Single-frequency DBR lasing by integrating FBGs into germanium-free photosensitive highly Yb3+-doped silica fibers.

Monolithic distributed Bragg reflector (DBR) cavity which directly integrates fiber Bragg gratings (FBGs) into the photosensitive RE-doped fibers is a promising configuration in constructing compact and efficient single frequency fiber lasers (SFFLs). Yet, the doping level of rare-earth (RE) ions has generally to be sacrificed in the classical Ge-photosensitized RE-doped silica fibers because of the dramatic refractive index increase caused by the introduction of Ge. Here, we demonstrate an approach to realize the trade-off between photosensitivity and RE doping concentration. We validate that the addition of a small amount of cerium (0.37wt.%) instead of Ge could photosensitize Yb3+-doped silica fiber (YDF), while maintaining fiber numerical aperture (NA) at 0.12 under a high 2.5-wt.% Yb doping level. Based on the short monolithic DBR cavity constructed by this germanium-free photosensitive highly YDF, a 1064 nm fiber laser with a 48.6% slope efficiency and an over 200 mW power on two orthogonally polarized modes could be realized. Further stable and linear-polarized 1064 nm SFFL is also demonstrated in a designed monolithic polarization maintaining cavity with an output power of 119 mW and an efficiency of 26.4%. Our results provide an alternative way to develop photosensitive highly RE-doped fibers towards monolithic laser cavity application.

Er-doped silicate fiber amplifiers in the L-band with flat gain.

We demonstrated an efficient way to enhance and flatten the emission cross sections of Er3+ ions at the L-band in the silicate fiber amplifier by increasing Mg2+ (up to 22.5 mol%) with high field strength. High values of Er3+ concentration, lifetime, and L-band emission cross section were achieved in our silicate fibers. Particularly, the flatness at the L-band was achieved to be 0.8 dB, and a high gain coefficient at 1625 nm (4.7 dB/m) was demonstrated by pumping meter-scale Er-silicate fibers. The as-prepared Er-silicate fibers are attractive for the L-band fiber amplifier.

Theoretical and experimental investigation of Al3+ ion-suppressed phase-separation structures in rare-earth-doped high-phosphorus silica glasses.

Rare-earth-doped silica-based composite glasses (Re-SCGs) are widely used as high-quality laser gain media in defense, aerospace, energy, power, and medical applications. The variable regional chemical environments of Re-SCGs can induce new photoluminescence properties of rare-earth ions but can cause the selective aggregation of rare-earth ions, limiting the application of Re-SCGs in the field of high-power lasers. Here, topological engineering is proposed to adjust the degree of cross-linking of phase-separation network chains in Re-SCGs. A combination of experimental and theoretical characterization techniques suggested that the selective aggregation of rare-earth ions originates from the formation of phase-separated structures in glasses. The decomposition of nanoscale phase separation structures to the sub-nanometer scale, enabled by incorporating Al3+ ions, not only maintains the high luminescence efficiency of rare earth ions but also increases light transmittance and reduces light scattering. Furthermore, our investigation encompassed the exploration of the inhibitory mechanism of Al3+ ions on phase-separation structures, as well as their influence on the spectral characteristics of Re-SCGs. This work provides a new design concept for composite glass materials doped with rare-earth ions and could broaden their application in the field of high-power lasers.

Tex10 interacts with STAT3 to regulate hepatocellular carcinoma growth and metastasis.

Testis expression 10 (Tex10) is reported to be associated with tumorigenesis in several types of cancer types, but its role in hepatocellular carcinoma (HCC) metastasis has not been investigated. In this study, the expression of Tex10 in the HCC cell line and tissue microarray was determined by Western blot and immunohistochemistry (IHC), respectively. RNA sequencing-based transcriptome analysis was performed to identify the Tex10-mediated biological process. Cell Counting Kit-8, colony formation, transwell assays, xenograft tumor growth, and lung metastasis experiments in nude mice were applied to assess the effects of Tex10 on cell proliferation, migration, invasion, and metastasis. The underlying mechanisms were further investigated using dual-luciferase reporter, co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. We found that Tex10 was upregulated in HCC tumor tissues compared to adjacent normal tissues, with its expression correlated with a poor prognosis. Gene ontology function enrichment analysis revealed alterations in several biological processes in response to Tex10 knockdown, especially cell motility and cell migration. Functional studies demonstrated that Tex10 promotes HCC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Moreover, Tex10 was shown to regulate invasion and epithelial-mesenchymal transition via signal transducer and activator of transcription 3 (STAT3) signaling. Mechanistically, Tex10 was found to interact with STAT3 and promote its transcriptional activity. In addition, we found that Tex10 promotes p300-mediated STAT3 acetylation, while p300 silencing abolishes Tex10-enhanced STAT3 transcriptional activity. Together, these findings indicate that Tex10 functions as an oncogene by upregulating STAT3 activity, thus suggesting that Tex10 may serve as a prognostic biomarker and/or therapeutic target for HCC patients.

