Design, synthesis, and biological activity of novel para-substituted phenylamino and phenyl derivatives of northebaine as selective delta opioid receptor agonists.

The delta opioid receptor (DOR) is a promising target for developing analgesics with fewer side effects compared to mu opioid receptor (MOR) agonists. However, non-peptidyl DOR-selective agonists remain limited. Using the "message-address" concept in opioid ligand design, we designed and synthesized a series of para-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoetheno-tetrahydronorthebaines to explore their binding affinity and selectivity for DOR over MOR and kappa opioid receptor (KOR).

Correlation between unconventional superconductivity and strange metallicity revealed by operando superfluid density measurements.

Strange-metal behavior has been observed in superconductors ranging from cuprates to pressurized nickelates, but its relationship to unconventional superconductivity remains elusive. Here, we perform operando superfluid density measurements on ion-gated FeSe films. We observe a synchronized evolution of the superconducting condensate and the strange-metal phase with electron doping, from which a linear scaling between zero-temperature superfluid density and strange-metal resistivity coefficient is further established.

A Theoretical Study on Tailoring the Nitrile Substitution Strategy in Carbonates for Lithium-Ion Batteries.

Improving the operating voltage is an effective strategy for enhancing the energy density of lithium-ion batteries. However, this approach raises critical challenges, including oxidative decomposition of the electrolyte and degradation of electrode materials, which urgently require solutions. In this context, nitrile compounds, characterized by their strong electron-withdrawing effect, high dielectric constant, and excellent oxidation stability, have emerged as ideal materials for optimizing high-voltage electrolytes.

Quantum spin liquid from electron-phonon coupling.

A quantum spin liquid (QSL) is an exotic insulating phase with emergent gauge fields and fractionalized excitations. However, the unambiguous demonstration of the existence of a QSL in a "nonengineered" microscopic model (or in any material) remains challenging. Here, using numerically exact sign-problem-free quantum Monte Carlo simulations, we show that a QSL arises in a nonengineered electron-phonon model.

Structure-Activity Relationship of -Cyclopropylmethyl-7α-[-(arylcarboxamido)phenyl]-6,14-ethano-tetrahydronorthebaines as Potent and Selective Kappa Opioid Receptor Agonists.

Research on KOR agonists with reduced central nervous system side effects represents a significant area in analgesic studies. Herein, a structure-activity relationship analysis was performed for a series of -cyclopropylmethyl-7α-[-(arylcarboxamido)phenyl]-6,14-ethano-tetrahydronorthebaines. Several highly selective and potent KOR agonists have been identified.

Anisotropic phase stiffness in infinite-layer nickelates superconductors.

In unconventional superconductors such as cuprates and iron pnictides and chalcogenides, phase stiffness-a measure of the energy cost associated with superconducting phase variations-governs the formation of superconductivity. Here we demonstrate a vector current technique enabling in-situ angle-resolved transport measurements to reveal anisotropic phase stiffness in infinite-layer nickelate superconductors. Pronounced anisotropy of in-plane resistance manifests itself in both normal and superconducting transition states, indicating crystal symmetry breaking.

LncRNA small nucleolar RNA host gene 1 (SNHG1) mediates acidic bile salt-induced EMT via the ULK1-Notch1 axis in Barrett's esophagus.

Barrett's esophagus (BE) is a precancerous condition closely linked to chronic gastroesophageal reflux disease, characterized by the abnormal transformation of esophageal squamous mucosa into specialized intestinal-type epithelium, significantly elevating the risk of esophageal adenocarcinoma (EAC). Recurrent acidic bile reflux promotes epithelial-mesenchymal transition (EMT), a critical event driving malignant progression. However, the underlying molecular mechanisms remain incompletely understood.

Finite-time scaling beyond the Kibble-Zurek prerequisite in Dirac systems.

The conventional Kibble-Zurek mechanism and the finite-time scaling provide universal descriptions of the driven critical dynamics from gapped initial states based on the adiabatic-impulse scenario. Here we investigate the driven critical dynamics in two-dimensional Dirac systems, which harbor semimetal and Mott insulator phases separated by the quantum critical point triggered by the interplay between fluctuations of gapless Dirac fermions and order parameter bosons. We find that despite the existence of the gapless initial phase, the driven dynamics can still be captured by the finite-time scaling form.

Insight into the Tuning Fluorination of Carbonates for Lithium-Ion Batteries: A Theoretical Study.

In the field of lithium-ion batteries, fluorinated solvents and additives have been proven to be crucial for enhancing battery performance, including cyclic stability, energy density, and high-low temperature adaptability. However, the impact of the number and position of fluorine substitutions on the properties of fluorinated solvents remains underexplored. To address this knowledge gap, we conducted quantum chemical calculations and molecular dynamics simulations on a series of fluorinated cyclic carbonates based on ethylene carbonate (EC) and propylene carbonate (PC).

Unraveling the mysterious veil of ULK1: From non-canonical functions to therapeutic applications.

ULK1 (Unc-51-like kinase 1) is a pivotal regulator of autophagy, now recognized for its roles in cellular homeostasis, metabolism, immune modulation, and disease progression. Beyond autophagy, ULK1 influences inflammasome activation, metabolic reprogramming, and immune signaling, revealing its dual role in cancer and neurodegenerative disorders. The complexity of ULK1's functions necessitates the development of selective small-molecule modulators to precisely target its non-canonical pathways.

