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Improved Safety of New MicroRNA-Regulated Oncolytic Coxsackievirus B3 Observed After Intravenous Administration in Colorectal-Tumor-Bearing Mice
No full textOncolytic coxsackievirus B3 (oCVB3) strain PD-H has shown potent oncolytic efficacy and a remarkable safety profile in the treatment of colorectal cancer in vivo after intratumoral (i.t.) injection. In this study, we investigated the safety and efficiency of PD-H following intravenous (i.v.) virus administration. When injected i.v. into Balb/C mice bearing subcutaneous Colon-26 tumors, PD-H led to slightly reduced tumor progression and a significant increase in animal survival, but it also caused multi-organ infection and tissue damage. To improve the safety profile of PD-H, we inserted microRNA target sites (miR-TS) of the heart-specific miR-1, pancreas-specific miR-375, liver-specific miR-122, and brain-specific miR-124 or the tumor-suppressor miR-145 into the genome of PD-H and generated the viruses PD-622TS and PD-145TS. Both viruses replicated similarly and induced cytotoxicity comparable to that of PD-H in the colorectal carcinoma cell lines Colon-26 and CT-26Luc. Their replication was inhibited in HEK293T cells transiently transfected with the cognate microRNAs. In vivo, i.v. administration of PD-145TS and PD-622TS to healthy Balb/C mouse resulted in significantly lower viral titers in the organs of mice and led to significantly less-intense pathological alterations compared to PD-H. PD-622TS injected i.v. into Balb/C mice with CT-26Luc-induced peritoneal carcinomatosis did not induce off-target alterations in normal organs, but it failed to induce a therapeutic effect. These data indicate that PD-H or microRNA-regulated PD derivatives exhibit only limited therapeutic efficacy following i.v. injection in colorectal tumor-bearing mice. However, the newly engineered microRNA-regulated PD-H variants demonstrate improved safety profiles
Exploring the association between housing insecurity and mental health among renters: A systematic review of quantitative primary and secondary studies
No full textAdverse social and economic conditions negatively impact mental health and well-being. To the best of the authors’ knowledge, the present systematic review is the first to investigate the association between housing insecurity and mental health outcomes among renters, with a focus on housing affordability and instability. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted in December 2022 across four databases (MEDLINE, PsycINFO, Web of Science, and ASSIA). Quantitative studies from OECD (Organisation for Economic Co-operation and Development) member countries were eligible for inclusion if they investigated housing insecurity by examining at least one independent variable related to housing affordability and/or instability, and included at least one mental health-related outcome among adult renters. Studies needed to specifically distinguish effects for renters, not simply adjust for tenure or include an interaction. Studies were excluded if they analyzed other forms of housing insecurity, examining residential satisfaction and general health outcomes, or populations other than adult renters (< 15 years of age). The methodological quality of the included studies was rated with the JBI Critical Appraisal Tools, and the certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Due to heterogeneity of the identified studies, we performed a narrative synthesis. Twenty-two studies with sample sizes ranging from n = 89 to n = 179,037 met the inclusion criteria (resulting in a total sample size of at least N = 336,775), of which 14 applied a longitudinal design, five a cross-sectional design, and three a quasi-experimental design. Based on the JBI ratings, the overall methodological quality of the included studies was good. The overall ratings of certainty of evidence, based on the GRADE ratings, were between low and very low – mainly due to the non-controlled study designs of included studies. Among the nine studies examining housing affordability, six reported significant associations between unaffordable rent and poor mental health in low-income renters. Regarding housing instability, 12 out of 14 studies reported significant associations between unstable housing and renters’ mental health issues. Measures of housing insecurity varied, with rent-to-income ratio and forced moves being most commonly employed. Mental health outcomes focused primarily on overall mental health, well-being, and depressive symptoms, while few studies explored other mental health outcomes. Despite methodological limitations due to the non-controlled studies included in the review, the findings suggest overall that experiencing unaffordable or unstable housing has a negative impact on renters’ overall mental health and depressive symptoms. Housing insecurity poses a significant challenge for renters in OECD countries, highlighting the need for policymakers to implement supportive housing policies and tenure protection measures in order to improve renters’ housing security and ultimately public health. Nevertheless, more research with robust study designs is needed to draw further conclusions. The systematic review has been conducted without external funding. It has not been pre-registered and no study protocol has been published
Continuous-wave all-optical single-photon transistor based on a Rydberg-atom ensemble
No full textContinuous-wave (cw) architectures provide a promising route to interface disparate quantum systems by relaxing the need for precise synchronization. While essential cw components, including microwave single-photon transistors and microwave–optical converters, have been explored, an all-optical cw single-photon transistor has remained a missing piece. We propose a high-efficiency, high-gain implementation using Rydberg atoms, in which a control photon disrupts the transmission of a continuous probe beam via the van der Waals interaction. This device completes the set of components required for cw processing of quantum signals and paves the way for all-optical processing at the quantum level
Correlation of near-field optical microscopy and tip-assisted photoluminescence
