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

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

Objective: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. Methods: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca Results: An increase of cytoplasmic Ca Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
Animals ; Calcium/metabolism* ; Cerebral Arteries ; Homeostasis ; Male ; Mitochondria/physiology* ; Myocytes, Smooth Muscle/physiology* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/physiology* ; Weightlessness Simulation

OBJECTIVE: To investigate whether collagen peptides can improve the immune functions of mice under the condition of simulated weightlessness. METHODS: Mouse tail-suspension model was used to simulate the effects of weightlessness. Tail-suspended mice were intraperitoneally injected with 600 mg collagen peptides per kilogram body weight once a day for 10 days. Then, the mice were killed, and white blood cells were counted and classified. Lymphocyte subsets and T lymphocyte proliferations in spleens were analyzed. RESULTS: Compared with normal control group, total and differential count of leukocytes, lymphocytes, T cells，CD4 and CD8 T cells, B cells and NK cells, and splenic T lymphocyte proliferation all decreased in the weightlessness simulated mice (P＜0.05). Except for NK cells, the above-mentioned parameters were increased after administration of collagen peptides, and some of the parameters were recovered to the levels of normal control mice (P＜0.05). CONCLUSION Collagen peptides can effectively improve peripheral blood lymphocyte distributions and T lymphocyte proliferations of mice under the condition of simulated weightlessness. This study nay provid the experimental basis for improvement of immune functions of astronauts.
Animals ; CD8-Positive T-Lymphocytes ; Cell Proliferation ; Collagen ; Lymphocyte Count ; Mice ; Peptides ; Spleen ; Weightlessness ; Weightlessness Simulation

OBJECTIVE: To explore the dynamic impacts of simulated microgravity (SM) on different vital brain regions of rats. METHODS: Microgravity was simulated for 7 and 21 days, respectively, using the tail-suspension rat model. Histomorphology, oxidative stress, inflammatory cytokines and the expression of some key proteins were determined in hippocampus, cerebral cortex and striatum. RESULTS: 21-day SM decreased brain derived neurotrophic factor and induced neuron atrophy in the cerebral cortex. Strong oxidative stress was triggered at day 7 and the oxidative status returned to physiological level at day 21. Inflammatory cytokines were gradually suppressed and in striatum, the suppression was regulated partially through c-Jun/c-Fos. CONCLUSION The results revealed that the significant impacts of SM on rat brain tissue depended on durations and regions, which might help to understand the health risk and to prevent brain damage for astronauts in space travel.
Animals ; Brain ; metabolism ; pathology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cytokines ; metabolism ; Male ; Oxidative Stress ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; Random Allocation ; Rats ; Weightlessness Simulation

