Microgravity-like Crystallization of Paramagnetic Species in Strong Magnetic Fields.

The crystallization of paramagnetic species in a magnetic field gradient under microgravity-like conditions is an area of interest for both fundamental and applied science. In this paper, a setup for the crystallization of paramagnetic species in the magnetic field up to 7 T generated by a superconducting magnet is described. The research includes calculations of the conditions necessary to compensate for the gravitational force for several types of paramagnetic substances using the magnetic field of superconducting magnets (4.7 T, 7 T, 9.4 T, and 16.4 T). Additionally, for the first time, the crystallization of copper sulfate and cobalt sulfate, as well as a mixture of copper sulfate and cobalt sulfate under gravitational force compensation in a superconducting magnet, was performed. This paper experimentally demonstrates the feasibility of growing paramagnetic crystals within the volume of a test tube on the example of copper and cobalt sulfate crystals. A comparison of crystals grown from the solution of a mixture of copper and cobalt sulfates under the same conditions, with and without the presence of a magnetic field, showed changes in both the number and size of crystals.

Oscillations of Hemodynamic Parameters Induced by Negative Pressure Breathing in Healthy Humans.

INTRODUCTION: Negative pressure breathing is breathing with decreased pressure in the respiratory tract without lowering pressure acting on the torso. We lowered air pressure only during inspiration (NPBin). NPBin, used to increase venous return to the heart, is considered a countermeasure against redistribution of body fluids toward the head during spaceflight. We studied NPBin effects on circulation in healthy humans with an emphasis on NPBin-induced oscillations of hemodynamic parameters synchronous with breathing. We propose an approach to analyze the oscillations based on coherent averaging.METHODS: Eight men ages 24-42 yr participated in the NPBin and control series. During the series, to reproduce fluids shift observed under microgravity, subjects were supine and head down (-8°). Duration of NPBin was 20 min, rarefaction -20 cm H2O. Hemodynamic parameters were measured by Finometer. Electrical impedance measurements were used to estimate changes in blood filling of cerebral vessels.RESULTS: Mean values of hemodynamic parameters virtually did not change under NPBin, but NPBin induced oscillations of the parameters synchronous with respiration. Peak-to-peak amplitude under NPBin were: mean arterial pressure, 4 ± 1 (mmHg); stroke volume, 7 ± 3 (mL); and heart rate, 4 ± 1 (bpm). Electrical impedance of the head increased during inspiration. The increase under NPBin was three times greater than under normal breathing.DISCUSSION: Analysis of oscillations gives more information than analysis of mean values. NPBin induces short-term decrease in left ventricle stroke volume and arterial blood pressure during each inspiration; the decrease is compensated by increase after inspiration. NPBin facilitates redistribution of body fluids away from the head.Semenov YS, Melnikov IS, Luzhnov PV, Dyachenko AI. Oscillations of hemodynamic parameters induced by negative pressure breathing in healthy humans. Aerosp Med Hum Perform. 2024; 95(6):297-304.

A Novel 3D-Printed Gravity-Independent Air-Eliminating Filter for Rapid Intravenous Infusions.

INTRODUCTION: The absence of a consistent downward G vector can make separation of gases from liquids challenging, such as in field medicine without stable upright equipment or during spaceflight. This limits the use of medical equipment and procedures like administration of intravenous (IV) fluids in microgravity and can make field medicine hazardous. Administering IV fluids and medications in microgravity requires a technique to separate air from the liquid phase. Current commercial filters for separation of gases are incompatible with high flow and blood. We present a novel filter designed to provide adequate air clearance without a consistent downward G vector.METHODS: Inline air-eliminating filters were designed for use with IV fluid tubing in microgravity using computer-aided design software and printed using nylon 12 on an EOS Selective Laser Sintering 3D printer. A 0.2-µm membrane filter was adhered around a central, hollow pillar with external spiral baffles allowing separation and venting of air from the fluid. Results were compared against commercially available inline air-eliminating filters.RESULTS: The 3D-printed filters outperformed the commercial filters in both percentage of air removed and flow rates. The centrifugal, baffled filter had flow rates that far exceeded the commercial filters during rapid transfusion.DISCUSSION: IV fluid administration is an often underappreciated and a necessary basic requirement for medical treatment. An air-eliminating filter compatible with blood and rapid transfusion was developed and validated with crystalloid solutions to allow the successful administration of IV fluid and medication without a consistent downward G vector.Formanek A, Townsend J, Ottensmeyer MP, Kamine TH. A novel 3D-printed gravity-independent air-eliminating filter for rapid intravenous infusions. Aerosp Med Hum Perform. 2024; 95(6):327-332.

