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We intended to explore the mechanism ofThirty Sprague-Dawley rats were randomly assigned to the blank control group (N), the pneumonia group (P), and theLung tissue inflammation was prevented by

Histone modifications are precisely controlled within the developing germ line. During first meiotic prophase in C. elegans, H3K9me2 immunolabeling detects a relatively bright focus of signal on unsynapsed chromosomes and a relatively weak, diffuse signal on synapsed chromosomes (Bean et al. 2004, Kelly et al. 2002, Reuben and Lin 2002). The naturally occurring unsynapsed chromosome is the single male X. Examples of other chromatin that is enriched for H3K9me2 at pachytene stage include single-copy free chromosomal duplications, chromosomes that fail to pair due to certain mutations, and multicopy extrachromosomal arrays. In all cases, the enriched H3K9me2 signal decreases sharply as nuclei move into diplotene stage, and H3K9me2 is not detected in diakinesis nuclei. As the naturally occurring example of H3K9me2 enrichment, the male X is commonly used to evaluate this meiotic targeting phenomenon (Fig. 1). We previously showed that meiotic H3K9me2 distribution is altered in males lacking CSR-1 Argonaute or factors required for accumulation of CSR-1-associated 22G RNAs, including EGO-1 RdRP, DRH-3 helicase, and the Tudor domain protein, EKL-1 (Maine et al. 2005, She et al. 2009). In mutants lacking any of these factors, pachytene H3K9me2 signal intensity is reduced on unsynapsed chromosomes and, in all cases except ego-1(null) mutants, ectopic H3K9me2 foci are detected on synapsed chromosomes. Interestingly, as in wildtype, H3K9me2 signal is not detected in diakinesis nuclei in these mutants. CSR-1 pathway activity is essential for germ line development where it is thought to license the correct pattern of gene expression (Yigit et al. 2006, Ashe et al. 2012, Shirayama et al. 2012). EGO-1, DRH-3, and EKL-1 are critical for biogenesis and stability of 22G RNAs that associate with CSR-1 (reviewed in Billi et al. 2014).

Background Emergence of bla KPC and bla NDM co-producing Klebsiella pneumoniae strains have led to the limited therapeutic options for clinical treatment. Understanding the diversity and frequency of resistance and virulence genes of these isolates is of great significance. Purpose The aim of this study is to research the diversity and frequency of resistance and virulence genes in the bla KPC and bla NDM co-producing Klebsiella pneumoniae strains. Methods and results In this study, 117 K. pneumonia strains were isolated from China, and among of which, 24 were found to be bla KPC and bla NDM co-producing with significant resistance against almost all the commonly used antibiotics. Additionally, 4 strains were hypermucoviscous and 8 showed high serum resistance. Overall, bla SHV, bla CTX-M, tetA and sul1 resistance genes found in 100% of the isolates, followed by bla TEM (95.8%), oqxA/B (91.7%), qnrB (87.5%), aac(6')Ib-cr (83.3%), bla DHA (79.2%), rmtB (66.7%), qnrS (54.2%), cat(54.2%), floR (50.0%), sul2 (45.8%) cmlA (20.8%)andbla CMY (8.33%), respectively. What' more, seven bla CTX-M subtypes [bla CTX-M-14 (n=18), bla CTX-M-3(n=11), bla CTX-M-65 (n=4), bla CTX-M-15 (n=3), bla CTX-M-28 (n=2), bla CTX-M-55 (n=2), bla CTX-M-22 (n=1)] and six bla SHV subtypes [bla SHV-12(n=16), bla SHV-11 (n=4), bla SHV-2a(n=1), bla SHV-1(n=1), bla SHV-38(n=1) and bla SHV-28(n=1)] were detected. The frequency of virulence genes was as follows: 100% for entB, ybtS and irp, 95.8% for mrkD, 91.66% for fimH, 79.2% for iutA, 62.5% for iroBCDE, aerobactin and kfu, 66.7% for allS, 45.8% for wcaG, 37.5% for rmpA, 20.8% for pagO and 16.7% for magA. Conclusion From this study, we concluded that the bla KPC and bla NDM co-producing Klebsiella pneumoniae strains have a high diversity and frequency of resistance and virulence genes. This study may offer hospitals important information about the control of infections caused by bla KPC and bla NDM co-producing Klebsiella pneumoniae.

