A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors.

In 2024, several human infections with highly pathogenic clade 2.3.4.

Subradiant plasmonic cavities make bright polariton states dark.

Nanostructured plasmonic surfaces allow for precise tailoring of electromagnetic modes within sub-diffraction mode volumes, boosting light-matter interactions. This study explores vibrational strong coupling (VSC) between molecular ensembles and subradiant "dark" cavities that support infrared quadrupolar plasmonic resonances (QPLs). The QPL mode exhibits a dispersion characteristic of bound states in the continuum (BIC).

Multimaterial Thermoset Synthesis: Switching Polymerization Mechanism with Light Dosage.

The synthesis of polymeric thermoset materials with spatially controlled physical properties using readily available resins is a grand challenge. To address this challenge, we developed a photoinitiated polymerization method that enables the spatial switching of radical and cationic polymerizations by controlling the dosage of monochromatic light. This method, which we call Switching Polymerizations by Light Titration (SPLiT), leverages the use of substoichiometric amounts of a photobuffer in combination with traditional photoacid generators.

Fluorescence imaging of individual ions and molecules in pressurized noble gases for barium tagging in Xe.

The imaging of individual Ba ions in high pressure xenon gas is one possible way to attain background-free sensitivity to neutrinoless double beta decay and hence establish the Majorana nature of the neutrino. In this paper we demonstrate selective single Ba ion imaging inside a high-pressure xenon gas environment. Ba ions chelated with molecular chemosensors are resolved at the gas-solid interface using a diffraction-limited imaging system with scan area of 1 × 1 cm located inside 10 bar of xenon gas.

Creating novel metabolic pathways by protein engineering for bioproduction.

A diverse array of natural products has been produced by cell biofactories through metabolic engineering, in which enzymes play essential roles in the complex metabolic network. However, the scope of such biotransformation can be limited by the capacities of natural enzymes. To broaden their scope, many natural enzymes have recently been engineered to activate non-native substrates and/or to employ new-to-nature reaction mechanisms, but most of these systems are only demonstrated for in vitro applications.

Atmospheric deposition of pollutants at three altitudes on Mount Emei, Sichuan Basin, southwestern China.

Comparing the atmospheric deposition chemistry between above and below the planetary boundary layer (PBL) may help understand the impacts from inter-regional air pollutant transport and local emissions to air pollutant deposition. In this study, we monitored ions, soluble and insoluble potentially toxic elements (PTEs), and dissolved organic nitrogen and carbon at the base (M-base: 551 m asl), middle (M-middle: 2400 m asl), and summit (M-summit: 3077 m asl) on Mount Emei. The annual volume-weighted mean (VWM) concentrations of all measured components were substantially higher at M-base than at M-summit, except for Na, Cl, and NO as Na and Cl at M-summit may be largely from ocean and NO to NO transformation may be faster at M-base.

Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.

Receptor tyrosine kinases (RTKs) regulate many cellular functions and are important targets in pharmaceutical development, particularly in cancer treatment. EGFR and EphA2 are two key RTKs that are associated with oncogenic phenotypes. Several studies have reported functional interplay between these receptors, but the mechanism of interaction is still unresolved.

Discovery of ART0380, a Potent and Selective ATR Kinase Inhibitor Undergoing Phase 2 Clinical Studies for the Treatment of Advanced or Metastatic Solid Cancers.

One of the hallmarks of cancer is high levels of DNA replication stress and defects in the DNA damage response (DDR) pathways, which are critical for maintaining genomic integrity. Ataxia telangiectasia and Rad3-related protein (ATR) is a key regulator of the DDR machinery and an attractive therapeutic target, with multiple ATR inhibitors holding significant promise in ongoing clinical studies. Herein, we describe the discovery and characterization of ART0380 (), a potent and selective ATR inhibitor with a compelling in vitro and in vivo pharmacological profile currently undergoing Phase 2 clinical studies in patients with advanced or metastatic solid tumors as monotherapy and in combination with DNA-damaging agents (NCT04657068 and NCT05798611).

Efficacy and Safety of Selective RET Inhibitors in Patients with Advanced Hereditary Medullary Thyroid Carcinoma.

Two selective RET inhibitors (RETis) are effective in treating ()-altered medullary thyroid carcinoma (MTC), but clinical trials did not distinguish responses between hereditary MTC (hMTC) and sporadic MTC (sMTC) cases. We reviewed our single-center experience using a RETi to treat advanced hMTC. We conducted a retrospective cohort study of patients with hMTC treated with a selective RETi at a tertiary cancer center.

Atomistic Origins of Conductance Switching in an ε-CuVO Neuromorphic Single Crystal Oscillator.

Building artificial neurons and synapses is key to achieving the promise of energy efficiency and acceleration envisioned for brain-inspired information processing. Emulating the spiking behavior of biological neurons in physical materials requires precise programming of conductance nonlinearities. Strong correlated solid-state compounds exhibit pronounced nonlinearities such as metal-insulator transitions arising from dynamic electron-electron and electron-lattice interactions.

Synthesis of a PVA-GO drug delivery system for sustained release of 4-methyl umbelliferon.

Introduction: 4-methyl umbelliferon (4MU) is a coumarin with anti-inflammatory, anti-thrombotic, enzyme-inhibiting, and antioxidant properties. Despite the benefits of the compound, it is eliminated very quickly from the blood circulation through the liver, kidney, and digestive system due to its hydrophobic properties. In this study we proposed to improve the durability of 4MU by binding of 4MU to poly vinyl alcohol (PVA) and graphene oxide (GO).

