摘要：Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds: hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer's disease(AD). We analyzed by an inverse docking procedure(INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE,PSEN, IDE, CASP, calpain and TNF-a, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aβ deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.

摘要：Manipulation of gene expression through targeting specific DNA or RNA sequences is a significant challenge, tn the past decade, transcription activator-like （TAL） effectors and zinc fingers （ZFs） have been successfully developed into useful tools for DNA recognition （Bogdanove and Voytas, 2011; Deng et al., 2012a, 2012b）. However, little progress has been made in the realm of RNA targeting due to the lack of understanding about the modular RNA recognition mechanism.

摘要：Statistical energy functions are general models about atomic or residue-level interactions in biomolecules, derived from existing experimental data. They provide quantitative foundations for structural modeling as well as for structure-based protein sequence design. Statistical energy functions can be derived computationally either based on statistical distributions or based on variational assumptions. We present overviews on the theoretical assumptions underlying the various types of approaches. Theoretical considerations underlying important pragmatic choices are discussed.

摘要：Cytosolic protein delivery techniques are of great importance for cell biology,biotechnology and protein drug *** design of carriers with robust efficiency in cytosolic protein delivery is *** account provides a progress report of polymeric carriers for this purpose in our *** the past years,we have developed several types of functionalized polymers for cytosolic protein and peptide delivery by engineering polymers with ligands such as guanidinium,boronate,coordination ligands and *** designed polymers showed improved protein/peptide binding affinities,and successfully delivered various cargo proteins into the cytosol of living cells,while maintaining their *** addition,the polymers showed potent efficiencies in the delivery of tumor antigens,therapeutic peptides,toxins and antioxidant proteins in *** hope these polymers could be translated for protein delivery in the treatment of various diseases in the future.

摘要：Restricted genetic diversity can supply only a limited number of elite genes for modern plant cultivation and *** this study,we demonstrate that rational design enables the engineering of geranyl-geranyl diphosphate synthase(NtGGPPS),an enzyme of the methylerythritol phosphate pathway(MEP)in the model plant Nicotiana *** the crucial bottleneck in carotenoid biosynthesis,NtGGPPS1 interacts with phytoene synthase(NtPSY1)to channel GGPP into the production of *** of this enzyme in the ntggpps1 mutant leads to decreased carotenoid *** the aim of enhanc-ing NtGGPPS1 activity,we undertook structure-guided rational redesign of its substrate binding pocket in combination with sequence *** activity of the designed NtGGPPS1(a pentuple mutant of five sites V154A/I161L/F218Y/I209S/V233E,d-NtGGPPS1)was measured by a high-throughput colorimetric assay.d-NtGGPPS1 exhibited significantly higher conversion of IPP and each co-substrate(DMAPP~1995.5-fold,GPP~25.9-fold,and FPP~16.7-fold)for GGPP synthesis compared with wild-type ***,the transient and stable expression of d-NtGGPPS1 in the ntggpps1 mutant increased carotenoid levels in leaves,improved photosynthetic efficiency,and increased biomass relative to *** findings provide a firm basis for the engineering of GGPPS and will facilitate the development of quality and yield *** results open the door for the structure-guided rational design of elite genes in higher plants。

摘要：The process of wound healing is routinely evaluated by histological evaluation in the clinic,which may cause scarring and secondary *** confocal microscopy(RCM)represents a noninvasive,real-time imaging technique that allows in vivo evaluation of the *** RCM was wide-probe-based,which limited its application on uneven and covered *** this study,we report the development of a portable reflectance confocal microscope(PRCM)in which all components were assembled in a handheld *** the size and weight of the PRCM were reduced based on the use of a microelectromechanical system,the resolution was kept at 0.91μm,and the field of view of the system was 343μm×532μ*** used in vivo,the PRCM was able to visualize cellular and nuclear morphology for both mouse and human *** evaluations were then performed on wounds after topically applied mesenchymal stem cells(MSCs)or saline *** PRCM allowed visualization of the formation of collagen bundles,re-epithelization from the wound edge to the wound bed,and hair follicle regeneration,which were consistent with histological ***,we offer new insights into monitoring the effects of topically applied MSCs on the process of wound healing by using *** study illustrates that the newly developed PRCM represents a promising device for real-time,noninvasive monitoring of the dynamic process of wound healing,which demonstrates its potential to diagnose,monitor,or predict disease in clinical wound therapy.