Background The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC). Methods Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC. Results A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC. Conclusions The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.

Highly efficient light-emitting materials are essential for achieving high-performance devices. Here, a novel composite system, as well as enhanced luminescence processes, was designed, where NaLn(MoO4)2 ultra-small nucleus can be effectively isolated by In(OH)3 to form NaLn(MoO4)2@In(OH)3 composite nanoclusters due to the different nucleation rate between NaLn(MoO4)2 and In(OH)3, and then these small composite clusters gradually self-assemble into hierarchical structures. As we expected, the enhanced luminescence was achieved from hierarchical NaLn(MoO4)2 nanostructures with adjusting the distance among NaLn(MoO4)2 ultra-small nucleus by inserting In(OH)3. A series of spectroscopy results show that the In(OH)3 not only acts as an energy transfer bridge from CTB Eu3+ → O2− (or MoO42− absorption) to Eu3+, but also can effectively alleviate the concentration quenching of Ln3+ and change the J-O parameters. The Raman peak at 134 cm−1 is helpful to populate the 5D0 level of Eu3+ or the excited states of Er3+, resulting in stronger up/down-conversion emissions. The use of NaLn(MoO4)2@In(OH)3 in white light-emitting diodes (LEDs) has been demonstrated. The combination of red emission from NaLn(MoO4)2@In(OH)3 with blue, green, and yellow emission from halide perovskites could achieve white light with excellent vision performance (an LER of 376 lm/W) and superior color quality (CRI > 92). The findings of this experiment provide a new idea for the design of composite interface materials.

Background : The present study attempted to detect a specific circular RNA (circRNA) for the early diagnosis of gastric cancer (GC). Methods: We selected four patients with GC for this study. The total RNA of the malignant and adjacent tissues was extracted, and the circRNA was screened. The eight most upregulated and downregulated circRNAs with a statistically significant relation to GC and paired adjacent nontumorous tissues were identified using real-time fluorescent quantitative polymerase chain reaction (PCR). CircRNA expression was identified by quantitative reverse transcriptase PCR in 78 cases of GC and adjacent tissues, and in the gastric fluids of 30 patients with chronic nonatrophic gastritis, 30 patients with chronic atrophic gastritis, 21 with early GC, and 57 with advanced GC. Results: A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significant aberrant expression in GC tissues. A majority of the differentially expressed circRNAs originated from chr1, chr3, chr4, chr6, and chr11. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissues, and its level in GC tissues correlated with the tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen, and carbohydrate antigen 19-9 expression. A crucial observation was the presence of this circRNA in the gastric fluid of patients with early and advanced GC. Conclusions: The present study uncovered a new hsa_circRNA expression profile in human GC, of which hsa_circ_000780 was significantly downregulated in GC tissues and in gastric fluid. It can be potentially used as a novel biomarker for early GC screening.

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The CRISPR-based genome perturbation opened a new avenue to the genetic screen by providing a toolkit to conveniently change the DNA sequence, transcription and epigenetic modifications . However, it has remained challenging to assay the complex molecular readouts at high resolution and at scale after perturbation. By introducing an A/G mixed capture sequence into the gRNA scaffold, we demonstrated that the gRNA transcripts could be directly reverse transcribed by poly(dT) primer together with the endogenous mRNA, and followed by high-content molecular phenotyping in scRNA-seq. With this method, the CRISPR perturbation and its transcriptional readouts can be profiled together in a streamlined workflow.

