HER3 upregulation reduces DS-8201 sensitivity in HER2-positive tumor cells by ATR/CHK1/FoxO1 signaling cascade.

The anti-HER2 antibody‒drug conjugate (ADC) DS-8201 presents new hope for patients with advanced HER2-positive tumors. Its clinical application, however, is hindered by serious adverse reactions and reduced efficacy following long-term treatment. In this study, we investigated the factors influencing the sensitivity of DS-8201 and developed effective combination regimens to optimize its therapeutic efficacy.

Antiemetic drug fosaprepitant exerts anti-tumor effects against NSCLC by targeting FAK to inhibit AKT and JNK/c-Jun pathways.

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with a poor prognosis. Abnormal expression of focal adhesion kinase (FAK) is closely linked to NSCLC progression, highlighting the need for effective FAK inhibitors in NSCLC treatment. In this study we conducted high-throughput virtual screening combined with cellular assays to identify potential FAK inhibitors for NSCLC treatment.

GluN2A-NMDA receptor inhibition disinhibits the prefrontal cortex, reduces forced swim immobility, and impairs sensorimotor gating.

Recent investigations into the rapid antidepressant effects of ketamine, along with studies on schizophrenia-related susceptibility genes, have highlighted the GluN2A subunit as a critical regulator of both emotion and cognition. However, the specific impacts of acute pharmacological inhibition of GluN2A-containing NMDA receptors on brain microcircuits and the subsequent behavioral consequences remain poorly understood. In this study, we first examined the effects of MPX-004, a selective GluN2A NMDA receptor inhibitor, on behavior within the dorsomedial prefrontal cortex (dmPFC).

Peripheral vitreoretinal abnormality and its correlation with malignant glaucoma in nanophthalmos with secondary angle closure glaucoma.

Background: To evaluate the peripheral vitreoretinal abnormality (PVA) and its correlation with the risk of malignant glaucoma (MG) in nanophthalmos with secondary angle closure glaucoma (NSACG).

Methods: This prospective case series included 47 NSACG eyes with axial length (AL) < 21 mm from 25 patients. PVA was defined as a hyperreflective echo at the peripheral vitreoretinal region under ultrasound biomicroscopy (UBM).

Color-thermal multispectral camouflage with VO-based dynamic regulator.

Camouflage technology has garnered increasing attention for various applications. With the continuous advancement of detection technologies and the increasing variability of camouflage scenarios, the demand for multispectral dynamic camouflage has been steadily growing. In this work, we present a multispectral dynamic regulator based on phase-changing material vanadium dioxide (VO) that can be dynamically and functional-independently regulated for reflective color and thermal radiation.

Loss-of-function variations in solute carrier family 38 member 6 are associated with essential tremor.

Essential tremor (ET) is a common neurological disease that is characterized by 4-12 Hz kinetic tremors of the upper limbs and high genetic heterogeneity. Although numerous candidate genes and loci have been reported, the etiology of ET remains unclear. A novel ET-related gene was initially identified in a five-generation family via whole-exome sequencing, and other variants were identified in 772 familial ET probands and 640 sporadic individuals via whole-genome sequencing.

Reconfigurable nonlinear Pancharatnam-Berry diffractive optics with photopatterned ferroelectric nematics.

Planar optical elements incorporating space-varying Pancharatnam-Berry phase have revolutionized the manipulation of light fields by enabling continuous control over amplitude, phase, and polarization. While previous research focusing on linear functionalities using apolar liquid crystals (LCs) has attracted much attention, extending this concept to the nonlinear regime offers unprecedented opportunities for advanced optical processing. Here, we demonstrate the reconfigurable nonlinear Pancharatnam-Berry LC diffractive optics in photopatterned ion-doped ferroelectric nematics.

Unveiling Distinct Ultrafast Photocarrier Dynamics and Tailored Nonlinear Optical Absorption in Phase-Engineered Two-Dimensional MoTe.