Large mode-field area multi-element silica glass fibers for gigahertz ultrafast lasers.

Multi-gigahertz ultrafast fiber lasers are critical for many significant applications, including bioimaging, optical communications, and laser frequency combs. The gain fiber which is expected to simultaneously satisfy large mode-field area, highly gain coefficient and resistance to photodarkening, will effectively protect mode-locked materials/devices that generally possesses low damage threshold (<10 mJ/cm2) and enhance stability in the centimeter-scale fiber lasers. However, the gain fiber still remains a significant challenge. In this study, multi-element Er-Yb: silica glass fibers with large mode-field area are fabricated. Benefiting from the multi-element design, normalized frequency V-parameter of the silica glass fiber with a core diameter of around 10 µm is <2.405. Using the large mode-field area fibers, ultrafast fiber lasers with 1.6 GHz fundamental repetition rate are proposed and demonstrated. The signal-to-noise rate of the radio-frequency signal reaching up to 90 dB and the long-term stability are realized. The results indicated the fabricated large mode-field area fibers are demonstrated to be ultrafast fiber lasers with short resonant cavities, which could be extended to other rare-earth glass fiber device for exploration of high-power amplification systems.

Efficient three-level continuous-wave and GHz passively mode-locked laser by a Nd3+-doped silicate glass single mode fiber.

Nd3+-doped three-level (4F3/2-4I9/2) fiber lasers with wavelengths in the range of 850-950 nm are of considerable interest in applications such as bio-medical imaging and blue and ultraviolet laser generation. Although the design of a suitable fiber geometry has enhanced the laser performance by suppressing the competitive four-level (4F3/2-4I11/2) transition at ∼1 µm, efficient operation of Nd3+-doped three-level fiber lasers still remains a challenge. In this study, taking a developed Nd3+-doped silicate glass single-mode fiber as gain medium, we demonstrate efficient three-level continuous-wave lasers and passively mode-locked lasers with a gigahertz (GHz) fundamental repetition rate. The fiber is designed using the rod-in-tube method and has a core diameter of 4 µm with a numerical aperture of 0.14. In a short 4.5-cm-long Nd3+-doped silicate fiber, all-fiber CW lasing in the range of 890 to 915 nm with a signal-to-noise ratio (SNR) greater than 49 dB is achieved. Especially, the laser slope efficiency reaches 31.7% at 910 nm. Furthermore, a centimeter-scale ultrashort passively mode-locked laser cavity is constructed and ultrashort pulse at 920 nm with a highest GHz fundamental repetition is successfully demonstrated. Our results confirm that Nd3+-doped silicate fiber could be an alternative gain medium for efficient three-level laser operation.

High ytterbium concentration Yb/Al/P/Ce co-doped silica fiber for 1-µm ultra-short cavity fiber laser application.

We demonstrate a high ytterbium concentration Yb/Al/P/Ce co-doped silica fiber by conventional modified chemical vapor deposition (MCVD) technology and solution doping process. The fiber has a Yb concentration of about 2.5 wt%, and the corresponding core absorption coefficient is measured to be ∼1400 dB/m at 976 nm. The gain coefficient was measured to be approximately 1.0 dB/cm. It is found that the Yb/Al/P/Ce co-doped silica shows a lower photodarkening-induced equilibrium loss of 52 dB/m at 633 nm than the Yb/Al/P co-doped silica fiber of 117 dB/m. Using the heavily Yb3+-doped silica fiber, a compact and robust ultrashort cavity single-frequency fiber laser was achieved with a maximum output power of 75 mW and a linewidth of 14 kHz. Furthermore, a compact passively mode-locked fiber laser (MLFL) with a repetition rate of 1.23 GHz was also proposed using our developed Yb-doped fiber. The laser properties of the proposed lasers were systematically investigated, demonstrating the superior performance of this fiber in terms of photodarkening resistance and ultrashort-cavity laser application. Furthermore, utilizing an all-fiber structure based on silica-based fiber offers the significant advantage of high stability and reliability.