摘要：Engineered sequence-specific zinc finger nucleases (ZFNs) make the highly efficient modification of eukaryotic genomes ***,most current strategies for developing zinc finger nucleases with customized sequence specificities require the construction of numerous tandem arrays of zinc finger proteins (ZFPs),and subsequent largescale in vitro validation of their DNA binding affinities and specificities via bacterial *** labor and expertise required in this complex process limits the broad adoption of ZFN *** effective computational assisted design strategy will lower the complexity of the production of a pair of functional *** we used the FoldX force field to build 3D models of 420 ZFP-DNA complexes based on zinc finger arrays developed by the Zinc Finger Consortium using OPEN (oligomerized pool engineering).Using nonlinear and linear regression analysis,we found that the calculated protein-DNA binding energy in a modeled ZFP-DNA complex strongly correlates to the failure rate of the zinc finger array to show significant ZFN activity in human *** our models,less than 5% of the three-finger arrays with calculated protein-DNA binding energies lower than 13.132 kcal mol 1 fail to form active ZFNs in human *** contrast,for arrays with calculated protein-DNA binding energies higher than 5 kcal mol 1,as many as 40% lacked ZFN activity in human ***,we suggest that the FoldX force field can be useful in reducing the failure rate and increasing efficiency in the design of ZFNs.

摘要：The development of safe technologies to genetically modify neurons is of great interest in regenerative neurology, for both translational and basic science applications. Such approaches have conventionally been heavily reliant on viral transduction methods, which have safety and production limitations. Magnetofection （magnet-assisted gene transfer using iron oxide nanoparticles as vectors） has emerged as a highly promising non-viral alternative for safe and reproducible genetic modification of neurons. Despite the high potential of this technology, there is an important gap in our knowledge of the safety of this approach, namely, whether it alters neuronal function in adverse ways, such as by altering neuronal excitability and signaling. We have investigated the effects of magnetofection in primary cortical neurons by examining neuronal excitability using the whole cell patch clamp technique. We found no evidence that magnetofection alters the voltage-dependent sodium and potassium ionic currents that underpin excitability. Our study provides important new data supporting magnetofection as a safe technology for bioengineering of neuronal cell populations.

摘要：In a recent publication [1], these images in Figures 6(b, c)(^NPEG-NPCe6 group), S7, S9 and S10 were inadvertently taken the incorrect images in the production. The corrected versions are shown below. And, the quantification of Ce6 fluorescence(as performed in Figure 6(c)) was also corrected(Figure S12).

摘要：The robust porous architectures of active materials are highly desired for oxygen electrodes in lithium–oxygen batteries to enable high capacities and excellent reversibility. Herein, we report a novel three-dimensional replication strategy to fabricate three-dimensional architecture of porous carbon for oxygen electrodes in lithium–oxygen batteries. As a demonstration, ball-flower-like carbon microspheres assembled with tortuous hollow carbon nanosheets are successfully prepared by completely replicating the morphology of the nanostructured zinc oxide template and utilizing the polydopamine coating layer as the carbon *** used as the active material for oxygen electrodes, the three-dimensional porous architecture of the prepared ballflower-like carbon microspheres can accommodate the discharge product lithium peroxide and simultaneously maintain the ions and gas diffusion paths. Moreover, their high degrees of defectiveness by nitrogen doping provide sufficient active sites for oxygen reduction/evolution *** the prepared ball-flower-like carbon microspheres demonstrate a high capacity of 9,163.7 mA h g-1 and excellent reversibility. This work presents an effective way to prepare three-dimensional architectures of porous carbon by replicating the controllable nanostructures of transition metal oxide templates for energy storage and conversion applications.