摘要：Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanofiller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

摘要：As we navigate the transition from the Fourth to the Fifth Industrial Revolution,the emerging fields of biomanufacturing and biofabrication are transforming life sciences and *** sectors are benefiting from a synergy of synthetic and engineering biology,sustainable manufacturing,and integrated design *** techniques such as 3D bioprinting,tissue engineering,directed assembly,and self-assembly are instrumental in creating biomimetic scaffolds,tissues,organoids,medical devices,and biohybrid *** field of biofabrication in the United Kingdom and Ireland is emerging as a pivotal force in bioscience and healthcare,propelled by cutting-edge research and *** on the production of biologically functional products for use in drug delivery,in vitro models,and tissue engineering,research institutions across these regions are dedicated to innovating healthcare solutions that adhere to ethical standards while prioritising sustainability,affordability,and healthcare system benefits.

摘要：背景：人们对基因与环境在原发性帕金森病（Parkinson disease,PD)中的相对作用，一直存在争论。虽然基因研究已识别出2个基因，它们的突变可引起罕见的单基因PD变异型，观察研究也提示有遗传成分，但是孪生子研究却表明遗传在PD常见型中几乎不起作用。目的：确定原发性PD的遗传性危险因素。设计、地点和参加者：于1995－2000年进行的基因连锁研究。该研究在美国大陆和澳大利亚的13个临床人群，通过先证者找出174个有多人被诊断患原发性PD的家系，进行了全基因组搜索（n=344标记物）。共检查870名家庭成员：378人诊断患PD，379人无PD，113人未定。主要观察指标：从参数和非参数遗传连锁分析得出优势对数（logarithm of odds,lod)得分。结果：用两点参数的最大参数Lod得分（MLOD）和多点非参数lod得分（LOD）的连锁分析检查5个不同的染色体区连锁的重要证据：在至少有1人于40岁前发生PD的家系中，是6号染色体上的parkin基因（MLOD＝5．07；LOD＝5．47），在全部家系及晚发PD的家系中，是染色体17q(MLOD=2.28;LOD=2.62),8p(MLOD=2.01;LOD=2.22)和5q(MLOD=2.39;LOD=1.50)，在含左旋多巴有效和无效的两种患者的家系中，是染色体9q(MLOD=1.52;LOD=2.59).结论：我们的数据表明，在早发PD中parkin基因是重要的，在原发性晚发PD的发生中则可能有多个遗传因素具有重要作用。