Biobased Nonisocyanate Polyurethanes as Recyclable and Intrinsic Self-Healing Coating with Triple Healing Sites.

Polymer coatings having high amounts of renewable carbon and self-healing properties are highly sought after in a sustainability perspective. We report here the development of bio-/CO-derived nonisocyanate polyurethane (NIPU) coatings which are recyclable and healable via three different types of healing mechanisms. These NIPUs contain furan rings in their main chain which after cross-linking with bismaleimides form organogels having a thermo-reversible sol-gel transition and solvent-borne coatings with improved properties.

Immuno-Modulatory Effects of Microparticles Formulated from Degradable Polystyrene Analogue.

Environmental accumulation of non-degradable polystyrene (PS) microparticles from plastic waste poses potential adverse impact on marine life and human health. Herein, microparticles from a degradable PS analogue (dePS) are formulated and their immuno-modulatory characteristics are comprehensively evaluated. Both dePS copolymer and microparticles are chemically degradable under accelerated hydrolytic condition.

High molecular weight hyper-branched PCL-based thermogelling vitreous endotamponades.

Vitreous endotamponades play essential roles in facilitating retina recovery following vitreoretinal surgery, yet existing clinically standards are suboptimal as they can cause elevated intra-ocular pressure, temporary loss of vision, and cataracts while also requiring prolonged face-down positioning and removal surgery. These drawbacks have spurred the development of next-generation vitreous endotamponades, of which supramolecular hydrogels capable of in-situ gelation have emerged as top contenders. Herein, we demonstrate thermogels formed from hyper-branched amphiphilic copolymers as effective transparent and biodegradable vitreous endotamponades for the first time.

Visualizing and Quantifying Wettability Alteration by Silica Nanofluids.

An aqueous suspension of silica nanoparticles or nanofluid can alter the wettability of surfaces, specifically by making them hydrophilic and oil-repellent under water. Wettability alteration by nanofluids has important technological applications, including for enhanced oil recovery and heat transfer processes. A common way to characterize the wettability alteration is by measuring the contact angles of an oil droplet with and without nanoparticles.

Liposome Click Membrane Permeability Assay for Identifying Permeable Peptides.

Purpose: To develop a novel, target agnostic liposome click membrane permeability assay (LCMPA) using liposome encapsulating copper free click reagent dibenzo cyclooctyne biotin (DBCO-Biotin) to conjugate azido modified peptides that may effectively translocate from extravesicular space into the liposome lumen.

Method: DBCO-Biotin liposomes were prepared with egg phosphatidylcholine and cholesterol by lipid film rehydration, freeze/thaw followed by extrusion. Size of DBCO-Biotin liposomes were characterized with dynamic light scattering.

Granzyme B PET Imaging of Combined Chemotherapy and Immune Checkpoint Inhibitor Therapy in Colon Cancer.

Purpose: Chemotherapeutic adjuvants, such as oxaliplatin (OXA) and 5-fluorouracil (5-FU), that enhance the immune system, are being assessed as strategies to improve durable response rates when used in combination with immune checkpoint inhibitor (ICI) monotherapy in cancer patients. In this study, we explored granzyme B (GZB), released by tumor-associated immune cells, as a PET imaging-based stratification marker for successful combination therapy using a fluorine-18 (F)-labelled GZB peptide ([F]AlF-mNOTA-GZP).

Methods: Using the immunocompetent CT26 syngeneic mouse model of colon cancer, we assessed the potential for [F]AlF-mNOTA-GZP to stratify OXA/5-FU and ICI combination therapy response via GZB PET.

Effect of salts on size and morphology of extruded dimethyldioctadecylammonium bromide or chloride vesicle for polymeric nanocapsules synthesis via templating emulsion polymerization.

In preparing polymer capsules by vesicle templated emulsion polymerization, the initial size and morphology of the biomimetic vesicle template dictate the final size and morphology of the capsules. The presence of salts (NaCl, NaBr and LiCl) influences the size, dispersity (PDI) and morphology of dimethyldioctadecylammonium bromide or chloride (DODAX, X  = Br or Cl) vesicles, prepared via membrane extrusion. DODAX vesicles in pure water exhibit broad size distributions with PDI of 0.

