In-depth understanding of the structure-based reactive metabolite formation of organic functional groups.

Idiosyncratic drug-induced liver injury (DILI) is a leading cause of drug attrition and/or withdrawal. The formation of reactive metabolites is widely accepted as a key factor contributing to idiosyncratic DILI. Therefore, identifying reactive metabolites has become a critical focus during lead optimization, and a combination of GSH-/cyano-trapping and cytochrome P450 inactivation studies is recommended to identify compounds with the potential to generate reactive metabolites.

Unraveling the Solution Aggregation Structures and Processing Resiliency of High-Efficiency Organic Photovoltaic Blends.

The solution aggregation structure of conjugated polymers is crucial to the morphology and resultant optoelectronic properties of organic electronics and is of considerable interest in the field. Precise characterizations of the solution aggregation structures of organic photovoltaic (OPV) blends and their temperature-dependent variations remain challenging. In this work, the temperature-dependent solution aggregation structures of three representative high-efficiency OPV blends using small-angle X-ray/neutron scattering are systematically probed.

Controlled Assembly and Disassembly of Higher-Order Peptide Nanotubes.

The controlled peptide self-assembly and disassembly are not only implicated in many cellular processes but also possess huge application potential in a wide range of biotechnology and biomedicine. β-sheet peptide assemblies possess high kinetic stability, so it is usually hard to disassemble them rapidly. Here, we reported that both the self-assembly and disassembly of a designed short β-sheet peptide IIIGGHK could be well harnessed through the variations of concentration, pH, and mechanical stirring.

A Dual-Polythiophene Blending Strategy to Reduce the Efficiency-Stability-Cost Gap of Solar Cells.

Benefiting from the photovoltaic material innovation and delicate device optimization, high-efficiency solar cells employing polymeric materials are thriving. Reducing the gap of cost, efficiency, and stability is the critical challenge faced by the emerging solar cells such as organics, quantum dots and perovskites. Poly(3-alkylthiophene) demonstrates great potential in organic solar cells and quantum dot solar cells as the active layer or the hole transport layer due to its large scalability, excellent photoelectric performance, and favorable hydrophobicity.

Achieving Record-High Stretchability and Mechanical Stability in Organic Photovoltaic Blends with a Dilute-absorber Strategy.

Organic solar cells (OSCs) have potential for applications in wearable electronics. Except for high power conversion efficiency (PCE), excellent tensile properties and mechanical stability are required for achieving high-performance wearable OSCs, while the present metrics barely meet the stretchable requirements. Herein, this work proposes a facile and low-cost strategy for constructing intrinsically stretchable OSCs by introducing a readily accessible polymer elastomer as a diluent for all-polymer photovoltaic blends.

Development of an automatic sample changer with variable temperature for small-angle neutron scattering at China Spallation Neutron Source.

A small-angle neutron scattering (SANS) instrument at the China Spallation Neutron Source (CSNS) is an operating instrument for studying structures and inhomogeneities with dimensions ranging from 1 to 100 nm. Preparing multiple samples at once and measuring them sequentially is a common approach in SANS experiments to reduce neutron beamline wastes and increase experimental efficiency. We present the development of an automatic sample changer for the SANS instrument, including system design, thermal simulation, optimization analysis, structure design details, and temperature control test results.

Effect of Achiral Glycine Residue on the Handedness of Surfactant-Like Short Peptide Self-Assembly Nanofibers.

Surfactant-like short peptides are a kind of ideal model for the study of chiral self-assembly. At present, there are few studies on the chiral self-assembly of multicharged surfactant-like peptides. In this study, we adopted a series of short peptides of Ac-IKGK-NH with different combinations of -lysine and -lysine residues as the model molecules.

Preclinical evaluation of chemically reactive metabolites and mitigation of bioactivation in drug discovery.

The formation of reactive metabolites (RMs) is thought to be one of the pathogeneses for some idiosyncratic adverse drug reactions (IADRs) which are considered one of the leading causes of some drug attritions and/or recalls. Minimizing or eliminating the formation of RMs via chemical modification is a useful tactic to reduce the risk of IADRs and time-dependent inhibition (TDI) of cytochrome P450 enzymes (CYPs). The RMs should be carefully handled before making a go-no-go decision.

