ISG15 is involved in chondrogenic differentiation through activation of IFN-γ signaling.

Interferon-gamma (IFN-γ) was found to increase in the synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). However, few studies have been conducted to elucidate the role of IFN-γ in cartilage metabolism and regeneration. In this study, we investigated whether cartilage regeneration is driven by interferon-stimulated gene 15 (ISG15) under the control of IFN-γ. IFN-γ significantly increased ITS-induced chondrogenic differentiation of ATDC5 cells. Knockdown of IFN-γ receptor (IFN-γR) inhibited IFN-γ-induced chondrogenic differentiation and reduced ACAN and Col II expression. In addition, ISG15 expression was highly elevated in response to IFN-γ, whereas its expression was downregulated by knockdown of IFN-γR, indicating that ISG15 is closely related to IFN-γ signaling. Furthermore, chondrogenic differentiation and expression of ACAN and Col II were significantly reduced following knockdown of ISG15 in ATDC5 cells despite the presence of IFN-γ. ISGylation of cellular proteins found in chondrogenic differentiated cells was related to activation of IFN-γ signaling. In addition, ISG15/ISGylation was significantly observed in the regenerated cartilage tissue 7 days after FTCI of young mice compared with sham control. Our findings showed that upregulation of ISG15 and/or ISGylation of cellular proteins may play a critical role in cartilage regeneration through activation of IFN-γ signaling.

The effect of lung-recruitment maneuver on postoperative shoulder pain in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

PURPOSE: Lung-recruitment maneuvers (LRM) have been shown to reduce postoperative pain after laparoscopic surgery. This study aimed to investigate the association of LRM with the incidence of shoulder pain after laparoscopic cholecystectomy. METHODS: A randomized controlled study was conducted with 110 patients undergoing elective laparoscopic cholecystectomy from July 2022 to March 2023. Participants were randomized to receive either routine exsufflation or LRM at pneumoperitoneum release. The postoperative shoulder pain and abdominal pain were assessed at 1, 4, 6, 12, and 24 h after surgery using a numeric rating scale. Analgesic consumption and postoperative nausea or vomiting (PONV) were evaluated during the first 24 h after surgery. RESULTS: The incidence of shoulder pain during the first 24 h after surgery was significantly lower in the LRM group compared to the control group (26.9 vs. 59.3%; P = 0.001). The median [interquartile range] score of worst shoulder pain was significantly lower compared to the control group (3 [2-3] vs 4 [3-5.5]; P = 0.003). Participants in the LRM group showed reduced abdominal pain at rest at 4 and 24 h after surgery, and experienced significantly lower intensities of abdominal pain during mobilization at all time points over 24 h after surgery. There were no significant differences in opioid consumption or the incidence of PONV between the groups. CONCLUSIONS: LRM reduces both the incidence and intensity of shoulder pain during 24 h after laparoscopic cholecystectomy. Additionally, LRM was associated with reduced intensity of abdominal pain during mobilization over the study period.

Predicting sleep based on physical activity, light exposure, and Heart rate variability data using wearable devices.

OBJECTIVE: We aimed to improve the performance of sleep prediction algorithms by increasing the data amount, adding variables reflecting psychological state, and adjusting the data length. MATERIALS AND METHODS: We used ActiGraph GT3X+® and Galaxy Watch Active2™ to collect physical activity and light exposure data. We collected heart rate variability (HRV) data with the Galaxy Watch. We evaluated the performance of sleep prediction algorithms based on different data sources (wearable devices only, sleep diary only, or both), data lengths (1, 2, or 3 days), and analysis methods. We defined the target outcome, 'good sleep', as ≥90% sleep efficiency. RESULTS: Among 278 participants who denied having sleep disturbance, we used data including 2136 total days and nights from 230 participants. The performance of the sleep prediction algorithms improved with an increased amount of data and added HRV data. The model with the best performance was the extreme gradient boosting model; XGBoost, using both sources combined data with HRV, and 2-day data (accuracy=.85, area under the curve =.80). CONCLUSIONS: The results show that the performance of the sleep prediction models improved by increasing the data amount and adding HRV data. Further studies targeting insomnia patients and applied researches on non-pharmacological insomnia treatment are needed.

Evaluation of the sensitivity of a measles diagnostic real-time RT-PCR assay incorporating recently observed priming mismatch variants, 2024.

