Total hip arthroplasty for adults with sequelae from childhood hip disorders poses significant challenges due to altered anatomy.The paper published by Oommen et al reviews the essential management strategies for thes...Total hip arthroplasty for adults with sequelae from childhood hip disorders poses significant challenges due to altered anatomy.The paper published by Oommen et al reviews the essential management strategies for these complex cases.This article explores the integration of finite element analysis(FEA)to enhance surgical precision and outcomes.FEA provides detailed biomechanical insights,aiding in preoperative planning,implant design,and surgical technique optimization.By simulating implant configurations and assessing bone quality,FEA helps in customizing implants and evaluating surgical techniques like subtrochanteric shortening osteotomy.Advanced imaging techniques,such as 3D printing,virtual reality,and augmented reality,further enhance total hip arthroplasty precision.Future research should focus on validating FEA models,developing patient-specific simulations,and promoting multidisciplinary collaboration.Integrating FEA and advanced technologies in total hip arthroplasty can improve functional outcomes,reduce complications,and enhance quality of life for patients with childhood hip disorder sequelae.展开更多
Micro-grinding has been widely used in aerospace and other industry.However,the small diameter of the micro-grinding tool has limited its machining performance and efficiency.In order to solve the above problems,micro...Micro-grinding has been widely used in aerospace and other industry.However,the small diameter of the micro-grinding tool has limited its machining performance and efficiency.In order to solve the above problems,micro-structure has been applied on the micro-grinding tool.A morphology modeling has been established in this study to characterize the surface of microstructured micro-grinding tool,and the grinding performance of micro-structured micro-grinding tool has been analyzed through undeformed chip thickness,abrasive edge width,and effective distance between abrasives.Then deviation analysis,path optimization and parameter optimization of microchannel array precision grinding have been finished to improve processing quality and efficiency,and the deflection angle has the most obvious effects on the rectangular slot depth,micro-structured micro-grinding tool could reduce 10%surface roughness and 20%grinding force compared to original micro-grinding tool.Finally,the microchannel array has been machined with a size deviation of 2μm and surface roughness of 0.2μm.展开更多
The dynamic model of the ball screw mechanism(BSM)in spatial motion,developed in Part I of the study titled‘research and experimental analysis on precision degradation of BSM at low speed’,has been validated through...The dynamic model of the ball screw mechanism(BSM)in spatial motion,developed in Part I of the study titled‘research and experimental analysis on precision degradation of BSM at low speed’,has been validated through a comparison between calculated values and experimentally measured data obtained from a comprehensive ball-screw test bench.In order to study the perform-ance parameters related to the precision degradation characteristics of ball screw under different pre-loads and speeds,the precision degradation test bench for ball screw is set up.Through the experi-ment on the ball-screw comprehensive test bench,the drag torque,stroke deviation,acceleration peak value,axial contact stiffness and other parameters of the BSM under different speeds are ob-tained,and the different preloads are obtained by the drag torque,the changing regularity of which is consistent with the simulation results.A comprehensive analysis of the experimental data reveals that the dynamic characteristics of the ball screw’s spatial motion are significantly influenced by gy-roscopic torque effects.By incorporating these parametric effects,the accuracy degradation charac-teristics of ball screw under different preloads and speeds can be well analyzed.This methodology establishes a technical foundation for investigating ball screw accuracy retention characteristics.展开更多
Design a precision electroplating mechanical structure for automobiles based on finite element analysis method and analyze its mechanical properties.Taking the automobile steering knuckle as the research object,ABAQUS...Design a precision electroplating mechanical structure for automobiles based on finite element analysis method and analyze its mechanical properties.Taking the automobile steering knuckle as the research object,ABAQUS parametric modeling technology is used to construct its three-dimensional geometric model,and geometric simplification is carried out.Two surface treatment processes,HK-35 zinc nickel alloy electroplating and pure zinc electroplating,were designed,and the influence of different coatings on the mechanical properties of steering knuckles was compared and analyzed through numerical simulation.At the same time,standard specimens were prepared for salt spray corrosion testing and scratch method combined strength testing to verify the numerical simulation results.The results showed that under emergency braking and composite working conditions,the peak Von Mises stress of the zinc nickel alloy coating was 119.85 MPa,which was lower than that of the pure zinc coating and the alkaline electroplated zinc layer.Its equivalent strain value was 652×10^(-6),which was lower than that of the pure zinc coating and the alkaline electroplated zinc layer.Experimental data confirms that zinc nickel alloy coatings exhibit significant advantages in stress distribution uniformity,strain performance,and load-bearing capacity in high stress zones.The salt spray corrosion test further indicates that the coating has superior corrosion resistance and coating substrate interface bonding strength,which can significantly improve the mechanical stability and long-term reliability of automotive precision electroplating mechanical structures.展开更多