Exploiting terminal charged residue shift for wide bilayer nanotube assembly.

Hypothesis: Self-assembly of peptides is influenced by both molecular structure and external conditions, which dictate the delicate balance of different non-covalent interactions that driving the self-assembling process. The shifting of terminal charge residue is expected to influence the non-covalent interactions and their interplay, thereby affecting the morphologies of self-assemblies. Therefore, the morphology transition can be realized by shifting the position of the terminal charge residue.

Determination of the Structures of Lignin Subunits and Nanoparticles in Solution by Small-Angle Neutron Scattering: Towards Improving Lignin Valorization.

Lignin nanoparticles (LNPs) are usually produced from lignin solution through supersaturation. The structure of the lignin in solution is still poorly understood due to structural variability of isolated lignins. Here, lignins were extracted from different plants to establish a general pattern of their structure in several lignin solvents.

Optimizing the Intercrystallite Connection of a Donor-Acceptor Conjugated Semiconductor Polymer by Controlling the Crystallization Rate via Temperature.

The charge carrier transport of conjugated polymer thin film is mainly decided by the crystalline domain and intercrystallite connection. High-density tie-chain can provide an effective bridge between crystalline domains. Herein, the tie-chain connection behavior is optimized by decreasing the crystal region length (l ) and increasing the crystallization rate.

Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers.

The RAS-RAF-MEK-ERK signaling pathway plays a key role to regulate multiple cellular functions. Acquired resistance to the first-generation RAF inhibitors that only targeted the bRAF mutation prompted the need for a new generation of RAF inhibitors to target cancers bearing mutant RAS and wild type RAF activity by inhibition of paradoxical activation. Starting from the company's previously reported RAF inhibitor 1, extensive drug potency and drug-like properties optimizations led to the discovery of molecule 33 (SHR902275) with greatly improved in vitro potency and solubility.

Enhancing the interaction between cellulose and dilute aqueous ionic liquid solutions and its implication to ionic liquid recycling and reuse.

Cellulose-dissolving ionic liquids (ILs) have been used in biomass pretreatment for over a decade. Cellulose solubility in the ILs is strongly inhibited by water, which has negative impacts on IL pretreatment and reuse of the recycled ILs. Here, a distillation and aeration apparatus was used as the reactor for biomass pretreatment in dilute aqueous IL solutions and in recycled IL liquor without drying or purification.

Ordered Packing of β-Sheet Nanofibrils into Nanotubes: Multi-hierarchical Assembly of Designed Short Peptides.

Although it is well-known proteins and their complexes are hierarchically organized and highly ordered structures, it remains a major challenge to replicate their hierarchical self-assembly process and to fabricate multihierarchical architectures with well-defined shapes and monodisperse characteristic sizes via peptide self-assembly. Here we describe an amphiphilic short peptide Ac-IGGHK-NH that first preassembles into thin, left-handed β-sheet nanofibrils, followed by their ordered packing into right-handed nanotubes. The key intermediate morphology and structures featuring the hierarchical process are simultaneously demonstrated.

Unraveling the Molar Mass Dependence of Shearing-Induced Aggregation Structure of a High-Mobility Polymer Semiconductor.

Aggregation-structure formation of conjugated polymers is a fundamental problem in the field of organic electronics and remains poorly understood. Herein, the molar mass dependence of the aggregation structure of a high-mobility conjugated copolymer (TDPP-Se) comprising thiophene-flanked diketopyrrolopyrrole and selenophene is thoroughly shown. Five batches of TDPP-Se are prepared with the number-average molecular weights (M ) varied greatly from 21 to 135 kg mol .

Unique Dynamics of Hierarchical Constrained Macromolecular Ligands on Coordination Nanocage Surface Promotes Facile and Precise Assembly of Polymers.

