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SOX9, as a transcript factor, has been confirmed to boost proliferation and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC), but the underlying mechanism remains incompletely elucidated. A bioinformatics analysis web, Jaspar, manifested that SOX9 can transcriptionally regulate an lncRNA, MKLN1-AS. To determine the role of MKLN1-AS in HCC, this study measured MKLN1-AS expression in HCC and the paracancerous tissues and conducted a series of assays, including MTT, colony formation, and transwell assays, in vitro. EMT of HCC was evaluated by E-cadherin and vimentin protein levels. The regulatory effect of SOX9 on MKLN1-AS was determined using dual luciferase reporter and ChIP assays. Both MKLN1-AS and SOX9 were up-regulated in HCC tissues compared to paracancerous tissues. SOX9 promoted cell viability, proliferation, invasion, and EMT of HCCs, but these promoting effects of SOX9 were attenuated after the knockdown of MKLN1-AS. Overexpression of SOX9 increased MKLN1-AS in HCCs, whereas silencing SOX9 decreased MKLN1-AS expression. According to dual luciferase reporter and ChIP assays, SOX9 can bind to the promoter of MKLN1-AS gene to stimulate the expression. MKLN1-AS is transcriptionally regulated by SOX9 and mediates the effects of SOX9 on the proliferation and EMT of HCCs.

Background Long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is an oncogenic lncRNA that has been reported in many cancers, but the role of SNHG3 in cholangiocarcinoma (CCA) remains largely unknown. Bioinformatic analysis revealed a regulatory relationship among SNHG3, miR-3173-5p, and ERG. miR-3173-5p is a tumour suppressive miRNA, while ERG is an oncogene. In the present study, we focused on the regulatory effects and molecular mechanisms of SNHG3 in CCA. Method The expression of SNHG3 and miR-3173-5p was evaluated using qRT-PCR analysis. Knockdown of SNHG3 was achieved by shRNA. Cell viability was assessed by MTT assay. Migration and invasion were determined by Transwell assay. Flow cytometry was used to assess cell apoptosis. Western blots were applied to quantify protein levels. Furthermore, using RNA pulldown and dual luciferase assays, the interactions between SNHG3 and miR-3173-5p and between miR-3173-5p and ERG in CCA cells were validated. Results SNHG3 was significantly upregulated in CCA cells compared with normal human intrahepatic biliary epithelial cells. Knockdown of SNHG3 inhibited the proliferation and migration of CCA cells. Mechanistically, SNHG3-sponged miR-3173-5p, thus releasing the repression of ERG by miR-3173-5p. Rescue experiments showed that the miR-3173-5p/ERG axis mediated the oncogenic effect of SNHG3. Conclusion Taken together, our data suggest that SNHG3 is a pleiotropic oncogenic lncRNA in CCA. Knockdown of SNHG3 expression suppressed malignant phenotypes in CCA cells via the miR-3173-5p/ERG axis.

TPS635 Background: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer, accounting for 75%–85% of cases, for which surgical resection represents the most effective treatment, with curative potential. However, the high incidence of tumor relapse (50%–70% 5 years after surgery) has hindered improved survival. Furthermore, early recurrence within 2 years after surgery accounts for 70% of relapsed HCC cases, is rarely treatable, and has been associated with poor survival. With the development of novel tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, no guidelines for novel systematic therapy to treat high risk of relapse HCC have been established. Targeted therapy combined with immunotherapy as systemic treatment has become a new approach in high risk of relapse HCC. Hyperthermic intraperitoneal chemotherapy (HIPEC), as an adjuvant treatment of abdominal malignant tumors, has achieved unique effects in the treatment of many cancers. The aim of this study was to assess the activity and feasibility of a combination of HIPEC with Tislelizumab and TKIs for the treatment of high risk of relapse HCC. Methods: The single-center, open-label, one-armed, Phase 2 study (NCT05546619) will enroll ~30 adults who meet the diagnostic criteria of high risk of relapse HCC (multiple tumors or satellite lesions; tumor diameter > 5cm; HCC rupture and bleeding; combined with vascular invasion; AFP > 32ng/ml). Patients will receive the following treatments as noted in the table. The primary and secondary endpoints are listed in the table. Tumor response will be evaluated once every 6 weeks for the first 48 weeks of treatment, and once every 12 weeks thereafter according to RECIST v1.1; safety will be assessed through monitoring the incidence and severity of adverse events graded according to CTCAE 5.0, vital signs and clinical laboratory results. Clinical trial information: NCT05546619 . [Table: see text]

Background Gastric cancer was still one of the commonly diagnosed cancer types and the third-most common cause of cancer-related death in the world. Gentiopicroside, which is extracted from the Gentianella acuta, is commonly used in both traditional treatment and modern clinical care; therefore, its anticancer effects have been attracted more attention. However, the systematic analysis of action mechanism of Gentiopicroside on gastric cancer (GC) has not yet been carried out. Aim A network pharmacology-based strategy combined with molecular docking studies and in vitro validation was employed to investigate potential targets and molecular mechanism of Gentiopicroside against GC. Materials and Methods Potential targets of Gentiopicroside, as well as related genes of GC, were acquired from public databases. Potential targets, and signaling pathways were determined through bioinformatic analysis, including protein–protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the above findings. Results Our findings revealed that the anticancer activity of Gentiopicroside potentially involves 53 putative identified target genes. In addition, GO, KEGG, and network analyses revealed that these targets were associated with cell proliferation, metabolic process, and other physiological processes. Furthermore, we have proved that critical compound affected the expression of CCND1, CCNE1, p-AKT and p-P38 at protein levels. These findings provide an overview of the anticancer action of Gentiopicroside from a network perspective; meanwhile, it might also set an example for future studies of other materials used in traditional Chinese medicine (TCM). Conclusion This study comprehensively illuminated the potential targets and molecular mechanism of Gentiopicroside against GC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of TCM treating for disease.