We investigated a variant of measles virus that encodes three mismatches to the reverse priming site for a widely used diagnostic real-time RT-PCR assay; reduction of sensitivity was hypothesised. We examined performance of the assay in context of the variant using in silico data, synthetic RNA templates and clinical specimens. Sensitivity was reduced observed at low copy numbers for templates encoding the variant sequence. We designed and tested an alternate priming strategy, rescuing the sensitivity of the assay.

Molecular mechanisms of circular RNA translation.

Circular RNAs (circRNAs) are covalently closed single-stranded RNAs without a 5' cap structure and a 3' poly(A) tail typically present in linear mRNAs of eukaryotic cells. CircRNAs are predominantly generated through a back-splicing process within the nucleus. CircRNAs have long been considered non-coding RNAs seemingly devoid of protein-coding potential. However, many recent studies have challenged this idea and have provided substantial evidence that a subset of circRNAs can associate with polysomes and indeed be translated. Therefore, in this review, we primarily highlight the 5' cap-independent internal initiation of translation that occurs on circular RNAs. Several molecular features of circRNAs, including the internal ribosome entry site, N6-methyladenosine modification, and the exon junction complex deposited around the back-splicing junction after back-splicing event, play pivotal roles in their efficient internal translation. We also propose a possible relationship between the translatability of circRNAs and their stability, with a focus on nonsense-mediated mRNA decay and nonstop decay, both of which are well-characterized mRNA surveillance mechanisms. An in-depth understanding of circRNA translation will reshape and expand our current knowledge of proteomics.

Sn-Doped Zinc Oxide as an Electron Transporting Layer for Enhanced Performance in PbS Quantum Dot Solar Cells.

Colloidal PbS quantum dot solar cells (QDSCs) have been primarily demonstrated in n-i-p structures by incorporating a solution-processed ZnO electron transporting layer (ETL). Nevertheless, the inherent energy barrier for the electron extraction at the ZnO/PbS junction along with the defective nature significantly diminishes the performance of the PbS QDSCs. In this study, by employing Sn-doped ZnO (ZTO) ETL, we have tuned the conduction band offset at the junction from spike-type to cliff-type so that the electron extraction barrier can be eliminated and the overall photovoltaic parameters can be enhanced (open-circuit voltage of 0.7 V, fill factor over 70%, and efficiency of 11.3%) as compared with the counterpart with the undoped ZnO ETL. The X-ray photoelectron spectroscopy (XPS) analysis revealed a mitigation of oxygen vacancies in the ZTO ETL of our PbS QDSCs. Our work signifies the importance of Sn doping into the conventional ZnO ETL for the superior electron extraction in PbS QDSCs.

Short-term aerobic exercise prevents development of glucocorticoid myopathic features in aged skeletal muscle in a sex-dependent manner.

Older adults are vulnerable to glucocorticoid-induced muscle atrophy and weakness, with sex potentially influencing their susceptibility to those effects. Aerobic exercise can reduce glucocorticoid-induced muscle atrophy in young rodents. However, it is unknown whether aerobic exercise can prevent glucocorticoid myopathy in aged muscle. The objectives of this study were to define the extent to which sex influences the development of glucocorticoid myopathy in aged muscle, and to determine the extent to which aerobic exercise training protects against myopathy development. Twenty-four-month-old female (n = 30) and male (n = 33) mice were randomized to either sedentary or aerobic exercise groups. Within their respective groups, mice were randomized to either daily treatment with dexamethasone (DEX) or saline. Upon completing treatments, the contractile properties of the triceps surae complex were assessed in situ. DEX marginally lowered muscle mass and soluble protein content in both sexes, which was attenuated by aerobic exercise only in females. DEX increased sub-tetanic force and rate of force development only in females, which was not influenced by aerobic exercise. Muscle fatigue was higher in both sexes following DEX, but aerobic exercise prevented fatigue induction only in females. The sex-specific differences to muscle function in response to DEX treatment coincided with sex-specific changes to the content of proteins related to calcium handling, mitochondrial quality control, reactive oxygen species production, and glucocorticoid receptor in muscle. These findings define several important sexually dimorphic changes to aged skeletal muscle physiology in response to glucocorticoid treatment and define the capacity of short-term aerobic exercise to protect against those changes. KEY POINTS: There are sexually dimorphic effects of glucocorticoids on aged skeletal muscle physiology. Glucocorticoid-induced changes to aged muscle contractile properties coincide with sex-specific differences in the content of calcium handling proteins. Aerobic exercise prevents glucocorticoid-induced fatigue only in aged females and coincides with differences in the content of mitochondrial quality control proteins and glucocorticoid receptors.

