Phosphoric Acid-Catalyzed Alkene Difunctionalization of 2-Vinylpyridines via HOMO/LUMO Biactivated Diels-Alder Reaction.

The difunctionalization of vinylpyridines based on the cyclization strategy remains rare and underdeveloped, in contrast to the well-developed hydrogen functionalization. Current exploration on [4 + 2] cyclization of vinylpyridines mainly relies on extremely high temperatures and the LUMO activation of vinylpyridines using boron trifluoride as a strong Lewis acid. Herein, we established a phosphoric acid-catalyzed [4 + 2] cyclization reaction of 3-vinyl-1H-indoles and 2-vinylpyridines by means of the LUMO/HOMO bifunctional activation model. This protocol features mild reaction conditions, high functional group tolerance, broad substrate compatibility, and high diastereoselectivity, enabling the efficient construction of various functionalized pyridine-substituted tetrahydrocarbazoles with prominent potential in drug discovery.

Evaluating Fluorinated-Aniline Units with Functionalized Spiro[Fluorene-9,9'-Xanthene] as Hole-Transporting Materials in Perovskite Solar Cells and Light-Emitting Diodes.

In the field of perovskite optoelectronics, developing hole-transporting materials (HTMs) on the spiro[fluorene-9,9'-xanthene] (SFX) platform is one of the current research focuses. The SFX inherits the merits of spirobifluorene in terms of the configuration and property, but it is more easily derivatized and regulated by virtue of its binary structure. In this work, we design and synthesize four isomeric SFX-based HTMs, namely m-SFX-mF, p-SFX-mF, m-SFX-oF, and p-SFX-oF, through varying the positions of fluorination on the peripheral aniline units and their substitutions on the SFX core, and the optoelectronic performance of the resulting HTMs is evaluated in both perovskite solar cells (PSCs) and light-emitting diodes (PeLEDs) by the vacuum thermal evaporating hole-transporting layers (HTLs). The HTM p-SFX-oF exhibits an improved power conversion efficiency of 15.21% in an inverted PSC using CH3NH3PbI3 as an absorber, benefiting from the deep HOMO level and good HTL/perovskite interface contact. Meanwhile, the HTM m-SFX-mF provides a maximum external quantum efficiency of 3.15% in CsPb(Br/Cl)3-based PeLEDs, which is attributed to its perched HOMO level and shrunken band-gap for facilitating charge carrier injection and then exciton combination. Through elucidating the synergistic position effect of fluorination on aniline units and their substitutions on the SFX core, this work lays the foundation for developing low-cost and efficient HTMs in the future.

Selective Detection of Dynamics-Complete Set of Correlations via Quantum Channels.

Correlations of fluctuations are essential to understanding many-body systems and key information for advancing quantum technologies. To fully describe the dynamics of a physical system, all time-ordered correlations (TOCs), i.e., the dynamics-complete set of correlations are needed. The current measurement techniques can only access a limited set of TOCs, and there has been no systematic and feasible solution for extracting the dynamic-complete set of correlations hitherto. Here we propose a platform-universal protocol to selectively detect arbitrary types of TOCs via quantum channels. In our method, the quantum channels are synthesized with various controls, and engineer the evolution of a sensor-target system along a specific path that corresponds to a desired correlation. Using nuclear magnetic resonance, we experimentally demonstrate this protocol by detecting a specific type of fourth-order TOC that has never been accessed previously. We also show that the knowledge of the TOCs can be used to significantly improve the precision of quantum optimal control. Our method provides a new toolbox for characterizing the quantum many-body states and quantum noise, and hence for advancing the fields of quantum sensing and quantum computing.

The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Utility Analyses of AVITI Sequencing Chemistry.

BACKGROUND: DNA sequencing is a critical tool in modern biology. Over the last two decades, it has been revolutionized by the advent of massively parallel sequencing, leading to significant advances in the genome and transcriptome sequencing of various organisms. Nevertheless, challenges with accuracy, lack of competitive options and prohibitive costs associated with high throughput parallel short-read sequencing persist. RESULTS: Here, we conduct a comparative analysis using matched DNA and RNA short-reads assays between Element Biosciences AVITI chemistry and Illumina NextSeq 550. Similar comparisons were evaluated for synthetic long-read sequencing for RNA and targeted single-cell transcripts between the AVITI and Illumina NovaSeq 6000. For both DNA and RNA short-read applications, the study found that the AVITI produced significantly higher per sequence quality scores. For PCR-free DNA libraries, we observed up to a 10-fold lower experimentally determined error rate for using the AVITI chemistry compared to the NextSeq 550. For short-read RNA quantification, both AVITI and the NextSeq 550 demonstrated comparable accuracy. With regards to synthetic long-read mRNA and targeted synthetic long read single cell mRNA sequencing, both platforms respective chemistries performed comparably in quantification of genes and isoforms. The AVITI displayed a marginally lower error rate for long reads, with fewer chemistry-specific errors and a higher mutation detection rate. CONCLUSION: These results point to the potential of the AVITI platform as a competitive candidate in high-throughput short read sequencing analyses when juxtaposed with the Illumina NextSeq 550.

