Effects of long-term simulated microgravity on liver metabolism in rhesus macaques.

The liver is an essential multifunctional organ and constantly communicates with nearly all the tissues in the body. Spaceflight or simulated microgravity has a significant impact on the livers of rodent models, including lipid accumulation and inflammatory cell infiltration. Whether similar liver lipotoxicity could occur in humans is not known, even though altered circulating cholesterol profile has been reported in astronauts. Using a 42-day head-down bed rest (HDBR) model in rhesus macaques, the present study investigated whether simulated microgravity alters the liver of non-human primates at the transcriptome and metabolome levels. Its association with stress and intestinal changes was also explored. Compared to the controls, the HDBR monkeys showed mild liver injury, elevated ANGPTL3 level in the plasma, and accumulation of fat vacuoles and inflammatory cells in the liver. Altered transcriptome signatures with up-regulation of genes in lipid metabolisms and down-regulation of genes in innate immune defense were also found in HDBR group-derived liver samples. The metabolic profiling of the liver revealed mildly disturbed fatty acid metabolism in the liver of HDBR monkeys. The intestinal dysbiosis, its associated endotoxemia and changes in the composition of bile acids, and elevated stress hormone in HDBR monkeys may contribute to the altered lipid metabolisms in the liver. These data indicate that liver metabolic functions and gut-liver axis should be closely monitored in prolonged spaceflight to facilitate strategy design to improve and maintain metabolic homeostasis.

Multi-cation hybrid stannic oxide electron transport layer for high-efficiency perovskite solar cells.

The performance of perovskite solar cells (PSCs) can be improved by optimizing the perovskite film quality and electron transfer layers (ETLs). In this study, high-efficient PSCs with multi-cation hybrid electron transport layer (SnO2@Na:Cs ETL) were fabricated using continuous spin-coating. Compared to the pristine SnO2, the power conversion efficiency (PCE) of device based on SnO2@Na:Cs ETL have reached 22.06% (with an open circuit voltage of 1.13 V), up approximately 21%. The photovoltaic performance of the device is enhanced due to the increase in the transmission rate, electrical conductivity, electron mobility and surface state owing to the multi-cation hybrid. In addition, because SnO2@Na:Cs ETL can significantly improve interface contact with the perovskite film and improve its crystallinity, the transport defect state and carrier transport efficiency are significantly improved at the ETL/Perovskite interface. Therefore, the open circuit voltage (Voc) and fill factor (FF) of PSCs was significantly increased. The application of SnO2@Na:Cs ETL provides a simple and efficient method to obtain highly-efficient PSCs.

Interface Regulation by an Ultrathin Wide-Bandgap Halide for Stable and Efficient Inverted Perovskite Solar Cells.

The nonradiative recombination between hole transport layers (HTLs) and perovskites generally leads to obvious energy losses. The trap states at the HTL/perovskite interface directly influence the improvement of the power conversion efficiency (PCE) and stability. Interface regulation is a simple and commonly used method to decrease nonradiative recombination in inverted perovskite solar cells (PSCs). Here, a wide-bandgap halide was used to regulate the PTAA/MAPbI3 interface, in which n-hexyltrimethylammonium bromide (HTAB) was used to modify the upper surface of poly[bis(4-phenyl)-(2,4,6-trimethylphenyl)amine] (PTAA). Upon introduction of the HTAB layer, the contact between PTAA and MAPbI3 is strengthened, the defect state density in PSCs is reduced, the MAPbI3 crystallinity is improved, and the nonradiative recombination loss is suppressed. The device with HTAB delivers the highest PCE of 21.01% with negligible hysteresis, which is significantly higher than that of the control device (17.71%), and it maintains approximately 87% of its initial PCE for 1000 h without encapsulation in air with a relative humidity of 25 ± 5%. This work reveals an effective way of using a wide-bandgap halide to regulate the PTAA/MAPbI3 interface to simultaneously promote the PCE and stability of PSCs.

High-efficiency planar heterojunction perovskite solar cell produced by using 4-morpholine ethane sulfonic acid sodium salt doped SnO2.

