ABSTRACT
Autophagy is closely related to the occurrence and development of human malignancies; however, the detailed mechanisms underlying autophagy in cervical cancer require further investigation. Previously, we found that the ectopic expression of NCAPH, a regulatory subunit of condensed protein complexes, significantly enhanced the proliferation of tumor cells; however, the underlying mechanisms were unclear. Here, we revealed that NCAPH is a novel autophagy-associated protein in cervical cancer that promotes cell proliferation by inhibiting autophagosome formation and reducing autophagy, with no effect on the cell cycle, apoptosis, or aging. Tripartite motif-containing protein 21 (TRIM21) is well known to be involved in inflammation, autoimmunity and cancer, mainly via its E3 ubiquitin ligase activity. Mass spectrometry and immunoprecipitation assays showed that TRIM21 interacted with NCAPH and decreased the protein stability of NCAPH via ubiquitination at the K11 lysine residue. Structural domain mutation analysis revealed that TRIM21 combined with NCAPH through its PRY/SPRY and CC domains and accelerated the degradation of NCAPH through the RING domain. Furthermore, TRIM21 promoted autophagosome formation and reduced cell proliferation by inhibiting NCAPH expression and the downstream AKT/mTOR pathway in cervical cancer cells. Immunohistochemical staining revealed that the protein expression of TRIM21 was negatively correlated with that of NCAPH and positively correlated with that of beclin-1 in cervical cancer tissues. Therefore, we provide evidence for the role of the TRIM21-NCAPH axis in cervical cancer autophagy and proliferation and the involvement of the AKT/mTOR signaling pathway in this process. These results deepen our understanding of the carcinogenesis of cervical cancer, broaden the understanding of the molecular mechanisms of TRIM21 and NCAPH, and provide guidance for individualized treatment of cervical cancer in the future.
Subject(s)
Autophagy , Cell Proliferation , Proto-Oncogene Proteins c-akt , Ribonucleoproteins , Signal Transduction , TOR Serine-Threonine Kinases , Ubiquitination , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/genetics , Female , TOR Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Ribonucleoproteins/metabolism , Ribonucleoproteins/genetics , Cell Line, Tumor , Animals , HeLa Cells , Mice , Mice, NudeABSTRACT
This study utilizes polyethylene terephthalate (PET) aggregate of different particle sizes (21 µm, 107 µm, and 244 µm) to replace natural aggregate in the preparation of PET-modified engineered cementitious composite (P-ECC). The impact of PET aggregate particle size on the performance of P-ECC is examined herein from micro to macro levels. The focus is on the influence patterns and mechanisms of P-ECC's workability, its basic mechanical properties, and its microstructure. Crack parameters are processed to quantitatively analyze crack development patterns. Using microscopic techniques, the interfacial transition zone (ITZ) between different aggregates and the cement matrix is compared, and the failure mechanism of P-ECC is analyzed. The results show that the incorporation of PET aggregate can improve P-ECC's workability and reduce its self-weight, but incorporation has a negative effect on compressive strength. Additionally, the particle size of PET aggregate significantly affects the uniaxial tensile performance of P-ECC. Compared to conventional ECC, the tensile strength of P-S (21 µm PET) increased the most markedly (18.1%), and the ultimate tensile strain of P-M (107 µm PET) increased the most markedly (66.0%), with both demonstrating good crack control and deformation energy dissipation capabilities. The uniaxial tensile performance of P-L (244 µm PET) was lower than that of the conventional ECC. Microscopic tests revealed that the increase in PET aggregate particle size enlarges the ITZ width and its surrounding pores. Appropriate pore enlargement is beneficial for enhancing tensile ductility, while excessive pores have a negative effect. The study results reveal the impact of PET aggregate particle size on the performance of P-ECC, providing new insights for the performance optimization of ECC.
