MicroRNA-605-3p Inhibited the Growth and Chemoresistance of Osteosarcoma Cells via Negatively Modulating RAF1.

BACKGROUND: Osteosarcoma (OS) is the leading cancer-associated mortality in childhood and adolescence. Increasing evidence has demonstrated the key function of microRNAs (miRNAs) in OS development and chemoresistance. Among them, miRNA-605-3p acted as an important tumor suppressor and was frequently down-regulated in multiple cancers. However, the function of miR-650-3p in OS has not been reported. OBJECTIVE: The aim of this work is to explore the novel role of miR-605-3p in osteosarcoma and its possible involvement in OS chemotherapy resistance. METHODS: The expression levels of miR-605-3p in OS tissues and cells were assessed by reverse transcription quantitative PCR (RT-qPCR). The relevance of miR-605-3p with the prognosis of OS patients was determined by the Kaplan-Meier analysis. Additionally, the influence of miR-605-3p on OS cell growth was analyzed using the cell counting kit-8, colony formation assay, and flow cytometry. The mRNA and protein expression of RAF1 were detected by RT-qPCR and western blot. The binding of miR-605-3p with the 3'-UTR of RAF1 was confirmed by dual-luciferase reporter assay. RESULTS: Our results showed that miR-605-3p was markedly decreased in OS tissues and cells. A lower level of miR-605-3p was strongly correlated with lymph node metastasis and poor 5-year overall survival rate of OS patients. In vitro assay found that miR-605-3p suppressed OS cell proliferation and promoted cell apoptosis. Mechanistically, the proto-oncogene RAF1 was seen as a target of miR-605-3p and strongly suppressed by miR-605-3p in OS cells. Restoration of RAF1 markedly eliminated the inhibitory effect of miR-605-3p on OS progression, suggesting RAF1 as a key mediator of miR-605-3p. Consistent with the decreased level of RAF1, miR-605-3p suppressed the activation of both MEK and ERK in OS cells, which are the targets of RAF1. Moreover, lower levels of miR-605-3p were found in chemoresistant OS patients, and downregulated miR-605-3p increased the resistance of OS cells to therapeutic agents. CONCLUSION: Our data revealed that miR-605-3p serves as a tumor suppressor gene by regulating RAF1 and increasing the chemosensitivity of OS cells, which provided the novel working mechanism of miR-605-3p in OS. Engineering stable nanovesicles that could efficiently deliver miR-605-3p with therapeutic activity into tumors could be a promising therapeutic approach for the treatment of OS.

Long non-coding RNA HANR modulates the glucose metabolism of triple negative breast cancer via stabilizing hexokinase 2.

Increasing evidence has demonstrated the oncogenic roles of long non-coding RNA (lncRNA) hepatocellular carcinoma (HCC)-associated long non-coding RNA (HANR) in the development of HCC and lung cancer; however, the involvement of HANR in triple-negative breast cancer (TNBC) remains largely unknown. Our results demonstrated the significant overexpression of HANR in TNBC tissues and cells. Higher HANR levels significantly correlated with the poorer phenotypes in patients with TNBC. HANR down-regulation inhibited the proliferation and cell cycle progression and increased the apoptosis of TNBC cells. Mechanistically, immunoprecipitation-mass spectrometry revealed hexokinase II (HK2) as a direct binding target of HANR. HANR binds to and stabilizes HK2 through the proteasomal pathway. Consistent with the important role of HK2 in cancer cells, HANR depletion represses the glucose absorbance and lactate secretion, thus reprogramming the metabolism of TNBC cells. An in vivo xenograft model also demonstrated that HANR promoted tumor growth and aerobic glycolysis. This study reveals the role of HANR in modulating the glycolysis in TNBC cells by regulating HK2 stability, suggesting that HANR is a potential drug target for TNBC.

Circ_0059457 Promotes Proliferation, Metastasis, Sphere Formation and Glycolysis in Breast Cancer Cells by Sponging miR-140-3p to Regulate UBE2C.

