摘要：Polypharmacology,which focuses on designing drugs to target multiple receptors,has emerged as a new paradigm in drug *** rationally design multi-target drugs,it is fundamental to understand protein-ligand interactions on a proteome *** have developed a Proteome-wide Off-target Pipeline （POP） that integrates ligand binding site analysis,protein-ligand docking,the statistical analysis of docking scores,and electrostatic potential *** utility of POP is demonstrated by a case study,in which the molecular mechanism of anti-cancer effect of Nelfinavir is *** combining structural proteome-wide off-target identification and systems biology,it is possible for us to correlate drug perturbations with clinical outcomes.

摘要：We described herein structure-based design, synthesis and evaluation of conformationally constrained, cyclic peptidomimetics to block the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 histone methyltransferase activity. Our study has yielded cyclic peptidomimetics with very high binding affinities to WDR5 （Ki values 〈1 nmol/L） and function as antagonists of the MLL1 histone methyltransferase activity.

摘要：Brain tumors’severity ranges from benign to highly aggressive and *** tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral ***,we first describe the physiology and cellular composition of brain ***,we discuss the development of threedimensional tissue models utilizing brain tumor *** particular,we highlight the role of hydrogels in providing a biomimetic support for the cells to grow into defined *** technologies,such as electrospinning and bioprinting,and advanced cellular models aim to mimic the extracellular matrix and natural cellular localization in engineered tumor ***,we review current applications and prospects of hydrogels for therapeutic purposes,such as drug delivery and co-administration with other *** further development,hydrogels can serve as a reliable option for in vitro modeling and treatment of brain tumors for translational medicine.

摘要：This paper presents the design and control of a pneumatically actuated transtibial prosthesis, which utilizes a pneumatic cylinder-type actuator to power the prosthetic ankle joint to support the user＇s locomotion. The pneumatic actuator has multiple advantages over the traditional electric motor, such as light weight, low cost, and high power-to-weight ratio. The objective of this work is to develop a compact and lightweight transtibial prosthesis, leveraging the multiple advantages provided by this highly competitive actuator. In this paper, the design details of the prosthesis are described, including the determination of performance specifications, the layout of the actuation mechanism, and the calculation of the torque capacity. Through the authors＇ design calculation, the prosthesis is able to provide sufficient range of motion and torque capacity to support the lo- comotion of a 75 Kg individual. The controller design is also described, including the underlying biomechanical analysis and the formulation of the finite-state impedance controller. The testing results of human subject indicate that the prosthesis is able to generate a natural walking gait and sufficient power output for its amputee user.

摘要：The female reproductive system consists of the ovaries,the female gonads,and the reproductive tract organs of the fallopian tubes,uterus,cervix,and *** functions to provide hormonal support and anatomical structure for the production of new offspring.A number of endogenous and exogenous factors can impact female reproductive health and fertility,including genetic vulnerability,medications,environmental exposures,age,nutrition,and *** date,due to the ethical concerns of using human subjects in biomedical research,the majority of studies use in vivo animal models and 2D cell/tissue culture models to study female ***,the complexity and species difference of the female reproductive system in humans make it difficult to compare to those of ***,the monolayered cells cultured on flat plastics or glass lose their 3D architecture as well as the physical and/or biochemical contacts with other cells in ***,all reproductive organs do not work alone but interconnect with each other and also with non-reproductive organs to support female reproductive,endocrine,and systemic *** facts suggest that there is an urgent and unmet need to develop representative,effective,and efficient in vitro models for studying human female *** prodigious advancements of bioengineering(e.g.,biomaterials,3D printing,and organ-on-a-chip)allow us to study female reproduction in an entirely new ***,we review recent advances that use bioengineering methods to study female reproduction,including the bioengineering models of the ovary,fallopian tube,uterus,embryo implantation,placenta,and reproductive disease.

