A Biomimetic Nanoparticle to “Lure and Kill” Phospholipase A2

Inhibition of phospholipase A2 (PLA2) has long been considered for treating various diseases associated with an elevated PLA2 activity. However, safe and effective PLA2 inhibitors remain unavailable. Herein, we report a biomimetic nanoparticle design that enables a “lure and kill” mechanism designed for PLA2 inhibition (denoted “L&K-NP”). The L&K-NPs are made of polymeric cores wrapped with modified red blood cell membrane with two inserted key components: melittin and oleyloxyethyl phosphorylcholine (OOPC). Melittin acts as a PLA2 attractant that works together with the membrane lipids to “lure” in-coming PLA2 for attack. Meanwhile, OOPC acts as inhibitor that “kills” PLA2 upon enzymatic attack. Both compounds are integrated into the L&K-NP structure, which voids toxicity associated with free molecules. In the study, L&K-NPs effectively inhibit PLA2-induced hemolysis. In mice administered with a lethal dose of venomous PLA2, L&K-NPs also inhibit hemolysis and confer a significant survival benefit. Furthermore, L&K-NPs show no obvious toxicity in mice. and the design provides a platform technology for a safe and effective anti-PLA2 approach.     

Chromophore-Assisted Proximity Labeling of DNA Reveals Chromosomal Organization in Living Cells

The spatial arrangement of chromosome within the nucleus is linked to genome function and gene expression regulation. Existing genome-wide mapping methods often rely on chemically crosslinking DNA with protein baits, which raises concerns of artifacts being introduced during cell fixation. By genetically targeting a photosensitizer protein to specific subnuclear locations, we achieved blue-light-activated labeling of local DNA with a bioorthogonal functional handle for affinity purification and sequence identification through next-generation sequencing. When applied to the nuclear lamina in human embryonic kidney 293T cells, it revealed lamina-associated domains (LADs) that cover 37.6 % of the genome. These LADs overlap with heterochromatin hallmarks and are depleted with CpG islands. This simple labeling method avoids the harsh treatment of chemical crosslinking and is generally applicable to the genome-wide high-resolution mapping of the spatial chromosome organization in living cells.     

Facile Preparation of WO3−x Dots with Remarkably Low Toxicity and Uncompromised Activity as Co-reactants for Clinical Diagnosis by Electrochemiluminescence

The exceptional nature of WO_3−x dots has inspired widespread interest, but it is still a significant challenge to synthesize high-quality WO_3−x dots without using unstable reactants, expensive equipment, and complex synthetic processes. Herein, the synthesis of ligand-free WO_3−x dots is reported that are highly dispersible and rich in oxygen vacancies by a simple but straightforward exfoliation of bulk WS₂ and a mild follow-up chemical conversion. Surprisingly, the WO_3−x dots emerged as co-reactants for the electrochemiluminescence (ECL) of Ru(bpy)₃²⁺ with a comparable ECL efficiency to the well-known Ru(bpy)₃²⁺/tripropylamine (TPrA) system. Moreover, compared to TPrA, whose toxicity remains a critical issue of concern, the WO_3−x dots were ca. 300-fold less toxic. The potency of WO_3−x dots was further explored in the detection of circulating tumor cells (CTCs) with the most competitive limit of detection so far.     

Divergent Total Synthesis of Euphoranginol C,Euphoranginone D,ent-Trachyloban-3β-ol,ent-Trachyloban-3-one,Excoecarin E,and ent-16α-Hydroxy-atisane-3-one

A divergent synthetic approach to biogenetically related diterpenoids such as ent-kauranes, ent-trachylobanes, ent-beyerane, and ent-atisane has been developed. The unified synthetic route involves the De Mayo reaction to rapidly generate the bicyclo[3.2.1]-octane moiety of ent-kaurane. The key reactions also include bioinspired nucleophilic cyclopropanation generating the [3.2.1.0^2,7]-tricyclic core of ent-trachylobane and regioselective cyclopropane fragmentation furnishing ent-beyerane and ent-atisane through the nucleophilic attack and protonation of the cyclopropane ring. This strategy enables the asymmetric total syntheses of six diterpenoids from the commercially available geraniol.     

Dual Illumination Enhances Transformation of an Engineered Green-to-Red Photoconvertible Fluorescent Protein

The molecular mechanisms for the photoconversion of fluorescent proteins remain elusive owing to the challenges of monitoring chromophore structural dynamics during the light-induced processes. We implemented time-resolved electronic and stimulated Raman spectroscopies to reveal two hidden species of an engineered ancestral GFP-like protein LEA, involving semi-trapped protonated and trapped deprotonated chromophores en route to photoconversion in pH 7.9 buffer. A new dual-illumination approach was examined, using 400 and 505 nm light simultaneously to achieve faster conversion and higher color contrast. Substitution of UV irradiation with visible light benefits bioimaging, while the spectral benchmark of a trapped chromophore with characteristic ring twisting and bridge-H bending motions enables rational design of functional proteins. With the improved H-bonding network and structural motions, the photoexcited chromophore could increase the photoswitching-aided photoconversion while reducing trapped species.     

Multiple Stimuli-Responsive Conformational Exchanges of Biphen[3]arene Macrocycle

Conformational exchanges of synthetic macrocyclic acceptors are rather fast, which is rarely studied in the absence of guests. Here, we report multiple stimuli-responsive conformational exchanges between two preexisting conformations of 2,2′,4,4′-tetramethoxyl biphen[3]arene (MeBP3) macrocycle. Structures of these two conformations are both observed in solid state, and characterized by ¹H NMR, ¹³C NMR and 2D NMR in solution. In particular, conformational exchanges can respond to solvents, temperatures, guest binding and acid/base addition. The current system may have a role to play in the construction of molecular switches and other stimuli-responsive systems.     

Ultranarrow bandwidth Faraday atomic filter approaching natural linewidth based on cold atoms

An ultranarrow bandwidth Faraday atomic filter is realized based on cold ~(87)Rb atoms. The atomic filter operates at 780 nm on the 5~2 S_(1/2), F = 2 to 5~2 P_(3/2), F'= 3 transition with a bandwidth of 7.1(8) MHz, which is approaching the natural linewidth of the transition. The peak transmission achieves 2.6(3)% by the multi-pass probe method. This atomic filter based on cold atoms may find potential applications in self-stabilizing lasers in the future.     

光引发体系对有机硅光固化材料感光性能的影响

裂解型光引发剂中以IR1700的引发效果最好,其感度值为10.6 mJ.cm-2,二苯甲酮(BP)和三乙醇胺(TEOA)组成的夺氢光引发体系的最高感度为26.8 mJ.cm-2,BP和TEOA的最佳质量比为1∶2。混合光引发体系的引发效果最好,其最佳组成为IR651∶TEOA∶IR1700=1∶1∶1(质量比),感度最高可达7.9 mJ.cm-2。光引发剂最佳含量为4%(wt)~6%(wt)。     

Rapid non-resonant intermodal targeted energy transfer (IMTET) caused by vibro-impact nonlinearity

Nonlinear Dynamics - This paper describes a rapid and efficient nonlinear non-resonance mechanism for low-to-high-frequency energy scattering, which is referred to as intermodal targeted energy...