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Inspired by the Contino-Pomarol-Rattazzi mechanism we explore scenarios with a very light (1 keV to 10 GeV) radion which could be associated with the suppression of the electroweak contribution to vacuum energy. We construct explicit, realistic models that realize this mechanism and explore the phenomenological constraints on this class of models. Compared with axion-like particles in this mass range, the bounds from SN 1987a and from cosmology can be much weaker, depending on the mass of the radion and its coupling to other particles. With couplings suppressed by a scale lower than 100 TeV, much of the mass window from 100 keV to 10 GeV is still open.

Controlling the succession of chemical processes with high specificity in complex systems is advantageous for widespread applications, from biomedical research to drug manufacturing. Despite synthetic advances in bioorthogonal and photochemical methodologies, there is a need for generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers. Herein we present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. We demonstrate that the photocatalytic activity of nitrobenzoselenadiazoles can be fully blocked by site-selective incorporation of electron-withdrawing carbamate moieties and restored on demand upon uncaging with a wide range of molecular triggers, including abiotic transition-metal catalysts. We also prove that this strategy can be expanded to most photosensitizers, including diverse structures and spectral properties. Finally, we show that such advanced control of singlet oxygen generation can be broadly applied to the photodynamic ablation of human cells as well as to regulate the release of singlet oxygen in the semi-synthesis of natural product drugs. Generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers are of high interest. Here, the authors present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. [ABSTRACT FROM AUTHOR]

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD. [ABSTRACT FROM AUTHOR]

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly in heterogeneous malignancies like adult soft tissue sarcomas, where conventional markers are inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD‐IMC‐1, BD‐IMC‐2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker for CSCs in sarcoma in clinical pathology. Based on their structures, BD‐IMC‐1 showcased higher susceptibility to disaggregation compared to BD‐IMC‐2, consistent with their selective interaction with COX. Notably, the BD‐IMC‐1 revealed positive cooperativity binding to COX‐2 at sub‐micromolar ranges. Both probes showed significant fluorescence turn‐on upon LPS or PMA triggered COX‐2 upregulation in live RAW264.7, HeLa, and human sarcoma cell line (Saos‐LM2) up to 2‐fold increase with negligible toxicity. More importantly, the BD‐IMC‐1 demonstrated their practical imaging for COX‐2 positive cells in paraffin‐fixed human sarcoma tissue. Considering the fixed tissues are most practiced pathological sample, our finding suggests a potential of disaggregation activated chemosensor for clinical applications. [ABSTRACT FROM AUTHOR]

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox‐related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker‐based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs. [ABSTRACT FROM AUTHOR]

The development of a small‐molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron‐selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin‐mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures. [ABSTRACT FROM AUTHOR]

Recently, a paste-type premixed calcium silicate-based mineral trioxide aggregate (MTA) product that quickly solidifies through a pozzolanic reaction was introduced to replace existing MTA, which has the disadvantage of a long setting time. In this study, we evaluated the effect of moisture content in the root canal on the setting time of premixed calcium silicate-based MTA in a simulated root canal environment using Endoseal MTA and Well-Root ST, among commercially available products. The setting time was measured according to ISO 6876/2012. A mold made using grades 2, 3, and 4 dental gypsum according to the classification of ISO 6873/2013 was used to reproduce the difference in moisture environment. Differences in moisture content were measured using micro-computed X-ray tomography (micro-CT). The micro-CT results showed that the moisture content was the highest and lowest in the grade 2 and 4 gypsum molds, respectively. Moreover, the setting time indicated by the manufacturer was the shortest for the grade 2 gypsum mold. Hence, the differences in moisture content significantly affect the setting time of MTA. This result can help set future experimental conditions and develop premixed calcium silicate-based MTA products. [ABSTRACT FROM AUTHOR]