Systemic autoimmune diseases (sAIDs) affect 1 in 10 people and represent a leading cause of death in women under the age of 65 years. Despite the emergence of targeted‐biologic therapies, mortality rates for sAIDs have not improved. Emerging cellular therapies represent a promising therapeutic strategy for patients living with sAIDs given their potential to induce sustained remission and limit long‐term exposure to glucocorticoids. Encouraging outcomes from a case series of patients with systemic lupus erythematosus, idiopathic inflammatory myopathy, and systemic sclerosis (SSc) have ignited clinical development in this therapeutic area. However, numerous questions remain regarding cellular therapy clinical trial design, ranging from the optimal time to intervene with cellular therapies during a sAID to the appropriate duration of the washout period, conditioning regimen, and management of serious treatment‐related adverse events in these patients. Building the infrastructure and multidisciplinary teams necessary to conduct cellular therapy trials for sAIDs also represents a major challenge. To address these critical issues, the National Cancer Institute's Center for Cancer Research and the National Institute of Arthritis and Musculoskeletal and Skin Diseases convened a workshop in which stakeholders from diverse areas addressed strategies to bridge the gap between preclinical and clinical research, foster collaboration between rheumatologists and hematologists‐oncologists, and develop optimal treatment protocols grounded in solid science. This manuscript summarizes the main concepts put forward and makes practical recommendations for advancing the development of cellular therapy for sAIDs.
Titanium electroreduction is desired for a variety of medical, electronic, and bonding applications but has not been possible until recently. Titanium electrodeposition with leveler and brightener additives in the deep eutectic solvent ethaline has been studied for effects on spectroscopic reflectance. Polymeric leveling agents and several small‐molecule brighteners produce level/bright films (respectively) with high values for both specular and diffuse reflectance. The application of these leveling and brightening agents can produce films with appearances and surface roughnesses that may be suitable for application in medical implants such as stents, corrosion protection of electronics for wearable technology, and as interlayers between dissimilar metals.
Abstract Despite the significant milestones in the half‐reduction process of photocatalysis, challenges remain in fully utilizing electron–hole pairs in the simultaneous redox reactions. Herein, a Z‐scheme ZnIn 2 S 4 /W 18 O 49 (ZW) hybrid with complementary band edge potential is in situ constructed. The resultant fuzzy 1D‐assembled sea‐urchin photocatalyst demonstrates an optimal H 2 and benzaldehyde yield of 122 and 106 µmol h −1 under λ > 420 nm light irradiation. This sacrificial‐agent‐free system entails solar‐to‐hydrogen (STH) and apparent quantum efficiency (AQE) values of 0.466% and 2.48% (420 nm), respectively, surpassing most of the recently reported photocatalytic systems without the aid of noble metal cocatalysts. The outstanding performance is mainly attributed to the synergistic formation of intimate Z‐scheme heterojunction and the induction of localized surface plasmon resonances. Comprehensive characterization studies prove the direct injection of energetic hot electrons to promote the number of long‐lived active electrons. Besides, electron paramagnetic resonance and scavenger tests clarify the complicated mechanistic puzzle of the dual‐redox reaction, where benzaldehyde is formed dominantly via O─H activation followed by C─H cleavage of benzyl alcohol over ZW hybrid. Lastly, the universal use of the ZnIn 2 S 4 /W 18 O 49 composites is testified in various dual‐redox systems. This study offers a novel outlook for designing dual‐functioning heterojunctions toward a feasible photoredox application.
Abstract Classical photoresists utilized in direct laser writing (DLW) rely on photoinitiators and radical polymerization mechanisms to induce the cross‐linking process. Herein, a simple initiator‐free photoresist is introduced that enables the rapid fabrication of intrinsically thermally degradable 3D microstructures via DLW. The reported photoresist exploits the [2 + 2] photo‐dimerization reaction of a multifunctional monosubstituted thiomaleimide compound while harvesting on‐demand microstructure degradation through the intrinsic thermally reversible nature of the photocrosslinks. The photoresist exceeds attainable DLW printing speeds for non‐chain growth resins, readily attaining 1500 µm s −1 and up to 5000 µm s −1 , making it a promising system to compete with traditional photo‐initiator containing resists while introducing on‐demand post‐printing degradability.
