Molecular mechanism of pancreatic ductal adenocarcinoma:The heterogeneity of cancer-associated fibroblasts and key signaling pathways

Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

基于FBS-TRIZ的园艺拖拉机设计研究

目的关注园艺拖拉机使用过程中驾驶者的相关行为,提取园艺拖拉机驾驶者的使用需求,并将其转化为产品技术特性的设计要求,提升园艺拖拉机驾驶者的用户需求满意度。方法将FBS-TRIZ理论融合作为研究园艺拖拉机功能需求映射的方法。通过对用户行为特征的分析,结合用户访谈、问卷调研等方式获取用户需求,运用FBS模型,构建出园艺拖拉机功能需求模型,将行为作为连接功能需求与产品结构的纽带,通过分析获取解决设计问题的方法;运用TRIZ理论进行冲突问题的分析与转化,并针对设计层面产品特性的矛盾提出解决方案。结论FBS与TRIZ理论的融合应用能够将用户需求精准转化为技术特性层面的设计要求,对园艺拖拉机用户需求设计方面的不足提出了相应的解决方案,为设计师提供了将用户需求向功能结构的映射转化的指导,验证了该方法的有效性。

基于AHP/QFD/FBS模型的果园管理机创新设计研究

目的 改善本土农机装备现行设计流程在方案创新中的不足,实现果园管理机要素的优化和设计的创新。方法 面向农业4.0场景应用,引入工业设计创新思维到农机装备设计,构建层次分析法(AHP)、质量功能展开(QFD)和FBS(Function-Behavior-Structure)模型相结合的创新设计流程。首先,通过AHP和QFD的分析过程,将用户需求转化为关键产品特性。然后,结合相关特性指标,优化、更新、重组产品功能的内在属性,逐步建立概念性功能系统。最后,通过FBS模型的“功能-行为-结构”映射,求解功能实现的结构载体,以满足产品功能创新和结构要素为设计条件。最终完成果园管理机创新设计。结果 集成AHP/QFD/FBS的创新设计流程包含完整的需求分析、特性发掘、功能创新和结构求解过程。通过设计实践,果园管理机在用户体验、功能配置、适应性和智能化方面得到了提升。结论 该流程在农机装备方案创新中呈现出的有效性,能够为农业4.0中相关产品设计提供新思路和参考。

基于Kano-FAST-FBS的智能扫地机改良设计研究

目的智能扫地机是智能家居生活中不可或缺的产品,但现有扫地机交互性和功能性趋于一致,为了有效识别居家清扫需求,进一步提升交互性和趣味性,并将其科学转化为产品的功能要素及结构参数,提出一种基于Kano-FAST-FBS模型的产品改良设计方法,以提升智能家居产品的满意度。方法首先,基于Kano模型量化评估智能家居产品的用户需求属性,获得用户需求优先级;其次,运用功能分析系统技术(FAST)将用户需求分别转化为对应的产品功能要素;最后,以功能-行为-结构(FBS)设计模型为基础,实现了产品功能到结构参数的合理映射,进而得到改良产品的各个结构模块,输出最终设计方案。结果以扫地机器人为例,验证了基于Kano-FAST-FBS模型的设计流程。结论在该方法指导下的产品设计能系统地解决用户需求和功能结构模块之间的匹配问题,从而得出更符合用户功能预期的设计方案,并可以为其他类似产品设计提供参考思路。

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Computed tomography-based radiomics predicts the fibroblastrelated gene EZH2 expression level and survival of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of liver cancer.The primary treatment strategies for HCC currently include liver transplantation and surgical resection.However,these methods often yield unsatisfactory outcomes,leading to a poor prognosis for many patients.This underscores the urgent need to identify and evaluate novel therapeutic targets that can improve the prognosis and survival rate of HCC patients.AIM To construct a radiomics model that can accurately predict the EZH2 expression in HCC.METHODS Gene expression,clinical parameters,HCC-related radiomics,and fibroblastrelated genes were acquired from public databases.A gene model was developed,and its clinical efficacy was assessed statistically.Drug sensitivity analysis was conducted with identified hub genes.Radiomics features were extracted and machine learning algorithms were employed to generate a radiomics model related to the hub genes.A nomogram was used to illustrate the prognostic significance of the computed Radscore and the hub genes in the context of HCC patient outcomes.RESULTS EZH2 and NRAS were independent predictors for prognosis of HCC and were utilized to construct a predictive gene model.This model demonstrated robust performance in diagnosing HCC and predicted an unfavorable prognosis.A negative correlation was observed between EZH2 expression and drug sensitivity.Elevated EZH2 expression was linked to poorer prognosis,and its diagnostic value in HCC surpassed that of the risk model.A radiomics model,developed using a logistic algorithm,also showed superior efficiency in predicting EZH2 expression.The Radscore was higher in the group with high EZH2 expression.A nomogram was constructed to visually demonstrate the significant roles of the radiomics model and EZH2 expression in predicting the overall survival of HCC patients.CONCLUSION EZH2 plays significant roles in diagnosing HCC and therapeutic efficacy.A radiomics model,developed using a logistic algorithm,efficiently predicted EZH2 expression and exhibited strong correlation with HCC prognosis.

RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration

Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.

Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

隔代抚育背景下基于AHP、FBS的学龄前儿童餐具设计

为满足我国隔代抚育环境下儿童的实际需要,研究提出一种基于层次分析法(AHP)与“功能―行为―结构”模型(FBS)的学龄前儿童餐具设计研究方法。首先,通过访谈与问卷的形式获取目前隔代抚育过程中涉及儿童进食方面的问题与需求,使用AHP对目标用户的需求进行量化处理和权重排序;其次,使用FBS模型构建产品的功能需求数据库,推导隔代抚育儿童进食过程中的用户行为,求解功能实现的结构载体;最后将AHP与FBS模型得出的设计点进行整合,经过测试迭代后确定最优方案。

基于Kano-FBS模型的智能桌面便签机设计

为帮助办公人群更高效率地完成工作并获得更多乐趣,同时缓解工作压力,将使用便利贴记事这一行为向智能化趋势靠拢,文章首先基于Kano模型深入分析智能桌面便签机用户需求,确定功能特性类型,并明确相对重要的用户体验需求。其次采用FBS模型将关键需求与产品设计相对应,确保设计方案的合理性。最后通过理论模型的应用得到更具创新性和实用性的设计方案,提高用户工作效率的同时增添趣味性,为办公用品创新发展和改进提供有针对性的指导。

基于FBS-AHP方法的老年运动鞋设计

本文基于AHP和FBS模型,深入研究了老年运动鞋设计,提出创新方案以提升舒适性和美观性。通过用户调研和权重分析,为设计实践提供科学依据,有助于推动老年运动鞋市场的发展,提升老年人生活质量。

基于可供性理论与FBS模型的台灯创新体验设计

目的设计一款具有创意交互方式的台灯产品。方法以可供性理论为研究基础,使用交互方式发掘设计点,构建可供性与FBS集成设计模型,采用问卷调查和访谈法挖掘台灯创新设计的用户需求,与产品功能发生映射关系,并运用AHP层次分析法对需求重要度进行排序,将预期可供性转化为实际可供性。继而运用FBS模型对台灯结构设计构建情境、分析冲突,完成期望功能、预期行为以及结构的映射,对相关要素及操作方式逐层进行关联分析。结果最终设计出创新交互形式的、适合各个年龄段与各种家庭环境使用的台灯创新设计。结论将可供性理论、AHP和FBS框架结合起来,形成一个跨学科的新方法,用于优化设计和决策过程,通过理论融合、方法创新、技术开发和实践应用,提高设计的功能性、行为预测和结构的有效性,为台灯创新设计的研究提供了新思路。

基于QFD-FBS的儿童游泳辅助产品创新设计研究

目的为消除儿童游泳时的恐水心理,助其更好地学习游泳,探索儿童游泳辅助产品的创新设计路径。方法首先,采用实地问卷调查法提取儿童初学游泳的需求并在层次分析法(AHP)中筛选出最大权重项;其次,运用QFD建立“用户需求-设计要求”关系矩阵,将关键设计目标转化为主要功能;最后,在FBS模型中映射出功能对应的结构模块。结果提出儿童游泳辅助产品以用户行为需求为导向的四大功能模块,即预警功能模块、学习功能模块、娱乐功能模块、调节功能模块,并以此为起点完成功能层-行为层-结构层的映射,从而指导游泳辅助产品的创新设计表现。结论QFD-FBS相结合能够填补空白点,在游泳辅助产品创新开发领域具有较好的指导意义,提高了儿童学习游泳的满意度,为游泳辅助产品设计领域引入新思路。

结合FAST-FAHP-FBS整合模型的适老化智能床头柜设计研究

为了优化现有适老化智能床头柜设计,改善当今适老化家具市场存在的定位失焦、同质化严重、智能乱象等问题。首先,依据扎根理论构建需求体系,通过FAST理论将需求转化为功能并进一步功能细化;其次,采用FAHP进行功能权重求解。基于权重计算结果并借助FBS将权重较高的功能转化为结构设计点进行设计,应用模糊综合评价方法进行设计反馈。FAST-FAHP-FBS整合模型设计流程将质性与量化研究整合,将适老化智能床头柜设计建立于用户需求之上,为今后适老化家具的设计提供理论与实践参考。