Perovskite solar cells (PSCs) have become a promising photovoltaic (PV) technology. Meanwhile, developing an electron transport layer (ETL) has been an effective way to promote the power conversion efficiency (PCE) of PSCs. Here, a 4-morpholine ethane sulfonic acid sodium salt (MES Na+) doped SnO2 ETL is utilized in planar heterojunction PSCs. The results show that the MES Na+ doped ETL can improve the crystallinity, and absorbance of perovskite films, and passivate interface defects between the perovskite film and SnO2 ETL. The doping effect accounts for the enhancement of conductivity and the decreasing work function of SnO2. When 10 mg mL-1 MES Na+ was added to the SnO2 precursor solution, the device showed the best performance Jsc, Voc, and FF of the PSCs values, which were 23.88 mA cm-2, 1.12 V and 78.69%, respectively, and the PCE was increased from 17.43% to 21.05%. This doping ETL strategy provides an avenue for defect passivation to further increase the efficiency of perovskite solar cells.

Blocking the death checkpoint protein TRAIL improves cardiac function after myocardial infarction in monkeys, pigs, and rats.

Myocardial infarction (MI) is a leading cause of death worldwide for which there is no cure. Although cardiac cell death is a well-recognized pathological mechanism of MI, therapeutic blockade of cell death to treat MI is not straightforward. Death receptor 5 (DR5) and its ligand TRAIL [tumor necrosis factor (TNF)-related apoptosis-inducing ligand] are up-regulated in MI, but their roles in pathological remodeling are unknown. Here, we report that blocking TRAIL with a soluble DR5 immunoglobulin fusion protein diminished MI by preventing cardiac cell death and inflammation in rats, pigs, and monkeys. Mechanistically, TRAIL induced the death of cardiomyocytes and recruited and activated leukocytes, directly and indirectly causing cardiac injury. Transcriptome profiling revealed increased expression of inflammatory cytokines in infarcted heart tissue, which was markedly reduced by TRAIL blockade. Together, our findings indicate that TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic strategy for treating MI.

Interface passivation and electron transport improvement via employing calcium fluoride for polymer solar cells.

To enhance the performance of inverted structure polymer solar cells (PSCs), interfacial engineering considered as an effective and straightforward method was employed. In this study, to overcome the surface traps and energy level mismatches of the electron transport layer, a means of interface passivation by evaporating an ultrathin CaF2 layer above ZnO thin film as the electron transport layer was successfully adopted. We display that CaF2 layer could passivate the surface traps of ZnO thin film and decrease the interfacial barrier between PC61BM and ZnO, so that electron transfer efficiency is facilitated, the recombination of electrons and holes is inhibited at the contact interface, and the series resistance is reduced. After the introduction of the CaF2 layer, the short-circuit current and the fill factor was greatly improved, also the power conversion efficiency (PCE) was increased from 3.21% of the reference device without the CaF2 layer to 4.22% in the inverted PSCs based on P3HT:PC61BM bulk heterojunction photoactive layer. These results could have special guiding significance for high-efficiency PSCs and also great potential for applications of photovoltaic devices in the future.

Highly stable hole-conductor-free perovskite solar cells based upon ammonium chloride and a carbon electrode.

Organic-inorganic hybrid perovskite solar cells (PSCs) have become a research hotspot due to the impressive photovoltaic performance. The perovskite film plays an extremely important role in the light-to-electricity conversion, meanwhile, the stability of PSCs is also an important factor affecting the application of devices. Here we demonstrate a kind of stable PSCs by using simple solution-process in an air enviroment with about 45% relative humidity. Firstly, the NH4Cl was added to the perovskite precursor solution to adjust the kinetics of crystallization and growth of active layer, and then obtain high-quality CH3NH3PbI3 perovskite films. Hydrophobic carbon electrode was used to protect the perovskite active layers and further improve the stability of PSCs, which optimized the structure of the devices at the same time. We adjusted the amount of NH4Cl in the perovskite precursor solution (PbI2: CH3NH3I: NH4Cl = 1: 1: x (x = 0 ∼ 1), and investigated the effect of that on the properties of perovskite active layers and PSCs. The above results showed that the devices achieved fully covered perovskite thin films and improved the photovoltaic performance of PSCs when the NH4Cl additive was x  = 0.8. The short-circuit current density (Jsc), fill factor (FF) and power conversion efficiency (PCE) were significantly enhenced. Under the condition of ambient air and no encapsulation, the PSCs exhibited good stability after 576 h test, and the PCE was still about 96% of the initial efficiency.