Abstract Functionalized glass plays a crucial role in various fields, including materials and biomedical sciences. Traditionally, it has been produced through silanization reactions or by coating the glass with polymers. But these approaches involve toxic chemicals and result in films that are prone to hydrolysis upon long‐term exposure to water. In this report, a novel, simple method for functionalizing glass using ultrasonication of aryl diazonium salts is introduced. When these salts are exposed to ultrasound under mild conditions (24 kHz/400 W), aryl radicals are generated, which spontaneously react with the glass surface. This reaction forms a thin organic polymeric film whose surface properties, such as hydrophobicity or charge, can be tailored by the terminal group of the diazonium salt employed. The film is covalently bonded to the glass surface via Si–O–C bonds, which offer enhanced stability compared to the more hydrolysis‐prone Si–O–Si bonds that govern traditional silanization techniques. This newly functionalized glass is shown to adhere microorganisms such as microalgae ( Chlorella vulgaris C. vulgaris ), bacteria ( Escherichia coli, E. coli ), and yeast ( Saccharomyces cerevisiae, S. cerevisiae ), suggesting potential applications in enzyme production, filtration, environmental remediation technologies, biofuels, and biofuel cells.
Abstract Osteosarcoma (OS), the most common bone cancer in children, is characterized by aggressive tumors and subclinical metastasis. Metastasis significantly impacts OS patient survival rate, highlighting the need for frequent assessment of disease progression and treatment response. The study introduces OS extracellular vesicles (EV) matrix metalloproteinase (MMP) Activity Assay, noninvasively analyzing six combinations of OS EV surface markers and OS‐associated MMPs to generate a unique OS EV MMP profile for each patient. An OS EV MMP Activity Score is established from logistic regression of three top‐performing combinations to specifically distinguish metastatic OS from localized OS, achieving an area under the receiver operating characteristic (AUROC) curve of 0.97. The Scores from longitudinal monitoring of six OS patients strongly correlate with disease progression and treatment response, as confirmed by radiographic imaging. The OS EV MMP Activity Assay enables noninvasive and timely monitoring of disease progression and treatment response during the critical disease window of progression to metastatic OS, enhancing clinical management for OS patients.
Liquid Biopsy In their Research Article ( 10.1002/adfm.202422469), Junseok Lee, Steven John Jonas, Shaohua Lu, Yazhen Zhu, Hsian‐Rong Tseng, and co‐workers present a novel osteosarcoma extracellular vesicle matrix metalloproteinase activity assay (OS EV MMP activity assay) for noninvasive and real‐time monitoring of disease progression and treatment response in pediatric osteosarcoma. By combining click chemistry‐enabled tumor EV enrichment with FRET‐based protease activity profiling, the assay quantitatively evaluates six specific EV surface marker/MMP combinations. This minimally invasive platform enables early detection of metastasis and longitudinal disease monitoring, offering a powerful tool to improve clinical management of osteosarcoma.
Abstract This research focuses on developing and characterizing islatravir‐loaded dissolving microarray patches (MAPs) to provide an effective, minimally invasive treatment option for human immunodeficiency virus (HIV‐1) prevention and treatment. The research involves manufacturing these MAPs using a double‐casting approach, and conducting in vitro and in vivo evaluations. Results show that the MAPs have excellent needle fidelity, structural integrity, and mechanical strength. in vitro studies demonstrate that the MAPs can penetrate skin up to 580 µm and dissolve within 2 hours. Permeation studies reveal that the delivery efficiency of islatravir across the skin is around 40%. In rodent models, these dissolving MAPs sustain islatravir delivery for up to 3 months. Scaling up the MAPs and increasing drug loading produced detectable levels in minipig. Projections from animal data suggest that these dissolving MAPs can achieve effective islatravir levels for a month after a single application in humans. These findings indicate dissolving MAPs as a minimally invasive approach to sustained release of islatravir.
Abstract This study presents a semiconducting optoelectronic system for light‐controlled non‐genetic neuronal stimulation using visible light. The system architecture is entirely wireless, comprising a thin film of nitrogen‐doped ultrananocrystalline diamond directly grown on a semiconducting silicon substrate. When immersed in a physiological medium and subjected to pulsed illumination in the visible (595 nm) or near‐infrared wavelength (808 nm) range, charge accumulation at the device‐medium interface induces a transient ionic displacement current capable of electrically stimulating neurons with high temporal resolution. With a measured photoresponsivity of 7.5 mA W −1 , the efficacy of this biointerface is demonstrated through optoelectronic stimulation of degenerate rat retinas using 595 nm irradiation, pulse durations of 50–500 ms, and irradiance levels of 1.1–4.3 mW mm −2 , all below the safe ocular threshold. This work presents the pioneering utilization of a diamond‐based optoelectronic platform, capable of generating sufficiently large photocurrents for neuronal stimulation in the retina.