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The importance of angiogenesis in multiple myeloma (MM) is unquestionable; however, to date, the success of antiangiogenic therapies has been fairly limited. Exosomal circular RNAs (circRNAs) have been proven to be pivotal players in angiogenesis in various cancers. Nevertheless, their role in MM remains unknown. Therefore, we aimed to identify differentially expressed circRNAs in peripheral blood exosomes from MM patients and explore their diagnostic and prognostic values. We screened 2,052 circRNAs with significant differential expression between MM patients and healthy controls via high-throughput sequencing. qRT-PCR confirmed that the expression of circ-ATP10A was significantly increased in MM patients. The bioinformatics analyses suggested that circ-ATP10A can act as a microRNA (miRNA) sponge and regulate the expression of downstream vascular endothelial growth factor-B (VEGFB), hypoxia-inducible factor-1alpha (HIF1A), platelet-derived growth factor subunit A (PDGFA), and fibroblast growth factor (FGF). The immunohistochemical results indicated that the circ-ATP10A level was positively correlated with the protein levels of VEGFB and marrow microvessel density (MVD) in MM patients, and the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and Kaplan-Meier survival curve analyses confirmed it as a prognostic biomarker. Collectively, our study indicates that exosomal circ-ATP10A is a valuable prognostic biomarker in MM and may promote MM angiogenesis by targeting hsa-miR-6758-3p/hsa-miR-3977/hsa-miR-6804-3p/hsa-miR-1266-3p/hsa-miR-3620-3p and modulating their downstream mRNAs, such as VEGFB, HIF1A, PDGF, and FGF.

Ten new C9 polyketides (asperochratides A-J, 1-10) and 14 known miscellaneous compounds (11-24) were isolated from the deep-sea-derived fungus Aspergillus ochraceus. Structures of the new compounds were elucidated by extensive spectroscopic analyses, modified Mosher's method, Mo2(OAc)4 induced circular dichroism (ICD) experiments, and ECD calculations. Structurally, compounds 1-11 and 16-18 share the same polyketide origin of the skeleton and belong to aspyrone co-metabolites. All isolates were tested for cytotoxic, anti-food allergic, anti-H1N1 virus, anti-microbe, and anti-inflammatory activities in vitro. Results showed that compounds 5-8 and 13-17 exerted significant cytotoxic effects on BV-2 cell line, and compound 16 showed the potential of anti-inflammatory activities.

Background: Myocardial fibrosis is closely associated with cardiac dysfunction, arrhythmia, and sudden cardiac death. A model of myocardial fibrosis induced by isoprenaline was used to determine the influence of exogenous adiponectin on myocardial fibrosis. Materials and Methods: A total of 30 mice were equally and randomly divided into three groups as follows: isoproterenol (ISO, n = 10), adiponectin and isoproterenol (APN + ISO, n = 10), and sham (n = 10). ISO (7.5 mg/kg/day) was injected intraperitoneally (i. p.) in the ISO group and APN + ISO group for three consecutive days to establish a model of myocardial fibrosis; normal saline was injected in the sham group. From day 4, adiponectin was injected (10 μg/kg/day; i. p.) in the APN + ISO group for 32 days; normal saline was injected in ISO and sham groups for 32 days. Five weeks later, mice were sacrificed, and myocardial tissue was dyed by Sirius Red to observe the collagen morphology. The collagen volume fraction was calculated. Protein and messenger RNA (mRNA) expression of type-I and type-III collagen in the myocardium was detected by reverse transcription-polymerase chain reaction and western blotting, respectively. Results: Type-I collagen in myocardial interstitial tissue was significantly increased in the ISO group. Collagen in myocardial interstitial tissue in the ISO + APN group was decreased significantly compared with the ISO group. Expression of type-I collagen mRNA in ISO and ISO + APN groups was significantly higher than that in the sham group (3.01 ± 0.78, 2.32 ± 0.82 vs. 1, respectively; P < 0.01). Expression of type-I collagen mRNA in the ISO + APN group was significantly lower than that in the ISO group (2.32 ± 0.82 vs. 3.01 ± 0.78, respectively; P < 0.01). Expression of type-III collagen mRNA in the ISO group, and ISO + APN group was significantly higher than that in the sham group (2.39 ± 0.70, 1.62 ± 0.57 vs. 1, respectively; P < 0.01). Expression of type-III collagen mRNA in the ISO + APN group was significantly lower than that in the ISO group (1.62 ± 0.57 vs. 2.39 ± 0.70, respectively; P < 0.01). Expression of type-I collagen protein in the myocardium in the ISO + APN group was significantly higher than that in the sham group (0.73 ± 0.19 vs. 0.28 ± 0.15, respectively; P < 0.001), but it was significantly lower than the expression of type-I collagen protein in the ISO group (0.53 ± 0.17 vs. 0.73 ± 0.19, respectively; P < 0.001). Conclusions: Supplementation with exogenous adiponectin can inhibit myocardial fibrosis induced by ISO.