We report a dramatic fast X-ray dimming event in a z=2.627 radio-quiet type 1 quasar, which has an estimated supermassive black hole (SMBH) mass of $6.3\times 10^{9} M_\odot$. In the high X-ray state, it showed a typical level of X-ray emission relative to its UV/optical emission. Then its 0.5-2 keV (rest-frame 1.8-7.3 keV) flux dropped by a factor of $\approx7.6$ within two rest-frame days. The dimming is associated with spectral hardening, as the 2-7 keV (rest-frame 7.3-25.4 keV) flux dropped by only $17\%$ and the effective power-law photon index of the X-ray spectrum changed from $\approx2.3$ to $\approx0.9$. The quasar has an infrared (IR)-to-UV spectral energy distribution and a rest-frame UV spectrum similar to those of typical quasars, and it does not show any significant long-term variability in the IR and UV/optical bands. Such an extremely fast and large-amplitude X-ray variability event has not been reported before in luminous quasars with such massive SMBHs. The X-ray dimming is best explained by a fast-moving absorber crossing the line of sight and fully covering the X-ray emitting corona. Adopting a conservatively small size of $5 {G} M_{\rm BH}/c^2$ for the X-ray corona, the transverse velocity of the absorber is estimated to be $\approx 0.9c$. The quasar is likely accreting with a high or even super-Eddington accretion rate, and the high-velocity X-ray absorber is probably related to a powerful accretion-disk wind. Such an energetic wind may eventually evolve into a massive galactic-scale outflow, providing efficient feedback to the host galaxy., 16 pages, 6 figures, accepted for publication in ApJ

Intrahepatic cholangiocarcinoma (ICC) is a primary malignant liver tumour whose incidence is second only to that of hepatocellular carcinoma. ICC is a highly heterogeneous disease arising from neoplastic transformation of intrahepatic biliary epithelial cells (cholangiocytes), and it is characterized by a very poor prognosis. Signal transducer and activator of transcription 3 (STAT3) is an important oncogene that is widely expressed in numerous cancers. STAT3 is a candidate target for the treatment of ICC. However, studies on STAT3 and the occurrence and development of ICC require improvements. Therefore, the present review summarized the mechanism of STAT3 in ICC and provided a theoretical basis for STAT3 to become an effective target for determining the prognosis and treatment of ICC.

Quasar outflows may play a crucial role in regulating the host galaxy, although the spatial scale of quasar outflows remain a major enigma, with their acceleration mechanism poorly understood. The kinematic information of outflow is the key to understanding its origin and acceleration mechanism. Here, we report the galactocentric distances of different outflow components for both a sample and an individual quasar. We find that the outflow distance increases with velocity, with a typical value from several parsecs to more than one hundred parsecs, providing direct evidence for an acceleration happening at a scale of the order of 10 parsecs. These outflows carry ~1% of the total quasar energy, while their kinematics are consistent with a dust driven model with a launching radius comparable to the scale of a dusty torus, indicating that the coupling between dust and quasar radiation may produce powerful feedback that is crucial to galaxy evolution., 10 pages, 4 figures in main text. Published in Science Advances on 11 Feb 2022

We present the first near-IR spectroscopy and joint analyses of multi-wavelength observations for SDSS J082747.14+425241.1, a dust-reddened, weak broad emission-line quasar (WLQ) undergoing a remarkable broad absorption line (BAL) transformation. The systemic redshift is more precisely measured to be $z=2.070\pm0.001$ using H$\beta$ compared to $z=2.040\pm0.003$ using \mgii\ from the literature, signifying an extreme \mgii\ blueshift of $2140\pm530$ \kms\ relative to H$\beta$. Using the H$\beta$-based single-epoch scaling relation with a systematic uncertainty of 0.3 dex, its black hole (BH) mass and Eddington ratio are estimated to be $M_{\rm BH}\sim6.1\times10^8M_\odot$ and $\lambda_{\rm Edd}\sim0.71$, indicative of being in a rapidly accreting phase. Our investigations confirm the WLQ nature and the LoBAL$\rightarrow$HiBAL transformation, along with a factor of 2 increase in the \mgii+\feii\ emission strength and a decrease of 0.1 in $E(B-V)$ over two decades. The kinetic power of this LoBAL wind at $R\sim$15 pc from its BH is estimated to be $\sim$43\% of the Eddington luminosity, sufficient for quasar feedback upon its host galaxy albeit with an order-of-magnitude uncertainty. This quasar provides a clear example of the long-sought scenario where LoBAL quasars are surrounded by dust cocoons, and wide-angle nuclear winds play a key role in the transition for red quasars evolving into the commonly seen blue quasars., Comment: 11 pages, 6 figures, accepted for publication in ApJ

Background. This study is aimed at investigating the feasibility and safety of the laparoscopic radical resection for treating type III and IV hilar cholangiocarcinoma (III/IV Hilar C). Methods. Six patients with III/IV Hilar C were enrolled in our hospital. All patients underwent total laparoscopic surgery, including basic surgery (laparoscopic gallbladder, hilar bile duct, and common bile duct resection and hepatoduodenal ligament lymph node dissection) combined with left hepatic and caudate lobe resection/portal resection. The tumor size, operation time, intraoperative blood loss, and postoperative complications were observed. The follow-up of the patients after discharge was recorded. Results. Surgery was successfully completed in 6 patients. We found that the tumor size of 6 patients ranged from 1.5 to 3.6 cm, with 4 lymph nodes. The operation time was 540-660 minutes, and the blood loss was 300-500 ml. One patient developed bile leakage after surgery, healed within 2 weeks after drainage. The postoperative hospital stay was 16 (13-24) days. There were 4 cases of negative bile duct margin tumor, 1 case was positive, and 1 case was not reported. All 6 patients were discharged smoothly without perioperative death. Regular examinations were conducted every 3 months after discharge, and the median duration was 7 months. Only 1 patient had a marginal dysplasia, and 5 patients had no obvious signs of recurrence. Conclusions. Application of laparoscopic radical resection for III/IV Hilar C is safe and feasible and has good short-term efficacy with adequate preoperative evaluation, appropriate case selection, and precise operative strategy.

