Zinc finger protein 468 up-regulation of TFAM contributes to the malignant growth and cisplatin resistance of breast cancer cells.

BACKGROUND: Because of the progress on the diagnosis and treatment for patients with breast cancer (BC), the overall survival of the patients has been improved. However, a number of BC patients cannot benefit from the existing therapeutic strategies as the essential molecular events triggering the development of BC are not well understood. Previous studies have shown that abnormal expression of zinc finger proteins is involved in the development of various malignancies, whereas it remains largely unclear on their significance during the progression of BC. In this study, we aimed to explore the clinical relevance, cellular function and underlying mechanisms of zinc finger protein 468 (ZNF468) in BC. METHODS: The clinical relevance of ZNF468 and TFAM was analyzed based on TCGA database. Overexpression or knockdown of ZNF468 and TFAM were performed by transfecting the cells with overexpression plasmids and siRNAs, respectively. Overexpression and knockdown efficacy was checked by immunoblotting. CCK-8, colony formation, transwell and apoptosis experiments were conducted to check the cellular function of ZNF468 and TFAM. The content of mtDNA was measured by the indicated assay kit. The effects of cisplatin on BC cells were detected by CCK-8 and colony formation assays. The regulation of ZNF468 on TFAM was analyzed by RT-qPCR, immunoblotting, dual luciferase activity and ChIP-qPCR assays. RESULTS: ZNF468 was overexpressed in BC patients and inversely correlated with their prognosis. Based on overexpression and knockdown assays, we found that ectopic expression of ZNF468 was essential for the proliferation, growth and migration of BC cells. The expression of ZNF468 also negatively regulated the sensitivity of BC cells to the treatment of cisplatin. Mechanistically, ZNF468 potentiated the transcription activity of TFAM gene via direct binding on its promoter. Lastly, we demonstrated that ZNF468 up-regulation of TFAM was important for the growth, migration and cisplatin resistance in BC cells. CONCLUSION: Our study indicates that ZNF468 promotes BC cell growth and migration via transcriptional activation of TFAM. ZNF468/TFAM axis can serve as the diagnostic and therapeutic target, as well as the predictor of cisplatin effectiveness in BC patients.

[Impacts of Extreme Climate Events at Different Altitudinal Gradients on Vegetation NPP in Songhua River Basin].

Vegetation net primary production (NPP) is an essential index for determining the quality of terrestrial ecosystems and their potential carbon storage ability. The impacts of extreme climate events on vegetation NPP are different under different altitude gradients. However, the research on the impact of extreme climate events on the spatial variation in vegetation NPP and the coupling effects under different altitude conditions remain insufficient. Using the MOD17A3HGF remote sensing data set and RClimDex 1.9 software, the vegetation NPP and 10 extreme climate indices in the Songhua River Basin from 2001 to 2020 were calculated, respectively. The spatial and temporal evolution characteristics of vegetation NPP and its response mechanism to extreme climate events in the Songhua River Basin under different altitude gradients were analyzed by means of trend analysis, correlation analysis, regression analysis, GeoDetector, and relative importance analysis. The results showed that:① the vegetation NPP (calculated by C) in the Songhua River Basin increased significantly at the rate of 4.13 g·(m2·a)-1 from 2001 to 2020 (P < 0.01), and the rates of 3.65, 4.04, 4.70, 5.09, and 4.57 g·(m2·a)-1 at the altitude gradients of 29-255, 255-440, 440-658, 658-935, and 935-2 589 m, respectively (P < 0.01). ② The spatial distribution pattern of vegetation NPP presented "high around and low in the middle," and the fluctuation of vegetation NPP in high altitude areas was more obvious than that in low altitude areas; for example, the average value of vegetation NPP at an altitude gradient from 29 to 255 m had a lower value, whereas the other altitude gradients had higher mean values than the mean value of the basin. ③ The extreme precipitation events in the Songhua River Basin were the main influencing factors of vegetation NPP, i.e., the vegetation NPP in low-altitude areas was mainly affected by extreme precipitation events, whereas the values in high-altitude areas were affected by both extreme precipitation events and extreme temperature events. The results of this research can provide a scientific basis for improving the carbon cycle model of the terrestrial ecosystem in the Songhua River Basin, quantifying the ability of carbon storage of vegetation and formulating policies to deal with climate change.