Brillouin gain spectrum characterization in an acoustic anti-guided delivery fiber for high power narrow linewidth laser.

The Brillouin gain spectrum (BGS) provides key information for stimulated Brillouin scattering (SBS), such as the Brillouin frequency shift (BFS), Brillouin spontaneous linewidth, and Brillouin gain coefficient. In this study, we theoretically investigate the field distributions and BGS characterization of Ge-doped, Al-doped, and Al/Ge co-doped fibers. Additionally, we analyzed and compared the relationship between the BGS and acoustic refractive index. In particular, we demonstrate the crucial role played by acoustic modes in anti-waveguide structures. The simulation results show that the Brillouin gain coefficient decreases with a decreasing acoustic index in the fiber core region. Furthermore, we experimentally measure the SBS threshold and BGS of the Al/Ge co-doped fiber to examine the validity of the numerical model. The simulated and experimental results are consistent.

Sub-kHz linewidth 1.6-µm single-frequency fiber laser based on a heavily erbium-doped silica fiber.

We present a single-frequency erbium-doped fiber laser operated at 1608.8 nm using a homemade, heavily erbium-doped silica fiber as gain medium. The laser configuration is based on a ring cavity, which is combined with a fiber saturable absorber to achieve single-frequency operation. The measured laser linewidth is less than 447 Hz and the optical signal-to-noise ratio exceeds 70 dB. The laser exhibits an excellent stability, without any instance of mode-hopping during 1-hour observing. The fluctuations in both wavelength and power were measured to be 0.002 nm and less than 0.09 dB in a 45-minutes period. The laser produces over 14 mW of output power with a slope efficiency of 5.3%, which, to the best of our knowledge, is currently the highest power directly obtained from a single-frequency cavity based on an erbium-doped silica fiber above 1.6 µm.

Extending laser wavelengths to 1630†nm in centimeter-scale Er-phosphate fiber.

The spectral bandwidth of Er-doped fibers limits their lasing wavelength at longer wave band. Here, to the best of our knowledge, we report a broad emission band (1420‒1680 nm) of Er3+ and demonstrate for the first time an Er-phosphate fiber, which supports laser oscillation at the extended wavelengths of 1627 nm and 1630 nm, with the output powers and slope efficiencies of 44 mW/12.5% and 16.5 mW/5.6%, respectively, pumped at 1480 nm. To the best of our knowledge, these are the highest output powers and slope efficiencies at 1627 nm and 1630 nm from an Er3+-doped all-fiber configuration.

Transcriptome sequencing identifies prognostic genes involved in gastric adenocarcinoma.

Gastric adenocarcinoma (GAC) is one of the world's most lethal malignant tumors. It has been established that the occurrence and progression of GAC are linked to molecular changes. However, the pathogenesis mechanism of GAC remains unclear. In this study, we sequenced 6 pairs of GAC tumor tissues and adjacent normal tissues and collected GAC gene expression profile data from the TCGA database. Analysis of this data revealed 465 differentially expressed genes (DEGs), of which 246 were upregulated and 219 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were observably enriched in ECM-receptor interaction, protein digestion and absorption, and gastric acid secretion pathways. Six key genes (MATN3, COL1A1, COL5A2, P4HA3, SERPINE1 and VCAN) associated with poor GAC prognosis were screened from the protein‒protein interaction (PPI) network by survival analysis, and P4HA3 and MATN3 have rarely been reported to be associated with GAC. We further analyzed the function of P4HA3 in the GAC cell line SGC-7901 by RT‒qPCR, MTT, flow cytometry, colony formation, wound healing, Transwell and western blot assays. We found that P4HA3 was upregulated in the SGC-7901 cell line versus normal control cells. The outcomes of the loss-of-function assay illustrated that P4HA3 significantly enhanced the ability of GAC cells to proliferate and migrate. This study provides a new basis for the selection of prognostic markers and therapeutic targets for GAC.

STS1 and STS2 Phosphatase Inhibitor Baicalein Enhances the Expansion of Hematopoietic and Progenitor Stem Cells and Alleviates 5-Fluorouracil-Induced Myelosuppression.

