Discovery of Salidroside as a Novel Non-Coding RNA Modulator to Delay Cellular Senescence and Promote BK-Dependent Apoptosis in Cerebrovascular Smooth Muscle Cells of Simulated Microgravity Rats.

Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts' health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague-Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K+ channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights.

Simulated Microgravity Promotes Angiogenesis through RhoA-Dependent Rearrangement of the Actin Cytoskeleton.

BACKGROUND/AIMS: Microgravity leads to hydrodynamic alterations in the cardiovascular system and is associated with increased angiogenesis, an important aspect of endothelial cell behavior to initiate new vessel growth. Given the critical role of Rho GTPase-dependent cytoskeleton rearrangement in cell migration, small GTPase RhoA might play a potential role in microgravity-induced angiogenesis. METHODS: We examined the organization of actin filaments by FITC-conjugated phalloidin staining, as well as the expression and activity of RhoA by quantitative PCR and Western blot, in human umbilical vein endothelial cells (HUVECs) under normal gravity and simulated microgravity. Effect of simulated microgravity on the wound closure and tube formation in HUVECs, and their dependence on RhoA, were also analyzed by cell migration and tube formation assays. RESULTS: We show that in HUVECs actin filaments are disorganized and RhoA activity is reduced by simulated microgravity. Blocking RhoA activity either by C3 transferase Rho inhibitor or siRNA knockdown mimicked the effect of simulated microgravity on inducing actin filament disassembly, followed by enhanced wound closure and tube formation in HUVECs, which closely resembled effects seen on microgravity-treated cells. In contrast, overexpressing RhoA in microgravity-treated HUVECs restored the actin filaments, and decreased wound closure and tube formation abilities. CONCLUSION: These results suggest that RhoA inactivation is involved in the actin rearrangement-associated angiogenic responses in HUVECs during simulated microgravity.

The Impact of Simulated Weightlessness on Endothelium-Dependent Angiogenesis and the Role of Caveolae/Caveolin-1.

BACKGROUND/AIMS: The potential role of caveolin-1 in modulating angiogenesis in microgravity environment is unexplored. METHODS: Using simulated microgravity by clinostat, we measured the expressions and interactions of caveolin-1 and eNOS in human umbilical vein endothelial cells. RESULTS: We found that decreased caveolin-1 expression is associated with increased expression and phosphorylation levels of eNOS in endothelial cells stimulated by microgravity, which causes a dissociation of eNOS from caveolin-1 complexes. As a result, microgravity induces cell migration and tube formation in endothelial cell in vitro that depends on the regulations of caveolin-1. CONCLUSION: Our study provides insight for the important endothelial functions in altered gravitational environments.

Clinorotation enhances autophagy in vascular endothelial cells.

Individuals exposed to extended periods of spaceflight or prolonged 6° head-down-tilt bed rest often suffer from health hazards represented by cardiovascular deconditioning. Many studies have reported that alterations in vascular endothelial cells contribute to cardiovascular dysfunction induced by microgravity. Autophagy, a lysosomal degradation pathway, serves an adaptive role for survival, differentiation, and development in cellular homeostasis, and can be triggered by various environmental stimuli. However, whether autophagy can be induced in endothelial cells by real or simulated microgravity remains to be determined. This study was designed to investigate the effects of simulated microgravity on the activation of autophagy in human umbilical vein endothelial cells (HUVECs). We report here that clinorotation, a simulated model of microgravity, enhances autophagosome formation, increases LC3 and beclin-1 expression, and promotes the conversion of LC3-I to LC3-II in HUVECs. These results demonstrate that simulated microgravity for 48 h activates autophagy of vascular endothelial cells.

Electroacupuncture improves orthostatic tolerance in healthy individuals via improving cardiac function and activating the sympathetic system.

