In recent years, China's manned space program has advanced rapidly, with deep space exploration missions such as manned lunar landing steadily progressing, leading to a significant extension of astronauts' duration in outer space. In this context, the impact of the space magnetic field environment on astronaut health has become increasingly conspicuous. Characterized by its complexity, the spatial magnetic field indirectly regulates the circadian rhythm system by interfering with mitochondrial functions, such as electron transport chain activity, ATP synthesis efficiency, and reactive oxygen species (ROS) balance. This disruption can lead to circadian misalignment, sleep disorders, metabolic dysregulation, and other issues, severely compromising astronauts' physical and mental well-being, as well as mission performance. Currently, researchers have carried out extensive investigations into the influence of the space magnetic environment on circadian rhythms. Nevertheless, due to disparities in magnetic field parameters, exposure durations, and the model organisms employed in experiments, the results have been inconsistent. This review systematically elaborates on ground-based simulation technologies for spatial magnetic field environments and their applications, summarizes the effects of magnetic fields with varying intensities and types on core circadian rhythm biomarkers in model organisms and humans, and explores the underlying molecular and physiological mechanisms of magnetic field-induced circadian rhythm perturbation. This work aims to deepen the understanding of the mechanisms of the space magnetic environment on biological rhythms, and establish a scientific basis for formulating adaptive protective strategies centered on circadian regulation for astronauts, thereby ensuring the successful implementation of long-term deep-space missions.
Circadian Rhythm/physiology* ; Humans ; Magnetic Fields/adverse effects* ; Space Flight ; Animals ; Extraterrestrial Environment

Neuropsychiatric disorders arise from complex interactions between genetic and environmental factors. DNA methylation, a reversible and environmentally responsive epigenetic regulatory mechanism, serves as a crucial bridge linking environmental exposure, gene expression regulation, and neurobehavioral outcomes. During long-duration deep-space missions, astronauts face multiple stressors-including microgravity, cosmic radiation, circadian rhythm disruption, and social isolation, which can induce alterations in DNA methylation and increase the risk of neuropsychiatric disorders. Genome-wide DNA methylation research can be divided into 3 major methodological stages: Study design, sample preparation and detection, and data analysis, each of which can be applied to astronaut neuropsychiatric health monitoring. Systematic comparison of the Illumina MethylationEPIC array and whole-genome bisulfite sequencing reveals their complementary strengths in terms of genomic coverage, resolution, cost, and application scenarios: the array method is cost-effective and suitable for large-scale population studies and longitudinal monitoring, whereas sequencing provides higher resolution and coverage and is more suitable for constructing detailed methylation maps and characterizing individual variation. Furthermore, emerging technologies such as single-cell methylation sequencing, nanopore long-read sequencing, and machine-learning-based multi-omics integration are expected to greatly enhance the precision and interpretability of epigenetic studies. These methodological advances provide key support for establishing DNA-methylation-based monitoring systems for neuropsychiatric risk in astronauts and lay an epigenetic foundation for safeguarding neuropsychiatric health during future long-term deep-space missions.
DNA Methylation ; Humans ; Space Flight ; Mental Disorders/genetics* ; Epigenesis, Genetic ; Astronauts/psychology* ; Weightlessness/adverse effects* ; Epigenomics

As human deep space exploration enters a practical phase, ensuring astronaut health and safety has become a critical determinant of mission success. The cerebrovascular system, essential for maintaining brain function, is highly sensitive to environmental changes. Cerebrovascular diseases represent one of the characteristic adverse effects of deep space conditions such as microgravity and high-energy radiation, and have emerged as a frontier challenge in space medicine. Based on experiences from manned space missions, major research challenges persist, particularly the lack of experimental data specific to the lunar environment and the unclear threshold for low-dose radiation-induced injury. Elucidating the mechanisms and multifactorial interactions by which deep space environments impact cerebrovascular structure and function, and summarizing the key risk factors, pathological processes, and recent advances in monitoring and early-warning technologies for cerebrovascular diseases in lunar astronauts, and of crucial importance. A comprehensive understanding of the interplay between deep space environmental stressors and cerebrovascular injury, as well as the development of personalized prevention and intervention strategies, will provide both theoretical and practical foundations for safeguarding cerebrovascular health in future Chinese deep space missions, while promoting progress in related biomedical research, technological innovation, and international collaboration.
Humans ; Astronauts ; Cerebrovascular Disorders/etiology* ; Space Flight ; Weightlessness/adverse effects* ; Risk Factors ; Moon

