Laboratory evidence of Weibel magnetogenesis driven by temperature gradient using three-dimensional synchronous proton radiography.

The origin of the cosmic magnetic field remains an unsolved mystery, relying not only on specific dynamo processes but also on the seed field to be amplified. Recently, the diffuse radio emission and Faraday rotation observations reveal that there has been a microgauss-level magnetic field in intracluster medium in the early universe, which places strong constraints on the strength of the initial field and implies the underlying kinetic effects; the commonly believed Biermann battery can only provide extremely weak seed of 10-21 G. Here, we present evidence for the spontaneous Weibel-type magnetogenesis in laser-produced weakly collisional plasma with the three-dimensional synchronous proton radiography, where the distribution anisotropy directly arises from the temperature gradient, even without the commonly considered interpenetrating plasmas or shear flows. This field can achieve sufficient strength and is sensitive to Coulomb collision. Our results demonstrate the importance of kinetics in magnetogenesis in weakly collisional astrophysical scenarios.

Exploring personalized treatment for cardiac graft rejection based on a four-archetype analysis model and bioinformatics analysis.

Heart transplantation is the gold standard for treating patients with advanced heart failure. Although improvements in immunosuppressive therapies have significantly reduced the frequency of cardiac graft rejection, the incidences of T cell-mediated rejection (TCMR) and antibody-mediated rejection remain almost unchanged. A four-archetype analysis (4AA) model, developed by Philip F. Halloran, illustrated this problem well. It provided a new dimension to improve the accuracy of diagnoses and an independent system for recalibrating the histology guidelines. However, this model was based on the invasive method of endocardial biopsy, which undoubtedly increased the postoperative risk of heart transplant patients. Currently, little is known regarding the associated genes and specific functions of the different phenotypes. We performed bioinformatics analysis (using machine-learning methods and the WGCNA algorithm) to screen for hub-specific genes related to different phenotypes, based Gene Expression Omnibus accession number GSE124897. More immune cell infiltration was observed with the ABMR, TCMR, and injury phenotypes than with the stable phenotype. Hub-specific genes for each of the four archetypes were verified successfully using an external test set (accession number GSE2596). Logistic-regression models based on TCMR-specific hub genes and common hub genes were constructed with accurate diagnostic utility (area under the curve > 0.95). RELA, NFKB1, and SOX14 were identified as transcription factors important for TCMR/injury phenotypes and common genes, respectively. Additionally, 11 Food and Drug Administration-approved drugs were chosen from the DrugBank Database for each four-archetype model. Tyrosine kinase inhibitors may be a promising new option for transplant rejection treatment. KRAS signaling in cardiac transplant rejection is worth further investigation. Our results showed that heart transplant rejection subtypes can be accurately diagnosed by detecting expression of the corresponding specific genes, thereby enabling precise treatment or medication.

Experimental confirmation of driving pressure boosting and smoothing for hybrid-drive inertial fusion at the 100-kJ laser facility.

In laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43-50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6-4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8-4.0 and 3.5-3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured.

Target Density Effects on Charge Transfer of Laser-Accelerated Carbon Ions in Dense Plasma.

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2 mg/cm^{3} density and 1 mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17 eV and n_{e}=4×10^{20} cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.

NONO regulates multiple cytokine production in sepsis via the ERK1/2 signaling pathway.

The massive release of pro-inflammatory cytokines is a crucial step in triggering the inflammatory cascade in sepsis. Exploring the key molecules regulating the expression and release of multiple cytokines has important value for revealing the mechanism of the cytokine storm in sepsis. This study aimed to investigate the role of multifunctional nuclear protein non-POU domain containing octamer-binding protein (NONO) in the sepsis cytokine storm and to elucidate the underlying mechanism. We found that NONO expression in tissues and cells of sepsis mice was significantly upregulated. Downregulation of NONO expression inhibited the mRNA expression of multiple cytokines, including IL-6, IL-1ß, MCP-1, MIP-1α, and MIP-1ß in inflammatory cells from mice and human leukemic monocyte-THP1 cells challenged with lipopolysaccharide (LPS), and significantly decreased the level of these cytokines and TNF-α in the supernatant of THP1 cells challenged by LPS. Nono knockout also reduced the levels of TNF-α, IL-6, MIP-1α, and MIP-1ß in serum, alleviated hepatocyte edema, and improved the survival rate of sepsis mice. Reduced NONO expression decreased the phospho-ERK1/2 level in inflammatory cells from sepsis mice or THP1 cells challenged by LPS. Phospho-ERK1/2 inhibitor decreased the mRNA expression and concentration of cytokines in the culture supernatant of LPS-induced THP1 cells, similar to the effect of NONO knockdown. After LPS challenge, the levels of phospho-ERK1/2 and NONO were increased, with obvious colocalization in the nucleus and vesicular-like organelles in macrophages. NONO knockdown decreased nuclear translocation of phospho-ERK1/2 in LPS-challenged THP1 cells. These results suggest that NONO is a potentially critical molecule involved in multiple cytokine production in sepsis. Upregulated NONO in sepsis may promote the expression and release of multiple cytokines to participate in a sepsis cytokine storm by promoting ERK1/2 phosphorylation.