ABSTRACT
Currently, oil-coated PVA fibers are the most commonly used material in ECC research. However, the high price limits the application of PVA-ECC in practical engineering. In order to reduce the cost, one of the methods is to partially replace the PVA fibers in ECC. In order to demonstrate the feasibility of PVA/BF-ECC and PVA/PP-ECC, polyvinyl alcohol fibers (PVA), basalt fibers (BFs) and polypropylene fibers (PP) were added at 0.5%, 1.0% and 1.5% by volume of PVA in addition to 1% by volume of PVA. Subsequently, tensile, compression and drop-weight impact tests were conducted on single or hybrid fiber concrete. The results showed that the post-peak compression toughness, tensile strength, and initial cracking impact strength of PVA/BF-ECC and PVA/PP-ECC increased significantly with the increase in the volume ratio of BF and PP fibers, while the performance of PVA-ECC materials with the same fiber volume ratio decreased slightly. Therefore, the cost can be reduced by designing hybrid PVA/BF-ECC materials that meet the performance requirements. The experimental evidence presented in this study demonstrates the feasibility and reasonable prospect of the new hybrid PVA/BF-ECC.
ABSTRACT
Cervical cancer is the second most common malignancy of the female reproductive tract worldwide. Although cervical cancer is caused by human papillomavirus (HPV) infection, its underlying pathogenesis requires further investigation. The present study investigated the role of kinetochore associated protein 1 (KNTC1) in cervical cancer and its association with the key virus oncoprotein, HPV E7. A series of bioinformatic analyses revealed that KNTC1 might be involved in the tumorigenesis of multiple human malignancies, including cervical cancer. Tissue microarray analysis showed that in vivo KNTC1 expression was higher in high-grade squamous intraepithelial lesions (HSILs) than in normal cervix and even higher in cervical cancer. In vitro silencing of KNTC1 increased the proliferation, invasion and migration of cervical cancer cell lines. Although not affecting apoptosis, KNTC1 silencing significantly promoted G1/S phase transition of the cell cycle. High-throughput analysis of mRNA expression showed that KNTC1 could regulate its downstream target protein Smad2 at the transcriptional level. Moreover, as the key oncoprotein of the virus, HPV E7 could inhibit the expression of KNTC1 protein, and decrease Smad2 protein expression with or without the aid of KNTC1. These results indicated that KNTC1 is a novel tumor suppressor that can impede the initiation and progression of cervical carcinoma, providing insight into the molecular mechanism by which HPV induces cervical cancer.
Subject(s)
Oncogene Proteins, Viral , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Cervix Uteri/metabolism , Uterine Cervical Neoplasms/pathology , Papillomavirus Infections/genetics , Papillomavirus E7 Proteins/genetics , Smad2 Protein/genetics , Smad2 Protein/metabolism , Oncogene Proteins, Viral/genetics , Oncogene Proteins, Viral/metabolism , Carcinogenesis/genetics , Microtubule-Associated Proteins/metabolism , Cell Cycle Proteins/metabolismABSTRACT
To confirm the feasibility of waste incineration fly ash applied in asphalt pavement materials, the waste fly ash from the waste incineration station in Dongguan (DG-FA) and Guangzhou (GZ-FA) were selected as mineral filler replacing limestone powder (LF) to prepare asphalt mortar. The physical properties, chemical composition, and thermal characteristics of FA were analyzed. The effect of FA on the physical properties and rheological properties of asphalt binder was investigated systematically. The micromorphology of FA asphalt mortar was characterized. Finally, the blocking effect of asphalt binder on the leaching of toxic elements from FA was evaluated through XRF test. The results showed that the granular composition of FA particles was similar to that of LF. Furthermore, compared to LF, the specific surface area and the pore structure of FA were more developed, and the high active amorphous material was higher. Adding FA to asphalt mortar and increasing replacing amount improved its high-temperature rutting resistance as well as its ability to adhere to asphalt, while the low-temperature crack resistance was decreased. Further, the asphalt binder provided the good shielding effect against the migration of heavy metals in FA. While the leaching concentration of Pb element slightly exceeded the hazardous waste leaching standard (GB5085.3-2007), the remaining elements met the standard requirements. Overall, FA improved asphalt mortar performance, and the asphalt had a good curing and stabilizing effect on the toxic elements in fly ash, indicating that FA could be used as a filler in asphalt pavements.
