摘要：This review offers an overview of the latest developments in metal-covalent organic framework(MCOF)and covalent metal-organic framework(CMOF)materials,whose construction entails a combination of reversible coordination and covalent bonding adapted from metal-organic frameworks(MOFs)and covalent organic frameworks(COFs),*** an emphasis on the MCOF and CMOF structures,this review surveys their building blocks and ***,the frameworks are classified based on the dimensions of their components(building blocks),namely,discrete building blocks and one-dimensional infinite building *** the first category,the materials are further divided into collections of two-and three-dimensional networks based on their *** the second category,the recently emerging MCOFs with woven structures are ***,the state-of-the-art in MCOF and CMOF chemistry has been laid out for promising avenues in future developments.

摘要：Drug resistance is one of the major obstacles in the drug therapy of *** in this area in pre-clinical research have focused on developing novel platforms to evaluate and decrease drug *** this paper,inspired by the structure of hives where swarms live and breed,we propose porous hydrogel arrays with a uniform pore structure for the generation of hepatoma cell spheroids and the investigation of drug *** porous hydrogel arrays were fabricated using polyeth-ylene glycol diacrylate(PEGDA)hydrogel to negatively replicate a well-designed *** from the elaborate processing of the template,the prepared porous hydrogel arrays possessed a uniform pore *** to their anti-adhesion properties and the excellent biocompatibility of the PEGDA hydrogel,the hepatoma cells could form well-defined and uni-form hepatoma cell spheroids in the porous hydrogel *** found that the resistant hepatoma cell spheroids showed more significant Lenvatinib resistance and a migratory phenotype compared with a two-dimensional(2D)cell culture,which reveals the reason for the failure of most 2D cell-selected drugs for in vivo *** features give such porous hydrogel arrays promising application prospects in the investigation of tumor cell spheroid culture and in vitro drug resistance.

摘要：There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising *** aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic *** SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory *** in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell *** model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune *** also consider the practical issues that may influence the design and fabrication of *** role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

摘要：Fail-safe topology optimization is valuable for ensuring that optimized structures remain operable even under damaged *** selectively removing material stiffness in patches with a fixed shape,the complex phenomenon of local failure is modeled in fail-safe topology *** this work,we first conduct a comprehensive study to explore the impact of patch size,shape,and distribution on the robustness of fail-safe *** findings suggest that larger sizes and finer distribution of material patches can yield more robust fail-safe ***,a finer patch distribution can significantly increase computational costs,particularly for 3D *** keep computational efforts tractable,an efficient fail-safe topology optimization approach is established based on the framework of multi-resolution topology optimization(MTOP).Within the MTOP framework,the extended finite element method is introduced to establish a decoupling connection between the analysis mesh and the topology description *** examples demonstrate that the developed methodology is 2 times faster for 2D problems and over 25 times faster for 3D problems than traditional fail-safe topology optimization while maintaining similar levels of robustness.

摘要：The World Health Organization has declared the rapidly spreading coronavirus to be a global *** FDA is yet to approve a vaccine for human novel ***,we developed a peptide-based vaccine and used high-throughput screening by molecular dynamics simulation to identify T-cell-and p-cell-recognized epitopes for producing specific antibod-ies against *** construct~12 P'antigenic epitope peptides to develop a more effective vaccine and identify specific *** epitope peptides selectively presented the best antigen presentation scores for both human pMHC class I and II alleles to develop a strong binding *** antigens identified of SARS-nCoV-2 different proteins by each attached specific~1-7 L linker adaptor were used to construct a broad single peripheral peptide *** is expected to be highly antigenic with a minimum allergic *** a result of these exciting outcomes,expressing a vaccine using the intimated peptide was highly promising and positive to be highly proposed as epitope-based peptide vaccine of specific antibody against SARS-nCoV-2 by initiating T cells and β-*** in vitro study for the proposed peptide-based vaccine *** *** clinical trials are required to check the efficacy of this vaccine.

摘要：Simultaneous inhibition of MDM2 and CDK4 may be an effective treatment against glioblastoma. A collection of chiral spirocyclic tetrahydronaphthalene(THN)-oxindole hybrids for this purpose have been developed. Appropriate stereochemistry in THN-fused spirooxindole compounds is key to their inhibitory activity: selectivity differed by over 40-fold between the least and most potent stereoisomers in time-resolved FRET and KINOMEscan~? in vitro assays. Studies in glioblastoma cell lines showed that the most active compound ent-4g induced apoptosis and cell cycle arrest by interfering with MDM2-P53 interaction and CDK4 activation. Cells treated with ent-4g showed up-regulation of proteins involved in P53 and cell cycle pathways. The compound showed good anti-tumor efficacy against glioblastoma xenografts in mice. These results suggested that rational design, asymmetric synthesis and biological evaluation of novel tetrahydronaphthalene fused spirooxindoles could generate promising MDM2-CDK4 dual inhibitors in glioblastoma therapy.

摘要：本文介绍一个可以用于研究遗传与环境互动的新颖方法。此研究收集了上千个4～10岁儿童的数据。这些儿童的出生都借助于不同的辅助受孕技术（Assisted Reproductive Technologies），包括试管婴儿、精子捐赠、卵子捐赠、胚胎捐赠及代孕技术。本项目通过妇科（助孕）医院收集被试的行为数据，包括家庭互动、养育方式、父母婚姻质量、家庭成员的心理健康及经济状况等。本文选择性地介绍一些分析的结果，以彰显这种设计在分离遗传和产前产后环境对儿童发展的贡献。首先，我们比较了“助孕”儿童与“自然孕”儿童在父母冲突、父母对子女敌意以及儿童抑郁症状之间关系的异同。其次，我们比较了这两组儿童在父母抑郁症状、家庭关系质量以及儿童抑郁症状之间关系的异同。再次，本文介绍了这一可分离遗传与环境因素的研究设计。最后，我们讨论了这一设计对发展心理病干预及预防的意义。

摘要：Lactic acidosis is a rare complication of malignancies and is seen more frequently in high grade lymphoma and leukemia. Although, its pathogenesis is not well understood, it remains a surrogate of poor prognosis. Herein, we present a case of Burkitt-like lymphoma presenting with metabolic abnormalities including lactic acidosis and hypoglycemia along with atrial tachycardia. We will discuss the different mechanisms involved in these metabolic disturbances and we will provide insight on novel therapeutic strategies based on our understanding of the underlying pathophysiology.

摘要：Paper devices have recently attracted considerable attention as a class of cost-effective cell culture substrates for various biomedical *** paper biomaterial can be used to partially mimic the in vivo cell microenvironments mainly due to its natural three-dimensional *** paper-based devices provide precise control over their structures as well as cell distributions,allowing recapitulation of certain interactions between the cells and the extracellular *** features have shown great potential for the development of normal and diseased human tissue *** this review,we discuss the fabrication of paper-based devices for in vitro tissue modeling,as well as the applications of these devices toward drug screening and personalized *** is believed that paper as a biomaterial will play an essential role in the field of tissue model engineering due to its unique performances,such as good biocompatibility,eco-friendliness,cost-effectiveness,and amenability to various biodesign and manufacturing needs.

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.