Single and multiple systems in probabilistic categorization
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Derivation of human toxicokinetic parameters and internal threshold of toxicological concern for tenuazonic acid through a human intervention trial and hierarchical Bayesian population modeling
Tenuazonic acid (TeA), a mycotoxin produced by Alternaria alternata, contaminates various food commodities and is known to cause acute and chronic health effects. However, the lack of human toxicokinetic (TK) data and the reliance on external exposure estimates have stalled a comprehensive risk assessment for TeA.
Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects
The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.
Type 2 immunity in allergic diseases
Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.
Optical sorting: past, present and future
Optical sorting combines optical tweezers with diverse techniques, including optical spectrum, artificial intelligence (AI) and immunoassay, to endow unprecedented capabilities in particle sorting. In comparison to other methods such as microfluidics, acoustics and electrophoresis, optical sorting offers appreciable advantages in nanoscale precision, high resolution, non-invasiveness, and is becoming increasingly indispensable in fields of biophysics, chemistry, and materials science. This review aims to offer a comprehensive overview of the history, development, and perspectives of various optical sorting techniques, categorised as passive and active sorting methods. To begin, we elucidate the fundamental physics and attributes of both conventional and exotic optical forces. We then explore sorting capabilities of active optical sorting, which fuses optical tweezers with a diversity of techniques, including Raman spectroscopy and machine learning. Afterwards, we reveal the essential roles played by deterministic light fields, configured with lens systems or metasurfaces, in the passive sorting of particles based on their varying sizes and shapes, sorting resolutions and speeds. We conclude with our vision of the most promising and futuristic directions, including AI-facilitated ultrafast and bio-morphology-selective sorting. It can be envisioned that optical sorting will inevitably become a revolutionary tool in scientific research and practical biomedical applications.
Spotiphy enables single-cell spatial whole transcriptomics across an entire section
Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization of gene expression within whole-tissue sections, but current approaches remain plagued by the challenge of achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome images. Spotiphy delivers the most precise cellular proportions in extensive benchmarking evaluations. Spotiphy-derived inferred single-cell profiles reveal astrocyte and disease-associated microglia regional specifications in Alzheimer’s disease and healthy mouse brains. Spotiphy identifies multiple spatial domains and alterations in tumor–tumor microenvironment interactions in human breast ST data. Spotiphy bridges the information gap and enables visualization of cell localization and transcriptomic profiles throughout entire sections, offering highly informative outputs and an innovative spatial analysis pipeline for exploring complex biological systems.
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