Search Results (118)

Long-duration space missions expose astronauts to galactic cosmic radiation (GCR), a complex spectrum of high-charge, high-energy (HZE) ions that pose significant risks of chronic tissue injury. To model these effects, we examined intestinal outcomes in wild-type mice 5 months after low-dose (50 cGy) 33-ion mixed-field GCR simulation (GCRsim). GCRsim induced sustained DNA double-strand breaks (DSBs) and oxidative stress, as shown by elevated γH2AX foci and 4-HNE staining. Intestinal epithelial cells (IECs) exhibited pronounced senescence, marked by increased SA-β-gal activity, p16 upregulation, LaminB1 loss, and induction of senescence-associated secretory phenotype (SASP) cytokines (Cxcl10, IL-6, IL-1β, Icam1). GCRsim also elevated circulating LINE-1 DNA and reduced expression of DNA-degrading nucleases (DNase2, TREX1), indicating impaired extracellular DNA clearance. Targeted molecular study revealed persistent activation of the cGAS–STING pathway, with elevated cGAS, STING, pTBK1, pIKKα/β, and nuclear pIRF3, pIRF7, and p65, consistent with chronic innate immune signaling. Functionally, GCRsim altered nutrient absorption gene expression—upregulating glucose transporters (Slc2a2, Slc2a5, Slc5a1) and gut hormones (Cck, Gip), while downregulating cholesterol/fat transporters (Npc1, Npc1l1). Biochemical markers supported intestinal injury, with decreased serum citrulline and increased intestinal fatty acid-binding protein (I-FABP), indicating barrier compromise. Collectively, these findings demonstrate that GCRsim drives sustained intestinal dysfunction, highlighting the need for countermeasures to protect GI health during deep-space missions. Full article

Radiotherapy (RT) remains a cornerstone of cancer treatment, offering spatially precise cytotoxicity against malignant cells. However, emerging evidence reveals that ionizing radiation (IR) exerts biological effects beyond the targeted tumor volume, manifesting as radiation bystander effects (BEs) and other non-targeted effects (NTEs). These phenomena challenge the traditional paradigm of RT as a localized intervention, highlighting systemic and long-term consequences in non-irradiated tissues. This comprehensive review synthesizes molecular, cellular, and clinical insights about BEs, elucidating the complex intercellular signaling networks gap junctions, cytokines, extracellular vesicles, and oxidative stress that propagate damage, genomic instability, and inflammation. We explore the role of mitochondrial dysfunction, epigenetic reprogramming, immune modulation, and stem cell niche disruption in shaping BEs outcomes. Clinically, BEs contribute to neurocognitive decline, cardiovascular disease, pulmonary fibrosis, gastrointestinal toxicity, and secondary malignancies, particularly in pediatric and long-term cancer survivors. The review also evaluates countermeasures including antioxidants, COX-2 inhibitors, exosome blockers, and FLASH RT, alongside emerging strategies targeting cfCh, inflammasomes, and senescence-associated secretory phenotypes. We discuss the dual nature of BEs: their potential to both harm and heal, underscoring adaptive responses and immune priming in specific contexts. By integrating mechanistic depth with translational relevance, this work posits that radiation BEs are a modifiable axis of RT biology. Recognizing and mitigating BEs is imperative for optimizing therapeutic efficacy, minimizing collateral damage, and enhancing survivorship outcomes. This review advocates for a paradigm shift in RT planning and post-treatment care, emphasizing precision, personalization, and systemic awareness in modern oncology. Full article

