Biofunctional Nanodot Arrays in Living Cells Uncover Synergistic Co-Condensation of Wnt Signalodroplets.

Qualitative and quantitative analysis of transient signaling platforms in the plasma membrane has remained a key experimental challenge. Here, biofunctional nanodot arrays (bNDAs) are developed to spatially control dimerization and clustering of cell surface receptors at the nanoscale. High-contrast bNDAs with spot diameters of ≈300 nm are obtained by capillary nanostamping of bovine serum albumin bioconjugates, which are subsequently biofunctionalized by reaction with tandem anti-green fluorescence protein (GFP) clamp fusions. Spatially controlled assembly of active Wnt signalosomes is achieved at the nanoscale in the plasma membrane of live cells by capturing the co-receptor Lrp6 into bNDAs via an extracellular GFP tag. Strikingly, co-recruitment is observed of co-receptor Frizzled-8 as well as the cytosolic scaffold proteins Axin-1 and Disheveled-2 into Lrp6 nanodots in the absence of ligand. Density variation and the high dynamics of effector proteins uncover highly cooperative liquid-liquid phase separation (LLPS)-driven assembly of Wnt "signalodroplets" at the plasma membrane, pinpointing the synergistic effects of LLPS for Wnt signaling amplification. These insights highlight the potential of bNDAs for systematically interrogating nanoscale signaling platforms and condensation at the plasma membrane of live cells.

Near-Infrared-II Light Induced Mild Hyperthermia Activate Cisplatin-Artemisinin Nanoparticle for Enhanced Chemo/Chemodynamic Therapy and Immunotherapy.

Chemodynamic therapy (CDT) is an effective cancer treatment that uses Fenton reaction to induce cancer cell death. Current clinical applications of CDT are limited by the dependency of external supply of metal ions as well as low catalytic efficiency. Here, a highly efficient metal-free CDT by using endoperoxide bridge-containing artesunate as free radical-generating substance is developed. A Pt(IV) prodrug (A-Pt) containing two artesunate molecules in the axial direction is synthesized, which can be decomposed into cisplatin and artesunate under reducing intracellular environment in tumor cells. To improve the catalytic efficiency for Fenton reaction, a near-infrared-II (NIR-II) photothermal agent IR1048 is incorporated to achieve a mild hyperthermia effect. By encapsulating the A-Pt and IR1048 with human serum albumin, A-Pt-IR NP are formulated for efficient drug delivery in 4T1 tumor-bearing mice. NIR-II light irradiation of A-Pt-IR NP treated mice show accelerated Fenton reaction. In addition, A-Pt-IR NP could also induce strong immunogenic cell death, which effectively reverses the immunosuppressive tumor microenvironment, and augments antitumor immunity. This study demonstrates that A-Pt-IR NP are potent biodegradable NIR-II active chemotherapy/CDT nanomedicine for clinical translation.

Structural and socio-cultural barriers to accessing mental healthcare among Syrian refugees and asylum seekers in Switzerland.

Background: Due to their experiences of major stressful life events, including post-displacement stressors, refugees and asylum seekers are vulnerable to developing mental health problems. Yet, despite the availability of specialized mental health services in Western European host countries, refugees and asylum seekers display low mental healthcare utilization. Objective: The aim of this study was to explore structural and socio-cultural barriers to accessing mental healthcare among Syrian refugees and asylum seekers in Switzerland. Method: In this qualitative study, key-informant (KI) interviews with Syrian refugees and asylum seekers, Swiss healthcare providers and other stakeholders (e.g. refugee coordinators or leaders) were conducted in the German-speaking part of Switzerland. Participants were recruited using snowball sampling. Interviews were audiotaped and transcribed, and then analysed using thematic analysis, combining deductive and inductive coding. Results: Findings show that Syrian refugees and asylum seekers face multiple structural and socio-cultural barriers, with socio-cultural barriers being perceived as more pronounced. Syrian key informants, healthcare providers, and other stakeholders identified language, gatekeeper-associated problems, lack of resources, lack of awareness, fear of stigma and a mismatch between the local health system and perceived needs of Syrian refugees and asylum seekers as key barriers to accessing care. Conclusions: The results show that for Syrian refugees and asylum seekers in Switzerland several barriers exist. This is in line with previous findings. A possible solution for the current situation might be to increase the agility of the service system in general and to improve the willingness to embrace innovative paths, rather than adapting mental healthcare services regarding single barriers and needs of a new target population.