AIMS: Orthostatic intolerance (OI) is a common clinical problem; however, effective and applicable clinical prevention/treatment is limited. The aim of this study was to investigate whether electroacupuncture (EA) is a novel effective treatment in attenuating OI in healthy individuals. METHODS AND RESULTS: This study used a randomized, controlled, crossover design using two protocols. Orthostatic intolerance was induced with a combination of head-up tilt (HUT) and lower body negative pressure (LBNP). Twenty healthy individuals in Protocol 1 and 10 healthy individuals in Protocol 2 received no EA, EA at PC-6 acupuncture points (acupoint), and EA at a non-acupoint in a random order with an interim of 1 week. Electroacupuncture was administered prior to HUT/LBNP in Protocol 1 and simultaneously during HUT/LBNP in Protocol 2. Electroacupuncture at PC-6 administered either before or during HUT/LBNP postponed the occurrence of pre-syncopal symptoms, improved haemodynamic responses to HUT/LBNP (including increased diastolic blood pressure, stroke volume, and total peripheral resistance and a decreased heart rate), blunted decreases of maximum velocity and velocity time integral of blood flow in the middle cerebral artery, and increased plasma noradrenalin and adrenalin concentrations. In addition, heart rate variability analysis revealed that EA at PC-6 either before or during HUT/LBNP decreased high-frequency ranges of R-R interval while increasing low-frequency ranges of R-R interval, which indicates an elevated heart sympathetic tone. CONCLUSION: Electroacupuncture at PC-6 is effective in improving orthostatic tolerance. Cardiac function improvement and sympathetic activation are responsible for the improved orthostatic tolerance after EA. EA represents a novel intervention against OI.

Stromal Interaction Molecule 1-Mediated Store-Operated Calcium Entry Promotes Autophagy Through AKT/Mammalian Target of Rapamycin Pathway in Hippocampal Neurons After Ischemic Stroke.

The pathophysiological process of neuronal injury due to cerebral ischemia is complex among which disturbance of calcium homeostasis and autophagy are two major pathogenesis. However, it remains ambiguous whether the two factors are independent. Stromal interaction molecule 1 (STIM1) is the most important Ca2+ sensor mediating the store-operated Ca2+ entry (SOCE) through interacting with Orai1 and has recently been proven to participate in autophagy in multiple cells. In this study, we aimed to investigate the potential role of STIM1-induced SOCE on autophagy and whether its regulator function contributes to neuronal injury under hypoxic conditions using in vivo transient middle cerebral artery occlusion (tMCAO) model and in vitro oxygen and glucose deprivation (OGD) primary cultured neuron model respectively. The present data indicated that STIM1 induces autophagic flux impairment in neurons through promoting SOCE and inhibiting AKT/mTOR signaling pathway. Pharmacological inhibition of SOCE or downregulation of STIM1 with siRNA suppressed the autophagic activity in neurons. Moreover, stim1 knockdown attenuated neurological deficits and brain damage after tMCAO, which could be reversed by AKT/mTOR pathway inhibitor AZD5363. Together, the modulation of STIM1 on autophagic activation indicated the potential link between Ca2+ homeostasis and autophagy which provided evidence that STIM1 could be a promising therapeutic target for ischemic stroke.

Differential bone remodeling mechanism in hindlimb unloaded and hibernating Daurian ground squirrels: a comparison between artificial and natural disuse within the same species.

Loss of bone mass can occur in mammals after prolonged disuse but the situation for hibernators that are in a state of torpor for many months of the year is not yet fully understood. The present study assesses the bone remodeling mechanisms present in Daurian ground squirrels (Spermophilus dauricus) during hibernation as compared with a model of hindlimb disuse. Differences in microstructure, mechanical properties, bone remodeling-related proteins (Runx2, OCN, ALP, RANKL, CTK and MMP-9) and key proteins of Wnt/ß-catenin signaling pathway (GSK-3ß and phospho-ß-catenin) were evaluated in ground squirrels under 3 conditions: summer active (SA) vs. hibernation (HIB) vs. hindlimb unloaded (HLU). The results indicated that the body weight in HLU ground squirrels was lower than the SA group, and the middle tibia diameter in the HLU group was lower than that in SA and HIB groups. The thickness of cortical and trabecular bone in femurs from HLU ground squirrels was lower than in SA and HIB groups. Most parameters of the tibia in the HLU group were lower than those in SA and HIB groups, which indicated cortical bone loss in ground squirrels. Moreover, our data showed that the changes in microscopic parameters in the femur were more obvious than those in the tibia in HLU and HIB ground squirrels. The levels of Runx2 and ALP were lower in HLU ground squirrels than SA and HIB groups. The protein levels of OCN were unchanged in the three groups, but the protein levels of ALP were lower in the HLU group than in SA and HIB groups. RANKL, CTK and MMP-9 protein levels were significantly decreased in tibia of HLU ground squirrels as compared with SA and HIB groups. In addition, the protein expression levels of RANKL, CTK and MMP-9 showed no statistical difference between SA and HIB ground squirrels. Thus, the mechanisms involved in the balance between bone formation and resorption in hibernating and hindlimb unloading ground squirrels may be different. The present study showed that in femur, the Wnt signaling pathway was inhibited, the protein level of GSK-3ß was increased, and the protein expression of phospho-ß-catenin was decreased in the HIB group as compared with the SA group, which indicates that the Wnt signaling pathway has a great influence on the femur of the HIB group. In conclusion, the natural anti-osteoporosis properties of Daurian ground squirrels are seasonal. The squirrels do not experience bone loss when they are inactive for a long time during hibernation, but the mechanisms of anti-osteoporosis did not work in HLU summer active squirrels.