[Soluble Uric Acid Activates NLRP3 Inflammasome in Myocardial Cells Through Down-regulating UCP2].

OBJECTIVE: To determine the H9C2 cell damage and NLRP3 inflammasome activation trigged by soluble uric acid (UA). METHODS: H9C2 cells were treated with UA. The cellular damage was examined after 12 h, 24 h and 48 h of treatment using MTS and lactic dehydrogenase (LDH). The apoptosis of H9C2 cells was analyzed by flow cytometry (FCM). NLRP3 inflammasome activation was reflected by the protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase-1 detected by Western blot. The mitochondria and cytoplasm were separated and the release of cytochrome C was detected by Western blot to analyze the damage of mitochondria. The impacts of NAC, a ROS inhibitor, on the cell viability and NLRP3 inflammasome activation were analyzed. The expression of UCP2 was detected by Western blot and immunofluorescence (IF). RESULTS: Dose response and time dependent effects of UA on cellular damage and cell apoptosis was observed. UA up-regulated the expression of NLRP3 inflammasome-related molecules. UA damaged the mitochondria. NAC improved the cell viability and inhibited NLRP3 inflammasome activation. UA down-regulated the expression of UCP2. CONCLUSION: Soluble UA can down-regulate the expression of UCP2, damage the mitochondria and activate NLRP3 inflammasome, resulting in cellular damage of H9C2 cells.

Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation.

Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome is closely associated with intestinal inflammation because of its ability to increase IL-1ß secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sodium sulfate (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index, shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1ß secretion and NLRP3 inflammasome activation in colon samples and RAW 264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the Toll-like receptor 4/NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC. NEW & NOTEWORTHY Here, we identify a new role for growth differentiation factor 11 (GDF11), which ameliorates dextran sodium sulfate-induced acute colitis. Meanwhile, we discover a new phenomenon of GDF11 inhibiting IL-1ß secretion and Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome activation. These findings reveal that GDF11 is a new potential candidate for the treatment of ulcerative colitis patients with a hyperactive NLRP3 inflammasome.

Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP3 inflammasome activation.

NLRP3 inflammasome activation plays an important role in diabetic cardiomyopathy (DCM), which may relate to excessive production of reactive oxygen species (ROS). Gypenosides (Gps), the major ingredients of Gynostemma pentaphylla (Thunb.) Makino, have exerted the properties of anti-hyperglycaemia and anti-inflammation, but whether Gps improve myocardial damage and the mechanism remains unclear. Here, we found that high glucose (HG) induced myocardial damage by activating the NLRP3 inflammasome and then promoting IL-1ß and IL-18 secretion in H9C2 cells and NRVMs. Meanwhile, HG elevated the production of ROS, which was vital to NLRP3 inflammasome activation. Moreover, the ROS activated the NLRP3 inflammasome mainly by cytochrome c influx into the cytoplasm and binding to NLRP3. Inhibition of ROS and cytochrome c dramatically down-regulated NLRP3 inflammasome activation and improved the cardiomyocyte damage induced by HG, which was also detected in cells treated by Gps. Furthermore, Gps also reduced the levels of the C-reactive proteins (CRPs), IL-1ß and IL-18, inhibited NLRP3 inflammasome activation and consequently improved myocardial damage in vivo. These findings provide a mechanism that ROS induced by HG activates the NLRP3 inflammasome by cytochrome c binding to NLRP3 and that Gps may be potential and effective drugs for DCM via the inhibition of ROS-mediated NLRP3 inflammasome activation.