Revista Europea de PsicotraumatologíaAntecedentes: Debido a sus experiencias de eventos vitales estresantes mayores, incluidos los estresores posteriores al desplazamiento, los refugiados y solicitantes de asilo son vulnerables a desarrollar problemas de salud mental. Sin embargo, a pesar de la disponibilidad de servicios especializados de salud mental en los países hospedadores de Europa occidental, los refugiados y los solicitantes de asilo muestran una baja utilización de cuidados salud mental.Objetivo: El objetivo de este estudio fue explorar las barreras estructurales y socioculturales para acceder a cuidados de salud mental para refugiados y solicitantes de asilo sirios, en Suiza.Método: En este estudio cualitativo, se realizaron entrevistas informante-clave (IC) con refugiados y solicitantes de asilo sirios, proveedores de cuidados de salud suizos y otros grupos de interes (por ejemplo, coordinadores o líderes de refugiados) en la parte de habla alemana de Suiza. Los participantes fueron reclutados mediante muestreo de bola de nieve. Las entrevistas fueron grabadas en audio y transcritas, y luego analizadas mediante análisis temático, combinando codificación deductiva e inductiva.Resultados: Los resultados muestran que los refugiados y solicitantes de asilo sirios, enfrentan múltiples barreras estructurales y socioculturales, siendo las socio-culturales percibidas como más pronunciadas. Los informantes-clave sirios, los proveedores de cuidados de salud y otras grupos de interes, identificaron el idioma, problemas asociados con la puerta de entrada a las instituciones, falta de recursos, falta de conciencia, miedo al estigma y discordancia entre el sistema de salud local y las necesidades percibidas de los sirios refugiados y solicitantes de asilo como barreras clave para acceder a la atención.Conclusiones: Los resultados muestran que para los refugiados y solicitantes de asilo sirios en Suiza existen varias barreras. Esto está en línea con hallazgos previos. Una posible solución para la situación actual podría ser aumentar la agilidad del sistema de servicios en general y mejorar la disposición a adoptar caminos innovadores, en lugar de adaptar los servicios de salud mental con respecto a las barreras y necesidades individuales de una nueva población objetivo.

Self-assembly of robust gold nanoparticle monolayer architectures for quantitative protein interaction analysis by LSPR spectroscopy.

Localized surface plasmon resonance (LSPR) detection offers highly sensitive label-free detection of biomolecular interactions. Simple and robust surface architectures compatible with real-time detection in a flow-through system are required for broad application in quantitative interaction analysis. Here, we established self-assembly of a functionalized gold nanoparticle (AuNP) monolayer on a glass substrate for stable, yet reversible immobilization of Histidine-tagged proteins. To this end, one-step coating of glass substrates with poly-L-lysine graft poly(ethylene glycol) functionalized with ortho-pyridyl disulfide (PLL-PEG-OPSS) was employed as a reactive, yet biocompatible monolayer to self-assemble AuNP into a LSPR active monolayer. Site-specific, reversible immobilization of His-tagged proteins was accomplished by coating the AuNP monolayer with tris-nitrilotriacetic acid (trisNTA) PEG disulfide. LSPR spectroscopy detection of protein binding on these biocompatible functionalized AuNP monolayers confirms high stability under various harsh analytical conditions. These features were successfully employed to demonstrate unbiased kinetic analysis of cytokine-receptor interactions. Graphical abstract.