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Behavioral and neurophysiological effects of electrical stunning on zebrafish larvae
Two methods dominate the way that zebrafish larvae are euthanized after experimental procedures: anesthetic overdose and rapid cooling. Although MS-222 is easy to apply, this anesthetic takes about a minute to act and fish show aversive reactions and interindividual differences, limiting its reliability. Rapid cooling kills larvae after several hours and is not listed as an approved method in the relevant European Union directive. Electrical stunning is a promising alternative euthanasia method for zebrafish but has not yet been fully established. Here we characterize both behavioral and neurophysiological effects of electrical stunning in 4-day-old zebrafish larvae. We identified the electric field characteristics and stimulus duration (50 V/cm alternating current for 32 s) that reliably euthanizes free-swimming larvae and agarose-embedded larvae with an easy-to-implement protocol. Behavioral analysis and calcium neurophysiology show that larvae lose consciousness and stop responding to touch and visual stimuli very quickly (<1 s). Electrically stunned larvae no longer show coordinated brain activity. Their brains instead undergo a series of concerted whole-brain calcium waves over the course of many minutes before the cessation of all brain signals. Consistent with the need to implement the 3R at all stages of animal experimentation, the rapid and reliable euthanasia achieved by electrical stunning has potential for refinement of the welfare of more than 5 million zebrafish used annually in biomedical research worldwide.
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.
Innovating beyond electrophysiology through multimodal neural interfaces
Neural circuits distributed across different brain regions mediate how neural information is processed and integrated, resulting in complex cognitive capabilities and behaviour. To understand dynamics and interactions of neural circuits, it is crucial to capture the complete spectrum of neural activity, ranging from the fast action potentials of individual neurons to the population dynamics driven by slow brain-wide oscillations. In this Review, we discuss how advances in electrical and optical recording technologies, coupled with the emergence of machine learning methodologies, present a unique opportunity to unravel the complex dynamics of the brain. Although great progress has been made in both electrical and optical neural recording technologies, these alone fail to provide a comprehensive picture of the neuronal activity with high spatiotemporal resolution. To address this challenge, multimodal experiments integrating the complementary advantages of different techniques hold great promise. However, they are still hindered by the absence of multimodal data analysis methods capable of providing unified and interpretable explanations of the complex neural dynamics distinctly encoded in these modalities. Combining multimodal studies with advanced data analysis methods will offer novel perspectives to address unresolved questions in basic neuroscience and to develop treatments for various neurological disorders.
An umbrella review of health outcomes following traumatic brain injury
While numerous reviews have assessed the association between traumatic brain injury (TBI) and various mental and physical health outcomes, a comprehensive evaluation of the scope, validity, and quality of evidence is lacking. Here we present an umbrella review of a wide range of health outcomes following TBI and outline outcome risks across subpopulations. On 17 May 2023, we searched Embase, Medline, Global Health, PsycINFO, and Cochrane Database of Systematic Reviews for systematic reviews and meta-analyses. We compared risk ratios across different outcomes for risks compared with people without TBI and examined study quality, including heterogeneity, publication bias, and prediction intervals. The study was registered with PROSPERO (CRD42023432255). We identified 24 systematic reviews and meta-analyses covering 24 health outcomes in 31,397,958 participants. The current evidence base indicates an increased risk of multiple mental and physical health outcomes, including psychotic disorders, attention-deficit/hyperactivity disorder, suicide, and depression. Three outcomes—dementia, violence perpetration, and amyotrophic lateral sclerosis—had meta-analytical evidence of at least moderate quality, which suggest targets for more personalized assessment. Health-care services should review how to prevent adverse long-term outcomes in TBI.
Decarbonizing urban residential communities with green hydrogen systems
Community green hydrogen systems, typically consisting of rooftop photovoltaic panels paired with hybrid hydrogen-battery storage, offer urban environments with improved access to clean, on-site energy. However, economically viable pathways for deploying hydrogen storage within urban communities remain unclear. Here we develop a bottom-up energy model linking climate, human behavior and community characteristics to assess the impacts of pathways for deploying community green hydrogen systems in North America from 2030 to 2050. We show that for the same community conditions, the cost difference between the best and worst pathways can be as high as 60%. In particular, the household centralized option emerges as the preferred pathway for most communities. Furthermore, enhancing energy storage demands within these deployment pathways can reduce system design costs up to fourfold. To achieve cost-effective urban decarbonization, the study underscores the critical role of selecting the right deployment pathway and prioritizing the integration of increased energy storage in pathway designs.
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