Effect of tea polyphenols supplement on growth performance, antioxidation, and gut microbiota in squabs.

Early life nutritional supplementation can significantly improve pigeon health. Both the nutritional crops of parental pigeons and the intestinal development of squabs play key roles in the growth rate of squabs. Tea polyphenols (TPs), as natural plant extracts, exhibit potential biological activities. However, the impact of TPs on the intestinal function of squabs is not known. This study evaluated the effects of TPs on growth performance, immunity, antioxidation, and intestinal function in squabs. A total of 432 young pigeons (1 day old) were divided into four groups: a control group (fed a basic diet) and three treatment groups (low, medium, and high dose groups; 100, 200, and 400 mg/kg TPs, respectively). On the 28th day, samples of serum, mucosal tissue, and digests from the ileum of squabs were collected for analysis. The results revealed that TP supplementation significantly reduced the feed-to-meat ratio and improved the feed utilization rate and serum biochemical indices in squabs. Additionally, it enhanced the intestinal barrier function of birds by promoting intestinal development and integrity of tight junctions and regulating digestive enzyme activities and intestinal flora. Mechanistically, TPs activated the Nrf2-ARE signaling pathway, which may be associated with improved antioxidant and immune responses, correlating with an increased abundance of Candida arthritis and Corynebacterium in the ileum.

Excretion of Amyloid-ß in the Gastrointestinal Tract and Regulation by the Gut Microbiota.

BACKGROUND: Amyloid-ß (Aß) is important in the etiology of Alzheimer's disease (AD). Removal of Aß from the brain is a major strategy for the prevention and treatment of AD. OBJECTIVE: To clarify whether Aß42 can be cleared by intestinal excretion and whether the gut microbiota (GM) can affect the excretory clearance of Aß42 in the peripheral blood and intestines. METHODS: Male 8-month-old C57BL6 mice were maintained on either normal chow or received broad-spectrum antibiotics in their drinking water for one week. Sterile saline, fluorescein isothiocyanate (FITC), or FITC-Aß42 (fluorescein isothiocyanate-labeled amyloid-ß42 peptides) was injected 1 h before sampling. Related changes of Aß42 before and after injection were evaluated. RESULTS: FITC-Aß42 was injected into mice through the tail vein and could later be detected in feces. Furthermore, the fecal concentrations of FITC-Aß42 were higher in mice that had been fed antibiotics to alter their GM than in normal mice. However, the FITC-Aß42 concentrations in blood showed the opposite pattern. CONCLUSION: Aß42 can be excreted into the intestinal lumen and is regulated by the GM.

AMP-activated protein kinase α2 contributes to acute and chronic hyperuricemic nephropathy via renal urate deposition in a mouse model.

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney.

The Navigation of Mobile Robot in the Indoor Dynamic Unknown Environment Based on Decision Tree Algorithm.

This study proposes an optimized algorithm for the navigation of the mobile robot in the indoor and dynamic unknown environment based on the decision tree algorithm. Firstly, the error of the yaw value outputted from IMU sensor fusion module is analyzed in the indoor environment; then, the adaptive FAST SLAM is proposed to optimize the yaw value from the odometer; in the next, a decision tree algorithm is applied which predicts the correct moving direction of the mobile robot through the outputted yaw value from the IMU sensor fusion module and adaptive FAST SLAM of the odometer data in the indoor and dynamic environment; the following is the navigation algorithm proposed for the mobile robot in the dynamic and unknown environment; finally, a real mobile robot is designed to verify the proposed algorithm.The final result shows the proposed algorithms are valid and effective.