Inflammation as a key mediator: linking triglyceride-glucose index to prognosis in non-muscle-invasive bladder cancer.

Background: Bladder carcinoma (BCa) is a prevalent urological malignancy characterised by high recurrence and progression rates, posing significant challenges in clinical management. The triglyceride-glucose (TyG) index has emerged as a promising prognostic marker for metabolic health in various cancers. This study explores the prognostic value of the TyG index in non-muscle-invasive bladder cancer (NMIBC), with a focus on its association with high-grade recurrence-free survival (RFS) and progression-free survival (PFS) and the mediating role of systemic inflammation.

Superconductivity and Charge Density Wave in the Holstein Model on the Penrose Lattice.

The exotic quantum states emerging in the quasicrystal (QC) have attracted extensive interest because of various properties absent in the crystal. In this Letter, we systematically study the Holstein model at half filling on a prototypical structure of QC, namely rhombic Penrose lattice, aiming at investigating the superconductivity (SC) and other intertwined ordering arising from the interplay between quasiperiodicity and electron-phonon interaction. Through unbiased sign-problem-free determinant quantum Monte Carlo simulations, we reveal the salient features of the ground state phase diagram.

Niacin skin flushing response in patients with schizophrenia: Associations with the efficacy of modified electroconvulsive therapy and clinical symptoms.

Objective: Schizophrenia (SZ) is a group of chronic neurodevelopmental disorders, and antipsychotic medication is the main clinical treatment. However, approximately one-third of patients demonstrate inadequate response to these medications, which is termed treatment-resistant schizophrenia (TRS). The primary objective of this study was to explore the clinical characteristics of patients with TRS, including positive, negative, general psychotic symptoms and niacin skin flushing response (NSFR), which is considered an auxiliary diagnostic biomarker for SZ, and the improvement of these characteristics after modified electroconvulsive therapy (MECT).

Structure-activity relationship analysis of meta-substituted N-cyclopropylmethyl-nornepenthones with mixed KOR/MOR activities.

Substance Use Disorder (SUD) remains a significant global challenge, with current treatment options offering limited efficacy. Agonists targeting the kappa opioid receptor (KOR), especially those with additional mu opioid receptor (MOR) antagonistic activity, have shown promise in addressing SUD. In this study, a series of meta-substituted N-cyclopropylmethyl-nornepenthone derivatives were designed and synthesized, and their biological activities were assessed, leading to the identification of a KOR/MOR dual modulator, compound 10a.

Tumor burden with AFP improves survival prediction for TACE-treated patients with HCC: An international observational study.

Background & Aims: Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification.

Methods: Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets.

Uncovering Emergent Spacetime Supersymmetry with Rydberg Atom Arrays.

In the zoo of emergent symmetries in quantum many-body physics, the previously unrealized emergent spacetime supersymmetry (SUSY) is particularly intriguing. Although it was known that spacetime SUSY could emerge at the (1+1)d tricritical Ising transition, an experimental realization is still absent. In this Letter, we propose to realize emergent spacetime SUSY using reconfigurable Rydberg atom arrays featuring two distinct sets of Rydberg excitations, tailored for implementation on dual-species platforms.

Avicularin inhibits ferroptosis and improves cognitive impairments in Alzheimer's disease by modulating the NOX4/Nrf2 axis.

Background: Alzheimer's disease (AD) is a widespread neurodegenerative disorder for which effective therapies remain elusive, primarily due to the complexity of its underlying pathophysiology. In recent years, natural products have gained attention for their therapeutic potential in AD, owing to their multi-targeted actions and low toxicity profiles. Avicularin (Avi), a flavonoid derived from the peels of Zanthoxylum bungeanum Maxim.

Targeting eukaryotic elongation factor 2 kinase (eEF2K) with small-molecule inhibitors for cancer therapy.

Eukaryotic elongation factor 2 kinase (eEF2K) is a member of the α-kinase family that is activated by calcium/calmodulin. Of note, eEF2K is crucial for regulating translation and is often highly overexpressed in malignant cells. Therefore in this review, we summarize the molecular structure of eEF2K and its oncogenic roles in cancer.

A contrast-enhanced computed tomography-based radiomics nomogram for preoperative differentiation between benign and malignant cystic renal lesions.

Background: There is lack of discrimination as to traditional imaging diagnostic methods of cystic renal lesions (CRLs). This study aimed to evaluate the value of machine learning models based on clinical data and contrast-enhanced computed tomography (CECT) radiomics features in the differential diagnosis of benign and malignant CRL.

Methods: There were 192 patients with CRL (Bosniak class ≥ II) enrolled through histopathological examination, including 144 benign cystic renal lesions (BCRLs) and 48 malignant cystic renal lesions (MCRLs).

Nanozymes: Potential Therapies for Reactive Oxygen Species Overproduction and Inflammation in Ischemic Stroke and Traumatic Brain Injury.

Nanozymes, which can selectively scavenge reactive oxygen species (ROS), have recently emerged as promising candidates for treating ischemic stroke and traumatic brain injury (TBI) in preclinical models. ROS overproduction during the early phase of these diseases leads to oxidative brain damage, which has been a major cause of mortality worldwide. However, the clinical application of ROS-scavenging enzymes is limited by their short in vivo half-life and inability to cross the blood-brain barrier.