Nanomicellar Electrolyte To Control Release Ions and Reconstruct Hydrogen Bonding Network for Ultrastable High-Energy-Density Zn-Mn Battery.

Zn-Mn batteries with two-electron conversion reactions simultaneously on the cathode and anode harvest a high voltage plateau and high energy density. However, the zinc anode faces dendrite growth and parasitic side reactions while the Mn/MnO reaction on the cathode involves oxygen evolution and possesses poor reversibility. Herein, a novel nanomicellar electrolyte using methylurea (Mu) has been developed that can encapsulate ions in the nanodomain structure to guide the homogeneous deposition of Zn/Mn in the form of controlled release under an external electric field.

Prussian-blue-analogue derived FeNiS/NiS nanoframes supported by N-doped graphene for highly efficient methanol oxidation electrocatalysis.

The design of effective and robust non-noble metal electrocatalysts to enhance catalytic reaction kinetic is critical to promote methanol oxidation catalysis. Herein, hierarchical Prussian blue analogue (PBA)-derived sulfide heterostructures supported by N-doped graphene (FeNiS/NiS-NG) as efficient catalysts have been developed for methanol oxidation reaction (MOR). Benefiting from the merits of hollow nanoframes structure and heterogeneous sulfide synergy, FeNiS/NiS-NG composite not only possesses abundant active sites to boost the catalytic properties but also alleviates the CO poisoning effect during the process exhibiting favorable kinetic behavior toward MOR.

A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma.

Unlabelled: Nasopharyngeal carcinoma (NPC) is a serious and highly invasive epithelial malignancy that is closely associated with Epstein-Barr virus (EBV). Due to the lack of therapeutic vaccines for NPC, we selected EBV latent membrane protein 2 (LMP2) as a preferable targeting antigen to develop a lipid-based LMP2-mRNA (mLMP2) vaccine. Full-length mLMP2 expressing LMP2 was first synthesized using an transcription method and then encapsulated into (2,3-dioleacyl propyl) trimethylammonium chloride (DOTAP)-based cationic liposomes to obtain the mRNA vaccine (LPX-mLMP2).

Polysaccharide hydrogel electrolytes with robust interfacial contact to electrodes for quasi-solid state flexible aqueous zinc ion batteries with efficient suppressing of dendrite growth.

Flexible aqueous zinc-ion batteries (AZIBs) require high conductive and adhesive hydrogel electrolytes. However, high adhesion tends to hinder ion conduction rate. Herein, we designed a water/glycerol binary solvent coordinating the hydrophilic polymers to reconstruct the water molecules' environment in the hydrogel.

Interface engineering of Ni/NiO heterostructures with abundant catalytic active sites for enhanced methanol oxidation electrocatalysis.

Designing efficient and stable non-noble metal electrocatalysts with good performance in reaction kinetics is desirable yet challenging for the study of methanol oxidation reaction (MOR). Herein, we have reported well-defined nanoscale nickel/nickel oxide (Ni/NiO) heterostructures supported by a three-dimensional (3D) porous graphene network (RG) via a delicate interface engineering technique. The as-prepared 3D Ni/NiO/RG composites achieve outstanding catalytic activity (79.

Silanized Graphene Oxide-Supported Pd Nanoparticles and Silicone Rubber for Enhanced Hydrogen Elimination.

Hydrogen is a dangerous gas because it reacts very easily with oxygen to explode, and the accumulation of hydrogen in confined spaces is a safety hazard. Composites consisting of polymers and catalysts are a common getter, where the commonly used catalyst is usually commercial Pd/C. However, it often shows poor compatibility with polymers, making it difficult to form a homogeneous and stable composite.

Polypeptide Radical Cathode for Aqueous Zn-Ion Battery with Two-Electron Storage and Faster Charging Rate.

The rapidly growing demand for batteries has led to a lack of global mineral resources and rechargeable organic batteries are paid extensive attention, owing to the abundance resources, light weight, and high flexibility of organic electrodes. However, most organic electrodes that use aliphatic backbones are nondegradable, leading to unsustainability when active sites fail. In this study, a poly(aspartic acid) polypeptide (PASP) with amide links in the backbone and nitroxide radical pendant groups in the side chains is synthesized by modifying the polypeptides with 4-amino-2,2,6,6-tetramethylpiperidine.