Chemical characteristics, distribution patterns, and source apportionment of particulate elements and inorganic ions in snowpack in Harbin, China.

Snowpack, which serves as a natural archive of atmospheric deposition of multiple pollutants, is a practical environmental media that can be used for assessing atmospheric records and input of the pollutants to the surface environments and ecosystems. A total of 29 snowpack samples were collected at 20 sampling sites covering three different functional areas of a major city (Harbin) in Northeast China. Two samples at the "snow layer" and one or two samples at the "particulate layer" were collected at each sampling site in the industrial areas characterized by multi-layer snowpack, and only one sample at the "snow layer" was collected at each sampling site in the cultural and recreational as well as agricultural areas. The snow contents of 31 elements (Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Y, Cd, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and Pb) and six major water-soluble inorganic ions (WSIIs, NH4+, K+, Ca2+, NO2-, NO3-, and SO42-) were analyzed. The total mass of the measured elements is dominated (95.8%-99.2%) by crustal elements. Heavy metals only account for 0.77%-4.07% of the total mass of the elements, but are occasionally close to or even above the standard limit in the "Environmental Quality Standards for Surface Water" of China (GB3838-2002). SO42- and Ca2+ are the main anion and cation, accounting for 34.9%-81.1% and 1.43%-29.9%, respectively, of the measured total ions. Total atmospheric deposition of crustal elements and heavy metals is dominated by wet deposition in areas near the petrochemical plant and by dry deposition in areas near the cement plant. Coal combustion, industrial emissions, and traffic-related activities lead to the enrichment of heavy metals in the snowpacks of urban and suburban areas, while coal combustion and biomass burning contribute to pollution in rural areas. The cities and regions situated in the western, northwestern, northern, and northeastern directions from Harbin are potential source regions of these pollutant species.

Effect of High Pressure Homogenization-Modified Soy 11S Globulin on the Gel and Rheological Properties of Pork Myofibrillar Protein.

The changes in texture and rheological characteristics, water holding capacity, and microstructure of pork myofibrillar protein with high-pressure homogenization-modified (0-150 MPa) soy 11S globulin were studied. The cooking yield, whiteness values, texture properties, shear stress, initial apparent viscosity, storage modulus (G'), and loss modulus (G″) of pork myofibrillar protein with high-pressure homogenization-modified soy 11S globulin were significantly increased (p < 0.05) compared with the sample of 0 MPa, and centrifugal yield was significantly decreased, except for the sample of 150 MPa. Therein, the sample of 100 MPa had the largest values. Meanwhile, the water and proteins bonded more tightly because the initial relaxation times of T2b, T21 and T22 from pork myofibrillar protein with high-pressure homogenization-modified soy 11S globulin were shorter (p < 0.05). Overall, the water-holding capacity, gel texture and structure, and rheological properties of pork myofibrillar protein could improve when adding soy 11S globulin treated with 100 MPa.

Ubiquitin specific protease 46 potentiates triple negative breast cancer development by stabilizing PGAM1-mediated glycolysis.

Triple-negative breast cancer (TNBC) is a malignancy with high metastasis rate and poor prognosis. Limited drugs are effective for the treatment of TNBC patients. Ubiquitin specific proteases (USPs) are important posttranscription modulators that promote protein stability by reducing the ubiquitination of the proteins. Aberrant expression of USPs is involved in the development of numerous cancers. However, it remains poorly understood on the role of USP46 in TNBC growth and metastasis. In this study, we explored the clinical relevance, function and molecular mechanisms of USP46 in TNBC. USP46 expression was increased in breast cancer tissues. High expression of USP46 was associated with the poorer prognosis of the patients. Overexpression and knockdown experiments demonstrated that USP46 was critical for TNBC cell growth, migration, and tumorigenesis. Mechanistically, USP46 enhanced the protein stability of phosphoglycerate mutase 1 (PGAM1) via direct interaction. Importantly, USP46 stimulated the glycolysis and promoted the malignant growth of TNBC cells through upregulation of PGAM1. Our study reveals that USP46/PGAM1 axis contributes to TNBC progression and is a potential target for the treatment of TNBC patients.

A comparative study of vacuum tumbling and immersion marination on quality, microstructure, and protein changes of Xueshan chicken.