STS1 and STS2, as the protein phosphatases that dephosphorylate FLT3 and cKIT, negatively regulate the self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs). To obtain the small molecule inhibitors of STS1/STS2 phosphatase activity used to expand HSPCs both in vitro and in vivo, we establish an in vitro phosphatase assay using the recombinant proteins of the STS1/STS2 histidine phosphatase (HP) domain, by which we screened out baicalein (BC) as one of the effective inhibitors targeting STS1 and STS2. Then, we further demonstrate the direct binding of BC with STS1/STS2 using molecular docking and capillary electrophoresis and verify that BC can restore the phosphorylation of FLT3 and cKIT from STS1/STS2 inhibition. In a short-term in vitro culture, BC promotes profound expansion and enhances the colony-forming capacity of both human and mouse HSPCs along with the elevation of phospho-FLT3 and phospho-cKIT levels. Likewise, in vivo administration with BC significantly increases the proportions of short-term hematopoietic stem cells (ST-HSCs), multipotent progenitors (MPPs) and especially long-term HSCs (LT-HSCs) in healthy mouse bone marrow and increases the numbers of colony-forming units (CFU) formed by HSPCs as well. More importantly, pre-administration of BC significantly enhances the survival of mice with lethal 5-fluorouracil (5-FU) injection due to the alleviation of 5-FU-induced myelosuppression, as evidenced by the recovery of bone marrow histologic injury, the increased proportions of LT-HSCs, ST-HSCs and MPPs, and enhanced colony-forming capacity. Collectively, our study not only suggests BC as one of the small molecule candidates to stimulate HSPC expansion both in vitro and in vivo when needed in either physiologic or pathologic conditions, but also supports STS1/STS2 as potential therapeutic drug targets for HSPC expansion and hematopoietic injury recovery.

Improved radiation resistance of an Er-doped silica fiber by a preform pretreatment method.

We report a novel pretreatment method to improve the radiation resistance of Er-doped fiber (EDF). The processing object of this method is EDF preform, and the pretreatment processing involves three steps: deuterium loading, pre-irradiation, and thermal annealing. The effects of pretreatment conditions on the optical loss, gain performance, and radiation resistance of EDF were systematically studied. The relevant mechanisms were revealed using Fourier transform infrared (FTIR), radiation-induced absorption (RIA), and electron paramagnetic resonance (EPR) spectroscopies. The results show that the pretreatment can not only greatly reduce the hydroxyl content of the EDF core, but it can also effectively improve the radiation resistance of EDF. The online test results show that the gain of the commercial, pristine, and pretreated EDFs were reduced by 19.0, 4.2, and 1.3 dB, respectively, corresponding to a decrease of 68.1, 16.2, and 4.7% after 98 krad X-rays irradiation. The high vacuum experiments show that the pretreatment method can maintain long-term stable high radiation resistance. This work provides a reference for the development of high-performance radiation resistant EDFs for use in the lower, middle, and geosynchronous earth orbit.

Saikosaponin A Inhibits Growth of Human Bladder Carcinoma T24 and 5637 Cells Both in Vitro and in Vivo.

Saikosaponin A (SSA)-a natural compound extracted from Radix bupleuri-possesses antitumor properties in several types of carcinomas. However, the role of SSA on bladder cancer and the mechanisms remain unclear. In this study, we have described the effect of SSA on human bladder cancer cell lines T24 and 5637 in the context of the regulation of mitochondrial pathways of apoptosis. In vitro, the Cell Counting Kit-8 (CCK-8) assay and cell wound healing assays were used to determine the proliferative effect of SSA treatment. Flow cytometry and Western blotting were performed to evaluate the apoptosis and related mechanisms. To further confirm that apoptosis is mediated through Caspase activation, Hoechst 33258 fluorescence staining assay was done after cells were treated with SSA and caspase inhibitor-Z-VAD-FMK. In vivo, an orthotopic xenograft mice model was adopted to evaluate the effect of SSA. The tumors were analyzed by hematoxylin-eosin (H&E) staining, immunohistochemical analysis, and Western blotting. In vitro, the results with CCK-8 assay showed obvious SSA-induced suppression in cell growth in a dose- and time-dependent manner. Flow cytometry analysis, Hoechst 33258 fluorescence staining assay and the assessment of the changes in the B-cell lymphoma 2 (Bcl-2) family protein expression level revealed that SSA could significantly induce cell apoptosis, which was associated with apoptosis via the mitochondrial pathways. In vivo, the results revealed a reduction in cell proliferation. In conclusion, our data suggest that SSA inhibits the growth of bladder cancer cells by activating the mitochondrial apoptosis pathway and inducing cell apoptosis.

