Berberine (BBR), a traditional Chinese medicine, has therapeutic effects on a variety of inflammation-related diseases, but its direct proteomic targets remain unknown. Using activity-based protein profiling, we first demonstrated that BBR directly targets the NEK7 protein via the hydrogen bond between the 2,3-methylenedioxy and 121-arginine (R121) residues. The fact that R121 is located precisely within the key domain involved in the NEK7-NLRP3 interaction allows BBR to specifically block the NEK7-NLRP3 interaction and successively inhibit IL-1β release, independent of the NF-κB and TLR4 signaling pathways. Moreover, BBR displays in vivo anti-inflammatory efficacy in a NEK7-dependent manner. Therefore, we consider NEK7 to be a key target of BBR in the treatment of NLRP3-related inflammatory diseases, and the development of novel NEK7-NLRP3 interaction inhibitors might be easily achieved using NEK7 as a target.The unprecedented development of inorganic nanostructure synthesis has paved the way toward their broad applications in areas such as food science, agroforestry, energy conversion, and biomedicine. The precise manipulation of the nucleation and subsequent growth has been recognized as the central guiding principle for controlling the size and morphology of the nanostructures. However, conventional colloid syntheses based on direct precipitation reactions still have limitations in their versatility and extendibility. The crystal structure of a material determines the limited number of possible morphologies that its nanostructures can adopt. Further, as nucleation and growth kinetics are sensitive to not only the nature of the precipitation reactions but also ligands and ripening effect, rigorous control of reaction conditions must be established for every specific synthesis. In addition, multiple experimental parameters are entangled with each other, thereby requiring rigorous control of all reaction conditionons.Nanocarriers (NCs) are an attractive class of vehicles for drug delivery with the potential to improve drug efficacy and safety, particularly for intravenous parenteral delivery. Many therapeutics remain challenging to formulate in NCs due to their intrinsic solubilities that frustrate NC loading or result in too rapid release in vivo. Therapeutic conjugate approaches that alter the solubility of a conjugate "prodrug" have been used to enable NC formation and controlled release from NCs using labile linker chemistry. A limitation of this approach has been that a different linker chemistry must be used to produce an adjustable release rate for a single therapeutic. We report on a new approach where the therapeutic conjugate hydrolysis rates are varied by adjusting the excipient formulation of the NC core, not the conjugate linker chemistry. A hydrophobic therapeutic conjugate of camptothecin (PROCPT) is synthesized by conjugating camptothecin (CPT) with an acid derivative of α-tocopherol (vitamin E).  https://www.selleckchem.com/products/guanosine.html  The PROCPgate.Amyloid β-protein (Aβ) oligomers are broadly viewed as the proximate mediators of toxicity in Alzheimer's disease (AD). Recent studies, however, provide substantial evidence that Aβ is involved in protection and repair of the central nervous system whereby Aβ oligomer and subsequent fibril formation are integral to its normal antimicrobial and antiviral function. These developments raise a question of what exactly makes Aβ oligomers toxic in the context of AD. This Perspective describes a paradigm shift in the search for toxic Aβ oligomer species that involves oxidative-stress-induced stabilization of Aβ oligomers via cross-linking and reviews most recent research elucidating structural aspects of cross-linked Aβ oligomers and potential inhibition of their toxicity.Among gene delivery systems, peptide-based gene carriers have received significant attention because of their selectivity, biocompatibility, and biodegradability. Since cellular membranes function as a barrier toward exogenous molecules, cell-penetrating peptides (CPPs), which are usually cationic and/or amphiphilic, can serve as efficient carriers to deliver cargo into the cytosol. Here, we examined the interactions of carrier peptides and their DNA complexes with lipid membranes using a quartz crystal microbalance (QCM) and high-speed atomic force microscopy (HS-AFM). The carrier peptides are a 12-residue partial presequence of yeast cytochrome c oxidase subunit IV (Cytcox) and BP100, which are a mitochondria-targeting signal peptide and a CPP, respectively. QCM data showed that BP100 has a higher binding affinity than Cytcox to both plasma membrane- and mitochondrial membrane-mimicking lipid bilayers. The DNA complexes with either Cytcox or BP100 exhibited the same tendency. Furthermore, HS-AFM data demonstrated that the DNA complexes of either peptide can disrupt the lipid membranes, forming larger pores in the case of Cytcox. Our results suggest that the binding affinity of the peptide/DNA complex to the plasma membrane is more critical than its membrane disruption ability in enhancing the cellular uptake of DNA.This article describes the full details of our synthetic efforts toward the enantioselective total synthesis of the complex alkaloid methoxystemofoline. The enantioselective construction of the tetracyclic core features (1) the Keck allylation at the N-α bridgehead carbon to forge the tetrasubstituted stereocenter; (2) an olefin cross-metathesis reaction for the side-chain elongation that is amenable for the synthesis of congeners and analogues; and (3) a regioselective aldol addition reaction with methyl pyruvate that ensured the subsequent regioselective cyclization reaction to construct the fourth ring. Overman's method was employed to install the 5-(alkoxyalky1idene)-3-methyl-tetronate moiety. In the last step, a nonstereoselective reaction resulted in the formation of both the proposed structure of methoxystemofoline and its E-stereoisomer, the natural product (revised structure), in a 11 ratio. We suggest to rename the natural product as isomethoxystemofoline, and report for the first time the complete 1H NMR data for this natural product.