Engineering considerations for next-generation oligonucleotide therapeutics
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Engineering bone/cartilage organoids: strategy, progress, and application
The concept and development of bone/cartilage organoids are rapidly gaining momentum, providing opportunities for both fundamental and translational research in bone biology. Bone/cartilage organoids, essentially miniature bone/cartilage tissues grown in vitro, enable the study of complex cellular interactions, biological processes, and disease pathology in a representative and controlled environment. This review provides a comprehensive and up-to-date overview of the field, focusing on the strategies for bone/cartilage organoid construction strategies, progresses in the research, and potential applications. We delve into the significance of selecting appropriate cells, matrix gels, cytokines/inducers, and construction techniques. Moreover, we explore the role of bone/cartilage organoids in advancing our understanding of bone/cartilage reconstruction, disease modeling, drug screening, disease prevention, and treatment strategies. While acknowledging the potential of these organoids, we discuss the inherent challenges and limitations in the field and propose potential solutions, including the use of bioprinting for organoid induction, AI for improved screening processes, and the exploration of assembloids for more complex, multicellular bone/cartilage organoids models. We believe that with continuous refinement and standardization, bone/cartilage organoids can profoundly impact patient-specific therapeutic interventions and lead the way in regenerative medicine.
Anthropogenic organic aerosol in Europe produced mainly through second-generation oxidation
Exposure to anthropogenic atmospheric aerosol is a major health issue, causing several million deaths per year worldwide. The oxidation of aromatic hydrocarbons from traffic and wood combustion is an important anthropogenic source of low-volatility species in secondary organic aerosol, especially in heavily polluted environments. It is not yet established whether the formation of anthropogenic secondary organic aerosol involves mainly rapid autoxidation, slower sequential oxidation steps or a combination of the two. Here we reproduced a typical urban haze in the ‘Cosmics Leaving Outdoor Droplets’ chamber at the European Organization for Nuclear Research and observed the dynamics of aromatic oxidation products during secondary organic aerosol growth on a molecular level to determine mechanisms underlying their production and removal. We demonstrate that sequential oxidation is required for substantial secondary organic aerosol formation. Second-generation oxidation decreases the products’ saturation vapour pressure by several orders of magnitude and increases the aromatic secondary organic aerosol yields from a few percent to a few tens of percent at typical atmospheric concentrations. Through regional modelling, we show that more than 70% of the exposure to anthropogenic organic aerosol in Europe arises from second-generation oxidation.
On-patient medical record and mRNA therapeutics using intradermal microneedles
Medical interventions often require timed series of doses, thus necessitating accurate medical record-keeping. In many global settings, these records are unreliable or unavailable at the point of care, leading to less effective treatments or disease prevention. Here we present an invisible-to-the-naked-eye on-patient medical record-keeping technology that accurately stores medical information in the patient skin as part of microneedles that are used for intradermal therapeutics. We optimize the microneedle design for both a reliable delivery of messenger RNA (mRNA) therapeutics and the near-infrared fluorescent microparticles that encode the on-patient medical record-keeping. Deep learning-based image processing enables encoding and decoding of the information with excellent temporal and spatial robustness. Long-term studies in a swine model demonstrate the safety, efficacy and reliability of this approach for the co-delivery of on-patient medical record-keeping and the mRNA vaccine encoding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This technology could help healthcare workers make informed decisions in circumstances where reliable record-keeping is unavailable, thus contributing to global healthcare equity.
Regulation of mammalian cellular metabolism by endogenous cyanide production
Small, gaseous molecules such as nitric oxide, carbon monoxide and hydrogen sulfide are produced as signalling molecules in mammalian cells. Here, we show that low concentrations of cyanide are generated endogenously in various mammalian tissues and cells. We detect cyanide in several cellular compartments of human cells and in various tissues and the blood of mice. Cyanide production is stimulated by glycine, occurs at the low pH of lysosomes and requires peroxidase activity. When generated at a specific rate, cyanide exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism and cell proliferation, but impairs cellular bioenergetics at high concentrations. Cyanide can modify cysteine residues via protein S-cyanylation, which is detectable basally in cells and mice, and increases in response to glycine. Low-dose cyanide supplementation exhibits cytoprotective effects in hypoxia and reoxygenation models in vitro and in vivo. Conversely, pathologically elevated cyanide production in nonketotic hyperglycinaemia is detrimental to cells. Our findings indicate that cyanide should be considered part of the same group of endogenous mammalian regulatory gasotransmitters as nitric oxide, carbon monoxide and hydrogen sulfide.
Solar-driven interfacial evaporation technologies for food, energy and water
Solar-driven interfacial evaporation technologies use solar energy to heat materials that drive water evaporation. These technologies are versatile and do not require electricity, which enables their potential application across the food, energy and water nexus. In this Review, we assess the potential of solar-driven interfacial evaporation technologies in food, energy and clean-water production, in wastewater treatment, and in resource recovery. Interfacial evaporation technologies can produce up to 5.3 l m–2 h−1 of drinking water using sunlight as the energy source. Systems designed for food production in coastal regions desalinate water to irrigate crops or wash contaminated soils. Technologies are being developed to simultaneously produce both clean energy and water through interfacial evaporation and have reached up to 204 W m–2 for electricity and 2.5 l m–2 h–1 for water in separate systems. Other solar evaporation approaches or combinations of approaches could potentially use the full solar spectrum to generate multiple products (such as water, food, electricity, heating or cooling, and/or fuels). In the future, solar evaporation technologies could aid in food, energy and water provision in low-resource or rural settings that lack reliable access to these essentials, but the systems must first undergo rigorous, scaled-up field testing to understand their performance, stability and competitiveness.
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