Synthesis of Highly Ion-Conductive Lignin Eutectogels in a Ternary Deep Eutectic Solvent and Nitrogen-Doped 3D Hierarchical Porous Carbons for Supercapacitors.

A new strategy has been developed to synthesize deep eutectic solvent (DES)-based lignin eutectogels by the chemical crosslinking of homogeneously dispersed lignin with poly(ethylene glycol)diglycidyl ether (PEGDE) in a ternary DES of choline chloride (ChCl)/urea/glycerol. The as-prepared lignin eutectogels have high ionic conductivity, high strength, and extreme temperature stability, which can be used as sensors for flexible electronics. N-doped hierarchical porous carbons (HPCs) are prepared when the eutectogels were solvent-replaced and sintered in the atmosphere of N and CO, which results in the formation of porous carbon with a sufficient specific surface area and a three-dimensional framework composed of a hierarchical porous structure.

Discovery of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold.

A series of IDO1 inhibitors containing a decahydroquinoline, decahydro-1,6-naphthyridine, or octahydro-1H-pyrrolo[3,2-c]pyridine scaffold were identified with good cellular and human whole blood activity against IDO1. These inhibitors contain multiple chiral centers and all diastereomers were separated. The absolute stereochemistry of each isomers were not determined.

SAR towards indoline and 3-azaindoline classes of IDO1 inhibitors.

A novel series of IDO1 inhibitors have been identified with good IDO1 Hela cell and human whole blood activity. These inhibitors contain an indoline or a 3-azaindoline scaffold. Their structure-activity-relationship studies have been explored.

Carbamate and -Pyrimidine Mitigate Amide Hydrolysis: Structure-Based Drug Design of Tetrahydroquinoline IDO1 Inhibitors.

Indoleamine-2,3-dioxygenase-1 (IDO1) has emerged as an attractive target for cancer immunotherapy. An automated ligand identification system screen afforded the tetrahydroquinoline class of novel IDO1 inhibitors. Potency and pharmacokinetic (PK) were key issues with this class of compounds.

A high-voltage quasi-solid-state flexible supercapacitor with a wide operational temperature range based on a low-cost "water-in-salt" hydrogel electrolyte.

Recently, "water-in-salt" electrolytes have provided a huge boost to the realization of high energy density for water-based supercapacitors by broadening the electrochemical stability window. However, the high cost and low conductivity of high concentration LiTFSI greatly restrict the possibility of practical application. Herein, we adopt a new strategy to develop a low-cost and quasi-solid-state polyelectrolyte hydrogel accommodating a superhigh concentration of CHCOOK through in situ polymerization, avoiding the problem that many conventional polymers cannot accommodate ultra-high ion concentration.

In Situ Formation of "Dimethyl Sulfoxide/Water-in-Salt"-Based Chitosan Hydrogel Electrolyte for Advanced All-Solid-State Supercapacitors.

Biodegradable hydrogel electrolytes are particularly attractive in the fabrication of all-solid-state supercapacitors due to environmental benignity and avoiding of leakage. The introduction of "water-in-salt" (WIS) electrolytes into hydrogels will further broaden the electrochemical stability window of aqueous supercapacitors significantly. Meanwhile, the addition of an organic co-solvent can effectively overcome the inevitable salt precipitation and extend the temperature adaptability.

Pien Tze Huang alleviate the joint inflammation in collagen-induced arthritis mice.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Pien Tze Huang (PZH) is a Chinese patent medicine with anti-inflammatory and immunomodulatory effects. However, whether PZH could be used in RA therapy is still unknown.

Discovery of Amino-cyclobutarene-derived Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitors for Cancer Immunotherapy.

Checkpoint inhibitors have demonstrated unprecedented efficacy and are evolving to become standard of care for certain types of cancers. However, low overall response rates often hamper the broad utility and potential of these breakthrough therapies. Combination therapy strategies are currently under intensive investigation in the clinic, including the combination of PD-1/PD-L1 agents with IDO1 inhibitors.