Polymorphic two-dimensional (2D) transition metal dichalcogenides (TMDCs) exhibit diverse properties for optoelectronic applications. Here, utilizing phase-engineered MoTe as a prototypical platform, we comprehensively explored its ultrafast and nonlinear optical properties to complete the fundamental framework of phase-dependent optical phenomena in 2D TMDCs. Starting with the phase-selective synthesis of 2H- and 1T'-MoTe with tailored thicknesses, we revealed their distinct photocarrier relaxation mechanisms using intensive power-/temperature-/thickness-dependent transient absorption spectra (TAS).

PAZ Domain Pivoting is the Rate-Limiting Step for Target DNA Recognition in the Middle Region of Argonaute.

Argonaute (Ago) is a DNA-guided programmable endonuclease with emerging applications in genome engineering, yet the rate-determining dynamic mechanisms governing its transition from guide-target hybridization to catalytic activation remain unresolved. Here, we employ molecular dynamics simulations and the Traveling-salesman-based Automated Path Searching (TAPS) approach to dissect the target DNA recognition in the middle region (nt 9-12) of Ago. We designed two paths to tackle this problem: one assumed that coordination of the target DNA backbone occurs before base-pairing between the target and guide DNA; the other hypothesized a concerted transition without preferred order between backbone-coordination and base-pairing.

Scalable Photothermal Superhydrophobic Deicing Coating with Mechanochemical-Thermal Robustness.

Developing scalable and robust deicing coatings is essential for real-world applications, yet current coatings either suffer from intrinsic fragility or low thermal conductivity, limiting sustainability and deicing effectiveness. Here, we report a scalable and durable photothermal superhydrophobic coating coupling with enhanced thermal conductivity, engineered by embedding carbon nanotubes within a perfluoroalkoxy polymer matrix. Our design achieved 97.

Unveiling Condensed Aromatic Amines as Noteworthy Genotoxic Components in PM Dissolved Organic Matter.

The potential of PM to cause lung cancer has been well established; however, evidence regarding which specific components are responsible remains limited. We investigated dissolved organic matter (DOM) in PM using high-resolution mass spectrometry (HRMS) and cellular DNA damage assays to elucidate molecular composition and sources of carcinogenic components. Our analysis revealed hundreds of genotoxic compounds, with condensed aromatic amines predominating in number, abundance, and contribution to overall genotoxicity.

Activating the Oxygen Evolution Performance of NiCuFe by Phosphorus Doping.

The oxygen evolution reaction (OER), a critical yet kinetically sluggish process in electrochemical water splitting, severely limits efficient hydrogen production. Herein, a simple one-step dynamic hydrogen bubble templated electrodeposition technique is used to prepare a self-supported 3D porous NiCuFeP catalyst with outstanding OER performance. In 1.

Revisiting the Synthesis of Tetramethoxyindolo[3,2-]indole Derivatives and the Study of Their Photoinduced Radical Formation in Halogenated Solvents.

We previously reported that the attempt to synthesize tetramethoxyindolo[3,2-]indole led to an undefined product. Now, it is confirmed that its instability is derived from the one-electron transfer from the tetramethoxyindolo[3,2-]indole derivatives to halogenated solvents under ultraviolet-visible (UV-vis) light irradiation, forming a stable indolo[3,2-]indole radical cation while causing the carbon-halogen (C-X, X = Cl, Br, I) bond scission.

High-Performance Zirconium Disilicide Ceramics Fabricated via High-Pressure and High-Temperature Sintering.

Zirconium disilicide (ZrSi) ceramics have excellent physical and chemical properties and are employed in aerospace, energy, and chemical industries. Currently, the preparation and properties of ZrSi ceramics have been less studied. To comprehensively study the characteristics of ZrSi ceramics, in this study, dense bulk ZrSi ceramic samples are successfully prepared by the high-pressure-high-temperature (HPHT) sintering technique.

Palladium-Catalyzed Cascade Cross-Coupling/Retro-Claisen Reaction of CF-Substituted β-Diketones with -Difluorocyclopropanes.

A palladium-catalyzed cascade coupling/retro-Claisen reaction of CF-substituted β-diketones with readily available -difluorocyclopropanes has been developed. This methodology allows for the expedient synthesis of γ-fluorinated γ,δ-unsaturated ketones in a one-pot procedure with a broad scope and good to excellent yields.

