The asb5 gene, a member of the Asb protein subfamily characterized by six ankyrin repeat domains, is highly conserved and comprises two subtypes, asb5a and asb5b, in zebrafish. Our previous research has demonstrated that a deficiency of the asb5 gene significantly impairs early cardiac contractile function, highlighting its close relationship with heart development. Zebrafish asb5 expression was disrupted by both morpholino (MO) antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. A high-throughput RNA-Seq analysis was used to analyze the possible molecular regulatory mechanism of asb5 gene deletion leading to left–right (L-R) asymmetry defects in the heart. Whole-mount in situ hybridization (WISH) was conducted to evaluate gene expression patterns of Nodal signaling components and the positions of heart organs. Heart looping was defective in zebrafish asb5 morphants. Rescue experiments in the asb5-deficiency group (inactivating both asb5a and asb5b) demonstrated that the injection of either asb5a-mRNA or asb5b-mRNA alone was insufficient to rectify the abnormal L-R asymmetry of the heart. In contrast, the simultaneous injection of both asb5a-mRNA and asb5b-mRNA successfully rescued the morphological phenotype. A high-throughput RNA-Seq analysis of embryos at 48 h post fertilization (hpf) revealed that numerous genes associated with L-R asymmetry exhibited expression imbalances in the asb5-deficiency group. WISH further confirmed that the expression of genes such as fli1a, acta1b, hand2, has2, prrx1a, notch1b, and foxa3 were upregulated, while the expression of mei2a and tal1 was downregulated. These results indicated that loss of the asb5 gene in zebrafish led to the disordered development of L-R asymmetry in the heart, resulting in an imbalance in the expression of genes associated with the regulation of L-R asymmetry. Subsequently, we examined the expression patterns of classical Nodal signaling pathway-related genes using WISH. The results showed that the midline barrier factor gene lefty1 was downregulated at early stages in the asb5-deficiency group, and the expression of spaw and lefty2, which are specific to the left lateral plate mesoderm (LPM), was disrupted. This study reveals that the two subtypes of the asb5 gene in zebrafish, asb5a and asb5b, interact and jointly regulate the establishment of early cardiac L-R asymmetry through the Nodal-spaw-lefty signaling pathway.

Introduction: Coordinating extreme-heat adaptation at mega-sporting events is a time-dependent public health challenge because public authorities, event organizers, and participating teams control different protective measures while heat risk evolves over a finite competition horizon. Existing sport-heat research describes exposure and prevention yet provides limited guidance on how adaptation should be timed, coordinated, and financed across responsible institutions. Methods: We develop a three-actor linear-quadratic differential game with gross event heat-risk pressure and accumulated adaptive capacity as state variables. Open-loop Nash, government-led Stackelberg, and cooperative solutions are evaluated under four normalized heat-shock structures. Early-warning lead time enters through a piecewise information structure, and a budget-balanced cost-sharing rule supports decentralized implementation of the cooperative path. Results: In the baseline late-peak scenario with a lead time of three normalized units, cooperation reduces modeled social loss by 21.9% relative to Nash and 23.1% relative to government-led Stackelberg; peak residual heat-risk pressure falls by 28.0% and 28.7%, respectively. Under the baseline parameterization, social loss in the government-led regime exceeds the Nash value by 1.6%. Earlier warning lowers loss, residual pressure, and peak effort, although its marginal value declines once a usable preparation window is available. Across the tested combinations of warning lead time and organizer mitigation efficiency, cooperative social gains range from 16.7 to 24.4%. Within the model, the effective preparation-window threshold—defined as the first normalized lead time capturing 80% of the cooperative warning benefit available between L = 0 and L = 6—ranges from 2.2 to 2.6 and responds mainly to heat-shock duration. Cooperation also shifts effort toward organizer-controlled measures, while cost sharing compensates the organizer for carrying greater responsibility despite receiving the smallest uncompensated private gain. Discussion: The Nash—Stackelberg ordering is conditional on the government-first sequence, actor-specific objectives, and parameter values used in the analysis. Within the normalized model, these findings indicate that coordinated extreme-heat adaptation can benefit from aligning actor objectives and linking warning information to actionable time, institutional capability, and financing. Event-specific application requires empirical calibration.

The Popeye domain-containing protein 1 (Popdc1), also known as Bves, plays a crucial role in maintaining skeletal muscle homeostasis, with its variants leading to limb–girdle muscular dystrophy type R25. Skeletal muscles of patients with the homozygous missense variant of Bves exhibit impaired membrane trafficking, while skeletal muscle fibers in bves^S191F homozygous mutant zebrafish are significantly reduced and disorganized. However, the mechanism by which the absence of bves induces skeletal muscle atrophy remains unclear. In this study, we discovered a novel mechanism whereby bves deficiency drives skeletal muscle atrophy by disrupting mitochondrial structure and function. Our findings indicate that bves knockout leads to a significant decrease in zebrafish’s ability to swim, atrophy of skeletal muscle tissue, loss of cell membrane localization signals, and abnormalities in mitochondrial structure and function. After an 8-week intervention of regular aerobic exercise, the symptoms of skeletal muscle atrophy in bves knockout zebrafish were significantly alleviated, and the expression levels of genes and proteins related to mitochondrial were effectively rescued. These findings establish a connection between bves deficiency-induced disruption of mitochondrial structure and function and the onset and progression of skeletal muscle tissue atrophy symptoms, thereby laying a molecular foundation for exercise rehabilitation strategies in atrophic myopathy.