First Indirect Drive Experiment Using a Six-Cylinder-Port Hohlraum.

The new hohlraum experimental platform and the quasi-3D simulation model are developed to enable the study of the indirect drive experiment using the six-cylinder-port hohlraum for the first time. It is also the first implosion experiment for the six laser-entrance-hole hohlraum to effectively use all the laser beams of the laser facility that is primarily designed for the cylindrical hohlraum. The experiments performed at the 100 kJ Laser Facility produce a peak hohlraum radiation temperature of ∼222 eV for ∼80 kJ and 2 ns square laser pulse. The inferred x-ray conversion efficiency η∼87% is similar to the cylindrical hohlraum and higher than the octahedral spherical hohlraum at the same laser facility, while the low laser backscatter is similar to the outer cone of the cylindrical hohlraum. The hohlraum radiation temperature and M-band (>1.6 keV) flux can be well reproduced by the quasi-3D simulation. The variations of the yield-over-clean and the hot spot shape can also be semiquantitatively explained by the calculated major radiation asymmetry of the quasi-3D simulation. Our work demonstrates the capability for the study of the indirect drive with the six-cylinder-port hohlraum at the cylindrically configured laser facility, which is essential for numerically assessing the laser energy required by the ignition-scale six-cylinder-port hohlraum.

Metformin improves renal injury of MRL/lpr lupus-prone mice via the AMPK/STAT3 pathway.

OBJECTIVE: Lupus nephritis (LN) is a major complication and cause of death among patients with SLE. This research used in vivo and in vitro experiments to explore the therapeutic potential of metformin in kidney injury from LN-induced inflammation. METHODS: In vivo study, 8-week-old MRL/MpJ-Faslpr/J (MRL/lpr) mice were randomly divided into two groups (n=12 each): daily administration of 0.3 mg/mL metformin in drinking water and control (water only). Body weight and urinary samples were measured biweekly. Mice were sacrificed after 8-week treatment to harvest serum, lymph nodes, spleen and kidneys. In vitro study, human kidney-2 (HK-2) cells were pretreated with 1 mM metformin for 1 hour and then stimulated with 20 µg/mL lipopolysaccharides (LPS) or 10 ng/mL tumour necrosis factor-α (TNF-α) for another 48 hours. Protein was collected for subsequent analysis. RESULTS: We found that metformin administration improved renal function in MRL/lpr lupus-prone mice, measured by decreased urea nitrogen and urinary proteins. Metformin reduced immunoglobulin G and complement C3 deposition in glomeruli. The treatment also downregulated systemic and renal inflammation, as seen in decreased renal infiltration of F4/80-positive macrophages and reduced splenic and renal MCP-1 (monocyte chemoattractant protein-1) and TNF-α, and renal IL-1ß (interleukin 1ß) expression. Metformin administration decreased renal expression of necroptosis markers p-RIPK1 (phosphorylated receptor-interacting protein kinase 1) and p-MLKL, along with tubular injury marker KIM-1 (kidney injury molecule-1) in lupus mice. In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-α, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1. Mechanistically, metformin treatment upregulated p-AMPK (phosphorylated AMP-activated protein kinase) and downregulated p-STAT3 (phosphorylated signal transducer and activator of transcription 3) expression in the kidneys. Moreover, AMPKα2 knockdown abolished the protective effects of metformin in vitro. CONCLUSIONS: Metformin alleviated kidney injury in LN though suppressing renal necroptosis and inflammation via the AMPK/STAT3 pathway.

Integrative analysis of multiomics data identified acetylation as key variable of excessive energy metabolism in hyperthyroidism-induced osteoporosis rats.