Background: This study aimed to find the specific circular RNA (circRNA) for gastric cancer (GC) and lay the foundation for the early diagnosis of GC.Methods: Four patients with GC were selected for this study. The total RNA of their cancer tissues and adjacent tissues was extracted, and the circRNA was screened. The top eight upregulated and downregulated circRNAs with statistical significance between GC and paired adjacent nontumorous tissues were identified using real-time fluorescent quantitative polymerase chain reaction (PCR). The expression level of circRNA was identified by quantitative reverse transcription PCR in 78 cases of GC and its adjacent tissues, and in the gastric juice of 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, 21 with early GC, and 57 with advanced GC.Results: A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, were found to be significantly aberrantly expressed in GC tissues. Most of the differentially expressed circRNAs originated from chr1, chr3, chr4, chr6, and chr11. Hsa_circRNA_000780 was significantly downregulated in 80.77% of GC tissues. Its level in GC tissues correlated with the tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen, and carbohydrate antigen 19-9 expression. More importantly, hsa_circRNA_000780 was found in the gastric juice of early and advanced GC.Conclusions: This study uncovered the new hsa_circRNA expression profile in human GC. Among them, hsa_circRNA_000780 was significantly downregulated in GC tissues and gastric juice. It had the potential to be used as a novel biomarker for the screening of early GC.

It is well known that the upconversion luminescence from lanthanide metal-organic frameworks (Ln-MOFs) is difficult to achieve, and thus, there are few reports on dual luminescence-based MOFs. Here, dual-mode light-emitting Ln-MOFs are synthesized using a low-cost hydrothermal method. Our results show that the obtained Ln-MOFs not only have high thermal stability (up to 420°) but also are stable in deionized water. The dual-mode up- and downconversion luminescence is simultaneously observed from Er-Eu-MOFs. The temperature-dependent fluorescence decay time is calculated to be ranging from 0.46 to 0.36 ms for temperatures from 100 to 300 K. We suggested that this phenomenon was because the number of phonons participating in the MOF matrix increases with temperature during the luminescence process, and the phonons interact with the electrons in the material. The values of the J-O parameters calculated from the emission spectra indicated that the symmetry around Eu3+ ions in Eu-MOF is the highest, which was also higher than that of Er-Eu-MOF. To explore the potential applications of Eu-MOFs in white light-emitting diodes (LEDs), red emission from Eu-MOFs was combined with blue, green, and yellow emissions from metal halide perovskites to achieve white light emission. White light with excellent color quality and vision performance was obtained. These findings demonstrate that Ln-MOFs are potentially successful materials for applications in white LEDs.

Additional file 6. Review history.

Additional file 1: Figure S1. An illustration shows the stem extension when incorporating longer loop in order to main stable secondary structure. Figure S2. The off-target rate was examined for six known off-targeting sites of the VEGFA gRNA. Figure S3. Workflows of applying the programmed scaffold in different single cell RNA-seq platforms. Figure S4. The products from gRNA transcripts were effectively enriched by the nested PCR as exhibited from the fragment size analysis. Figure S5. The pearson correlation of UMI per cell between the two index gRNA libraries. Figure S6. Histogram of the gRNA UMI per cell from the index gRNA library II. Figure S7. Transcriptome profiling and KEGG enrichment of gRNA targeting genes in single cell sequencing. Figure S8. The sequencing reads from gRNA transcripts in each single cell were estimated using single cell RNA-seq conducted on the Fluidigm C1 platform. Figure S9. Different scaffold variants were examined, including G addition at different frequencies and A/G mixed sequence with different tractors.

