High-velocity delivery of biologics via the gastrointestinal tract by self-pressurized oral capsules.

Biologic drugs have transformed medicine, but are limited by their need for administration by injection. To enable oral delivery of biologics, we propose convective force as a physical method to overcome the barriers of the gastrointestinal tract (GIT). We designed oral capsules that self-pressurize in the GIT, mechanically fail at a specific pressure (100-170 kPa), and eject lyophilized drug with sufficient velocity to penetrate the mucosal barrier.

Rapid local anesthesia in children enhanced by STAR particles: a first-in-humans, randomized clinical trial.

Healthcare-related pain associated with hypodermic needles is prevalent and undertreated in pediatric patients. Currently available topical anesthetics provide insufficient pain relief due to poor drug skin permeability, especially when rapid onset is desired. Herein, our goal was to assess the speed and efficacy of local lidocaine/epinephrine/tetracaine (LET) gel enabled by STAR particles in a first-in-humans clinical trial.

The SHFV nsp2 and nucleocapsid proteins recruit G3BP1 to sites of viral replication, but stress granules are not induced by the infection.

Stress granules (SGs) are dynamic, cytoplasmic foci that form in response to environmental stresses, including viral infections, and function to restore cellular homeostasis by regulating mRNA translation, storage, and decay. To inhibit SG formation and subvert their antiviral effects, viruses from diverse families sequester or cleave G3BP1, the key SG nucleating protein. We found that an infection with simian hemorrhagic fever virus (SHFV), a member of the family , does not induce the formation of SGs despite inducing phosphorylation of PKR and eIF2α.

Computationally integrating radiology and pathology image features for predicting treatment benefit and outcome in lung cancer.

Lung cancer, the leading cause of cancer-related deaths globally, includes non-small cell lung cancer (NSCLC) (85% of cases) and small cell lung cancer (SCLC) (13-15%). While accurate diagnosis and treatment selection are critical, the absence of reliable predictive or prognostic biomarkers remains a significant challenge. This study explored the combined use of radiomics from CT scans and pathomics from H&E slides in three contexts: (1) predicting disease recurrence in early-stage NSCLC, (2) predicting immunotherapy response in advanced-stage NSCLC, and (3) predicting chemotherapy response in SCLC.

Suprachoroidal Drug Delivery for VEGF Suppression in Wet AMD and Other Diseases With Choroidal Neovascularization.

Purpose: Choroidal neovascularization caused by age-related macular degeneration, among other diseases, causes significant visual impairment. Intravitreal therapeutics inhibiting vascular endothelial growth factor (VEGF) signaling have shown excellent safety and efficacy in regressing choroidal neovascularization and improving vision. Current US Food and Drug Administration (FDA)-approved treatments deliver these drugs into the vitreous cavity, even though choroidal neovascularization originates from aberrant signaling in the choroid.

Management of Levonorgestrel and Etonogestrel Adsorption to Polypropylene During in Vitro Release from Long-Acting Release Dosage Forms.

Adsorption of active pharmaceutical ingredients (APIs) to various surfaces of labware can skew data during drug development. We observed substantial loss of two clinically significant hydrophobic contraceptive steroids, levonorgestrel (LNG) and etonogestrel (ENG), during in vitro release evaluation from poly(lactic--glycolic acid) (PLGA) microspheres and microneedles, leading to incomplete drug recovery. Our investigation identified the adsorption of these APIs to polypropylene (PP) as a key factor adversely affecting both the drug loss and sensitivity/linearity of ultra performance liquid chromatography (UPLC)-ultraviolet (UV) assays during in vitro release tests.

Measurement of CSF flow and brain motion in Chiari malformation type I subjects undergoing posterior fossa decompression surgery.

Objective: Radiologically, Chiari malformation type I (CM-I) is characterized by cerebellar tonsil herniation of at least 5 mm through the foramen magnum. In symptomatic cases, posterior fossa decompression (PFD) surgery is often performed and improves symptoms in approximately 75% of patients. However, the surgery involves risks, and identifying which candidates will benefit from surgery is important.

Design considerations for optogenetic applications of soft micro-LED-based device systems across diverse nervous systems.

Optogenetics enables precise, cell-specific control of neural activity, surpassing traditional electrical stimulation methods that indiscriminately activate nearby cells, making it crucial for rehabilitation, neurological disorder treatment, and understanding neural circuits. Among light sources for delivering light to genetically modified cells, bio-implants integrated with Light Emitting Diodes (LEDs) have recently been the focus of extensive research due to their advantage of enabling local photogeneration. Unlike laser-based systems, which require tethered setups that hinder behavioral experiments, μ-LED-based devices allow for wireless operation, facilitating more natural movement in subjects.

A possible pathway to freezing of gait in Parkinson's disease.

Freezing of gait (FOG), a common, perplexing gait disorder observed in Parkinson's disease (PD), is a leading cause of injurious falls and contributes significantly to social isolation. Unlike other PD cardinal features, FOG appears to develop independently, and its heterogeneity presents challenges for both definition and measurement. The pathophysiological mechanisms underlying FOG remain poorly understood, limiting the development of effective treatments.

