TM7SF2-induced lipid reprogramming promotes cell proliferation and migration via CPT1A/Wnt/ß-Catenin axis in cervical cancer cells.

Cervical cancer poses a serious threat to women's health globally. Our previous studies found that upregulation of TM7SF2, which works as an enzyme involved in the process of cholesterol biosynthesis expression, was highly correlated with cervical cancer. However, the mechanistic basis of TM7SF2 promoting cervical cancer progression via lipid metabolism remains poorly understood. Therefore, quantification of fatty acids and lipid droplets were performed in vitro and in vivo. The protein-protein interaction was verified by Co-IP technique. The mechanism and underlying signaling pathway of TM7SF2 via CPT1A associated lipid metabolism in cervical cancer development were explored using Western blotting, IHC, colony formation, transwell assay, and wound healing assay. This study reported that overexpression of TM7SF2 increased fatty acids content and lipid droplets both in vivo and in vitro experiments. While knockout of TM7SF2 obviously attenuated this process. Moreover, TM7SF2 directly bonded with CPT1A, a key enzyme in fatty acid oxidation, and regulated CPT1A protein expression in cervical cancer cells. Notably, the proliferation and metastasis of cervical cancer cells were elevated when their CPT1A expression was upregulated. Then, rescue assay identified that CPT1A overexpressed could enhance the cell viability and migration in TM7SF2-knockout cells. Furthermore, depletion of TM7SF2 significantly inhibited WNT and ß-catenin proteins expression, which was enhanced by CPT1A-overexpressed. The proliferation and migration of cervical cancer cells were reversed in CPT1A-overexpressed cells with the treatment of MSAB, an inhibitor of Wnt/ß-Catenin pathway. This study put forward an idea that TM7SF2-induced lipid reprogramming promotes proliferation and migration via CPT1A/Wnt/ß-Catenin axis in cervical cancer, underlying the progression of cervical cancer.

Highly efficient and fast modulation of magnetic coupling interaction in the SrCoO2.5/La0.7Ca0.3MnO3 heterostructure.

Effective manipulation of magnetic properties in transition-metal oxides is one of the crucial issues for the application of materials. Up to now, most investigations have focused on electrolyte-based ionic control, which is limited by the slow speed. In this work, the interfacial coupling of the SrCoO2.5/La0.7Ca0.3MnO3 (LCMO) bilayer is effectively modulated with fast response time. After being treated with diluted acetic acid, the bilayer changes from antiferromagnetic/ferromagnetic (AFM/FM) coupling to FM/FM coupling and the Curie temperature is also effectively increased. Meanwhile, the corresponding electric transport properties are modulated within a very short time. Combined with the structure characterization and X-ray absorption measurements, we find that the top SrCoO2.5 layer is changed from the antiferromagnetic insulator to the ferromagnetic metal phase, which is attributed to the formation of the active oxygen species due to the reaction between the protons in the acid and the SrCoO2.5 layer. The bottom LCMO layer remains unchanged during this process. The response time of the bilayer with the acid treatment method is more than an order of magnitude faster than other methods. It is expected that this acid treatment method may open more possibilities for manipulating the magnetic and electric properties in oxide-based devices.

Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis.

Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell-cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.

The Role of ZNF275/AKT Pathway in Carcinogenesis and Cisplatin Chemosensitivity of Cervical Cancer Using Patient-Derived Xenograft Models.