In this work, bioleaching and dissolution processes of chalcopyrite from three different regions were investigated and compared mainly by leaching experiments, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and electrochemical analysis. Hall effect experiments showed that one (chalcopyrite A) belonged to p-type chalcopyrite whose carrier concentrations were high, while the other two (chalcopyrite B and C) were both n-type chalcopyrite whose carrier concentrations were low. A remarkably higher copper extraction of p-type chalcopyrite could be achieved during bioleaching by L. ferriphilum compared with n-type chalcopyrite. Redox potential in bioleaching of p-type chalcopyrite can be maintained at the appropriate range (about 380–480 mV vs. Ag/AgCl) for a longer period of time. Acid consumption in bioleaching of p-type chalcopyrite was significantly lower than that of n-type chalcopyrite. SEM analysis indicated that p-type chalcopyrite was more easily corroded by microorganism than n-type chalcopyrite. XPS analysis revealed that monosulfide (S2−), disulfide (S22−), polysulfide (Sn2−) and sulfate (SO42−) were the main intermediate species during bioleaching of both p-type and n-type chalcopyrite. Electrochemical analysis showed that the electrochemical dissolution processes of p-type and n-type chalcopyrite were similar, while the conductivity and oxidation-reduction rate of p-type chalcopyrite was significantly higher than those of n-type chalcopyrite, thus resulting in significant higher electrochemical dissolution kinetics and copper extraction. This work is potentially useful in explaining the inconsistences in chalcopyrite hydrometallurgy.

Purpose To report the 1-year visual and keratometric results of epithelium-on corneal collagen crosslinking (CXL) for advanced keratoconus (median maximum keratometry [K] ≥58.0 diopters [D]). Setting School of Ophthalmology and Optometry and Eye Hospital of Wenzhou Medical College, Wenzhou, China. Design Prospective case series. Methods Patients with bilateral progressive keratoconus had tetracaine-enhanced epithelium-on CXL. The worse eye had CXL, and the fellow eye was not treated. Results were reported 1, 3, 6, and 12 months postoperatively. The outcomes were compared with those in the fellow untreated eyes. Results Twenty-one eyes of 21 patients with a median age of 20.4 years (interquartile range [IQR], 9.5 years) were treated. A significant improvement in postoperative uncorrected distance visual acuity was observed at 12 months ( P = .002). Postoperative corrected distance visual acuity improved at 6 months and 12 months ( P ≤ .009) compared with baseline values. The maximum K decreased by 1.63 D from the median preoperative maximum K of 62.7 D (IQR, 12.9 D) at 12 months ( P P = .001). Correlation analysis between the preoperative maximum K values and the change over 6 to 12 months between different studies showed a significant correlation ( r = −0.764, P Conclusions Epithelium-on CXL was an effective treatment for patients with advanced keratoconus. A higher preoperative maximum K value correlated with greater corneal flattening after CXL. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

Introduction Susceptibility to lipid metabolic dysfunction are more frequent in individuals with dampness-heat (DH) constitution, which might be caused by the changes in the gut microbiome. This study is to explore the structural and functional characteristics of the fecal-associated microbiome (FAM) in DH constitution and screen FAM-related biomarkers of DH constitution. Methods Fecal samples were collected. The FAM structure was described with alpha/beta diversity indexes and relative abundances of dominant taxa; the distribution/functional differences of the FAM between DH and balanced constitutions were analyzed by Wilcoxon rank-sum test, MetagenomeSeq and LEfSe analysis, and the specific OTUs were screened to construct ROC curve. Results There was a significant difference between the groups in the sweet preference, ACE and Chao1 indexes. In PCoA and PLS-DA, the bacterial communities in the balanced samples and DH samples clustered separately. Notably, there were 115 differentially distributed OTUs between groups identified in the MetagenomeSeq analysis and 213 OTUs identified with the Wilcoxon rank-sum test. Predicted functions showed that 12 metabolic pathways were differentially distributed between groups, including the pathway related to glycerolipid metabolism. The AUC of ROC curve based on the 4 screened specific OTUs was 0.91, and the relative abundance of these 4 OTUs could result in changes in lipid metabolism. Conclusion Unique FAM structural characteristics were identified in DH constitution, which might involve in changes in lipid metabolism and susceptibility to lipid metabolic dysfunction. The 4 screened specific OTUs could be used as potential biomarkers of DH constitution to assist clinical diagnosis.

