Molecular rotor-based fluorophores (RBFs) have been widely used in many fields.H owever,t he lacko fcontrol of their viscosity sensitivity limits their application. Herein, this problem is resolved by chemically installing extended p-rich alternating carbon-carbon linkages between the rotational electron donors and acceptors of RBFs.T he data reveal that the length of the linkage strongly influences the viscosity sensitivity,l ikely resulting from varying height of the energy barriers between the fluorescent planar and the dark twisted configurations.T hree RBF derivatives that span aw ide range of viscosity sensitivities were designed. These RBFs demonstrated, through ad ual-color imaging strategy,t hat they can differentiate misfolded protein oligomers and insoluble aggregates,b oth in test tubes and live cells.B eyond RBFs,i ti s envisioned that this chemical mechanismm ight be generally applicable to awide range of photoisomerizable and aggregation-induced emission fluorophores.

Aberrantly processed or mutant proteins misfold and assemble into a variety of soluble oligomers and insoluble aggregates, a process that is associated with an increasing number of diseases that are not curable or manageable. Herein, we present a chemical toolbox, AggFluor, that allows for live cell imaging and differentiation of complex aggregated conformations in live cells. Based on the chromophore core of green fluorescent proteins, AggFluor is comprised of a series of molecular rotor fluorophores that span a wide range of viscosity sensitivity. As a result, these compounds exhibit differential turn-on fluorescence when incorporated in either soluble oligomers or insoluble aggregates. This feature allows us to develop, for the first time, a dual-color imaging strategy to distinguish unfolded protein oligomers from insoluble aggregates in live cells. Furthermore, we have demonstrated how small molecule proteostasis regulators can drive formation and disassembly of protein aggregates in both conformational states. In summary, AggFluor is the first set of rationally designed molecular rotor fluorophores that evenly cover a wide range of viscosity sensitivities. This set of fluorescent probes not only change the status quo of current imaging methods to visualize protein aggregation in live cells but also can be generally applied to study other biological processes that involve local viscosity changes with temporal and spatial resolutions.

An increasing number of studies have indicated that long-non-coding RNAs (lncRNAs) play critical roles in many important biological processes. Predicting potential lncRNAdisease associations can improve our understanding of the molecular mechanisms of human diseases and aid in finding biomarkers for disease diagnosis, treatment, and prevention. In this paper, we constructed a bipartite network based on known lncRNA-disease associations; based on this work, we proposed a novel model for inferring potential lncRNA disease associations. Specifically, we analyzed the properties of the bipartite network and found that it closely followed a power-law distribution. Moreover, to evaluate the performance of our model, a leaveone-out cross-validation (LOOCV) framework was implemented, and the simulation results showed that our computational model significantly outperformed previous state-of-the-art models, with AUCs of 0.8825, 0.9004 and 0.9292 for known lncRNAdisease associations obtained from the LncRNADisease database, Lnc2Cancer database, and MNDR database, respectively. Thus, our approach may be an excellent addition to the biomedical research field in the future.

Aberrant protein aggregation leads to various human diseases, but little is known about the physical chemical properties of these aggregated proteins in cells. Herein, we developed a boron-dipyrromethene (BODIPY)-based HaloTag probe, whose conjugation to HaloTag-fused proteins allows us to study protein aggregates using both fluorescence intensity and lifetime. Modulation of BODIPY fluorophore reveals key structural features to attain the dual function. The optimized probe exhibits increased fluorescence intensity and elongated fluorescence lifetime in protein aggregates. Fluorescence lifetime imaging using this probe indicates that protein aggregates afford different viscosity in the forms of soluble oligomers and insoluble aggregates in live cells. The strategy presented in this work can be extended to enable a wide class of HaloTag probes that can be used to study a variety of physical properties of protein aggregates, thus helping unravel the pathogenic mechanism and develop therapeutic strategy.

A series of rod-shaped polyoxometalates (POMs) [Bu N] [Mo O NC(CH O) MnMo O (OCH ) CNMo O ] and [Bu N] [ArNMo O NC(CH O) MnMo O (OCH ) CNMo O NAr] (Ar=2,6-dimethylphenyl, naphthyl and 1-methylnaphthyl) were chosen to study the effects of cation-π interaction on macroionic self-assembly. Diffusion ordered spectroscopy (DOSY) and isothermal titration calorimetry (ITC) techniques show that the binding affinity between the POMs and Zn ions is enhanced significantly after grafting aromatic groups onto the clusters, leading to the effective replacement of tetrabutylammonium counterions (TBAs) upon the addition of ZnCl . The incorporation of aromatic groups results in the significant contribution of cation-π interaction to the self-assembly, as confirmed by the opposite trend of assembly size vs. ionic strength when compared with those without aromatic groups. The small difference between two aromatic groups toward the Zn ions is amplified after combining with the clusters, which consequently triggers the self-recognition behavior between two highly similar macroanions.