Zinc finger protein 275 (ZNF275) is a C2H2-type transcription factor that is localized on chromosome Xq28. Whether ZNF275 participates in modulating the biological behaviors of cervical cancer has not been determined to our knowledge. The present study employed CCK-8, BrdU, flow cytometry, and a transwell assay to investigate the cell viability, proliferation, apoptosis, migration, and invasion of cervical cancer cells. The application of Western blotting and immunohistochemistry (IHC) aims to assess ZNF275 protein expression and identify the signaling pathway relevant to ZNF275-mediated effects on cervical cancer. The therapeutic impact of the combined therapy of the AKT inhibitor triciribine and cisplatin was evaluated on cervical cancer patient-derived xenograft (PDX) models expressing high ZNF275. The current research illustrated that cervical cancer tissue exhibited a higher expression of ZNF275 in contrast to the surrounding normal cervical tissue. The downregulation of ZNF275 suppressed cell viability, migration, and invasion, and facilitated the apoptosis of SiHa and HeLa cells via weakening AKT/Bcl-2 signaling pathway. Moreover, triciribine synergized with cisplatin to reduce cell proliferation, migration, and invasion, and enhanced the apoptosis of SiHa cells expressing high ZNF275. In addition, the combination treatment of triciribine and cisplatin was more effective in inducing tumor regression than single agents in cervical cancer PDX models expressing high ZNF275. Collectively, the current findings demonstrated that ZNF275 serves as a sufficiently predictive indicator of the therapeutic effectiveness of the combined treatment of triciribine and cisplatin on cervical cancer. Combining triciribine with cisplatin greatly broadens the therapeutic options for cervical cancer expressing high ZNF275, but further research is needed to confirm these results.

Prostate zones and tumor morphological parameters on magnetic resonance imaging for predicting the tumor-stage diagnosis of prostate cancer.

PURPOSE: To determine whether the morphological parameters of prostate zones and tumors on magnetic resonance imaging (MRI) can predict the tumor-stage (T-stage) of prostate cancer (PCa) and establish an optimal T-stage diagnosis protocol based on three-dimensional reconstruction and quantization after image segmentation. METHODS: A dataset of the prostate MRI scans and clinical data of 175 patients who underwent biopsy and had pathologically proven PCa from January 2018 to November 2020 was retrospectively analyzed. The authors manually segmented and measured the volume, major axis, and cross-sectional area of the peripheral zone (PZ), transition zone, central zone (CZ), anterior fibromuscular stroma, and tumor. The differences were evaluated by the One-Way analysis of variance, Pearson's chi-squared test, or independent samples t-test. Spearman's correlation coefficient and receiver operating characteristic curve analyses were also performed. The cut-off values of the T-stage diagnosis were generated using Youden's J index. RESULTS: The prostate volume (PV), PZ volume (PZV), CZ volume, tumor's major axis (TA), tumor volume (TV), and volume ratio of the TV and PV were significantly different among stages T1 to T4. The cut-off values of the PV, PZV, CZV, TA, TV, and the ratio of TV/PV for the discrimination of the T1 and T2 stages were 53.63 cm3, 11.60 cm3, 1.97 cm3, 2.30 mm, 0.90 cm3, and 0.03 [area under the curves (AUCs): 0.628, 0.658, 0.610, 0.689, 0.724, and 0.764], respectively. The cut-off values of the TA, TV, and the ratio of TV/PV for the discrimination of the T2 and T3 stages were 2.80 mm, 8.29 cm3, and 0.12 (AUCs: 0.769, 0.702, and 0.688), respectively. The cut-off values of the TA, TV, and the ratio of TV/PV for the discrimination of the T3 and T4 stages were 4.17 mm, 18.71 cm3, and 0.22 (AUCs: 0.674, 0.709, and 0.729), respectively. CONCLUSION: The morphological parameters of the prostate zones and tumors on the MRIs are simple and valuable diagnostic factors for predicting the T-stage of patients with PCa, which can help make accurate diagnoses and lateral treatment decisions.

Investigating the potential mechanism of quercetin against cervical cancer.

