Generation of functional oligopeptides that promote osteogenesis based on unsupervised deep learning of protein IDRs

Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug development has been limited,likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models.Here,we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of~171 known osteogenic proteins.Subsequently,oligopeptides were generated from this semantic pattern based on Monte Carlo simulation,followed by in vivo functional characterization.A five amino acid oligopeptide(AIB5P)had strong bone-formation-promoting effects,as determined in multiple mouse models(e.g.,osteoporosis,fracture,and osseointegration of implants).Mechanistically,we showed that AIB5P promotes osteogenesis by binding to the integrinα5 subunit and thereby activating FAK signaling.In summary,we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification.

Translational perspective on bone-derived cytokines in inter-organ communications

OSTEOKINES IN INTER-ORGAN COMMUNICATIONS The concept of“organic wholeness”permeates all the fields of traditional Chinese medicine,which is also widely accepted by modern medicine.The wealth of knowledge regarding inter-organ communications generated in the latest decades provided solid evidence that human physiology and pathophysiology involve systematic interactions between multiple organs or tissues.Therefore,advancing our understanding of the inter-organ communication process is believed to provide a new perspective for treating various human diseases.

复杂高耸观光塔钢结构分析与设计

观光塔凭借其结构高度高、造型细长等特点,极大提升了游客观感体验,同时也给结构设计带来了巨大挑战。结合某复杂高耸观光塔工程,介绍了观光塔钢结构设计的特点与难点。观光塔总高度为204.4 m,主要包含裙房、主塔塔身、塔楼及塔顶游乐设备四部分,其功能涵盖商场、物业、旋转餐厅、观光平台和游乐设施等,钢塔主体结构采用钢结构筒体结构,筒身由钢管混凝土柱及钢支撑构成,其平面为八边形,共布置8个钢管混凝土柱,竖向沿八边形外围布置跨层X形支撑作为主要抗侧力体系。在介绍整体结构体系及功能分布的基础上,结合结构各部位特点与难点对结构设计方案展开阐述。观光塔主塔结构高宽比大,塔楼处直径较大且所处位置较高,放大了高宽比大这一不利影响。针对该特点,在塔身底部设置四个伸臂支撑桁架,并通过对比分析确定伸臂支撑桁架与钢柱连接点的标高位置,有效减轻了观光塔主塔结构高宽比大的不利影响;对于楼面大开洞导致的刚度削弱,在楼面内布置水平钢支撑,结合楼面钢梁共同形成抵抗水平侧力的一道通长桁架;将塔楼底层设置为转换桁架层,以实现塔楼大悬挑,悬挑桁架杆件均采用H型钢;为有效锚固观光塔顶部太空梭游乐设备,在太空梭支座底部设置转换桁架,将荷载直接传递到塔体外筒钢管混凝土柱上;布置专门的钢梁用于支承旋转餐厅设备,分别采用变桁架高度与变截面高度梁的方式解决了旋转设备高度导致的结构高差问题。利用有限元软件对观光塔结构开展了模态分析、风荷载及地震作用分析、结构变形与受力分析,并对结构中的关键节点如底部伸臂支撑桁架与裙房连接节点开展了精细化有限元分析。分析结果表明:结构振型模态与周期、结构在风荷载与地震作用下的侧向变形、结构竖向变形与杆件承载力验算等各项性能指标均满足规范要求;铸钢节点完全处于弹性范围内,满足设计要求;风荷载在该观光塔结构设计中为控制荷载,地震作用影响较小。