摘要：Type 1 diabetes is caused by insulin deficiency due to the loss of beta cells in the islets of *** severe cases,islet transplantation into the portal vein is ***,due to the loss of transplanted islets and the failure of islet function,the 5-year insulin independence rate of these patients is<50%.In this study,we developed a long-term,insulin-secreting,3 Dbioprinted construct implanted subcutaneously with the aim of preventing islet *** bioprinted construct was fabricated by the multi-layer bioprinting of beta-cell(mouse insulinoma-6:MIN-6)-encapsulated alginate bioink and poly(caprolactone)biodegradable polymer.A glucose response assay revealed that the bioprinted constructs proliferated and released insulin normally during the 4-week in vitro *** MIN-6 generated clusters with a diameter of 100-200μm,similar to the original pancreatic islets in the *** an in vivo study using type 1 diabetes mice,animals implanted with bioprinted constructs showed three times higher insulin secretion and controlled glucose levels at 8 weeks after *** the implanted,bioprinted constructs had a positive effect on insulin secretion in the experimental animals,the survival rate of the implanted group(75%)was three times higher than that of the non-implanted group(25%).The results suggest that the proposed,3 D-bioprinted,subcutaneous construct can be a better alternative to portal vein islet transplantation.

摘要：酸的 oligosaccharide 糖链(AOSC ) ， D-mannuronic 酸 oligosaccharide，源于棕色的水藻多糖，被完成了阶段我在是的中国的临床的试用 anti-Alzheimer 的疾病(广告) 药候选人。在神经原的 AOSC 有约束力的蛋白质的鉴定为理解它的行动机制是很重要的。为了在调停的神经原决定 AOSC 的有约束力的蛋白质，它的反广告活动，共焦的显微镜学，亲密关系层析，和液体层析双人脚踏车集中 spectrometry (LC-MS/MS ) 分析被使用。AOSC 在集中绑在 SH-SY5Y 房间的共焦的显微镜学分析表演 -- ，时间 -- ，并且温度依赖者时尚。AOSC 有约束力的蛋白质被亲密关系层析净化并且由 LC-MS/MS 分析识别了。结果证明有 349 蛋白质绑定 AOSC，包括 clathrin，适配器 protein-2 (AP-2 ) 和淀粉的先锋蛋白质(应用软件) 。这些结果建议到神经原的 AOSC 的绑定 / 入口为反广告活动可能负责。

摘要：Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2,has spread globally and threatens public *** in vitro models that recapitulate the architecture and functioning of specific tissues and organs are in high demand for COVID-19-related pathology studies and drug *** three-dimensional in vitro cultures,such as self-assembled and engineered organoid cultures,surpass conventional two-dimensional cultures and animal models with respect to increased cellular complexity,an environment more relevant to humans,and reduced cost,they are promising platforms for understanding viral pathogenesis and developing new *** review highlights the recent advances in self-assembled and engineered organoid technologies that are used for COVID-19 *** challenges and future perspectives are also discussed.

摘要：Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory ***,the development of a model for effective drug screening is urgently *** the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug ***,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural ***,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo *** 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)*** screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional *** study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.

摘要：Wnts 包括出现了是包括 organogenesis，中脑发展以及干细胞增长调整几 aspectsof 开发的发信号的串联的部分的蛋白质的一个大家庭。在在成年大脑的 neuronal 电路并且也的发展的 Wnt 发信号小径 playsdifferent 角色，在它调整 synaptic transmissionand 的地方粘性。它也包括癌症和 neurodegenerative 疾病在各种各样的疾病被含有，在基本生物过程的 reflectingits 关联。这评论与 Alzheimer 的疾病(广告) 的一个焦点在成熟 nervoussystem 关于 Wnts 功能总结进步。我们讨论正规的 modulating 和不在经典中的 Wnt signalingas 的前景为 neuroprotection 的策略。这将包括 Wnts 的潜力到：是的(i) 行为在学习和记忆的 hippocampalsynapses 和影响的有势力管理者；(ii ) 调整成年神经发生；并且(iii ) 最后控制广告致病。

