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Low-labor production of tissue-engineered muscles (TEMs) is one of the key technologies to realize the practical use of muscle-actuated devices. This study developed and then demonstrated the daily maintenance-free culture system equipped with both electrical stimulation and medium replacement functions. To avoid ethical issues, immortal myoblast cells C2C12 were used. The system consisting of gel culture molds, a medium replacement unit, and an electrical stimulation unit could produce 12 TEMs at one time. The contractile forces of the TEMs were measured with a newly developed microforce measurement system. Even the TEMs cultured without electrical stimulation generated forces of almost 2 mN and were shortened by 10% in tetanic contractions. Regarding the contractile forces, electrical stimulation by a single pulse at 1 Hz was most effective, and the contractile forces in tetanus were over 2.5 mN. On the other hand, continuous pulses decreased the contractile forces of TEMs. HE-stained cross-sections showed that myoblast cells proliferated and fused into myotubes mainly in the peripheral regions, and fewer cells existed in the internal region. This must be due to insufficient supplies of oxygen and nutrients inside the TEMs. By increasing the supplies, one TEM might be able to generate a force up to around 10 mN. The tetanic forces of the TEMs produced by the system were strong enough to actuate microstructures like previously reported crawling robots. This daily maintenance-free culture system which could stably produce TEMs strong enough to be utilized for microrobots should contribute to the advancement of biohybrid devices.

This comprehensive review explores the critical role of fatty acid (FA) metabolism in cardiac diseases, particularly heart failure (HF), and the implications for therapeutic strategies. The heart's reliance on ATP, primarily sourced from mitochondrial oxidative metabolism, underscores the significance of metabolic flexibility, with fatty acid oxidation (FAO) being a dominant source. In HF, metabolic shifts occur with an altered FA uptake and FAO, impacting mitochondrial function and contributing to disease progression. Conditions like obesity and diabetes also lead to metabolic disturbances, resulting in cardiomyopathy marked by an over-reliance on FAO, mitochondrial dysfunction, and lipotoxicity. Therapeutic approaches targeting FA metabolism in cardiac diseases have evolved, focusing on inhibiting or stimulating FAO to optimize cardiac energetics. Strategies include using CPT1A inhibitors, using PPARα agonists, and enhancing mitochondrial biogenesis and function. However, the effectiveness varies, reflecting the complexity of metabolic remodeling in HF. Hence, treatment strategies should be individualized, considering that cardiac energy metabolism is intricate and tightly regulated. The therapeutic aim is to optimize overall metabolic function, recognizing the pivotal role of FAs and the need for further research to develop effective therapies, with promising new approaches targeting mitochondrial oxidative metabolism and FAO that improve cardiac function.

ABSTRACTSmall non-coding RNAs (sncRNAs) are non-coding RNA molecules that play various roles in metazoans. Among the sncRNAs, microRNAs (miRNAs) guide post-translational gene regulation during cellular development, proliferation, apoptosis, and differentiation, while PIWI-interacting RNAs (piRNAs) suppress transposon activity to safeguard the genome from detrimental insertion mutagenesis. While an increasing number of piRNAs are being identified in the soma and germlines of various organisms, they are scarcely reported in molluscs. To unravel the small RNA (sRNA) expression patterns and genomic function in molluscs, we generated a comprehensive sRNA dataset by sRNA sequencing (sRNA-seq) of eight mollusc species. Abundant miRNAs were identified and characterized in all investigated molluscs, and ubiquitous piRNAs were discovered in both somatic and gonadal tissues in six of the investigated molluscs, which are more closely associated with transposon silencing. Tens of piRNA clusters were also identified based on the genomic mapping results, which varied among different tissues and species. Our dataset serves as important reference data for future genomic and genetic studies on sRNAs in these molluscs and related species, especially in elucidating the ancestral state of piRNAs in bilaterians.

Background: Intracranial histiocytic sarcoma (HS) is uncommon in dogs, and no standard treatment has yet been defined for this disease. Herein, we describe a case of intracranial HS that responded favorably to nimustine treatment. Case Description: A 9-year-old, castrated Welsh Corgi Pembroke presented with a two-month history of quadriplegia. Intracranial disease was suspected on neurological examination, and magnetic resonance imaging (MRI) revealed a contrast-enhanced mass in the left frontal lobe. Following tissue biopsy, the patient received intravenous nimustine (ACNU) treatment. The patient's neurological symptoms partially improved, and a reduction in tumor volume was observed on MRI on day 99. After three administrations of ACNU, tumor regrowth was confirmed on day 124, and temozolomide was subsequently administered. The patient subsequently showed no major changes in clinical symptoms, but subsequently died suddenly on day 195. Conclusion: In this case, administration of ACNU provided temporary symptom improvement and tumor reduction. Therefore, ACNU monotherapy may be a therapeutic option for canine intracranial HS. [Open Vet J 2024; 14(10.000): 2700-2706]