Synthesis, Antiproliferative Activity and Molecular Docking Analysis of Both Enantiomerically Pure Decursin Derivatives as Anticancer Agents.

Using (S)-decursinol isolated from root of Angelica gigas Nakai (AGN), we semi-synthesized and evaluated a series of both enantiomerically pure decursin derivatives for their antiproliferative activities against A549 human lung cancer cells. All synthesized compounds showed a broad spectrum of inhibitory activities against the growth of A549 cells. Especially, compound (S)-2d with (E)-(furan-3-yl)acryloyl group showed the most potent activity (IC50: 14.03 µM) against A549 cancer cells as compared with the reference compound, decursin (IC50: 43.55 µM) and its enantiomer, (R)-2d (IC50: 151.59 µM). Western blotting assays indicated that (S)-2d more strongly inhibited Janus kinase 1 (JAK1) and signal transducer and activator of transcription activation 3 (STAT3) phosphorylation than decursin in a dose-dependent manner, while having no effect on CXCR7 overexpression and total STAT3 level. In addition, (S)-2d induced cell cycle arrest at G1 phase and subsequent apoptotic cell death in A549 cancer cells. Our combined analysis of molecular docking studies and biological data suggests that the inhibition of JAK1 with (S)-2d resulted in loss of STAT3 phosphorylation and inhibition of cell growth in A549 cancer cells. These overall results strongly suggest that (S)-2d (MRC-D-004) as a novel JAK1 inhibitor may have therapeutic potential in the treatment of A549 human lung cancers by targeting the JAK1/STAT3 signaling pathway.

FLRT2 prevents endothelial cell senescence and vascular aging by regulating the ITGB4/mTORC2/p53 signaling pathway.

The roles of fibronectin leucine-rich transmembrane protein 2 (FLRT2) in physiological and pathological processes are not well known. Here, we identify a potentially novel function of FLRT2 in preventing endothelial cell senescence and vascular aging. We found that FLRT2 expression was lower in cultured senescent endothelial cells as well as in aged rat and human vascular tissues. FLRT2 mediated endothelial cell senescence via the mTOR complex 2, AKT, and p53 signaling pathway in human endothelial cells. We uncovered that FLRT2 directly associated with integrin subunit beta 4 (ITGB4) and thereby promoted ITGB4 phosphorylation, while inhibition of ITGB4 substantially mitigated the induction of senescence triggered by FLRT2 depletion. Importantly, FLRT2 silencing in mice promoted vascular aging, and overexpression of FLRT2 rescued a premature vascular aging phenotype. Therefore, we propose that FLRT2 could be targeted therapeutically to prevent senescence-associated vascular aging.

Effect of Oxidizing Agent on the Synthesis of ZnO Nanoparticles for Inverted Phosphorescent Organic Light-Emitting Devices without Multiple Interlayers.

Inverted organic light-emitting devices (OLEDs) have been aggressively developed because of their superiorities such as their high stability, low driving voltage, and low drop of brightness in display applications. The injection of electrons is a critical issue in inverted OLEDs because the ITO cathode has an overly high work function in injecting electrons into the emission layer from the cathode. We synthesized hexagonal wurtzite ZnO nanoparticles using different oxidizing agents for an efficient injection of electrons in the inverted OLEDs. Potassium hydroxide (KOH) and tetramethylammonium hydroxide pentahydrate (TMAH) were used as oxidizing agents for synthesizing ZnO nanoparticles. The band gap, surface defects, surface morphology, surface roughness, and electrical resistivity of the nanoparticles were investigated. The inverted devices with phosphorescent molecules were prepared using the synthesized nanoparticles. The inverted devices with ZnO nanoparticles using TMAH exhibited a lower driving voltage, lower leakage current, and higher maximum external quantum efficiency. The devices with TMAH-based ZnO nanoparticles exhibited the maximum external quantum efficiency of 19.1%.

Stepwise Flux Optimization for Enhanced GABA Production from Acetate in Escherichia coli.