Future Artemis-class missions to Mars will expose astronauts to prolonged space radiation (SR), sleep disruption, and operational demands requiring greater autonomy, placing decision making and executive function at heightened risk. Both SR and sleep fragmentation (SF) independently impair cognition, yet their combined effects remain poorly understood. Using the Associative Recognition Memory and Interference (ARMIT) task, we assessed cognitive performance in male rats exposed to 10 cGy of Galactic Cosmic Ray simulation (GCRsim), SF, or both. Under well-rested conditions, GCRsim-exposed rats exhibited overt deficits in the C.1.2 stage, performing at chance when reinforcement contingencies shifted, consistent with impaired cognitive flexibility. In contrast, high-performing GCRsim-exposed rats that initially performed comparably to Sham s revealed latent deficits following a single night of SF. Specifically, the SF-induced loss of C.1.3 performance was accompanied by perseverative errors (persistently selecting outdated cues despite negative feedback), reflecting impaired attentional control and decision updating. Sham s maintained stable performance after SF. These findings support a two-hit vulnerability model in which SR primes corticostriatal and frontoparietal networks for collapse under subsequent sleep disruption. Operationally, this suggests that astronauts may display either persistent or stress-induced deficits, with both modes threatening mission success. Identifying mechanisms of such vulnerabilities is essential for countermeasure development. Full article

Introduction: The work presented here is part of our study series aimed at investigating the countermeasure effectiveness of apigenin (AP) against both early and late effects of heavy silicon (²⁸Si) on the same cohort of exposed male C57BL/6 mice. We previously reported the countermeasure of AP against ²⁸Si-induced early effects of ²⁸Si ions. This section focuses on the protective effects of AP on late effects, specifically on the induction of acute lymphoma/lymphoblastic leukemia. Method: Mice received a diet containing 20 mg/kg body weight of AP for five days before and after total-body irradiation with either 0 or 0.5 Gy of 260 MeV ²⁸Si ions. They were divided into four groups based on AP intake and irradiation status. At one-week after irradiation, six mice from each group were euthanized to assess AP’s effectiveness against early inflammation (in the bone marrow and gut tissues) and gut dysbiosis. The remaining mice were monitored until approximately 770 days of age. Incidence rates were analyzed using Chi-Square tests, while survival data were evaluated with Kaplan–Meier plots and log-rank tests, setting significance at p ≤ 0.05. Results: At 770 days, survival rates were 37% for ²⁸Si-exposed mice and 63% for those consuming AP, despite irradiation. There was a 2.57-fold increase in acute lymphoma/lymphoblastic leukemia incidence among ²⁸Si-exposed mice not receiving AP compared to controls and AP-fed mice. Together with our previous report on the countermeasure activity of AP against early effects, these findings suggest that the gut–bone marrow axis plays an important role in ²⁸Si-induced acute lymphoma/lymphoblastic leukemia. Conclusion: Our findings demonstrate that AP is an effective means of tackling the challenges posed by space radiation, and it has the potential to revolutionize protection in this critical area. Full article

The complexity of adverse responses from radiation injury (RI) followed by physical trauma, namely, radiation combined injury (RCI), is unique and more pronounced than either insult alone due to a poor understanding of the integration of these insults at the molecular/cellular/tissue and/or organ levels. It was shown that mice receiving ⁶⁰Co γ-photon RCI with wounding had a lower LD_50/30 than RI alone. This survival synergism was observed in bone marrow and the gastrointestinal system, as evidenced by an increase in γ-H2AX expression in bone marrow cell DNA, loss of circulatory blood cells, elevation of serum cytokine concentration, and activation of nuclear factor-κB/inducible nitric oxide synthase, and an earlier onset of bacterial infection and sepsis after RCI than after RI was detected. Dysbiosis (imbalance of the gut microbiota) was observed. There remains a pressing need for both prophylactic countermeasures and therapeutic remedies to deal with RCI threats. Investigations of how RCI can affect this important network of communication between the gut microbiota and other organs, including the brain, lung, heart, liver, kidney, and skin, could lead to new and critical interventions and prevention strategies. This review provides an update on new RCI animal models, dynamic changes in cytokine expression, dysbiosis, as well as links between the gut microbiome and other organs after RCI. Full article

