The Lungs in Space: A Review of Current Knowledge and Methodologies.

Space travel presents multiple risks to astronauts such as launch, radiation, spacewalks or extravehicular activities, and microgravity. The lungs are composed of a combination of air, blood, and tissue, making it a complex organ system with interactions between the external and internal environment. Gravity strongly influences the structure of the lung which results in heterogeneity of ventilation and perfusion that becomes uniform in microgravity as shown during parabolic flights, Spacelab, and Skylab experiments. While changes in lung volumes occur in microgravity, efficient gas exchange remains and the lungs perform as they would on Earth; however, little is known about the cellular response to microgravity. In addition to spaceflight and real microgravity, devices, such as clinostats and random positioning machines, are used to simulate microgravity to study cellular responses on the ground. Differential expression of cell adhesion and extracellular matrix molecules has been found in real and simulated microgravity. Immune dysregulation is a known consequence of space travel that includes changes in immune cell morphology, function, and number, which increases susceptibility to infections. However, the majority of in vitro studies do not have a specific respiratory focus. These studies are needed to fully understand the impact of microgravity on the function of the respiratory system in different conditions.

Interplay of miRNAs and molecular pathways in spaceflight-induced depression: Insights from a rat model using simulated complex space environment.

Depression is a significant concern among astronauts, yet the molecular mechanisms underlying spaceflight-induced depression remain poorly understood. MicroRNAs (miRNAs) have emerged as potential regulators of neuropsychiatric disorders, including depression, but their specific role in space-induced depression remains unexplored. This study aimed to elucidate the involvement of candidate miRNAs (miR-455-3p, miR-206-3p, miR-132-3p, miR-16-5p, miR-124-3p, and miR-145-3p) and their interaction with differentially expressed genes (DEGs) in the neurobiology of spaceflight-induced depressive behavior. Using a simulated space environmental model (SCSE) for 21 days, depressive behavior was induced in rats, and candidate miRNA expressions and DEGs in the cortex region were analyzed through qRT-PCR and HPLC, respectively. Results showed that SCSE-exposed rats exhibited depressive behaviors, including anhedonia, increased immobility, and anxiousness compared to controls. Further analysis revealed increased hydrogen peroxide levels and decreased superoxide dismutase levels in the SCSE group, indicating abnormal oxidative stress in the cerebral cortex. Moreover, miRNA analysis demonstrated significant upregulation of miR-455-3p, miR-206-3p, miR-132-3p, and miR-16-5p expression. Among the DEGs identified, the in silico analysis highlighted their involvement in crucial pathways such as glutamatergic signaling, GABA synaptic pathway, and calcium signaling, implicating their role in spaceflight-induced depression. Protein-protein interaction analysis identified hub genes, including DLG4, DLG3, GRIN1, GRIN2B, GRIN2A, SYNGAP1, DLGAP1, GRIK2, and GRIN3A, impacting neuronal dysfunction functions in the cortex region of SCSE depressive rats. DLG4 emerged as a core gene regulated by miR-455-3p and miR-206-3p. Overall, this study underscores the potential of miRNAs as biomarkers for mood disorders and neurological abnormalities associated with spaceflight, advancing health sciences, and space health care.

Protective alleles and precision healthcare in crewed spaceflight.

Common and rare alleles are now being annotated across millions of human genomes, and omics technologies are increasingly being used to develop health and treatment recommendations. However, these alleles have not yet been systematically characterized relative to aerospace medicine. Here, we review published alleles naturally found in human cohorts that have a likely protective effect, which is linked to decreased cancer risk and improved bone, muscular, and cardiovascular health. Although some technical and ethical challenges remain, research into these protective mechanisms could translate into improved nutrition, exercise, and health recommendations for crew members during deep space missions.

Sustainable wastewater treatment and reuse in space.

Exploring the vast extraterrestrial space is an inevitable trend with continuous human development. Water treatment and reuse are crucial in the limited and closed space that is available in spaceships or long-term use space bases that will be established in the foreseeable future. Dedicated water treatment technologies have experienced iterative development for more than 60 years since the first manned spaceflight was successfully launched. Herein, we briefly review the related wastewater characteristics and the history of water treatment in space stations, and we focus on future challenges and perspectives, aiming at providing insights for optimizing wastewater treatment technologies and closing the water cycle in future.