Therapeutic targeting at genome mutations of liver cancer by the insertion of HSV1 thymidine kinase through Cas9-mediated editing.

BACKGROUND: Liver cancer is one of the most lethal malignancies for humans. The treatment options for advanced-stage liver cancer remain limited. A new treatment is urgently needed to reduce the mortality of the disease. METHODS: In this report, we developed a technology for mutation site insertion of a suicide gene (herpes simplex virus type 1- thymidine kinase) based on type II CRISPR RNA-guided endonuclease Cas9-mediated genome editing to treat liver cancers. RESULTS: We applied the strategy to 3 different mutations: S45P mutation of catenin beta 1, chromosome breakpoint of solute carrier family 45 member 2-alpha-methylacyl-CoA racemase gene fusion, and V235G mutation of SAFB-like transcription modulator. The results showed that the herpes simplex virus type 1-thymidine kinase insertion rate at the S45P mutation site of catenin beta 1 reached 77.8%, while the insertion rates at the breakpoint of solute carrier family 45 member 2 - alpha-methylacyl-CoA racemase gene fusion were 95.1%-98.7%, and the insertion at V235G of SAFB-like transcription modulator was 51.4%. When these targeting reagents were applied to treat mouse spontaneous liver cancer induced by catenin beta 1S45P or solute carrier family 45 member 2-alpha-methylacyl-CoA racemase, the mice experienced reduced tumor burden and increased survival rate. Similar results were also obtained for the xenografted liver cancer model: Significant reduction of tumor volume, reduction of metastasis rate, and improved survival were found in mice treated with the targeting reagent, in comparison with the control-treated groups. CONCLUSIONS: Our studies suggested that mutation targeting may hold promise as a versatile and effective approach to treating liver cancers.

Effect of different loads on facet joint motion during lumbar lateral bending in sitting position.

OBJECTIVE: To study the effect of weight-bearing on lumbar facet joint during lateral bending in sitting position. METHODS: Ten normal healthy people (5 males and 5 females) aged 25-39 years (mean 32 ± 4.29 years) were recruited. CT scanning was used to reconstruct the lumbar spine model, and then dual fluoroscopic image system (DFIS) was used to restore the lumbar facet joint movement in sitting position. Finally, the lumbar facet joint translation distance and rotation angle were measured. RESULTS: In L3-4 level, the displacement of right facet joint in Y-axis was the smallest at 0.05 ± 0.40 mm, the displacement of 0 kg left facet joint in X-axis was the largest at 1.68 ± 0.85 mm, and the rotation angle was - 0.57 ± 1.43° to 5.66 ± 2.70° at 10 kg; in L4-5 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, - 0.13 ± 0.91 mm, and the displacement of left facet joint in Z-axis was the largest at - 2.11 ± 0.88 mm, and the rotation angle was 0.21 ± 2.14° to 7.89 ± 2.59° at 10 kg; in L5-S1 level, the displacement of right facet joint in Y-axis was the smallest at 10 kg, - 0.17 ± 1.10 mm, and the displacement of 0 kg left facet joint in X-axis was the largest at 2.19 ± 2.28 mm, and the rotation angle was 0.03 ± 2.02° to 3.98 ± 0.37°. CONCLUSION: In sitting position, weight-bearing has certain influence on the displacement of facet joints during lumbar lateral bending movement, and this influence occurs simultaneously in translation and rotation; the left and right facet joints are not symmetrical during lumbar lateral bending movement.

Identification of prognostic risk score of disulfidptosis-related genes and molecular subtypes in glioma.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells.

The protein diversity of mammalian cells is determined by arrays of isoforms from genes. Genetic mutation is essential in species evolution and cancer development. Accurate long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPSeq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPSeq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.

HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression

Purpose To elucidate the underlying mechanism of HIF-1α in migration and invasion of choriocarcinoma. Methods Cell proliferation was determined by CCK-8 assay when cell invasion was detected by transwell assay. The protein expression was detected by western blotting, immunohistochemistry, and qPCR assay. Result HIF-1α was shown to be strongly expressed in both clinical tumour tissues and cell lines in choriocarcinoma. When HIF-1α was efficiently knocked down in JEG3 cells, the proliferation rate was reduced by approximately 50% and the number of cells that migrated through the transwell insert was greatly decreased. The cell invasion rate was also significantly reduced. Moreover, typical markers of epithelial–mesenchymal transition such as E-cadherin, were increased, while vimentin and α–SMA were decreased after HIF-1α knockdown. In contrast, overexpression of DEC1 reversed the effects of HIF-1α knockdown. Cell proliferation, migration, and invasion were partially recovered. The level of E-cadherin was decreased, while the level of vimentin and α–SMA was increased. In addition, the level of β-catenin and LEF1 was downregulated after HIF-1α knockdown. The expression of MMP2 and MMP9 also declined. However, overexpression of DEC1 after HIF-1α knockdown partially reversed the expression pattern of these molecules. Conclusion HIF-1α contributed to EMT and metastasis through activation of canonical β-catenin signalling in choriocarcinoma and this process was dependent on DEC1. This study provides a new mechanism of HIF-1α in choriocarcinoma and suggests that intervention with DEC1 might be a promising therapeutic choice for choriocarcinoma (AU)

[Research progress in control strategies of biological clock disorder].

Circadian clock is an internal mechanism evolved to adapt to cyclic environmental changes, especially diurnal changes. Keeping the internal clock in synchronization with the external clock is essential for health. Mismatch of the clocks due to phase shift or disruption of molecular clocks may lead to circadian disorders, including abnormal sleep-wake cycles, as well as disrupted rhythms in hormone secretion, blood pressure, heart rate, body temperature, etc. Long-term circadian disorders are risk factors for various common critical diseases such as metabolic diseases, cardiovascular diseases, and tumor. To prevent or treat the circadian disorders, scientists have conducted extensive research on the function of circadian clocks and their roles in the development of diseases, and screened hundreds of thousands of compounds to find candidates to regulate circadian rhythms. In addition, melatonin, light therapy, exercise therapy, timing and composition of food also play a certain role in relieving associated symptoms. Here, we summarized the progress of both drug- and non-drug-based approaches to prevent and treat circadian clock disorders.

Detection of Quantum Signals Free of Classical Noise via Quantum Correlation.

Extracting useful signals is key to both classical and quantum technologies. Conventional noise filtering methods rely on different patterns of signal and noise in frequency or time domains, thus limiting their scope of application, especially in quantum sensing. Here, we propose a signal-nature-based (not signal-pattern-based) approach which singles out a quantum signal from its classical noise background by employing the intrinsic quantum nature of the system. We design a novel protocol to extract the quantum correlation signal and use it to single out the signal of a remote nuclear spin from its overwhelming classical noise backgrounds, which is impossible to be accomplished by conventional filter methods. Our Letter demonstrates the quantum or classical nature as a new degree of freedom in quantum sensing. The further generalization of this quantum nature-based method opens a new direction in quantum research.

Long-read single-cell sequencing reveals expressions of hypermutation clusters of isoforms in human liver cancer cells.

The protein diversity of mammalian cells is determined by arrays of isoforms from genes. Genetic mutation is essential in species evolution and cancer development. Accurate Long-read transcriptome sequencing at single-cell level is required to decipher the spectrum of protein expressions in mammalian organisms. In this report, we developed a synthetic long-read single-cell sequencing technology based on LOOPseq technique. We applied this technology to analyze 447 transcriptomes of hepatocellular carcinoma (HCC) and benign liver from an individual. Through Uniform Manifold Approximation and Projection (UMAP) analysis, we identified a panel of mutation mRNA isoforms highly specific to HCC cells. The evolution pathways that led to the hyper-mutation clusters in single human leukocyte antigen (HLA) molecules were identified. Novel fusion transcripts were detected. The combination of gene expressions, fusion gene transcripts, and mutation gene expressions significantly improved the classification of liver cancer cells versus benign hepatocytes. In conclusion, LOOPseq single-cell technology may hold promise to provide a new level of precision analysis on the mammalian transcriptome.

Nanothermometry with Enhanced Sensitivity and Enlarged Working Range Using Diamond Sensors.