Effects of Chronic Remote Ischemic Conditioning on Atrial Fibrillation Burden in Patients with Permanent Pacemakers.

This study aimed to evaluate the effects of chronic remote ischemic conditioning (CRIC) on atrial fibrillation burden in patients with an implanted pacemaker. Sixty-six patients with permanent pacemakers were randomly divided into the CRIC group and control group after 4 weeks of screening. CRIC treatment was performed twice daily for 12 weeks. The remote ischemic conditioning protocol consisted of 4 × 5 minutes inflation/deflation of the blood pressure cuff applied in the upper arm to create intermittent arm ischemia. Sixty-one patients (31 patients in the CRIC group and 30 patients in the control group) completed the study. CRIC was well tolerated by patients after 12 weeks of treatment. The burden of atrial fibrillation (AF) in the CRIC group decreased significantly at 4 weeks compared with that at 0 weeks (14.7% ± 18.5% versus 17.0% ± 20.7%, P < 0.001), which further decreased at 12 weeks compared with that at 0 weeks (8.6% ± 10.2% versus 17.0% ± 20.7%, P < 0.001) and that at 4 weeks (8.6% ± 10.2% versus 14.7% ± 18.5%, P < 0.001), which was not observed in the control group. AF burden also reduced significantly after 12-week CRIC compared with that in the control group (8.6% ± 10.2% versus 17.6% ± 19.5%, P = 0.013). Repeated measurement ANOVA showed that the changes in AF burden were associated with CRIC instead of time (P < 0.01). In addition, there were trends that the longest duration of AF and cumulative numbers of atrial high-rate episodes (AHREs) reduced after 12-week CRIC. This study suggests that a 12-week course of CRIC treatment could reduce AF burden in patients with permanent pacemakers, supporting the widespread use of CRIC in the daily lives of these patients, which needs to be verified in the future.

Tectorigenin enhances PDX1 expression and protects pancreatic ß-cells by activating ERK and reducing ER stress.

Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet ß-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to ß-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve ß-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for the PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in ß-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of ß-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet ß-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring ß-cell mass and islet size, respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD-impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet ß-cells both in vitro and in vivo.

Discovery and Verification of Key Liver Cancer Genes and Alternative Splicing Events Based on Second-Generation Sequencing Data Analysis.

Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Existing screening and early diagnosis methods are not highly sensitive for HCC, and patients are likely to develop the disease to the middle and advanced stages before being diagnosed. Therefore, finding new and efficient diagnosis and treatment methods has become an urgent problem. We aimed at finding and verifying new liver cancer markers by combining informatics analysis with experimental exploration to provide new ideas and methods for the diagnosis and treatment of clinical liver cancer. We used two different bioinformatic pipelines to analyze sequencing data of clinical liver cancer samples and identify differentially expressed genes and key variants after combining them with The Cancer Genome Atlas sequencing data. Then, we explored the functions and mechanisms of the key variants to identify potential liver cancer markers. Through bioinformatic analysis of sequencing data, 139 differentially expressed genes were found, including 53 upregulated genes and 86 downregulated genes. Through enrichment and alternative splicing event analysis of sequencing data, we found nine key variants with exon skipping events. Metallothionein 1E (MT1E)-203 was found to be a key variant that influenced cell proliferation through the p53 cell cycle pathway through cell viability and proliferation assays, and MT1E-203 lost the ability to bind two zinc ions due to exon skipping according to the structure prediction of MT1E-203. MT1E-203 is a potential biomarker for HCC and may play an important role in the diagnosis and treatment of HCC.

KIAA1217 Promotes Epithelial-Mesenchymal Transition and Hepatocellular Carcinoma Metastasis by Interacting with and Activating STAT3.