The application of dynamic vibration absorbers (DVAs) is a countermeasure to suppress vibrations induced by railway traffic. A key advantage of the DVA application is that it does not require any changes to the path of vibration propagation or the receiver of vibration. A review of the literature reveals the necessity of deriving the optimum properties of DVA to mitigate railway vibrations. To this end, the optimum DVA properties were investigated through the development of a two-dimensional finite element model of the track-tunnel-soil system. The model was validated using the results of a field test. A parametric study was made to obtain the optimum properties of DVA for different soils surrounding the tunnel. The results of the model analysis indicate that the DVA has better vibration reduction for metro tunnels built in soft soils as compared to those surrounded by medium and stiff soils. Also, the results disclose that the DVA reduces vibration radiated on the ground surface when the DVA natural frequency is tuned to a low frequency. Using the results of the parametric study, graphs are suggested to select the optimum properties of the DVA as a function of the soil around the tunnel. Full article

(1) Background: Over the years, technology and space missions have advanced, although the development of potential functional food and food supplements must be improved for maintaining astronauts’ health and helping them overcome space-specific challenges during long missions. (2) Scope and approach: Using a review approach, this study aimed to investigate the potential of functional food to counteract radiation and microgravity spaceflight-related health problems. (3) Results: Microgravity and space radiation affect the body’s biochemical processes and increase levels of reactive oxygen species, which may lead to health problems, including musculoskeletal deconditioning, cardiovascular degeneration, disruptions in gastrointestinal health, ocular problems, alterations to the immune system, and hormonal imbalances, among others. In addition to medical care, functional food plays a key role as a countermeasure against space-induced physiological issues. Previous research showed that functional food rich in flavonoids, omega-3 fatty acids, vitamins, minerals, antioxidant compounds, proteins, probiotics, or prebiotics strengthens the immune system and reduces risks associated with long spaceflights, such as bone density loss, muscle atrophy, oxidative stress, and other health alterations. (4) Conclusions: Despite the fundamental role of functional food in spaceflights, the main challenges remain in preserving and packaging these foods to ensure their safety on long space missions. Future innovations include 3D food printing, space algae cultivation, and novel preservation technologies. Full article

Background: Irradiation-induced injury is a common fallout of radiological/nuclear accidents or therapeutic exposures to high doses of radiation at high dose rates. Currently, there are no prophylactic drugs available to mitigate radiation injury as a result of exposure to lethal doses of ionizing radiation. Gamma-tocotrienol (GT3) of vitamin E is a promising radioprotector under advanced development which has been tested for efficacy in both murine and nonhuman primate (NHP) models. Previously, we have demonstrated that GT3 has radioprotective efficacy in intestinal epithelial and crypt cells, and restores transcriptomic changes in NHPs with a supralethal dose of 12 Gy total-body irradiation (TBI). Methods: In this study, we evaluated the effect of 12 Gy partial-body irradiation (PBI) or TBI on metabolomic changes in serum samples and the extent to which GT3 was able to modulate these irradiation-induced changes. A total of 32 nonhuman primates were used for this study, and blood sample were collected 3 days (d) prior to irradiation, and 4 h, 8 h, 12 h, 1 d, 2 d, and 6 d post-irradiation. Results: Our results demonstrate that exposure to a supralethal dose of radiation induces a complex range of metabolomic shifts with similar degrees of dysregulation in both partial- and total-body irradiated animals. The C21-steroid hormone biosynthesis and metabolism pathway was significantly dysregulated in both PBI and TBI groups, with minimal protection afforded by GT3 administration. Conclusions: GT3 offered a differential response in terms of protected metabolites and pathways in either group that was most effective at the early post-irradiation time points. Full article