Toward Next-Generation Phenomics: Precision Medicine, Spaceflight, Astronaut Omics, and Beyond.

Large investments over many decades in genomics in diverse fields such as precision medicine, plant biology, and recently, in space life science research and astronaut omics were not accompanied by a commensurate focus on high-throughput and granular characterization of phenotypes, thus resulting in a "phenomics lag" in systems science. There are also limits to what can be achieved through increases in sample sizes in genotype-phenotype association studies without commensurate advances in phenomics. These challenges beg a question. What might next-generation phenomics look like, given that the Internet of Things and artificial intelligence offer prospects and challenges for high-throughput digital phenotyping as a key component of next-generation phenomics? While attempting to answer this question, I also reflect on governance of digital technology and next-generation phenomics. I argue that it is timely to broaden the technical discourses through a lens of political theory. In this context, this analysis briefly engages with the recent book "The Earthly Community: Reflections on the Last Utopia," written by the historian and political theorist Achille Mbembe. The question posed by the book, "Will we be able to invent different modes of measuring that might open up the possibility of a different aesthetics, a different politics of inhabiting the Earth, of repairing and sharing the planet?" is directly relevant to healing of human diseases in ways that are cognizant of the interdependency of human and nonhuman animal health, and critical and historically informed governance of digital technologies that promise to benefit next-generation phenomics.

Cultivation and nutritional characteristics of Chlorella vulgaris cultivated using Martian regolith and synthetic urine.

Long-term spatial missions will require sustainable methods for biomass production using locally available resources. This study investigates the feasibility of cultivating Chlorella vulgaris, a high value microalgal specie, using a leachate of Martian regolith and synthetic human urine as nutrient sources. The microalga was grown in a standard medium (BBM) mixed with 0, 20, 40, 60, or 100 % Martian medium (MM). MM did not significantly affect final biomass concentrations. Total carbohydrate and protein contents decreased with increasing MM fractions between 0 % and 60 %, but biomass in the 100% MM showed the highest levels of carbohydrates and proteins (25.2 ± 0.9 % and 37.1 ± 1.4 % of the dry weight, respectively, against 19.0 ± 1.7 % and 32.0 ± 2.7 % in the absence of MM). In all MM-containing media, the fraction of the biomass represented by total lipids was lower (by 3.2 to 4.5%) when compared to BBM. Conversely, total carotenoids increased, with the highest value (97.3 ± 1.5 mg/100 g) measured with 20% MM. In a three-dimensional principal component analysis of triacylglycerols, samples clustered according to growth media; a strong impact of growth media on triacylglycerol profiles was observed. Overall, our findings suggest that microalgal biomass produced using regolith and urine can be used as a valuable component of astronauts' diet during missions to Mars.

Organ dose equivalents of albedo protons and neutrons under exposure to large solar particle events during lunar human landing missions.

Astronauts participating in lunar landing missions will encounter exposure to albedo particles emitted from the lunar surface as well as primary high-energy particles in the spectra of galactic cosmic rays (GCRs) and solar particle events (SPEs). While existing studies have examined particle energy spectra and absorbed doses in limited radiation exposure scenarios on and near the Moon, comprehensive research encompassing various shielding amounts and large SPEs on the lunar surface remains lacking. Additionally, detailed organ dose equivalents of albedo particles in a human model on the lunar surface have yet to be investigated. This work assesses the organ dose equivalents of albedo neutrons and albedo protons during historically large SPEs in August 1972 and September 1989 utilizing realistic computational anthropomorphic human phantom for the first time. Dosimetric quantities within human organs have been evaluated based on the PHITS Monte Carlo simulation results and quality factors of the state-of-the-art NASA Space Cancer Risk (NSCR) model, as well as ICRP publications. The results with the NSCR model indicate that the albedo contribution to organ dose equivalent is less than 3 % for 1 g/cm2 aluminum shielding, while it increases to more than 30 % in some organs for 50 g/cm2 aluminum shielding during exposure to low-energy-proton-rich SPEs.