We present Chandra observations of 2106 radio-quiet quasars in the redshift range 1.799.99% level) between $\alpha_{ox}$ and these emission-line parameters, as well as between $\Delta\alpha_{ox}$ and CIV EW. Slight correlations are found between $\Delta\alpha_{ox}$ and CIV blueshift, MgII EW, and the CIV EW to MgII EW ratio. The best-fit trend in each parameter space is used to compare the X-ray weakness ($\Delta\alpha_{ox}$) and optical/UV emission properties of typical quasars and weak-line quasars (WLQs). The WLQs typically exhibit weaker X-ray emission than predicted by the typical quasar relationships. The best-fit relationships for our typical quasars are consistent with predictions from the disk-wind quasar model. The behavior of the WLQs compared to our typical quasars can be explained by an X-ray "shielding" model., Comment: 24 pages, 16 Figures

Purpose. The aim of the study was to investigate the effect of hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) combined with radical surgery and capecitabine on stage III gallbladder cancer. Method. Seventy-eight patients with stage III gallbladder cancer treated in our hospital between December 2015 and April 2019 were retrospectively enrolled. Depending on the treatment approach, the patients were divided into the control group (radical surgery and capecitabine) and the HIPEC group (hyperthermic intraperitoneal perfusion chemotherapy combined with radical surgery and capecitabine). The patients were followed up by outpatient or through telephone until April 1, 2020. SPSS 19.0 software was applied for data analysis. Survival analysis was performed using the Kaplan–Meier method and parallel log-rank test. Results. There were 43 cases in the control group and 35 cases in the HIPEC group. There were no significant differences in operation time, lymph node metastasis, microvascular infiltration, and nerve invasion; there was no significant difference in postoperative complications between the two groups ( P > 0.05 ). The average hospitalization time of the HIPEC group was 23.0 ± 6.9 days, which was longer than the 20.0 ± 5.8 days of the control group ( P < 0.05 ). The body temperatures of HIPEC group patients at 0 h and 6 h after operation were higher than those of patients in the control group ( P < 0.05 ); however, the body temperature of the two groups gradually became the same at 12–24 h after operation. There was no liver and kidney damage in the two groups after surgery. The platelets in the HIPEC group were less than those in the control group ( P < 0.05 ). The median survival time of HIPEC was 19.2 months, which was longer than 15.3 months in the control group. The 1-year survival rates of the two groups were 91.43% vs. 76.71%, and the 2-year survival rates were 26.29% vs. 17.53%, respectively ( P < 0.05 ). Conclusion. HIPEC combined with radical surgery and capecitabine for stage III gallbladder cancer can effectively prolong survival time without increasing surgery-related complications.

We present ultraviolet spectroscopy covering the Lyα + N v complex of six candidate low-redshift (0.9 < z < 1.5) weak emission-line quasars (WLQs) based on observations with the Hubble Space Telescope. The original systematic searches for these puzzling Type 1 quasars with intrinsically weak broad emission lines revealed an N ≈ 100 WLQ population from optical spectroscopy of high-redshift (z > 3) quasars, defined by a Lyα + N v rest-frame equivalent width (EW) threshold z < 3) WLQ candidates, however, has relied primarily on optical spectroscopy of weak broad emission lines at longer rest-frame wavelengths. With these new observations expanding existing optical coverage into the ultraviolet, we explore unifying the low- and high-z WLQ populations via EW[Lyα+N v]. Two objects in the sample unify with high-z WLQs, three others appear consistent with the intermediate portion of the population connecting WLQs and normal quasars, and the final object is consistent with typical quasars. The expanded wavelength coverage improves the number of available line diagnostics for our individual targets, allowing a better understanding of the shapes of their ionizing continua. The ratio of EW[Lyα+N v] to EW[Mg ii] in our sample is generally small but varied, favoring a soft ionizing continuum scenario for WLQs, and we find a lack of correlation between EW[Lyα+N v] and the X-ray properties of our targets, consistent with a “slim-disk” shielding gas model. We also find indications that weak absorption may be a more significant contaminant in low-z WLQ populations than previously thought.

Built upon a sample of 134 quasars that was dedicated to a systematic study of \mgii-BAL variability from Yi et al. (2019a), we investigate these quasars showing \mgii-BAL disappearance or emergence with the aid of at least three epoch optical spectra sampled more than 15 yr in the observed frame. We identified 3/3 quasars undergoing pristine/tentative BAL transformations. The incidence of pristine BAL transformations in the sample is therefore derived to be 2.2$_{-1.2}^{+2.2}$\%, consistent with that of high-ionization BAL transformations from the literature. Adopting an average \mgii-BAL disappearance timescale of rest-frame 6.89 yr among the six quasars, the average characteristic lifetime of \mgii\ BALs in the sample is constrained to be $>$160 yr along our line of sight. There is a diversity of BAL-profile variability observed in the six quasars, probably reflecting a variety of mechanisms at work. Our investigations of \mgii-BAL transitions, combined with observational studies of BAL transitions from the literature, imply an overall FeLoBAL/LoBAL$\rightarrow$HiBAL/non-BAL transformation sequence along with a decrease in reddening. This sequence is consistent with the evacuation models for the origin of commonly seen blue quasars, in which LoBAL quasars are in a shorted-lived, blowout phase., Accepted by ApJS; 14 pages with 5 figures and 2 tables

Background The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare. Case presentation A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up. Conclusions We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.