3-Nitro-1,2,4-triazol-5-one(NTO)is a typical high-energy,low-sensitivity explosive,and accurate concentration monitoring is critical for crystallization process control.In this study,a high-precision quantitative anal...3-Nitro-1,2,4-triazol-5-one(NTO)is a typical high-energy,low-sensitivity explosive,and accurate concentration monitoring is critical for crystallization process control.In this study,a high-precision quantitative analytical model for NTO concentration in ethanol solutions was developed by integrating real-time ATR-FTIR spectroscopy with chemometric and machine learning techniques.Dynamic spectral data were obtained by designing multi-concentration gradient heating-cooling cycle experiments,abnormal samples were eliminated using the isolation forest algorithm,and the effects of various preprocessing methods on model performance were systematically evaluated.The results show that partial least squares regression(PLSR)exhibits superior generalization ability compared to other models.Vibrational bands corresponding to C=O and–NO_(2)were identified as key predictors for concentration estimation.This work provides an efficient and reliable solution for real-time concentration monitoring during NTO crystallization and holds significant potential for process analytical applications in energetic material manufacturing.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Six new lanthanide complexes:[Ln(3,4-DEOBA)3(4,4'-DM-2,2'-bipy)]2·2C_(2)H_(5)OH,[Ln=Dy(1),Eu(2),Tb(3),Sm(4),Ho(5),Gd(6);3,4-DEOBA-=3,4-diethoxybenzoate,4,4'-DM-2,2'-bipy=4,4'-dimethyl-2,2'...Six new lanthanide complexes:[Ln(3,4-DEOBA)3(4,4'-DM-2,2'-bipy)]2·2C_(2)H_(5)OH,[Ln=Dy(1),Eu(2),Tb(3),Sm(4),Ho(5),Gd(6);3,4-DEOBA-=3,4-diethoxybenzoate,4,4'-DM-2,2'-bipy=4,4'-dimethyl-2,2'-bipyridine]were successfully synthesized by the volatilization of the solution at room temperature.The crystal structures of six complexes were determined by single-crystal X-ray diffraction technology.The results showed that the complexes all have a binuclear structure,and the structures contain free ethanol molecules.Moreover,the coordination number of the central metal of each structural unit is eight.Adjacent structural units interact with each other through hydrogen bonds and further expand to form 1D chain-like and 2D planar structures.After conducting a systematic study on the luminescence properties of complexes 1-4,their emission and excitation spectra were obtained.Experimental results indicated that the fluorescence lifetimes of complexes 2 and 3 were 0.807 and 0.845 ms,respectively.The emission spectral data of complexes 1-4 were imported into the CIE chromaticity coordinate system,and their corre sponding luminescent regions cover the yellow light,red light,green light,and orange-red light bands,respectively.Within the temperature range of 299.15-1300 K,the thermal decomposition processes of the six complexes were comprehensively analyzed by using TG-DSC/FTIR/MS technology.The hypothesis of the gradual loss of ligand groups during the decomposition process was verified by detecting the escaped gas,3D infrared spectroscopy,and ion fragment information detected by mass spectrometry.The specific decomposition path is as follows:firstly,free ethanol molecules and neutral ligands are removed,and finally,acidic ligands are released;the final product is the corresponding metal oxide.CCDC:2430420,1;2430422,2;2430419,3;2430424,4;2430421,5;2430423,6.展开更多
Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remai...Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.展开更多
Chilo suppressalis(Walker)is one of the most important rice pests worldwide,posing a significant challenge to effective control.To develop a precision-timed,eco-friendly management strategy,overwintering population in...Chilo suppressalis(Walker)is one of the most important rice pests worldwide,posing a significant challenge to effective control.To develop a precision-timed,eco-friendly management strategy,overwintering population investigation and dynamic monitoring of C.suppressalis populations were conducted in the Meishan region of Sichuan,China,from 2023 to 2024.The optimal timing for insecticide application was estimated,followed by field trials evaluating the efficacy of different insecticides.Results demonstrated that the peak emergence of first-generation adults typically occurred in early July(under the environmental conditions of the Meishan region),with the ambient humidity below 75%and temperature around 29◦C.Pesticide efficacy trials show that insecticide combinations exhibited superior control.Notably,a combined treatment of emamectin benzoate⋅methoxyfenozide+chlorantraniliprole achieved the highest control efficacy(90.05%)and a corresponding yield of 12,491.55 kg/ha.All tested treatments were determined to be safe for rice growth.Furthermore,this optimized strategy resulted in notable economic benefits,including a 50%reduction in pesticide usage and cost savings of 4796.15 CNY compared to conventional practices.This study provides valuable insights into sustainable rice production and pest management and,for the first time,proposes a precision application time window based on intelligent monitoring.展开更多
The Savitzky-Golay(SG)filter,which employs polynomial least-squares approximations to smooth data and estimate derivatives,is widely used for processing noisy data.However,noise suppression by the SG filter is recogni...The Savitzky-Golay(SG)filter,which employs polynomial least-squares approximations to smooth data and estimate derivatives,is widely used for processing noisy data.However,noise suppression by the SG filter is recognized to be limited at data boundaries and high frequencies,which can significantly reduce the signal-to-noise ratio(SNR).To solve this problem,a novel method synergistically integrating Principal Component Analysis(PCA)with SG filtering is proposed in this paper.This approach avoids the is-sue of excessive smoothing associated with larger window sizes.The proposed PCA-SG filtering algorithm was applied to a CO gas sensing system based on Cavity Ring-Down Spectroscopy(CRDS).The perform-ance of the PCA-SG filtering algorithm is demonstrated through comparison with Moving Average Filtering(MAF),Wavelet Transformation(WT),Kalman Filtering(KF),and the SG filter.The results demonstrate that the proposed algorithm exhibits superior noise reduction capabilities compared to the other algorithms evaluated.The SNR of the ring-down signal was improved from 11.8612 dB to 29.0913 dB,and the stand-ard deviation of the extracted ring-down time constant was reduced from 0.037μs to 0.018μs.These results confirm that the proposed PCA-SG filtering algorithm effectively improves the smoothness of the ring-down curve data,demonstrating its feasibility.展开更多