Marination is a common technology in meat processing with advantages of enhancing tenderness, water retention, and overall quality. This study was conducted to investigate the effect of vacuum tumbling and immersion marination on meat quality, microstructure, water mobility, protein changes, and denaturation of Xueshan chicken. Results showed that vacuum tumbling significantly increased the marinating rate of chicken, tenderness, meat texture, and water retention. Meanwhile, vacuum tumbling decreased total sulfhydryl content alongside an increased protein surface hydrophobicity and free sulfhydryl content, indicating that vacuum tumbling elevated the degree of protein denaturation. Further, the peak area corresponding to the relaxation time T22 after vacuum tumbling was significantly higher than that of immersion marination, suggesting that the stability of the immobilized water of chicken was reduced by vacuum tumbling. Compared to immersion marination, vacuum tumbling improved myofibril fragmentation index (MFI) presenting fewer myofibrillar protein bands in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gel and more damaged muscular cells. Overall, vacuum tumbling could improve the marination absorptivity, protein degradation, and denaturation, resulting in changes in myofibril structure and meat quality of Xueshan chicken.

Dramatically Improved Thermoelectric Properties by Defect Engineering in Cement-Based Composites.

In recent years, the problem of overheating in summer has been of great concern. Pavements are continuously exposed to solar radiation, and because of high temperatures, pavement temperatures reach 60 to 70 °C. This potential low-grade heat has been unused. Cement-based composites with thermoelectric properties can convert this low-grade heat to useful electrical energy. The importance of this green technology for generating renewable energy and sustainable development has been widely accepted and noticed. However, the power factor of current cement-based composites is too low, and harvesting low-grade heat on a large scale and at low cost requires improving the thermoelectric properties of cement-based composites. In this paper, we present a method to increase the electrical conductivity of ZnO and thus improve the thermoelectric properties of cement-based composites by defect engineering, obtaining a high power factor of 224 µWm-1 K-2 at 70 °C, a record value recently reported for thermoelectric cement-based composites. Zinc oxide powder was treated with a reducing atmosphere to increase the content of oxygen defects and thus improve the electrical conductivity. Pretreated ZnO powder of 5.0 and 10.0 wt % expanded graphite were added to the cement matrix. The ZnO/expanded graphite cement-based composites were made and tested for their thermoelectric properties using a dry pressing process, which exhibited excellent thermoelectric properties. The result showed high conductivity (12.78 S·cm-1), a high Seebeck coefficient (-419 µV/°C), a high power factor (224 µWm-1 K-2), and a high figure of merit value (8.7 × 10-3), which facilitate future large-scale applications. Using the cement-based composites to lay a road of 1 km in length and 10 m in width, 35.2 kW·h of electricity can be collected in 8 h. This study will inspire how to improve thermoelectric performance of cement-based composites.

Long non-coding RNA ASB16-AS1 enhances cell proliferation, migration and invasion via functioning as a ceRNA through miR-1305/Wnt/ß-catenin axis in cervical cancer.

BACKGROUND: Cervical cancer (CC) is one of the most common cancers in women. Long non-coding RNAs (lncRNAs) have been proposed as therapeutic targets in CC. Hence, the present study evaluated the effect of ASB16-AS1 on CC via regulating miR-1305. METHODS: Differentially expressed lncRNAs associated with CC were screened using bioinformatics database. The expression of ASB16-AS1 and miR-1305 were measured by qRT-PCR in CC tissues and CC cells. Cell proliferation was assessed by CCK-8 and colon formation assays. Cell abilities of migration and invasion were detected by Transwell migration and invasion assays. Luciferase report assays were used to explore the correction between ASB16-AS1, miR-1305 and Wnt2 in CC. Western blot assay detect the activity of Wnt/ß-catenin pathway. The xenograft tumor in nude mice was observed to evaluate tumor formation in vivo. RESULTS: In our study, we showed that the expression of ASB16-AS1 was increased while miR-1305 reduced was re in CC. Clinically, ASB16-AS1 and miR-1305 were correlated with poor-associated clinicopathological features of CC patients. Knockdown of ASB16-AS1 reduced CC cells proliferation, migration and invasion abilities by regulating miR-1305 in vitro and in vivo. Moreover, miR-1305 was directly bound to ASB16-AS1 and Wnt2, regulated their expression negatively. Western blot assays showed that ASB16-AS1 functioned as an oncogene by Wnt/ß-catenin pathway. CONCLUSIONS: This study reveals that ASB16-AS1 promotes cell proliferation, migration, invasion via binding miR-1305 with Wnt2, and enhancing the Wnt/ß-catenin pathway. ASB16-AS1 may play a new therapeutic target for CC.