With the continuous advancement of deep space exploration missions, maintaining astronaut skin health has become a critical medical issue affecting the safety and effectiveness of long-duration missions. Deep space environmental stressors, including microgravity, ionizing radiation, lunar dust exposure, and microbiome dysbiosis, can synergistically disrupt the skin barrier structure, leading to immune homeostasis imbalance and impaired wound healing. In recent years, research on skin protection in deep space has gradually evolved into a systematic "multi-dimensional integrated protective" framework. From the engineering protection perspective, optimization of multi-layer composite spacesuit structures, the use of hydrogen-rich and boron-containing shielding materials, as well as cabin temperature-humidity regulation and debris-resistant technologies, have greatly enhanced environmental defense capacity. From the biomedical protection perspective, functional hydrogels, antimicrobial dressings, and active compounds derived from traditional Chinese medicine have demonstrated remarkable potential in repairing the skin barrier, modulating immunity, and providing antioxidant defense. Meanwhile, the development of skin microecological interventions and wearable physiological monitoring systems has fostered a trend toward personalized health management. Future research should focus on elucidating the interactive mechanisms among the space environment, skin, and immune barrier, while exploring intelligent monitoring and nanotechnology-based protection strategies. Establishing a predictive and preventive skin health safeguarding system will provide comprehensive medical support for future deep space missions.
Humans ; Astronauts ; Skin/radiation effects* ; Space Flight ; Weightlessness/adverse effects* ; Wound Healing ; Extraterrestrial Environment

Long-term spaceflight exposes astronauts to multiple extreme environmental factors, such as cosmic radiation, microgravity, social isolation, and circadian rhythm disruption, that markedly increase the risk of depressive symptoms, posing a direct threat to mental health and mission safety. However, the underlying biological mechanisms remain complex and incompletely understood. The potential mechanisms of spaceflight-induced depressive symptoms involve multiple domains, including alterations in brain structure and function, dysregulation of neurotransmitters and neurotrophic factors, oxidative stress, neuroinflammation, neuroendocrine system imbalance, and gut microbiota disturbances. Collectively, these changes may constitute the biological foundation of depressive in astronauts during spaceflight. Space-related stressors may increase the risk of depressive symptoms through several pathways: impairing hippocampal neuroplasticity, suppressing dopaminergic and serotonergic system function, reducing neurotrophic factor expression, triggering oxidative stress and inflammatory responses, activating the hypothalamic-pituitary-adrenal axis, and disrupting gut microbiota homeostasis. Future research should integrate advanced technologies such as brain-computer interfaces to develop individualized monitoring and intervention strategies, enabling real-time detection and effective prevention of depressive symptoms to safeguard astronauts' psychological well-being and mission safety.
Space Flight ; Humans ; Astronauts/psychology* ; Depression/physiopathology* ; Gastrointestinal Microbiome ; Weightlessness/adverse effects* ; Oxidative Stress ; Brain/physiopathology* ; Hypothalamo-Hypophyseal System ; Neuronal Plasticity ; Pituitary-Adrenal System

During long-duration manned space missions, the complex and extreme space environment exerts significant impacts on astronauts' physiological, psychological, and cognitive functions, thereby posing direct risks to mission safety and operational efficiency. As a key bridge between the brain and external devices, brain-computer interface (BCI) technology enables precise acquisition and interpretation of neural signals, offering a novel paradigm for human-machine collaboration in manned spaceflight. Non-invasive BCI technology shows broad application prospects across astronaut selection, mission training, in-orbit task execution, and post-mission rehabilitation. During mission preparation, multimodal signal assessment and neurofeedback training based on BCI can effectively enhance cognitive performance and psychological resilience. During mission execution, BCI can provide real-time monitoring of physiological and psychological states and enable intention-based device control, thereby improving operational efficiency and safety. In the post-mission rehabilitation phase, non-invasive BCI combined with neuromodulation may improve emotional and cognitive functions, support motor and cognitive recovery, and contribute to long-term health management. However, the application of BCI in space still faces challenges, including insufficient signal robustness, limited system adaptability, and suboptimal data processing efficiency. Looking forward, integrating multimodal physiological sensors with deep learning algorithms to achieve accurate monitoring and individualized intervention, and combining BCI with virtual reality and robotics to develop intelligent human-machine collaboration models, will provide more efficient support for space missions.
Brain-Computer Interfaces ; Humans ; Space Flight ; Astronauts/psychology* ; Neurofeedback ; Cognition ; Electroencephalography ; Man-Machine Systems