Nanothermometry is increasingly demanded in frontier research in physics, chemistry, materials science and engineering, and biomedicine. An ideal thermometer should have features of reliable temperature interpretation, high sensitivity, fast response, minimum disturbance of the target's temperature, applicability in a variety of environments, and a large working temperature range. For applications in nanosystems, high spatial resolution is also desirable. Such requirements impose great challenges in nanothermometry since the shrinking of the sensor volume usually leads to a reduction in sensitivity.Diamond with nitrogen-vacancy (NV) centers provides opportunities for nanothermometry. NV center spins have sharp resonances due to their superb coherence. NV centers are multimodal sensors. They can directly sense magnetic fields, electric fields, temperature, pressure, and nuclear spins and, through proper transduction, measure other quantities such as the pH and deformation. In particular, their spin resonance frequencies vary with temperature, making them a promising thermometer. The high thermal conductivity, high hardness, chemical stability, and biocompatibility of diamond enable reliable and fast temperature sensing in complex environments ranging from erosive liquids to live systems. Chemical processing of diamond surfaces allows various functionalities such as targeting. The small size and the targeting capability of nanodiamonds then enable site-specific temperature sensing with nanoscale spatial resolution. However, the sensitivity of NV-based nanothermometry is yet to meet the requirement of practical systems with a large gap of a few orders of magnitude. On the other hand, although NV-based quantum sensing works well from 0.3 to 600 K, extending the sensing scheme to high temperature remains challenging due to uncertainty in identifying the exact physical limits and possible solution at elevated temperatures.This Account focuses on our efforts to enhance the temperature sensitivity and widen the working temperature range of diamond-based nanothermometry. We start with explaining the working principle and features of NV-based thermometry with examples of applications. Then a transducer-based concept is introduced with practical schemes to improve the sensitivity of the nanodiamond thermometer. Specifically, we show that the temperature signal can be transduced and amplified by adopting hybrid structures of nanodiamond and magnetic nanoparticles, which results in a record temperature sensitivity of 76 µK/√Hz. We also demonstrate quantum sensing with NV at high temperatures of up to 1000 K by adopting a pulsed heating-cooling scheme to carry out the spin polarization and readout at room temperature and the spin manipulation (sensing) at high temperatures. Finally, unsolved problems and future endeavors of diamond nanothermometry are discussed.

Effect of dietary supplementation of Bacillus subtilis TLRI 211-1 on laying performance, egg quality and blood characteristics of Leghorn layers.

OBJECTIVE: TLRI 211-1 is a novel Bacillus subtilis strain. This experiment was to investigate dietary supplementation of TLRI 211-1 on laying performance, egg quality and blood characteristics of layers. METHODS: One hundred and twenty 65-wk-old Leghorn layers were divided into four treatment groups for 8 weeks experiment. Each treatment had three replicates. The basal diet was formulated as control group with crude protein 17% and metabolizable energy 2,850 kcal/kg and supplemented with TLRI 211-1 0.1%, 0.3%, and commercial Bacillus amyloliquefaciens 0.1% as treatment 2, 3 and 4 groups, respectively. Both TLRI 211-1 and commercial Bacillus amyloliquefaciens were adjusted to contain 1×109 colony-forming unit (CFU)/mL (g), hence the 0.1% supplemental level was 1×109 CFU/kg. RESULTS: The results showed that TLRI 211-1 0.3% and commercial B. amyloliquefaciens groups had higher weight gain than the other groups; TLRI 211-1 0.1% group had better feed to eggs conversion ratio than the control and commercial B. amyloliquefaciens groups (p<0.05). Bacillus subtilis supplementation increased yolk weight (p<0.05). In egg quality during storage, TLRI 211-1 0.1% had higher breaking strength than the control group at the second week of storage (p<0.05). At the third week of storage, TLRI 211-1 0.3% had higher Haugh unit (p<0.05). Hens fed diets supplemented with TLRI 211-1 0.3% significantly decreased blood triglyceride levels and increased blood calcium levels (p< 0.05). TLRI 211-1 0.3% group had lower H2S (p<0.05) and hence had less unpleasant odor in excreta of hens. CONCLUSION: In conclusion, supplementation with 0.1% TLRI 211-1 can significantly improve feed to eggs conversion ratio. TLRI 211-1 supplementation also can maintain eggs at their optimum quality level during storage. The study showed that B. subtilis TLRI 211-1 can be used as feed additives for improving egg production performance and egg quality.

Fusion Gene Detection in Prostate Cancer Samples Enhances the Prediction of Prostate Cancer Clinical Outcomes from Radical Prostatectomy through Machine Learning in a Multi-Institutional Analysis.