Bioregenerative dietary supplementation in space: Brassica rapa var. nipposinica and other Brassica cultivars.

Despite the precise environmental manipulation enabled by controlled environment agriculture (CEA), plant genotype remains a key factor in producing desirable traits. Brassica rapa var. nipposinica (mizuna) is a leading candidate for supplementing deficiencies in the space diet, however, which cultivar of mizuna will respond best to the environment of the international space station (ISS) is unknown. It is also unclear if there are more inter-varietal (mizuna - mustards) or intra-varietal (mizuna - mizuna) differences in response to the ISS environment. Twenty-two cultivars of mustard greens, including 13 cultivars of mizuna, were grown under ISS-like conditions to determine which would provide the greatest yield and highest concentrations of carotenoids, anthocyanins, calcium, potassium, iron, magnesium, ascorbic acid, thiamine, and phylloquinone. The experiment was conducted thrice, and data were analyzed to determine which cultivar is most suited for further optimization of space-based cultivation. It was found that phylloquinone and ß-carotene concentrations did not vary between cultivars, while all other metrics of interest showed some variation. 'Amara' mustard (B. carinata) provided the best overall nutritional profile, despite its low biomass yield of 36.8 g, producing concentrations of 27.85, 0.40, and 0.65 mg·g - 1 of ascorbic acid, thiamine, and lutein, respectively. Of the mizuna cultivars evaluated, open pollinated mibuna provided the best profile, while 'Red Hybrid' mizuna provided a complimentary profile to that of 'Amara', minimally increasing dietary iron while providing beneficial anthocyanins lacking in 'Amara'.

Challenges and innovations in food and water availability for a sustainable Mars colonization.

In recent years, extensive research has been dedicated to Mars exploration and the potential for sustainable interplanetary human colonization. One of the significant challenges in ensuring the survival of life on Mars lies in the production of food as the Martian environment is highly inhospitable to agriculture, rendering it impractical to transport food from Earth. To improve the well-being and quality of life for future space travelers on Mars, it is crucial to develop innovative horticultural techniques and food processing technologies. The unique challenges posed by the Martian environment, such as the lack of oxygen, nutrient-deficient soil, thin atmosphere, low gravity, and cold, dry climate, necessitate the development of advanced farming strategies. This study explores existing knowledge and various technological innovations that can help overcome the constraints associated with food production and water extraction on Mars. The key lies in utilizing resources available on Mars through in-situ resource utilization. Water can be extracted from beneath the ice and from the Martian soil. Furthermore, hydroponics in controlled environment chambers, equipped with nutrient delivery systems and waste recovery mechanisms, have been investigated as a means of cultivating crops on Mars. The inefficiency of livestock production, which requires substantial amounts of water and land, highlights the need for alternative protein sources such as microbial protein, insects, and in-vitro meat. Moreover, the fields of synthetic biology and 3-D food printing hold immense potential in revolutionizing food production and making significant contributions to the sustainability of human life on Mars.

Integrated analysis of miRNAome and transcriptome reveals that microgravity induces the alterations of critical functional gene modules via the regulation of miRNAs in short-term space-flown C. elegans.

Microgravity, as a unique hazardous factor encountered in space, can induce a series of harmful effects on living organisms. The impact of microgravity on the pivotal functional gene modules stemming from gene enrichment analysis via the regulation of miRNAs is not fully illustrated. To explore the microgravity-induced alterations in critical functional gene modules via the regulation of miRNAs, in the present study, we proposed a novel bioinformatics algorithm for the integrated analysis of miRNAome and transcriptome from short-term space-flown C. elegans. The samples of C. elegans were exposed to two space conditions, namely spaceflight (SF) and spaceflight control (SC) onboard the International Space Station for 4 days. Additionally, the samples of ground control (GC) were included for comparative analysis. Using the present algorithm, we constructed regulatory networks of functional gene modules annotated from differentially expressed genes (DEGs) and their associated regulatory differentially expressed miRNAs (DEmiRNAs). The results showed that functional gene modules of molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathway were facilitated by 25 down-regulated DEmiRNAs (e.g., cel-miR-792, cel-miR-65, cel-miR-70, cel-lsy-6, cel-miR-796, etc.) in the SC vs. GC groups, whereas these modules were inhibited by 13 up-regulated DEmiRNAs (e.g., cel-miR-74, cel-miR-229, cel-miR-70, cel-miR-249, cel-miR-85, etc.) in the SF vs. GC groups. These findings indicated that microgravity could significantly alter gene expression patterns and their associated functional gene modules in short-term space-flown C. elegans. Additionally, we identified 34 miRNAs as post-transcriptional regulators that modulated these functional gene modules under microgravity conditions. Through the experimental verification, our results demonstrated that microgravity could induce the down-regulation of five critical functional gene modules (i.e., molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathways) via the regulation of miRNAs in short-term space-flown C. elegans.

