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People living in plains tend to decrease in body weight or body fat percentage after entering the plateau. Previous studies have found that plateau animals can burn fat and release calories through white adipose tissues (WATs) browning. However, these studies have focused on the effect of cold stimulation that induced WATs browning while there's hardly study on the effect of hypoxia. In this study, we investigate that whether and how hypoxia contributes to WATs browning in rats from acute to chronic hypoxia. We constructed hypobaric hypoxic rat models by exposing 9-week-old male SD rats to a hypobaric hypoxic chamber for 1, 3, 14 and 28 days (Group H) under simulated environment at altitude of 5000 m. We also established normoxic control groups for each time period (Group C), as well as paired 1-day and 14-day normoxic food-restriction rats that were fed the same amount of food as the hypoxic group ate (Group R). We then observed the growth status of rats and recorded dynamic changes in histologic, cellular and molecular levels of perirenal WATs (PWAT), epididymal WATs (EWAT) and subcutaneous WATs (SWAT) in each group. Results showed that (1) Hypoxic rats had lower food intake, significantly lower body weight than control rats, and showed lower WATs index. (2) In group H14, ASC1 mRNA expressions of PWAT and EWAT in rats were lower than that in group C14, and PAT2 mRNA expression of EWAT was higher than that in both group C14 and R14. In group R14, however, ASC1 mRNA expressions of PWAT and EWAT in rats were higher than both group C14 and H14, and that of SWAT was also significantly higher than group C14. (3) In group H3, both the mRNA and protein levels of uncoupling protein 1 (UCP1) of PWAT in rats were significantly increased than group C3. And in group H14, those of EWAT in rats were significantly increased than group C14. (4) In plasma of rats, norepinephrine (NE) level was significantly increased in group H3 than group C3, and free fatty acids (FFAs) level was significantly increased in group H14 than both group C14 and R14. In group R1, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated than group C1. In group H3, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated while ATGL mRNA expression of EWAT was up-regulated than group C3. Conversely, in group R14, FASN mRNA expressions of PWAT and EWAT in rats were significantly up-regulated than group C14 and H14. These results suggested that hypoxia promoted different WATs browning in rats under simulated environment at altitude of 5000 m and changed the lipid metabolism in WATs. Furthermore, rats in the chronic hypoxic group showed a completely different lipid metabolism of WATs from that in paired food-restriction group. • Hypoxia promotes PWAT and EWAT but not SWAT browning in rats. • Hypoxia promotes both the mRNA and protein expression of UCP1 in WATs. • Acute hypoxia increases the expression of FASN and decreases that of ATGL in WATs. • Chronic hypoxia regulates lipid metabolism different from paired restricting food. [ABSTRACT FROM AUTHOR]

It is difficult to fabricate magnetic films containing small nanoparticles with a narrow size distribution. The nanomagnetic structural evolutions inside the nanoparticles in these types of films play a key role in the development of the magnetic properties. Magnetic composite films with a cubic array distribution of the nanoparticles are obtained using the layered growth of FeNi–SiO and SiO by the vacuum thermal evaporation method. The films contain small nanoparticles with a narrow size distribution (4.59 ± 0.18 nm) and an ordered cubic array. In the films, the magnetic induction lines measured by the differential phase contrast microscopy of the transmission electron microscope confirm that the disordered domain becomes multi-domain with an ordered cubic array. Furthermore, the saturation magnetization of such a film is higher than that of a pure FeNi film, despite the presence of the nonmagnetic SiO dielectric. This type of new material can be used in magnetic shields with a weak magnetic field and highly sensitive magnetic sensors. [ABSTRACT FROM AUTHOR]