Artificial gravity with ergometric exercise can prevent enhancement of popliteal vein compliance due to 4-day head-down bed rest.

Changes of venous compliance may contribute in part to postflight orthostatic intolerance. The purpose of the present study was to determine whether intermittent artificial gravity exposure with ergometric exercise could prevent venous compliance changes in the lower limbs due to simulated weightlessness. Twelve healthy male volunteers were exposed to simulated microgravity for 4 days of head-down bed rest (HDBR). Six subjects were randomly loaded 1.0-2.0 Gz intermittent artificial gravity (at foot level) with 40 W of ergometric workload every day (countermeasure group, CM). The six others served as the control (CON group). Venous compliance was estimated by measuring the corresponding change of cross-sectional area (CSA) of popliteal vein at each minute of various venous occlusion pressure stages. Basal CSA was significantly lower after bed rest in the control group, and preserved in the countermeasure group. The percent increase in the CSA of CON group was significantly greater almost at each minute of various venous cuff pressures after bed rest than before. Compliance of popliteal vein of CON group was significant greater when 40, 60 and 80 mmHg cuff pressure applied after bed rest than before of CON group. In conclusions, a 4-day simulated weightlessness leads to increase of popliteal venous compliance; centrifuge-induced artificial gravity with ergometric exercise can prevent enhancement of popliteal venous compliance due to 4-day head-down tilt bed rest, the effect of the countermeasure on compliance might involve changes in venous filling and changes in venous structure.

Risk stratification in patients with upper gastrointestinal submucosal tumors undergoing submucosal tunnel endoscopic resection.

Background: A substantial heterogeneity exists in patients with upper gastrointestinal submucosal tumors (SMTs). This study aimed to identify predictors of long procedure time (≥60 min), occurrence of procedure-related complications, and long hospital stay (≥6 days) in patients with SMTs undergoing submucosal tunnel endoscopic resection (STER) and stratify risk based on the predictors. Methods: Sixty-six consecutive patients with upper gastrointestinal SMTs undergoing STER between January 2013 and December 2018 were retrospectively included. Binary logistic regression models were developed to identify predictors of outcomes. Receiver operating characteristic (ROC) curves were constructed to evaluate the discrimination of tumor size. Results: Complete resection and en bloc resection of tumor were achieved in 66 (100%) and 64 patients (97%), respectively. Twenty-seven patients (41%) had a long procedure time, 10 (15%) developed STER-related complications, and 17 (26%) had a long hospital stay. On multivariable analysis, tumor size was an independent predictor of long procedure time (OR 1.37, 95% CI 1.13-1.67; p = 0.001), occurrence of complications (OR 1.06, 95% CI 1.01-1.10; p = 0.012), and long hospital stay (OR 1.05, 95% CI 1.01-1.09; p = 0.035). ROC curves identified a tumor of size 25 mm as the best cutoff; those who had a tumor above this value had a 76-fold risk of long procedure time, 8.56-fold risk of occurrence of complications, and 6.35-fold risk of long hospital stay. Conclusion: Patients with a tumor size ≥25 mm had longer procedure time, higher risk of STER-related complications, and longer hospital stay; therefore, they should be classified as a high-risk group.

Sequential oxygen supply system promotes peripheral nerve regeneration by enhancing Schwann cells survival and angiogenesis.

