Notes

Full-color nanorouter with regard to high-resolution image.
Three-dimensional (3D) biomimetic systems hold great promise for the study of biological systems in vitro as well as for the development and testing of pharmaceuticals. Here, we test the hypothesis that an intact segment of lumbar rat spinal cord will form functional neuromuscular junctions (NMJs) with engineered, 3D muscle tissue, mimicking the partial development of the peripheral nervous system (PNS). Muscle tissues are grown on a 3D-printed polyethylene glycol (PEG) skeleton where deflection of the backbone due to muscle contraction causes the displacement of the pillar-like "feet." We show that spinal cord explants extend a robust and complex arbor of motor neurons and glia in vitro. We then engineered a "spinobot" by innervating the muscle tissue with an intact segment of lumbar spinal cord that houses the hindlimb locomotor central pattern generator (CPG). Within 7 days of the spinal cord being introduced to the muscle tissue, functional neuromuscular junctions (NMJs) are formed, resulting in the development of an early PNS in vitro. The newly innervated muscles exhibit spontaneous contractions as measured by the displacement of pillars on the PEG skeleton. Upon chemical excitation, the spinal cord-muscle system initiated muscular twitches with a consistent frequency pattern. These sequences of contraction/relaxation suggest the action of a spinal CPG. Chemical inhibition with a blocker of neuronal glutamate receptors effectively blocked contractions. Overall, these data demonstrate that a rat spinal cord is capable of forming functional neuromuscular junctions ex vivo with an engineered muscle tissue at an ontogenetically similar timescale.Biohybrid microswimmers, which are realized through the integration of motile microscopic organisms with artificial cargo carriers, have a significant potential to revolutionize autonomous targeted cargo delivery applications in medicine. Nonetheless, there are many open challenges, such as motility performance and immunogenicity of the biological segment of the microswimmers, which should be overcome before their successful transition to the clinic. Here, we present the design and characterization of a biohybrid microswimmer, which is composed of a genetically engineered peritrichously flagellated Escherichia coli species integrated with red blood cell-derived nanoliposomes, also known as nanoerythrosomes. Initially, we demonstrated nanoerythrosome fabrication using the cell extrusion technique and characterization of their size and functional cell membrane proteins with dynamic light scattering and flow cytometry analyses, respectively. Then, we showed the construction of biohybrid microswimmers through the conjugation of streptavidin-modified bacteria with biotin-modified nanoerythrosomes by using non-covalent streptavidin interaction. Finally, we investigated the motility performance of the nanoerythrosome-functionalized biohybrid microswimmers and compared it with the free-swimming bacteria. The microswimmer design approach presented here could lead to the fabrication of personalized biohybrid microswimmers from patients' own cells with high fabrication efficiencies and motility performances.Safety evaluation of drugs requires examination of the risk of generating Torsade de Pointes (TdP) because it can lead to sudden cardiac death. selleck kinase inhibitor Until recently, the QT interval in the electrocardiogram (ECG) has been used in the evaluation of TdP risk because the QT interval is known to be associated with the development of TdP. Although TdP risk evaluation based on QT interval has been successful in removing drugs with TdP risk from the market, some safe drugs may have also been affected due to the low specificity of QT interval-based evaluation. For more accurate evaluation of drug safety, the comprehensive in vitro proarrhythmia assay (CiPA) has been proposed by regulatory agencies, industry, and academia. Although the CiPA initiative includes in silico evaluation of cellular action potential as a component, attempts to utilize in silico simulation in drug safety evaluation are expanding, even to simulating human ECG using biophysical three-dimensional models of the heart and torso under the effects of drugs. Here, we review recent developments in the use of in silico models for the evaluation of the proarrhythmic risk of drugs. We review the single cell, one-dimensional, two-dimensional, and three-dimensional models and their applications reported in the literature and discuss the possibility of utilizing ECG simulation in drug safety evaluation.[This corrects the article DOI 10.1210/jendso/bvz028.].Since 2015, a large heap of improperly disposed coal-mine waste in Ban Chaung, Dawei district, Myanmar, has repeatedly spontaneously combusted, affecting an indigenous community. Recently, the regional Myanmar government has compelled the mine to properly manage the mine waste heap, but there is no opportunity for affected villagers to participate. This study empowers the affected villagers to make risk management decisions via a community citizen science approach. First, field investigations were performed with the affected community to identify hot spots at the waste heap releasing gaseous pollutants that may exceed acceptable levels. Next, existing monitoring data previously collected by the community were interpreted as clear evidence of past poor waste management. Information about suppression of existing fire and mine waste storage options was presented to the community for them to make an informed decision about the most appropriate corrective action that should be taken by the mine. The mining company chose to use surface sealing for both suppression of existing fire and on-site storage of the mine waste but did not install any long-term monitoring system. Nevertheless, the community's choice was surface sealing with preventive monitoring together with emergency response, which is the more scientifically appropriate option. This outcome of a science-based risk management decision by the community will be forwarded to the regional government for enforcement. This process of community citizen science is in line with the normative rationale of public participation, which is meant to influence decisions, elevate democratic capacity, and empower marginalized individuals and communities.
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