Shades of gravity - effects of planetary gravity levels on electrocortical activity and neurocognitive performance.

The plans of international space agencies to return to the Moon and explore deep space, including Mars, highlight the challenges of human adaptation and stress the need for a thorough analysis of the factors that facilitate, limit and modify human performance under extreme environments. This study investigates the influence of partial gravity on behavioural (error rate and reaction time) and neuronal parameters (event-related potentials) through parabolic flights. Brain cortical activity was assessed using EEG from 18 participants who solved a neurocognitive task, consisting of a mental arithmetic task and an auditory oddball paradigm, during Earth (1G), Lunar (0.16G + 0.25G) and Martian gravity (0.38G + 0.5G) for 15 consecutive parabolas. Data shows higher electrocortical activity in Earth gravity compared to Lunar and Martian gravity in the parietal lobe. No differences in participants' performance were found among the gravity levels. Event-related potentials displayed gravity-dependent variations, though limited stimuli recording suggests caution in interpretation. Data suggests a threshold between Earth and Martian gravity within the different gravities responsible for physiological changes, but it seems to vary greatly between individuals. The altered neuronal communication could be explained with a model developed by Kohn and Ritzmann in 2018. The increasing intracranial pressure in weightlessness changes the properties of the cell membrane of neurons and leads to a depolarisation of the resting membrane potential. The findings underscore the individuality of physiological changes in response to gravity alterations, signalling the need for further investigations in future studies.

Exploring the influence of microgravity on chemotherapeutic drug response in cancer: Unveiling new perspectives.

Microgravity, an altered gravity condition prevailing in space, has been reported to have a profound impact on human health. Researchers are very keen to comprehensively investigate the impact of microgravity and its intricate involvement in inducing physiological changes. Evidenced transformations were observed in the internal architecture including cytoskeletal organization and cell membrane morphology. These alterations can significantly influence cellular function, signalling pathways and overall cellular behaviour. Further, microgravity has been reported to alter in the expression profile of genes and metabolic pathways related to cellular processes, signalling cascades and structural proteins in cancer cells contributing to the overall changes in the cellular architecture. To investigate the effect of microgravity on cellular and molecular levels numerous ground-based simulation systems employing both in vitro and in vivo models are used. Recently, researchers have explored the possibility of leveraging microgravity to potentially modulate cancer cells against chemotherapy. These findings hold promise for both understanding fundamental processes and could potentially lead to the development of more effective, personalized and innovative approaches in therapeutic advancements against cancer.

Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

The effects of microgravity on stem cells and the new insights it brings to tissue engineering and regenerative medicine.

Conventional two-dimensional (2D) cell culture techniques may undergo modifications in the future, as life scientists have widely acknowledged the ability of three-dimensional (3D) in vitro culture systems to accurately simulate in vivo biology. In recent years, researchers have discovered that microgravity devices can address many challenges associated with 3D cell culture. Stem cells, being pluripotent cells, are regarded as a promising resource for regenerative medicine. Recent studies have demonstrated that 3D culture in microgravity devices can effectively guide stem cells towards differentiation and facilitate the formation of functional tissue, thereby exhibiting advantages within the field of tissue engineering and regenerative medicine. Furthermore, We delineate the impact of microgravity on the biological behavior of various types of stem cells, while elucidating the underlying mechanisms governing these alterations. These findings offer exciting prospects for diverse applications.

"Spaceflight-to-Eye Clinic": Terrestrial advances in ophthalmic healthcare delivery from space-based innovations.

The phrase "Bench-to-Bedside" is a well-known phrase in medicine, highlighting scientific discoveries that directly translate to impacting patient care. Key examples of translational research include identification of key molecular targets in diseases and development of diagnostic laboratory tests for earlier disease detection. Bridging these scientific advances to the bedside/clinic has played a meaningful impact in numerous patient lives. The spaceflight environment poses a unique opportunity to also make this impact; the nature of harsh extraterrestrial conditions and medically austere and remote environments push for cutting-edge technology innovation. Many of these novel technologies built for the spaceflight environment also have numerous benefits for human health on Earth. In this manuscript, we focus on "Spaceflight-to-Eye Clinic" and discuss technologies built for the spaceflight environment that eventually helped to optimize ophthalmic health on Earth (e.g., LADAR for satellite docking now utilized in eye-tracking technology for LASIK). We also discuss current technology research for spaceflight associated neuro-ocular syndrome (SANS) that may also be applied to terrestrial ophthalmic health. Ultimately, various advances made to enable to the future of space exploration have also advanced the ophthalmic health of individuals on Earth.