Local hypoxia in cellular grafts remains a challenge during the repair of peripheral nerve injury. Oxygen carriers (perfluorotributylamine, PFTBA) have been shown to provide oxygen to Schwann cells (SCs) for a short period. However, the limited oxygen supply from oxygen-carrying materials hinders the ability of such systems to counteract hypoxia over an extended period and limits their therapeutic potential. In this study, PFTBA/VEGF core-shell fibers were fabricated through coaxial electrospinning to construct an oxygen supply system that can sequentially provide oxygen, first via the oxygen carrier and subsequently by promoting angiogenesis via VEGF. Then, the oxygen release and proangiogenic effects of the PFTBA/VEGF core-shell fibers were examined in vitro. Furthermore, sequential oxygen supply conduits prepared using the fibers and filled with SCs were used to bridge 15-mm-long sciatic nerve defects in rats. The PFTBA-VEGF system was confirmed to protect SCs from hypoxia and promote angiogenesis in vitro. Subsequent in vivo studies showed that after the oxygen carried by PFTBA was exhausted, the VEGF could induce neovascularization, and the nascent blood vessels acted as sequential oxygen suppliers for SCs during nerve regeneration. In addition, rats transplanted with the sequential oxygen supply system showed significant morphological and functional improvements in axonal regeneration, the sciatic function index, and the muscle wet weight ratio. The final functional outcomes were similar after treatment with the sequential oxygen supply conduits and autografts. Western blots revealed that the VEGF in the system could upregulate p-AMPK, contributing to axon regeneration after sciatic nerve injury. The sequential oxygen supply system offers essential insights into the oxygen regulation of biomaterials and highlights the potential of oxygen supply strategies as therapeutic approaches for repairing defects in peripheral nerves and other aerobic tissues.

Focal adhesion kinase signaling pathway is involved in mechanotransduction in MG-63 cells.

Interstitial fluid flow, generated upon induced movement of extracellular fluid after mechanical loading, activates many signal transduction pathways in bone cells. The mechanisms of mechanobiology in bone tissue are still not clearly understood. Recently focal adhesion kinase (FAK) was shown to be involved in mechanotransduction in a number of cells. This study was designed to characterize the functional roles of FAK in mediating osteoblast response to mechanical steady-state fluid shear stress (FSS). We reported here that FSS (15 dynes/cm(2)) induced activation of FAK and formation of FAK·Grb2·Sos ternary complex in MG-63 cells, which was necessary for activation of the downstream mitogen-activated protein kinase pathway signaling molecules extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Our results also showed that transfection of FAK (F397Y) plasmid, a negative mutant of FAK, blocked the increased expression of binding factor alpha 1, osterix, osteocalcin and alkaline phosphatase induced by FSS in MG-63 cells. These results demonstrate that FAK signaling is critical for FSS-induced activation of ERK and JNK, and for promotion of osteoblast differentiation and osteogenesis via its association with Grb2/Sos complex.

Artificial gravity with ergometric exercise preserves the cardiac, but not cerebrovascular, functions during 4 days of head-down bed rest.

Cardiovascular and musculoskeletal deconditioning occurring in long-term spaceflight requires new strategies to counteract these adverse effects. We previously reported that a short-arm centrifuge produced artificial gravity (AG), together with ergometer, has an approving effect on promoting cardiovascular function. The current study sought to investigate whether the cardiac and cerebrovascular functions were maintained and improved using a strategy of AG combined with exercise training on cardiovascular function during 4-day head-down bed rest (HDBR). Twelve healthy male subjects were assigned to a control group (CONT, n=6) and an AG combined with ergometric exercise training group (CM, n=6). Simultaneously, cardiac pumping and systolic functions, cerebral blood flow were measured before, during, and after HDBR. The results showed that AG combined with ergometric exercise caused an increase trend of number of tolerance, however, there was no significant difference between the two groups. After 4-day HDBR in the CONT group, heart rate increased significantly (59±6 vs 66±7 beats/min), while stroke volume (98±12 vs 68±13 mL) and cardiac output (6±1 vs 4±1 L/min) decreased significantly (p<0.05). All subjects had similar drops on cerebral vascular function. Volume regulating hormone aldosterone increased in both groups (by 119.9% in CONT group and 112.8% in the CM group), but only in the CONT group there were a significant changes (p<0.05). Angiotensin II was significantly increased by 140.5% after 4-day HDBR in the CONT group (p<0.05), while no significant changes were observed in the CM group. These results indicated that artificial gravity with ergometric exercise successfully eliminated changes induced by simulated weightlessness in heart rate, volume regulating hormones, and cardiac pumping function and partially maintained cardiac systolic function. Hence, a daily 1h alternating +1.0 and +2.0 Gz with 40 W exercise training appear to be an effective countermeasure against cardiac deconditioning.