摘要：三星时差定位是星载高精度无源定位的重要形式,需要深入研究三星编队构型设计来改善其高精度定位性能。从三星时差定位原理出发,推导了地理经纬度位置下的误差分析模型,提出了基于最小定位误差均方差下的最佳构型数学表达式,并分析了不同构型对误差均方差的敏感程度;讨论了在三星编队飞行中进行构型设计与保持的问题,并根据定位误差周期稳定性和一致性设计要求,基于轨道相对动力学方程,提出了一种卫星编队的设计;通过仿真研究表明,三星形成的三角形构型中,其两腰长对应地心角距低于约0.3°时或三角形趋于共线时定位性能敏感;固定腰长情况下等腰直角三角形星座构型具有最佳误差特性;提出的具体编队方案,在运行周期内具有定位误差小和误差特性的良好一致性,对工程设计应用具有重要意义。

摘要：Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411,and a replaceable anti-biomarker probe(ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS 1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.

摘要：Background:When patients with cirrhosis develop ascites,it is associated with sharply increasedmortality and healthcare utilization with decreased quality of *** salt restriction is first-line therapy for ascites but it is limited by poor ***:We will recruit 40 patients with cirrhosis and ascites who have received a recent paracentesis or hospitalization for a 1:1 randomized trial of standard care(education on salt restriction)versus home-delivered *** primary outcome is the number of paracenteses needed over 12 *** outcomes include hospital-bed days,health-related quality of life(HRQOL,Ascites Symptom Inventory-7 and Visual Analogue Scale)and performance on batteries of physical function including hand grip(kg)and walk speed(m/s).All subjects follow up through a series of calls where any paracenteses,hospital readmissions,weight changes and diuretic dosage changes are *** a final Week 12 visit,knowledge of dietary sodium intake,quality of life and frailty are reassessed,and satisfaction with the meal-delivery program is *** comparison testing will be conducted between the two ***:A nutritionally standardized meal-delivery program for patients with cirrhosis and ascites post discharge has a variety of potential patient-based benefits,including the effective management of ascites,reduction of healthcare utilization and improvement of *** have three core ***,patients will report interest in and satisfaction with a home-delivered meals ***,subjects on a salt-restricted(2 g sodium)meal-delivery program will have fewer therapeutic paracenteses and all-cause readmissions than subjects receiving standard of ***,subjects on a saltrestricted(2 g sodium)meal-delivery program will report increased HRQOL compared to subjects receiving standard of care.

摘要：The growth of biotechnology in recent decades and the dual-use nature of most bioscience research are making their misuse,or accidental misuse or release,more likely and present as threats to biosecurity.A proactive approach is through educating the next generation of scientists to be more security ***,current educational and professional programs in biosecurity are *** this perspective,we recommend that biosecurity educational opportunities should be implemented and expanded for undergraduate and graduate students who will likely use one or more methods in the field of *** then propose that biosecurity education is a key factor in a path toward sustainable and safe ***,a set of 17 biosecurity competencies organized into 6 distinct themes is outlined.

摘要：This study presents a simple and robust three-dimensional human hepatic tissue model to emulate steatotic and fibrotic conditions and provide an in vitro model for drug testing and mechanistic *** a photolithographic biofabrication method with a photomask featuring hexagonal units,liver cells,including a human hepatic cell line(HepG2-C3A)and a human hepatic stellate cell line(LX-2)were embedded in gelatin methacryloyl *** steatosis was induced by supraphysiological concentration of free fatty acids;hepatic fibrosis was induced by transforming growth factor-β*** of steatosis was confirmed by Oil Red O and BODIPY staining and was inhibited with toyocamycin and obeticholic *** of fibrosis was confirmed by immunostaining for collagen type I and alpha smooth muscle actin and inhibited by rapamycin and curcumin *** model was further preliminarily validated using primary human hepatocytes in a similar *** constructs provide a viable,biologically relevant,and higher throughput model of hepatic steatosis and fibrosis and may facilitate the study of the mechanisms of disease and testing of liver-directed drugs.