BACKGROUND: Results from the previous experiment have demonstrated bone loss and excess metabolism in Hyperthyroidism-induced rats. Thus, an underlying relationship between metabolism and bone loss was speculated. In addition, previous studies have shown the influence of acetylation on metabolism in tissues and diseases. The hypothesis from this case study suggests that excessive metabolism is induced by acetylation of vital metabolism enzymes. RESULTS: In the case study, a HYP-induced osteoporosis rat model was used and the glucose metabolite was tested through the acetylation of proteins by the mass spectrometer. The results showed that pivotal enzymes of Glycolysis-Tricarboxylic acid cycle-Oxidative phosphorylation were acetylated along with upregulated metabolites. With all acetyly-lysine sites of related enzymes listed, the results in this study showed that bone loss in HYP rats was accompanied by the upregulation of CREB-binding protein (Crebbp, CBP). Furthermore, it is also indicated that CBP has a close relationship with the enhancement of LDHA which promotes glucose metabolism. CONCLUSIONS: Acetylation is highly correlated with excessive energy metabolism in HYP-induced osteoporotic rats, where a representation relationship between CBP and LDHA is demonstrated. SIGNIFICANCE: Hyperthyroidism may lead to osteoporosis. Our study found an interesting phenomenon of hyperthyroidism induced-osteoporosis is that osteoporosis is accompanied by excessive glucose metabolism. In this process, some molecular mechanisms are still unclear. This study indicates a high degree of acetylation of metabolic enzymes, which may be closely related to excessive glucose metabolism. The relationship between CBP and LDHA was also investigated in this study, which showed that CBP and LDHA had some extent interaction. Glucose metabolism and acetylation maybe all associated with hyperthyroidism induced-osteoporosis. This data provides new insights into the molecular mechanisms of hyperthyroidism induced-osteoporosis.

Full particle-in-cell simulation of the formation and structure of a collisional plasma shock wave.

The formation and structure of a collisional shock wave in a fully ionized plasma is studied via full particle-in-cell simulations, which allows the complex momentum and energy transfer processes between different charged particles to be treated self-consistently. The kinetic energy of the plasma flow drifting towards a reflecting piston is found to be rapidly converted into thermal motion under the cooperative effects of ion-ion collisions, ion-electron collisions, and electric field charged-particle interactions. The subsequent shock evolution is influenced by the "precursor" ion beam before a quasisteady state is reached. The shock wave structure is then analyzed from a two-fluid transport viewpoint, which is found to be affected by "flux-limiting" electron transport, the nonthermal ions, and the charge separation electric field.

Observation of a high degree of stopping for laser-accelerated intense proton beams in dense ionized matter.

Intense particle beams generated from the interaction of ultrahigh intensity lasers with sample foils provide options in radiography, high-yield neutron sources, high-energy-density-matter generation, and ion fast ignition. An accurate understanding of beam transportation behavior in dense matter is crucial for all these applications. Here we report the experimental evidence on one order of magnitude enhancement of intense laser-accelerated proton beam stopping in dense ionized matter, in comparison with the current-widely used models describing individual ion stopping in matter. Supported by particle-in-cell (PIC) simulations, we attribute the enhancement to the strong decelerating electric field approaching 1 GV/m that can be created by the beam-driven return current. This collective effect plays the dominant role in the stopping of laser-accelerated intense proton beams in dense ionized matter. This finding is essential for the optimum design of ion driven fast ignition and inertial confinement fusion.

High Salt Elicits Brain Inflammation and Cognitive Dysfunction, Accompanied by Alternations in the Gut Microbiota and Decreased SCFA Production.

BACKGROUND: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. OBJECTIVE: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. METHODS: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. RESULTS: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1ß, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. CONCLUSION: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment.

Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well-known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood-brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3ß (GSK-3ß) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin-1ß, and tumour necrosis factor-α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK-3ß pathway and finally leading to cognitive impairment.

Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study.

PURPOSE: Age-related macular degeneration (AMD) can cause irreversible vision loss leading to blindness. We aim to evaluate the efficacy and safety of intravitreal injections of 0.5 mg conbercept, a new anti-vascular endothelial growth factor (anti-VEGF) drug, for treatment of AMD on a schedule more manageable for patients. DESIGN: A prospective, double-masked, multicenter, sham-controlled, phase III randomized trial. METHODS: Patients: Patients with choroidal neovascularization (CNV) secondary to AMD were enrolled and randomized to the conbercept group or the sham control group. INTERVENTION: The conbercept group received intravitreal injections of conbercept (0.5 mg) once monthly for the first 3 months, then once quarterly until month 12 (3 + Q3M). The sham group received first 3 monthly sham injections and then 3 monthly injections of conbercept (0.5 mg) followed by quarterly administrations until month 12. MAIN OUTCOME MEASURES: The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 3. RESULTS: A total of 114 patients (91.9%) from 9 sites in China completed the 12-month study. At the 3-month primary endpoint, the mean changes in BCVA from baseline were +9.20 letters in the conbercept group and +2.02 letters in the sham group, respectively (P < .001). At 12 months, the mean changes from baseline in BCVA letter score were +9.98 letters in the conbercept group and +8.81 letters in the sham group (P = .64). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage, and increased intraocular pressure. CONCLUSIONS: A conbercept dosing regimen of 3 initial monthly administrations followed by quarterly treatments is effective for treatment of AMD. In previous reports, other anti-VEGF agents were unable to maintain similar clinical benefits with the same regimen.