IOP Reduction in Nonhuman Primates by Microneedle Injection of Drug-Free Hydrogel to Expand the Suprachoroidal Space.

Purpose: Expansion of the suprachoroidal space (SCS) by a hydrogel injection has been shown to reduce intraocular pressure (IOP) in rabbits as a potential treatment for ocular hypertension in glaucoma. Here, we evaluate the safety and efficacy of this approach in hypertensive and normotensive eyes in nonhuman primates.

Methods: A microneedle was used to inject a hyaluronic acid-based hydrogel or saline solution (control) into the SCS of cynomolgus monkey eyes that were either normotensive (n = 7 experimental; n = 2 control eyes) or had induced ocular hypertension (n = 6 experimental; n = 3 control eyes).

Smart filtering facepiece respirator with self-adaptive fit and wireless humidity monitoring.

The widespread emergence of airborne diseases has transformed our lifestyle, and respirators have become an essential part of daily life. Nevertheless, finding respirators that fit well can be challenging due to the variety of human facial sizes and shapes, potentially compromising protection. In addition, the current respirators do not inform the user of the air quality in case of continuous long-term use.

Stretchable and biodegradable self-healing conductors for multifunctional electronics.

As the regenerative mechanisms of biological organisms, self-healing provides useful functions for soft electronics or associated systems. However, there have been few examples of soft electronics where all components have self-healing properties while also ensuring compatibility between components to achieve multifunctional and resilient bio-integrated electronics. Here, we introduce a stretchable, biodegradable, self-healing conductor constructed by combination of two layers: (i) synthetic self-healing elastomer and (ii) self-healing conductive composite with additives.

Sound-seeking before and after hearing loss in mice.

How we move our bodies affects how we perceive sound. For instance, head movements help us to better localize the source of a sound and to compensate for asymmetric hearing loss. However, many auditory experiments are designed to restrict head and body movements.

Diffusion-Based Generation of Neural Activity from Disentangled Latent Codes.

Recent advances in recording technology have allowed neuroscientists to monitor activity from thousands of neurons simultaneously. Latent variable models are increasingly valuable for distilling these recordings into compact and interpretable representations. Here we propose a new approach to neural data analysis that leverages advances in conditional generative modeling to enable the unsupervised inference of disentangled behavioral variables from recorded neural activity.

Tolerability of a piezoelectric microneedle electroporator in human subjects.

Electroporation, or the use of electric pulses to facilitate the intracellular delivery of DNA, RNA, and other molecules, is a well-established technique, that has been demonstrated to significantly augment the immunogenicity of DNA/mRNA vaccines and therapeutics. However, the clinical translation of traditional electroporators has been limited due to high costs, large size, complex user operation, and poor tolerability in humans due to nerve stimulation. In prior work, we introduced ePatch: an ultra-low-cost, handheld, battery-free electroporator employing a piezoelectric pulser coupled with a microneedle electrode array that showed enhanced immunogenic responses to an intradermal SARS-CoV-2 DNA vaccine in mice.

Flexible Thermoelectric Wearable Architecture for Wireless Continuous Physiological Monitoring.

Continuous monitoring of physiological signals from the human body is critical in health monitoring, disease diagnosis, and therapeutics. Despite the needs, the existing wearable medical devices rely on either bulky wired systems or battery-powered devices needing frequent recharging. Here, we introduce a wearable, self-powered, thermoelectric flexible system architecture for wireless portable monitoring of physiological signals without recharging batteries.

All-in-One, Wireless, Multi-Sensor Integrated Athlete Health Monitor for Real-Time Continuous Detection of Dehydration and Physiological Stress.

Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non-invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives.

GABAergic synaptic scaling is triggered by changes in spiking activity rather than AMPA receptor activation.

Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking.

Recent advances in soft, implantable electronics for dynamic organs.

Unlike conventional rigid counterparts, soft and stretchable electronics forms crack- or defect-free conformal interfaces with biological tissues, enabling precise and reliable interventions in diagnosis and treatment of human diseases. Intrinsically soft and elastic materials, and device designs of innovative configurations and structures leads to the emergence of such features, particularly, the mechanical compliance provides seamless integration into continuous movements and deformations of dynamic organs such as the bladder and heart, without disrupting natural physiological functions. This review introduces the development of soft, implantable electronics tailored for dynamic organs, covering various materials, mechanical design strategies, and representative applications for the bladder and heart, and concludes with insights into future directions toward clinically relevant tools.

Mesenchymal Stromal Cell (MSC) Functional Analysis-Macrophage Activation and Polarization Assays.

Stem cell-based therapies have evolved to become a key component of regenerative medicine approaches to human pathologies. Exogenous stem cell transplantation takes advantage of the potential of stem cells to self-renew, differentiate, home to sites of injury, and sufficiently evade the immune system to remain viable for the release of anti-inflammatory cytokines, chemokines, and growth factors. Common to many pathologies is the exacerbation of inflammation at the injury site by proinflammatory macrophages.