MiR-218 restrains proliferation of cervical cancer cells via targeted regulation of HMGB1/RAGE pathway.

PURPOSE: To explore the role of micro ribonucleic acid (miR)-218 in cervical cancer (CC) and the regulatory mechanism between the high mobility group box 1 (HMGB1)/receptor for advanced glycation end-product (RAGE) pathway and miR-218. METHODS: The CC HeLa cells were first transfected with miR-218 mimic (miR-218 mimic group) or miR-218 negative control (NC group) using Lipofectamine 2000 transfection reagent, and those only added with Lipofectamine 2000 transfection reagent were taken as Control group. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the level of miR-218 in CC cell line. Besides, the migration and invasion abilities of the cells were measured via Transwell chamber assay, and the apoptosis was analyzed using a flow cytometer. Finally, the protein levels of HMGB1 and RAGE were determined via Western blotting. RESULTS: The expression of miR-218 declined in the CC HeLa cell line. After overexpression of miR-218, the proliferation ability of the CC cells was weakened, and the migration and invasion of CC cells were repressed. Moreover, miR-218 was observed to directly regulate the HMGB1/RAGE signaling pathway in a targeted manner to affect the proliferation and migration of CC cells. CONCLUSIONS: MiR-218 inhibits the HMGB1/RAGE pathway to suppress the proliferation, migration and invasion of CC cells.

Coupling Niobia Nanorods with a Multicomponent Carbon Network for High Power Lithium-Ion Batteries.

High power lithium-ion batteries require highly conductive electrodes. For an active electrode material that has limited electron conductivity, it is critical to build a carbon network that is not only highly conductive itself but also highly compatible with the electroactive material for efficient interfacial charge transfer. Herein, we design a multicomponent carbon network that is optimized for electrical coupling with the electroactive Nb2O5 nanorods for efficient electron injection. The self-support electrode is constructed by using 0D polypyrrole-derived (Ppy) carbon nanoparticles as glue to bind the Nb2O5 nanorods with 1D carbon nanotubes (CNTs) and 2D graphene nanosheets (GNSs). The 0D carbon nanoparticles also cross-link 1D CNTs with 2D GNSs, which can effectively prevent the GNSs from aggregation and form the 3D CNT/GNS network that provides continuous electronic and ionic pathways. This 3D Nb2O5@C self-support electrode exhibits a high discharge capacity of 246.3 mA h g-1 at 0.5 C and 100 mA h g-1 at 20 C and excellent Coulombic efficiency of 99.98% at 20 C. Even increasing the mass loading to 7.1 mg cm-2, the Nb2O5@C electrode can still reach a discharge capacity of 172.4 mA h g-1 at 0.5 C after 100 cycles. A high power density of 1043 W kg-1 can be achieved at an energy density of 104.3 W h kg-1 based on the electrode weight, which is among the highest values demonstrated so far for Nb2O5 electrodes. The results pave the way toward practical applications of Nb2O5 anodes in high-power lithium-ion batteries.

LncRNA-CTS promotes metastasis and epithelial-to-mesenchymal transition through regulating miR-505/ZEB2 axis in cervical cancer.