Imaging in spaceflight associated neuro-ocular syndrome (SANS): Current technology and future directions in modalities.

With plans for future long-duration crewed exploration, NASA has identified several high priority potential health risks to astronauts in space. One such risk is a collection of neurologic and ophthalmic findings termed spaceflight associated neuro-ocular syndrome (SANS). The findings of SANS include optic disc edema, globe flattening, retinal nerve fiber layer thickening, chorioretinal folds, hyperopic shifts, and cotton-wool spots. The cause of SANS was initially thought to be a cephalad fluid shift in microgravity leading to increased intracranial pressure, venous stasis and impaired CSF outflow, but the precise etiology of SANS remains ill defined. Recent studies have explored multiple possible pathogenic mechanisms for SANS including genetic and hormonal factors; a cephalad shift of fluid into the orbit and brain in microgravity; and disruption to the brain glymphatic system. Orbital, ocular, and cranial imaging, both on Earth and in space has been critical in the diagnosis and monitoring of SANS (e.g., fundus photography, optical coherence tomography (OCT), magnetic resonance imaging (MRI), and orbital/cranial ultrasound). In addition, we highlight near-infrared spectroscopy and diffusion tensor imaging, two newer modalities with potential use in future studies of SANS. In this manuscript we provide a review of these modalities, outline their current and potential use in space and on Earth, and review the reported major imaging findings in SANS.

Biological culture module for plant research from seed-to-seed on the Chinese Space Station.

The long-term cultivation of higher plants in space plays a substantial role in investigating the effects of microgravity on plant growth and development, acquiring valuable insights for developing a self-sustaining space life supporting system. The completion of the Chinese Space Station (CSS) provides us with a new permanent space experimental platform for long-term plant research in space. Biological Culture Module (GBCM), which was installed in the Wentian experimental Module of the CSS, was constructed with the objective of growing Arabidopsis thaliana and rice plants a full life cycle in space. The techniques of LED light control, gas regulation and water recovery have been developed for GBCM in which dry seeds of Arabidopsis and rice were set in root module of four culture chambers (CCs) and launched with Wentian module on July 24, 2022. These seeds were watered and germinated from July 28 and grew new seeds until November 26 within a duration of 120 days. To this end, both Arabidopsis and rice plants completed a full life cycle in microgravity on the CSS. As we know, this is the first space experiment achieving rice complete life cycle from seed-to-seed in space. This result demonstrates the possibility to cultivate the important food crop rice throughout its entire life cycle under the spaceflight environment and the technologies of GBCM have effectively supported the success of long-term plant culture experiments in space. These results can serve as invaluable references for constructing more expansive and intricate space plant cultivation systems in the future.

rTMS Ameliorates time-varying depression and social behaviors in stimulated space complex environment associated with VEGF signaling.

Studies have indicated that medium- to long-duration spaceflight may adversely affect astronauts' emotional and social functioning. Emotion modulation can significantly impact astronauts' well-being, performance, mission safety and success. However, with the increase in flight time, the potential alterations in emotional and social performance during spaceflight and their underlying mechanisms remain to be investigated, and targeted therapeutic and preventive interventions have yet to be identified. We evaluated the changes of emotional and social functions in mice with the extension of the time in simulated space complex environment (SSCE), and simultaneously monitored changes in brain tissue of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and inflammation-related factors. Furthermore, we assessed the regulatory role of repetitive transcranial magnetic stimulation (rTMS) in mood and socialization with the extension of the time in SSCE, as well as examining alterations of VEGF signaling in the medial prefrontal cortex (mPFC). Our findings revealed that mice exposed to SSCE for 7 days exhibited depressive-like behaviors, with these changes persisting throughout SSCE period. In addition, 14 days of rTMS treatment significantly ameliorated SSCE-induced emotional and social dysfunction, potentially through modulation of the level of VEGF signaling in mPFC. These results indicates that emotional and social disorders increase with the extension of SSCE time, and rTMS can improve the performance, which may be related to VEGF signaling. This study offers insights into potential pattern of change over time for mental health issues in astronauts. Further analysis revealed that rTMS modulates emotional and social dysfunction during SSCE exposure, with its mechanism potentially being associated with VEGF signaling.

