Search

Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes. However, the invasive nature of intratracheal administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method of delivering microrobots to the lungs. A nebulizer is employed to encapsulate picoeukaryote algae microrobots within small aerosol particles, enabling them to reach the lower respiratory tract. Post nebulization, the microrobots retain their motility (~55 μm s-1) to help achieve a homogeneous lung distribution and long-term retention exceeding five days in the lungs. Therapeutic efficacy is demonstrated in a mouse model of acute methicillin-resistant Staphylococcus aureus pneumonia using this pulmonary inhalation approach to deliver microrobots functionalized with platelet membrane-coated polymeric nanoparticles loaded with vancomycin. These promising findings underscore the benefits of inhalable biohybrid microrobots in a setting that does not require anesthesia, highlighting the substantial translational potential of this delivery system for routine clinical applications.

Precision-cut lung slices (PCLS) are commonly used as an ex vivo model to study lung fibrosis; however, traditional models lack immune cell infiltration, including the recruitment of monocytes and macrophages, which are critical for inflammation and fibrosis. To address this limitation, we developed novel autologous PCLS-immune co-culture models that better replicate the processes of inflammation, repair, and immune cell recruitment associated with fibrosis. Fibrotic responses to nicotine, cigarette smoke extract (CSE), and a fibrosis-inducing cocktail (FC) were first evaluated in PCLS containing only tissue-resident macrophages, with upregulation of α-SMA-expressing fibroblasts confirmed by immunofluorescence and Western blotting, and collagen deposition quantified using Sirius Red staining. To study macrophage recruitment, we employed an indirect co-culture model using transwells to approximate blood vessel function. Chemotactic studies revealed increased migration of autologous bone marrow-derived macrophages (BMDMs) toward and infiltration into CSE-injured PCLS. In a direct co-culture model simulating the repair phase of fibrosis, PCLS exposed to CSE and FC showed further increased collagen deposition in the presence of autologous BMDMs, but not heterologous ones. These findings suggest that our novel PCLS-immune co-culture models provide a platform for studying macrophage involvement in fibrosis and offer potential for developing macrophage-targeted therapeutic strategies in pulmonary fibrosis.

The intensifying global opioid crisis, majorly attributed to fentanyl (FT) and its analogs, has necessitated the development of rapid and ultrasensitive remote/on-site FT sensing modalities. However, current approaches for tracking FT exposure through wastewater-based epidemiology (WBE) are unadaptable, time-consuming, and require trained professionals. Toward developing an extended in situ wastewater opioid monitoring system, we have developed a screen-printed electrochemical FT sensor and integrated it with a customized submersible remote sensing probe. The sensor composition and design have been optimized to address the challenges for extended in situ FT monitoring. Specifically, ZIF-8 metal-organic framework (MOF)-derived mesoporous carbon (MPC) nanoparticles (NPs) are incorporated in the screen-printed carbon electrode (SPCE) transducer to improve FT accumulation and its electrocatalytic oxidation. A rapid (10 s) and sensitive square wave voltammetric (SWV) FT detection down to 9.9 µgL-1 is thus achieved in aqueous buffer solution. A protective mixed-matrix membrane (MMM) has been optimized as the anti-fouling sensor coating to mitigate electrode passivation by FT oxidation products and enable long-term, intermittent FT monitoring. The unique MMM, comprising an insulating polyvinyl chloride (PVC) matrix and carboxyl-functionalized multi-walled carbon nanotubes (CNT-COOH) as semiconductive fillers, yielded highly stable FT sensor operation (> 95% normalized response) up to 10 h in domestic wastewater, and up to 4 h in untreated river water. This sensing platform enables wireless data acquisition on a smartphone via Bluetooth. Such effective remote operation of submersible opioid sensing probes could enable stricter surveillance of community water systems toward timely alerts, countermeasures, and legal enforcement.

In this study, three levels of grape load (15, 20, and 25 spikes/m shelf) were set for the primary wine grape cultivar ‘Cabernet Sauvignon’. The effect of different harvest times, four growth stages according to the Eichhorn-Lorenz scale: E-L35, E-L36, E-L37, and E-L38 was investigated on the compositions of organic acids, monomeric phenols and volatile compounds and sensory quality of wine. The results showed that at the E-L38 stage, the total acid of grape berries in the medium-load group significantly increased, while the opposite was true for the low- and high-load groups. For all groups, the total acid content of wine peaked at the E-L35 stage and reached its lowest point at the E-L37 stage. The total phenol content reached its peak at the E-L36 stage, and then decreased rapidly. Under the low-load condition, the sensory quality of wine produced from early harvested grapes was superior to that of late harvested grapes, whereas the opposite result was found at the high load. The typicality and richness of wine were significantly improved with the delay of harvest time, samples J-20-6 (medium load + E-L37) and J-20-7 (medium load + E-L38) outperforming all other samples. The overall sensory score of sample J-20-5 (medium load + E-L36) was the highest, and the total volatile content and sensory richness score of sample J-25-7 (high load + E-L38) were the highest among all tested samples. Thus, meticulous regulation of grape load and harvest time holds substantial promise for enhancing wine quality.

The skin, as the body’s largest organ, is vital for protecting against environmental stressors, regulating temperature, and preventing water loss. Here, we examined the potential of a mixture of five traditional Korean herbal extracts—Cimicifuga racemosa, Paeonia lactiflora, Phellodendron amurense, Rheum rhaponticum, and Scutellaria baicalensis—referred to as herbal medicine composite 5 (HRMC5) for enhancing skin health and managing menopausal symptoms. High-performance liquid chromatography identified 14 bioactive compounds, including flavonoids, phenolic acids, anthraquinones, and alkaloids. In vitro studies revealed an optimal concentration of 0.625 g/L for cell survival and UV protection, with the mixture demonstrating significant wound-healing properties comparable to epidermal growth factor. HRMC5 exhibited anti-inflammatory effects by downregulating COX2 expression and upregulating the key skin barrier proteins. A 4-week clinical trial involving 20 postmenopausal women showed significant improvements in skin redness, hemoglobin concentration, and skin moisture content. Visual analog scale assessments indicated substantial reductions in facial flushing severity and the associated sweating. The topical application of HRMC5 cream offered potential advantages over ingested phytoestrogens by reducing the systemic side effects. These findings suggest that HRMC5 is a promising non-invasive treatment for vasomotor symptoms in menopausal women and overall skin health, warranting further research on its long-term efficacy and safety in larger populations.