Objective:To evaluate the global,regional,and national burden and determinants of Acute Respiratory Infections(ARIs)among children and adolescents from 1990 to 2021.Methods:We analysed ARI mortality and disability-adj...Objective:To evaluate the global,regional,and national burden and determinants of Acute Respiratory Infections(ARIs)among children and adolescents from 1990 to 2021.Methods:We analysed ARI mortality and disability-adjusted life years(DALYs),stratified by age,sex,and economic development level based on data retrieved from the Global Burden of Disease study 2021.Decomposition and frontier analyses were employed to identify key drivers of burden variation and visualize potential reductions based on development levels.Results:Between 1990 and 2021,the global burden of ARIs showed a significant decline in both achievable age-standardized DALYs rate and age-standardized mortality rates(EAPC=-3.87 and-3.81,respectively).Different age groups and sex witnessed different levels of ARI burden,males experienced heavier burden than females and the 0-4 years-old group experienced heavier burden than other study age groups.Most of the 204 countries and territories experienced a downward trend of ARI burden,with slight increases observed only in Lesotho and Dominica.A negative correlation was found between the Socio-demographic Index and ARI burden.Decomposition analysis indicated that the significant decreases in deaths and DALYs were primarily driven by epidemiological changes.Conclusions:The global burden of ARIs among children and adolescents has declined over the past three decades,but substantial regional disparities persist.Targeted public health strategies are needed to address the continued ARI burden in high-risk regions and vulnerable age groups.展开更多
The detection and characterization of non-metallic inclusions are essential for clean steel production.Recently,imaging analysis combined with high-dimensional data processing of metallic materials using artificial in...The detection and characterization of non-metallic inclusions are essential for clean steel production.Recently,imaging analysis combined with high-dimensional data processing of metallic materials using artificial intelligence(AI)-based machine learning(ML)has developed rapidly.This technique has achieved impressive results in the field of inclusion classification in process metallurgy.The present study surveys the ML modeling of inclusion prediction in advanced steels,including the detection,classification,and feature prediction of inclusions in different steel grades.Studies on clean steel with different features based on data and image analysis via ML are summarized.Regarding the data analysis,the inclusion prediction methodology based on ML establishes a connection between the experimental parameters and inclusion characteristics and analyzes the importance of the experimental parameters.Regarding the image analysis,the focus is placed on the classification of different types of inclusions via deep learning,in comparison with data analysis.Finally,further development of inclusion analyses using ML-based methods is recommended.This work paves the way for the application of AIbased methodologies for ultraclean-steel studies from a sustainable metallurgy perspective.展开更多
Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing can...Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.展开更多
Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study ...Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study revealed that removing bags from‘Gengcunyangtao’red-fleshed peach fruits triggers the rapid and uniform accumulation of anthocyanins in the flesh,resulting in anthocyanin levels that exceed those in unbagged fruits.The exposure to light after bag removal triggered significant increases in anthocyanin levels within 24 h.This was accompanied by the rapid upregulation of light-responsive and flavonoid biosynthetic gene expression levels within 6 h.A metabolomic analysis indicated that anthocyanin precursors,especially p-coumaric acid,accumulated before bag removal,thereby increasing substrate availability for rapid anthocyanin synthesis.On the basis of a weighted gene co-expression network analysis,MYB transcription factors,anthocyanin transporters,glutathione S-transferase,and multidrug and toxic compound extrusion(MATE)were identified as key regulators that coordinate precursor storage along with light-induced transcriptional activation.Notably,PpMYB4 binds to the promoter of PpGSTF14 and activates its expression,thereby promoting anthocyanin accumulation.The study findings elucidated the temporal coordination of metabolic priming and light-responsive transcriptional regulation driving rapid anthocyanin biosynthesis,with possible implications for improving peach fruit flesh coloration.展开更多
Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
The latest generation of aero engines has set higher standards for thrust-to-weight ratio and energy conversion efficiency,making it imperative to address the challenge of efficiently and accurately machining film coo...The latest generation of aero engines has set higher standards for thrust-to-weight ratio and energy conversion efficiency,making it imperative to address the challenge of efficiently and accurately machining film cooling holes.It has been demonstrated that conventional long-pulse lasers are incapable of meeting the elevated quality surface finish requirements for these holes,a consequence of the severe thermal defects.The employment of backside water-assisted laser drilling technology confers a number of distinct advantages in terms of mitigating laser thermal damage,thus representing a highly promising solution to this challenge.However,significant accumulation of bubbles and machining products during the backside water-assisted laser drilling process has been demonstrated to have a detrimental effect on laser transmission and machining stability,thereby reducing machining quality.In order to surmount these challenges,a novel method has been proposed,namely an ultrasonic shock water flow-assisted picosecond laser drilling technique.Numerical models for ultrasonic acoustic streaming and particle tracking for machining product transport have been established to investigate the mechanism.The simulation results demonstrated that the majority of the machining products could rapidly move away from the machining area because of the action of acoustic streaming,thereby avoiding the accumulation of bubbles and products.Subsequent analysis,comparing the process performance in micro-hole machining,confirmed that the ultrasonic field could effectively eliminate bubble and chip accumulation,thus significantly improving micro-hole quality.Furthermore,the impact of ultrasonic and laser parameters on micro-hole quality under varying machining methods was thoroughly investigated.The findings demonstrated that the novel methodology outlined in this study yielded superior-quality micro-holes at elevated ultrasonic and laser power levels,in conjunction with reduced laser frequency and scanning velocity.The taper of the micro-holes produced by the new method was reduced by more than 25%compared with the other conventional methods.展开更多
