Ligand Induced CuII Transport Restricts Cancer and Mycobacterial Growth: Towards a Plug-and-Select Ion Channel Scaffold

Synthetic channels with high ion selectivity are attractive drug targets for diseases involving ion dysregulation. Achieving selective transport of divalent ions is highly challenging due their high hydration energies. A small tripeptide amphiphilic scaffold installed with a pybox ligand selectively transports Cu^II ions across membranes. The peptide forms stable dimeric pores in the membrane and transports ions by a Cu²⁺/H⁺ antiport mechanism. The ligand-induced excellent Cu^II selectivity as well as high membrane permeability of the peptide is exploited to promote cancer cell death. The peptide's ability to restrict mycobacterial growth serves as seeds to evolve antibacterial strategies centred on selectively modulating ion homeostasis in pathogens. This simple peptide can potentially function as a universal, yet versatile, scaffold wherein the ion selectivity can be precisely controlled by modifying the ligand at the C terminus.     

From Channels to Canonical Wnt Signaling: A Pathological Perspective

Wnt signaling is an important pathway mainly active during embryonic development and controlling cell proliferation. This regulatory pathway is aberrantly activated in several human diseases. Ion channels are known modulators of several important cellular functions ranging from the tuning of the membrane potential to modulation of intracellular pathways, in particular the influence of ion channels in Wnt signaling regulation has been widely investigated. This review will discuss the known links between ion channels and canonical Wnt signaling, focusing on their possible roles in human metabolic diseases, neurological disorders, and cancer.     

Versatile Oral Insulin Delivery Nanosystems: From Materials to Nanostructures

Diabetes is a chronic metabolic disease characterized by lack of insulin in the body leading to failure of blood glucose regulation. Diabetes patients usually need frequent insulin injections to maintain normal blood glucose levels, which is a painful administration manner. Long-term drug injection brings great physical and psychological burden to diabetic patients. In order to improve the adaptability of patients to use insulin and reduce the pain caused by injection, the development of oral insulin formulations is currently a hot and difficult topic in the field of medicine and pharmacy. Thus, oral insulin delivery is a promising and convenient administration method to relieve the patients. However, insulin as a peptide drug is prone to be degraded by digestive enzymes. In addition, insulin has strong hydrophilicity and large molecular weight and extremely low oral bioavailability. To solve these problems in clinical practice, the oral insulin delivery nanosystems were designed and constructed by rational combination of various nanomaterials and nanotechnology. Such oral nanosystems have the advantages of strong adaptability, small size, convenient processing, long-lasting pharmaceutical activity, and drug controlled-release, so it can effectively improve the oral bioavailability and efficacy of insulin. This review summarizes the basic principles and recent progress in oral delivery nanosystems for insulin, including physiological absorption barrier of oral insulin and the development of materials to nanostructures for oral insulin delivery nanosystems.     

Versatile bio-based epoxy resin: From banana waste to applied materials

Bio-based epoxy resin is a promising candidate for petroleum-based resins due to its abundant reserves and low-cost products, which mainly use polyphenolic composites as precursors. Liquefied banana pseudo stem (LBPS), a highly active compound obtained by liquefaction with 7.5% of sulfuric acid as catalyst at 160°C, was used to synthesize bio-based epoxy resin. FTIR and SEM demonstrated the synthetic process of LBPS-based epoxy resin (LBPSER) from waste banana pseudo stem (BPS). Mechanical test, reagent resistance, dynamic mechanical analysis, and thermogravimetric analysis were utilized to evaluate the mechanical and chemical properties of LBPSER. With polyamide (PA) as hardener, LBPSER-PA adhesive exhibited an optimum shear strength that is comparable with that of commercial diglycidyl ether of bisphenol A (DGEBA), corresponding to 11.86 vs 11.89 MPa. Interestingly, the shear strength of this adhesive curing at 40°C could get 9.52 MPa for wood materials. The adhesive also performed excellent resistance to organic agents, adverse acidic, and alkaline environments. Notably, as the content of LBPSER in adhesive increased, an increase of glass transition temperature could be verified from 42 to 100°C. The LBPSER-PA adhesive presented good thermal and physicochemical performances, thereby suggesting the potential of utilizing liquefied product from BPS as alternative to toxic bisphenol A in synthesizing bio-based epoxy resin. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47135.     

Efflux Transporters as a Novel Herbivore Countermechanism to Plant Chemical Defenses

The recent discovery of efflux transporters in the gut has revolutionized our understanding of the absorption and bioavailability of pharmaceuticals and other xenobiotics in humans. Despite the celebrity of efflux transporters in the areas of pharmacology and medicine, their significance is only beginning to be realized in the area of plant–herbivore interactions. This review integrates reports on the importance of gut efflux transporters to diet selection by herbivores. The diets of herbivores are laden with toxic plant secondary metabolites (PSMs) that until recently were thought to be processed almost exclusively by detoxification enzymes in the liver. We describe how efflux transporters in the gut may play a critical role in regulating the absorption of PSMs in herbivores and dictating diet selection. Recent studies suggest that the role of efflux transporters in mediating diet selection in herbivores may be as critical as detoxification enzymes. In addition to diet selection, gut efflux transporters have implications for other aspects of plant–animal interactions. They may be significant components of the evolutionary arms race that influences chemical diversity in plants. Furthermore, in agricultural systems, gut efflux transporters may play an important role in the effectiveness of pesticides. This synthesis paper introduces a new direction in plant–herbivore interactions by providing a complementary mechanism, regulated absorption, to detoxification that may define tolerance to PSMs by herbivores.     

