107 papers
The novel SERCA pump positive allosteric modulator NDC-1171 significantly attenuates cardiac functional decline in a mouse model of Duchenne muscular dystrophy without improving skeletal muscle function.
This study presents an AI-guided strategy for designing the cyclic peptide CIP-3, a controllable CD28 antagonist that reversibly suppresses T-cell activation and treats colitis in preclinical models, offering a tunable synthetic alternative to traditional biologic immune checkpoint therapies.
This study demonstrates that spider venom lethality (LD50) and paralysis efficiency (ED50) are strongly and isometrically coupled, indicating that historically available LD50 values can serve as reliable proxies for ecologically relevant venom potency when derived from the same prey model.
This study utilizes extensive atomistic molecular dynamics simulations to demonstrate that cholesterol stabilizes the human Sigma-1 receptor trimer and that distinct agonist and antagonist ligands differentially modulate its oligomeric dynamics through specific interactions involving the 6-strand and residue W136.
This study reports the development and evaluation of novel 3-hydroxypyridin-4(1H)-one-based hybrid compounds (5a-f) that exhibit potent, selective, and non-toxic antifungal activity against *Cryptococcus neoformans* var. *grubii*, highlighting their potential as promising therapeutic candidates for treating cryptococcal meningitis.
This study demonstrates that incorporating taste-masking agents, such as Bitter Drug Powder or a combination of artificial sweeteners and a thickening agent, into a palatable vehicle significantly improves the reliability of voluntary oral dosing for bitter compounds in rats and mice, offering a refined alternative to oral gavage.
This study identifies RGS6 as a highly specific, non-redundant modulator of kappa opioid receptor-mediated antinociception that exhibits sex-specific effects, highlighting its potential as a target for developing novel analgesic therapeutics.
This study presents the first global assessment of PFAS contamination in odontocetes, revealing that genus and location are the primary predictors of accumulation, with higher concentrations found in males and younger individuals across the Pacific Ocean, indicating that contamination is widespread and increasing despite regulatory efforts.
This study reveals that the clinical-stage TREM2 agonist VG-3927 directly binds to the receptor's ectodomain hydrophobic groove, an Aβ-binding site, such that Aβ occupancy interferes with VG-3927 binding and attenuates its signaling activity, suggesting that amyloid levels may modulate agonist efficacy in Alzheimer's disease.
This study successfully extended the integrated glucose-insulin (IGI) model to quantify disease progression in individuals with impaired glucose tolerance by characterizing the annual decline in insulin secretion and sensitivity, while demonstrating that lifestyle intervention significantly slows this deterioration and improves beta-cell function.
This paper presents a Bayesian hierarchical pharmacokinetic framework that propagates uncertainty through allometric scaling to generate probability-based, risk-informed first-in-human dose recommendations for therapeutic monoclonal antibodies, demonstrating high predictive accuracy and conservative safety margins in retrospective validation against Alzheimer's disease mAbs.
This study reveals that cisplatin-induced ototoxicity is driven by the activation of MMP-2 and MMP-9, which cleave RAB proteins like RAB9A to disrupt intracellular trafficking, thereby identifying MMP-2 as a promising therapeutic target for preventing cisplatin-induced hearing loss.
This paper presents an AI-assisted workflow that streamlines the implementation of spatial Partial Differential Equation (PDE) models in NONMEM by automatically translating reaction-diffusion equations into executable Method of Lines (MOL) ODE systems, thereby overcoming the operational complexity of manual coding to enable practical, transparent, and maintainable modeling of intra-tumoral drug distribution.
This study demonstrates that while common post-hoc outlier filtering and exponential-tail residual models can be unreliable due to variance masking or insufficient tail heaviness, adopting a Student's t-distribution for residual errors provides a more robust and stable approach for handling extreme outliers in population pharmacokinetic modeling.
This paper demonstrates that the Cauchy distribution serves as a computationally efficient and robust alternative to the Student's t-distribution for handling outliers and below-quantification data in CAR-T kinetics, while a semi-mechanistic model with smooth, asynchronous transition functions enhances the physiological plausibility of expansion, conversion, and decay timing.
This study advances CAR-T cellular kinetics modeling by integrating smooth S-shaped gating and delay differential equations to better capture expansion dynamics and biological lags, revealing that a delay in effector-to-memory conversion best fits pooled data from BCMA- and CD19-targeted therapies while highlighting distinct product-specific kinetic profiles.
The paper introduces vToxiNet, a biologically constrained deep learning framework that integrates chemical, assay, and transcriptomic data with Reactome pathway hierarchies to achieve both accurate and mechanistically interpretable predictions of drug-induced hepatotoxicity.
This study establishes a tetracycline-regulated inducible CB2 expression system in AtT20 cells as a robust platform for quantifying and comparing the operational efficacy of various CB2 ligands using the Black and Leff operational model.
This study establishes that pharmaceutical-grade nicotinamide riboside chloride exhibits route-dependent acute toxicity in rats, with intravenous administration showing an estimated LD50 of approximately 2000 mg/kg while intramuscular and subcutaneous routes demonstrated LD50 values exceeding 2000 mg/kg.
This study optimized a green deep eutectic solvent extraction method for total flavonoids from *Hemerocallis citrina* and validated their multi-target antidepressant mechanism, which involves suppressing neuroinflammation and modulating the HPA axis via the PI3K-AKT pathway, through integrated network pharmacology and in vitro experiments.