High altitude hypobaric hypoxia environment impairs male's reproductive function. Leptin is an adipose tissue-derived hormone which regulates body weight homeostasis. Its receptor (LepR) has been found in all levels of male reproductive axis, indicating that it can affect male reproductive system in a direct or (and) indirect way. However, the role of leptin signaling in hypobaric hypoxia induced male reproductive dysfunction remains to be elucidated. In this study, we investigated the changes of leptin levels in male SD rats in stimulated altitude of 5500 m hypobaric hypoxia environment and their effects on the hypothalamus-pituitary-gonad axis (HPG axis). A hypoxia animal model was established using a hypobaric hypoxia chamber. Rats were divided randomly into 1, 7, 14, 28-day hypoxia group, recovery group (14 days hypoxia+14 days normoxia) and their control groups. Hypoxia groups displayed obvious changes of testicular and epididymis index compared to control groups. The total number of sperm and sperm motility rate decreased dramatically, while sperm deformity rate increased in hypoxia groups. The flow cytometry analysis showed that the percentage of haploid in 1-day, 7-day and 28-day hypoxia groups increased while the proportion of diploid decreased in 14-day and 28-day hypoxia group. TUNEL staining showed that the testis cells apoptosis index (AI) of hypoxia groups increased significantly, and the apoptosis of cells mainly focus on spermatogonia and spermatocytes. The expression of GnRH in hypothalamus decreased dramatically under hypoxia condition, accompanied with the reduction of serum testosterone (T) level in 1-day and 28-day hypoxia groups and free-testosterone level (FT) in 1-day and 14-day hypoxia groups. Importantly, ELISA analysis showed that serum leptin level decreased in 7-day hypoxia groups and acylated-ghrelin, gastrin also changed, accompanying with reduction of LepR in hypothalamus in hypoxia groups. Immunohistochemical staining exhibited increased leptin and LepR in testis under hypobaric hypoxia conditions. Our results suggested that simulated high altitude hypobaric hypoxia environment decreased male reproductive function, depressed HPG axis activity and altered the serum concentration of hormones related to food intake in adult male rats. Additionally, hypobaric hypoxia induced the leptin-LepR expression in adult male rats' testis, suggesting leptin-LepR signaling may mediate hypoxia-induced impairment in male rats' reproductive system. • Hypoxia alters the serum concentration of leptin. • Leptin receptor is expressed in all levels of male reproductive axis. • Hypoxia changes the leptin receptor's expression in HPG axis. • Leptin-LepR may mediate hypoxia-induced impairment in male's reproductive system. [ABSTRACT FROM AUTHOR]

Abstract This study assessed neuropeptide Y (NPY) expression in the hippocampus after long-term survival following traumatic brain injury (TBI) induced by controlled cortical impact (CCI) with or without the development of posttraumatic epilepsy (PTE). We hypothesized that following long-term survival after CCI, the severity of tissue injury and the development of PTE would correlate with the degree of hippocampal neurodegeneration as reflected by NPY + and neuronal nuclear antigen (NeuN)+ cell loss. Adult Sprague–Dawley rats of 2–3 months of age were lesioned in the right parietal cortex and monitored for seizure activity by video and/or video-EEG. Neuropeptide Y and NeuN immunoreactivities (IRs) were quantified by light microscopy and semiautomatic image analysis approaches for unbiased quantification. Severely injured animals, marked by extensive tissue loss in the ipsilateral neocortex and adjacent hippocampus, resulted in significantly lower NeuN + hilar cell density and NPY + cell loss in the contralateral Cornu Ammonis (CA)-3 and dentate hilus (DH). The degree of NPY + cell loss was more severe in CCI-injured animals with PTE than those animals that did not develop PTE. Mildly injured animals demonstrated no significant change of NPY expression compared with control animals. Our findings of long-term alterations of NPY expression in the hippocampus of severely brain-injured animals can provide important insights into the cellular and molecular consequences of severe TBI and posttraumatic epileptogenesis. Highlights • CCI-induced TBI in rats caused mild or severe tissue loss after long-term survival. • Rats with mild tissue loss had hippocampal NPY expression similar to controls. • With severe injury, the ipsilateral hippocampus was destroyed or markedly deformed. • Contralateral hippocampal NPY expression decreased with increased CCI severity. • NPY + cell loss was more pronounced in PTE vs. non-PTE animals. [ABSTRACT FROM AUTHOR]

Background & aims Leucine-rich repeat G-protein-coupled receptor 4 (LGR4) and its ligands R-spondin1-4 (Rspos) have been vastly investigated in embryonic development. The biological functions of Rspos-LGR4 system in liver remains largely unknown. Here, we explored whether it protects hepatocytes against hypoxia/reoxygenation (H/R) induced damage. Methods H/R injury was induced by dimethyloxalylglycine (DMOG) in AML12 cells and the effects of Rspo3 on cell proliferation and apoptosis were assessed. Specific shRNAs were used to interfere LGR4 or β-catenin. Results DMOG caused hepatocytes damage evidenced by increase in HIF-1α, cell death and apoptosis genes p27 and Bax , with concurrent decrease of cell proliferation genes PCNA and CyclinD1 . Of all the Rspos, Rspo3 is predominantly expressed in AML12 hepatocytes. Importantly, Rspo3 demonstrated an alteration in a manner similar to proliferation-related genes during H/R injury. Rspo3 pretreatment rendered hepatocytes less vulnerable to DMOG induced H/R injury. Ablation of LGR4 using shRNA attenuated the protective effects of Rspo3. Wnt3a also protected AML12 cells from damages caused by H/R, showing enhanced proliferation activity. Notably, knockdown of β-catenin in hepatocytes completely abolished the effect of Rspo3 pretreatment on the expression levels of PCNA and CyclinD1. Conclusion Rspo3-LGR4 axis protects hepatocytes from H/R injury via activating β-catenin. [ABSTRACT FROM AUTHOR]