Reduced ossification caused by 3D simulated microgravity exposure is short-term in larval zebrafish.

Understanding how skeletal tissues respond to microgravity is ever more important with the increased interest in human space travel. Here, we exposed larval Danio rerio at 3.5 dpf to simulated microgravity (SMG) using a 3D mode of rotation in a ground-based experiment and then studied different cellular, molecular, and morphological bone responses both immediately after exposure and one week later. Our results indicate an overall decrease in ossification in several developing skeletal elements immediately after SMG exposure with the exception of the otoliths, however ossification returns to normal levels seven days after exposure. Coincident with the reduction in overall ossification tnfsf11 (RANKL) expression is highly elevated after 24 h of SMG exposure and also returns to normal levels seven days after exposure. We also show that genes associated with osteoblasts are unaffected immediately after SMG exposure. Thus, the observed reduction in ossification is primarily the result of a high level of bone resorption. This study sheds insight into the nuances of how osteoblasts and osteoclasts in the skeleton of a vertebrate organism respond to an external environmental disturbance, in this case simulated microgravity.

The influence of simulated weightlessness on the composition and function of gut microbiota and bile acid metabolism products.

The aim of this study was to investigate the effects of simulated weightlessness on gut microbiota, bile acid metabolism, and inflammatory cytokines compared to the control group. The study compared the changes in gut microbiota at the phylum and genus levels in the feces of control and weightlessness rats after 1 and 8 weeks using fecal 16S rRNA sequencing. In the weightlessness group, there was an increase in the proportion of anaerobic bacteria and biofilm-forming bacteria, and a decrease in the proportion of aerobic and Gram-negative bacteria. Further investigations explored the impact of weightlessness on bile acid metabolism products. The levels of glycine ursodeoxycholic acid, glycine chenodeoxycholic acid, glycine deoxycholic acid and glycine cholic acid levels were lower in rats undergoing weightlessness for 1 week compared to the control group.Moreover, the study examined the relationship between gut microbiota and bile acid metabolism products.It was observed that, unlike the control group, there were significant positive correlations between Planctomycetes, Proteobacteria, Synergistetes, and GUDCA levels in rats after 1 week of weightlessness. Finally, ELISA results indicated significant differences in the levels of MDA, GSH, NLRP3, and SIgA inflammatory cytokines between rats undergoing weightlessness for 1 week and the control group rats. Our research confirmed that the simulated weightlessness environment significantly affects the gut microbiota and bile acid metabolism in rats, potentially leading to changes in inflammatory cytokines and causing intestinal tissue inflammation. Further exploring the relationship between gut microbiota and bile acid metabolism under weightless conditions will be crucial for understanding the functional changes in the intestines caused by weightlessness.

Amorphous calcium carbonate enhances osteogenic differentiation and myotube formation of human bone marrow derived mesenchymal stem cells and primary skeletal muscle cells under microgravity conditions.

Astronauts are exposed to severely stressful physiological conditions due to microgravity and increased space radiation. Space environment affects every organ and cell in the body and the significant adverse effects of long-term weightlessness include muscle atrophy and deterioration of the skeleton (spaceflight osteopenia). Amorphous Calcium Carbonate (ACC) emerges as a promising candidate for prevention of these effects, owing to its unique physicochemical properties and its potential to address the intricately linked nature of bone-muscle crosstalk. Reported here are two studies carried out on the International Space Station (ISS). The first, performed in 2018 as a part of the Ramon-Spacelab project, was a preliminary experiment, in which stromal murine cells were differentiated into osteoblasts when ACC was added to the culture medium. A parallel experiment was done on Earth as a control. The second study was part of Axiom-1's Rakia project mission launched to the ISS on 2022 utilizing organ-on-a-chip methodology with a specially designed autonomous module. In this experiment, human bone-marrow derived mesenchymal stem cells (hBM-MSCs) and human primary muscle cells were cultured in the presence or absence of ACC, in duplicates. The results showed that ACC enhanced differentiation of human primary skeletal muscle cells into myotubes. Similarly, hBM-MSCs were differentiated significantly better into osteocytes in the presence of ACC leading to increased calcium deposits. The results, combined with previous data, support the use of ACC as an advantageous supplement for preventing muscle and bone deterioration in outer space conditions, facilitating extended extraterrestrial voyages and colonization.

Construction of microgravity biological knowledge graph and its applications in anti-osteoporosis drug prediction.

