Development of a Pre‐assembled Through‐Bond Energy Transfer (TBET) Fluorescent Probe for Ratiometric Sensing of Anticancer Platinum(ll) Complexes

Fluorescence microscopy has emerged as an attractive technique to probe the intracellular processing of Pt‐based anticancer compounds. Herein, we reported the first through‐bond energy transfer (TBET) fluorescent probe NPR1 designed for sensitive detection and quantitation of Pt^II complexes. The novel TBET probe was successfully applied for ratiometric fluorescence imaging of anticancer Pt^II complexes such as cisplatin and JM118 in cells. Capitalizing on the ability of the probe to discriminate between Pt^II complexes and their Pt^IV derivatives, the probe was further applied to study the activation of Pt^IV prodrug complexes that are known to release active Pt^II species after intracellular reduction.     

The pressure of a hard sphere fluid on a curved surface

Utilizing the integral equation approach to the hard sphere fluid system developed in the preceding paper, the hard sphere-hard wall interaction is studied. For the case of a flat wall, perturbation solutions of the integral equation valid to second and third order in the packing fraction,y, are derived. For a surface of arbitrary curvature, an equation of state valid to second order in the packing fraction is also derived. When applied to very small cavities, it is found that the pressure at high densities is significantly higher than it would be for a flat wall.     

HL-1装置硬X射线能谱及长脉冲放电与硬X射线的发射关系

在HL-1装置上初步测硬(?)射线能谱,能量达5MeV。实验观测到长脉冲放电与硬(?)射线的关系,并得到逃逸电子的径向扩散。     

A hard sphere model of chemical reactions theory from the point of view of many-particle approach

On the basis of the previously obtained non-Markovian kinetic equation for irreversible chemical reaction A+B→C+B, we have examined a model of contact reaction between hard (impenetrable) spheres (singular force potential). The nature of the additional contribution to the rate constant is explained. As is found, for reactants with a hard core it is necessary to allow for the presence of initial correlations between them. A class of initial conditions for arbitrary form of the pair potential energy is established.     

High-Precision Mapping of Membrane Proteins on Synaptic Vesicles using Spectrally Encoded Super-Resolution Imaging

The spatial resolution of single-molecule localization microscopy is limited by the photon number of a single switching event because of the difficulty of correlating switching events dispersed in time. Here we overcome this limitation by developing a new class of photoswitching semiconducting polymer dots (Pdots) with structured and highly dispersed single-particle spectra. We imaged the Pdots at the first and the second vibronic emission peaks and used the ratio of peak intensities as a spectral coding. By correlating switching events using the spectral coding and performing 4–9 frame binning, we achieved a 2–3 fold experimental resolution improvement versus conventional superresolution imaging. We applied this method to count and map SV2 and proton ATPase proteins on synaptic vesicles (SVs). The results reveal that these proteins are trafficked and organized with high precision, showing unprecedented level of detail about the composition and structure of SVs.     

Fluorescent Flippers: Small-Molecule Probes to Image Membrane Tension in Living Systems

Flipper probes have been introduced as small molecule fluorophores to image physical forces, that is, membrane tension in living systems. Their emergence over one decade is described, from evolution in design and synthesis to spectroscopic properties. Responsiveness to physical compression in equilibrium at the ground state is identified as the ideal origin of mechanosensitivity to image membrane tension in living cells. A rich collection of flippers is described to deliver and release in any subcellular membrane of interest in a leaflet-specific manner. Chalcogen-bonding cascade switching and dynamic covalent flippers are developed for super-resolution imaging and dual-sensing of membrane compression and hydration. Availability and broad use in the community validate flipper probes as a fine example of the power of translational supramolecular chemistry, moving from fundamental principles to success on the market.     

A Fluorescent Probe for Investigating the Role of Biothiols in Signaling Pathways Associated with Cerebral Ischemia-Reperfusion Injury

Cerebral ischemia-reperfusion injury (CIRI) is intimately associated with the redox regulation of biothiol, a crucial antioxidant marker that precludes the onset of ROS. We designed a novel fluorescent probe, DCI-Ac-Py , showing various physicochemical properties, such as high selectivity, exceptional signal-to-noise ratio, near-infrared (NIR) optical window, and blood–brain barrier (BBB) penetrability, for detecting biothiols in the brain. The picolinate serves as a specific recognition group that is rapidly activated by biothiol and undergoes nucleophilic substitution with the adjacent acrylic ester to yield the desired NIR probe. Additionally, the probe's lipid solubility is improved through the inclusion of halogen atoms, which aids in penetrating the BBB. Using DCI-Ac-Py , we investigated changes of biothiols in vivo in the brains of mice during CIRI. We found that biothiol-mediated NF-kB classical (P65-related) and nonclassical (RelB-related) pathways contribute to abundant ROS production induced by CIRI and that biothiols are involved in redox regulation. These findings provide new insights into the study of CIRI and shed light on the physiological and pathological mechanisms of biothiols in the brain.     

Ligand Dilution Analysis Facilitates Aptamer Binding Characterization at the Single-Molecule Level

Cell-specific aptamers offer a powerful tool to study membrane receptors at the single-molecule level. Most target receptors of aptamers are highly expressed on the cell surface, but difficult to analyze in situ because of dense distribution and fast velocity. Therefore, we herein propose a random sampling-based analysis strategy termed ligand dilution analysis (LDA) for easily implemented aptamer-based receptor study. Receptor density on the cell surface can be calculated based on a regression model. By using a synergistic ligand dilution design, colocalization and differentiation of aptamer and monoclonal antibody (mAb) binding on a single receptor can be realized. Once this is accomplished, precise binding site and detailed aptamer-receptor binding mode can be further determined using molecular docking and molecular dynamics simulation. The ligand dilution strategy also sets the stage for an aptamer-based dynamics analysis of two- and three-dimensional motion and fluctuation of highly expressed receptors on the live cell membrane.     

An Activatable NIR-II Fluorescent Reporter for In Vivo Imaging of Amyloid-β Plaques

Fluorescence imaging in the second near-infrared (NIR-II) window holds great promise for in vivo visualization of amyloid-β (Aβ) pathology, which can facilitate characterization and deep understanding of Alzheimer's disease (AD); however, it has been rarely exploited. Herein, we report the development of NIR-II fluorescent reporters with a donor-π-acceptor (D-π-A) architecture for specific detection of Aβ plaques in AD-model mice. Among all the designed probes, DMP2 exhibits the highest affinity to Aβ fibrils and can specifically activate its NIR-II fluorescence after binding to Aβ fibrils via suppressed twisted intramolecular charge transfer (TICT) effect. With suitable lipophilicity for ideal blood–brain barrier (BBB) penetrability and deep-tissue penetration of NIR-II fluorescence, DMP2 possesses specific detection of Aβ plaques in in vivo AD-model mice. Thus, this study presents a potential agent for non-invasive imaging of Aβ plaques and deep deciphering of AD progression.     

From molecular to continuum modelling of bistable liquid crystal devices

We study nematic equilibria on a square with tangent Dirichlet conditions on the edges, in three different modelling frameworks: (i) the off-lattice Hard Gaussian Overlap and Gay–Berne models; (ii) the lattice-based Lebwohl–Lasher model; and the (iii) two-dimensional Landau-de Gennes model. We compare the modelling predictions, identify regimes of agreement and in the Landau-de Gennes case, find up to 21 different equilibria. Of these, two are physically stable.