Poly(U) polymerases (PUPs) catalyze 3′ uridylation of mRNAs and small RNAs, a modification often correlating with decreased RNA stability. We have investigated the importance of three proteins with in vitro PUP activity, PUP-1/CDE-1, PUP-2 and PUP-3, in C. elegans germline development. Genetic analysis indicates that PUP-1/CDE-1 and PUP-2 are developmentally redundant under conditions of temperature stress during which they ensure germline viability and development. Multiple lines of evidence indicate that pup-1/-2 double mutant germ cells fail to maintain their identity as distinct from soma. Consistent with phenotypic data, PUP-1 and PUP-2 are expressed in embryonic germ cell precursors and throughout germline development. The developmental importance of PUP activity is presumably in regulating gene expression as both a direct and indirect consequence of modifying target RNAs. PUP-3 is significantly overexpressed in the pup-1/-2 germline, and loss of pup-3 function partially suppresses pup-1/-2 germline defects. We conclude that one major function of PUP-1/-2 is to limit PUP-3 expression. Overall, the balance of PUP-1, PUP-2 and PUP-3 activities appears to ensure proper germline development.

The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding to cytochrome c and dATP, Apaf-1 oligomerizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing caspases. Here we present an atomic structure of an intact mammalian apoptosome at 3.8 Å resolution, determined by single-particle, cryo-electron microscopy (cryo-EM). Structural analysis, together with structure-guided biochemical characterization, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions with the WD40 repeats. Structural comparison with autoinhibited Apaf-1 revealed how dATP binding triggers a set of conformational changes that results in the formation of the apoptosome. Together, these results constitute the molecular mechanism of cytochrome c- and dATP-mediated activation of Apaf-1.

Many organisms alter the chromatin state of unsynapsed chromosomes during meiotic prophase, a phenomenon hypothesized to function in maintaining germline integrity. In Caenorhabditis elegans, histone H3 lysine 9 dimethylation (H3K9me2) is detected by immunolabeling as enriched on unsynapsed meiotic chromosomes. Loss of the SET domain protein, MET-2, greatly reduces H3K9me2 abundance and results in germline mortality. Here, we used him-8 mutations to disable X chromosome synapsis and performed a combination of molecular assays to map the sites of H3K9me2 accumulation, evaluate H3K9me2 abundance in germline vs. whole animals, and evaluate the impact of H3K9me2 loss on the germline transcriptome. Our data indicate that H3K9me2 is elevated broadly across the X chromosome and at defined X chromosomal sites in him-8 adults compared with controls. H3K9me2 levels are also elevated to a lesser degree at sites on synapsed chromosomes in him-8 adults compared with controls. These results suggest that MET-2 activity is elevated in him-8 mutants generally as well as targeted preferentially to the unsynapsed X. Abundance of H3K9me2 and other histone H3 modifications is low in germline chromatin compared with whole animals, which may facilitate genome reprogramming during gametogenesis. Loss of H3K9me2 has a subtle impact on the him-8 germline transcriptome, suggesting H3K9me2 may not be a major regulator of developmental gene expression in C. elegans. We hypothesize H3K9me2 may have a structural function critical for germline immortality, and a greater abundance of these marks may be required when a chromosome does not synapse.

Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is indispensable for caspase-9 activation by together forming a holoenzyme. The molecular mechanism of caspase-9 activation remains largely enigmatic. Here, we report the cryoelectron microscopy (cryo-EM) structure of an apoptotic holoenzyme and structure-guided biochemical analyses. The caspase recruitment domains (CARDs) of Apaf-1 and caspase-9 assemble in two different ways: a 4:4 complex docks onto the central hub of the apoptosome, and a 2:1 complex binds the periphery of the central hub. The interface between the CARD complex and the central hub is required for caspase-9 activation within the holoenzyme. Unexpectedly, the CARD of free caspase-9 strongly inhibits its proteolytic activity. These structural and biochemical findings demonstrate that the apoptosome activates caspase-9 at least in part through sequestration of the inhibitory CARD domain.