This paper studies the effects of high magnetic field (HMF) on the structure, optical and thermoelectric properties of the doped ZnO thin films. The results show that both Al dopant and application of HMF can affect the crystal structure, surface morphology, elemental distribution and so on. The particles of the thin films become small and regular by doping Al. The ZnO films oxidized from the Au/Zn bilayer have needle structure. The ZnO films oxidized from the Au/Zn-Al bilayer transform to spherical from hexagonal due to the application of HMF. The transmittance decreases with doping Al because of the opaque of Al element and decreases with the application of HMF due to the dense structure obtained under HMF. Electrical resistivity ( ρ ) of the ZnO films without Al decreases with increasing measurement temperature ( T ) and is about 1.5 × 10 −3 Ω·m at 210 °C. However, the ρ of the Al-doped ZnO films is less than 10 −5 Ω·m. The Seebeck coefficient ( S ) of the films oxidized from the Au/Zn-Al films reduces with increasing T . The S values oxidized under 0 T and 12 T conditions are 2.439 μV/K and −3.415 μV/K at 210 °C, respectively. Power factor reaches the maximum value (3.198 × 10 −4 W/m·K 2 ) at 210 °C for the film oxidized under 12 T condition. These results indicate that the Al dopant and the application of HMF can be used to control structure and thermoelectric properties of doped ZnO films. [ABSTRACT FROM AUTHOR]

Cleft lip with or without palate (CL/P) is a common congenital anomaly in humans and is thought to be caused by genetic and environmental factors. However, the epigenetic mechanisms underlying orofacial clefts are not fully understood. Here, we investigate how the overdose of retinoic acid (RA), which can induce cleft palate in mice and humans, regulates histone methyltransferase, Wolf–Hirschhorn syndrome candidate 1 (WHSC1) during palatal development in mice. We treated mouse embryonic fibroblasts (MEFs) with 1 μM all-trans RA and discovered that the global level of H3K36me3 was downregulated and that expression of the H3K36 methyltransferase gene, Whsc1 , was reduced. The expression level of WHSC1 in embryonic palatal shelves was reduced during palatogenesis, following maternal administration of 100 mg/kg body weight of RA by gastric intubation. Furthermore, the expression of WHSC1 in palatal shelves was observed in epithelial and mesenchymal cells at all stages, suggesting an important role for palatal development. Our results suggest that the pathogenesis of cleft palate observed after excessive RA exposure is likely to be associated with a reduction in the histone methyltransferase, WHSC1. [ABSTRACT FROM AUTHOR]

Highlights: [•] Seven S100 family members were almost totally undetectable in HepG2.2.15 cells. [•] S100 proteins rescue the defects in protrusion and migration of HepG2.2.15 cells. [•] S100 proteins promoted actin polymerization. [•] S100A10 may interact with β-actin, β-tubulin and annexin A2 protein. [•] Promotion of cell protrusion by S100A10 was dependent on Cdc42 activation. [Copyright &y& Elsevier]

We present a pH-responsive poly(ethyleneglycol)- b -poly(2-(diisopropylamino) ethyl methacrylate) block copolymer (MPEG-PPDA) that can self-assemble into micelles at very low critical micelle concentration. The formed micelles exhibit superior stability in physiological environment and pH-triggered transforming capability between self-assembly and disassembly. Moreover, the resulting micelles can load hydrophobic anticancer drug molecules such as doxorubicin in the core of micelles. The pH-triggered drug release kinetics matches the classical hydrazone bond model. The blank micelles demonstrate minimal cytotoxicity while the drug-loaded micelles exhibit significantly improved anticancer efficacy. These results indicate that this MPEG-PPDA block copolymer could be utilized as a universal pH-responsive delivery system for controlled release of hydrophobic anticancer drug in chemotherapy. [ABSTRACT FROM AUTHOR]