BACKGROUND: Cervical cancer is emerging as a potential target of increased susceptibility to coronavirus disease-2019 (COVID-19), leading to compromised survival rates. Despite this critical link, efficacious anti-cervical cancer/COVID-19 interventions remain limited. Quercetin, known for its efficacy against both cancer and viral infections, holds promise as a therapeutic agent. This study aims to elucidate quercetin's anti-cervical cancer/COVID-19 mechanisms and potential targets. METHODS: We initiated our investigation with differential gene expression analysis using cervical cancer transcriptome data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx), focusing on intersections with COVID-19-related genes. Network pharmacology was employed to identify the shared targets between cervical cancer/COVID-19 DEGs and quercetin's targets. Subsequently, Cox proportional hazards analyses were employed to establish a risk score based on these genes. Molecular docking techniques were applied to predict quercetin's therapeutic targets and mechanisms for mitigating cervical cancer and COVID-19. RESULTS: Our findings unveiled 45 potential quercetin targets with anti-cervical cancer/COVID-19 actions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted significant enrichment in immune pathways and COVID-19-related pathways. A refined risk score model, comprising PLA2G7, TNF, TYK2, F2, and NRP1, effectively stratified cervical cancer patients into distinct risk groups. Importantly, molecular docking analyses illuminated quercetin's remarkable binding affinity to the primary protease of the coronavirus. CONCLUSIONS: In summation, our study suggests that quercetin holds promise as a potential therapeutic agent for mitigating coronavirus function, specifically through its interaction with the primary protease. This research offers novel insights into exploring COVID-19 susceptibility and enhancing survival in cervical cancer patients.

Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion.

Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-ß signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.

Copine 1 predicts poor clinical outcomes by promoting M2 macrophage activation in ovarian cancer.

OBJECTIVE: Copine 1 (CPNE1), a membrane-binding protein, influences the prognosis of various cancers. According to cBioPortal, CPNE1 amplification is a prevalent genetic mutation in ovarian cancer but with unknown oncogenic mechanism. METHODS: This study analysed the CPNE1 expression in ovarian cancer using online datasets, as validated by immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) and western blotting. Concurrently, the prognostic value of CPNE1 was accessed. Cell Counting Kit-8, colony formation, transwells and xenograft experiments were performed to evaluate the functions of CPNE1 during ovarian cancer carcinogenesis. CPNE1 and its related genes were analysed by g:Profiler and Tumour Immune Estimation Resource. Furthermore, human monocytic THP-1 cells were co-cultured with ES2 cells to investigate the effect of CPNE1 on macrophage polarization. RESULTS: The results of bioinformatic analysis, IHC, qPCR and western blotting indicated a higher CPNE1 in ovarian cancer. CPNE1 overexpression demonstrated an association with a poor prognosis of ovarian cancer. Functionally, CPNE1 overexpression increased ES2 and SKOV3 cell proliferation, invasion and migration in vitro and promoted ovarian tumour xenograft growth in vivo, while CPNE1 knockdown led to opposite effects. Additionally, CPNE1 expression demonstrated an association with immune cell infiltration in ovarian cancer, especially macrophage. CPNE1 promoted protumour M2 macrophage polarization by upregulating cluster of differentiation 163 (CD163), CD206 and interleukin-10. CONCLUSIONS: Our study revealed that CPNE1 mediated M2 macrophage polarization and provided a therapeutic target for ovarian cancer.

The polar and nonpolar interfaces influenced of magnetism in LaMnO3-based superlattices.

The interface of perovskite heterostructures has been shown to exhibit various electronic and magnetic phases such as two-dimensional electron gas, magnetism, superconductivity, and electronic phase separation. These rich phases are expected due to the strong interplay between spin, charge, and orbital degree of freedom at the interface. In this work, the polar and nonpolar interfaces are designed in LaMnO3-based (LMO) superlattices to investigate the difference in magnetic and transport properties. For the polar interface in a LMO/SrMnO3 superlattice, a novel robust ferromagnetism, exchange bias effect, vertical magnetization shift, and metallic behaviors coexist due to the polar catastrophe, which results in a double exchange coupling effect in the interface. For the nonpolar interface in a LMO/LaNiO3 superlattice, only the ferromagnetism and exchange bias effect characteristics exist due to the polar continuous interface. This is attributed to the charge transfer between Mn3+ and Ni3+ ions at the interface. Therefore, transition metal oxides exhibit various novel physical properties due to the strong correlation of d electrons and the polar and nonpolar interfaces. Our observations may provide an approach to further tune the properties using the selected polar and nonpolar oxide interfaces.