RATIONALE Nitromezuril is a novel triazine compound possessing remarkable anticoccidial activity that could have possible future use in the prevention of coccidiosis; however, its metabolic characteristics have still not been revealed. METHODS In the present study, the in vitro metabolism of nitromezuril in HepG2 cells, rat S9 and primary hepatocytes was investigated using high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. The structures of metabolites and their product ions were easily and reliably characterized based on the accurate MS2 spectra and known structure of nitromezuril. RESULTS As expected, three metabolites (M1–M3) were detected in a HepG2 cells system, one metabolite was respectively detected and identified as M1 in rat S9 and M2 in rat primary hepatocytes. M1 and M2 were confirmed respectively based on comparing their retention times, full scan, product ion scan with available authentic standards and M3 was tentatively identified as hydroxyl compound of M2. CONCLUSIONS Pathways of nitromezuril were reported for the first time and no obvious species difference was shown. The proposed metabolic pathways of nitromezuril can be expected to play a key role in pharmacodynamics and food safety evaluations. Copyright © 2014 John Wiley & Sons, Ltd.

Several Acalypha australis Linn. species are used in traditional medicine in Southeast Asia. In this work, the ultra-performance liquid chromatography/mass spectrometry fingerprints and the antibacterial activities of A. australis Linn. were investigated. An in-depth discussion on the reliability of identifying and obtaining potentially active compounds by spectrum-effect relationship and semi-preparative high performance liquid chromatography was conducted. The result shows that gallic acid and a compound with molecular weight of 634.1 in the fingerprints were the main antibacterial compounds. Compared to the crude extract of A. australis Linn., both compounds increase the antibacterial efficacy 10 to 20 times. Compounds with molecular weights of 154.0, 292.0, and 485.1 in the fingerprints were the auxiliary antibacterial compounds. Through the entire isolation procedure, we obtained these antibacterial compounds with purities of 92.53, 87.98, 90.73, 89.36, and 88.14%, respectively. This work provides a general model of the combination of ultra-performance liquid chromatography/mass spectrometry fingerprinting and antibacterial test to study the spectrum-effect relationships of A. australis Linn. This model can be used to discover further the active compounds of this herb.