Cholangiocarcinoma (CCA) is a highly aggressive and malignant tumor. In this study, the effect and molecular mechanism of nuclear enriched abundant transcript 1 (NEAT1) in CCA were elucidated. The expressions of NEAT1, microRNA‐186‐5p (miR‐186‐5p), and PTP4A1 were measured by quantitative real‐time PCR. The protein levels were measured by Western blotting. Kaplan–Meier analysis was performed to create survival curves. The interactions between NEAT1, miR‐186‐5p, and PTP4A1 were assessed through the dual luciferase reporter assay. Additionally, the cell proliferation, apoptosis, migration, and invasion were measured by colony formation, flow cytometry, the Transwell assay, and the wound healing assay, respectively. NEAT1 and PTP4A1 were significantly upregulated in CCA tissues and cells, but miR‐186‐5p was downregulated. NEAT1 expression was negatively correlated with the survival of CCA patients and has remarkable correlation with serum CA199 levels and lymph node metastasis. Besides, NEAT1 could act as a molecular sponge for miR‐186‐5p to upregulate PTP4A1 expression. More importantly, the knockdown of NEAT1 or overexpression of miR‐186‐5p inhibited the proliferation, migration and invasion of CCA cells, and the inhibition of miR‐186‐5p reversed the effects of the knockdown of NEAT1. In addition, NEAT1 could also activate the PI3K/AKT signaling pathway and regulate the epithelial‐mesenchymal transition (EMT) through the miR‐186‐5p/PTP4A1 axis. In conclusion, NEAT1 was involved in cell proliferation, migration and invasion in CCA, and the NEAT1/miR‐186‐5p/PTP4A1/PI3K/AKT axis indicated novel regulatory mechanisms and therapeutics for the treatment of CCA.

We report the discovery of an extreme X-ray flux rise (by a factor of > 20) of the weak-line quasar SDSS J153913.47+395423.4 (hereafter SDSS J1539+3954) at z = 1.935. SDSS J1539+3954 is the most-luminous object among radio-quiet type 1 AGNs where such dramatic X-ray variability has been observed. Before the X-ray flux rise, SDSS J1539+3954 appeared X-ray weak compared with the expectation from its UV flux; after the rise, the ratio of its X-ray flux and UV flux is consistent with the majority of the AGN population. We also present a contemporaneous HET spectrum of SDSS J1539+3954, which demonstrates that its UV continuum level remains generally unchanged despite the dramatic increase in the X-ray flux, and its C iv emission line remains weak. The dramatic change only observed in the X-ray flux is consistent with a shielding model, where a thick inner accretion disk can block our line of sight to the central X-ray source. This thick inner accretion disk can also block the nuclear ionizing photons from reaching the high-ionization broad emission-line region, so that weak high-ionization emission lines are observed. Under this scenario, the extreme X-ray variability event may be caused by slight variations in the thickness of the disk. This event might also be explained by gravitational light-bending effects in a reflection model., 8 pages, 3 figures. Accepted for publication in ApJL

We continuously monitored the blazar S5 0716+714 in the optical $g$, $r$ and $i$ bands from Nov. 10, 2017 to Jun. 06, 2019. The total number of observations is 201 nights including 26973 data points. This is a very large quasi-simultaneous multicolor sample for the blazar. The average time spans and time resolutions are 3.4 hours and 2.9 minutes per night, respectively. During the period of observations, the target source in the $r$ band brightens from $14^{\rm m}.16$ to $12^{\rm m}.29$ together with five prominent sub-flares, and then first becomes fainter to $14^{\rm m}.76$ and again brightens to $12^{\rm m}.94$ with seven prominent sub-flares. For the long-term variations, we find a strong flatter when brighter (FWB) trend at a low flux state and then a weak FWB trend at a higher flux state. A weak FWB trend at a low flux state and then a strong FWB trend at a higher flux state are also reported. Most of sub-flares show the strong FWB trends, except for two flares with a weak FWB trend. The particle acceleration and cooling mechanisms together with the superposition of different FWB-slopes from sub-flares are likely to explain the optical color behaviours. A scenario of bent jet is discussed., Comment: 27 pages, 9 figures, 4 tables, accepted for publication in ApJS

Polycystic ovary syndrome (PCOS) is a common endocrinal metabolic disease, and its pathogenesis has not yet been thoroughly studied. The purpose of this experiment was to investigate the effect of RNA interference on Oatp3a1 gene expression on the biological viability and immune factors of ovarian granulosa cells in rats with PCOS. First, rats were intragastrically administered 1 mg/kg letrozole to successfully construct PCOS model. Western blot, qRT-PCR, CCK8 and flow cytometry were used to detect the gene expression, immune factor protein expression, cell proliferation and apoptosis in ovarian granulosa cells transfected with siRNA Oatp3a1 in rats with PCOS, respectively. The results showed that follicle stimulating hormone receptor (FSHR) was located on the cell membrane of rat ovarian granulosa cells, and letrozole successfully induced PCOS rat model. In PCOS rat ovarian granulosa cells, the mRNA expression level of Oapta1 was higher than that in normal rat ovarian granulosa cells. At the same time, compared with the sham group, the protein expression of NF-κB, TGF-β1 and VEGF in si-Oatp3a1 group was significantly down-regulated (P < 0.05), and the cell proliferation rate was significantly decreased in si-Oatp3a1 group (P < 0.05) in comparison with the sham group. The apoptotic rate was increased obviously (P < 0.05), which was about 2.5 times that of the sham group. This indicates that in the ovarian granulosa cells of rats with PCOS, the interference of Oatp3a1 gene expression can significantly inhibit cell proliferation and promote apoptosis, while inhibiting the expression of immune factors TGF-β1 and VEGF can reduce the expression of NF-κB protein, thereby suppressing the activation of the NF-κB signaling pathway.