Circular RNA (circRNA) has been confirmed to regulate breast cancer (BC) progression. However, the role of circ_0059457 in BC progression is still unclear.The expression of circ_0059457, taspase 1 (TASP1), microRNA (miR)-140-3p and ubiquitin-binding enzyme E2C (UBE2C) was detected by quantitative real-time PCR. Cell proliferation, migration, invasion and sphere formation ability were assessed by cell counting kit-8 assay, EdU assay, wound healing assay, transwell assay and sphere formation assay. Cell glycolysis was assessed by detecting glucose uptake, lactate levels and ATP/ADP ratio. Dual-luciferase reporter assay, RIP assay, RNA pull-down assay were used to validate RNA interaction. Xenograft tumor model to assess the effect of circ_0059457 on BC tumor growth in vivo. Circ_0059457 had elevated expression in BC tissues and cells. Circ_0059457 knockdown inhibited BC cell proliferation, metastasis, sphere formation ability, and glycolysis. In terms of mechanism, circ_0059457 sponged miR-140-3p, and miR-140-3p targeted UBE2C. MiR-140-3p inhibition reversed the effect of circ_0059457 knockdown on BC cell malignant behaviors. Besides, miR-140-3p overexpression inhibited BC cell proliferation, metastasis, sphere formation ability and glycolysis, and these effects were abrogated by UBE2C enhancement. Furthermore, circ_0059457 regulated UBE2C expression through sponging miR-140-3p. Additionally, circ_0059457 knockdown obviously inhibited BC tumor growth in vivo. Circ_0059457 promoted BC progression via miR-140-3p/UBE2C axis, which provided potential target for the treatment of BC.

Cancer cell-derived exosomal miR-20a-5p inhibits CD8+ T-cell function and confers anti-programmed cell death 1 therapy resistance in triple-negative breast cancer.

Circulating miRNAs (cirmiRNAs) can be packaged into the exosomes, participating in intercellular communication, which affects the malignant progression and therapy resistance of triple-negative breast cancer (TNBC). Currently, immune checkpoint inhibitors that regulate T-cell function, especially antibodies against programmed cell death 1 (PD-1) or its ligand PD-L1, are emerging as new promising therapy for TNBC patients. However, only very limited patients showed complete or partial response to anti-PD-1 treatment. Dysfunction of CD8+ T cells is one of the key reasons for the immune escape of TNBC. The regulation of exosome-derived cirmiRNAs on CD8+ T cells in TNBC deserves more investigation. Here, the cirmiR-20a-5p level was significantly upregulated in the plasma of TNBC patients and culture supernatant of TNBC cells. High abundance of cirmiR-20a-5p was correlated with a worse prognosis of TNBC. cirmiR-20a-5p was secreted in the form of exosomes by TNBC cells. Exosomal cirmiR-20a-5p was internalized into CD8+ T cells and resulted into the dysfunction of CD8+ T. A mechanism study uncovered that cirmiR-20a-5p targeted the nuclear protein ataxia-telangiectasia (NPAT) and decreased NPAT expression in CD8+ T cells. An in vivo xenograft mouse model showed that cirmiR-20a-5p conferred TNBC to anti-PD-1 treatment resistance. Collectively, these findings indicated that cirmiR-20a-5p released by TNBC cells via exosome promotes cancer cell growth and leads to the immunosuppression by inducing CD8+ T cell dysfunction. This study suggests that targeting cirmiR-20a-5p might be a novel strategy for overcoming the resistance of TNBC to anti-PD-1 immunotherapy.

Structure and Ecological Function of Fungal Endophytes from Stems of Different Mulberry Cultivars.