Establishment and genetically characterization of patient-derived xenograft models of cervical cancer.

PURPOSE: Patient-derived xenograft (PDX) models were established to reproduce the clinical situation of original cancers and have increasingly been applied to preclinical cancer research. Our study was designed to establish and genetically characterize cervical cancer PDX models. METHODS: A total of 91 fresh fragments obtained from 22 surgically resected cervical cancer tissues were subcutaneously engrafted into female NOD-SCID mice. Hematoxylin and eosin (H&E) staining was performed to assess whether the established PDX models conserved the histological features of original patient cervical cancer tissues. Moreover, a Venn diagram was applied to display the overlap of all mutations detected in whole-genome sequencing (WGS) data from patient original cervical cancer (F0) and F2-, F3-PDX models. The whole exome sequencing (WES) and the "maftools" package were applied to determine the somatic mutations among primary cervical cancers and the established PDX models. RESULTS: Our study successfully developed a panel of cervical cancer PDX models and the latency time of cervical cancer PDX model establishment was variable with a progressive decrease as the passage number increased, with a mean time to initial growth of 94.71 days in F1 engraftment to 40.65 days in F3 engraftment. Moreover, the cervical cancer PDX models preserved the histological features of their original cervical cancer. WGS revealed that the genome of original cervical cancer was preserved with high fidelity in cervical cancer PDX models throughout the xenografting and passaging process. Furthermore, WES demonstrated that the cervical cancer PDX models maintained the majority somatic mutations of original cervical cancer, of which the KMT2D, LRP1B, NAV3, TP53, FAT1, MKI67 and PKHD1L1 genes were identified as the most frequently mutated genes. CONCLUSIONS: The cervical cancer PDX models preserved the histologic and genetic characteristics of their original cervical cancer, which helped to gain a deeper insight into the genetic alterations and lay a foundation for further investigation of the molecular targeted therapy of cervical cancer.

Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer.

Understanding the role of N6-adenosine methylation (m6A) in the tumor microenvironment (TME) is important since it can contribute to tumor development. However, the research investigating the association between m6A and TME and cervical cancer is still in its early stages. The aim of this study was to discover the possible relationship between m6A RNA methylation regulators, TME, PD-L1 expression levels, and immune infiltration in cervical cancer. We gathered RNA-seq transcriptome data and clinical information from cervical cancer patients using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. To begin, researchers assessed the differences in m6A regulatory factor expression levels between cervical cancer and normal tissues. Clustering analysis was adapted to assess PD-L1 expression, immunological score, immune cell infiltration, TME, and probable pathways in cervical cancer samples. The majority of m6A regulators were found to be considerably overexpressed in cervical cancer tissues. Using consensus clustering of 21 m6A regulators, we identified two subtypes (clusters 1/2) of cervical cancer, and we found that WHO stage and grade were associated with the subtypes. PD-L1 expression increased dramatically in cervical cancer tissues and was significantly linked to ALKBH5, FTO, METTL3, RBM15B, YTHDF1, YTHDF3, and ZC3H13 expression levels. Plasma cells and regulatory T cells (Tregs) were considerably elevated in cluster 2. Cluster 1 is involved in numerous signature pathways, including basal transcription factors, cell cycle, RNA degradation, and the spliceosome. The prognostic signature-based riskscore (METTL16, YTHDF1, and ZC3H13) was found to be an independent prognostic indicator of cervical cancer. The tumor immune microenvironment (TIME) was linked to m6A methylation regulators, and changes in their copy number will affect the quantity of tumor-infiltrating immune cells dynamically. Overall, our research discovered a powerful predictive signature based on m6A RNA methylation regulators. This signature correctly predicted the prognosis of cervical cancer patients. The m6A methylation regulator could be a critical mediator of PD-L1 expression and immune cell infiltration, and it could have a significant impact on the TIME of cervical cancer.

UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer mortality, and new therapeutic options are urgently needed. Long noncoding RNA H19 (H19) is known to promote PDAC progression, but the downstream genes of H19 are largely unknown. Five PDAC cell lines, nonmalignant pancreatic cells, TCGA, GEO-derived pancreatic tissues (malignant, n=413; nonmalignant, n=234), a pancreatic tissue array (n=96), and pancreatic tissues from our clinic (malignant, n=20; nonmalignant, n=20) were examined by a gene array, RT-qPCR, Western blotting, MTT, colony formation, wound-healing, siRNA-mediated gene silencing, bioinformatics, xenotransplantation, and immunohistochemistry assays. The cell cycle inhibitor, UHMK1, was identified to have the strongest correlation with H19. UHMK1 expression was enhanced in PDAC, and high UHMK1 expression correlated with tumor stage, and lower overall survival. siRNA-mediated UHMK1 downregulation inhibited progression signaling. siRNA-mediated downregulation of H19 or UHMK1 inhibited tumor proliferation and xenograft growth. Based on the correlation between UHMK1 expression and clinical parameters, we developed a nomogram that reliably predicts patient prognosis and overall survival. Together, we characterized UHMK1 as an H19-induced oncogene and verified it as a novel PDAC prognostic marker for overall survival.

Dimensionality control of magnetic coupling at interfaces of cuprate-manganite superlattices.

The dimensionality of the crystal structure plays a vital role in artificial heterostructures composed of different transition metal oxides. Nonlinear layer-thickness dependence of the exchange bias effect was observed in high-quality SrCuO2/La0.7Sr0.3MnO (LSMO) superlattices induced in the present work by dimensional evolution. In the SCO(n)/LSMO(8) superlattices with thickness below the critical value (5 u.c.), the exchange bias effect decreased and the saturated magnetization increased with increase in SCO thickness. By contrast, the exchange bias effect increased and the saturated magnetization decreased in S(n)L(8) superlattices with thickness above the critical value. This is because the lattice SCO material underwent a breathing-like structural transformation from the planar to a chain-like structure. The results indicate the interfacial superexchange coupling mainly present in the chain-like S(n)L(8) superlattices through X-ray absorption spectroscopy and first principles calculations. This superexchange coupling generated a weak localized magnetic moment to pin the adjacent ferromagnetic layer. However, in the thicker S(n)L(8) superlattices, evolution of magnetic properties was induced by the long-range antiferromagnetic order in the planar SCO layer. Our findings demonstrate that the dimensionality driven structural variation is an effective method to manipulate the electronic reconstruction and the associated physical properties, paving a pathway for the advancement of strongly correlated materials.

Sulforaphane Targets TRA-1/GLI Upstream of DAF-16/FOXO to Promote C. elegans Longevity and Healthspan.

Broccoli-derived isothiocyanate sulforaphane inhibits inflammation and cancer. Sulforaphane may support healthy aging, but the underlying detailed mechanisms are unclear. We used the C. elegans nematode model to address this question. Wild-type and 4 mutant C. elegans worm strains were fed in the presence or absence of sulforaphane and E. coli food bacteria transfected with RNA interference gene constructs. Kaplan-Meier survival analysis, live imaging of mobility and pharyngeal pumping, fluorescence microscopy, RT-qPCR, and Western blotting were performed. In the wild type, sulforaphane prolonged lifespan and increased mobility and food intake because of sulforaphane-induced upregulation of the sex-determination transcription factor TRA-1, which is the ortholog of the human GLI mediator of sonic hedgehog signaling. In turn, the tra-1 target gene daf-16, which is the ortholog of human FOXO and the major mediator of insulin/IGF-1 and aging signaling, was induced. By contrast, sulforaphane did not prolong lifespan and healthspan when tra-1 or daf-16 was inhibited by RNA interference or when worms with a loss-of-function mutation of the tra-1 or daf-16 genes were used. Conversely, the average lifespan of C. elegans with hyperactive TRA-1 increased by 8.9%, but this longer survival was abolished by RNAi-mediated inhibition of daf-16. Our data suggest the involvement of sulforaphane in regulating healthy aging and prolonging lifespan by inducing the expression and nuclear translocation of TRA-1/GLI and its downstream target DAF-16/FOXO.