[Objective]This study aims to investigate the multi-body hydrodynamic interaction mechanisms during offshore lifting operations of aquaculture net cages in wind-fishery integration systems.By integrating numerical sim...[Objective]This study aims to investigate the multi-body hydrodynamic interaction mechanisms during offshore lifting operations of aquaculture net cages in wind-fishery integration systems.By integrating numerical simulations and dynamic analysis methods,this study systematically investigates the coupled dynamic response characteristics during the cage-carrier vessel separation process to reveal its dynamic evolution patterns and key influence mechanisms.[Method]Based on potential flow theory,a fully coupled dynamic analysis model of crane vessel-net cage-semi-submersible barge was established for a marine ranch project in Guangdong.The complete lifting process was dynamically simulated using SESAM software.Five typical operating sea states were configured to investigate the influence of wave parameters on the system's motion response under combined wave-current-wind actions.[Result]The results demonstrate that wave period dominates the system stability.Under short-period conditions,the system maintains stable motion with relatively small horizontal relative displacements,while long-period conditions excite low-frequency resonance,leading to significant slow-drift motions.Vertical response analysis reveals that long-period waves cause severe relative displacement fluctuations between the cage and semi-submersible vessel,with actual displacement amplitudes doubling the preset safety target of 2.045 m.Quantitative analysis further indicates that when significant wave height increases from 1.0 m to 1.5 m,the actual displacement amplitude increases by approximately 20%relative to the target displacement of 2.045 m,demonstrating that its influence is significantly weaker than the displacement variations induced by wave period changes.The complete dynamic simulation successfully captures the continuous dynamic response characteristics during the lifting process.[Conclusion]This research clarifies the influence mechanisms of wave parameters on the cage lifting process,identifying wave period as the crucial factor for operational safety.An operation window assessment method incorporating multi-body coupling effects is established,proposing a safety criterion with peak period not exceeding six seconds as the core requirement.The findings provide theoretical foundation for safe installation of marine ranch net cages and offer valuable references for similar offshore lifting operations.展开更多
Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through...Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.展开更多
1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrie...1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrient malnutrition and yield reductions from climate change with sufficient speed or precision[1].Consequently,agriculture is transitioning from selection-based breeding to designbased engineering.Synthetic biology enables the precision modification of metabolic pathways and the construction of novel trait combinations[1,2].This special issue,Synthetic Biology for Crop Improvement,brings together 26 articles that showcase the field’s transition from laboratory curiosity to field-validated agricultural technology.The collection spans 13 plant species,from staple grains and major industrial crops to horticultural and medicinal plants,demonstrating the universal applicability of metabolic engineering.These studies reveal maturation toward field readiness:independent groups achieving reproducible results in identical pathways,greenhouse concepts advancing to multi-season field trials,and engineered traits delivering measurable agronomic value.This progression answers the central question in crop synthetic biology,shifting the paradigm from asking“can it work?”to demonstrating“how it works,and here are the yields”.This transformation is grounded in understanding and manipulating plant metabolism at molecular resolution[3].展开更多
Real-world studies(RWSs)have emerged as a transformative force in oncology research,complementing traditional randomized controlled trials(RCTs)by providing comprehensive insights into cancer care within routine clini...Real-world studies(RWSs)have emerged as a transformative force in oncology research,complementing traditional randomized controlled trials(RCTs)by providing comprehensive insights into cancer care within routine clinical settings.This review examines the evolving landscape of RWSs in oncology,focusing on their implementation,methodological considerations,and impact on precision medicine.We systematically analyze how RWSs leverage diverse data sources,including electronic health records(EHRs),insurance claims,and patient registries,to generate evidence that bridges the gap between controlled clinical trials and real-world clinical practice.The review underscores the key contributions of RWSs,including capturing therapeutic outcomes in traditionally underrepresented populations,expanding drug indications,and evaluating long-term safety and effectiveness in routine clinical settings.While acknowledging significant challenges,including data quality variability and privacy concerns,we discuss how emerging technologies like artificial intelligence are helping to address these limitations.The integration of RWSs with traditional clinical research is revolutionizing the paradigm of precision oncology and enabling more personalized treatment approaches based on real-world evidence.展开更多
文摘Total hip arthroplasty for adults with sequelae from childhood hip disorders poses significant challenges due to altered anatomy.The paper published by Oommen et al reviews the essential management strategies for these complex cases.This article explores the integration of finite element analysis(FEA)to enhance surgical precision and outcomes.FEA provides detailed biomechanical insights,aiding in preoperative planning,implant design,and surgical technique optimization.By simulating implant configurations and assessing bone quality,FEA helps in customizing implants and evaluating surgical techniques like subtrochanteric shortening osteotomy.Advanced imaging techniques,such as 3D printing,virtual reality,and augmented reality,further enhance total hip arthroplasty precision.Future research should focus on validating FEA models,developing patient-specific simulations,and promoting multidisciplinary collaboration.Integrating FEA and advanced technologies in total hip arthroplasty can improve functional outcomes,reduce complications,and enhance quality of life for patients with childhood hip disorder sequelae.
