Population Pharmacokinetics of Telmisartan in Healthy Subjects and Hypertensive Patients.

Background And Objective: Telmisartan exhibits significant pharmacokinetic (PK) variability, but it remains unclear whether its PK profile is altered in hypertensive patients. This study aimed to characterize telmisartan PKs by conducting a meta-analysis and developing a pooled population PK model based on data from healthy subjects and hypertensive patients.

Methods: Relevant literature was identified by a systematic approach.

Nanoparticle-protein interactions: Spectroscopic probing of the adsorption of serum albumin to graphene oxide‑gold nanocomplexes surfaces.

Graphene oxide‑gold nanocomposites (GO-AuNCPs) are promising candidates in nanomedicine. They will inevitably bind with biomolecules such as serum albumin (SA) in the body while they enter the organism. The interaction between GO-AuNCPs and human serum albumin (HSA)/bovine serum albumin (BSA) were investigated by using multispectroscopic methods, elucidating the binding principles through molecular simulations.

Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases.

Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients.

A Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets.

Objective: X-linked adrenoleukodystrophy (ALD) is caused by mutations in ABCD1, a peroxisomal gene. More than half of males with an ABCD1 mutation develop inflammatory cerebral demyelination (cALD), but underlying mechanisms remain unknown and therapies are limited. We sought to develop and characterize a mouse model of cALD to facilitate study of disease mechanisms and therapy development.

A transparent p-type semiconductor designed a polarizability-enhanced strongly correlated insulator oxide matrix.

Electron-transporting transparent conducting oxides (TCOs) are a commercial reality, however, hole-transporting counterparts are far more challenging because of limited material design. Here, we propose a strategy for enhancing the hole conductivity without deteriorating the band gap () and workfunction () by Cu incorporation in a strongly correlated NiWO insulator. The optimal Cu-doped NiWO (CuNiWO) exhibits a resistivity reduction of ∼10 times NiWO as well as band-like charge transport with the hole mobility approaching 7 cm V s at 200 K, a deep of 5.

PDCdb: the biological activity and pharmaceutical information of peptide-drug conjugate (PDC).

Peptide-drug conjugates (PDCs) have emerged as a promising class of targeted therapeutics with substantial pharmaceutical advantages and market potentials, which is a combination of a peptide (selective to the disease-relevant target), a linker (stable in circulation but cleavable at target site) and a cytotoxic/radioactive drug (efficacious/traceable for disease). Among existing PDCs, those based on radiopharmaceuticals (a.k.

Molecular mechanism of immunotoxicity: Binding interaction between perfluorinated compounds and human immunoglobulin G.

Perfluorinated compounds (PFCs) can induce immunotoxicity effect via binding with proteins. Immunoglobulin G (IgG) is a common four chain monomer protein in serum, and plays an important role in long-term body fluid immunity. Whether PFCs can bind with IgG and further induce immunotoxicity is not clear.

Nonarteritic Anterior Ischemic Optic Neuropathy and the Risk of Dementia: A Nationwide Cohort Study.

Background And Objectives: While emerging theories suggest that vascular dysfunction may occur concurrently with the amyloid cascade in Alzheimer disease (AD) pathogenesis, the role of vascular components as primary neurodegeneration triggers remains uncertain. The aim of this retrospective, population-based cohort study conducted in Korea was to explore the link between nonarteritic anterior ischemic optic neuropathy (NAION) and dementia risk.

Methods: In this nationwide, population-based, retrospective cohort study, we identified newly diagnosed NAION from 2010 to 2017 in the Korean National Health Insurance Service database.

The mechanism of interaction between tri-para-cresyl phosphate and human serum protein: A multispectroscopic and in-silico study.

Organophosphate flame retardants (OPFRs) pose the significant risks to the environment and human health and have become a serious public health issue. Tricresyl phosphates (TCPs), a group of aryl OPFRs, exhibit neurotoxicity and endocrine disrupting toxicity. However, the binding mechanisms between TCPs and human serum albumin (HSA) remain unknown.

Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication.

Zolpidem is a widely prescribed hypnotic Z-drug used to treat short-term insomnia. However, a growing number of individuals intentionally overdose on these drugs. This study aimed to develop a predictive tool for physicians to assess patients with zolpidem overdose.

Insights into interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin via multi-spectral analysis.

In this study, the interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin (HSA) are investigated through UV-vis, fluorescence, and circular dichroism (CD) spectra. The mechanisms on the fluorescence quenching of HSA initiated by triazine herbicides are obtained using Stern-Volmer, Lineweaver-Burk and Double logarithm equations. The quenching rate constant (K), Stern-Volmer quenching constant (K), binding constant (K), thermodynamic parameters such as enthalpy change (∆H), entropy change (∆S) and Gibbs free energy (∆G) and number of binding site (n) are calculated and compared.