Alpha-Lipoic Acid Prevents Side Effects of Therapeutic Nanosilver without Compromising Cytotoxicity in Experimental Pancreatic Cancer.

Silver nanoparticles (AgNPs) have attracted attention in cancer therapy and might support the treatment of pancreatic ductal adenocarcinoma (PDAC). Silver is in clinical use in wound dressings, catheters, stents and implants. However, the side effects of systemic AgNP treatment due to silver accumulation limit its therapeutic application. We evaluated whether the antioxidant and natural agent α-lipoic acid might prevent these side effects. We synthesized AgNPs using an Ionic-Pulser® Pro silver generator and determined the concentration by inductively coupled plasma-optical emission spectrometry. The effect of α-lipoic acid was examined in four PDAC and two nonmalignant cell lines by MTT, FACS analysis, TEM, xenotransplantation and immunohistochemistry. The viability of PDAC cells was nearly totally abolished by AgNP treatment, whereas nonmalignant cells largely resisted. α-Lipoic acid prevented AgNP-induced cytotoxicity in nonmalignant cells but not in PDAC cells, which might be due to the higher sensitivity of malignant cells to silver-induced cytotoxicity. α-Lipoic acid protected mitochondria from AgNP-induced damage and led to precipitation of AgNPs. AgNPs reduced the growth of tumor xenografts, and cotreatment with α-lipoic acid protected chick embryos from AgNP-induced liver damage. Together, α-lipoic acid strongly reduced AgNP-induced side effects without weakening the therapeutic efficacy.

Discovery of key genes as novel biomarkers specifically associated with HPV-negative cervical cancer.

Cervical cancer is a common female malignancy that is mainly caused by human papillomavirus (HPV) infection. However, the incidence of HPV-negative cervical cancer has shown an increasing trend in recent years. Because the mechanism of HPV-negative cervical cancer development is unclear, this study aims to find the pattern of differential gene expression in HPV-negative cervical cancer and verify the underlying potential mechanism. Differentially expressed genes were compared among HPV-positive cervical cancer, HPV-negative cervical cancer, and normal cervical tissues retrieved from TCGA. Subsequently, dysregulated differentially expressed genes specifically existed in HPV-negative cervical cancer tissues and HPV-negative cell lines were validated by qRT-PCR, western blotting, and immunohistochemical staining. We found seventeen highly expressed genes that were particularly associated with HPV-negative cervical cancer from analysis of TCGA database. Among the 17 novel genes, 7 genes (preferentially expressed antigen in melanoma [PRAME], HMGA2, ETS variant 4 [ETV4], MEX3A, TM7SF2, SLC19A1, and tweety-homologs 3 [TTYH3]) displayed significantly elevated expression in HPV-negative cervical cancer cells and HPV-negative cervical cancer tissues. Additionally, higher expression of MEX3A and TTYH3 was associated with a shorter overall survival of patients with HPV-negative cervical cancer. Our study implies that these seven genes are more likely to provide novel insights into the occurrence and progression of HPV-negative cervical cancer.

Direct C-H aminocarbonylation of N-heteroarenes with isocyanides under transition metal-free conditions.

A C-C bond forming amide synthesis through direct C-H aminocarbonylation of N-heteroarenes with isocyanides was developed. The reaction was mediated by an inorganic persulfate salt under transition metal-free conditions. Mechanistic studies suggested a radical pathway for this reaction without the participation of H2O and O2. This method also showed merits of substrate availability, easy operation and atom economy. It provided an efficient route for straightforward synthesis of N-heteroaryl amides.