Microgravity in the space environment can potentially have various negative effects on the human body, one of which is bone loss. Given the increasing frequency of human space activities, there is an urgent need to identify effective anti-osteoporosis drugs for the microgravity environment. Traditional microgravity experiments conducted in space suffer from limitations such as time-consuming procedures, high costs, and small sample sizes. In recent years, the in-silico drug discovery method has emerged as a promising strategy due to the advancements in bioinformatics and computer technology. In this study, we first collected a total of 184,915 literature articles related to microgravity and bone loss. We employed a combination of dependency path extraction and clustering techniques to extract data from the text. Afterwards, we conducted data cleaning and standardization to integrate data from several sources, including The Global Network of Biomedical Relationships (GNBR), Curated Drug-Drug Interactions Database (DDInter), Search Tool for Interacting Chemicals (STITCH), DrugBank, and Traditional Chinese Medicines Integrated Database (TCMID). Through this integration process, we constructed the Microgravity Biology Knowledge Graph (MBKG) consisting of 134,796 biological entities and 3,395,273 triplets. Subsequently, the TransE model was utilized to perform knowledge graph embedding. By calculating the distances between entities in the model space, the model successfully predicted potential drugs for treating osteoporosis and microgravity-induced bone loss. The results indicate that out of the top 10 ranked western medicines, 7 have been approved for the treatment of osteoporosis. Additionally, among the top 10 ranked traditional Chinese medicines, 5 have scientific literature supporting their effectiveness in treating bone loss. Among the top 20 predicted medicines for microgravity-induced bone loss, 15 have been studied in microgravity or simulated microgravity environments, while the remaining 5 are also applicable for treating osteoporosis. This research highlights the potential application of MBKG in the field of space drug discovery.

Cellular and Molecular Effects of Microgravity on the Immune System: A Focus on Bioactive Lipids.

Microgravity is one of the main stressors that astronauts are exposed to during space missions. This condition has been linked to many disorders, including those that feature dysfunctional immune homeostasis and inflammatory damage. Over the past 30 years, a significant body of work has been gathered connecting weightlessness-either authentic or simulated-to an inefficient reaction to pathogens, dysfunctional production of cytokines and impaired survival of immune cells. These processes are also orchestrated by a plethora of bioactive lipids, produced by virtually all cells involved in immune events, which control the induction, magnitude, outcome, compartmentalization and trafficking of immunocytes during the response to injury. Despite their crucial importance in inflammation and its modulation, however, data concerning the role of bioactive lipids in microgravity-induced immune dysfunctions are surprisingly scarce, both in quantity and in variety, and the vast majority of it focuses on two lipid classes, namely eicosanoids and endocannabinoids. The present review aims to outline the accumulated knowledge addressing the effects elicited by microgravity-both simulated and authentic-on the metabolism and signaling of these two prominent lipid groups in the context of immune and inflammatory homeostasis.

Effect of Spaceflight and Microgravity on the Musculoskeletal System: A Review.

With National Aeronautics and Space Administration's plans for longer distance, longer duration spaceflights such as missions to Mars and the surge in popularity of space tourism, the need to better understand the effects of spaceflight on the musculoskeletal system has never been more present. However, there is a paucity of information on how spaceflight affects orthopaedic health. This review surveys existing literature and discusses the effect of spaceflight on each aspect of the musculoskeletal system. Spaceflight reduces bone mineral density at rapid rates because of multiple mechanisms. While this seems to be recoverable upon re-exposure to gravity, concern for fracture in spaceflight remains as microgravity impairs bone strength and fracture healing. Muscles, tendons, and entheses similarly undergo microgravity adaptation. These changes result in decreased muscle mass, increased tendon laxity, and decreased enthesis stiffness, thus decreasing the strength of the muscle-tendon-enthesis unit with variable recovery upon gravity re-exposure. Spaceflight also affects joint health; unloading of the joints facilitates changes that thin and atrophy cartilage similar to arthritic phenotypes. These changes are likely recoverable upon return to gravity with exercise. Multiple questions remain regarding effects of longer duration flights on health and implications of these findings on terrestrial medicine, which should be the target of future research.

Effects of simulated microgravity on current generation of electrochemically active bacteria: Insights from case-control study using random positioning machine.

Electrochemically active bacteria (EAB) exhibit promising prospects for space exploration and life support systems. However, the effects of the space environment on EAB are unclear. In this study, the effects of simulated microgravity on the current generation of mixed-culture EAB were illustrated, and the underlying mechanism was elucidated. The results demonstrated that the electrochemical activity of mixed-culture EAB was enhanced, which was mainly due to the enrichment of Geobacter and the increase in EAB biomass. Additionally, the genes and proteins of the biofilm changed obviously under simulated microgravity conditions, including: I) genes related to signal transfer, II) genes related to cell wall synthesis, and III) genes related to riboflavin synthesis. This study first revealed the enrichment in EAB abundance, the increase in EAB biomass, and the promotion of current generation under simulated microgravity.