Strategic allocation of metabolic flux is essential for achieving a higher production performance in genetically engineered organisms. Flux optimization between cell growth and chemical production has led to the establishment of cost-effective chemical production methods in microbial cell factories. This effect is amplified when utilizing a low-cost carbon source. γ-Aminobutyric acid (GABA), crucial in pharmaceuticals and biodegradable polymers, can be efficiently produced from acetate, a cost-effective substrate. However, a balanced distribution of acetate-derived flux is essential for optimizing the production without hindering growth. In this study, we demonstrated GABA production from acetate using Escherichia coli by focusing on optimizing the metabolic flux at isocitrate and α-ketoglutarate nodes. Through a series of flux optimizations, the final strain produced 2.54 g/L GABA from 5.91 g/L acetate in 24 h (0.43 g/g yield). These findings suggest that delicate flux balancing with the application of a cheap substrate can contribute to cost-effective production of GABA.

Systematic Engineering of Genistein Biosynthetic Pathway through Genetic Regulators and Combinatorial Enzyme Screening.

Microbial production of genistein, an isoflavonoid primarily found in soybeans, is gaining prominence in the food industry due to its significant nutritional and health benefits. However, challenges arise in redesigning strains due to intricate regulatory nodes between cell growth and genistein production and in systematically exploring core enzymes involving genistein biosynthesis. To address this, this study devised a strategy that simultaneously and precisely rewires flux at both acetyl-CoA and malonyl-CoA nodes toward genistein synthesis. In particular, naringenin, the primary precursor of genistein, was accumulated 2.6 times more than the unoptimized strain through transcriptional repressor-based genetic regulators. Building upon this, a combination of isoflavone synthase and cytochrome P450 reductase with the remarkable conversion of naringenin to genistein was screened from enzyme homologue libraries. The integrated metabolic engineering strategy yields the highest reported production (98 mg/L of genistein) to date, providing a framework for the biosynthesis of diverse flavonoids, including genistein.

Convergent Synthesis of Two Heterogeneous Fluxes from Glucose and Acetate for High-Yield Citramalate Production.

Biological production of citramalate has garnered attention due to its wide application for food additives and pharmaceuticals, although improvement of yield is known to be challenging. When glucose is used as the sole carbon source, carbon loss through decarboxylation steps for providing acetyl-CoA from pyruvate is inevitable. To avoid this, we engineered a strain to co-utilize glucose and cost-effective acetate while preventing carbon loss for enhancing citramalate production. The production pathway diverged to independently supply the precursors required for the synthesis of citramalate from glucose and acetate, respectively. Moreover, the phosphotransferase system was inactivated and the acetate assimilation pathway and the substrate ratio were optimized to enable the simultaneous and efficient utilization of both carbon sources. This yielded results (5.0 g/L, 0.87 mol/mol) surpassing the yield and titer of the control strain utilizing glucose as the sole carbon source in flask cultures, demonstrating an economically efficient strain redesign strategy for synthesizing various products.

Effects of Extracellular Calcium Concentration on Hepatic Ischemia-Reperfusion Injury in a Rat Model.

OBJECTIVES: Hypocalcemia is frequently identified during liver transplant. However, supplementation of extracellular calcium could induce increased intracellular calcium concentration, as a potential factor for injury to the liver graft. We evaluated the effects of regulating extracellular calcium concentrations on hepatic ischemia-reperfusion injury. MATERIALS AND METHODS: We randomly divided 24 Sprague-Dawley rats into 3 groups: group C received normal saline (n = 8), group L received citrate to induce hypocalcemia (n = 8), and group L-Co received citrate followed by calcium gluconate to ameliorate hypocalcemia (n = 8). Liver enzyme levels and extracellular calcium were measured before surgery, 1 hour after ischemia, and 2 hours after reperfusion. The primary outcome was liver enzyme levels measured 2 hours after reperfusion. In addition, we evaluated intracellular calcium levels, lactate dehydrogenase activity, and histopathological results in liver tissue. RESULTS: Three groups demonstrated significant differences in extracellular calcium concentrations, but intracellular calcium concentrations in liver tissue were not significantly different. Group L showed significantly lower mean arterial pressure than other groups at 1 hour after ischemia (93.6 ± 20.8 vs 69.4 ± 14.2 vs 86.6 ± 10.4 mmHg; P = .02, for group C vs L vs L-Co, respectively). At 2 hours after reperfusion, group L showed significantly higher liver enzymes than other groups (aspartate aminotransferase 443.0 ± 353.2 vs 952.3 ± 94.8 vs 502.4 ± 327.3 U/L, P = .01; and alanine aminotransferase 407.9 ± 406.5 vs 860.6 ± 210.9 vs 333.9 ± 304.2 U/L, P = .02; for group C vs L vs L-Co, respectively). However, no significant difference was shown in lactate dehydrogenase and histological liver injury grade. CONCLUSIONS: Administering calcium to rats with hypocalcemia did not increase intracellular calcium accumulation but instead resulted in less hepatic injury compared with rats with low extracellular calcium concentrations in this rat model study.

