innovation and Entrepreneurship Practice Project(2022cxcysj090)+2 种基金China Baowu Low Carbon Metallurgy Innovation Foundation(BWLCF202202)the University Synergy Innovation Program of Anhui Province(GXXT-2020-072)the Outstanding Youth Fund of Anhui Province(2208085J19).
文摘Steel slag(SS)accumulates unavoidably due to its complex and unstable composition,high production volumes,and limited value-added resource utilization.Single or multiple interface modifiers were proposed to enhance the properties of SS through high-speed dispersion,transforming its inherent hydrophilic and oleophobic characteristics into hydrophily and lipophilicity.The modification effects were innovatively assessed by observing the color changes of modified steel slag solutions following the dissolution-settlement equilibrium constant.This approach avoided human-induced errors and improved estimated accuracy in conformance with conventional methods such as oil absorption value,activation index,sedimentation volume,and lipophilicity.The hydrolysis of 3-aminopropyltriethoxysilane(KH)generated–Si(OH)_(3)structure to form hydrogen or covalent bonds with active substances(OH groups)from SS.Concurrently,SS underwent encapsulation via Si–O–Si structure resulting from the dehydration of–Si(OH)_(3).The stearic acid coupling agent(SA),aluminate coupling agent(AC),and titanate coupling agent(TN)underwent chemical reactions with Ca(OH)_(2),Al(OH)_(3),and CaCO_(3)in SS.The acidic SA primarily created stable chemical bonds and acted as a supplement due to its package,reducing surface activity and hydrophilicity while enhancing lipophilicity.Specifically,the optimal modification effect was obtained at 3 wt.%SA.Consequently,3 wt.%SA was established as the benchmark for multiple modifiers and the most effective combination was 3 wt.%SA and 3 wt.%AC.Compared with a single interface modifier,SA corroded the SS surface to provide numerous active sites for further modification by KH,AC,or TN,resulting in a more densely packed structure.In addition,more organic groups on SS prevent the proximity of other particles from agglomerating to achieve dispersion and a synergistic modification,laying a theoretical foundation of SS in a new pathway for organic composite materials.