Background: Sulfur fumigation is one of the processing methods of Chinese medicinal herbs. This method can be used in bleaching herbs and controlling microorganisms, parasites and insects. Codonopsis Radix (Dangshen in Chinese), dried roots of Codonopsis pilosula, is one of the herbs commonly processed by sulfur fumigation. This study reports the influence of sulfur fumigation on the chemical constituents of the volatile oil of Dangshen.Materials and Methods: The volatile oil of air-dried or sulfur fumigated Dangshen was extracted by water-steam distillation and separated by GC capillary column chromatography. The components in the individual volatile oil were identified and quantitatively determined by GC-MS.Results: The results showed that 45 compounds were separated and identified from the volatile oil of Dangshen samples. Among them, the contents of 23 compounds in sulfur-fumigated Dangshen were much lower than that in air-dried Dangshen, such as 4-bromo-1-cyclohexene (6), 3,5-dimethylcyclopentene (7), phenylethyl alcohol (11), 2,3 diazabicyclo[2.2.1]hepy-2-ene,4-methyl-1-(pent-4-en-1-yl)- (22) and cedren-13-ol, 8- (35). On the contrary, the contents of 12 compounds were increased after sulfur fumigation, such as (+)-sativene (25), thujopsene (27), chamigren (30), a-guaiene (32) and 3- buten-2-one, 3-methyl-4-[(1R,2R,6S)-1,3,3-trimethyl-7-oxabicyclo[4.1.0]hept-2-yl] , (3E)-rel- (43). Furthermore, two peaks [bicyclo[3.2.0]heptan-2-one,6 hydroxy-5-methyl-6-vinyl- (17) and bornyl bromide (20)] disappeared and four peaks [3-(decyloxy)-2-hydroxy-1-propanesulfonic acid (18), α-lonone (19) tetradecanoic acid (42) and methyl cis-9,10 epoxystearate (45)] newly appeared in the chromatogram of the volatile oil of sulfur-fumigated Dangshen.Conclusions: Sulfur fumigation caused significant variations in the constituents of volatile oil of Dangshen. Further explorations are needed to investigate how these chemical variations occurred and whether these variations would affect the clinical efficacy and safety of Dangshen in human use.Keywords: Sulfur fumigation; volatile oil; Dangshen; Codonopsis pilosula; GC-MS

Nitrogen use efficiency (NUE) was very low in China and a loss of as much as 70% of the applied nitrogen fertilizers was reported in high-yielding rice fields. In order to investigate the molecular basis of high-affinity ammonium transport or uptake into rice (Oryza sativa L.), we analyzed the expression profiles of nine ammonium transporters (AMT), three each of OsAMT1, OsAMT2 and OsAMT3, at two different N requirement stages (young seedling stage and tillering stage) of rice growth as well as the changes in these expression patterns according to external N status using real-time reverse transcription polymerase chain reaction (RT-PCR). The results suggested that the nine OsAMT genes were expressed in different organs of rice plants, including mature roots, new roots, stems, old leaves and new leaves and that the expression patterns were organ specific and independent of the positions of the corresponding proteins in the phylogenetic tree. OsAMT1; 1, 3;2 and 3;3 were expressed in the roots and shoots, primarily old leaves, OsAMT1;2 and 1;3 mainly in the roots, and OsAMT2;1, 2;2, 2;3 and 3;1 mainly in the shoots, primarily in new leaves, and relatively more in the stems than other genes. The expression patterns at the two different N requirement stages were the same; however, at the tillering stage with greater N requirements, the OsAMTs transcript levels were greater than those at the young seedling stage with low N requirements. N starvation for 48 h up-regulated OsAMT1;1, 1;2, 3;1, 3;2, 3;3 and down-regulated OsAMT1;3 mRNA abundance. Following N starvation, NH4+ and NH4NO3 re-supply down-regulated OsAMT1;2 and 3;3 and up-regulated OsAMT1;3, whereas NO3− re-supply down-regulated OsAMT1;1 and 1;2. These suggested that the organ-specific expression pattern of OsAMT could be regulated by N requirement and external N status.

