A human kidney and liver organoid-based multi-organ-on-a-chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell-derived extracellular vesicles.

Mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) show therapeutic potential in multiple disease models, including kidney injury. Clinical translation of sEVs requires further preclinical and regulatory developments, including elucidation of the biodistribution and mode of action (MoA). Biodistribution can be determined using labelled sEVs in animal models which come with ethical concerns, are time-consuming and expensive, and may not well represent human physiology.

Logic-gated antibody pairs that selectively act on cells co-expressing two antigens.

The use of therapeutic monoclonal antibodies is constrained because single antigen targets often do not provide sufficient selectivity to distinguish diseased from healthy tissues. We present HexElect, an approach to enhance the functional selectivity of therapeutic antibodies by making their activity dependent on clustering after binding to two different antigens expressed on the same target cell. lmmunoglobulin G (lgG)-mediated clustering of membrane receptors naturally occurs on cell surfaces to trigger complement- or cell-mediated effector functions or to initiate intracellular signaling.

An efficient method to prepare supported bismuth nanoparticles as highly selective electrocatalyst for the conversion of CO into formate.

We report a cost-effective, straightforward synthesis of a novel electrocatalyst for the reduction of CO2 to formate, which achieves nearly complete Faradaic efficiency (FE) at an overpotential (η) of 0.88 V under ambient conditions. The electrocatalyst was prepared using bismuth subsalicylate as precursor and consists of bismuth nanoparticles (Bi NPs) with an average diameter of 5.

Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine.

Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential.

Dual Epitope Targeting and Enhanced Hexamerization by DR5 Antibodies as a Novel Approach to Induce Potent Antitumor Activity Through DR5 Agonism.

Higher-order death receptor 5 (DR5) clustering can induce tumor cell death; however, therapeutic compounds targeting DR5 have achieved limited clinical efficacy. We describe HexaBody-DR5/DR5, an equimolar mixture of two DR5-specific IgG1 antibodies with an Fc-domain mutation that augments antibody hexamerization after cell surface target binding. The two antibodies do not compete for binding to DR5 as demonstrated using binding competition studies, and binding to distinct epitopes in the DR5 extracellular domain was confirmed by crystallography.

Detection of Barrett's oesophagus through exhaled breath using an electronic nose device.

Timely detection of oesophageal adenocarcinoma (OAC) and even more so its precursor Barrett's oesophagus (BO) could contribute to decrease OAC incidence and mortality. An accurate, minimally-invasive screening method for BO for widespread use is currently not available. In a proof-of-principle study in 402 patients, we developed and cross-validated a BO prediction model using volatile organic compounds (VOCs) analysis with an electronic nose device.

DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing.

Background: DuoBody®-CD3xCD20 (GEN3013) is a full-length human IgG1 bispecific antibody (bsAb) recognizing CD3 and CD20, generated by controlled Fab-arm exchange. Its Fc domain was silenced by introduction of mutations L234F L235E D265A.

Methods: T-cell activation and T-cell-mediated cytotoxicity were measured by flow cytometry following co-culture with tumour cells.

Satellite cells maintain regenerative capacity but fail to repair disease-associated muscle damage in mice with Pompe disease.

Pompe disease is a metabolic myopathy that is caused by glycogen accumulation as a result of deficiency of the lysosomal enzyme acid alpha glucosidase (GAA). Previously, we showed that adult muscle stem cells termed satellite cells are present at normal levels in muscle from patients with Pompe disease, but that these are insufficiently activated to repair the severe muscle pathology. Here we characterized the muscle regenerative response during disease progression in a mouse model of Pompe disease and investigated the intrinsic capacity of Gaa satellite cells to regenerate muscle damage.

Why and when hierarchy impacts team effectiveness: A meta-analytic integration.

Hierarchy has the potential to both benefit and harm team effectiveness. In this article, we meta-analytically investigate different explanations for why and when hierarchy helps or hurts team effectiveness, drawing on results from 54 prior studies (N = 13,914 teams). Our findings show that, on net, hierarchy negatively impacts team effectiveness (performance: ρ = -.

Trust and team performance: A meta-analysis of main effects, moderators, and covariates.

Cumulating evidence from 112 independent studies (N = 7,763 teams), we meta-analytically examine the fundamental questions of whether intrateam trust is positively related to team performance, and the conditions under which it is particularly important. We address these questions by analyzing the overall trust-performance relationship, assessing the robustness of this relationship by controlling for other relevant predictors and covariates, and examining how the strength of this relationship varies as a function of several moderating factors. Our findings confirm that intrateam trust is positively related to team performance, and has an above-average impact (ρ = .

Papillary fill response in single-tooth implants using abutments of different geometry.

Objective: To evaluate the influence of abutment geometry on papillary fill in the esthetic zone in a delayed crown protocol.

Materials And Methods: Twenty-six subjects received two non-adjacent endosseous implants in the esthetic zone. Functional temporary crowns were installed 17-19 weeks later, using conventional (control) and curved (experimental) abutments.

Beyond shared perceptions of trust and monitoring in teams: implications of asymmetry and dissensus.

Past research has implicitly assumed that only mean levels of trust and monitoring in teams are critical for explaining their interrelations and their relationships with team performance. In this article, the authors argue that it is equally important to consider the dispersion in trust and monitoring that exists within teams. The authors introduce "trust asymmetry" and "monitoring dissensus" as critical dispersion properties of trust and monitoring and hypothesize that these moderate the relationships between mean monitoring, mean trust, and team performance.