基金co-supported by the Enterprise Innovation and Development Joint Program of the National Natural Science Foundation of China(No.U20B2032)Open Project Funding of State Key Laboratory for High Performance Tools(GXNGJSKL-2024-08)+1 种基金Open Foundation of the State Key Laboratory of Intelligent Manufacturing Equipment and Technology(IMETKF2023005)Introduced Innovative Scientific Research Team Project of Zhongshan(the tenth batch)(CXTD2023008)。
文摘Micro-grinding has been widely used in aerospace and other industry.However,the small diameter of the micro-grinding tool has limited its machining performance and efficiency.In order to solve the above problems,micro-structure has been applied on the micro-grinding tool.A morphology modeling has been established in this study to characterize the surface of microstructured micro-grinding tool,and the grinding performance of micro-structured micro-grinding tool has been analyzed through undeformed chip thickness,abrasive edge width,and effective distance between abrasives.Then deviation analysis,path optimization and parameter optimization of microchannel array precision grinding have been finished to improve processing quality and efficiency,and the deflection angle has the most obvious effects on the rectangular slot depth,micro-structured micro-grinding tool could reduce 10%surface roughness and 20%grinding force compared to original micro-grinding tool.Finally,the microchannel array has been machined with a size deviation of 2μm and surface roughness of 0.2μm.
基金Supported by the National Natural Science Foundation of China(No.51575014,51505020)the Key Foundation Project of China Academy of Railway Sciences(No.2021YJ200).
文摘The dynamic model of the ball screw mechanism(BSM)in spatial motion,developed in Part I of the study titled‘research and experimental analysis on precision degradation of BSM at low speed’,has been validated through a comparison between calculated values and experimentally measured data obtained from a comprehensive ball-screw test bench.In order to study the perform-ance parameters related to the precision degradation characteristics of ball screw under different pre-loads and speeds,the precision degradation test bench for ball screw is set up.Through the experi-ment on the ball-screw comprehensive test bench,the drag torque,stroke deviation,acceleration peak value,axial contact stiffness and other parameters of the BSM under different speeds are ob-tained,and the different preloads are obtained by the drag torque,the changing regularity of which is consistent with the simulation results.A comprehensive analysis of the experimental data reveals that the dynamic characteristics of the ball screw’s spatial motion are significantly influenced by gy-roscopic torque effects.By incorporating these parametric effects,the accuracy degradation charac-teristics of ball screw under different preloads and speeds can be well analyzed.This methodology establishes a technical foundation for investigating ball screw accuracy retention characteristics.
文摘Design a precision electroplating mechanical structure for automobiles based on finite element analysis method and analyze its mechanical properties.Taking the automobile steering knuckle as the research object,ABAQUS parametric modeling technology is used to construct its three-dimensional geometric model,and geometric simplification is carried out.Two surface treatment processes,HK-35 zinc nickel alloy electroplating and pure zinc electroplating,were designed,and the influence of different coatings on the mechanical properties of steering knuckles was compared and analyzed through numerical simulation.At the same time,standard specimens were prepared for salt spray corrosion testing and scratch method combined strength testing to verify the numerical simulation results.The results showed that under emergency braking and composite working conditions,the peak Von Mises stress of the zinc nickel alloy coating was 119.85 MPa,which was lower than that of the pure zinc coating and the alkaline electroplated zinc layer.Its equivalent strain value was 652×10^(-6),which was lower than that of the pure zinc coating and the alkaline electroplated zinc layer.Experimental data confirms that zinc nickel alloy coatings exhibit significant advantages in stress distribution uniformity,strain performance,and load-bearing capacity in high stress zones.The salt spray corrosion test further indicates that the coating has superior corrosion resistance and coating substrate interface bonding strength,which can significantly improve the mechanical stability and long-term reliability of automotive precision electroplating mechanical structures.
基金supported by the Aeronautical Science Foundation of China(Grant No.20230018072011)。
文摘3-Nitro-1,2,4-triazol-5-one(NTO)is a typical high-energy,low-sensitivity explosive,and accurate concentration monitoring is critical for crystallization process control.In this study,a high-precision quantitative analytical model for NTO concentration in ethanol solutions was developed by integrating real-time ATR-FTIR spectroscopy with chemometric and machine learning techniques.Dynamic spectral data were obtained by designing multi-concentration gradient heating-cooling cycle experiments,abnormal samples were eliminated using the isolation forest algorithm,and the effects of various preprocessing methods on model performance were systematically evaluated.The results show that partial least squares regression(PLSR)exhibits superior generalization ability compared to other models.Vibrational bands corresponding to C=O and–NO_(2)were identified as key predictors for concentration estimation.This work provides an efficient and reliable solution for real-time concentration monitoring during NTO crystallization and holds significant potential for process analytical applications in energetic material manufacturing.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
文摘Six new lanthanide complexes:[Ln(3,4-DEOBA)3(4,4'-DM-2,2'-bipy)]2·2C_(2)H_(5)OH,[Ln=Dy(1),Eu(2),Tb(3),Sm(4),Ho(5),Gd(6);3,4-DEOBA-=3,4-diethoxybenzoate,4,4'-DM-2,2'-bipy=4,4'-dimethyl-2,2'-bipyridine]were successfully synthesized by the volatilization of the solution at room temperature.The crystal structures of six complexes were determined by single-crystal X-ray diffraction technology.The results showed that the complexes all have a binuclear structure,and the structures contain free ethanol molecules.Moreover,the coordination number of the central metal of each structural unit is eight.Adjacent structural units interact with each other through hydrogen bonds and further expand to form 1D chain-like and 2D planar structures.After conducting a systematic study on the luminescence properties of complexes 1-4,their emission and excitation spectra were obtained.Experimental results indicated that the fluorescence lifetimes of complexes 2 and 3 were 0.807 and 0.845 ms,respectively.The emission spectral data of complexes 1-4 were imported into the CIE chromaticity coordinate system,and their corre sponding luminescent regions cover the yellow light,red light,green light,and orange-red light bands,respectively.Within the temperature range of 299.15-1300 K,the thermal decomposition processes of the six complexes were comprehensively analyzed by using TG-DSC/FTIR/MS technology.The hypothesis of the gradual loss of ligand groups during the decomposition process was verified by detecting the escaped gas,3D infrared spectroscopy,and ion fragment information detected by mass spectrometry.The specific decomposition path is as follows:firstly,free ethanol molecules and neutral ligands are removed,and finally,acidic ligands are released;the final product is the corresponding metal oxide.CCDC:2430420,1;2430422,2;2430419,3;2430424,4;2430421,5;2430423,6.
