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Background Baicalin, which is isolated from Radix Scutellariae , possesses strong biological activities including an anti-inflammation property. Recent studies have shown that the anti-inflammatory effect of baicalin is linked to toll-like receptor 4 (TLR4), which participates in pathological changes of central nervous system diseases such as depression. In this study, we explored whether baicalin could produce antidepressant effects via regulation of TLR4 signaling in mice and attempted to elucidate the underlying mechanisms. Methods A chronic unpredictable mild stress (CUMS) mice model was performed to explore whether baicalin could produce antidepressant effects via the inhibition of neuroinflammation. To clarify the role of TLR4 in the anti-neuroinflammatory efficacy of baicalin, a lipopolysaccharide (LPS) was employed in mice to specially activate TLR4 and the behavioral changes were determined. Furthermore, we used LY294002 to examine the molecular mechanisms of baicalin in regulating the expression of TLR4 in vivo and in vitro using western blot, ELISA kits, and immunostaining. In the in vitro tests, the BV2 microglia cell lines and primary microglia cultures were pretreated with baicalin and LY292002 for 1 h and then stimulated 24 h with LPS. The primary microglial cells were transfected with the forkhead transcription factor forkhead box protein O 1 (FoxO1)-specific siRNA for 5 h and then co-stimulated with baicalin and LPS to investigate whether FoxO1 participated in the effect of baicalin on TLR4 expression. Results The administration of baicalin (especially 60 mg/kg) dramatically ameliorated CUMS-induced depressive-like symptoms; substantially decreased the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the hippocampus; and significantly decreased the expression of TLR4. The activation of TLR4 by the LPS triggered neuroinflammation and evoked depressive-like behaviors in mice, which were also alleviated by the treatment with baicalin (60 mg/kg). Furthermore, the application of baicalin significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and FoxO1. The application of baicalin also promoted FoxO1 nuclear exclusion and contributed to the inhibition of the FoxO1 transactivation potential, which led to the downregulation of the expression of TLR4 in CUMS mice or LPS-treated BV2 cells and primary microglia cells. However, prophylactic treatment of LY294002 abolished the above effects of baicalin. In addition, we found that FoxO1 played a vital role in baicalin by regulating the TLR4 and TLR4-mediating neuroinflammation triggered by the LPS via knocking down the expression of FoxO1 in the primary microglia. Conclusion Collectively, these results demonstrate that baicalin ameliorated neuroinflammation-induced depressive-like behaviors through the inhibition of TLR4 expression via the PI3K/AKT/FoxO1 pathway.

This study investigated the effect of a novel progestin and its combination with metformin on the growth of endometrial cancer (EC) cells. Inhibitory effects of four progestins, including nomegestrol acetate (NOMAC), medroxyprogesterone acetate, levonorgestrel, and cyproterone acetate, were evaluated in RL95-2, HEC-1A, and KLE cells using cell counting kit-8 assay. Flow cytometry was performed to detect cell cycle and apoptosis. The activity of Akt (protein kinase B), mTOR (mammalian target of rapamycin) and its downstream substrates 4EBP1 (4E-binding protein 1) and eIF4G (Eukaryotic translation initiation factor 4G) were assayed by Western blotting. Nude mice were used to assess antitumor effects in vivo. NOMAC inhibited the growth of RL95-2 and HEC-1A cells, accompanied by arresting the cell cycle at G0/G1 phase, inducing apoptosis, and markedly down-regulating the level of phosphorylated mTOR/4EBP1/eIF4G in both cell lines (p < 0.05). Metformin significantly increased the inhibitory effect of and apoptosis induced by NOMAC and strengthened the depressive effect of NOMAC on activity of mTOR and its downstream substrates, compared to their treatment alone (p < 0.05). In xenograft tumor tissues, metformin (100 mg/kg) enhanced the suppressive effect of NOMAC (100 mg/kg) on mTOR signaling and increased the average concentration of NOMAC by nearly 1.6 times compared to NOMAC treatment alone. Taken together, NOMAC suppressing the growth of EC cells likely correlates to down-regulating the activity of the mTOR pathway and metformin could strengthen this effect. Our findings open a new window for the selection of progestins in hormone therapy of EC.