Cardiovascular adaptations in microgravity conditions.

Gravity has had a significant impact on the evolution of life on Earth with organisms developing necessary biological adaptations over billions of years to counter this ever-existing force. There has been an exponential increase in experiments using real and simulated gravity environments in the recent years. Although an understanding followed by discovery of counter measures to negate diminished gravity in space had been the driving force of research initially, there has since been a phenomenal leap wherein a force unearthly as microgravity is beginning to show promising potential. The current review summarizes pathophysiological changes that occur in multiple aspects of the cardiovascular system when exposed to an altered gravity environment leading to cardiovascular deconditioning and orthostatic intolerance. Gravity influences not just the complex multicellular systems but even the survival of organisms at the molecular level by intervening fundamental cellular processes, directly affecting those linked to actin and microtubule organization via mechano-transduction pathways. The reach of gravity ranges from cytoskeletal rearrangement that regulates cell adhesion and migration to intracellular dynamics that dictate cell fate commitment and differentiation. An understanding that microgravity itself is not present on Earth propels the scope of simulated gravity conditions to be a unique and useful environment that could be explored for enhancing the potential of stem cells for a wide range of applications as has been highlighted here.

Neurostimulation as a technology countermeasure for dry eye syndrome in astronauts.

Dry eye syndrome (DES) poses a significant challenge for astronauts during space missions, with reports indicating up to 30% of International Space Station (ISS) crew members. The microgravity environment of space alters fluid dynamics, affecting distribution of fluids on the surface of the eye as well as inducing cephalad fluid shifts that can alter tear drainage. Chronic and persistent DES not only impairs visual function, but also compromises the removal of debris, a heightened risk for corneal abrasions in the microgravity environment. Despite the availability of artificial tears on the ISS, the efficacy is challenged by altered fluid dynamics within the bottle and risks of contamination, thereby exacerbating the potential for corneal abrasions. In light of these challenges, there is a pressing need for innovative approaches to address DES in astronauts. Neurostimulation has emerged as a promising technology countermeasure for DES in spaceflight. By leveraging electrical signals to modulate neural function, neurostimulation offers a novel therapeutic avenue for managing DES symptoms. In this paper, we will explore the risk factors and current treatment modalities for DES, highlighting the limitations of existing approaches. Furthermore, we will delve into the novelty and potential of neurostimulation as a countermeasure for DES in future long-duration missions, including those to the Moon and Mars.

Lower body negative pressure as a research tool and countermeasure for the physiological effects of spaceflight: A comprehensive review.

Lower Body Negative Pressure (LBNP) redistributes blood from the upper body to the lower body. LBNP may prove to be a countermeasure for the multifaceted physiological changes endured by astronauts during spaceflight related to cephalad fluid shift. Over more than five decades, beginning with the era of Skylab, advancements in LBNP technology have expanded our understanding of neurological, ophthalmological, cardiovascular, and musculoskeletal adaptations in space, with particular emphasis on mitigating issues such as bone loss. To date however, no comprehensive review has been conducted that chronicles the evolution of this technology or elucidates the broad-spectrum potential of LBNP in managing the diverse physiological challenges encountered in the microgravity environment. Our study takes a chronological perspective, systematically reviewing the historical development and application of LBNP technology in relation to the various pathophysiological impacts of spaceflight. The primary objective is to illustrate how this technology, as it has evolved, offers an increasingly sophisticated lens through which to interpret the systemic effects of space travel on human physiology. We contend that the insights gained from LBNP studies can significantly aid in formulating targeted and effective countermeasures to ensure the health and safety of astronauts. Ultimately, this paper aspires to promote a more cohesive understanding of the broad applicability of LBNP as a countermeasure against multiple bodily effects of space travel, thereby contributing to a safer and more scientifically informed approach to human space exploration.

