Post-exercise increases in muscle stiffness contribute to reduced muscle flexibility and increased injury risk. While electrical stimulation (ES) is used for recovery, its effect on muscle stiffness remains unclear. This study aimed to investigate the effect of ES on hamstring muscle stiffness following eccentric exercise. Fifteen healthy men participated in this study. Hamstring muscle stiffness (shear modulus), flexibility (passive straight leg raise angle), and maximal isometric knee flexion force were measured before and after a standardized leg curl exercise, and then at 0, 30, and 60 min following ES on one leg. The contralateral leg served as a control. ES was applied using interferential current in the device’s three-dimensional mode for 10 min at an intensity that induced visible muscle contraction. The leg curl exercise increased the stiffness in the semitendinosus (ST) and semimembranosus (SM). In the ST, the stiffness was significantly decreased at 30 min after ES (16.4 ± 8.36 kPa) compared with that immediately after exercise (22.1 ± 11.0 kPa). The passive straight leg raise angle was decreased after exercise and gradually increased over time, with faster recovery observed when ES was applied. Isometric knee flexion force decreased after exercise but did not significantly improve after ES. The application of ES following eccentric exercise may reduce stiffness in the ST and SM muscles and improve flexibility. These findings suggest a potential role for ES in post-exercise recovery protocols. Further investigation is needed to determine the long-term effects and optimal protocols for different muscle groups.
Sepsis is characterized by dysregulated inflammation leading to organ dysfunction. While immune activation and metabolic stress are central features, accumulating evidence suggests that regulated cell death programs actively influence inflammatory trajectories rather than serving as passive end-stage events. Apoptosis, pyroptosis, necroptosis, ferroptosis, and neutrophil extracellular trap (NET) formation have each been implicated in sepsis; however, their relative hierarchy, temporal dynamics, and compartment-specific relevance remain incompletely defined. To synthesize current evidence on regulated cell death pathways in sepsis and to propose a phase-specific and compartment-oriented framework that integrates apoptotic, inflammatory lytic, and NET-associated mechanisms within a unified inflammatory model. A narrative review of experimental, translational, and clinical studies examining apoptosis, pyroptosis, necroptosis, ferroptosis, PANoptosis, and NETosis in sepsis and related inflammatory states was conducted. Emphasis was placed on signaling dependency, inflammatory consequences, temporal phase distinctions, and cellular compartment heterogeneity. Apoptosis remains the dominant leukocyte death program associated with late-phase immune depletion and immunosuppression. In contrast, inflammasome-mediated pyroptosis and RIPK1/RIPK3-dependent necroptosis amplify early hyperinflammatory responses by inducing membrane permeabilization and damage-associated molecular pattern release. Ferroptosis represents an emerging iron-dependent metabolic-inflammatory interface with potential organ-specific relevance, although clinical validation remains limited. NET formation, often interpreted as a distinct death program, is more appropriately understood as a context-dependent effector mechanism linking innate immunity to thromboinflammation rather than representing the predominant terminal fate of leukocytes in sepsis. Increasing evidence supports pathway crosstalk and PANoptotic integration, suggesting that regulated cell death programs function as overlapping inflammatory networks rather than isolated processes.
p62/SQSTM1 self-assembles with polyubiquitin into liquid-like condensates ("p62 bodies") that function as stress-signaling hubs and selective autophagy cargo. We show that TBK1-dependent phosphorylation at Ser403 acts as a threshold-dependent modulator of a condensate's physical properties and promotes their rapid autophagic clearance. Phosphorylation within p62 bodies drives a transition from large, fluid droplets to compact, gel-like condensates that efficiently capture LC3-positive isolation membranes and accelerate the autophagic removal of ubiquitinated proteins. PP2A holoenzymes containing PPP2R5A/B/E, recruited via a KEAP1 bridge, counteract TBK1 by dephosphorylating Ser403. Homozygous p62S403E/S403E knock-in embryonic stem cells differentiate into post-mitotic neurons enriched in miniaturized, gel-like p62 bodies. Consistently, phosphorylation-mimetic knock-in mice show similar remodeling of p62 condensates in vivo, demonstrating that this phosphorylation-driven mechanism maintains proteostasis across scales. We propose that Ser403 phosphorylation functions as a molecular switch that couples the material state of p62 condensates to their stability and serves as a central control point for p62-mediated protein degradation.
The Oncotype DX 21-gene recurrence score (RS) is widely used to guide adjuvant chemotherapy decisions in early-stage estrogen receptor–positive, HER2-negative breast cancer. However, its high cost and frequent discordance with conventional clinicopathologic risk assessment raise questions regarding whether RS can be substituted by other indicators or selectively omitted in specific clinical settings. In this narrative review, we examined whether RS can be reliably predicted or replaced by clinicopathologic or pathology-derived factors, and whether there are patient groups in whom RS testing has limited impact on treatment decision-making. A comprehensive literature search and structured screening process identified 54 studies that treated RS as an outcome variable, together with additional reports addressing selective testing strategies. Across diverse analytical approaches, RS could not be consistently substituted by existing indicators. Although modest correlations were observed, substantial case-level discordance persisted, particularly within the intermediate RS range, where predictive performance deteriorated near clinically relevant decision thresholds. In contrast, RS testing appeared less influential in treatment decisions for patients with clearly defined low- or high-risk clinicopathologic profiles or favorable special histologic subtypes. Overall, current evidence indicates that RS cannot be reliably replaced by other indicators, while its clinical value varies by context, suggesting that a selective rather than uniform application of RS testing may be reasonable in some settings.
PurposeOur long-term goal is to develop fit and comfortable household masks. This study aimed to investigate the attitudes of Japanese youth towards wearing masks one year after the mask mandate was lifted, compared to their attitudes before the spread of COVID-19 infection. It also aimed to propose a physical evaluation method to assess the fit of masks. Design/methodology/approachIn 2024, a questionnaire was sent to young Japanese men and women to assess their frequency of mask usage, awareness of proper fit, and the problems associated with improper fit. In addition, a pilot study was conducted to measure the distance between the mask and face, using a flat mask with numerous holes and a dummy. FindingsAlthough the proportion of youth who frequently wore masks increased, the proportion of men and women who did not wear them remained the same as before the spread of infection. In addition, a significantly high proportion paid attention to the fit and reported that their masks fit them well. The distribution of the mask–face gap was illustrated. A continuous gap was observed from the top edge of the mask for female dummies and from the top and side edges to the nose and mouth area for male dummies. Originality/valueThe results of this study will be beneficial to mask manufacturers in developing new mask designs with improved fit and in providing accurate instructions on the proper method of wearing masks.