With access to the solution structures of nanocomposites of coordination nanocages (CNCs) via scattering and chromatography techniques, their mysterious solution dynamics have been, for the first time, resolved, and interestingly, the surface macromolecules can be substituted by extra free macromolecules in solutions. Obvious exchange of macromolecules can be observed in the solution mixtures of CNC nanocomposites at high temperatures, revising the understanding of the dynamics of CNC nanocomposites. Being distinct from nanocomposites of a simple coordination complex, the quantified solution dynamics of CNC nanocomposites indicates a typical logarithmic time dependence with the dissociation of surface macromolecules as the thermodynamically limiting step, suggesting strongly coupled and hierarchically constrained dynamics among the surface macromolecules.

High-resolution mass spectrometry-based methodology for the identification of the metabolites of pterostilbene produced by rat, dog and human hepatocytes.

Pterostilbene, a natural bibenzjyl compound, has been demonstrated to have pleiotropic anticancer effects against a variety of cancer types. The aim of this study was carried out to disclose the metabolic profiles of pterostilbene using rat, dog and human hepatocytes. Metabolites were characterized by ultra-high-performance liquid chromatography/quadrupole Orbitrap mass spectrometry with electrospray ionization interface operating in positive ion mode.

A Tensile-Strained Pt-Rh Single-Atom Alloy Remarkably Boosts Ethanol Oxidation.

The rational design and control of electrocatalysts at single-atomic sites could enable unprecedented atomic utilization and catalytic properties, yet it remains challenging in multimetallic alloys. Herein, the first example of isolated Rh atoms on ordered PtBi nanoplates (PtBi-Rh ) by atomic galvanic replacement, and their subsequent transformation into a tensile-strained Pt-Rh single-atom alloy (PtBi@PtRh ) via electrochemical dealloying are presented. Benefiting from the Rh -tailored Pt (110) surface with tensile strain, the PtBi@PtRh nanoplates exhibit record-high and all-round superior electrocatalytic performance including activity, selectivity, stability, and anti-poisoning ability toward ethanol oxidation in alkaline electrolytes.

A rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry method for the determination of notoginsenoside Ft1 in rat plasma with application to pharmacokinetic study.

Notoginsenoside Ft1 (NGFt1), a dammarane triterpene glycoside isolated from Panax notoginseng, showed potent effective in stimulating platelet aggregation in our previous assay, yet its pharmacokinetic behavior is still unclear. This study describes a rapid and sensitive ultra-high-pressure LC-tandem mass spectrometry assay for determining of NGFt1 in rat plasma. Methanol-mediated precipitation was used for sample pre-treatment.

Drug metabolism and metabolite safety assessment in drug discovery and development.

Drug metabolism is one of the most important processes involving a drug after administration. Undesirable pharmacokinetic properties may lead to drug discontinuation. In the past several decades, a number of drugs have been withdrawn from the market due to safety issues caused by metabolites, especially reactive metabolites (RMs).

Two-dimensional TaC nanosheets on a reduced graphene oxide hybrid as an efficient and stable electrocatalyst for water splitting.

A novel highly active and stable HER catalyst containing two-dimensional TaC nanosheets hybridized with reduced graphene oxide (2D TaC-RGO) was prepared as an efficient and stable hydrogen evolution reaction catalyst.

Identification of Human UDP-Glucuronosyltransferase 1A4 as the Major Isozyme Responsible for the Glucuronidation of 20(S)-Protopanaxadiol in Human Liver Microsomes.

20(S)-protopanaxadiol (PPD), one of the representative aglycones of ginsenosides, has a broad spectrum of pharmacological activities. Although phase I metabolism has been investigated extensively, information regarding phase II metabolism of this compound remains to be elucidated. Here, a glucuronidated metabolite of PPD in human liver microsomes (HLMs) and rat liver microsomes (RLMs) was unambiguously identified as PPD-3-O-β-D-glucuronide by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.

Fluorine-Doped and Partially Oxidized Tantalum Carbides as Nonprecious Metal Electrocatalysts for Methanol Oxidation Reaction in Acidic Media.

A nonprecious metal electrocatalyst based on fluorine-doped tantalum carbide with an oxidative surface on graphitized carbon (TaCx FyOz/(g)C) is developed by using a simple one-pot in situ ion exchange and adsorption method, and the TaCxFyOz/(g)C shows superior performance and durability for methanol oxidation reaction and extreme tolerance to CO poisoning in acidic media.