Backgrounds/aims Hepatocellular carcinoma is recognized as the most common subtype of hepatic cancer. Muskelin 1 antisense RNA (MKLN1-AS) shows prognostic value in hepatitis B virus-hepatocellular carcinoma. The aim of this study is to investigate the detailed biological role of MKLN1-AS and Yes-associated transcriptional regulator 1 (YAP1)-related mechanisms. Methods Based on online databases (GEPIA, TCGA, and GEO), the expression of MKLN1-AS and YAP1 in patients with hepatocellular carcinoma was analyzed. The IntaRNA algorithm was used to predict complementary sites between MKLN1-AS and YAP1 mRNA. Hepatocellular carcinoma tumor tissues and cells were collected for the quantification of MKLN1-AS and YAP1. FISH was performed to explore the location of MKLN1-AS in cells. The effects of MKLN1-AS and YAP1 on proliferation, migration and invasionof hepatocellular carcinoma were determined in vitro and in vivo. Actinomycin D and RNA immunoprecipitation were resorted to confirm the regulatory role of MKLN1-AS in YAP1 expression. Results The up-regulation of MKLN1-AS contributed to the poor prognosis of patients with hepatocellular carcinoma. MKLN1-AS and YAP1 were overexpressed in hepatocellular carcinoma tissues and cells. MKLN1-AS positively modulated YAP1 expression through targeting and stabilizing YAP1 mRNA.MKLN1-AS was predominantly located in the cytoplasm of the cells. MKLN1-AS intensified proliferation, migration and invasion of hepatocellular carcinoma cells via YAP1. MKLN1-AS also caused hepatocarcinogenesis through inducing YAP1 expression in vivo. Conclusions MKLN1-AS overexpression enhances the stability of YAP1 mRNA, which is necessary for the oncogenic activity of MKLN1-AS. MKLN1-AS can be utilized in the diagnosis and prognosis of hepatocellular carcinoma as an upstream factor of YAP1.

As hybrids of narrow-line Seyfert 1 (NLS1) galaxies and blazars, {\gamma}-ray emitting NLS1s are important probes of jet physics in the high Eddington-ratio regime. Only very few of them are known to date; the majority of them below redshift z = 0.5. Here we present the identification of the {\gamma}-ray emitting AGN TXS 0943+105 (SDSS J094635.06+101706.1) as a high-redshift NLS1 galaxy. It turns out to be one of the radio-loudest NLS1s known, highly variable at all wavelengths, and shows widely extended radio emission at a (projected) > 100 kpc scale. It is a known strong {\gamma}-ray emitter with a luminous flare reported previously. At redshift z=1.004, this is the most distant {\gamma}-NLS1 known to date., Comment: 6 pages, 5 figures, MNRAS Letters in press

Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) has a role in various common types of human malignancy, including cholangiocarcinoma; however, the expression and function of UCA1 in intrahepatic cholangiocarcinoma (ICC) has remained elusive. In the present study, it was observed that UCA1 expression was significantly upregulated in ICC tissues and cell lines compared with that in the adjacent non-tumour tissues and a human intrahepatic biliary epithelial cell line, respectively. The increased expression of UCA1 was significantly associated with lymph node metastasis and clinical T-stage in ICC. Furthermore, the ICC patients with high expression of UCA1 had a shorter survival time when compared with that of patients with low UCA1 expression. Knockdown of UCA1 caused a significant decrease in ICC cell proliferation and invasion, while ectopic overexpression of UCA1 significantly promoted the proliferation and invasion of ICC cells. Furthermore, it was revealed that UCA1 directly binds to microRNA (miR)-122 to negatively regulate its expression in ICC cells. In addition, miR-122 mimics abrogated the promoting effects of UCA1 on ICC cell proliferation and invasion. In addition, an inverse correlation between miR-122 and UCA1 expression in ICC tissues was observed. In conclusion, the present study demonstrates that the lncRNA UCA1 promotes ICC cell proliferation and invasion at least in part by targeting miR-122, suggesting that the UCA1/miR-122 interaction may become a potential therapeutic target for the treatment of ICC.

We report the discovery of disappearance of Mg ii, Al iii, C iv, and Si iv broad absorption lines (BALs) at the same velocity, accompanied by a new Civ BAL emerging at a higher velocity, in the quasar J0827+4252 at z = 2.038. This is the first report of BAL disappearance (i) over Mg ii, Al iii, C iv, and Si iv ions and (ii) in a weak emission-line quasar (WLQ). The discovery is based on four spectra from the SDSS and one follow-up spectrum from HET/LRS2. The simultaneous Civ BAL disappearance and emergence at different velocities, together with no variations in the CRTS light curve, indicate that ionization changes in the absorbing material are unlikely to cause the observed BAL variability. Our analyses reveal that transverse motion is the most likely dominant driver of the BAL disappearance/emergence. Given the presence of mildly relativistic BAL outflows and an apparently large C iv emission-line blueshift that is likely associated with strong bulk outflows in this WLQ, J0827+4252 provides a notable opportunity to study extreme quasar winds and their potential in expelling material from inner to large-scale regions., Comment: Published in 2019 ApJL, 870, 2