Objective To compare the effects of 50-Hz 0.6-mT low-frequency pulsed electromagnetic fields(PEMFs) and 50-Hz 1.8-mT sinusoidal alternating electromagnetic fields(SEMFs) in preventing bone loss in tail-suspended rats,with an attempt to improve the prevention and treatment of bone loss caused by weightlessness.Methods Tail-suspension rat models were used to simulate microgravity on the ground. Forty rats were randomly divided into four groups[control group,hindlimb-suspended(HLS) group,HLS+PEMFs group,and HLS+SEMFs group],with 10 rats in each group. In the PEMFs treatment group and SEMFs treatment group,the intervention was 90 min per day. Rats were sacrificed after four weeks. Bone mineral density(BMD) of femur and vertebra was measured by dual-energy X-ray absorptiometry and biomechanical strength by AG-IS biomechanical instrument. Serum osteocalcin(OC),tartrate-resistant acid phosphatase 5b(Tracp 5b),parathyroid hormone(PTH),and cyclic adenosine monophosphate(cAMP) were detected by ELISA. The microstructure of bone tissue was observed by Micro-CT and HE staining.Results The BMD of the femur(P=0.000) and vertebrae(P=0.001) in the HLS group was significantly lower than in the control group;the BMD of the femurs(P=0.001) and vertebrae(P=0.039) in the HLS+PEMFs group was significantly higher than in the HLS group;the BMD of the femurs in the HLS+SEMFs group was significantly higher than in the HLS group(P=0.003),but the BMD of the vertebrae showed no significant difference(P=0.130). There was no significant difference in the BMD of the femur(P=0.818) and vertebrae(P=0.614) between the HLS+PEMFs group and the HLS+SEMFs group. The maximum load(P=0.000,P=0.009) and elastic modulus(P=0.015,P=0.009) of the femurs and vertebrae in the HLS group were significantly lower than those in the control group;the maximum load of the femur(P=0.038) and vertebrae(P=0.087) in the HLS+PEMFs group was significantly higher than that in the HLS group,but the elastic modulus was not significantly different from that in the HLS group(P=0.324,P=0.091). The maximum load(P=0.190,P=0.222) and elastic modulus(P=0.512,P=0.437) of femurs and vertebrae in the HLS+SEMFs group were not significantly different from those in the HLS group. There were no significant differences in the maximum load and elastic modulus of femurs(P=0.585,P=0.948) and vertebrae(P=0.668,P=0.349) between the HLS+PEMFs group and the HLS+SEMFs group. The serum OC level in the HLS group was significantly lower than that in the control group(P=0.000),and the OC level in HLS+PEMFs group(P=0.000) and HLS+SEMFs group(P=0.006) were significantly higher than that in the HLS group. The serum Tracp 5b concentration in the HLS group was significantly higher than that in the control group(P=0.011). There was no significant difference between the HLS+PEMFs group(P=0.459) and the HLS+SEMFs group(P=0.469) compared with the control group.Serum Tracp 5b concentrations in the HLS+PEMFs group(P=0.056) and the HLS+SEMFs group(P=0.054) were not significantly different from those in the HLS group. The PTH(P=0.000) and cAMP concentrations(P=0.000) in the HLS group were significantly lower than those in the control group. The PTH(P=0.000,P=0.000) and cAMP concentrations(P=0.000,P=0.000) in the HLS+PEMFs group and the HLS+SEMFs group were significantly higher than in the HLS group. The femoral cancellous bone of the HLS group was very sparse and small compared with the control group. The density and volume of the cancellous bone were similar among the control group,HLS+PEMFs group,and HLS+SEMFs group. Compared with the control group,the HLS group had lower BMD(P=0.000),bone volume (BV)/tissue volume(TV)(P=0.000),number of trabecular bone (Tb.N)(P=0.000),and trabecular thickness(Tb.Th)(P=0.000) and higher trabecular bone dispersion(Tb.Sp)(P=0.000) and bone surface area(BS)/BV(P=0.000). Compared with the HLS group,the HLS+PEMFs group and the HLS+SEMFs group had significantly lower Tb.Sp(P=0.000,P=0.000) and BS/BV(P=0.000,P=0.000) and significantly increased BMD(P=0.000,P=0.000),BV/TV(P=0.001,P=0.004),Tb.Th(P=0.000,P=0.001),and Tb.N(P=0.000,P=0.001). The trabecular thickness significantly differed between the HLS+PEMFs group and the HLS+SEMFs group(P=0.024). The HLS group(P=0.000),HLS+PEMFs group(P=0.000),and HLS+SEMFs group(P=0.000) had the significantly lower osteoblast density on the trabecular bone surface than the control group;however,it was significantly higher in the HLS+SEMFs group(P=0.000) and the HLS+PEMFs group(P=0.000) than in the HLS group. The HLS group had significantly lower density of osteoblasts in the endothelium than the control group(P=0.000);however,the density of osteoblasts was significantly higher in HLS+PEMFs group(P=0.000) and HLS+SEMFs group(P=0.000) than HLS group and was significantly higher in HLS+PEMFs group than in HLS+SEMFs group(P=0.041). Compared with the control group,a large number of fatty cavities were produced in the bone marrow cavity in the HLS group,but the fat globules remarkably decreased in the treatment groups,showing no significant difference from the control group. The number of adipose cells per mm bone marrow in the HLS group was 4 times that of the control group(P=0.000);it was significantly smaller in the HLS+PEMFs group(P=0.000) and HLS+SEMFs group(P=0.000) than in the HLS group,whereas the difference between the HLS+PEMFs group and the HLS+SEMFs group was not statistically significant(P=0.086). Conclusions 50-Hz 0.6-mT PEMFs and 50-Hz 1.8-mT SEMFs can effectively increase bone mineral density and biomechanical values in tail-suspended rats,increase the concentration of bone formation markers in rat blood,activate the cAMP pathway by affecting PTH levels,and thus further increase the content of osteoblasts to prevent the deterioration of bone micro-structure. In particular,PEMFs can prevent the reduction of bone mineral density and maximum load value by about 50% and increase the bone mass of tail-suspended rats by promoting bone formation.
Absorptiometry, Photon ; Animals ; Bone Density ; Electromagnetic Fields ; Femur ; Rats ; Rats, Sprague-Dawley ; Weightlessness

In this study, we aim to investigat the effect of microgravity on osteoblast differentiation in osteoblast-like cells (MC3T3-E1). In addition, we explored the response mechanism of nuclear factor-kappa B (NF-κB) signaling pathway to "zero- " in MC3T3-E1 cells under the simulated microgravity conditions. MC3T3-E1 were cultured in conventional (CON) and simulated microgravity (SMG), respectively. Then, the expression of the related osteoblastic genes and the specific molecules in NF-κB signaling pathway were measured. The results showed that the mRNA and protein levels of alkaline phosphatase (ALP), osteocalcin (OCN) and type Ⅰ collagen (CoL-Ⅰ) were dramatically decreased under the simulated microgravity. Meanwhile, the NF-κB inhibitor α (IκB-α) protein level was decreased and the expressions of phosphorylation of IκB-α (p-IκB-α), p65 and phosphorylation of p65 (p-p65) were significantly up-regulated in SMG group. In addition, the IL-6 content in SMG group was increased compared to CON. These results indicated that simulated microgravity could activate the NF-κB pathway to regulate MC3T3-E1 cells differentiation.
3T3 Cells ; Animals ; Cell Differentiation ; Mice ; NF-kappa B ; physiology ; Osteoblasts ; Signal Transduction ; Weightlessness Simulation