Seeking to advance mutual clustering of the tourism economy and cultural industries while safeguarding cultural sustainability in tourism, this paper delves into the patterns of co-development and the contributing forces across spatial and temporal dimensions in the Yellow River Basin. Using a combined spatial and temporal analytical lens, along with spatial autocorrelation testing and a spatial Durbin model embedded in a synergetic systems approach, the present study analyzes the evolutionary characteristics of the spatiotemporal pattern of the collaborative agglomeration of the Yellow River Basin’s tourism and cultural industries in 2011 and 2021 and the internal mechanism of its influencing factors. We then propose countermeasures and suggestions to boost the quality–efficiency synergy agglomeration of the basin’s tourism and cultural industries. The results showed the following: ① From 2011 to 2021, a positive overall spatial autocorrelation was noted in the basin’s tourism and cultural industries. Temporally, it presented a variation trend of “rise–fall–rise”, and spatially, it presented a distribution characteristic of “higher in the central and eastern regions versus in its western parts”. ② From 2011 to 2021, the local spatial autocorrelation (LSA) of the basin’s tourism and cultural industries remained at a low level. Moreover, significant differences were noted in the LSA among different regions. In spatial terms, the clustering intensity of tourism and cultural industries was stronger in the central and eastern parts of the basin versus in its western parts. ③ Influencing variables for tourism–culture collaborative agglomeration across the basin involve both temporal superposition effects and spatial radiation driving effects. The industrial economy, policies, and innovation exert enduring effects on the development and cross-regional spillover outcomes of the two collaborative agglomerations. Serving as a theoretical reference and policy resource, this study addresses how to promote the quality–efficiency synergy in the Yellow River Basin’s tourism and cultural industries while enhancing cultural sustainability in the tourism industry. Moreover, it can also provide experiences and references for other similar regions. Full article

Spaceflight-associated dry eye syndrome (SADES) has been reported among astronauts during both International Space Station (ISS) and Space Transportation System (STS) missions. As future missions extend beyond low Earth orbit, the physiological challenges of spaceflight include microgravity, radiation, and environmental stressors, which may further exacerbate the development of ocular surface disease. A deeper understanding of the underlying pathophysiology, along with the exploration of innovative countermeasures, is critical. In this review, we examine nanomedicine as a promising countermeasure for managing ophthalmic conditions in space, with the goal of enhancing visual health and mission readiness for long-duration exploration-class missions. Full article

Weather patterns substantially influence extreme weathers in Japan. Extreme high temperature events can cause serious health problems, including heat stroke. Therefore, understanding weather patterns, along with their impacts on human health, is critically important for developing effective public health measures. This study examines the impact of weather patterns on heat stroke risk, focusing on a two-tiered high-pressure system (DH: double high) consisting of a lower tropospheric western Pacific subtropical high (WPSH) and an overlapping upper tropospheric South Asian high (SAH), which is thought to cause high-temperature events in Japan. In this study, the self-organizing map technique was utilized to investigate the relationship between pressure patterns and the number of heat stroke patients in four populous cities. The study period covers July and August from 2008 to 2021. The results show that the average number of heat stroke patients in these cities is higher on DH days than on WPSH days in which SAH is absent. The probability of an extremely high daily number of heat stroke patients is more than twice as high on DH days compared to WPSH days. Notably, this result remains true even when WPSH and DH days are compared within the same air temperature range. This is attributable to the higher humidity and stronger solar radiation under DH conditions, which enhances the risk of heat stroke. Large-scale circulation anomalies similar to the Pacific–Japan teleconnection are found on DH days, suggesting that both high humidity and cloudless conditions are among the large-scale features controlled by this teleconnection. Early countermeasures to mitigate heat stroke risk, including advisories for outdoor activities, should be taken when DH-like weather patterns are predicted. Full article

Substantial progress has been made in the development of radiation countermeasures, resulting in the recent approval of several mitigators; however, there has yet to be an approved prophylactic radioprotectant. Research on countermeasure performance in mixed neutron and gamma radiation fields has also been scarce. Fibroblast-stimulating lipopeptide (FSL-1) is a novel synthetic agonist for toll-like receptor 2/6. In previous studies, the administration of FSL-1 before and after gamma radiation significantly improved survival outcomes for mice through the activation of the NF-κB pathway. In the current study, we tested FSL-1’s radioprotective abilities in a mixed radiation field that models one produced by a nuclear detonation in 11–14-week-old C57BL/6 male and female mice. We demonstrate that a single dose of 1.5 mg/kg of FSL-1 administered 12 h prior to 65% neutron 35% gamma mixed-field (MF) irradiation enhances survival, accelerates recovery of hematopoietic cell and stem cell populations, reduces inflammation, and protects innate immune function in mice. FSL-1’s ability to recover blood and protect immune functions is important in countering the high rate of incidence of sepsis caused by MF radiation’s damaging effects. These results demonstrate that FSL-1 is a promising prophylactic countermeasure where exposure to MF radiation is anticipated. Full article