Cervical carcinoma (CC) is the second most common cancer in females. In order to improve current anti-metastasis strategies for CC, it is important to improve our understanding of the mechanisms involved in epithelial-to-mesenchymal transition (EMT). This study aimed to elucidate the potential role of a novel long non-coding RNA (lncRNA)-CTS and the mechanisms underlying EMT in CC. The expression levels of lncRNA-CTS and miR-505 were detected using quantitative reverse transcriptase polymerase chain reaction in CC specimens and cells (HeLa, SiHa, Ca-Ski, C-33A, and HT-3). Further experiments including wound scratch and transwell invasion assays, Western blotting, immunofluorescence, and luciferase assays were used to investigate the function of lncRNA-CTS/miR-505/ZEB2 in vitro. In addition, a tumor xenograft model was used to assess the effect of lncRNA-CTS in vivo. The expression levels of lncRNA-CTS and miR-505 were correlated with the metastasis-associated clinicopathological features of CC patients. Moreover, lncRNA-CTS was associated with a poor prognosis in CC patients. In vitro and in vivo experiments, along with gain- and loss-of-function studies, showed that lncRNA-CTS enhanced cell migration, invasion, and the transforming growth factor (TGF)-ß1-induced-EMT process. Data also showed that lncRNA-CTS could function as a competing endogenous RNA for miR-505 in CC cells. Further investigations disclosed that ZEB2 was demonstrated as a downstream target of miR-505, and subsequently exerted its metastatic effects via the lncRNA-CTS/miR-505/ZEB2 axis in CC cells. Finally, lncRNA-CTS activated the SMAD/TGF pathway via miR-505 in CC cells. Collectively, our results demonstrate the importance of the lncRNA-CTS/miR-505/ZEB2 axis in CC. LncRNA-CTS can predispose CC patients to metastases and may represent a promising therapeutic target for CC.

Expression of miR-146a-5p in breast cancer and its role in proliferation of breast cancer cells.

In the present study, the expression level of microRNA-146a-5p (miR-146a-5p) in breast cancer tissue and cell lines was investigated and its effects on proliferation of breast cancer cells. miR-146a-5p expression was detected by reverse transcription-quantitative polymerase chain reaction in breast cancer tissues, paraneoplastic tissue (collected by The Department of Oncology of Changhai Hospital from January 2014 to June 2015), breast cancer cell line MCF-7 and normal breast epithelial cell line MCF 10A. Bioinformatics analysis was conducted to forecast target genes of miR-146a-5p, which was further verified by fluorescent reporter gene detection. The results demonstrated the expression level of miR-146a-5p in breast cancer tissue was significantly higher, compared with paraneoplastic tissue (P<0.01), and the expression level of miR-146a-5p in MCF-7 cells was significantly higher, compared with MCF 10A cells (P<0.01). Overexpression of miR-146a-5p in MCF-7 cells can promote the proliferation, and low expression miR-146a-5p in MCF-7 can inhibit the proliferation. BRCA1 was further identified as a target gene of miR-146a-5p by bioinformatics analysis and fluorescent reporter gene detection. It was concluded that miR-146a-5p is expressed in breast cancer tissue and breast cancer cell line and may regulate the proliferation of MCF-7 via BRCA1.

Study on the Mechanism of Cell Cycle Checkpoint Kinase 2 (CHEK2) Gene Dysfunction in Chemotherapeutic Drug Resistance of Triple Negative Breast Cancer Cells.

BACKGROUND This study aimed to investigate the mechanism of CHEK2 gene dysfunction in drug resistance of triple negative breast cancer (TNBC) cells. MATERIAL AND METHODS To perform our study, a stable CHEK2 wild type (CHEK2 WT) or CHEK2 Y390C mutation (CHEK2 Y390C) expressed MDA-MB-231 cell line was established. MTT assay, cell apoptosis assay and cell cycle assay were carried out to analyze the cell viability, apoptosis, and cell cycle respectively. Western blotting and qRT-PCR were applied for related protein and gene expression detection. RESULTS We found that the IC50 value of DDP (Cisplatin) to CHEK2 Y390C expressed MDA-MB-231 cells was significantly higher than that of the CHEK2 WT expressed cells and the control cells. After treatment with DDP for 48 h, cells expressing CHEK2 WT showed lower cell viability than that of the CHEK2 Y390C expressed cells and the control cells; compared with the CHEK2 Y390C expressed cells and the control cells, cells expressing CHEK2 WT showed significant G1/S arrest. Meanwhile, we found that compared with the CHEK2 Y390C expressed cells and the control cells, cell apoptosis was significantly increased in CHEK2 WT expressed cells. Moreover, our results suggested that cells expressing CHEK2 WT showed higher level of p-CDC25A, p-p53, p21, Bax, PUMA, and Noxa than that of the CHEK2 Y390C expressed cells and the control cells. CONCLUSIONS Our findings indicated that CHEK2 Y390C mutation induced the drug resistance of TNBC cells to chemotherapeutic drugs through administrating cell apoptosis and cell cycle arrest via regulating p53 activation and CHEK2-p53 apoptosis pathway.