Investigation into the Regulation of Ag NPs/ZnO NRs/GaN Heterostructure SERS Substrate via Pyroelectric Effects.

Heterostructures have emerged as promising contenders for surface-enhanced Raman scattering (SERS) applications. Nevertheless, the construction of a composite SERS substrate with well-matched energy levels persists as a challenge, primarily due to the restricted selection of SERS-active materials. In this study, we successfully synthesized a Ag nanoparticles (NPs)/ZnO nanorods (NRs)/GaN heterojunction featuring type II staggered energy bands, which provides an outstanding platform for efficient SERS detection.

High Current Gain Endowed by Heterojunction Engineering Coupling Interfacial Molecular Modulation: A Low-Ascorbic Acid-Dependent Organic Photoelectrochemical Transistor Aptasensing Platform.

To balance the "detection sensitivity" and "device stability" of the organic photoelectrochemical transistor (OPECT) aptasensors, it has become an urgent challenge for achieving effective signal modulation under low ascorbic acid (AA) conditions. To address this, our work proposed a collaborative optimization strategy by coupling heterojunction engineering with interfacial molecular modulation, to endow a high current gain of OPECT with low-AA -dependence. First, a CdZnS-SnInS heterojunction gate was constructed by in situ growth of CdZnS quantum dots (QDs) on SnInS nanoflowers, which enhanced the light trapping ability and photoelectric conversion efficiency of the photoactive gate.

Mapping multitissue regulatory variants reveals a liver-centric coexpression network associated with duck egg-laying performance.

Poultry egg production is shaped by the intertwined action of multiple physiological systems, greatly magnifying the complexity of its underlying genetic regulation. Although multitissue mapping of regulatory variants offers a powerful route to untangle this complexity, comprehensive data sets in ducks remain scarce. Meanwhile, the contributions of peripheral systems beyond neuroendocrine regulation on poultry egg production are still largely unexplored.

enhances oligodendrocyte differentiation via nonsense-mediated mRNA decay of variant transcripts.

Nonsense-mediated mRNA decay (NMD) is a conserved RNA surveillance mechanism that degrades transcripts with premature termination codons (PTCs) and finetunes gene expression by targeting RNA transcripts with other NMD inducing features. This study demonstrates that conditional knockout of , a key NMD component, in oligodendrocyte lineage cells disrupts the degradation of PTC-containing transcripts, including aberrant variants of the RNA-binding protein The loss of SMG5 in both sexes of mice impaired oligodendrocyte differentiation, reduced myelin gene expression, and led to thinner myelin sheaths and compromised motor function in mice. Mechanistically, HNRNPL was shown to regulate the alternative splicing of myelin-associated genes and , and promote oligodendrocyte differentiation.

Mixed functional consequences of the N651D variant: a case of early-onset developmental and epileptic encephalopathy with parkinsonism.

Rare variants in , the gene encoding the GluA3 subunit of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs), are associated with defects in early brain development. Disease-causing variants are generally categorised as either loss of function (LoF) or gain of function (GoF) that appear to be linked to different symptoms. Here, we reported a de novo variant (N651D) that has mixed LoF and GoF in a female patient with a devastating developmental and epileptic encephalopathy, parkinsonism and cortical malformation.

Causal associations of mood swings with preterm birth: a Mendelian randomization analysis.

Background: Mood swings are associated with an elevated risk of preterm birth. However, the causal relationships between them still remain unclear.

Methods: We performed a two-sample Mendelian randomization (MR) analysis to clarify the association between mood swings and preterm birth.

Graded nomograms based on perioperative parameters for predicting New-Onset severe acute kidney injury following liver transplantation in patients with normal preoperative renal function: the SALT scale.

This study aimed to develop a predictive model and construct a graded nomogram to estimate the risk of severe acute kidney injury (AKI) in patients without preexisting kidney dysfunction undergoing liver transplantation (LT). Patients undergoing LT between January 2022 and June 2023 were prospectively screened. Severe AKI was defined as Kidney Disease: Improving Global Outcomes stage 3.