Biophysics of ophthalmic medications during spaceflight: Principles of ocular fluid dynamics and pharmacokinetics in microgravity.

As spaceflight becomes increasingly accessible and expansive to humanity, it is becoming ever more essential to consider the treatment of various eye diseases in these challenging environments. This paper delves into the increasing fascination with interplanetary travel and its implications for health management in varying environments. It specifically discusses the pharmacological management of ocular diseases, focusing on two key delivery methods: topical eye drops and intravitreal injections. The paper explores how microgravity impacts the administration of these treatments, a vital aspect in understanding drug delivery in space. An extensive analysis is presented on the pharmacokinetics of eye medications, examining the interaction between pharmaceuticals and ocular tissues in zero gravity. The goal of the paper is to bridge the understanding of fluid dynamics, microgravity and the human physiological systems to pave the way for innovative solutions faced by individuals in microgravity.

Impedance threshold device as a countermeasure for spaceflight associated neuro-ocular syndrome (SANS): Mitigating mechanisms in proposed pathophysiology.

Long-duration spaceflight (LDSF) is associated with unique hazards and linked with numerous human health risks including Spaceflight Associated Neuro-ocular Syndrome (SANS). The proposed mechanisms for SANS include microgravity induced cephalad fluid shift and increased Intracranial Pressure (ICP). SANS is a disorder seen only after LDSF and has no direct terrestrial pathologic counterpart as the zero G environment cannot be completely replicated on Earth. Head-down tilt, bed rest studies however have been used as a terrestrial analog and produce the cephalad fluid shift. Some proposed countermeasures for SANS include vasoconstrictive thigh cuffs and lower body negative pressure. Another potential researched countermeasure is the impedance threshold device (ITD) which can reduce ICP. We review the mechanisms of the ITD and its potential use as a countermeasure for SANS.

Musculoskeletal perturbations of deep space radiation: Assessment using a Gateway MRI.

Human space exploration expansion from Low-Earth Orbit to deep space is accelerating the need to monitor and address the known health concerns related to deep space radiation. The human musculoskeletal system is vulnerable to these risks (alongside microgravity) and its health reflects the well-being of other body systems. Multiparametric magnetic resonance imaging (MRI) is an important approach for assessing temporal physiological changes in the musculoskeletal system. We propose that ultra-low-field MRI provides an optimal low Size Weight and Power (SwaP) solution for non-invasively monitoring muscle and bone changes on the planned Gateway lunar space station. Our proposed ultra-low-field Gateway MRI meets low SWaP design specifications mandated by limited room in the lunar space station. This review summarizes the current state of our knowledge on musculoskeletal consequences of spaceflight, especially with respect to radiation, and then elaborates how MRI can be used to monitor the deleterious effects of space travel and the efficacy of putative countermeasures. We argue that an ultra-low-field MRI in cis-lunar space on the Gateway can provide valuable research and medical insights into the effects of deep space radiation exposure on astronauts. Such an MRI would also allow the development of imaging protocols that would facilitate Earth-bound teams to monitor space personnel musculoskeletal changes during future interplanetary spaceflight. It will especially have a role in monitoring countermeasures, such as the use of melanin, in protecting space explorers.

Coordinated lunar time (LTC): Implications of a lunar-centric time zone on astronaut health and space medicine.

Lunar exploration offers an exciting opportunity for humanity to advance scientific knowledge and future potential economic growth and possibly allow humans to become a multi-planetary species. On April 2, 2024 the US Office of Science and Technology Policy released a memorandum outlining the current Biden-Harris Administration's policy on the need to establish time standards at celestial bodies other than Earth. This memorandum also introduced the need for Coordinated Lunar Time (CLT), the concept of having a reference time for the moon. The establishment of CLT would provide a multitude of benefits for astronaut health, from expedition planning, to maintaining a sense of order in an austere environment. International agreements and collaboration will be required prior to the recognition of CLT.