Artificial gravity with ergometric exercise as a countermeasure against cardiovascular deconditioning during 4 days of head-down bed rest in humans.

We have shown previously that combined short-arm centrifuge and aerobic exercise training preserved several physiologically important cardiovascular functions in humans. We hypothesized that artificial gravity (AG) and exercise is effective to prevent changes of physical problems during head-down bed rest (HDBR). To test this hypothesis, 12 healthy male subjects had undergone 4 days of 6° HDBR. Six of them were exposed to AG of an alternating 2-min intervals of +1.0 and +2.0 Gz at foot level for 30 min twice per day with ergometric exercise of 40 W as a countermeasure during bed rest (CM group), while the remaining six served as untreated controls (no-CM group). Before and after 4 days of bed rest, leg venous hemodynamics was assessed by venous occlusion plethysmography and autonomic cardiovascular control estimated by power spectral analysis of blood pressure and heart rate. Further, orthostatic tolerance was evaluated by a 75° head-up tilt test and physical working capacity was surveyed by near maximal physical working capacity test before and after bed rest. The data showed that combined centrifuge and exercise applied twice daily for a total of 60 min during 4 days of HDBR prevented (a) a decrease in working capacity, (b) autonomic dysfunction (a decrease in the activity of parasympathetic cardiac innervation) and (c) an increase in leg venous flow resistance. The combination of a 30 min alternating of +1.0 and +2.0 Gz for twice per day of AG with 40 W ergometric exercise may offer a promising countermeasure to short duration simulated microgravity.

Novel Natural Inhibitors Targeting Enhancer of Zeste Homolog 2: A Comprehensive Structural Biology Research.

The enhancer of zeste homolog 2 (EZH2) is a methylated modification enzyme of Histone H3-Lys 27. The high expression of EZH2 in cells is closely related to the progression, invasion, and metastasis of neoplasm. Therefore, this target is gradually becoming one of the research hot spots of tumor pathogenesis, and the inhibitors of the EZH2 enzyme are expected to become new antitumor drugs. This study used a series of virtual screening technologies to calculate the affinity between the compounds obtained from the ZINC15 database and the target protein EZH2, the stability of the ligand-receptor complex. This experiment also predicted the toxicity and absorption, distribution, metabolism, and excretion (ADME) properties of the candidate drugs in order to obtain compounds with excellent pharmacological properties. Finally, the ligand-receptor complex under in vivo situation was estimated by molecular dynamics simulation to observe whether the complex could exist steadily in the body. The experimental results showed that the two natural compounds ZINC000004217536 and ZINC000003938642 could bind tightly to EZH2, and the ligand-receptor complex could exist stably in vivo. Moreover, these two compounds were calculated to be nontoxic. They also had a high degree of intestinal absorption and high bioavailability. In vitro experiments confirmed that drug ZINC000003938642 could inhibit the proliferation and migration of osteosarcoma, which could serve as potential lead compounds. Therefore, the discovery of these two natural products had broad prospects in the development of EZH2 inhibitors, providing new clues for the treatment or adjuvant treatment of tumors.

Antidepressant Effect of Paeoniflorin Is Through Inhibiting Pyroptosis CASP-11/GSDMD Pathway.

Nod-like receptor protein 3 (NLRP3)-associated neuroinflammation mediated by activated microglia is involved in the pathogenesis of depression. The role of the pore-forming protein gasdermin D (GSDMD), a newly identified pyroptosis executioner downstream of NLRP3 inflammasome mediating inflammatory programmed cell death, in depression has not been well defined. Here, we provide evidence that paeoniflorin (PF), a monoterpene glycoside compound derived from Paeonia lactiflora, ameliorated reserpine-induced mouse depression-like behaviors, characterized as increased mobility time in tail suspension test and forced swimming test, as well as the abnormal alteration of synaptic plasticity in the depressive hippocampus. The molecular docking simulation predicted that PF would interact with C-terminus of GSDMD. We further demonstrated that PF administration inhibited the enhanced expression of GSDMD which mainly distributed in microglia, along with the proteins involved in pyroptosis signaling transduction including caspase (CASP)-11, CASP-1, NLRP3, and interleukin (IL)-1ß in the hippocampus of mice treated with reserpine. And also, PF prevented lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced pyroptosis in murine N9 microglia in vitro, evidenced by inhibiting the expression of CASP-11, NLRP3, CASP-1 cleavage, as well as IL-1ß. Furthermore, VX-765, an effective and selective inhibitor for CASP-1 activation, reduced the expression of inflammasome and pyroptosis-associated proteins in over-activated N9 and also facilitated PF-mediated inhibition of pyroptosis synergistically. Collectively, the data indicated that PF exerted antidepressant effects, alleviating neuroinflammation through inhibiting CASP-11-dependent pyroptosis signaling transduction induced by over-activated microglia in the hippocampus of mice treated with reserpine. Thus, GSDMD-mediated pyroptosis in activated microglia is a previously unrecognized inflammatory mechanism of depression and represents a unique therapeutic opportunity for mitigating depression given PF administration.