Subject(s)
Metals, Heavy , Refuse Disposal , Coal Ash/chemistry , Incineration , Particulate Matter , Feasibility Studies , Solid Waste/analysis , Carbon , Metals, Heavy/analysisABSTRACT
The influence of different replacement ratios of steel-slag powder as cement-replacement material on the fracture performance of concrete is studied in this paper. A three-point bending fracture test is carried out on slag powder-cement-based concrete (SPC)-notched beams with steel-slag powder as cementitious materials, partially replacing cement (0%, 5%, 10%, 15%, and 20%). Load-deflection curves and load-crack-opening displacement curves of SPC-notched beams with five different replacement ratios of steel-slag powder were obtained. The effects of different steel-slag-powder replacement ratios on the fracture properties (fracture energy, fracture toughness, and double-K fracture parameters) of the SPC were analyzed and discussed. The results showed that the incorporation of appropriate steel-slag powder can affect the fracture performance of SPC. Compared with concrete without steel-slag powder, adding appropriate steel-slag powder can effectively improve the bond performance between aggregate and matrix because the steel-slag powder contains hydration activity substances such as calcium oxide and aluminium trioxide. The fracture energy and fracture toughness of SPC increased and then decreased with the increase in steel-slag-powder replacement ratios, and the SPC concrete showed best fracture performance with a 5% steel slag powder replacement ratio. Its fracture energy increases by 13.63% and fracture toughness increases by 53.22% compared with NC.
ABSTRACT
Using a homemade pressure device, we explored the synergistic effect of pressurization rate and ß-form nucleating agent (ß-NA) on the crystallization of an isotactic polypropylene (iPP) melt. The obtained samples were characterized by combining small angle X-ray scattering and synchrotron wide angle X-ray diffraction. It was found that the synergistic application of pressurization and ß-NA enables the preparation of a unique multi-phase crystallization of iPP, including ß-, γ- and/or mesomorphic phases. Pressurization rate plays a crucial role on the formation of different crystal phases. As the pressurization rate increases in a narrow range between 0.6-1.9 MPa/s, a significant competitive formation between ß- and γ-iPP was detected, and their relative crystallinity are likely to be determined by the growth of the crystal. When the pressurization rate increases further, both ß- and γ-iPP contents gradually decrease, and the mesophase begins to emerge once it exceeds 15.0 MPa/s, then mesomorphic, ß- and γ- iPP coexist with each other. Moreover, with different ß-NA contents, the best pressurization rate for ß-iPP growth is the same as 1.9 MPa/s, while more ß-NA just promotes the content of ß-iPP under the rates lower than 1.9 MPa/s. In addition to inducing the formation of ß-iPP, it shows that ß-NA can also significantly promote the formation of γ-iPP in a wide pressurization rate range between 3.8 to 75 MPa/s. These results were elucidated by combining classical nucleation theory and the growth theory of different crystalline phases, and a theoretical model of the pressurization-induced crystallization is established, providing insight into understanding the multi-phase structure development of iPP.
ABSTRACT
Geopolymer concrete (GC) has been gaining attention in research and engineering circles; however, it is a brittle material with poor tensile performance and crack resistance. To address these problems, we introduced fibers into GC. In this study, axial compression and scanning electron microscope (SEM) tests were carried out on polyvinyl alcohol (PVA) short fiber reinforced low-calcium fly ash-slag-based geopolymer concrete (PFRGC). The ratio of PVA short fibers and low-calcium fly ash on the compression behavior of fiber reinforced geopolymer concrete (FRGC) were investigated and discussed. The test results show that PVA fibers play a bridging role in the cracks of the specimen and bear the load together with the matrix, so the addition of PVA fibers delayed the crack propagation of GC under axial compression. However, with the increase of low-calcium fly ash/PVA fibers, the number of unreacted fly ash particles in PFRGCs increases. Too many unreacted fly ash particles make GC more prone to micro-cracks during loading, adversely affecting compressive properties. Therefore, the axial compressive strength, elastic modulus, and Poisson's ratio of GC decrease with the increasing low-calcium fly ash/PVA fibers.