The unique characteristics of the deep space environment, microgravity, cosmic radiation, and extreme temperature fluctuations, are emerging as major driving forces for pharmaceutical innovation. These factors provide new avenues for optimizing drug formulations, improving crystal structure quality, and accelerating the discovery of therapeutic targets. Advances in deep space research not only help overcome critical bottlenecks in terrestrial drug development but also promote progress in structure-based drug design and deepen understanding of cellular stress-response mechanisms. Current progress in space-based pharmaceutical research primarily includes the study of disease mechanisms under microgravity, protein crystallization in microgravity, and drug development utilizing deep space radiation and resources. However, the operational complexity, high costs, and limited data reproducibility of space experiments remain key challenges hindering widespread application. Looking ahead, with the integration of automation, artificial intelligence analysis, and on-orbit manufacturing, deep space drug development is expected to achieve greater scalability and precision, opening a new frontier in biopharmaceutical science.
Drug Design ; Drug Development/methods* ; Humans ; Weightlessness ; Space Flight ; Artificial Intelligence ; Extraterrestrial Environment

The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures against such effects. In this paper, we described the development of countermeasure systems in the Chinese space program. To emphasize the need of the Chinese space program to implement its own program for developing countermeasures, we reviewed the literature on the negative physiological effects of weightlessness, the challenges of completing missions, the development of countermeasure devices, the establishment of countermeasure programs, and the efficacy of the countermeasure techniques in American and Russian manned spaceflights. In addition, a brief overview was provided on the Chinese research and development on countermeasures to discuss the current status and goals of the development of countermeasures against physiological problems associated with weightlessness.
China ; Humans ; Program Evaluation ; Space Flight ; Weightlessness ; Weightlessness Simulation

BACKGROUND: To develop human space exploration, it is necessary to study the effects of an isolated and confined environment, as well as a microgravity environment, on cerebral circulation. However, no studies on cerebral circulation in an isolated and confined environment have been reported. Therefore, we investigated the effects of a 14-day period of confinement in an isolated environment on dynamic cerebral autoregulation. METHODS: We participated in an isolation and confinement experiment conducted by the Japan Aerospace Exploration Agency in 2016. Eight healthy males were isolated and confined in a facility for 14 days. Data were collected on the days immediately before and after confinement. Arterial blood pressure waveforms were obtained using a finger blood pressure monitor, and cerebral blood flow velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography for 6 min during quiet rest in a supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between spontaneous variability of beat-to-beat mean arterial blood pressure and mean cerebral blood flow velocity. RESULTS: Transfer function gain in the low- and high-frequency ranges increased significantly (0.54 ± 0.07 to 0.69 ± 0.09 cm/s/mmHg and 0.80 ± 0.05 to 0.92 ± 0.09 cm/s/mmHg, respectively) after the confinement. CONCLUSION: The increases observed in transfer function gain may be interpreted as indicating less suppressive capability against transmission from arterial blood pressure oscillation to cerebral blood flow velocity fluctuation. These results suggest that confinement in an isolated environment for 14 days may impair dynamic cerebral autoregulation. TRIAL REGISTRATION UMIN000020703 , Registered 2016/01/22.
Adult ; Cerebrovascular Circulation ; physiology ; Confined Spaces ; Homeostasis ; physiology ; Humans ; Male ; Middle Aged ; Space Flight ; Young Adult

Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports. Next, we demonstrated that the cell proliferation activity, determined by Ki67, PCNA and PH3, was significantly decreased at the different TS time points (TS for 14, 28 and 42 days) compared with that in the control group. Consistently, the positive cell cycle regulators Ccna2, Ccnd1, Cdk1, Cdk2 and cyclin D3 were also significantly decreased in the TS groups as shown by quantitative real-time PCR and western blotting analysis. Subsequent analysis revealed that the aberrant hepatocyte proliferation inhibition under simulated microgravity was associated with the upregulation of miR-223 in the liver. We further found that miR-223 inhibited the proliferation of Hepa1-6 cells and identified CDK2 and CUL1 as its direct targets. In addition, the decreased expression of CDK2 and CUL1 was negatively correlated with the level of p27 in vitro and in vivo, which may have been responsible for retarding hepatocyte proliferation. Collectively, these data indicate that upregulation of miR-223 was associated with the inhibition of liver cell growth and reveal the role of miR-223 in rat hepatocyte proliferation disorders and the pathophysiological process under simulated microgravity.
Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Aspartate Aminotransferases ; Biomarkers ; Blotting, Western ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Cyclin D3 ; Hepatocytes* ; Hindlimb Suspension ; In Vitro Techniques ; Liver* ; Proliferating Cell Nuclear Antigen ; Rats* ; Real-Time Polymerase Chain Reaction ; Space Flight ; Up-Regulation* ; Weightlessness*