摘要：The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the *** between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological *** most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune ***,each pathway is intertwined with a complex *** the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative *** paper briefly retraces the possible communication pathways between the gut microbiome and the *** further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the *** diseases also decrease patients’quality of ***,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the *** of MGBA in the laboratory uses many molecular technologies and biomaterial *** and organoids provide a more realistic picture of the cell and tissue structure than *** them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between ***-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

摘要：Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural *** in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted *** oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain *** study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with *** report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide ***,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase *** study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release ***,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal *** showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new *** findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated *** work thereby offers a promising avenue for the development of functional tissues with e

摘要：A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as *** hydrogel patterningwith awell-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a ***,these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo ***,we present a novel dissolvable temporary barrier(DTB)strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular *** key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology,followed by a barrier-free medium perfusion after the dissolution of the *** and multiple tissue compartments with different geometries can be established using either straight or curved DTB *** effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor *** a new proof-of-concept in vasculature-on-a-chip,DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices,which is an improved protocol for the fabrication ofmultiorgan ***,we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.

摘要：作为细胞中的主要运输系统,天然囊泡在物质的定点输运过程中具有至关重要的作用.高分子囊泡是与之结构相似的一种人工囊泡,具有优异的膜稳定性和胶体稳定性、高药物负载率、低膜穿透性、优异的可修饰性和长循环时间等优势,在生物医用领域具有广泛的应用前景.然而,目前该领域尚面临一系列重要挑战,如合成和制备方法较为复杂、生物相容性较难预测、功能和递送途径有限等,限制了其临床转化之路.本文从囊泡的构建模块合成、自组装技术和潜在的生物医学应用等角度,提出了设计和制备下一代高分子囊泡需要解决的五个关键科学问题,指出了未来面临的重要挑战和发展方向,例如简化设计和合成过程,优化和规范自组装过程,拓展潜在的应用前景.

摘要：Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering ***,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface ***,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different *** porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL *** a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was *** two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated *** addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface *** together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material ***,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(m

摘要：Oxygen(O_(2))-sensing matrices are promising tools for the live monitoring of extracellular O_(2) consumption levels in long-term cell *** this study,ratiometric O_(2)-sensing membranes were prepared by electrospinning,an easy,low-cost,scalable,and robust method for fabricating ***(ε-caprolactone)and poly(dimethyl)siloxane polymers were blended with tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)dichloride,which was used as the O_(2)-sensing probe,and rhodamine B isothiocyanate,which was used as the reference *** functionalized scaffolds were morphologically characterized by scanning electron microscopy,and their physicochemical profiles were obtained by Fourier transform infrared spectroscopy,thermogravimetric analysis,and water contact angle *** sensing capabilities were investigated by confocal laser scanning microscopy,performing photobleaching,reversibility,and calibration curve studies toward different dissolved O_(2)(DO)*** sensing nanofibers showed a high response to changes in DO concentrations in the physiological-pathological range from 0.5%to 20%and good stability under ratiometric *** addition,the sensing systems were highly biocompatible for cell growth promoting adhesiveness and growth of three cancer cell lines,namely metastatic melanoma cell line SK-MEL2,breast cancer cell line MCF-7,and pancreatic ductal adenocarcinoma cell line Panc-1,thus recreating a suitable biological environment in *** O_(2)-sensing biomaterials can potentially measure alterations in cell metabolism caused by changes in ambient O_(2)content during drug testing/validation and tissue regeneration processes.

摘要：生物材料表面的物理性质,如拓扑结构,由于其易于加工和稳定的生物作用而受到广泛关注.虽然已有许多研究报道了材料表面拓扑结构与细胞的相互作用,但由于不同研究中使用的微结构和实验环境的多样性,生物材料表面不同微结构与细胞/组织行为之间的影响关系尚未得到很好的统一评价.在本研究中,我们设计了11种图案(三角形、矩形、圆形等),这些图案包含两种类型的形貌(微坑和微柱),这样一共得到22种表面拓扑结构.我们在体外和体内对这些微结构影响细胞和组织的生物作用进行了评估.我们的研究结果表明,由连续微坑形成的凹槽微结构促进细胞迁移效果相比其他微结构更强.其中,由三角形微坑组成的凹槽在体外对细胞迁移的促进作用最强.在大鼠皮下模型中,这种三角形微坑组成的凹槽结构减少了纤维组织的包封,促进了血管的形成.

摘要：Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor ***,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor *** study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I *** also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and ***,it compares two-dimensional(2D)and 3D *** comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D ***,the two models yielded significantly different cell ***,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D *** results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture *** developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

摘要：目的:作为遗传研究中最常用的设计之一,基于家系数据的实验设计因其优势而得到了广泛认可,例如家系数据在人群分层和混合情况下表现出来的稳健性。在疾病风险预测中,研究者对如何基于家系遗传数据,寻找和分析遗传标记的作用非常感兴趣。本研究旨在开发一种新的统计方法,用于基于家系数据的遗传风险预测。创新点:期望新方法能够捕捉小或中等边际效应的遗传因子,及其相互作用,与基于家族史或家系数据的现有风险预测方法相比,具有更高的预测准确性。方法:在这项研究中,我们提出了集群化似然比(ELR)的新方法,Fam-ELR,用于家系数据的基因组疾病风险预测。Fam-ELR采用集群化的受试者工作特征曲线(ROC)方法来考虑家系样本内部的相关性,并使用计算有效的集群树进行变量选择和模型构建。结论:通过模拟,Fam-ELR显示了其在各种疾病遗传模型和谱系结构中的稳健性,并且获得了比现有的两种基于家系数据的风险预测方法更好的性能。同时,在基于全基因组行为障碍家系数据集的实际应用中,Fam-ELR展示了其将潜在风险预测因子和其相互作用整合到模型中以提高准确性的能力,尤其是在全基因组水平上。通过比较现有方法,例如遗传风险评分方法等,Fam-ELR被证实具有将较小或中等边际效应的遗传变异及其相互作用纳入改进的风险预测模型的能力。因此,它是一种强有力且实用的方法,适用于基于家系数据的高维度遗传风险预测中,特别是对于病因未知或知之甚少的人类复杂疾病。

摘要：电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度,对于了解大脑中一氧化氮的功能至关重要.然而,在大脑中使用的传统刚性传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的问题.在这里,我们报道了一种结合物理和化学吸附能力、具有高灵敏度和准确性的电化学一氧化氮传感器.其对一氧化氮的物理和化学吸附能力分别来自于电极的高比表面积和丰富的羧基官能团.此外,柔软的电极可以与脑组织的力学性能相匹配,实现了一个高度适应的电极/组织界面.由此设计的颅内一氧化氮传感器表现出迄今为止所报道文献中最高的灵敏度,为3245 pA nmol^(-1)L,检测限为0.1 nmol L^(-1).电极在植入后未观察到显著的炎症反应以及过量的一氧化氮表达,提高了检测的准确性.该传感器成功捕捉了大脑中的一氧化氮波动,并实现了对多个脑区的同时检测,促进了对大脑中一氧化氮生理病理作用的研究.