ABSTRACT
Cervical cancer is one of the most common gynecological tumors in the world, and human papillomavirus (HPV) infection is its causative agent. However, the molecular mechanisms involved in the carcinogenesis of cervical cancer still require clarification. Here we found that knockdown of Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) gene expression significantly inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of cervical cancer cells in vitro, and restrained xenograft tumor formation in vivo. Intriguingly, HPV E7 could form a positive feedback loop with NCAPH. E7 upregulated NCAPH gene expression via E2F1 which initiated NCAPH transcription by binding to its promoter directly. Silencing of NCAPH reduced E7 transcription via promoting the transition of AP-1 heterodimer from c-Fos/c-Jun to Fra-1/c-Jun. Moreover, the E7-mediated NCAPH overexpression was involved in the activation of the PI3K/AKT/SGK signaling pathway. In vivo, NCAPH expression in cervical cancer tissues was significantly higher than which in normal cervix and high-grade squamous intraepithelial lesion (HSIL) tissues, and its expression was significantly correlated with tumor size, depth of invasion and lymph node metastasis. Patients with high NCAPH expression had a significantly better survival outcomes than those with low-expression, suggesting that NCAPH-induced cell proliferation might sensitize cancer cells to adjuvant therapy. In conclusion, our results revealed the role of NCAPH in the carcinogenesis of cervical cancer in vitro and in vivo. The interaction between E7 and NCAPH expands the mechanism of HPV induced tumorigenesis and that of host genes regulating HPV E7.
Subject(s)
Carcinogenesis/genetics , Cell Cycle Proteins/genetics , Ectopic Gene Expression , Immediate-Early Proteins/metabolism , Nuclear Proteins/genetics , Papillomavirus E7 Proteins/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Uterine Cervical Neoplasms/genetics , Adult , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , E2F1 Transcription Factor/metabolism , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Mice, Nude , Models, Biological , Neoplasm Invasiveness , Prognosis , Promoter Regions, Genetic/genetics , Protein Binding , Protein Multimerization , Signal Transduction , Transcription Factor AP-1/metabolism , Treatment Outcome , Tumor Stem Cell Assay , Uterine Cervical Neoplasms/pathologyABSTRACT
Subtropical natural exposure may significantly affect the bonding behavior of fiber reinforced polymer (FRP) externally bonded to concrete. To study the effect of subtropical natural climates on the FRP-concrete interface, natural exposure tests and an analytical approach were carried out on specimens externally bonded with carbon fiber reinforced polymer (CFRP) and basalt fiber reinforced polymer (BFRP). The bilinear bond stress-slip relationships for different exposure periods were derived from the experimental results of the strengthened reinforced concrete (RC) beams. Based on these bond-slip relationships, the full-range behavior of shear stress along the bond length and debonding load can be obtained through the analytical solution. The testing and numerical results showed that subtropical natural exposure can greatly affect the bond behavior of CFRP-concrete and BFRP-concrete interfaces in the early exposure period. In the late exposure period, the bond behavior was basically stable. With the increase of exposure time, the position of maximum shear stress tended to move backward, which indicated that the behavior of the FRP-concrete interface was weakened by natural exposure. Compared to the CFRP-concrete interface, subtropical natural exposure has greater influence on the bond behavior of the BFRP-concrete interface.
ABSTRACT
Cervical squamous cell carcinoma develops through a series of stages, including low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), microinvasive squamous cell carcinoma (MISCC), and invasive squamous cell carcinoma (ISCC). The difference between HSIL and MISCC is the appearance of microinvasion, which determines the treatment for patients. However, sometimes it is difficult to differentiate HSIL from MISCC in morphology, and no effective markers are available to help determine microinvasion. Here, we evaluated the expression patterns of podoplanin in cervical tissues by immunohistochemistry staining. Results showed that podoplanin was specifically expressed in a continuous or discontinuous linear pattern within the basal layer of cells from normal cervical squamous epithelium (NS) (100%, 96/96) and HSIL (81%, 57/70). However, its expression was completely absent in microinvasive lesions (0%, 72/72), and the location of podoplanin expression loss was consistent with that of microinvasive lesions. Thus, for HSIL with positive podoplanin expression, the sudden loss of podoplanin represents the occurrence of early invasion. Furthermore, podoplanin was expressed in 3.4% (4/118) of ISCC, and its expression was not correlated with the age of the patient, tumor size, differentiation, FIGO stage, depth of invasion, lymph node, or distant metastasis. The prognosis of patients with positive podoplanin was slightly better than those without it (p > 0.05). Therefore, we found that podoplanin, as a new specific marker for the basal layer cells of cervical squamous epithelium, could assist the diagnosis of microinvasion in cervical squamous cell carcinoma. The specific staining pattern of podoplanin provides the possibility of clinical application in the future.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/diagnosis , Membrane Glycoproteins/metabolism , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adult , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Female , Humans , Immunohistochemistry , Middle Aged , Uterine Cervical Neoplasms/pathology , Uterine Cervical Dysplasia/pathologyABSTRACT
The lower critical solution temperature (LCST) phase separation behaviors of thermosensitive poly(N-isopropylacrylamide) (PNIPAM) aqueous solutions were investigated by power-compensation differential scanning calorimetry (DSC). The entropic effect and hence the change of swelling state of PNIPAM polymer coils in homogeneous concentrated aqueous solutions with varied solution composition was elucidated by the isothermal enthalpy demixing recovery behaviors in distinct concentration regions.