基金supported by grants from the Open Research Fund of the Zhejiang Key Laboratory of Precision Psychiatry(2025A2)the Natural Science Foundation of Zhejiang Province(LY23C090002)。
文摘Machado-Joseph disease,or spinocerebellar ataxia type 3(SCA3),represents the most common autosomal dominant cerebellar ataxia worldwide.Despite its progressive and debilitating nature,disease-modifying therapies remain elusive.Repetitive transcranial magnetic stimulation(rTMS)has emerged as a promising non-invasive intervention;however,its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding.A recent landmark study published in Brain Stimulation by Chen et al.addressed these challenges by combining a high-dose intermittent theta-burst stimulation(iTBS)protocol with concurrent transcranial magnetic stimulation-electroencephalography(TMS-EEG).This commentary provides an in-depth analysis of their findings,highlighting the restoration of cerebello-cortical inhibition(CBI)as a key therapeutic mechanism.Furthermore,we discuss the broader implications of this work,proposing that future translational research should integrate accelerated iTBS(aiTBS)paradigms,cortical response measurements(CRM),and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.
基金funded by the National Key R&D Project‘Innovation and Integration of Key Technologies for Integration of Agricultural Machinery and Agronomy in Weak Links of Hybrid Mid-season Rice in Hilly Areas of Southwest China’(2023YFD2301901).
文摘Chilo suppressalis(Walker)is one of the most important rice pests worldwide,posing a significant challenge to effective control.To develop a precision-timed,eco-friendly management strategy,overwintering population investigation and dynamic monitoring of C.suppressalis populations were conducted in the Meishan region of Sichuan,China,from 2023 to 2024.The optimal timing for insecticide application was estimated,followed by field trials evaluating the efficacy of different insecticides.Results demonstrated that the peak emergence of first-generation adults typically occurred in early July(under the environmental conditions of the Meishan region),with the ambient humidity below 75%and temperature around 29◦C.Pesticide efficacy trials show that insecticide combinations exhibited superior control.Notably,a combined treatment of emamectin benzoate⋅methoxyfenozide+chlorantraniliprole achieved the highest control efficacy(90.05%)and a corresponding yield of 12,491.55 kg/ha.All tested treatments were determined to be safe for rice growth.Furthermore,this optimized strategy resulted in notable economic benefits,including a 50%reduction in pesticide usage and cost savings of 4796.15 CNY compared to conventional practices.This study provides valuable insights into sustainable rice production and pest management and,for the first time,proposes a precision application time window based on intelligent monitoring.
文摘The Savitzky-Golay(SG)filter,which employs polynomial least-squares approximations to smooth data and estimate derivatives,is widely used for processing noisy data.However,noise suppression by the SG filter is recognized to be limited at data boundaries and high frequencies,which can significantly reduce the signal-to-noise ratio(SNR).To solve this problem,a novel method synergistically integrating Principal Component Analysis(PCA)with SG filtering is proposed in this paper.This approach avoids the is-sue of excessive smoothing associated with larger window sizes.The proposed PCA-SG filtering algorithm was applied to a CO gas sensing system based on Cavity Ring-Down Spectroscopy(CRDS).The perform-ance of the PCA-SG filtering algorithm is demonstrated through comparison with Moving Average Filtering(MAF),Wavelet Transformation(WT),Kalman Filtering(KF),and the SG filter.The results demonstrate that the proposed algorithm exhibits superior noise reduction capabilities compared to the other algorithms evaluated.The SNR of the ring-down signal was improved from 11.8612 dB to 29.0913 dB,and the stand-ard deviation of the extracted ring-down time constant was reduced from 0.037μs to 0.018μs.These results confirm that the proposed PCA-SG filtering algorithm effectively improves the smoothness of the ring-down curve data,demonstrating its feasibility.
文摘Objective:To evaluate the global,regional,and national burden and determinants of Acute Respiratory Infections(ARIs)among children and adolescents from 1990 to 2021.Methods:We analysed ARI mortality and disability-adjusted life years(DALYs),stratified by age,sex,and economic development level based on data retrieved from the Global Burden of Disease study 2021.Decomposition and frontier analyses were employed to identify key drivers of burden variation and visualize potential reductions based on development levels.Results:Between 1990 and 2021,the global burden of ARIs showed a significant decline in both achievable age-standardized DALYs rate and age-standardized mortality rates(EAPC=-3.87 and-3.81,respectively).Different age groups and sex witnessed different levels of ARI burden,males experienced heavier burden than females and the 0-4 years-old group experienced heavier burden than other study age groups.Most of the 204 countries and territories experienced a downward trend of ARI burden,with slight increases observed only in Lesotho and Dominica.A negative correlation was found between the Socio-demographic Index and ARI burden.Decomposition analysis indicated that the significant decreases in deaths and DALYs were primarily driven by epidemiological changes.Conclusions:The global burden of ARIs among children and adolescents has declined over the past three decades,but substantial regional disparities persist.Targeted public health strategies are needed to address the continued ARI burden in high-risk regions and vulnerable age groups.