结合AHP/QFD/FBS模型的智能学习桌产品设计研究

针对智能学习桌开发设计过程中过度依赖生产企业和设计人员的主观判断、缺少用户参与导致用户对于现有产品满意度较低的问题,结合AHP/QFD/FBS模型辅助设计,得到更加贴合用户实际需求的智能学习桌。首先,通过访谈法和问卷调查法获得学习桌的初始用户需求,利用层次分析法(AHP,Analytic Hierarchy Process)计算得出用户需求权重和优先级;其次,利用QFD(质量功能展开,Quality Function Deployment)将用户需求进行分析得出产品技术特性,进而将其量化得到关键设计要素;将获取的关键设计要素转化为功能导入FBS(Function-Behavior-Structure)模型中完成“功能—行为—结构”映射,得出智能学习桌的关键设计结构。最终输出更加贴合用户实际需求的智能学习桌,并利用模糊综合评价法对设计方案的可行性进行验证。结合AHP-QFD-FBS模型的产品设计方法可以更加有效地将实际用户需求与产品方案相结合,为解决此类问题提供了新的思路。

基于FBS的汽车起重机远程操控系统人机交互设计研究

目的通过人机交互分析与FBS设计模型得出远程操控过程中的用户交互范式与原型设计,构建出远程操控系统的人机交互过程,形成起重机远程操控系统设计方案。方法首先,根据用户调研与实验对现有起重机操控系统中的人机交互特征进行分析和研究,构建起重机远程操控系统的人机交互模型;其次,结合功能需求与用户行为特征,结合FBS(功能-行为-结构)的设计分析方法得出起重机远程交互系统的结构组成,根据人机交互相关研究设计出具体的解决方案;最后,运用CreoManikin进行人机工程仿真分析验证。结论通过人机交互分析和FBS设计模型确定设计因素并进行方案设计,形成起重机远程操控系统设计方案,对工程机械远程操作系统产品的设计研发具有一定的理论研究意义与应用价值。

基于AHP/QFD/FBS/FCE集成理论的高铁站候车座椅创新设计

为提升用户出行途中的候车体验,以用户切实需求为导向,提出一种基于AHP/QFD/FBS/FCE集成理论的高铁站候车座椅设计分析方法,指导完成候车座椅的创新设计方案。首先通过用户访谈获取用户需求,然后再运用层次分析法求解出用户需求权重,在此基础上借助于质量功能展开将用户需求转化为座椅设计要求,再应用FBS模型将设计要求按照功能-行为-结构进一步映射为座椅的结构化设计信息,指导高铁站候车座椅设计方案的生成,最后再引入模糊综合评价法验证设计方案的合理性与可行性。基于AHP/QFD/FBS/FCE集成理论展开的高铁站候车座椅设计研究,能有效地将用户需求转化为具体的产品设计要求,实现产品的客观表现功能与用户需求精准的匹配,为高铁站候车座椅的创新设计提供了一条新的思路,同时该方法也可为其他同类产品的设计研究提供参考。

The Combined Effect of Lumenato and Ceramide in the Protection of Collagen Damage Induced by Neutrophils in Normal Human Dermal Fibroblasts

Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and contributes to photoaging. Methods: To study the combined effect of Lumenato and ceramide in preventing collagen-1 damage induced by phagocytes, we used co-cultures of normal human dermal fibroblasts (fibroblasts) and activated human neutrophils. The present study aimed to determine the protective effect of the combination of Lumenato and ceramide on fibroblast collagen-1 damage induced by neutrophils. Results: Lumenato (in the range of 6.5 - 208 μg/ml) or ceramide (in the range of 0.1 - 50 μM) inhibited the production of superoxides and MPO by TNFα-stimulated neutrophils, as well as the production of NO by LPS-stimulated macrophages in a dose-dependent manner. The combinations of Lumenato and ceramide, in low concentrations, caused synergistic prevention of fibroblasts’ collagen-1 damage induced by TNFα-activated neutrophils, detected by fluorescence immunostaining and WB analysis. MPO activity in the supernatants of the co-cultures was also synergistically inhibited. Adding Lumenato or ceramide singly or in combinations in these low concentrations to the fibroblast cultures did not affect the expression of collagen-1. The combinations of Lumenato or ceramide in these concentrations also caused a synergistic inhibition of NO production by activated macrophages. Conclusions: The results suggest that combining low concentrations of Lumenato and ceramide results in synergistic protection against fibroblasts’ collagen-1 damage induced by neutrophils, thus indicating their possible potential for enhanced skin health.

结合KANO-FBS-TRIZ模型的居家办公家具设计方法与实践

为弥补市面上的居家办公家具功能与种类方面的缺漏,以20~35岁职场青壮年群体为研究对象。首先通过桌面研究与线下访谈提炼需求关键词并利用KJ法绘制亲和图以划分需求维度;其次借助KANO模型判别需求类型,提炼关键需求功能点导入FBS模型,进而转化为结构要素为设计提供参考。最终基于上述研究结果并结合TRIZ理论提出居家办公家具的设计方案。基于KANO-FBS-TRIZ模型的居家办公家具的创新设计着眼于居家办公者的使用需求,采用量化与质性相结合的研究方法,优化现有家庭办公类家具设计,丰富现有设计方法研究,为相关产品的研发提供理论与实践参考。