To explore the microbial community structure and ecological function of mulberry and their potential relationship with the resistance of mulberry, the community structure and function of endophytic fungi in 18 mulberry cultivars were analyzed and predicted by using high-throughput sequencing technology and the FUNGuild database. A total of 352 operational taxonomic units of fungi were observed at a 97% similarity level, representing six phyla of fungi, Fungi_unclassified, Ascomycota, Basidiomycota, Zygomycota, Rozellomycota, and Chytridiomycota. Fungi_unclassified was dominant, and Ascomycota was relatively dominant in all cultivars. At the genus level, Ascomycota_unclassified was dominant, and Ampelomyces was relatively dominant, with a richness in TAIWANCHANGGUOSANG 16.47-8975.69 times that in the other cultivars. Classified Ascomycota_unclassified was 4.75-296.65 times more common in NANYUANSIJI than in the other cultivars. Based on the FUNGuild analysis method, we successfully annotated six nutrient types, namely, pathotroph, pathotroph-saprotroph, pathotroph-saprotroph-symbiotroph, saprotroph, saprotroph-symbiotroph, and symbiotroph, among which saprophytic-symbiotic accounted for the largest proportion and was absolutely dominant in TWC. This research suggests that community composition differs among cultivars and that the diversity and richness of endophytic fungi in resistant cultivars are higher than those in susceptible cultivars. The ecological functions of cultivars with different resistances are quite different.

Non-destructive detection of protein content in mulberry leaves by using hyperspectral imaging.

Protein content is one of the most important indicators for assessing the quality of mulberry leaves. This work is carried out for the rapid and non-destructive detection of protein content of mulberry leaves using hyperspectral imaging (HSI) (Specim FX10 and FX17, Spectral Imaging Ltd., Oulu, Finland). The spectral range of the HSI acquisition system and data processing methods (pretreatment, feature extraction, and modeling) is compared. Hyperspectral images of three spectral ranges in 400-1,000 nm (Spectral Range I), 900-1,700 nm (Spectral Range II), and 400-1,700 nm (Spectral Range III) were considered. With standard normal variate (SNV), Savitzky-Golay first-order derivation, and multiplicative scatter correction used to preprocess the spectral data, and successive projections algorithm (SPA), competitive adaptive reweighted sampling, and random frog used to extract the characteristic wavelengths, regression models are constructed by using partial least square and least squares-support vector machine (LS-SVM). The protein content distribution of mulberry leaves is visualized based on the best model. The results show that the best results are obtained with the application of the model constructed by combining SNV with SPA and LS-SVM, showing an R 2 of up to 0.93, an RMSE of just 0.71 g/100 g, and an RPD of up to 3.83 based on the HSI acquisition system of 900-1700 nm. The protein content distribution map of mulberry leaves shows that the protein of healthy mulberry leaves distributes evenly among the mesophyll, with less protein content in the vein of the leaves. The above results show that rapid, non-destructive, and high-precision detection of protein content of mulberry leaves can be achieved by applying the SWIR HSI acquisition system combined with the SNV-SPA-LS-SVM algorithm.

Non-destructive prediction and visualization of anthocyanin content in mulberry fruits using hyperspectral imaging.

Being rich in anthocyanin is one of the most important physiological traits of mulberry fruits. Efficient and non-destructive detection of anthocyanin content and distribution in fruits is important for the breeding, cultivation, harvesting and selling of them. This study aims at building a fast, non-destructive, and high-precision method for detecting and visualizing anthocyanin content of mulberry fruit by using hyperspectral imaging. Visible near-infrared hyperspectral images of the fruits of two varieties at three maturity stages are collected. Successive projections algorithm (SPA), competitive adaptive reweighted sampling (CARS) and stacked auto-encoder (SAE) are used to reduce the dimension of high-dimensional hyperspectral data. The least squares-support vector machine and extreme learning machine (ELM) are used to build models for predicting the anthocyanin content of mulberry fruit. And genetic algorithm (GA) is used to optimize the major parameters of models. The results show that the higher the anthocyanin content is, the lower the spectral reflectance is. 15, 7 and 13 characteristic variables are extracted by applying CARS, SPA and SAE respectively. The model based on SAE-GA-ELM achieved the best performance with R2 of 0.97 and the RMSE of 0.22 mg/g in both the training set and testing set, and it is applied to retrieve the distribution of anthocyanin content in mulberry fruits. By applying SAE-GA-ELM model to each pixel of the mulberry fruit images, distribution maps are created to visualize the changes in anthocyanin content of mulberry fruits at three maturity stages. The overall results indicate that hyperspectral imaging, in combination with SAE-GA-ELM, can help achieve rapid, non-destructive and high-precision detection and visualization of anthocyanin content in mulberry fruits.