基金support from the National Key Research and Development Program of China(No.2024YFB3713705)is acknowledgedWangzhong Mu would like to acknowledge the Strategic Mobility,Sweden(SSF,No.SM22-0039)+1 种基金the Swedish Foundation for International Cooperation in Research and Higher Education(STINT,No.IB2022-9228)the Jernkontoret(Sweden)for supporting this clean steel research.Gonghao Lian would like to acknowledge China Scholarship Council(CSC,No.202306080032).
文摘The detection and characterization of non-metallic inclusions are essential for clean steel production.Recently,imaging analysis combined with high-dimensional data processing of metallic materials using artificial intelligence(AI)-based machine learning(ML)has developed rapidly.This technique has achieved impressive results in the field of inclusion classification in process metallurgy.The present study surveys the ML modeling of inclusion prediction in advanced steels,including the detection,classification,and feature prediction of inclusions in different steel grades.Studies on clean steel with different features based on data and image analysis via ML are summarized.Regarding the data analysis,the inclusion prediction methodology based on ML establishes a connection between the experimental parameters and inclusion characteristics and analyzes the importance of the experimental parameters.Regarding the image analysis,the focus is placed on the classification of different types of inclusions via deep learning,in comparison with data analysis.Finally,further development of inclusion analyses using ML-based methods is recommended.This work paves the way for the application of AIbased methodologies for ultraclean-steel studies from a sustainable metallurgy perspective.
文摘Gastrointestinal(GI)cancers remain a leading cause of cancer-related morbidity and mortality worldwide.Artificial intelligence(AI),particularly machine learning and deep learning(DL),has shown promise in enhancing cancer detection,diagnosis,and prognostication.A narrative review of literature published from January 2015 to march 2025 was conducted using PubMed,Web of Science,and Scopus.Search terms included"gastrointestinal cancer","artificial intelligence","machine learning","deep learning","radiomics","multimodal detection"and"predictive modeling".Studies were included if they focused on clinically relevant AI applications in GI oncology.AI algorithms for GI cancer detection have achieved high performance across imaging modalities,with endoscopic DL systems reporting accuracies of 85%-97%for polyp detection and segmentation.Radiomics-based models have predicted molecular biomarkers such as programmed cell death ligand 2 expression with area under the curves up to 0.92.Large language models applied to radiology reports demonstrated diagnostic accuracy comparable to junior radiologists(78.9%vs 80.0%),though without incremental value when combined with human interpretation.Multimodal AI approaches integrating imaging,pathology,and clinical data show emerging potential for precision oncology.AI in GI oncology has reached clinically relevant accuracy levels in multiple diagnostic tasks,with multimodal approaches and predictive biomarker modeling offering new opportunities for personalized care.However,broader validation,integration into clinical workflows,and attention to ethical,legal,and social implications remain critical for widespread adoption.
基金supported by the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties(Grant No.2021C12066-4)Huzhou Agricultural Science and Technology Innovation Team Project(Grant No.2022HN01).
文摘Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study revealed that removing bags from‘Gengcunyangtao’red-fleshed peach fruits triggers the rapid and uniform accumulation of anthocyanins in the flesh,resulting in anthocyanin levels that exceed those in unbagged fruits.The exposure to light after bag removal triggered significant increases in anthocyanin levels within 24 h.This was accompanied by the rapid upregulation of light-responsive and flavonoid biosynthetic gene expression levels within 6 h.A metabolomic analysis indicated that anthocyanin precursors,especially p-coumaric acid,accumulated before bag removal,thereby increasing substrate availability for rapid anthocyanin synthesis.On the basis of a weighted gene co-expression network analysis,MYB transcription factors,anthocyanin transporters,glutathione S-transferase,and multidrug and toxic compound extrusion(MATE)were identified as key regulators that coordinate precursor storage along with light-induced transcriptional activation.Notably,PpMYB4 binds to the promoter of PpGSTF14 and activates its expression,thereby promoting anthocyanin accumulation.The study findings elucidated the temporal coordination of metabolic priming and light-responsive transcriptional regulation driving rapid anthocyanin biosynthesis,with possible implications for improving peach fruit flesh coloration.