Diatomite-based porous ceramics were adopted as carriers to immobilize nano-TiO2 via a hydrolysis-deposition technique. The thermal degradation of as-prepared composites was investigated using thermogravimetric–differential thermal analysis, and the phase and microstructure were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. The results indicated that the carriers were encapsulated by nano-TiO2 with a thickness of 300–450 nm. The main crystalline phase of TiO2 calcined at 650℃ was anatase, and the average grain size was 8.3 nm. The FT-IR absorption bands at 955.38 cm-1 suggested that new chemical bonds among Ti, O, and Si had formed in the composites. The photocatalytic（PC） activity of the composites was investigated under UV irradiation. Furthermore, the photodegradation kinetics of formaldehyde was investigated using the composites as the cores of an air cleaner. A kinetics study showed that the reaction rate constants of the gas-phase PC reaction of formaldehyde were κ = 0.576 mg·m–3·min–1 and K = 0.048 m3/mg.

Background: Spermatozoa become mature and acquire fertilizing capacity during their passage through the epididymal lumen. In this study, we identified new epididymal luminal fluid proteins involved in sperm maturation in infertile rats by dutasteride, a dual 5α-reductase inhibitor, in order to provide potential epididymal targets for new contraceptives and infertility treatment. Methods: Male rats were treated with dutasteride for 28 consecutive days. We observed the protein expression profiles in the epididymal luminal fluids in infertile and normal rats using isobaric tags for relative and absolute quantitation (iTRAQ) technique. The confidence of proteome data was validated by enzyme-linked immunosorbent assays. Results: 1045 proteins were tested, and 23 of them presented different expression profiling in the infertile and normal rats. The seven proteins were down-regulated, and 16 proteins were up-regulated. Among the seven proteins which were significantly down-regulated by dutasteride in the epididymal luminal fluids, there were three β-defensins (Defb2, Defb18 and Defb39), which maybe the key proteins involved in epididymal sperm maturation and male fertility. Conclusions: We report for the first time that dutasteride influences the protein expression profiling in the epididymal luminal fluids of rats, and this result provides some new epididymal targets for male contraception and infertility therapy.

Cymbidium ensifolium is one of the national orchids in China, which has high ornamental value with changeable flower colors. To understand the formation mechanism of different flower colors of C. ensifolium, this research conducted transcriptome and metabolome analyses on four different colored sepals of C. ensifolium. Metabolome analysis detected 204 flavonoid metabolites, including 17 polyphenols, 27 anthocyanins, 75 flavones, 34 flavonols, 25 flavonoids, 18 flavanones, and 8 isoflavones. Among them, purple-red and red sepals contain a lot of anthocyanins, including cyanidin, pelargonin, and paeoniflorin, while yellow-green and white sepals have less anthocyanins detected, and their metabolites are mainly flavonols, flavanones and flavonoids. Transcriptome sequencing analysis showed that the expression levels of the anthocyanin biosynthetic enzyme genes in red and purple-red sepals were significantly higher than those in white and yellow-green sepals of C. ensifolium. The experimental results showed that CeF3′H2, CeDFR, CeANS, CeF3H and CeUFGT1 may be the key genes involved in anthocyanin production in C. ensifolium sepals, and CeMYB104 has been proved to play an important role in the flower color formation of C. ensifolium. The results of transformation showed that the CeMYB104 is involved in the synthesis of anthocyanins and can form a purple-red color in the white perianth of Phalaenopsis. These findings provide a theoretical reference to understand the formation mechanism of flower color in C. ensifolium.Key messageThis study identified the differential metabolites and differential genes among different color sepals, determined the key regulatory genes, and constructed a regulatory network for the flower color formation of Cymbidium ensifolium.

For a better understanding of the dynamics of rehabilitated grassland, carbon storage in the underground including soil and roots were studied in a space series of replaced time courses.Soil organic carbon (SOC) of the 0-100cm layer increased with the addition of restoration years.It was much more than the average of 4.46-9.95 kg m-2 in central Plateau. SOC in surface soil (layer 0-20cm) fell slightly in early stage (0-2a) and then rose rapidly. In 30a, the increase amplitude turned to be 123% and it reached the maxmum.SOC in this layer was significantly correlated with an average value for the whole 0-100 cm profile.So SOC storage, in the 0-100cm layer, can be well estimated using values for the 0-20 cm layer. Alfalfa underground biomass carbon storage rose first and then reduced. It reached the maxmum in 10a. The carbon storage of weed roots increased continuously and was still less than that of alfalfa roots in 30a.