A New SiF–Dipropargyl Glycerol Scaffold as a Versatile Prosthetic Group to Design Dimeric Radioligands: Synthesis of the [18F]BMPPSiF Tracer to Image Serotonin Receptors

A novel SiX–dipropargyl glycerol scaffold (X: H, F, or ¹⁸F) was developed as a versatile prosthetic group that provides technical advantages for the preparation of dimeric radioligands based on silicon fluoride acceptor pre‐ or post‐labeling with fluorine‐18. Rapid conjugation with the prosthetic group takes place in microwave‐assisted click conjugation under mild conditions. Thus, a bivalent homodimeric SiX–dipropargyl glycerol derivatized radioligand, [¹⁸F]BMPPSiF, with enhanced affinity was developed by using click conjugation. High uptake of the radioligand was demonstrated in 5‐HT_1A receptor‐rich regions in the brain with positron emission tomography. Molecular docking studies (rigid protein–flexible ligand) of BMPPSiF and known antagonists (WAY‐100635, MPPF, and MefWAY) with monomeric, dimeric, and multimeric 5‐HT_1A receptor models were performed, with the highest G score obtained for docked BMPPSiF: ?6.766 as compared with all three antagonists on the monomeric model. Multimeric induced‐fit docking was also performed to visualize the comparable mode of binding under in vivo conditions, and a notably improved G score of ?8.455 was observed for BMPPSiF. These data directly correlate the high binding potential of BMPPSiF with the bivalent binding mode obtained in the biological studies. The present study warrants wide application of the SiX–dipropargyl glycerol prosthetic group in the development of ligands for imaging with enhanced affinity markers for specific targeting based on peptides, nucleosides, and lipids.     

Material advancements in supercapacitors: From activated carbon to carbon nanotube and graphene

The electrochemical capacitor (EC), also known as supercapacitor, is an energy storage device possessing a near infinite life‐cycle and high power density recognised to store energy in the double‐layer or through pseudocapacitance as a result of an applied potential. Fundamental principles of charge storage in relation to the important physical and chemical characteristics of electrode materials are addressed in the following review, with carbon‐made electrodes, specifically activated carbon, carbon fibres and aerogels, carbon nanotubes and graphene emphasised in regards to their enhancement of the characteristic energy and power densities of ECs. Pseudocapacitive materials, notably transition metal oxides and nitrides, and conducting polymers are remarked by the potential to further improve EC performance through synergistic effects and asymmetric design. Research towards gaining a better understanding of charge storage in sub‐micropores, material design and improving the performance of alternative electrolytes are expected to greatly enhance the capabilities of these devices in the near future.     

Versatile Types of Polysaccharide-Based Drug Delivery Systems: From Strategic Design to Cancer Therapy

Chemotherapy is still the most direct and effective means of cancer therapy nowadays. The proposal of drug delivery systems (DDSs) has effectively improved many shortcomings of traditional chemotherapy drugs. The technical support of DDSs lies in their excellent material properties. Polysaccharides include a series of natural polymers, such as chitosan, hyaluronic acid, and alginic acid. These polysaccharides have good biocompatibility and degradability, and they are easily chemical modified. Therefore, polysaccharides are ideal candidate materials to construct DDSs, and their clinical application prospects have been favored by researchers. On the basis of versatile types of polysaccharides, this review elaborates their applications from strategic design to cancer therapy. The construction and modification methods of polysaccharide-based DDSs are specifically explained, and the latest research progress of polysaccharide-based DDSs in cancer therapy are also summarized. The purpose of this review is to provide a reference for the design and preparation of polysaccharide-based DDSs with excellent performance.     

Purinergic Signaling in Pancreas—From Physiology to Therapeutic Strategies in Pancreatic Cancer

The purinergic signaling has an important role in regulating pancreatic exocrine secretion. The exocrine pancreas is also a site of one of the most serious cancer forms, the pancreatic ductal adenocarcinoma (PDAC). Here, we explore how the network of purinergic and adenosine receptors, as well as ecto-nucleotidases regulate normal pancreatic cells and various cells within the pancreatic tumor microenvironment. In particular, we focus on the P2X7 receptor, P2Y₂ and P2Y₁₂ receptors, as well as A₂ receptors and ecto-nucleotidases CD39 and CD73. Recent studies indicate that targeting one or more of these candidates could present new therapeutic approaches to treat pancreatic cancer. In pancreatic cancer, as much as possible of normal pancreatic function should be preserved, and therefore physiology of purinergic signaling in pancreas needs to be considered.     