Autologous cell transplantation for treatment of colorectal aganglionosis in mice.

Neurointestinal diseases cause significant morbidity and effective treatments are lacking. This study aimes to test the feasibility of transplanting autologous enteric neural stem cells (ENSCs) to rescue the enteric nervous system (ENS) in a model of colonic aganglionosis. ENSCs are isolated from a segment of small intestine from Wnt1::Cre;R26iDTR mice in which focal colonic aganglionosis is simultaneously created by diphtheria toxin injection.

Single-Strand "Short Isometric Construct" Medial Collateral Ligament Reconstruction Restores Valgus and Rotational Stability While Isolated Deep MCL and Superficial MCL Reconstruction Do Not.

Background: Historical MCL (medial collateral ligament) reconstruction (MCLR) techniques have focused on the superficial MCL (sMCL) to restore valgus stability while frequently ignoring the importance of the deep MCL (dMCL) in controlling tibial external rotation. The recent recognition of the medial ligament complex importance has multiple studies revisiting medial anatomy and questioning contemporary MCLR techniques.

Purpose: To assess whether (1) an isolated sMCL reconstruction (sMCLR), (2) an isolated dMCL reconstruction (dMCLR), or (3) a novel single-strand short isometric construct (SIC) would restore translational and rotational stability to a knee with a dMCL and sMCL injury.

Adaptive and Ultrahigh-Affinity Recognition in Water by Sulfated Conjugated Corral[5]arene.

The pursuit of synthetic receptors with high binding affinities has long been a central focus in supramolecular chemistry, driven by their significant practical relevance in various fields. Despite the numerous synthetic receptors that have been developed, most exhibit binding affinities in the micromolar range or lower. Only a few exceptional receptors achieve binding affinities exceeding 10  M , and their substrate scopes remain rather limited.

Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial.

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC.

A novel mouse model of cerebral adrenoleukodystrophy highlights NLRP3 activity in lesion pathogenesis.

Objective: We sought to create and characterize a mouse model of the inflammatory, cerebral demyelinating phenotype of X-linked adrenoleukodystrophy (ALD) that would facilitate the study of disease pathogenesis and therapy development. We also sought to cross-validate potential therapeutic targets such as fibrin, oxidative stress, and the NLRP3 inflammasome, in post-mortem human and murine brain tissues.

Background: ALD is caused by mutations in the gene encoding a peroxisomal transporter.

A Janus CrSSe monolayer with interesting ferromagnetism.

The search for intrinsic half-metallic ferromagnetic (FM) monolayers with a high Curie temperature (), considerable magnetic anisotropy energy (MAE), and multiferroic coupling is key for the development of ultra-compact spintronics. Here, we have identified a new stable FM Janus monolayer, the tetrahedral CrSSe, through first-principles structural search calculations, which not only exhibits very interesting magnetoelectric properties with a high of 790 K, a large MAE of 0.622 meV per Cr, and robust half-metallicity, but also shows obvious ferroelasticity with a modest energy barrier of 0.

Measurement of the Time-Integrated CP Asymmetry in D^{0}→K^{-}K^{+} Decays.

The time-integrated CP asymmetry in the Cabibbo-suppressed decay D^{0}→K^{-}K^{+} is measured using proton-proton collision data, corresponding to an integrated luminosity of 5.7  fb^{-1} collected at a center-of-mass energy of 13 TeV with the LHCb detector. The D^{0} mesons are required to originate from promptly produced D^{*+}→D^{0}π^{+} decays, and the charge of the companion pion is used to determine the flavor of the charm meson at production.

Peripapillary Vascular Density in Compressive Optic Neuropathy and Normal-Tension Glaucoma: A Severity-Controlled Comparison.

Purpose: To investigate the differences in peripapillary vessel density (VD) between compressive optic neuropathy (CON) and normal-tension glaucoma (NTG).

Methods: We compared patients with chronic CON and NTG, particularly after strictly controlling the mean extent of macular damage by the area of the ganglion cell-inner plexiform layer (GCIPL) loss in optical coherence tomography (OCT). We compared retinal nerve fiber layer (RNFL) and GCIPL thickness from OCT and peripapillary and macular VD from OCT angiography (OCTA) between the CON and NTG groups.

Barcoded multiple displacement amplification for high coverage sequencing in spatial genomics.

Determining mutational landscapes in a spatial context is essential for understanding genetically heterogeneous cell microniches. Current approaches, such as Multiple Displacement Amplification (MDA), offer high genome coverage but limited multiplexing, which hinders large-scale spatial genomic studies. Here, we introduce barcoded MDA (bMDA), a technique that achieves high-coverage genomic analysis of low-input DNA while enhancing the multiplexing capabilities.