Combined short-arm centrifuge and aerobic exercise training improves cardiovascular function and physical working capacity in humans.

BACKGROUND: Musculoskeletal and cardiovascular deconditioning occurring in long-term spaceflight gives rise to the needs to develop new strategies to counteract these adverse effects. Short-arm centrifuge combined with ergometer has been proposed as a strategy to counteract adverse effects of microgravity. This study sought to investigate whether the combination of short-arm centrifuge and aerobic exercise training have advantages over short-arm centrifuge or aerobic exercise training alone. MATERIAL/METHODS: One week training was conducted by 24 healthy men. They were randomly divided into 3 groups: (1) short-arm centrifuge training, (2) aerobic exercise training, 40 W, and (3) combined short-arm centrifuge and aerobic exercise training. Before and after training, the cardiac pump function represented by stroke volume, cardiac output, left ventricular ejection time, and total peripheral resistance was evaluated. Variability of heart rate and systolic blood pressure were determined by spectral analysis. Physical working capacity was surveyed by near maximal physical working capacity test. RESULTS: The 1-week combined short-arm centrifuge and aerobic exercise training remarkably ameliorated the cardiac pump function and enhanced vasomotor sympathetic nerve modulation and improved physical working capacity by 10.9% (P<.05, n=8). In contrast, neither the short-arm centrifuge nor the aerobic exercise group showed improvements in these functions. CONCLUSIONS: These results demonstrate that combined short-arm centrifuge and aerobic exercise training has advantages over short-arm centrifuge or aerobic exercise training alone in influencing several physiologically important cardiovascular functions in humans. The combination of short-arm centrifuge and aerobic exercise offers a promising countermeasure to microgravity.

Dual-Modal Photon Upconverting and Downshifting Emissions from Ultra-stable CsPbBr3 Perovskite Nanocrystals Triggered by Co-Growth of Tm:NaYbF4 Nanocrystals in Glass.

This work reports a novel dual-phase glass containing Tm:NaYbF4 upconverting nanocrystals (UCNCs) and CsPbBr3 perovskite nanocrystals (PNCs). The advantages of this kind of nanocomposite are that it provides a solid inorganic glass host for the in situ co-growth of UCNCs and PNCs, and protects PNCs against decomposition affected by the external environment. Tm:NaYbF4 NC-sensitized stable CsPbBr3 PNCs photon UC emission in PNCs is achieved under the irradiation of a 980 nm near-infrared (NIR) laser, and the mechanism is evidenced to be radiative energy transfer (ET) from Tm3+: 1G4 state to PNCs rather than nonradiative Förster resonance ET. Consequently, the decay lifetime of exciton recombination is remarkably lengthened from intrinsic nanoseconds to milliseconds since carriers in PNCs are fed from the long-lifetime Tm3+ intermediate state. Under the simultaneous excitation of the ultraviolet (UV) light and NIR laser, dual-modal photon UC and downshifting (DS) emissions from ultra-stable CsPbBr3 PNCs in the glass are observed, and the combined UC/DS emitting color can be easily altered by modifying the pumping light power. In addition, UC exciton recombination and Tm3+ 4f-4f transitions are found to be highly temperature sensitive. All these unique emissive features enable the practical applications of the developed dual-phase glass in advanced anti-counterfeit and accurate temperature detection.

Promoting photoluminescence quantum yields of glass-stabilized CsPbX3 (X = Cl, Br, I) perovskite quantum dots through fluorine doping.