Self-assembled monolayers of pyridylthio-functionalized carbon nanotubes used as a support to immobilize cytochrome c

Self-assembled monolayers (SAMs) of pyridylthio-functionalized multiwalled carbon nanotubes (pythio-MWNTs) have been constructed on the gold substrate surface, which were used as a support to immobilize cytochrome c (Cyt c). The assembly processes of the SAMs and adsorption of Cyt c were monitored by using quartz crystal microbalance (QCM). Based on the frequency change of the QCM resonator, the surface coverage for the SAMs of pythio-MWNTs was estimated to be about 5.2 μg/cm², and that of the Cyt c adsorbed was about 0.29 μg/cm². For the gold electrode modified by the SAMs of pythio-MWNTs-Cyt c, a quasi-reversible redox wave was recorded with the cathodic and anodic potentials at about −0.55 and −0.28 V vs Ag/AgCl, respectively. Compositions and morphologies of the SAMs before and after immobilization of Cyt c were characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, scanning electron microscopy, and atomic force microscopy.     

Coming of Age: Cryo-Electron Tomography as a Versatile Tool to Generate High-Resolution Structures at Cellular/Biological Interfaces

Over the last few years, cryo electron microscopy has become the most important method in structural biology. While 80% of deposited maps are from single particle analysis, electron tomography has grown to become the second most important method. In particular sub-tomogram averaging has matured as a method, delivering structures between 2 and 5 Å from complexes in cells as well as in vitro complexes. While this resolution range is not standard, novel developments point toward a promising future. Here, we provide a guide for the workflow from sample to structure to gain insight into this emerging field.     

Natural gas hydrate as a potential energy resource: From occurrence to production

Natural gas hydrate reservoirs have been strongly suggested as a potential energy resource. However, this potential is expected to be limited by geological factors, reservoir properties, and phase-equilibria considerations. Accordingly, sufficient understanding and accurate analyses for the complex surroundings in a natural gas hydrate system have to occur before methane recovery. In this paper, we discuss the formation and structure patterns of global natural gas hydrate, including the origins of hydrocarbon, crystal structures, and unique structure transition. We also summarize two important anomalies related to methane occupancy and chlorinity which were revealed very recently. Furthermore, we review the geological and chemical surroundings of the shallow hydrate deposits, the so-called brine patch discovered in the Cascadia Margin and Ulleung Basin, which are significantly related to tectonic conduits for methane gas and positive chlorinity.     

From Quinoline to Quinazoline-Based S. aureus NorA Efflux Pump Inhibitors by Coupling a Focused Scaffold Hopping Approach and a Pharmacophore Search

Antibiotic resistance breakers, such as efflux pump inhibitors (EPIs), represent a powerful alternative to the development of new antimicrobials. Recently, by using previously described EPIs, we developed pharmacophore models able to identify inhibitors of NorA, the most studied efflux pump of Staphylococcus aureus. Herein we report the pharmacophore-based virtual screening of a library of new potential NorA EPIs generated by an in-silico scaffold hopping approach of the quinoline core. After chemical synthesis and biological evaluation of the best virtual hits, we found the quinazoline core as the best performing scaffold. Accordingly, we designed and synthesized a series of functionalized 2-arylquinazolines, which were further evaluated as NorA EPIs. Four of them exhibited a strong synergism with ciprofloxacin and a good inhibition of ethidium bromide efflux on resistant S. aureus strains coupled with low cytotoxicity against human cell lines, thus highlighting a promising safety profile.     

Hofmeister Series: From Aqueous Solution of Biomolecules to Single Cells and Nanovesicles

Hofmeister effects play a critical role in numerous physicochemical and biological phenomena, including the solubility and/or accumulation of proteins, the activities of enzymes, ion transport in biochannels, the structure of lipid bilayers, and the dynamics of vesicle opening and exocytosis. This minireview focuses on how ionic specificity affects the physicochemical properties of biomolecules to regulate cellular exocytosis, vesicular content, and nanovesicle opening. We summarize recent progress in further understanding Hofmeister effects on biomacromolecules and their applications in biological systems. These important steps have increased our understanding of the Hofmeister effects on cellular exocytosis, vesicular content, and nanovesicle opening. Increasing evidence is firmly establishing that the ions along the Hofmeister series play an important role in living organisms that has often been ignored.     

Juxta‐terminal Helix Unwinding as a Stabilizing Factor to Modulate the Dynamics of Transmembrane Helices

Transmembrane helices of integral membrane proteins often are flanked by interfacial aromatic residues that can serve as anchors to aid the stabilization of a tilted transmembrane orientation. Yet, physical factors that govern the orientation or dynamic averaging of individual transmembrane helices are not well understood and have not been adequately explained. Using solid‐state ²H NMR spectroscopy to examine lipid bilayer‐incorporated model peptides of the GWALP23 (acetyl‐GGALW(LA)₆LWLAGA‐amide) family, we observed substantial unwinding at the terminals of several tilted helices spanning the membranes of DLPC, DMPC, or DOPC lipid bilayers. The fraying of helix ends might be vital for defining the dynamics and orientations of transmembrane helices in lipid bilayer membranes.