No full textNanoscale optical imaging has unlocked unprecedented opportunities for exploring the structural, electronic, and optical properties of low-dimensional materials with spatial resolutions far beyond the diffraction limit. Techniques such as tip-enhanced, and tip-assisted photoluminescence (TEPL and TAPL), as well as scattering-type scanning near-field optical microscopy (s-SNOM) offer unique insights into local strain distributions, exciton dynamics, and dielectric heterogeneities that are inaccessible through conventional far-field approaches, however their combination within the same setup remains challenging. Here we present the realisation of correlative TEPL/TAPL and s-SNOM measurements within a single side-illuminated near-field optical microscope. We address the key experimental challenges inherent to the side-illumination geometry, including precise laser focus alignment, suppression of far-field background signals, and the mitigation of competing scattering pathways. Utilising monolayer WSe2 as a model system, we demonstrate correlative imaging of material topography, strain-induced photoluminescence shifts, and dielectric function variations. We visualise nanoscale heterogeneities on a bubble-like structure, highlighting the complementary information from TAPL and s-SNOM. This correlative approach bridges the gap between nanoscale optical spectroscopy and near-field imaging, offering a powerful tool for probing local strain, doping, exciton behaviour, and dielectric inhomogeneities in low-dimensional materials
Classifications of global attractors for S1-equivariant parabolic equations: A survey
No full textWe survey the global dynamics of semiflows generated by scalar semilinear parabolic equations which are SO(2) equivariant under spatial shifts of x is an element of S-1 = R/2 pi Z, i.e. u(t) = u(xx) + f(u, u(x)), x is an element of S-1. (0.1) For dissipative C-2 nonlinearities f, the semiflow (0.1) possesses a compact global attractor A = A(f)(p) which we call Sturm attractor. The Sturm attractor A(f)(p) decomposes as A(f)(p) = epsilon(f) U F-f(p) U R-f(p) U H-f(p). where H-f(p) denotes heteroclinic orbits between distinct elements of spatially homogeneous equilibria epsilon(f) rigidly rotating waves R-f(p) and, as their non-rotating counterparts, frozen waves F-f(p) We therefore represent A(f)(p) by its connection graph C-f(p), with vertices in epsilon(f) F-f(p), R-f(p) and edges H-f(p). Under mild hyperbolicity assumptions, the directed graphs C-f(p) are finite and transitive. For illustration, we enumerate all 21 connection graphs C-f(p) with up to seven vertices. The result uses a lap signature of period maps associated to integrable versions of the steady state ODE of (0.1). Our results are based on a comparison with associated C-2 dissipative Neumann PDEs on the half-interval x is an element of (0, pi). After a suitable homotopy from to spatially reversible nonlinearities g(u, -p) = g(u, p), the Neumann problem gains a hidden symmetry O(2) spatially. Moreover, the Neumann dynamics become gradient-like. This leads to isomorphic connection graphs C-f(p) congruent to C-g(N) / similar to. Here similar to collapses the two shifted Neumann copies of each frozen or rotating wave to a single vertex. As an example, we freeze and reconstruct the connection graph of the Vas tulip attractor, known from delay differential equations, in setting (0.1)
The Effect of Age Diversity in Groups on Peer Evaluations and Individual Performance
No full textThis study analyzes how individuals evaluate their peers' performance in a high-stakes tournament in response to being randomly assigned to an age homogenous or heterogenous group using data from two TV shows. The data also allow us to explore expert evaluations because it contains objective ratings from an independent expert. Additionally, this study investigates how age-diverse groups affect individual performance in professional golf tournaments. The results show that peer and expert evaluations as well as individual performance are lower in age-diverse groups. Further evidence suggests that these effects occur when group members are unfamiliar but fade away once group members have gotten to know each other
Mobilizing Europe’s citizens to take action on migration and climate change: behavioral evidence from 27 EU member states
No full textThis paper investigates how two politicized issues – migration and climate change – mobilize citizens across European countries. Building on the concept of issue-specific mobilization potentials, we examine citizens’ willingness to support petitions related to the two issues using an original behavioral measure embedded in the 2024 European Parliament Election Study. We document variation in political engagement and examine how opposing stances on issues owned by the left or the right mobilize citizens, how citizens’ agreement with issue positions affects support, and whether grievances, participation cultures, politicization levels, and the ideology of the national government can explain national-level variation. Our results indicate substantial variation in petition support across countries and issues, with the right-wing petition on migration attracting the most support. However, our country-level measures do not explain this variation well. Overall, our findings highlight the need for more nuanced, issue-specific approaches to understanding cross-national patterns of political participation
Digital Governance in China
No full textDrawing on recent cases of digital technology adoption in China, this paper investigates changes in the digital reach of the Chinese state. We focus first on state capacity, a key dimension of state reach, and show that the adoption of digital technologies by central and local governments has increased coercive, administrative, and extractive capacity. We also examine the state's intrusiveness and show that digitalizing governance and regulatory processes has enabled new forms of power abuse, leading to resource waste and resistance among citizens. We contend that broader societal debate on the practices and outcomes of digital governance is essential to addressing these challenges. While digitalization poses unique challenges to regulators and societies worldwide, China's advanced experience offers important lessons
Fused 3D boron heterocycles via EnT catalysis: synthesis, modification and validation as beta-lactamase inhibitors
No full textThe installation of a boron unit into bioactive scaffolds continues to unlock novel modes of molecular recognition in drug discovery. As such, de novo strategies to access 3D boron-containing frameworks, that modulate the intrinsic reactivity at boron, are being intensively pursued. Herein, we report a visible light-mediated energy transfer (EnT) catalysis strategy that enables the [2 + 2] cycloaddition of boron-containing heterocycles to construct 3D frameworks with high structural complexity. Leveraging both inter- and intramolecular cycloadditions, a suite of angularly fused boron heterocycles was accessed, offering enhanced steric shielding and modular handles for additional interactions. A boron deletion strategy permits the synthesis of benzofuran scaffolds, otherwise inaccessible via direct EnT. Crucially, the resulting 3D architectures mimic structural motifs found in the potent β-lactamase inhibitor Xeruborbactam. The biological relevance of these frameworks was validated by NMR titration, pKa analysis, and co-crystallisation with serine β-lactamase CTX-M-14, revealing enantiospecific binding and a well-defined hydrogen bonding network. These results establish a versatile platform for the synthesis of functionalised boron heterocycles with direct translational potential in medicinal chemistry