摘要：In this issue of the Chinese Journal of Cancer,European,American,and Chinese experts review the current management and future perspectives of epithelial ovarian cancer(EOC),the leading cause of gynecological cancer *** major advances have been made in understanding the cellular and molecular biology of this highly heterogeneous malignancy,the survival rate of women with EOC has changed little since the introduction of platinum-based treatment as a front-line *** papers describe the progress in deciphering the molecular complexity of this disease and the newly available molecular-driven therapies,which have been applied by shifting trial designs toward restricting eligibility to specific subgroups of patients rather than testing agents in unselected *** new trial designs provide potential opportunities for improved efficacy in targeted *** the molecular complexity of this disease,patient survival may be increased by searching for new molecular prognostic/predictive signatures as well as by translating the recent insight of microRNA involvement in EOC progression into new,targeted *** attention has been given to the issue of fertility sparing for women affected by curable diseases.

摘要：Existing technologies used to detect monosodium urate(MSU)crystals for gout diagnosis are not ideal due to their low sensitivity and complexity of *** purpose of this study was to explore whether aggregation-induced emission luminogens(AIEgens)can be used for highly specific imaging of MSU crystals to assist in the diagnosis of ***,we developed a series of luminogens(i.e.,tetraphenyl ethylene(TPE)-NH_(2),TPE-2NH_(2),TPE-4NH_(2),TPE-COOH,TPE-2COOH,TPE-4COOH,and TPE-Ketoalkyne),each of which was then evenly mixed with MSU ***,optimal fluorescence imaging of each of the luminogens was characterized by a confocal laser scanning microscope(CLSM).This approach was used for imaging standard samples of MSU,hydroxyapatite(HAP)crystals,and mixed samples with 1:1 mass ratio of MSU/*** also imaged samples from mouse models of acute gouty arthritis,HAP deposition disease,and comorbidities of ***,CLSM imaging results were compared with those of compensated polarized light microscopy,and we assessed the biosafety of TPE-Ketoalkyne in the RAW264.7 cell ***,CLSM time series and three-dimensional imaging were performed on MSU crystal samples from human gouty synovial fluid and *** a promising candidate for MSU crystal labeling,TPE-Ketoalkyne was found to detect MSU crystals accurately and rapidly in standard samples,animal samples,and human samples,and could precisely distinguish gout from HAP deposition *** work demonstrates that TPE-Ketoalkyne is suitable for highly specific and timely imaging of MSU crystals in gouty arthritis and may facilitate future research on MSU crystal-related diseases.

摘要：Mdm2 是瘤 suppressor p53 的关键否定管理者，使它成为为反癌症药设计的一个吸引人的目标。我们最近通过它和 polycomb 组(PcG ) 的几蛋白质的直接相互作用在基因压抑识别了 Mdm2 的一个新角色家庭。PcG 蛋白质形成 polycomb 压抑的建筑群 PRC1 和 PRC2。PRC2 (经由 EZH2 ) 调停 histone 3 离氨酸 27 (H3K27 ) trimethylation，和 PRC1 (经由 RING1B ) 调停 histone 2A 离氨酸 119 (H2AK119 ) monoubiquitination。两个中华人民共和国主要支持一个协议和 transcriptionally 沉默的染色质结构。我们发现 Mdm2 调整类似于独立于 p53 的 PRC2 的基因表示侧面。而且， Mdm2 支持鼠科的导致的 pluripotent 干细胞和人的 stemness 间充质的干细胞，和支持瘤房间的幸存。Mdm2 被招募由 PRC2 成员和 histone methyltransferase EZH2 指向基因倡导者，并且提高中华人民共和国依赖者压抑的染色质修正，明确地 H3K27me3 和 H2AK119ub1。Mdm2 也与 PRC1 蛋白质 RING1B 在基因压抑合作， H2AK119 ubiquitin ligase。这里，我们在染色质动力学并且在干细胞显型讨论 Mdm2 的这些 p53 独立的功能的可能的含意。我们建议 Mdm2 的 p53 独立的功能应该为癌症药设计被考虑。到目前为止，临床上测试的 Mdm2 禁止者的多数指向它的绑定到 p53，但是不影响这里描述的 Mdm2 的新功能。不管多么当指向 Mdm2 的 E3 ligase 活动时，许多它的 oncogenic 活动可能成为 druggable。

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.