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
基金supported by the National Natural Science Foundation of China(No.52205468,No.52275431,No.52375186)China Postdoctoral Science Foundation(No.2025M771349)Zhejiang Province Natural Science Foundation(No.LD22E050001)。
文摘The latest generation of aero engines has set higher standards for thrust-to-weight ratio and energy conversion efficiency,making it imperative to address the challenge of efficiently and accurately machining film cooling holes.It has been demonstrated that conventional long-pulse lasers are incapable of meeting the elevated quality surface finish requirements for these holes,a consequence of the severe thermal defects.The employment of backside water-assisted laser drilling technology confers a number of distinct advantages in terms of mitigating laser thermal damage,thus representing a highly promising solution to this challenge.However,significant accumulation of bubbles and machining products during the backside water-assisted laser drilling process has been demonstrated to have a detrimental effect on laser transmission and machining stability,thereby reducing machining quality.In order to surmount these challenges,a novel method has been proposed,namely an ultrasonic shock water flow-assisted picosecond laser drilling technique.Numerical models for ultrasonic acoustic streaming and particle tracking for machining product transport have been established to investigate the mechanism.The simulation results demonstrated that the majority of the machining products could rapidly move away from the machining area because of the action of acoustic streaming,thereby avoiding the accumulation of bubbles and products.Subsequent analysis,comparing the process performance in micro-hole machining,confirmed that the ultrasonic field could effectively eliminate bubble and chip accumulation,thus significantly improving micro-hole quality.Furthermore,the impact of ultrasonic and laser parameters on micro-hole quality under varying machining methods was thoroughly investigated.The findings demonstrated that the novel methodology outlined in this study yielded superior-quality micro-holes at elevated ultrasonic and laser power levels,in conjunction with reduced laser frequency and scanning velocity.The taper of the micro-holes produced by the new method was reduced by more than 25%compared with the other conventional methods.
文摘[Objective]This study aims to investigate the multi-body hydrodynamic interaction mechanisms during offshore lifting operations of aquaculture net cages in wind-fishery integration systems.By integrating numerical simulations and dynamic analysis methods,this study systematically investigates the coupled dynamic response characteristics during the cage-carrier vessel separation process to reveal its dynamic evolution patterns and key influence mechanisms.[Method]Based on potential flow theory,a fully coupled dynamic analysis model of crane vessel-net cage-semi-submersible barge was established for a marine ranch project in Guangdong.The complete lifting process was dynamically simulated using SESAM software.Five typical operating sea states were configured to investigate the influence of wave parameters on the system's motion response under combined wave-current-wind actions.[Result]The results demonstrate that wave period dominates the system stability.Under short-period conditions,the system maintains stable motion with relatively small horizontal relative displacements,while long-period conditions excite low-frequency resonance,leading to significant slow-drift motions.Vertical response analysis reveals that long-period waves cause severe relative displacement fluctuations between the cage and semi-submersible vessel,with actual displacement amplitudes doubling the preset safety target of 2.045 m.Quantitative analysis further indicates that when significant wave height increases from 1.0 m to 1.5 m,the actual displacement amplitude increases by approximately 20%relative to the target displacement of 2.045 m,demonstrating that its influence is significantly weaker than the displacement variations induced by wave period changes.The complete dynamic simulation successfully captures the continuous dynamic response characteristics during the lifting process.[Conclusion]This research clarifies the influence mechanisms of wave parameters on the cage lifting process,identifying wave period as the crucial factor for operational safety.An operation window assessment method incorporating multi-body coupling effects is established,proposing a safety criterion with peak period not exceeding six seconds as the core requirement.The findings provide theoretical foundation for safe installation of marine ranch net cages and offer valuable references for similar offshore lifting operations.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2025ZFJH03)the Central Guidance Fund for Local Science and Technology Development(No.2024ZY01054)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045).
文摘Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.
文摘1.Introduction Crop breeding is transitioning to engineering by synthetic biology.Conventional breeding,constrained by limited genetic variation and lengthy development cycles,cannot meet the challenges of micronutrient malnutrition and yield reductions from climate change with sufficient speed or precision[1].Consequently,agriculture is transitioning from selection-based breeding to designbased engineering.Synthetic biology enables the precision modification of metabolic pathways and the construction of novel trait combinations[1,2].This special issue,Synthetic Biology for Crop Improvement,brings together 26 articles that showcase the field’s transition from laboratory curiosity to field-validated agricultural technology.The collection spans 13 plant species,from staple grains and major industrial crops to horticultural and medicinal plants,demonstrating the universal applicability of metabolic engineering.These studies reveal maturation toward field readiness:independent groups achieving reproducible results in identical pathways,greenhouse concepts advancing to multi-season field trials,and engineered traits delivering measurable agronomic value.This progression answers the central question in crop synthetic biology,shifting the paradigm from asking“can it work?”to demonstrating“how it works,and here are the yields”.This transformation is grounded in understanding and manipulating plant metabolism at molecular resolution[3].
基金supported by the Zhejiang Provincial Natural Science Foundation(No.ZCLY24H1601)the National Natural Science Foundation of China(No.82403697)+1 种基金the Medical and Health Science and Technology Project of Zhejiang Province(No.2025KY411)the National Key R&D Program of China(No.2022YFC2505100).
文摘Real-world studies(RWSs)have emerged as a transformative force in oncology research,complementing traditional randomized controlled trials(RCTs)by providing comprehensive insights into cancer care within routine clinical settings.This review examines the evolving landscape of RWSs in oncology,focusing on their implementation,methodological considerations,and impact on precision medicine.We systematically analyze how RWSs leverage diverse data sources,including electronic health records(EHRs),insurance claims,and patient registries,to generate evidence that bridges the gap between controlled clinical trials and real-world clinical practice.The review underscores the key contributions of RWSs,including capturing therapeutic outcomes in traditionally underrepresented populations,expanding drug indications,and evaluating long-term safety and effectiveness in routine clinical settings.While acknowledging significant challenges,including data quality variability and privacy concerns,we discuss how emerging technologies like artificial intelligence are helping to address these limitations.The integration of RWSs with traditional clinical research is revolutionizing the paradigm of precision oncology and enabling more personalized treatment approaches based on real-world evidence.
