Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.

Objective. The peripheral nervous system (PNS) connects the central nervous system with the rest of the body to regulate many physiological functions and is therapeutically targeted to treat diseases such as epilepsy, depression, intestinal dysmotility, chronic pain, and more. However, we still lack understanding of PNS innervation in most organs because the large span, diffuse nature, and small terminal nerve bundle fibers have precluded whole-organism, high resolution mapping of the PNS. We sought to produce a comprehensive peripheral nerve atlas for use in future interrogation of neural circuitry and selection of targets for neuromodulation. Approach. We used diffusion tensor magnetic resonance imaging (DT-MRI) with high-speed compressed sensing to generate a tractogram of the whole mouse PNS. The tractography generated from the DT-MRI data is validated using lightsheet microscopy on optically cleared, antibody stained tissue. Main results. Herein we demonstrate the first comprehensive PNS tractography in a whole mouse. Using this technique, we scanned the whole mouse in 28 h and mapped PNS innervation and fiber network in multiple organs including heart, lung, liver, kidneys, stomach, intestines, and bladder at 70 µ m resolution. This whole-body PNS tractography map has provided unparalleled information; for example, it delineates the innervation along the gastrointestinal tract by multiple sacral levels and by the vagal nerves. The map enabled a quantitative tractogram that revealed relative innervation of the major organs by each vertebral foramen as well as the vagus nerve. Significance. This novel high-resolution nerve atlas provides a potential roadmap for future neuromodulation therapies and other investigations into the neural circuits which drive homeostasis and disease throughout the body.

Renal cell carcinoma (RCC) accounts for 90% of adult renal cancer cases and is characterized by significant heterogeneity within its tumor microenvironment. This study tests the hypothesis that tumor-associated macrophages (TAMs) influence RCC progression and patient response to treatment by investigating the prognostic implications of TAM signatures. Utilizing independent single-cell RNA sequencing data from RCC patients, we developed eight distinct TAM signatures reflective of TAM presence. A LASSO Cox regression model was constructed to predict survival outcomes, evaluated using the TCGA dataset, and validated across independent RCC cohorts. Model performance was assessed through Kaplan–Meier survival plots, receiver operating characteristic (ROC) curves, and principal component analysis. Survival analysis demonstrated that specific TAM signature gene expressions serve as significant prognostic markers, identifying TAM signatures positively correlated with patient survival and macrophage infiltration. A 27-gene TAM risk model was established, successfully stratifying patients into risk categories, with low-risk patients showing improved overall survival. These findings provide insights into the role of TAMs in modulating the RCC tumor immune microenvironment and their impact on patient prognosis, suggesting that TAM-based signatures may serve as useful prognostic markers and potential targets to enhance RCC treatment strategies.

Stress-related endocrine responses are critical for understanding human performance and mental health. Conventional assessments rely heavily on subjective self-report questionnaires or invasive sampling such as venipuncture. Tears offer a noninvasive source of neurochemical biomarkers, including serotonin, a key regulator of stress and mood. However, real-time and continuous monitoring of tear serotonin has not yet been fully realized. Here, we present a reversible lab-on-a–contact lens platform that integrates a printable, stretchable ferrocene-based electrochemical sensor for in situ detection of serotonin in tear fluid. The device is fabricated on a soft hydrogel lens and uses an electrochemically refreshable redox surface to restore baseline between measurements. Calibration in artificial tears established a limit of detection of 72 picomolar and a dynamic range of 0.1 to 500 nanomolar. Function was maintained for more than 28 days in a tear-like environment and under repeated mechanical deformations (flipping, folding, stretching, and twisting), with stability confirmed by periodic redox cycling. Ocular safety and biocompatibility were demonstrated in a porcine eye model. In a chronic stress mouse model, tear serotonin concentrations inversely correlated with cortisol in both serum and tears, and a first-in-human pilot study further supported the relationship between tear serotonin and stress with off-line analysis by the lab-on-a–contact lens platform. This platform could enable applications in decentralized, noninvasive endocrine monitoring and holds promise as a clinically translatable tool for real-time mental health biomarker assessment.

Renal cell carcinoma (RCC) accounts for 90% of adult renal cancer cases and is characterized by significant heterogeneity within its tumor microenvironment. This study tests the hypothesis that tumor-associated macrophages (TAMs) influence RCC progression and patient response to treatment by investigating the prognostic implications of TAM signatures. Utilizing independent single-cell RNA sequencing data from RCC patients, we developed eight distinct TAM signatures reflective of TAM presence. A LASSO Cox regression model was constructed to predict survival outcomes, evaluated using the TCGA dataset, and independently validated across multiple RCC cohorts. Model performance was assessed through Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, principal component analysis. Survival analysis demonstrated that specific TAM signature gene expressions serve as significant prognostic markers, identifying TAM signatures positively correlated with patient survival and macrophage infiltration. A 27-gene TAM risk model was established, successfully stratifying patients into risk categories, with low-risk patients showing improved overall survival. These findings provide insights into the role of TAMs in modulating the RCC tumor immune microenvironment and their impact on patient prognosis, suggesting that TAM-based signatures may serve as useful prognostic markers and potential targets to enhance RCC treatment strategies.