The survival and prognosis of hepatocellular carcinoma (HCC) are poor, mainly due to metastasis. Therefore, insights into the molecular mechanisms underlying HCC invasion and metastasis are urgently needed to develop a more effective antimetastatic therapy. Here, we report that KIAA1217, a functionally unknown macromolecular protein, plays a crucial role in HCC metastasis. KIAA1217 expression was frequently upregulated in HCC cell lines and tissues, and high KIAA1217 expression was closely associated with shorter survival of patients with HCC. Overexpression and knockdown experiments revealed that KIAA1217 significantly promoted cell migration and invasion by inducing epithelial-mesenchymal transition (EMT) in vitro. Consistently, HCC cells overexpressing KIAA1217 exhibited markedly enhanced lung metastasis in vivo. Mechanistically, KIAA1217 enhanced EMT and accordingly promoted HCC metastasis by interacting with and activating JAK1/2 and STAT3. Interestingly, KIAA1217-activated p-STAT3 was retained in the cytoplasm instead of translocating into the nucleus, where p-STAT3 subsequently activated the Notch and Wnt/ß-catenin pathways to facilitate EMT induction and HCC metastasis. Collectively, KIAA1217 may function as an adaptor protein or scaffold protein in the cytoplasm and coordinate multiple pathways to promote EMT-induced HCC metastasis, indicating its potential as a therapeutic target for curbing HCC metastasis.

Stevioside Activates AMPK to Suppress Inflammation in Macrophages and Protects Mice from LPS-Induced Lethal Shock.

Stevioside, a diterpenoid glycoside, is widely used as a natural sweetener; meanwhile, it has been proven to possess various pharmacological properties as well. However, until now there were no comprehensive evaluations focused on the anti-inflammatory activity of stevioside. Thus, the anti-inflammatory activities of stevioside, both in macrophages (RAW 264.7 cells, THP-1 cells, and mouse peritoneal macrophages) and in mice, were extensively investigated for the potential application of stevioside as a novel anti-inflammatory agent. The results showed that stevioside was capable of down-regulating lipopolysaccharide (LPS)-induced expression and production of pro-inflammatory cytokines and mediators in macrophages from different sources, such as IL-6, TNF-α, IL-1ß, iNOS/NO, COX2, and HMGB1, whereas it up-regulated the anti-inflammatory cytokines IL-10 and TGF-ß1. Further investigation showed that stevioside could activate the AMPK -mediated inhibition of IRF5 and NF-κB pathways. Similarly, in mice with LPS-induced lethal shock, stevioside inhibited release of pro-inflammatory factors, enhanced production of IL-10, and increased the survival rate of mice. More importantly, stevioside was also shown to activate AMPK in the periphery blood mononuclear cells of mice. Together, these results indicated that stevioside could significantly attenuate LPS-induced inflammatory responses both in vitro and in vivo through regulating several signaling pathways. These findings further strengthened the evidence that stevioside may be developed into a therapeutic agent against inflammatory diseases.

Characterization and identification of long non-coding RNAs based on feature relationship.

MOTIVATION: The significance of long non-coding RNAs (lncRNAs) in many biological processes and diseases has gained intense interests over the past several years. However, computational identification of lncRNAs in a wide range of species remains challenging; it requires prior knowledge of well-established sequences and annotations or species-specific training data, but the reality is that only a limited number of species have high-quality sequences and annotations. RESULTS: Here we first characterize lncRNAs in contrast to protein-coding RNAs based on feature relationship and find that the feature relationship between open reading frame length and guanine-cytosine (GC) content presents universally substantial divergence in lncRNAs and protein-coding RNAs, as observed in a broad variety of species. Based on the feature relationship, accordingly, we further present LGC, a novel algorithm for identifying lncRNAs that is able to accurately distinguish lncRNAs from protein-coding RNAs in a cross-species manner without any prior knowledge. As validated on large-scale empirical datasets, comparative results show that LGC outperforms existing algorithms by achieving higher accuracy, well-balanced sensitivity and specificity, and is robustly effective (>90% accuracy) in discriminating lncRNAs from protein-coding RNAs across diverse species that range from plants to mammals. To our knowledge, this study, for the first time, differentially characterizes lncRNAs and protein-coding RNAs based on feature relationship, which is further applied in computational identification of lncRNAs. Taken together, our study represents a significant advance in characterization and identification of lncRNAs and LGC thus bears broad potential utility for computational analysis of lncRNAs in a wide range of species. AVAILABILITY AND IMPLEMENTATION: LGC web server is publicly available at http://bigd.big.ac.cn/lgc/calculator. The scripts and data can be downloaded at http://bigd.big.ac.cn/biocode/tools/BT000004. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.