Lijiang 2.4-meter Telescope(LJT), the largest common-purpose optical telescope in China, has been applied to the world-wide astronomers since 2008. It is located at Gaomeigu site, Lijiang Observatory(LJO), the southwest of China. The site has very good observational conditions. Since 10-year operation, several instruments have been equipped on the LJT. Astronomers can perform both photometric and spectral observations. The main scientific goals of LJT include photometric and spectral evolution of supernova, reverberation mapping of active galactic nucleus, physical properties of binary star and near-earth object(comet and asteroid), identification of exoplanet, and all kinds of transients. Until now, the masses of 41 high accretion rate black holes have been measured, and more than 168 supernova have been identified by the LJT. More than 190 papers related to the LJT have been published. In this paper, the general observation condition of the Gaomeigu site is introduced at first. Then, the LJT structure is described in detail, including the optical, mechanical, motion and control system. The specification of all the instruments, and some detailed parameters of the YFOSC is also presented. Finally, some important scientific results and future expectations are summarized., Comment: 20 pages, 14 figures, accepted by Research in Astronomy and Astrophysics(RAA)

Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. Cangfu Daotan Decoction (CFDTT) is one of the prescriptions in the stagnation of obesity-type PCOS. Our previous study showed that CFDTT treatment of obese PCOS was correlated with organic anion transporting polypeptides (OATPs). Methods Here, we studied the effects of CFDTT on obese PCOS and its underlying mechanism. We built an obese PCOS rat model and treated the rats with CFDTT. Then, we detected the serum levels of TCHO, TG, LDL-c, HDL-c, luteinizing hormone (LH), follicle stimulating growth hormone (FSH), testosterone (T), estradiol (E2), IL-1β, IL-6, and TNF-α in each group and adopted RT-PCR, western blotting and immunohistochemical staining to investigate the effects of CFDTT treatment on the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. In addition, we compared the pregnancy outcomes of each group. Results We found that CFDTT decreased the serum levels of TCHO, TG, LDL-c, LH, T, IL-1β, IL-6, and TNF-α and increased the levels of HDL-c, FSH and E2 in a dose-dependent manner. CFDTT could induce the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. Moreover, CFDTT could improve pregnancy outcomes. Conclusion These data suggested that the therapeutic mechanism of Cangfu Daotan Decoction on PCOS may be correlated with regulating lipid metabolism, sex hormone secretion and the inflammatory response and increasing OATP2B1 and OATP3A1 expression. Cangfu Daotan Decoction can be developed as a PCOS treatment drug.

We present optical spectroscopic and photometric observations of the nearby type Ic supernova (SN Ic) SN 2014L. This SN was discovered by the Tsinghua-NAOC Transient Survey (TNTS) in the nearby type-Sc spiral galaxy M99 (NGC 4254). Fitting to the early-time light curve indicates that SN 2014L was detected at only a few hours after the shock breakout, and it reached a peak brightness of $M_{\rm V} = -17.73 \pm 0.28$ mag ($L= [2.06\pm 0.50] \times 10^{42}$ erg s$^{-1}$) approximately 13 days later. SN 2014L shows a close resemblance to SN 2007gr in the photometric evolution, while it shows stronger absorption features of intermediate-mass elements (especially \CaII) in the early-time spectra. Based on simple modeling of the observed light curves, we derived the mass of synthesized $^{56}$Ni as $M_{\rm Ni} = 0.075 \pm 0.025 M_{\odot}$, and the mass and total energy of the ejecta as $M_{\rm ej} = 1.00 \pm 0.20 M_\odot$ and $E_{\rm ej}=1.45\pm0.25$ foe, respectively. Given these typical explosion parameters, the early detection, and the extensive observations, we suggest that SN 2014L could be a template sample for the investigation of SNe Ic., Comment: 14 pages, 12 figures, accepted for publication in ApJ

Leptin is an adipokine minimally known for its activities or underlying mechanisms in cholangiocarcinoma. The present study explored the effects of leptin on the epithelial‑mesenchymal transition (EMT) and pro‑angiogenic capability of cholangiocarcinoma cells, and investigated the underlying mechanisms. Cholangiocarcinoma cells were treated with leptin, and their migration and invasion rates were investigated using Transwell assays. Furthermore, conditioned medium was collected from cholangiocarcinoma cells following leptin treatment and applied to human umbilical vein endothelial cells to assess tube formation. The expression of EMT and pro‑angiogenic factors was examined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses. Mechanistically, the function of pyruvate kinase muscle isozyme M2 (PKM2) was assessed in leptin‑induced phenotypes using siRNA targeting PKM2 (si‑PKM2). Bioinformatics screening and luciferase reporter assays were used to reveal microRNA (miR)‑122 as the potential mediator between leptin and PKM2. Finally, the associations between leptin and miR‑122 or PKM2 levels in patients with cholangiocarcinoma were assessed by ELISA and RT‑qPCR. Leptin significantly increased the EMT and pro‑angiogenic capability of cholangiocarcinoma cells, visibly inhibited endogenous miR‑122 expression, and upregulated PKM2. Furthermore, si‑PKM2 inhibited leptin‑induced migration, invasion, EMT‑associated marker expression levels and the pro‑angiogenic capability in cholangiocarcinoma cells. In addition, miR‑122 negatively regulated the expression of PKM2. When applied together with leptin, miR‑122 was sufficient to reverse the multiple malignancy‑promoting effects of leptin. Consistently, the serum leptin level positively correlated with that of PKM2, but negatively with that of miR‑122 in patients with cholangiocarcinoma. Leptin, by downregulating miR‑122 and elevating PKM2 expression, acts as a pleiotropic pro‑malignancy cytokine for cholangiocarcinoma. Therefore, increasing miR‑122 expression and inhibiting PKM2 may be future approaches for cholangiocarcinoma treatment.

