Fluorescence Correlation Spectroscopy Analysis of Effect of Molecular Crowding on Self-Assembly of β-Annulus Peptide into Artificial Viral Capsid

Recent progress in the de novo design of self-assembling peptides has enabled the construction of peptide-based viral capsids. Previously, we demonstrated that 24-mer β-annulus peptides from tomato bushy stunt virus spontaneously self-assemble into an artificial viral capsid. Here we propose to use the artificial viral capsid through the self-assembly of β-annulus peptide as a simple model to analyze the effect of molecular crowding environment on the formation process of viral capsid. Artificial viral capsids formed by co-assembly of fluorescent-labelled and unmodified β-annulus peptides in dilute aqueous solutions and under molecular crowding conditions were analyzed using fluorescence correlation spectroscopy (FCS). The apparent particle size and the dissociation constant (K_d) of the assemblies decreased with increasing concentration of the molecular crowding agent, i.e., polyethylene glycol (PEG). This is the first successful in situ analysis of self-assembling process of artificial viral capsid under molecular crowding conditions.     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

An Injectable Hydrogel for Simultaneous Photothermal Therapy and Photodynamic Therapy with Ultrahigh Efficiency Based on Carbon Dots and Modified Cellulose Nanocrystals

The convenience of injectable hydrogels that can provide high loading of diverse phototherapy agents and further long-time retention at the tumor site has attracted tremendous interest in simultaneous photothermal and photodynamic cancer therapies. However, to incorporate the phototherapy agents into hydrogels, complex modifications are generally unavoidable. Moreover, these phototherapy agents usually suffer from low efficiency and work at different irradiation wavelengths outside the near infrared windows. Hence, a method for the fabrication of an injectable hydrogel for simultaneous photothermal therapy and photodynamic therapy, through the Schiff-base reaction between amido modified carbon dots (NCDs) and aldehyde modified cellulose nanocrystals is proposed. The NCDs act as both phototherapy agents and crosslinkers to form hydrogels. Significantly, the NCDs demonstrate an extremely high photothermal conversion efficiency of 77.6% which is among the highest levels for photothermal agents and a high singlet quantum yield of 0.37 under a single 660 nm light-emitting diode irradiation. The hydrogels are examined through in vitro and in vivo animal experiments which show nontoxic and effectively tumor inhibition. Thus, the strategy of direct reaction of phototherapy agents and the matrix not only provides new strategies for injectable hydrogel fabrication but paves a new road for advanced tumor treatment.     

Design of Ti4+-doped Li3V2(PO4)3/C fibers for lithium energy storage

In this work, we propose a facile approach to fabricate Ti⁴⁺-doped Li₃V₂(PO₄)₃/C (abbreviated as C-LVTP) nanofibers using an electrospinning route followed by a high temperature treatment. In this designed nanocomposite, the ultrafine LVTP dots are homogeneously dispersed into one-dimensional carbon nanofibers and the Ti⁴⁺ doping does not destroy the crystal structure of monoclinic Li₃V₂(PO₄)₃. Compared to the undoped Li₃V₂(PO₄)₃/C (abbreviated as C-LVP), the as-fabricated C-LVTP fibers present higher reversible capacity, superior high-rate capability as well as better cyclic property. Especially, the C-LVT_7%P cathode delivers not only high capacities of 187.2 and 160.3 mAh g^?1 at 0.5 and 10 C respectively, but also stable cyclic property with the reversible capacity of 135.8 mAh g^?1 at 20 C following 500-cycle spans. The good battery characteristics of C-LVT_7%P can be mainly ascribed to Ti⁴⁺ doping, which can increase the electrical conductivity and Li⁺ diffusion coefficient.     

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.     

Split Enzyme-Based Biosensors for Structural Characterization of Soluble and Insoluble β-Glucans

β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of glucose units with β-1,6- or β-1,4-linkage. Numerous studies have investigated different β-glucans and revealed their bioactivities. To understand the structure-function relationship of β-glucan, we constructed a split-luciferase complementation assay for the structural analysis of long-chain β-1,6-branched β-1,3-glucan. The N- and C-terminal fragments of luciferase from deep-sea shrimp were fused to insect-derived β-1,3-glucan recognition protein and fungal endo-β-1,6-glucanase (Neg1)-derived β-1,6-glucan recognition protein, respectively. In this approach, two β-glucan recognition proteins bound to β-glucan molecules come into close proximity, resulting in the assembly of the full-length reporter enzyme and induction of transient luciferase activity, indicative of the structure of β-glucan. To test the applicability of this assay, β-glucan and two β-glucan recognition proteins were mixed, resulting in an increase in the luminescence intensity in a β-1,3-glucan with a long polymer of β-1,6-glucan in a dose-dependent manner. This simple test also allows the monitoring of real-time changes in the side chain structure and serves as a convenient method to distinguish between β-1,3-glucan and long-chain β-1,6-branched β-1,3-glucan in various soluble and insoluble β-glucans.     

Effect of Cu-Rich Phase Precipitation on the Microstructure and Mechanical Properties of CoCrNiCux Medium-Entropy Alloys Prepared via Laser Directed Energy Deposition

CoCrNiCux (x=0.16,0.33,0.75,and 1) without macro-segregation medium-entropy alloys (MEAs) was prepared using laser directed energy deposition (LDED).The microstructure and mechanical properties of CoCrNiCux alloys with increas-ing Cu content were investigated.The results indicate that a single matrix phase changes into a dual-phase structure and the tensile fracture behaviors convert from brittle to plastic pattern with increasing Cu content in CoCrNiCux alloys.In addi-tion,the tensile strength of CoCrNiCux alloys increased from 148 to 820 MPa,and the ductility increased from 1 to 11％with increasing Cu content.The nano-precipitated particles had a mean size of approximately 20 nm in the Cu-rich phase area,and a large number of neatly arranged misfit dislocations were observed at the interface between the two phases due to Cu-rich phase precipitation in the CoCrNiCu alloy.These misfit dislocations hinder the movement of dislocations during tensile deformation,as observed through transmission electron microscopy.This allows the CoCrNiCu alloy to reach the largest tensile strength and plasticity,and a new strengthening mechanism was achieved for the CoCrNiCu alloy.Moreover,twins were observed in the matrix phase after tensile fracture.Simultaneously,the dual-phase structure with different elastic moduli coordinated with each other during the deformation process,significantly improving the plasticity and strength of the CoCrNiCu alloy.     

基于云网PoP的弹性边缘网络设计思路探讨

移动边缘云是公司“云+5G”双引擎战略的最佳契合点,边缘网络是发挥移动云“大云”产品和5G网络融合优势,实现云网统筹、构建运营商“连接+计算”核心能力的关键。运营商传统接入网存在云网割裂、分段入云和组网复杂等突出问题,难以适应边缘业务敏捷交付要求。本文通过深入分析边缘云业务特征和技术架构,对标业界主流云商建设实践,研究基于云网PoP网的边缘网络建设思路,创新性提出云网一体化规划设计和建设交付流程变革,基于云网POP统一网络和业务锚点,构建Overlay和Underlay融合双层加速网络架构,探索Spine-leaf化的新型城域接入网实现L3下沉和弹性扩容等方法,实现“云+网+应用”一体化敏捷交付的边缘网络能力。     

AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.