Pittssharp0851

Although on-demand cargo release has been demonstrated in a wide range of microparticle platforms, many existing methods lack specific loading interactions and/or undergo permanent damage to the microparticle to release the cargo. Here, we report a novel method for electrostatically loading negatively charged molecular cargo in oligoviologen-crosslinked microparticles, wherein the cargo can be released upon activation by visible light. A water-in-oil (W/O) emulsion polymerization method was used to fabricate narrowly dispersed microparticles crosslinked by a dicationic viologen-based dimer and a poly(ethylene glycol) diacrylate. A zinc-tetraphenyl porphyrin photocatalyst was also polymerized into the microparticle and used to photochemically reduce the viologen subunits to their monoradical cations through a visible-light-mediated photoredox mechanism with triethanolamine (TEOA) as a sacrificial reductant. The microparticles were characterized by microscopy methods revealing uniform, spherical microparticles 481 ± 20.9 nm in diameter. Negatively charged molecular cargo (methyl orange, MO) was electrostatically loaded into the microparticles through counteranion metathesis. Upon irradiation with blue (450 nm) light, the photo-reduced viologen crosslinker subunits lose positive charges, resulting in release of the anionic MO cargo. Controlled release of the dye, as tracked by absorption spectroscopy, was observed over time, yielding release of up to 40% of the cargo in 48 h and 60% in 120 h in single dynamic dialysis experiment. However, full release of cargo was achieved upon transferring the microparticles to a fresh TEOA solution after the initial 120 h period.COVID-19 has resulted in dramatic and widespread social network interventions across the globe, with public health measures such as distancing and isolation key epidemiological responses to minimize transmission. Because these measures affect social interactions between people, the networked structure of daily lives is changed. Such largescale changes to social structures, present simultaneously across many different societies and touching many different people, give renewed significance to the conceptualization of social network interventions. As social network researchers, we need a framework for understanding and describing network interventions consistent with the COVID-19 experience, one that builds on past work but able to cast interventions across a broad societal framework. In this theoretical paper, we extend the conceptualization of social network interventions in these directions. We follow Valente (2012) with a tripartite categorization of interventions but add a multilevel dimension to capture hierarchical aspects that are a key feature of any society and implicit in any network. This multilevel dimension distinguishes goals, actions, and outcomes at different levels, from individuals to the whole of the society. We illustrate this extended taxonomy with a range of COVID-19 public health measures of different types and at multiple levels, and then show how past network intervention research in other domains can also be framed in this way. We discuss what counts as an effective network, an effective intervention, plausible causality, and careful selection and evaluation, as central to a full theory of network interventions.Cascading activity is commonly observed in complex dynamical systems, including networks of biological neurons, and how these cascades spread through the system is reliant on how the elements of the system are connected and organized. In this work, we studied networks of neurons as they matured over 50 days in vitro and evaluated both their dynamics and their functional connectivity structures by observing their electrophysiological activity using microelectrode array recordings. Correlations were obtained between features of their activity propagation and functional connectivity characteristics to elucidate the interplay between dynamics and structure. The results indicate that in vitro networks maintain a slightly subcritical state by striking a balance between integration and segregation. Our work demonstrates the complementarity of these two approaches-functional connectivity and avalanche dynamics-in studying information propagation in neurons in vitro, which can in turn inform the design and optimization of engineered computational substrates.Trust in pension providers by participants is essential because pension providers try to fulfill their pension promises in a fundamentally uncertain world. Reforms and crises are therefore the ultimate testing ground for pension trust. In this paper we estimate with repeated cross-sectional survey data how trust and distrust in Dutch pension funds and the government have evolved over the period 2004-2021 and what the impact of financial stability on trust in these two institutions has been. NDI-091143 in vitro Financial stability of pension funds, measured by their funding ratio, is shown to affect trust positively, but it does not decrease distrust significantly. Based on the estimation results, achieving a situation where the majority of the adult population trusts pension funds is likely to be attained at funding ratios of 115 or higher. Financial stability of government (measured by government debt/GDP ratio) does not affect either trust or distrust levels. Underlying drivers of distrust and trust such as personal characteristics are also notable self-employed are more prone to distrust pension funds than employees. Women are more than men likely to take a neutral position.

Sporadic Inclusion Body Myositis (IBM) is an inflammatory muscle disease affecting individuals over the age of 45, leading to progressive muscle wasting, disability and loss of independence. Histologically, IBM is characterised by immune changes including myofibres expressing major histocompatibility complex molecules and invaded by CD8

T cells and macrophages, and by degenerative changes including protein aggregates organised in inclusion bodies, rimmed vacuoles and mitochondrial abnormalities. There is currently no cure, and regular exercise is currently the only recognised treatment effective at limiting muscle weakening, atrophy and loss of function. Testosterone exerts anti-inflammatory effects, inhibiting effector T-cell differentiation and pro-inflammatory cytokine production.