Suppressing Self-Discharge with Polymeric Sulfur in Li-S Batteries.

Lithium⁻sulfur (Li-S) batteries, due to their high theoretical capacity, intrinsic overcharge protection, and low cost, are considered as the most promising candidates for next-generation energy storage systems. To promote widespread use of Li-S batteries, various tactics have been reported to improve the columbic efficiency and to suppress the shuttle effect. Herein, we report a novel polymeric sulfur via heat radical polymerization, for the Li-S battery.

Pien Tze Huang Alleviates Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mice by Regulating Th1 and Th17 Cells.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by infiltrating inflammatory cells and demyelinating lesions, and T helper (Th) cells play critical roles in the pathogenesis of MS. There is still lack of effective treatments currently. Pien Tze Huang (PZH), a traditional Chinese medicine formula, has been proved to have anti-inflammatory, neuroprotective, and immunoregulatory effects.

MK-8353: Discovery of an Orally Bioavailable Dual Mechanism ERK Inhibitor for Oncology.

The emergence and evolution of new immunological cancer therapies has sparked a rapidly growing interest in discovering novel pathways to treat cancer. Toward this aim, a novel series of pyrrolidine derivatives (compound ) were identified as potent inhibitors of ERK1/2 with excellent kinase selectivity and dual mechanism of action but suffered from poor pharmacokinetics (PK). The challenge of PK was overcome by the discovery of a novel 3()-thiomethyl pyrrolidine analog .

Discovery of 3(S)-thiomethyl pyrrolidine ERK inhibitors for oncology.

Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 μM h; F% = 0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10 mpk = 26 μM h; F% = 70).

Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors.

Background: Constitutive activation of ERK1/2 occurs in various cancers, and its reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual mechanism inhibitor SCH772984 has shown promising preclinical activity across various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts.

Discovery of hydroxyaniline amides as selective Extracellular Regulated Kinase (Erk) inhibitors.

Starting from weak μM hits identified through affinity based Automated Ligand Identification System (ALIS) screenings, double digit nM hydroxyaniline amide Erk inhibitors were discovered. This class of compounds had the unique dual mechanism of inhibiting activated and non-activated forms of Erk. They generally had high degree of selectivity in kinase panel tested.

Discovery of novel, dual mechanism ERK inhibitors by affinity selection screening of an inactive kinase.

An affinity-based mass spectrometry screening technology was used to identify novel binders to both nonphosphorylated and phosphorylated ERK2. Screening of inactive ERK2 identified a pyrrolidine analogue 1 that bound to both nonphosphorylated and phosphorylated ERK2 and inhibited ERK2 kinase activity. Chemical optimization identified compound 4 as a novel, potent, and highly selective ERK1,2 inhibitor which not only demonstrated inhibition of phosphorylation of ERK substrate p90RSK but also demonstrated inhibition of ERK1,2 phosphorylation on the activation loop.

Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor.

A new class of quinoline-based kinase inhibitors has been discovered that both disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act as ATP competitive inhibitors. The key strategy for discovering this class of protein-protein disrupter compounds was to screen the monomer CDK2 in an affinity-selection/mass spectrometry-based technique and to perform secondary assays that identified compounds that bound only to the inactive CDK2 monomer and not the active CDK2/cyclin A heterodimer. Through a series of chemical modifications the affinity (Kd) of the original hit improved from 1 to 0.

Discovery of liver-targeted inhibitors of stearoyl-CoA desaturase (SCD1).

Inhibitors based on a benzo-fused spirocyclic oxazepine scaffold were discovered for stearoyl-coenzyme A (CoA) desaturase 1 (SCD1) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model. Initial optimization revealed potency preferences for the oxazepine core and benzylic positions, while substituents on the piperidine portions were more tolerant and allowed for tuning of potency and PK properties. After preparation and testing of a range of functional groups on the piperidine nitrogen, three classes of analogs were identified with single digit nanomolar potency: glycine amides, heterocycle-linked amides, and thiazoles.

The discovery of novel tartrate-based TNF-alpha converting enzyme (TACE) inhibitors.

A novel series of TNF-alpha convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's.