Abstract Introduction Mathematical modeling can provide quantitative understanding of the viral dynamics and viral reduction effects of drugs and enable simulations of the dynamics in various scenarios. In this study, a drug effect model of ensitrelvir was developed to describe the viral reduction effect. Using the model, we also estimated the impact of treatment with ensitrelvir on the reduction in the number of infected patients at the population level in Japan. Methods The drug effect model of ensitrelvir was developed based on a viral dynamic model for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a population pharmacokinetic model of ensitrelvir using 10,477 samples of viral load from 1447 patients with coronavirus disease 2019 (COVID-19) in a phase 2/3 study. It was assumed that the drug effect on SARS-CoV-2 promoted the viral clearance depending on the free plasma concentrations. We estimated the impact of ensitrelvir treatment on the reduction in the number of infected patients at the population level in Japan using the susceptible–infectious–recovered–susceptible (SIRS) model including transmission mitigation. Results The viral reduction effect of ensitrelvir was characterized as a promotion of viral clearance depending on the plasma ensitrelvir concentrations using the E max model. The maximum reduction effect was considered to depend on the time from symptom onset to treatment. The maximum transmission mitigation effect was observed when treatment was initiated within 12–24 h of symptom onset, and secondary infections could be reduced by administering ensitrelvir as soon as possible after symptom onset. Conclusion The viral reduction by ensitrelvir could be characterized based on the viral dynamics, and the dynamics could be estimated using the drug effect model. Furthermore, the drug effect on population level transmission based on the dynamics could be estimated. Thus, the simulation could be conducted for various conditions.

Abstract Background Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear. Case presentation A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25–75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV1 coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25–75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively. Conclusions This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs.

Background: Brain perfusion may differ between patients with corticobasal syndrome (CBS) with and without aphasia. Methods: Twenty-six (9 males and 17 females; mean age 76 ± 5.3 years) patients with CBS were enrolled in the study. Brain MRI and single-photon emission computed tomography were performed in all subjects. Language was evaluated using the Standard Language Test of Aphasia. The patients were divided into two subgroups according to the presence or absence of progressive aphasia. Differences in the regional cerebral blood flow (rCBF) between the two groups were detected based on voxel-by-voxel group analysis using Statistical Parametric Mapping 8. Results: All patients exhibited asymmetric motor symptoms and signs, including limb apraxia, bradykinesia, and akinetic rigidity. Of 26 patients, 9 had a clinically obvious language disturbance, characterized as nonfluent aphasia. Almost all CBS patients with aphasia exhibited cortical atrophy predominantly in the left frontal and temporal lobes with widening of the Sylvian fissure on MRI. The rCBF in the left middle frontal gyrus differed significantly between CBS patients with and without aphasia. Conclusion: CBS patients with aphasia exhibit motor symptoms predominantly on the right side and cortical atrophy mainly in the left perisylvian cortices. In particular, left frontal dysfunction might be related to nonfluent aphasia in CBS.

This paper presents a numerical optimization method to improve the performance of the propeller with Turbo-Ring using real-coded genetic algorithm. In the presented method, Unimodal Normal Distribution Crossover (UNDX) and Minimal Generation Gap (MGG) model are used as crossover operator and generation-alternation model, respectively. Propeller characteristics are evaluated by a simple surface panel method “SQCM” in the optimization process. Blade sections of the original Turbo-Ring and propeller are replaced by the NACA66 a = 0.8 section. However, original chord, skew, rake and maximum blade thickness distributions in the radial direction are unchanged. Pitch and maximum camber distributions in the radial direction are selected as the design variables. Optimization is conducted to maximize the efficiency of the propeller with Turbo-Ring. The experimental result shows that the efficiency of the optimized propeller with Turbo-Ring is higher than that of the original propeller with Turbo-Ring.

Bio-actuators that use insect muscular tissue have attracted attention from researchers worldwide because of their small size, self-motive property, self-repairer ability, robustness, and the need for less environment management than mammalian cells. To demonstrate the potential of insect muscular tissue for use as bio-actuators, three types of these robots, a pillar actuator, a walker, and a twizzer, have been designed and fabricated. However, a model of an insect muscular tissue-powered swimming robot that is able to float and swim in a solution has not yet been reported. Therefore, in this paper, we present a prototype of an insect muscular tissue-powered autonomous micro swimming robot that operates at room temperature and requires no temperature and pH maintenance. To design a practical robot body that is capable of swimming by using the force of the insect dorsal vessel (DV), we first measured the contraction force of the DV. Then, the body of the swimming robot was designed, and the design was confirmed by a simulation that used the condition of measured contraction force. After that, we fabricated the robot body using polydimethylpolysiloxane (PDMS). The PDMS body was obtained from a mold that was fabricated by a stereo lithography method. Finally, we carefully attached the DV to the PDMS body to complete the assembly of the swimming robot. As a result, we confirmed the micro swimming robot swam autonomously at an average velocity of 11.7 μm/s using spontaneous contractions of the complete insect DV tissue. These results demonstrated that the insect DV has potential for use as a bio-actuator for floating and swimming in solution.

Abstract The effect of gravity on the lungs has been evaluated using computed tomography (CT) in the supine and prone positions but not the standing position. However, as humans spend most of the daytime in the standing position, we aimed to compare lung attenuation gradients between the supine and standing positions, and to assess the correlations between the lung attenuation gradients and participant characteristics, including pulmonary function test results. Overall, 100 healthy participants underwent conventional/supine and upright CT, and lung attenuation gradients were measured. Lung attenuation gradients in anteroposterior direction were greater in the supine position than in standing position (all p values