We conducted a double-blind, placebo-controlled, cross-over trial in men with IBM, to assess whether a personalised progressive exercise training combined with application of testosterone, reduced the inflammatory immune reomitant testosterone supplementation provides some additional changes. Further studies combining testosterone and exercise would be worthwhile in larger cohorts and longer testosterone administration periods.

A subset of chronic obstructive pulmonary disease (COPD) patients have increased numbers of airway eosinophils associated with elevated markers of T2 inflammation. This analysis focussed on mast cell counts and mast cell-related gene expression in COPD patients with higher vs lower eosinophil counts.

We investigated gene expression of tryptase (

), carboxypeptidase A3

), chymase (

) and two mast cell specific gene signatures; a bronchial biopsy signature (MC

) and an IgE signature (MC

) using sputum cells and bronchial epithelial brushings. Gene expression analysis was conducted by RNA-sequencing. We also examined bronchial biopsy mast cell numbers by immunohistochemistry.

There was increased expression of

and MC

in eosinophil

than in eosinophil

COPD patients in sputum cells and bronchial epithelial brushings (fold change differences 1.21 and 1.28, respectively,

 0.01). Mast cell gene expression was associated with markers of T2 and eosinophilic inflammation (

, eosinophil counts in sputum and bronchial mucosa; rho = 0.4-0.8;

 0.05). There was no difference in MC

gene expression between groups. There was no difference in the total number of bronchial biopsy mast cells between groups.

These results demonstrate that eosinophilic inflammation is associated with altered mast cell characteristics in COPD patients, implicating mast cells as a component of T2 inflammation present in a subset of COPD patients.

These results demonstrate that eosinophilic inflammation is associated with altered mast cell characteristics in COPD patients, implicating mast cells as a component of T2 inflammation present in a subset of COPD patients.

Although adoptive cell therapy with T-cell receptor-engineered T cells (TCR-Ts) has mediated effective antitumor responses in several cancers, senescence of T cells could impair the therapeutic effect of TCR-Ts. Thus, it is essential to elucidate the characteristics of senescent TCR-Ts and how to subsequently improve their antitumor effect. Here, we focused on the influence of autophagy on TCR-Ts, since autophagy is tightly associated with the regulation of T-cell activation, proliferation and differentiation.

We first evaluated autophagy level of senescent TCR-Ts, and then the senescent TCR-Ts were expanded

for 7 days with and without spermidine treatment, respectively. Furthermore, the proliferative potential, phenotypical characteristics and functionality of the propagated senescent TCR-Ts were analysed

and

after 7-day

expansion.

We found that autophagic flux of senescent TCR-T cells was significantly impaired. The restoration of autophagic flux via spermidine treatment reduced the expression of inhibitory immunoreceptors (PD-1, TIM-3 or LAG-3), enhanced proliferation and effector functions and subsequently demonstrated the superior

and

antitumor activity of TCR-Ts.

These data suggest that spermidine treatment presents an opportunity to improve the antitumor effect of TCR-Ts for the treatment of solid tumors.

These data suggest that spermidine treatment presents an opportunity to improve the antitumor effect of TCR-Ts for the treatment of solid tumors.The tumor microenvironment (TME) plays a key role in the poor prognosis of many cancers. However, there is a knowledge gap concerning how multicellular communication among the critical players within the TME contributes to such poor outcomes. Using epithelial ovarian cancer (EOC) as a model, we show how crosstalk among cancer cells (CC), cancer associated fibroblasts (CAF), and endothelial cells (EC) promotes EOC growth. We demonstrate here that co-culturing CC with CAF and EC promotes CC proliferation, migration, and invasion in vitro and that co-implantation of the three cell types facilitates tumor growth in vivo. We further demonstrate that disruption of this multicellular crosstalk using a gold nanoparticle (GNP) inhibits these pro-tumorigenic phenotypes in vitro as well as tumor growth in vivo. Mechanistically, GNP treatment reduces expression of several tumor-promoting cytokines and growth factors, resulting in inhibition of MAPK and PI3K-AKT activation and epithelial-mesenchymal transition - three key oncogenic signaling pathways responsible for the aggressiveness of EOC. The current work highlights the importance of multicellular crosstalk within the TME and its role for the aggressive nature of EOC, and demonstrates the disruption of these multicellular communications by self-therapeutic GNP, thus providing new avenues to interrogate the crosstalk and identify key perpetrators responsible for poor prognosis of this intractable malignancy.