TSPAN7 promotes the migration and proliferation of lung cancer cells via epithelial-to-mesenchymal transition.

PURPOSE: To explore the effects and mechanisms of tetraspanin TSPAN7 on the progression of non-small-cell lung cancer (NSCLC) cells. PATIENTS AND METHODS: All 125 lung cancer specimens and 60 metastatic tissues were obtained from patients diagnosed with NSCLC, and we used immunohistochemistry to detect the expression of TSPAN7 in NSCLC tissues and adjacent normal tissues. Cell proliferation and invasion ability were determined by MTT, colony formation, and cell migration. The relative protein expression level was analyzed by Western blot analysis. RESULTS: Our clinical data showed that among 125 patients with lung cancer, TSPAN7 was associated with lymph node status, differentiation, tumor size, and poor prognosis. TSPAN7 knockout inhibited cell proliferation and migration. In addition, TSPAN7 increased the expression of N-cadherin in NSCLC cells by reducing the expression of E-cadherin and vimentin and promoting the cell epithelial-mesenchymal transition (EMT) process. Xenograft transplantation model confirmed the role of TSPAN7 in NSCLC metastasis. CONCLUSION: TSPAN7-mediated EMT is the key to NSCLC migration. TSPAN7 is a potential target for NSCLC therapy.

Protection against monocrotaline-induced pulmonary arterial hypertension and caveolin-1 downregulation by fluvastatin in rats.

Statins are Hydroxymethylglutaryl-coenzyme A reductase inhibitors, which are typically used to lower blood cholesterol. Additional beneficial effects, including improvement to pulmonary arterial hypertension (PAH), have also been confirmed. However, the mechanisms underlying this improvement have not yet been clarified. The present study was conducted to determine if fluvastatin was protective against experimental PAH development and to investigate the potential effects of fluvastatin on caveolin­1 (cav­1) expression. Rats were randomized to either receive a single subcutaneous injection of monocrotaline (MCT; 60 mg/kg; MCT group) or a single subcutaneous injection of MCT (60 mg/kg) followed by an oral gavage of fluvastatin (10 mg/kg) once daily until day 42 (M + F group). Rats in the MCT group received an equivalent volume of saline following the MCT injection. Six additional rats were given an equivalent volume of saline throughout as a control measure. PAH associated variables and cav­1 protein expression were measured in each group at various times during the experimental period. Hemodynamic and morphometric analysis revealed that M + F rats developed moderate, delayed PAH. Cav­1 western blot analysis demonstrated that cav­1 expression was not significantly different in fluvastatin treated rats; however, MCT injured rats given saline had markedly reduced cav­1 expression. It was concluded that fluvastatin may protect against PAH development and ameliorate MCT induced inhibition of cav­1 expression in rats.

Long intergenic non-protein coding RNA 00858 functions as a competing endogenous RNA for miR-422a to facilitate the cell growth in non-small cell lung cancer.

The expression of long non-coding RNAs (lncRNAs) is dysregulated in non-small cell lung cancer (NSCLC). However, the functions and contributions of lncRNAs remain largely unknown. Here, we identified a critical role of long intergenic non-protein coding RNA 00858 (LINC00858) in NSCLC. Ectopic expression of LINC00858 in NSCLC cells promoted cell proliferation and induced cell migration and invasion. Moreover, LINC00858 functioned as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-422a and thereby modulating the expression of kallikrein-related peptidase 4 (KLK4). In NSCLC patients, high expression of LINC00858 closely correlated with tumor progression. Thus, targeting the ceRNA network involving LINC00858 may be used as a treatment strategy against NSCLC.