(R)-9bMS Inhibited the Protein Synthesis and Autophagy of Triple Negative Breast Cancer Cells via Regulating miR-4660/mTOR Axis.

BACKGROUND: Unlike other subtypes of breast cancer, triple negative breast cancer (TNBC) exhibits aggressive and metastatic behaviors and a lack of effective targeted therapeutics. (R)-9bMS, a small-molecule inhibitor of the non-receptor tyrosine kinase 2 (TNK2), significantly inhibited TNBC cell growth; however, the functional mechanism of (R)-9bMS in TNBC remains largely unknown. OBJECTIVE: To explore the functional mechanism of (R)-9bMS in TNBC. METHODS: Cell proliferation, apoptosis and xenograft tumor growth assays were performed to evaluate the effects of (R)-9bMS on TNBC. The expression levels of miRNA and protein were detected by RTqPCR or western blot, respectively. Protein synthesis was determined by analyzing the polysome profile and 35S-met incorporation. RESULTS: (R)-9bMS attenuated TNBC cell proliferation, induced cell apoptosis, and inhibited xenograft tumor growth. Mechanism study indicated that (R)-9bMS upregulated the expression of miR-4660 in TNBC cells. The expression of miR-4660 is lower in TNBC samples than that of the non-cancerous tissues. miR-4660 overexpression inhibited TNBC cell proliferation by targeting the mammalian target of rapamycin (mTOR), which reduced mTOR abundance in TNBC cells. Consistent with the downregulation of mTOR, exposure of (R)-9bMS inhibited the phosphorylation of p70S6K and 4E-BP1, which consequently interrupted the total protein synthesis and autophagy of TNBC cells. CONCLUSION: These findings uncovered the novel working mechanism of (R)-9bMS in TNBC by attenuating mTOR signaling via up-regulating miR-4660. The potential clinical significance of (R)- 9bMS in TNBC treatment is interesting to explore.

Identification and Validation of a Novel Glycolysis-Related Gene Signature for Predicting the Prognosis and Therapeutic Response in Triple-Negative Breast Cancer.

INTRODUCTION: A high malignancy rate and poor prognosis are common problems with triple-negative breast cancer (TNBC). There is increasing evidence that glycolysis plays vital roles in tumorigenesis, tumor invasion, immune evasion, chemoresistance, and metastasis. However, a comprehensive analysis of the diagnostic and prognostic significance of glycolysis in TNBC is lacking. METHODS: Transcriptomic and clinical data of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, respectively. Glycolysis-related genes (GRGs) were collected from the Molecular Signatures Database (MSigDB). Differential comparative analysis was performed to obtain the differentially expressed (DE)-GRGs associated with TNBC. Based on the DE-GRGs, a glycolysis-related risk signature was established using Least Absolute Shrinkage and Selector Operation (LASSO) and multivariable Cox regression analyses. The prognostic value, tumor microenvironment, mutation status, and chemotherapy response of different risk groups were analyzed. An independent cohort from the METABRIC database was used for external validation. Furthermore, the expression patterns of five genes derived from the prognostic model were validated by quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: The glycolysis-related prognostic signature included five genes (IFNG, ACSS2, IRS2, GFUS, and GAL3ST1) and predicted the prognosis of TNBC patients independent of clinical factors (p < 0.05). Patients were divided into high- and low-risk groups based on the median risk score. Compared to low-risk TNBC patients, high-risk patients had significantly decreased overall survival (HR = 2.718, p < 0.001). Receiver operating characteristic and calibration curves demonstrated that the model had high performance in terms of predicting survival and risk stratification. The results remained consistent after external verification. Additionally, the tumor immune microenvironment significantly differed between the risk groups. Low-risk TNBC patients had a better immunotherapy response than high-risk patients. High-risk TNBC patients with a poor prognosis may benefit from targeted therapy. CONCLUSIONS: This study developed a novel glycolysis and prognosis-related (GRP) signature based on GRGs to predict the prognosis of TNBC patients, and may aid clinical decision-making for these patients.