The existence of black holes with masses of about one billion solar masses in quasars at redshifts z > 6 presents significant challenges to theories of the formation and growth of black holes and the black hole/galaxy co-evolution in the early Universe. Here we report a recent discovery of an ultra-luminous quasar at redshift z = 6.30, which has an observed optical and near-infrared luminosity a few times greater than those of previously known z > 6 quasars. With near-infrared spectroscopy, we obtain a black hole mass of about 12 billion solar masses, which is well consistent with the mass derived by assuming an Eddington-limited accretion. This ultra-luminous quasar with at z > 6 provides a unique laboratory to the study of the mass assembly and galaxy formation around the most massive black holes at cosmic dawn. It raises further challenges to the black hole/galaxy co-evolution in the epoch of cosmic reionization because the black hole needs to grow much faster than the host galaxy.

The optical observations of Ic-4 supernova (SN) 2016coi/ASASSN-16fp, from $\sim 2$ to $\sim450$ days after explosion, are presented along with analysis of its physical properties. The SN shows the broad lines associated with SNe Ic-3/4 but with a key difference. The early spectra display a strong absorption feature at $\sim 5400$ \AA\ which is not seen in other SNe~Ic-3/4 at this epoch. This feature has been attributed to He I in the literature. Spectral modelling of the SN in the early photospheric phase suggests the presence of residual He in a C/O dominated shell. However, the behaviour of the He I lines are unusual when compared with He-rich SNe, showing relatively low velocities and weakening rather than strengthening over time. The SN is found to rise to peak $\sim 16$ d after core-collapse reaching a bolometric luminosity of Lp $\sim 3\times10^{42}$ \ergs. Spectral models, including the nebular epoch, show that the SN ejected $2.5-4$ \msun\ of material, with $\sim 1.5$ \msun\ below 5000 \kms, and with a kinetic energy of $(4.5-7)\times10^{51}$ erg. The explosion synthesised $\sim 0.14$ \msun\ of 56Ni. There are significant uncertainties in E(B-V)host and the distance however, which will affect Lp and MNi. SN 2016coi exploded in a host similar to the Large Magellanic Cloud (LMC) and away from star-forming regions. The properties of the SN and the host-galaxy suggest that the progenitor had $M_\mathrm{ZAMS}$ of $23-28$ \msun\ and was stripped almost entirely down to its C/O core at explosion., Comment: Accepted for publication in MNRAS. Updated to reflect the published version, minor typographical changes only

We present initial results from the first systematic survey of luminous $z\sim 5.5$ quasars. Quasars at $z \sim$ 5.5, the post-reionization epoch, are crucial tools to explore the evolution of intergalactic medium, quasar evolution and the early super-massive black hole growth. However, it has been very challenging to select quasars at redshifts 5.3 $\le z \le$ 5.7 using conventional color selections, due to their similar optical colors to late-type stars, especially M dwarfs, resulting in a glaring redshift gap in quasar redshift distributions. We develop a new selection technique for $z \sim$ 5.5 quasars based on optical, near-IR and mid-IR photometric data from Sloan Digital Sky Survey (SDSS), UKIRT InfraRed Deep Sky Surveys - Large Area Survey (ULAS), VISTA Hemisphere Survey (VHS) and Wide field Infrared Survey Explorer (WISE). From our pilot observations in SDSS-ULAS/VHS area, we have discovered 15 new quasars at 5.3 $\le z \le$ 5.7 and 6 new lower redshift quasars, with SDSS z band magnitude brighter than 20.5. Including other two $z \sim$ 5.5 quasars already published in our previous work, we now construct an uniform quasar sample at 5.3 $\le z \le$ 5.7 with 17 quasars in a $\sim$ 4800 square degree survey area. For further application in a larger survey area, we apply our selection pipeline to do a test selection by using the new wide field J band photometric data from a preliminary version of the UKIRT Hemisphere Survey (UHS). We successfully discover the first UHS selected $z \sim$ 5.5 quasar., 10 pages, 5 figures, accepted by AJ

Very few low-ionization broad absorption line (LoBAL) QSOs have been found at high redshifts to date. One high-redshift LoBAL QSO, J0122+1216, was recently discovered at the Lijiang 2.4-m Telescope with an initial redshift determination of 4.76. Aiming to investigate its physical properties, we carried out follow-up observations in the optical and near-IR spectroscopy. Near-IR spectra from UKIRT and P200 confirms that it is a LoBAL, with a new redshift determination of $4.82\pm0.01$ based on the \mgii~ emission-line. The new \mgii~ redshift determination reveals strong blueshifts and asymmetry of the high-ionization emission lines. We estimated a black hole mass of $\sim 2.3\times 10^9 M_\odot$ and Eddington ratio of $\sim 1.0$ according to the empirical \mgii-based single-epoch relation and bolometric correction factor. It is possible that strong outflows are the result of an extreme quasar environment driven by the high Eddington ratio. A lower limit on the outflowing kinetic power ($>0.9\% L_{Edd}$) was derived from both emission and absorption lines, indicating these outflows play a significant role in the feedback process to regulate the growth of its black hole as well as host galaxy evolution., 12 pages, 10 figures. Accepted for publication in The Astrophysical Journal

Extensive and independent observations of Type Ia supernova (SN Ia) SN 2013dy are presented, including a larger set of $UBVRI$ photometry and optical spectra from a few days before the peak brightness to $\sim$ 200 days after explosion, and ultraviolet (UV) photometry spanning from $t \approx -10$ days to $t \approx\ +15$ days referring to the $B$ band maximum. The peak brightness (i.e., $M_{\rm B} = -19.65 \pm 0.40$ mag, $L_{\rm max} = [1.95 \pm 0.55] \times 10^{43}$ erg s$^{-1}$) and the mass of synthesised $^{56}$Ni (i.e., $M$($^{56}$Ni) = 0.90 $\pm$ 0.26 M$_{\odot}$) are calculated, and they conform to the expectation for a SN Ia with a slow decline rate (i.e., $\Delta m_{15}(B)$ = 0.90 $\pm$ 0.03 mag, Phillips 1993). However, the near infrared (NIR) brightness of this SN (i.e., $M_{\rm H} = -17.33 \pm 0.30$ mag) is at least 1.0 mag fainter than usual. Besides, spectroscopy classification reveals that SN 2013dy resides on the border of "core normal" and "shallow silicon" subclasses in the Branch et al. (2009) classification scheme, or on the border of the "normal velocity" SNe Ia and 91T/99aa-like events in the Wang et al. (2009a) system. These suggest that SN 2013dy is a slow-declining SN Ia located on the transitional region of nominal spectroscopic subclasses and might not be a typical normal sample of SNe Ia., Comment: 16pages, 14 figures and 8 tables. Accepted for publication in AJ