ABSTRACT
Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes. Amplification of CKS1BP7 (dot-like pattern) was found in 28.8% of all cases, while amplified IGF1R (cluster pattern) was identified in 24.2% of all patients. The two events often co-existed (p = 0.01). Within the same tumors, identical CNAs of CKS1BP7 and IGF1R were found in DCIS and invasive carcinoma. Moreover, amplification of both genes was more frequent in aneuploidy tumors and the tumors with high ki67, but wasn't associated with patients' outcome. In summary, CKS1BP7 amplification is a frequent event in breast cancer and often co-occurs with amplified IGF1R, which provides evidence supporting the interactions between CKS1BP7 and IGF1R during mammary carcinogenesis. Our findings suggest that CKS1BP7 as well as IGF1R may serve as potential biomarkers for early detection and predict prognosis in breast cancer.
Subject(s)
Breast Neoplasms/genetics , CDC2-CDC28 Kinases/genetics , Carcinoma, Ductal, Breast/genetics , Carcinoma, Intraductal, Noninfiltrating/genetics , Pseudogenes/genetics , Receptors, Somatomedin/genetics , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/mortality , Carcinoma, Intraductal, Noninfiltrating/pathology , Female , Gene Amplification , Gene Dosage , Humans , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Middle Aged , Receptor, IGF Type 1 , Young AdultABSTRACT
Previously, we found that cancerous inhibitor of protein phosphatase 2A (CIP2A) plays a key role in the malignant transformation of cervical cancer. Here, we further explore whether and how CIP2A is regulated by human papillomavirus E7 (HPV E7) and the prognostic value of CIP2A in cervical cancer. We demonstrated a positive feedback loop between the E2F transcription factor 1 (E2F1) and CIP2A at the transcription level in HeLa and SiHa cells by real-time PCR and western blot analysis. The feedback, regulated by HPV E7, was further confirmed by their sub-cellular co-expression seen on immunofluorescence and immunohistochemistry staining in vitro and in vivo. Moreover, CIP2A and E2F1 expression was greatly elevated in human cervical cancer tissue. CIP2A expression was tightly associated with tumor size, depth of invasion and lymph node metastasis in 184 cases of cervical cancer. Kaplan-Meier and Cox proportional-hazards regression analyses revealed poor overall and disease-free survival of patients with CIP2A-E2F1 co-expression, and high CIP2A-E2F1 co-expression was an independent risk factor for overall survival of patients. Therefore, CIP2A-E2F1 expression might be a valuable indicator to predict outcome and guide personal treatment in cervical cancer.
ABSTRACT
The electron microscopy is one of the major means to observe the virus. The view of virus microscope images is limited by making specimen and the size of the camera's view field. To solve this problem, the virus sample is produced into multi-slice for information fusion and image registration techniques are applied to obtain large field and whole sections. Image registration techniques have been developed in the past decades for increasing the camera's field of view. Nevertheless, these approaches typically work in batch mode and rely on motorized microscopes. Alternatively, the methods are conceived just to provide visually pleasant registration for high overlap ratio image sequence. This work presents a method for virus microscope image registration acquired with detailed visual information and subpixel accuracy, even when overlap ratio of image sequence is 10% or less. The method proposed focus on the correspondence set and interimage transformation. A mismatch removal strategy is proposed by the spatial consistency and the components of keypoint to enrich the correspondence set. And the translation model parameter as well as tonal inhomogeneities is corrected by the hierarchical estimation and model select. In the experiments performed, we tested different registration approaches and virus images, confirming that the translation model is not always stationary, despite the fact that the images of the sample come from the same sequence. The mismatch removal strategy makes building registration of virus microscope images at subpixel accuracy easier and optional parameters for building registration according to the hierarchical estimation and model select strategies make the proposed method high precision and reliable for low overlap ratio image sequence.