In the last few years, all-inorganic cesium lead halide (CsPbX3) quantum dots have shown unprecedented radical progress for practical applications in the optoelectronic field, but they quickly decompose when exposed to air. The in situ growth of the CsPbX3 particles inside amorphous glass can significantly improve their stability. Unfortunately, it is formidably difficult to precipitate whole-family CsPbX3 from a glass matrix and their photoluminescence quantum yields require further improvement. Herein, fluoride additives were introduced into oxyhalide borosilicate glasses to break the tight glass network, which promoted the nucleation/growth of CsPbX3 (X = Cl, Cl/Br, Br, Br/I and I) inside the glass. Importantly, the quantum efficiencies of glass-stabilized CsPbBr3, CsPb(Br/I)3 and CsPbI3 reached 80%, 60% and 50%, respectively, which are the highest efficiencies reported so far. Benefiting from the effective protection of robust glass, CsPbX3 quantum dots exhibited superior water resistance with more than 90% luminescence remaining after immersing them in water for 30 days, and halogen anion exchange among different CsPbX3 materials was completely inhibited. Two prototype light-emitting diodes were constructed by coupling green/red and green/orange/red quantum dots with InGaN blue chips, yielding bright white light with optimal luminous efficiency of 93 lm W-1, tunable color temperature of 2000-5800 K and high color rendering index of 90.

Effect of thigh cuffs on haemodynamic changes of the middle cerebral artery and on orthostatic intolerance induced by 10 days head-down bed rest.

Thigh cuffs are used by cosmonauts to limit fluid shift during space flight, but the appropriate level of cuff pressure and the duration of application to optimize their beneficial effects require further detailed investigations. In the present study, 10 days head-down tilt (HDT) bed rest was performed to assess the effects of thigh cuffs (40 mmHg, 10 h/day) on haemodynamic changes of the middle cerebral artery (MCA) and on orthostatic tolerance in six healthy male volunteers. Another six healthy male volunteers without thigh cuffs served as the control group. Haemodynamic parameters of the MCA were measured using transcranial Doppler. Orthostatic tolerance was assessed before and after HDT. After HDT, the mean upright time in the control and thigh cuff groups was 14.0 +/- 4.1 and 19.2 +/- 0.7 min, respectively. Compared with values before HDT, the percentage increase in heart rate from baseline in the upright position after HDT was significantly higher in the control group and the percentage change from baseline of mean diastolic arterial blood decreased more after HDT in this group. In the control group, systolic blood velocity (Vs) and mean blood velocity (Vm) of the right MCA decreased significantly during HDT. In the thigh cuffs group, the Vs of the right MCA decreased significantly on Days 3 and 7 of HDT and the Vm of the right MCA decreased significantly on Day 7 of HDT. The results indicate that daily use of thigh cuffs during 10 days of HDT does not completely prevent the decrease in haemodynamics of the right MCA, but is effective in preventing orthostatic intolerance.

Moderate exercise based on artificial gravity preserves orthostatic tolerance and exercise capacity during short-term head-down bed rest.

Numerous countermeasures have been proposed to minimize microgravity-induced physical deconditioning, but their benefits are limited. The present study aimed to investigate whether personalized aerobic exercise based on artificial gravity (AG) mitigates multisystem physical deconditioning. Fourteen men were assigned to the control group (n=6) and the countermeasure group (CM, n=8). Subjects in the CM group were exposed to AG (2 Gz at foot level) for 30 min twice daily, during which time cycling exercise of 80-95 % anaerobic threshold (AT) intensity was undertaken. Orthostatic tolerance (OT), exercise tests, and blood assays were determined before and after 4 days head-down bed rest (HDBR). Cardiac systolic function was measured every day. After HDBR, OT decreased to 50.9 % and 77.5 % of pre-HDBR values in control and CM groups, respectively. Exercise endurance, maximal oxygen consumption, and AT decreased to 96.5 %, 91.5 % and 91.8 % of pre-HDBR values, respectively, in the control group. Nevertheless, there were slight changes in the CM group. HDBR increased heart rate, sympathetic activity, and the pre-ejection period, but decreased plasma volume, parasympathetic activity and left-ventricular ejection time in the control group, whereas these effects were eliminated in the CM group. Aldosterone had no change in the control group but increased significantly in the CM group. Our study shows that 80-95 % AT aerobic exercise based on 2 Gz of AG preserves OT and exercise endurance, and affects body fluid regulation during short-term HDBR. The underlying mechanisms might involve maintained cardiac systolic function, preserved plasma volume, and improved sympathetic responses to orthostatic stress.