Exploring the potential of malononitrile functionalized donor-acceptor systems for non-volatile memory device applications.

A novel series of D-bridge-A type organic small molecules has been designed, synthesized, and evaluated for non-volatile resistive switching write-once read-many (WORM) memory application. This study explores structure-property relationships by coupling electron-deficient malononitrile units with donors such as dibenzofuran, dibenzothiophene, and triphenylamine. Photophysical investigations revealed significant intramolecular charge transfer interaction, while electrochemical analyses demonstrated optimal band gaps ranging from 2.

Urinary volatile organic compounds (VOCs) based prostate cancer diagnosis via high-dimensional classification.

Early detection of prostate cancer is critical for successful treatment and survival. However, current diagnostic methods such as prostate-specific antigen (PSA) testing and digital rectal examination (DRE) have limitations in accuracy, specificity, and sensitivity. Recent research suggests that urinary volatile organic compounds (VOCs) could serve as potential biomarkers for prostate cancer diagnosis.

Development of a UPLC-MS/MS Method for Bioanalysis of Ethoxysanguinarine and Its Application in Pharmacokinetic Study of Ethoxysanguinarine Nanoemulsion.

Ethoxysanguinarine (ETSG), a benzophenanthridine alkaloid, exhibits diverse biological activities, including antibacterial, antifungal, anti-inflammatory, antioxidant, and anti-tumor effects. Despite these properties, limited research exists on ETSG in vivo pharmacokinetics due to its poor solubility and low bioavailability. In this study, we developed a rapid and specific UPLC-MS/MS method for ETSG bioanalysis.

UBA1 inhibition sensitizes cancer cells to PARP inhibitors.

Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells.

Steric Selection of Anion Binding Sites by Organoantimony(V) Pnictogen Bond Donors: An Experimental and Computational Study.

Catecholatostiboranes have emerged as useful Lewis acids in several applications. To better understand the factors that control the properties of these species, we examined the Lewis acidities of (-CClO)Sb(-Tol) (, Tol = tolyl) and (-CClO)Sb(-Tol) (), two triarylcatecholatostiboranes that differ by the nature of the aryl substituent. Fluoride anion binding studies indicate that is more Lewis acidic than , a factor readily assigned to the steric crowding around antimony in the case of the -tolyl derivative.

New Insights into Thermal Degradation Products of Long-Chain Per- and Polyfluoroalkyl Substances (PFAS) and Their Mineralization Enhancement Using Additives.

The products of incomplete destruction (PIDs) of per- and polyfluoroalkyl substances (PFAS) represent a substantial ambiguity when employing thermal treatments to remediate PFAS-contaminated materials. In this study, we present new information on PIDs produced in both inert and oxidative environments from five long-chain PFAS, including three now regulated under the U.S.

Initiation, Propagation, and Termination in the Chemistry of Radical SAM Enzymes.

Radical -adenosyl-l-methionine (SAM) enzymes catalyze radical mediated chemical transformations notable for their diversity. The radical mediated reactions that take place in their catalytic cycles can be characterized with respect to one or more phases of initiation, propagation, and termination. Mechanistic models abound regarding these three phases of catalysis being regularly informed and updated by new discoveries that offer insights into their detailed workings.

Base-Free Borylation of Aryl Halides Enabled by Zn-Promoted Halide Abstraction.

Herein, we report the palladium-catalyzed borylation of aryl halides (iodides or bromides) under base-free conditions utilizing a commercially available Lewis acidic mediator, Zn(OTf). Under these conditions, an array of electronically and functional-group-diverse aryl iodides and bromides undergo borylation to afford the corresponding aryl boronic esters in ≤82% isolated yields. Mechanistic investigations are consistent with Zn(OTf) enabling transmetalation between a cationic Pd(II)-Ar intermediate and Bpin via halide abstraction.

Transition Metal as Template: Reversing the Synthesis Logic in the Preparation of Pincer Complexes.

The conventional synthetic approach to transition metal pincer complexes calls for the preparation of the tridentate pincer (pro)ligand first, with subsequent introduction of the transition metal center as the last step. This work demonstrates that the alternative synthetic logic, where the central main group element is introduced last, can be applicable to a number of PEP pincer complexes (E=B, Al, Si, P) derived from phosphinophenols and phosphinopyrroles. This approach obviates the need to isolate well-behaved propincer precursors, and instead relies on the formation of phosphine-metal adducts first, whose nature determines the stoichiometry of the needed main group reagent to complete the synthesis.

Rings of Power: Controlling SOD Mimic Activity by the Addition of Pyridine Rings within the Pyridinophane Scaffold.

Superoxide dismutase enzymes are a major defense against superoxide, which is a potent reactive oxygen species. Misregulation of reactive oxygen species and subsequent neuronal damage are etiological hallmarks of neurodegenerative disease. Macrocyclic small molecules have offered inroads toward functional SOD1 mimics.

Toxicity evaluation and degradation of cypermethrin-contaminated soil using biochar and Bacillus cereus amendments.

Cypermethrin (Cyp), a persistent synthetic pyrethroid insecticide widely used for insect control. The persistence of Cyp creates toxicity to both humans and the environment This study investigates biochar and Bacillus cereus distinct and collective effects on Cyp -contaminated soil during a 90-day incubation. This study also investigates the effects of different concentrations of Cyp (50, 100, ,500 to 1000 mg kg) on soil physicochemical and biological activities during a 90-day incubation period.