Prostate cancer remains one of the most fatal malignancies in men in the United States. Predicting the course of prostate cancer is challenging given that only a fraction of prostate cancer patients experience cancer recurrence after radical prostatectomy or radiation therapy. This study examined the expressions of 14 fusion genes in 607 prostate cancer samples from the University of Pittsburgh, Stanford University, and the University of Wisconsin-Madison. The profiling of 14 fusion genes was integrated with Gleason score of the primary prostate cancer and serum prostate-specific antigen level to develop machine-learning models to predict the recurrence of prostate cancer after radical prostatectomy. Machine-learning algorithms were developed by analysis of the data from the University of Pittsburgh cohort as a training set using the leave-one-out cross-validation method. These algorithms were then applied to the data set from the combined Stanford/Wisconsin cohort (testing set). The results showed that the addition of fusion gene profiling consistently improved the prediction accuracy rate of prostate cancer recurrence by Gleason score, serum prostate-specific antigen level, or a combination of both. These improvements occurred in both the training and testing cohorts and were corroborated by multiple models.

Resveratrol Attenuates Ankylosing Spondylitis in Mice by Inhibiting the TLR4/NF-κB/NLRP3 Pathway and Regulating Gut Microbiota.

Ankylosing spondylitis (AS) is an autoimmune disease associated with disturbed gut microbiota. Currently, the treatments and outcomes of AS are not satisfactory. It is reported that resveratrol (RES) is a major phytoalexin with anti-inflammatory, antibacterial and some other pharmacological effects. However, there are no studies on the role of RES in AS. Therefore, this study aimed to explore the effect and mechanism of RES on AS. Proteoglycan and complete freund's adjuvant were used to conduct an AS mouse model, and then the AS mice were gavaged with RES (20 mg/kg and 50 mg/kg) daily for 4 weeks. Subsequently, the effect of RES on AS mice was assessed by detecting disease severity, inflammatory cytokines, NLRP3 inflammasome, TLR4/NF-κB pathway, intestinal mucosal barrier function, intestinal microbial barrier function. The assessment results indicated that RES could significantly relieve progression and severity of AS, inhibit the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-17A, interferon-γ), and promote the expression of anti-inflammatory cytokines (interleukin-4). RES intervention caused the inhibition of NLRP3 inflammasome and TLR4/NF-κB pathway. In terms of intestinal barrier function, experimental results found RES increased zonula occludens-1 and occludin expression, and additionally, changed the composition of the gut microbiota by increasing levels of Lactobacillus and Bifidobacterium and reducing levels of Enterococcus faecalis and Escherichia coli. Collectively, RES protects PG-induced AS mice by inhibiting inflammatory responses and TLR4/NF-κB/NLRP3 pathway, restoring intestinal mucosal barrier function, and regulating the composition of the gut microbiota. In other words, RES is a potential candidate for the treatment of AS.

HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression.

PURPOSE: To elucidate the underlying mechanism of HIF-1α in migration and invasion of choriocarcinoma. METHODS: Cell proliferation was determined by CCK-8 assay when cell invasion was detected by transwell assay. The protein expression was detected by western blotting, immunohistochemistry, and qPCR assay. RESULT: HIF-1α was shown to be strongly expressed in both clinical tumour tissues and cell lines in choriocarcinoma. When HIF-1α was efficiently knocked down in JEG3 cells, the proliferation rate was reduced by approximately 50% and the number of cells that migrated through the transwell insert was greatly decreased. The cell invasion rate was also significantly reduced. Moreover, typical markers of epithelial-mesenchymal transition such as E-cadherin, were increased, while vimentin and α-SMA were decreased after HIF-1α knockdown. In contrast, overexpression of DEC1 reversed the effects of HIF-1α knockdown. Cell proliferation, migration, and invasion were partially recovered. The level of E-cadherin was decreased, while the level of vimentin and α-SMA was increased. In addition, the level of ß-catenin and LEF1 was downregulated after HIF-1α knockdown. The expression of MMP2 and MMP9 also declined. However, overexpression of DEC1 after HIF-1α knockdown partially reversed the expression pattern of these molecules. CONCLUSION: HIF-1α contributed to EMT and metastasis through activation of canonical ß-catenin signalling in choriocarcinoma and this process was dependent on DEC1. This study provides a new mechanism of HIF-1α in choriocarcinoma and suggests that intervention with DEC1 might be a promising therapeutic choice for choriocarcinoma.