As humanity advances into deep space exploration, astronauts on long-duration missions face significant challenges posed by circadian rhythm disruptions and sleep disorders, which arise from extreme environmental stressors such as microgravity, ionizing radiation, and operational workload. These disruptions not only compromise physiological and psychological health but also impair cognitive function and mission-critical performance. In this review, we summarized established countermeasures encompassing pharmacological interventions, light-based circadian regulation, and work–rest schedule optimization alongside innovative approaches such as gut microbiota modulation and traditional Chinese medicine. Full article

Background: With renewed interest in long-duration space missions, there is growing exploration into synthetic torpor as a countermeasure to mitigate physiological stressors. Sedative agents, particularly those used in clinical anesthesia, have been proposed to replicate aspects of natural torpor, including reduced metabolic rate, core temperature, and brain activity. Objectives: This systematic review aims to evaluate the potential of sedative agents to induce torpor-like states suitable for extended spaceflight. The review specifically investigates their pharmacokinetics, pharmacodynamics, and performance under space-related stressors such as microgravity and ionizing radiation. Methods: We conducted a comprehensive search across multiple databases (e.g., PubMed, Scopus, Web of Science) for studies published from 1952 to 2024. Eligible studies included experimental, preclinical, and clinical investigations examining sedative agents (especially inhalation anesthetics) in the context of metabolic suppression or space-relevant conditions. Screening, selection, and data extraction followed PRISMA guidelines. Results: Out of the screened records, 141 studies met the inclusion criteria. These were thematically grouped into seven categories, including torpor physiology, anesthetic uptake, metabolism, and inhalation anesthetics. Sedative agents showed variable success in inducing torpor-like states, with inhalation anesthetics demonstrating promising metabolic effects. However, concerns remain regarding delivery methods, safety, rewarming, and the unknown effects of prolonged use in space environments. Conclusions: Sedative agents, particularly volatile anesthetics, hold potential as tools for inducing synthetic torpor in space. Nevertheless, significant knowledge gaps and technical challenges persist. Further targeted research is required to optimize these agents for safe, controlled use in spaceflight settings. Full article

Acute radiation syndrome (ARS) occurs when hematopoietic or gastrointestinal cells are damaged by radiation exposure causing DNA damage to the bone marrow and gastrointestinal epithelial stem cell populations. In these highly proliferative cell types, DNA damage inhibits stem cell repopulation. In humans and animals, this inability to regenerate stem cells is lethal. Within this manuscript, several compounds, Amifostine, Captopril, Ciprofloxacin, PrC-210, 5-AED (5-androstene-3β,17β-diol), and 5-AET (5-androstene-3β,7β,17B-triol), are assessed for their ability to protect against ARS in an in vitro and/or in vivo setting. ARS was accomplished by irradiating mouse bone marrow cells or rat intestinal epithelial (IEC-6) cells in vitro with 4–8 Gy and in vivo by exposing Mus musculus to 7.3 Gy of whole-body irradiation. The primary endpoints of this study include cellular viability, DNA damage via γ-H2AX, colony formation, and overall survival at 30-days post-irradiation. In addition to evaluating the radioprotective performance of each compound, this study establishes a distinct set of in vitro assays to predict the overall efficacy of potential radioprotectors in an in vivo model of ARS. Furthermore, these results highlight the need for FDA-approved medical intervention to protect against ARS. Full article