Elucidating the Role of Interfacial Hydrogen Bonds on Glass Transition Temperature Change in a Poly(Vinyl Alcohol)/SiO Polymer-Nanocomposite by Noncovalent Interaction Characterization and Atomistic Molecular Dynamics Simulations.

A thorough experimental investigation of polymer-glass transition temperature (T ) is performed on poly(vinyl alcohol) (PVA) and fumed silica nanoparticle (SiNP) composite. This is done together with atomistic molecular dynamics simulations of PVA systems in contact with bare and fully hydroxylated silica. Experimentally, PVA-SiNP composites are prepared by simple solution casting from aqueous solutions followed by its characterization using Fourier-transform infrared spectroscopy (FTIR), dynamic mechanical analysis (DMA), and dynamic scanning calorimetry (DSC).

A visible light-mediated, decarboxylative, desulfonylative Smiles rearrangement for general arylethylamine syntheses.

A decarboxylative, desulfonylative Smiles rearrangement is presented that employs activated-ester/energy transfer catalysis to decarboxylate β-amino acid derived starting materials at room-temperature under visible light irradiation. The radical Smiles rearrangement gives a range of biologically active arylethylamine products highly relevant to the pharmaceutical industry, chemical biology and materials science. The reaction is then applied to the synthesis of a chiral unnatural amino acid, 2-thienylalanine, used in the treatment of phenylketonuria.

A general strategy for degradable single-chain nanoparticles via cross-linker mediated chain collapse of radical copolymers.

Radical ring-opening copolymerization (rROP) between 2-methylene-1,3-dioxepane (MDO) and methacrylic acid N-hydroxysuccinimide ester (NHSMA) furnishes a reactive polyester-based linear copolymer precursor. Subsequent cross-linker mediated chain collapse affords degradable single-chain nanoparticles (DSCNPs). This methodology is an experimentally robust and straightforward route to main-chain degradable polymeric nanoparticles in the sub-30 nm size range.

Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes.

Purpose: Immune checkpoint inhibitor (ICI) monotherapy and combination regimens are being actively pursued as strategies to improve durable response rates in cancer patients. However, the biology surrounding combination therapies is not well understood and may increase the likelihood of immune-mediated adverse events. Accurate stratification of ICI response by non-invasive PET imaging may help ensure safe therapy management across a wide number of cancer phenotypes.

Unraveling the History and Revisiting the Synthesis of Degradable Polystyrene Analogues via Radical Ring-Opening Copolymerization with Cyclic Ketene Acetals.

Degradable analogues of polystyrene are synthesized via radical ring-opening (co)polymerization (rROP) between styrene and two cyclic ketene acetals, namely 2-methylene-1,3-dioxepane (MDO) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO). This approach periodically inserts ester bonds throughout the main chain of polystyrene, imparting a degradation pathway via ester hydrolysis. We discuss the historical record of this approach, with careful attention paid to the conflicting findings previously reported.

A New Biosensor for Stilbenes and a Cannabinoid Enabled by Genome Mining of a Transcriptional Regulator.

biosensors are powerful tools for metabolic engineering and synthetic biology applications. However, the development of biosensors is hindered by the limited number of characterized transcriptional regulators. The versatile sensing abilities of microbes and genome sequences available hold great potential for developing novel biosensors via genome mining for new transcriptional regulators.

Examining Immunotherapy Response Using Multiple Radiotracers.

Purpose: Cancer immunotherapy has shown huge potential in the fight against cancer, but only a small proportion of patients respond successfully to treatment. Non-invasive methods to stratify responders from non-responders are critically important as immune therapies are often associated with immune-related side effects. Currently, conventional clinical imaging modalities do not provide a useful measure of immune therapy efficacy.

[2+2] Photodimerization of Stilbazoles Promoted by Oxalic Acid in Suspension.

In this study, a very simple technique to perform efficiently photodimerization of some vinylpyridines is reported. By irradiating a stirred mixture of several stilbazoles with solid oxalic acid dihydrate dispersed in a nonpolar (i.e.

Cobalt-Catalyzed Cross-Coupling Reactions of Aryl Triflates and Lithium Arylborates.

A catalyst system comprising CoCl/IAd·HBF enables the Suzuki-Miyaura cross-coupling reaction of a broad range of aryl triflates and arylboronic esters that are activated by -butyllithium.