To compare central corneal thickness (CCT), anterior chamber depth (ACD), and keratometry (K) readings measured using optical low-coherence reflectometry (OLCR) biometry and high-resolution rotating Scheimpflug photography.Eye Hospital of Wenzhou Medical College, Wenzhou, China.Comparative case series.The CCT, ACD endothelium to lens, ACD epithelium to lens, and K (mean; in flattest meridian; in steepest meridian) were measured 5 times using the LenStar/Biograph OLCR biometer and 3 times with the Pentacam Scheimpflug system in eyes of healthy volunteers. Concordance was evaluated using paired t tests, the Pearson correlation, and Bland-Altman analyses.The CCT, ACD endothelium to lens, and ACD epithelium to lens measured with the Scheimpflug system were slightly, albeit significantly, higher than with the OLCR biometer (P.05); the respective 95% limits of agreement (LoA) were -8.2 μm to 15.7 μm, -0.11 to 0.15 mm, and -0.13 to 0.17 mm. However, the Scheimpflug system gave significantly flatter readings for K in the flattest meridian (95% LoA, -0.54 to 0.32 diopters [D]), K in the steepest meridian (95% LoA, -0.63 to 0.45 D), and mean K (95% LoA, -0.53 to 0.33 D) (P.001). The CCT, ACD, and K readings were all highly correlated between the 2 devices (r0.95, P.001).The CCT and ACD measurements with the OLCR biometer and Scheimpflug system can be used interchangeably in healthy young subjects. However, for K measurements, these devices have wide LoA so may not be interchangeable under certain clinical circumstances.

The effects of pyrite and bornite on bioleaching of two different chalcopyrite samples by Leptospirillum ferriphilum were studied for the first time. Results showed that bioleaching behaviors of the two chalcopyrite samples were extremely different. Bornite decreased the redox potential (ORP) and maintained it at an appropriate range (380-480 mV vs. Ag/AgCl) to promote chalcopyrite (A) dissolution, but caused the redox potential out of the optimum range and inhibited chalcopyrite (B) dissolution. Large amount of pyrite decreased the redox potential and maintained it at an optimum range to promote chalcopyrite (A) dissolution, while increased the redox potential and kept it at appropriate range for a longer period of time to enhance the dissolution rate of chalcopyrite (B). Chalcopyrite (B) had significantly higher values of conductivity and oxidation-reduction rate when compared with those of chalcopyrite (A). The work is potentially useful in interpreting the inconsistence of the researches of chalcopyrite hydrometallurgy.

To construct a small interfering RNA (siRNA) vector targeting p63 and observe its effect on the proliferation and invasiveness of human cholangiocarcinoma cells in vitro.Real-time PCR was used to examine the expression of p63 in human cholangiocarcinoma QBC939 cells. The recombinant lentivirus shRNA-p63 vector was constructed and transfected into QBC939 cells via Lipofectamine 2000 to establish a cholangiocarcinoma cell line with stable expression of siRNA-p63. The interfering efficiency of the siRNA targeting p63 was assessed using Western blotting. MTT and soft agar colony formation assays were used to evaluate the changes in the cell proliferation, and Boyden test was employed to observe the cell invasiveness after the transfection.QBC939 cells showed a high expression of p63. The recombinant lentivirus shRNA-p63 vector was successfully constructed as verified by sequencing. Transfection with the vector significantly suppressed the proliferation and invasiveness of QBC939 cells.Down-regulation of p63 can inhibit the proliferation and invasiveness of human cholangiocarcinoma QBC939 cells in vitro.