Rice grows in flooded paddy fields and takes up ammonium as the preferred nitrogen (N) source. Ammonium uptake is facilitated by a family of integral membrane proteins known as ammonium transporters found in all domains of life. However, the molecular mechanism and functional characteristics of the ammonium transporters (AMT) in rice have not been determined in detail yet. In this review, we report a genome-wide search for AMT genes in rice, resulting in the increase of the number of potential AMT proteins to at least 12, including members of both the alpha and beta sub-groups. Analysis of the predicted protein sequences for the 12 OsAMT proteins identified many conserved phosphorylation sites in both the alpha and beta group members, which could potentially play a role in controlling the activity of the transporters. Present knowledge of the expression of rice AMT genes is also summarized in detail. Future studies should focus on the structural and functional characteristics of OsAMT proteins to provide insight into the mechanism of ammonium uptake and its regulation in rice. Such research could improve utilization and decrease wastage of N fertilizer in rice cultivation.

Shenmai injection (SMI) has been widely used as a therapy to treat a number of diseases. However, its anti-osteoarthritic properties have not yet been fully investigated. In the present study, the protective effect of SMI on knee articular cartilage of anterior cruciate ligament transected rabbits and interleukin-1β (IL-1β)-stimulated human chondrocytes was investigated. For the in vivo study, knee osteoarthritis (KOA) was induced in female New Zealand white rabbits by anterior cruciate ligament transection (ACLT) in the knee of right hind limb. Rabbits either underwent sham surgery or ACLT surgery. Out of the rabbits receiving ACLT surgery, half of the rabbits received one 0.3 ml Shenmai intra-articular injection in the knee per week for four weeks, following ACLT surgery. The other rabbits received the same volume of normal saline solution. The cartilage was subsequently collected for histological evaluation. For the in vitro study, cultured human chondrocytes were treated with 10 ng/ml IL-1β in the presence or absence of 5 and 2% (v/v) SMI for 24 h. Nitric oxide (NO) and prostaglandin E2 (PGE2) levels in cell culture supernatant were assessed using a Griess reaction and ELISA respectively. The mRNA expression of cyclooxgenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitors of metalloproteinase-1 (TIMP-1) in chondrocytes were detected by reverse transcription-quantitative polymerase chain reaction. The results of the current study revealed that treatment with SMI ameliorated cartilage degradation in the ACLT rabbit model, and decreased levels of NO and PGE2. Furthermore, treatment with SMI decreased levels of COX-2, iNOS, MMP-1 and MMP-13 mRNA expression and increased TIMP-1 mRNA expression in IL-1β-stimulated human chondrocytes. These results indicate that SMI suppresses inflammation and ameliorated cartilage degradation, making it a potential and promising therapeutic option to treat KOA.

The effects of acute exposure of intraperitoneal injection of aqueous 1-octyl-3-methylimidazolium bromide on the antioxidant enzymes and lipid peroxidation of the treated mouse liver were investigated in the present paper. Thirty mice were treated with 17.9 (0.5 median lethal dose, LD 50 ) and 35.7 mg/kg (1 LD 50 ) of the ionic liquid or saline solution by intraperitoneal injection for 10 h. Significant increase in hepatosomatic index and decrease in liver protein content were found in 1 LD 50 group. No statistically significant change was observed in the activity of superoxide dismutase in both treated groups compared to the control group. In the case of catalase activity, the decrease was recorded only at dose of 1 LD 50 . As for the activity of glutathione peroxidase, increase in 0.5 LD 50 group while significant decrease at dose of 1 LD 50 was noted. There was an increase in the activity of glutathione- S -transferase in these two treated groups in comparison to the control. However, no effect on the level of lipid peroxidation was found in the treated groups. These results showed that the acute exposure of aqueous ionic liquid could cause damage to mouse, leading to antioxidant responses in livers of the treated mice.

A Be δ-doped GaAs/AlAs three quantum wells emitter in the terahertz range is fabricated and electroluminescence is investigated. An electroluminescence peak centered at 23.4 meV with a full width at half maximum of 4.2 meV is observed under a bias of 2 V at low temperature (T=4.5 K). The emission peak is attributed to the 2p to 1s internal transitions of the Be acceptors in the center of δ-doped GaAs quantum well. The current-voltage characteristics of the device measured at different temperatures demonstrate a strong negative differential resistance and temperature dependence.