摘要：Fungi are nature’s recyclers,allowing for ecological nutrient cycling and,in turn,the continuation of life on *** fungi inhabit the human microbiome where they can provide health benefits,while others are opportunistic pathogens that can cause ***,members of the fungal kingdom,have been domesticated by humans for the production of beer,bread,and,recently,medicine and ***,the great untapped potential exists within the diverse fungal ***,many yeasts are intractable,preventing their use in biotechnology or in the development of novel treatments for pathogenic ***,as a first step for the domestication of new fungi,an efficient DNA delivery method needs to be ***,we report the creation of superior conjugative plasmids and demonstrate their transfer via conjugation from bacteria to 7 diverse yeast species including the emerging pathogen Candida *** create our superior plasmids,derivatives of the 57 kb conjugative plasmid pTA-Mob 2.0 were built using designed gene deletions and insertions,as well as some unintentional ***,a cluster mutation in the promoter of the conjugative gene traJ had the most significant effect on improving conjugation to *** addition,we created Golden Gate assembly-compatible plasmid derivatives that allow for the generation of custom plasmids to enable the rapid insertion of designer genetic ***,we demonstrated that designer conjugative plasmids harboring engineered restriction endonucleases can be used as a novel antifungal agent,with important applications for the development of next-generation antifungal therapeutics.

摘要：Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regenerative ***,lack of precise architectures and large-scale tissue sizes are some of the key limitations of current organoid technologies.3D bioprinting of organoids has recently emerged to address some of these *** this review,we discuss 3D bioprinting with respect to the use of bioinks and bioprinting methods and highlight recent studies that have shown success in bioprinting of stem cells and *** also summarize the use of several vascularization strategies for the bioprinted organoids,that are critical for a complex tissue *** fully realize the translational applications of organoids in disease modeling and regenerative medicine,these areas in 3D bioprinting need to be appropriately harnessed and channelized.

摘要：β-葡萄糖醛酸苷酶(GUS)在肿瘤的发生、转移和进展中具有关键作用,因而成为一种很有应用前景的癌症生物标志物.在本研究中,我们设计出一种酶激活的近红外荧光探针(DCM-βGlcA),可在体内和体外快速、准确地检测GUS的活性.该探针是由葡萄糖醛酸残基与荧光基团吡喃腈(DCM)衍生物构成.在GUS作用下,该探针在680 nm处具有明显的近红外荧光增强,而且它的斯托克位移达到了150 nm.此外,该探针对于GUS有很高的灵敏度,检测限低至0.19 U L^(-1).我们利用该探针分析了人血清样本中的GUS含量,其结果与ELISA检测结果一致.该探针还可用于示踪活细胞中的GUS,而且能够对荷瘤小鼠体内和肝癌组织中的GUS进行检测成像.因此,该探针可作为检测GUS的理想工具.

摘要：热休克蛋白90(Hsp90)通过对几百种蛋白质底物(客户蛋白质)进行合理的折叠、成熟其构象并且激活,在肿瘤细胞的生长和繁殖中发挥重要作用.因此,Hsp90成为非常有吸引力、有前途的抗肿瘤药物靶点,并且超过20种抑制剂已经进入临床实验阶段.我们在这里设计并合成了一个小分子抑制剂:FS36.收集了Hsp90~N-FS36复合物晶体结构的X射线衍射实验数据.高分辨率X射线晶体结构表明,FS36在ATP结合位点上与Hsp90~N相互作用,并且FS36可能替代核苷酸与Hsp90~N结合.FS36和Hsp90~N的复合物晶体结构和相互作用为后期设计和优化新型抗肿瘤药物奠定基础.