The molecular mechanism controlling the dismantling of naive pluripotency is poorly understood. Here we show that microRNAs （miRNAs） have important roles during naive to primed pluripotency transition. Dgcr8-/- embryon- ic stem cells （ESCs） failed to completely silence the naive pluripotency program, as well as to establish the primed pluripotency program during differentiation, miRNA profiling revealed that expression levels of a large number of miRNAs changed dynamically and rapidly during naive to primed pluripotency transition. Furthermore, a miRNA screen identified numerous miRNAs promoting naive to primed pluripotency transition. Unexpectedly, multiple miR- NAs from miR-290 and miR-302 clusters, previously shown as pluripotency-promoting miRNAs, demonstrated the strongest effects in silencing naive pluripotency. Knockout of both miR-290 and miR-302 clusters but not either alone blocked the silencing of naive pluripotency program. Mechanistically, the miR-290/302 family of miRNAs may facili- tate the exit of naive pluripotency in part by promoting the activity of MEK pathway and through directly repressing Aktl. Our study reveals miRNAs as an important class of regulators potentiating ESCs to transition from naive to primed pluripotency, and uncovers context-dependent functions of the miR-290/302 family of miRNAs at different developmental stages.

Diatomite-based porous ceramics were adopted as carriers to immobilize nano-TiO2 via a hydrolysis-deposition technique. The thermal degradation of as-prepared composites was investigated using thermogravimetric-differential thermal analysis, and the phase and microstructure were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. The results indicated that the carriers were encapsulated by nano-TiO2 with a thickness of 300-450 nm. The main crystalline phase of TiO2 calcined at 650~C was anatase, and the average grain size was 8.3 nm. The FT-IR absorption bands at 955.38 cm1 suggested that new chemical bonds among Ti, O, and Si had formed in the composites. The photocatalytic （PC） activity of the composites was investigated un- der UV irradiation. Furthermore, the photodegradation kinetics of formaldehyde was investigated using the composites as the cores of an air cleaner. A kinetics study showed that the reaction rate constants of the gas-phase PC reaction of formaldehyde were k = 0.576 mg＇m3·min^-1 and K = 0.048 m3/mg.

Concentrations of atmospheric nitrous oxide (N 2 O), a potent greenhouse gas, have been continuously increasing, and cropland soils are one of the largest sources of N 2 O. Variations in environmental and anthropogenic factors have substantial impacts on both the frequency and magnitude of N 2 O emissions. Based on measurements from a wheat-maize system in the North China Plain, the authors parameterized the Agricultural Production Systems Simulator (APSIM) model, which was initially developed in Australia, for simulating N 2 O emissions under different agricultural management practices. After calibrating one of the key parameters - the fraction of N 2 O lost in nitrification (k 2 ) - the results showed that the model successfully captured the daily N 2 O fluxes under different nitrogen fertilization treatments, but underestimated some large peak fluxes. By pooling all data together, the calibrated APSIM model also performed well in representing cumulative N 2 O emissions under various treatments at annual and finer (monthly and daily) time scales.

Compared with non-gray model, equivalent gray model has equal calculation accuracy but much higher computing speed. To solve the existing problems of the equivalent gray method, sole ternary model was developed. In the model, coupling solving process of energy balance equations is omitted and the model zone is real closed. Meanwhile, the full furnace temperature and heat flow calculations are avoided, which makes it easier to find the relationship between the equivalent gray gas radiation characteristic parameter and the initial conditions. The radiation characteristic parameter was calculated with different temperature combinations, different model zone sizes and different partial pressures of absorbent gas. The results show the similar variations in the absorption coefficient and emissivity for the equivalent gray model, which both decrease with the increase of the gas temperature and the surface temperature (especially the former one) as well as the model zone size while increase with the increase of the partial pressure of absorbent gas.