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Normalizing flows (NFs) provide uncorrelated samples from complex distributions, making them an appealing tool for parameter estimation. However, the practical utility of NFs remains limited by their tendency to collapse to a single mode of a multimodal distribution. In this study, we show that annealing with an adaptive schedule based on the effective sample size (ESS) can mitigate mode collapse. We demonstrate that our approach can converge the marginal likelihood for a biochemical oscillator model fit to time-series data in ten-fold less computation time than a widely used ensemble Markov chain Monte Carlo (MCMC) method. We show that the ESS can also be used to reduce variance by pruning the samples. We expect these developments to be of general use for sampling with NFs and discuss potential opportunities for further improvements. 

Fast and accurate assessment of skin mechanics holds great promise in diagnosing various epidermal diseases, yet substantial challenges remain in developing simple and wearable strategies for continuous monitoring. Here, we present a design concept, named active near-infrared spectroscopy patch (ANIRP) for continuously mapping skin mechanics. ANIRP addresses these challenges by integrating near-infrared (NIR) sensing with mechanical actuators, enabling rapid measurement (<1 s) of Young’s modulus, high spatial sensing density (~1 cm²), and high spatial sensitivity (<1 mm). Unlike conventional electromechanical sensors, NIR sensors precisely capture vibrational frequencies propagated from the actuators without needing ultraclose contact, enhancing wearing comfort. Demonstrated examples include ANIRPs for comprehensively moduli mapping of artificial tissues with varied mechanical properties emulating tumorous fibrosis. On-body validation of the ANIRP across skin locations confirms its practical utility for clinical monitoring of epidermal mechanics, promising considerable advancements in real-time, noninvasive skin diagnostics and continuous health monitoring. 

Abstract Transdermal drug delivery is of vital importance for medical treatments. However, user adherence to long-term repetitive drug delivery poses a grand challenge. Furthermore, the dynamic and unpredictable disease progression demands a pharmaceutical treatment that can be actively controlled in real-time to ensure medical precision and personalization. Here, we report a spatiotemporal on-demand patch (SOP) that integrates drug-loaded microneedles with biocompatible metallic membranes to enable electrically triggered active control of drug release. Precise control of drug release to targeted locations (<1 mm²), rapid drug release response to electrical triggers (<30 s), and multi-modal operation involving both drug release and electrical stimulation highlight the novelty. Solution-based fabrication ensures high customizability and scalability to tailor the SOP for various pharmaceutical needs. The wireless-powered and digital-controlled SOP demonstrates great promise in achieving full automation of drug delivery, improving user adherence while ensuring medical precision. Based on these characteristics, we utilized SOPs in sleep studies. We revealed that programmed release of exogenous melatonin from SOPs improve sleep of mice, indicating potential values for basic research and clinical treatments. 

Abstract Drawing inspiration from cohesive integration of skeletal muscles and sensory skins in vertebrate animals, we present a design strategy of soft robots, primarily consisting of an electronic skin (e-skin) and an artificial muscle. These robots integrate multifunctional sensing and on-demand actuation into a biocompatible platform using an in-situ solution-based method. They feature biomimetic designs that enable adaptive motions and stress-free contact with tissues, supported by a battery-free wireless module for untethered operation. Demonstrations range from a robotic cuff for detecting blood pressure, to a robotic gripper for tracking bladder volume, an ingestible robot for pH sensing and on-site drug delivery, and a robotic patch for quantifying cardiac function and delivering electrotherapy, highlighting the application versatilities and potentials of the bio-inspired soft robots. Our designs establish a universal strategy with a broad range of sensing and responsive materials, to form integrated soft robots for medical technology and beyond. 

Using simulations or experiments performed at some set of temperatures to learn about the physics or chemistry at some other arbitrary temperature is a problem of immense practical and theoretical relevance. Here we develop a framework based on statistical mechanics and generative artificial intelligence that allows solving this problem. Specifically, we work with denoising diffusion probabilistic models and show how these models in combination with replica exchange molecular dynamics achieve superior sampling of the biomolecular energy landscape at temperatures that were never simulated without assuming any particular slow degrees of freedom. The key idea is to treat the temperature as a fluctuating random variable and not a control parameter as is usually done. This allows us to directly sample from the joint probability distribution in configuration and temperature space. The results here are demonstrated for a chirally symmetric peptide and single-strand RNA undergoing conformational transitions in all-atom water. We demonstrate how we can discover transition states and metastable states that were previously unseen at the temperature of interest and even bypass the need to perform further simulations for a wide range of temperatures. At the same time, any unphysical states are easily identifiable through very low Boltzmann weights. The procedure while shown here for a class of molecular simulations should be more generally applicable to mixing information across simulations and experiments with varying control parameters. 

Abstract Precision healthcare relies upon ubiquitous biofeedback to optimize therapy individually for nuanced and dynamic needs. However, grand challenges reside in the lack of soft, highly personalizable monitors that are scalable in manufacturing and reversibly interchangeable upon the evolution of needs. Herein, a customizable soft wearable platform is presented that can seamlessly integrate diverse functional modules, including physical and biochemical sensors, stimulators, and energy storage devices, tailored to various health monitoring scenarios, while can self‐repair after certain mechanical damage. The platform supports versatile physiological sensing and therapeutic intervention due to its compatibility with wide‐ranging functional nanomaterials. A bilayer microporous foam embedded in the gel improves sweat management for comfortable and reliable on‐body biomarker monitoring. Furthermore, flexible self‐healing zinc‐air batteries using ion gel electrolytes provide opportunities for self‐powered, closed‐loop systems. On‐body demonstrations validate the platform's capability to monitor physiological and metabolic states under real‐world conditions. This work provides a scalable and adaptable materials‐based solution for real‐time personalized health monitoring, advancing wearable bioelectronics to meet evolving healthcare demands.