Vibration Rather than Microgravity Affects Bone Metabolism in Adult Zebrafish Scale Model.

Gravity and mechanical forces cause important alterations in the human skeletal system, as demonstrated by space flights. Innovative animal models like zebrafish embryos and medaka have been introduced to study bone response in ground-based microgravity simulators. We used, for the first time, adult zebrafish in simulated microgravity, with a random positioning machine (RPM) to study bone remodeling in the scales. To evaluate the effects of microgravity on bone remodeling in adult bone tissue, we exposed adult zebrafish to microgravity for 14 days using RPM and we evaluated bone remodeling on explanted scales. Our data highlight bone resorption in scales in simulated microgravity fish but also in the fish exposed, in normal gravity, to the vibrations produced by the RPM. The osteoclast activation in both rotating and non-rotating samples suggest that prolonged vibrations exposure leads to bone resorption in the scales tissue. Stress levels in these fish were normal, as demonstrated by blood cortisol quantification. In conclusion, vibrational mechanical stress induced bone resorption in adult fish scales. Moreover, adult fish as an animal model for microgravity studies remains controversial since fish usually live in weightless conditions because of the buoyant force from water and do not constantly need to support their bodies against gravity.

Simulation of Human Movement in Zero Gravity.

In the era of expanding manned space missions, understanding the biomechanical impacts of zero gravity on human movement is pivotal. This study introduces a novel and cost-effective framework that demonstrates the application of Microsoft's Azure Kinect body tracking technology as a motion input generator for subsequent OpenSim simulations in weightlessness. Testing rotations, locomotion, coordination, and martial arts movements, we validate the results' realism under the constraints of angular and linear momentum conservation. While complex, full-body coordination tasks face limitations in a zero gravity environment, our findings suggest possible approaches to device-free exercise routines for astronauts and reveal insights into the feasibility of hand-to-hand combat in space. However, some challenges remain in distinguishing zero gravity effects in the simulations from discrepancies in the captured motion input or forward dynamics calculations, making a comprehensive validation difficult. The paper concludes by highlighting the framework's practical potential for the future of space mission planning and related research endeavors, while also providing recommendations for further refinement.

Single drop cytometry onboard the International Space Station.

Real-time lab analysis is needed to support clinical decision making and research on human missions to the Moon and Mars. Powerful laboratory instruments, such as flow cytometers, are generally too cumbersome for spaceflight. Here, we show that scant test samples can be measured in microgravity, by a trained astronaut, using a miniature cytometry-based analyzer, the rHEALTH ONE, modified specifically for spaceflight. The base device addresses critical spaceflight requirements including minimal resource utilization and alignment-free optics for surviving rocket launch. To fully enable reduced gravity operation onboard the space station, we incorporated bubble-free fluidics, electromagnetic shielding, and gravity-independent sample introduction. We show microvolume flow cytometry from 10 µL sample drops, with data from five simultaneous channels using 10 µs bin intervals during each sample run, yielding an average of 72 million raw data points in approximately 2 min. We demonstrate the device measures each test sample repeatably, including correct identification of a sample that degraded in transit to the International Space Station. This approach can be utilized to further our understanding of spaceflight biology and provide immediate, actionable diagnostic information for management of astronaut health without the need for Earth-dependent analysis.

Trolox and recombinant Irisin as a potential strategy to prevent neuronal damage induced by random positioning machine exposure in differentiated HT22 cells.

Neuronal death could be responsible for the cognitive impairments found in astronauts exposed to spaceflight, highlighting the need to identify potential countermeasures to ensure neuronal health in microgravity conditions. Therefore, differentiated HT22 cells were exposed to simulated microgravity by random positioning machine (RPM) for 48 h, treating them with a single administration of Trolox, recombinant irisin (r-Irisin) or both. Particularly, we investigated cell viability by MTS assay, Trypan Blue staining and western blotting analysis for Akt and B-cell lymphoma 2 (Bcl-2), the intracellular increase of reactive oxygen species (ROS) by fluorescent probe and NADPH oxidase 4 (NOX4) expression, as well as the expression of brain-derived neurotrophic factor (BDNF), a major neurotrophin responsible for neurogenesis and synaptic plasticity. Although both Trolox and r-Irisin manifested a protective effect on neuronal health, the combined treatment produced the best results, with significant improvement in all parameters examined. In conclusion, further studies are needed to evaluate the potential of such combination treatment in counteracting weightlessness-induced neuronal death, as well as to identify other potential strategies to safeguard the health of astronauts exposed to spaceflight.