Highly monodisperse zwitterion functionalized non-spherical polymer particles with tunable iridescence.

A facile and simple synthetic route towards functionalized non-spherical polymer particles (NSP) with tunable morphologies and iridescence is presented. Monodisperse particles with unique zwitterionic functionality were synthesized emulsifier-free emulsion polymerization in a single step process. The sulfobetaine comonomer was utilized to induce phase separation in the course of polymerization to achieve anisotropic NSP with controlled morphologies such as quasi-spherical with protruding structures like bulge, eye-ball, and snowman-like nanostructures.

Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties.

Stapled α-helical peptides represent an emerging superclass of macrocyclic molecules with drug-like properties, including high-affinity target binding, protease resistance, and membrane permeability. As a model system for probing the chemical space available for optimizing these properties, we focused on dual Mdm2/MdmX antagonist stapled peptides related to the p53 N-terminus. Specifically, we first generated a library of ATSP-7041 (Chang et al.

Alkene Carboarylation through Catalyst-Free, Visible Light-Mediated Smiles Rearrangement.

A light-mediated Truce-Smiles arylative rearrangement is described that proceeds in the absence of any photocatalyst. The protocol creates two C-C bonds from simple starting materials, with the installation of an aryl ring and a difluoroacetate moiety across unactivated alkenes. The reaction proceeds via a radical mechanism, utilizing a light-mediated reduction of ethyl bromodifluoroacetate by N,N,N',N'-tetramethylethylenediamine (TMEDA) to set up intermolecular addition to an unactivated alkene, followed by Truce-Smiles rearrangement.

Intrinsic Xenobiotic Resistance of the Intestinal Stem Cell Niche.

The gut absorbs dietary nutrients and provides a barrier to xenobiotics and microbiome metabolites. To cope with toxin exposures, the intestinal epithelium is one of the most rapidly proliferating tissues in the body. The stem cell niche supplies essential signaling factors including Wnt proteins secreted by subepithelial myofibroblasts.

Synthesis of phosphine oxide based amphiphilic molecules ring-opening Wittig olefination of a macrocyclic phosphoranylidene and their property study as non-ionic surfactants.

A novel ring-opening Wittig olefination approach was developed for the synthesis of amphiphilic phosphine oxides (PO) as non-ionic surfactants. The approach concurrently introduces the crucial functional groups (lipophilic chain and phosphine oxide moiety) present in the known PO surfactants and additional hydrophilic group (, ethylene glycol units) in one step Wittig olefination of a macrocyclic phosphoranylidene. A series of novel PO compounds were obtained from a variety of aldehydes and selected compounds were examined for their physiochemical properties (surface tension, critical micelle concentration and interfacial tension) and also for their abilities to form emulsions as non-ionic surfactants.

Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR-Cas9 Activation.

Silent biosynthetic gene clusters represent a potentially rich source of new bioactive compounds. We report the discovery, characterization, and biosynthesis of a novel doubly glycosylated 24-membered polyene macrolactam from a silent biosynthetic gene cluster in Streptomyces roseosporus by using the CRISPR-Cas9 gene cluster activation strategy. Structural characterization of this polyketide, named auroramycin, revealed a rare isobutyrylmalonyl extender unit and a unique pair of amino sugars.

Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by bcr-abl1, a constitutively active tyrosine kinase fusion gene responsible for an abnormal proliferation of leukemic stem cells (LSCs). Inhibition of BCR-ABL1 kinase activity offers long-term relief to CML patients. However, for a proportion of them, BCR-ABL1 inhibition will become ineffective at treating the disease, and CML will progress to blast crisis (BC) CML with poor prognosis.

Toward Resolving the Resveratrol Conundrum: Synthesis and Pharmacokinetic Evaluation of BCP-Resveratrol.

Over the last few decades, resveratrol has gained significance due to its impressive array of biological activities; however, its true potential as a drug has been severely constrained by its poor bioavailability. Indeed, several studies have implicated this bioavailability trait as a major road-block to resveratrol's potential clinical applications. To mitigate this pharmacokinetic issue, we envisioned a tactical bioisosteric modification of resveratrol to bicyclo[1.