High-redshift quasars are important tracers of structure and evolution in the early universe. However, they are very rare and difficult to find when using color selection because of contamination from late-type dwarfs. High-redshift quasar surveys based on only optical colors suffer from incompleteness and low identification efficiency, especially at $z\gtrsim4.5$. We have developed a new method to select $4.7\lesssim z \lesssim 5.4$ quasars with both high efficiency and completeness by combining optical and mid-IR Wide-field Infrared Survey Explorer (WISE) photometric data, and are conducting a luminous $z\sim5$ quasar survey in the whole Sloan Digital Sky Survey (SDSS) footprint. We have spectroscopically observed 99 out of 110 candidates with $z$-band magnitudes brighter than 19.5 and 64 (64.6\%) of them are quasars with redshifts of $4.4\lesssim z \lesssim 5.5$ and absolute magnitudes of $-29\lesssim M_{1450} \lesssim -26.4$. In addition, we also observed 14 fainter candidates selected with the same criteria and identified 8 (57.1\%) of them as quasars with $4.74.5$, which will set strong constraints on the bright end of the quasar luminosity function. We also expand our method to select quasars at $z\gtrsim5.7$. In this paper we report the discovery of four new luminous $z\gtrsim5.7$ quasars based on SDSS-WISE selection., Comment: 15 pages, 10 figures

The ultraviolet broad absorption lines have been seen in the spectra of quasars at high redshift, and are generally considered to be caused by outflows with velocities from thousands kilometers per second to one tenth of the speed of light. They provide crucial implications for the cosmological structures and physical evolutions related to the feedback of active galactic nuclei (AGNs). Recently, through a dedicated program of optically spectroscopic identifications of selected quasar candidates at redshift 5 by using the Lijiang 2.4 m telescope, we discovered two luminous broad absorption line quasars (BALQSOs) at redshift about 4.75. One of them may even have the potentially highest absorption Balnicity Index (BI) ever found to date, which is remarkably characterized by its deep, broad absorption lines and sub-relativistic outflows. Further physical properties, including the metal abundances, variabilities, evolutions of the supermassive black holes (SMBH) and accretion disks associated with the feedback process, can be investigated with multi-wavelength follow-up observations in the future., 6 pages, 3 figures

The methods of root-excision and trenching were employed concurrently in the present study in order to partition total soil respiration (Rtotal) into root respiration (Rroot), rhizomicrobial respiration (Rrhizo) and root free soil microbial respiration (Rrfs). This study was conducted under the monsoon evergreen broad-leaf forest (BF), the pine forest (PF) and the pine and broad-leaf mixed forest (MF) in Dinghushan Biosphere Reserve, subtropical China from April 2001 to March 2002. The three forests represent different successional stages in this region. Our results showed that mean Rtotal were 477.9 ± 96.3, 429.5 ± 61.0 and 435.4 ± 95.1 mg CO2 m−2 h−1 in BF, PF and MF, respectively. Rtotal were significantly higher in rain season than those in dry season. However, no significant variations were found among three forests. Soil respiration rates were highly dependent on the combined effects of soil temperature and soil water content. Rroot was significantly higher in rain season than that in dry season, with the values of 113.8–166.0 mg CO2 m−2 h−1 in rain season and 48.6–97.1 mg CO2 m−2 h−1 in dry season. There were no significant differences for Rrfs and Rrhizo between rain and dry season. However, the contributions of each component to Rtotal in rain season differed from those in dry season. In rain season, Rroot-to-Rtotal, Rrfs-to-Rtotal and Rrhizo-to-Rtotal ratios were in the range of 26.1–35.4, 40.6–43.7, and 20.9–36.6%. In dry season, they were 18.1–22.1, 44.8–47.6 and 30.3–37.1%, respectively.

We report the discovery of an ultra-luminous quasar J030642.51+185315.8 (hereafter J0306+1853) at redshift 5.363, which hosts a super-massive black hole (SMBH) with $M_{BH} = (1.07 \pm 0.27) \times10^{10}~M_\odot$. With an absolute magnitude $M_{1450}=-28.92$ and bolometric luminosity $L_{bol}\sim3.4\times10^{14} L_{\odot}$, J0306+1853 is one of the most luminous objects in the early Universe. It is not likely to be a beamed source based on its small flux variability, low radio loudness and normal broad emission lines. In addition, a $z=4.986$ Damped Ly$\alpha$ system (DLA) with $\rm [M/H]=-1.3\pm0.1$, among the most metal rich DLAs at $z \gtrsim 5$, is detected in the absorption spectrum of this quasar. This ultra-luminous quasar puts strong constraint on the bright-end of quasar luminosity function and massive-end of black hole mass function. It will provide a unique laboratory to the study of BH growth and the co-evolution between BH and host galaxy with multi-wavelength follow-up observations. The future high resolution spectra will give more insights to the DLA and other absorption systems along the line-of-sight of J0306+1853., Comment: 5 pages, 3 figures, accepted for publication in ApJL