Effects of sports therapy on improvement of menopausal symptoms, psychological status, and body morphology in perimenopausal women.

OBJECTIVE: The aim of this study was to increase the treatment rate of perimenopausal women by providing evidence-based nonpharmaceutical treatments through developing scientific evidence-based sports therapy and verifying its effectiveness. METHODS: In a cross-over design, a total of 33 women were assigned to two different sequences of intervention: sports therapy and telephone intervention (n = 17) or telephone intervention and sports therapy (n = 16). A self-reported clinical symptom survey was conducted before and after the experimental and control periods using the following measures: the Menopause Rating Scale, Patient Health Questionnaire 9, and Patient Health Questionnaire 15. RESULTS: There were significant differences in the changes in the scores for Menopause Rating Scale total (exercise phase, 17.8 ± 5.5 at baseline [B] and 13.5 ± 4.2 at follow-up [F]; control phase, 15.9 ± 6.0 [B] and 15.4 ± 5.3 [F]; P < 0.01), somatic symptoms (exercise phase, 9.5 ± 2.6 [B] and 6.6 ± 2.0 [F]; control phase, 8.5 ± 2.8 [B] and 8.0 ± 1.3 [F], P < 0.01), and urogenital symptoms (exercise phase, 4.9 ± 1.7 [B] and 4.1 ± 1.4 [F]; control phase, 4.3 ± 1.6 [B] and 4.4 ± 1.5 [F]; P < 0.01) between the exercise and control phases. There were also significant differences in the changes in the scores for PHQ-9 (exercise phase, 4.6 ± 4.4 [B] and 3.6 ± 3.3 [F]; control phase, 4.5 ± 3.8 [B] and 5.5 ± 4.6 [F]; P = 0.008) and PHQ-15 (exercise phase, 7.2 ± 4.4 [B] and 5.5 ± 3.5 [F]; control phase, 6.8 ± 4.4 [B] and 7.2 ± 4.9 [F]; P = 0.009) between the two phases. CONCLUSIONS: Sports therapy would improve menopause symptoms, especially somatic and urogenital symptoms. In addition, sports therapy would improve depressive moods in perimenopausal women.

TRIM22 induces cellular senescence by targeting PHLPP2 in hepatocellular carcinoma.

The ubiquitin-proteasome system is a vital protein degradation system that is involved in various cellular processes, such as cell cycle progression, apoptosis, and differentiation. Dysregulation of this system has been implicated in numerous diseases, including cancer, vascular disease, and neurodegenerative disorders. Induction of cellular senescence in hepatocellular carcinoma (HCC) is a potential anticancer strategy, but the precise role of the ubiquitin-proteasome system in cellular senescence remains unclear. In this study, we show that the E3 ubiquitin ligase, TRIM22, plays a critical role in the cellular senescence of HCC cells. TRIM22 expression is transcriptionally upregulated by p53 in HCC cells experiencing ionizing radiation (IR)-induced senescence. Overexpression of TRIM22 triggers cellular senescence by targeting the AKT phosphatase, PHLPP2. Mechanistically, the SPRY domain of TRIM22 directly associates with the C-terminal domain of PHLPP2, which contains phosphorylation sites that are subject to IKKß-mediated phosphorylation. The TRIM22-mediated PHLPP2 degradation leads to activation of AKT-p53-p21 signaling, ultimately resulting in cellular senescence. In both human HCC databases and patient specimens, the levels of TRIM22 and PHLPP2 show inverse correlations at the mRNA and protein levels. Collectively, our findings reveal that TRIM22 regulates cancer cell senescence by modulating the proteasomal degradation of PHLPP2 in HCC cells, suggesting that TRIM22 could potentially serve as a therapeutic target for treating cancer.

Transcriptional and translational flux optimization at the key regulatory node for enhanced production of naringenin using acetate in engineered Escherichia coli.

