Anti-inflammatory effects of cyclodextrin nanoparticles enable macrophage repolarization and reduce inflammation.

Inflammation plays a critical role in the pathophysiology of many diseases, and dysregulation of the involved signaling cascades often culminates in uncontrollable disease progression and, ultimately, chronic manifestation. Addressing these disorders requires balancing inflammation control while preserving essential immune functions. Cyclodextrins (CDs), particularly β-CD, have gained attention as biocompatible biomaterials with intrinsic anti-inflammatory properties, and chemical modification of their backbone offers a promising strategy to enhance their physicochemical properties, adaptability, and therapeutic potential.

Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention.

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of chronic liver disease with few therapeutic options. To narrow the translational gap in the development of pharmacological MASH treatments, a 3D liver model from primary human hepatocytes and non-parenchymal cells derived from patients with histologically confirmed MASH was established. The model closely mirrors disease-relevant endpoints, such as steatosis, inflammation and fibrosis, and multi-omics analyses show excellent alignment with biopsy data from 306 MASH patients and 77 controls.

Predicting nanocarrier permeation across the human intestine : model matters.

For clinical translation of oral nanocarriers, simulation of the intestinal microenvironment during testing is crucial to evaluate interactions with the intestinal mucosa. However, studies are often conducted using simplistic cell culture models, overlooking key physiological factors, and potentially leading to an overestimation of nanocarrier permeation. In this study, we systematically investigate different tissue models of the human intestine under static cultivation and dynamic flow conditions and analyze the impact of altered tissue characteristics on nanocarrier permeation.

The XENONnT dark matter experiment.

The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.

Unlocking the potential of microfold cells for enhanced permeation of nanocarriers in oral drug delivery.

The therapeutic effects of orally administered nanocarriers depend on their ability to effectively permeate the intestinal mucosa, which is one of the major challenges in oral drug delivery. Microfold cells are specialized enterocytes in the intestinal epithelium known for their high transcytosis abilities. This study aimed to compare and evaluate two targeting approaches using surface modifications of polymer-based nanocarriers, whereas one generally addresses enterocytes, and one is directed explicitly to microfold cells via targeting the sialyl Lewis motif on their surface.

Final Results of GERDA on the Two-Neutrino Double-β Decay Half-Life of ^{76}Ge.

We present the measurement of the two-neutrino double-β decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.

Influence of drug molecular weight on self-assembly and intestinal permeation of polymer-based nanocarriers.

For oral delivery, the physicochemical properties of nanocarriers are decisive factors for permeation through the intestinal epithelium. These properties are determined by the composition of the nanocarriers as well as by the process parameters during their self-assembly. For macromolecular drugs, there is still little understanding of the drug-polymer interactions during nanocarrier self-assembly and the effects on carrier properties.

High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series.

The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies.

Search for tri-nucleon decays of Ge in GERDA.

We search for tri-nucleon decays of Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to Cu, Zn, and Ga nuclei, respectively.

Searching for Heavy Dark Matter near the Planck Mass with XENON1T.

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs).

Exploring New Electroencephalogram Parameters in Electroconvulsive Therapy.

Objective: This pilot study aims to evaluate a novel metric based on the power spectrum of the EEG recordings from ECT-induced seizures-its association to volume changes in the hippocampus after ECT and improvement in depression rating scores.

Methods: Depressed patients treated with ECT underwent brain magnetic resonance imaging before and after treatment and the EEG from each seizure was recorded (N = 29). Hippocampal volume changes and EEG parameters were recorded in addition to clinician-rated and self-reported measures of depressive symptoms.

Liquid argon light collection and veto modeling in GERDA Phase II.

The ability to detect liquid argon scintillation light from within a densely packed high-purity germanium detector array allowed the Gerda experiment to reach an exceptionally low background rate in the search for neutrinoless double beta decay of Ge. Proper modeling of the light propagation throughout the experimental setup, from any origin in the liquid argon volume to its eventual detection by the novel light read-out system, provides insight into the rejection capability and is a necessary ingredient to obtain robust background predictions. In this paper, we present a model of the Gerda liquid argon veto, as obtained by Monte Carlo simulations and constrained by calibration data, and highlight its application for background decomposition.

Efficient reconstruction of cell lineage trees for cell ancestry and cancer.

Mosaic mutations can be used to track cell ancestries and reconstruct high-resolution lineage trees during cancer progression and during development, starting from the first cell divisions of the zygote. However, this approach requires sampling and analyzing the genomes of multiple cells, which can be redundant in lineage representation, limiting the scalability of the approach. We describe a strategy for cost- and time-efficient lineage reconstruction using clonal induced pluripotent stem cell lines from human skin fibroblasts.

Monte Carlo simulation of background components in low level Germanium spectrometry.

This proceeding presents the decomposition of the background spectra of the four screening detectors GeMPI 1 - 4 at the Gran Sasso Underground Laboratory (LNGS) using Monte Carlo simulations in the Geant4-based framework MaGe. A detailed understanding of the composition of the background spectra was achieved, allowing for the proposal of two new shield designs for future GeMPI-like detectors and enabling a reduction of the integrated background count rate to 15 counts/d/kg in the interval [40, 2700] keV.

Engineered Self-Assembly of Amphiphilic Cyclodextrin Conjugates for Drug Encapsulation.

Cyclodextrins are a group of naturally occurring oligosaccharides that have widely been studied and applied in pharmaceutical formulations forming inclusion complexes with a broad variety of drugs exhibiting different hydrophilicity as well as molecular weights. Grafting aliphatic chains onto native cyclodextrins renders them amphiphilic and enables self-assembly into supramolecular structures that have already been explored for drug delivery. Based on the possibility of controlling the inherent physicochemical properties by modifying their chemical structure, amphiphilic cyclodextrin conjugates hold a great potential to become a drug delivery platform adaptable to the individual needs of specific active drug molecules.

Search for New Physics in Electronic Recoil Data from XENONnT.

We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.

Erratum: First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c^{2} with GERDA [Phys. Rev. Lett. 125, 011801 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.125.

Changes in ultrasound imaging of joints, entheses, bursae and tendons 24 and 48 h after adjusted weight training.

Background: Joint effusion and enthesitis are common ultrasound findings in rheumatic diseases such as rheumatoid arthritis or spondyloarthritis. However, changes of joints and entheses were not only observed in patients but also in physically active individuals and athletes.

Objectives: The purpose of this study was to evaluate joint, entheseal, bursal and tendon musculoskeletal ultrasound (MSUS) findings in large and medium joints of young healthy individuals after completing a standardised weight training.