As a key molecular scaffold for various flavonoids, naringenin is a value-added chemical with broad pharmaceutical applicability. For efficient production of naringenin from acetate, it is crucial to precisely regulate the carbon flux of the oxaloacetate-phosphoenolpyruvate (OAA-PEP) regulatory node through appropriate pckA expression control, as excessive overexpression of pckA can cause extensive loss of OAA and metabolic imbalance. However, considering the critical impact of pckA on naringenin biosynthesis, the conventional strategy of transcriptional regulation of gene expression is limited in its ability to cover the large and balanced solution space. To overcome this hurdle, in this study, pckA expression was fine-tuned at both the transcriptional and translational levels in a combinatorial expression library for the precise exploration of optimal naringenin production from acetate. Additionally, we identified the effects of regulating pckA expression by validating the correlation between phosphoenolpyruvate kinase (PCK) activity and naringenin production. As a result, the flux-optimized strain exhibited a 49.8-fold increase compared with the unoptimized strain, producing 122.12 mg/L of naringenin. Collectively, this study demonstrated the significance of transcriptional and translational flux rebalancing at the key regulatory node, proposing a pivotal metabolic engineering strategy for the biosynthesis of various flavonoids derived from naringenin using acetate. ONE-SENTENCE SUMMARY: In this study, transcriptional and translational regulation of pckA expression at the crucial regulatory node was conducted to optimize naringenin biosynthesis using acetate in E. coli.

Inhibition of protein-protein interactions using biodegradable depsipeptide nanoassemblies.

Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome. Optimized SdPNs displayed better tumor targeting and PPI inhibition properties than the comparable small molecule inhibitor in vivo. Kinetics of PPI inhibition for SdPNs were gradual and controllable in contrast to the rapid inhibition kinetics of the small molecule. Because SdPN is modular, any appropriate peptide inhibitor can be incorporated into the platform without concern for the poor pharmacokinetic properties of the peptide.

Evaluation of Factors Affecting Illumination Intensity in Lightwand Endotracheal Intubation.

BACKGROUND/AIM: A lightwand is a stylet with a light bulb at its tip that can be used to guide intubation by confirming the illumination through the anterior neck. We aimed to determine the factors affecting the illumination intensity during lightwand endotracheal intubation. PATIENTS AND METHODS: We retrospectively collected data from 180 patients who underwent lightwand endotracheal intubation. We recorded illumination intensity on a 5-point scale. The patients were categorized into weak (score <3) and bright (score ≥3) groups based on the illumination intensity scale score. RESULTS: A total of 176 patients were analyzed, of whom 125 (71.1%) were enrolled in the bright group, and 51 (29.0%) were enrolled in the weak group. Multivariable logistic regression analysis revealed that an increased body mass index (BMI) and mask ventilation grade were associated with light intensity. For mask ventilation, moderate vs. easy (p=0.010) and difficult vs. easy (p=0.008) were associated with the weak group. Receiver operating characteristic curve analysis showed that BMI ≥24.6 kg/m2 was correlated with the weak group. CONCLUSION: BMI ≥24.6 kg/m2 or mask ventilation grade above moderate indicates increased odds of weak illumination intensity in lightwand intubation. Pre-intubation examination of these factors helps increase the chances of successful intubation.

Space microgravity increases expression of genes associated with proliferation and differentiation in human cardiac spheres.

Efficient generation of cardiomyocytes from human-induced pluripotent stem cells (hiPSCs) is important for their application in basic and translational studies. Space microgravity can significantly change cell activities and function. Previously, we reported upregulation of genes associated with cardiac proliferation in cardiac progenitors derived from hiPSCs that were exposed to space microgravity for 3 days. Here we investigated the effect of long-term exposure of hiPSC-cardiac progenitors to space microgravity on global gene expression. Cryopreserved 3D hiPSC-cardiac progenitors were sent to the International Space Station (ISS) and cultured for 3 weeks under ISS microgravity and ISS 1 G conditions. RNA-sequencing analyses revealed upregulation of genes associated with cardiac differentiation, proliferation, and cardiac structure/function and downregulation of genes associated with extracellular matrix regulation in the ISS microgravity cultures compared with the ISS 1 G cultures. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes mapping identified the upregulation of biological processes, molecular function, cellular components, and pathways associated with cell cycle, cardiac differentiation, and cardiac function. Taking together, these results suggest that space microgravity has a beneficial effect on the differentiation and growth of cardiac progenitors.