Experimental and Finite Element Study on Bending Performance of Glulam-Concrete Composite Beam Reinforced with Timber Board.

In this research, experimental research and finite element modelling of glulam-concrete composite (GCC) beams were undertaken to study the flexural properties of composite beams containing timber board interlayers. The experimental results demonstrated that the failure mechanism of the GCC beam was the combination of bend and tensile failure of the glulam beam. The three-dimensional non linear finite element model was confirmed by comparing the load-deflection curve and load-interface slip curve with the experimental results. Parametric analyses were completed to explore the impacts of the glulam beam height, shear connector spacing, timber board interlayer thickness and concrete slab thickness on the flexural properties of composite beams. The numerical outcomes revealed that with an increase of glulam beam height, the bending bearing capacity and flexural stiffness of the composite beams were significantly improved. The timber boards were placed on top of the glulam members and used as the formwork for concrete slab casting. In addition, the flexural properties of composite beams were improved with the increase of the timber board thickness. With the elevation of the shear connector spacing, the ultimate bearing capacity and bending stiffness of composite beams were decreased. The bending bearing capacity and flexural rigidity of the GCC beams were ameliorated with the increase of concrete slab thickness.

A prospective, open-label, multicenter phase IV clinical trial on the safety and efficacy of lobaplatin-based chemotherapy in advanced breast cancer.

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2-5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

Volatile composition changes in lemon during fruit maturation by HS-SPME-GC-MS.

BACKGROUND: Volatiles are determinants of fruit aroma and flavor characteristics and also provide valuable information for lemon as ingredient for the food and drinks industry. Volatiles in 'Eureka' lemon and 'Xiangshui' lemon pulps from 130 to 186 days after flowering were enriched by headspace-solid-phase microextraction (HS-SPME), and analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS: Seventy-seven volatiles of two lemon cultivars at the different ripening stages were identified and divided into six categories. Varieties and ripening stages had significant effects on individual volatiles in each category. The proportion of monoterpenes was found to be higher in 'Eureka' lemon, while 'Xiangshui' lemon had a higher proportion of sesquiterpenes, aldehydes and alcohols. The proportion of monoterpene fluctuation decreased during fruit ripening, while fluctuation of sesquiterpenes, alcohols, aldehydes and esters increased. Among the hydrocarbons, monoterpenes decreased their relative abundance from 91.67% to 81.04% in 'Eureka' lemon, and from 83.01% to 60.04% in 'Xiangshui' lemon; conversely, sesquiterpenes increased from 0.73% to 2.89% in 'Eureka' lemon, and from 3.21% to 8.48% in 'Xiangshui' lemon. Among the oxygenated volatiles, the proportions of alcohols, aldehydes and esters were higher at 186 days after flowering in both two cultivars. CONCLUSION: The volatile organic compounds during fruit ripening of lemon varieties with different resistance were elucidated. The proportion of oxygenated volatiles increased during fruit ripening, and disease-resistant varieties had a higher proportion. These results provided important theoretical support for the utilization of lemon fruits and the innovation of disease-resistant germplasm resources. © 2021 Society of Chemical Industry.

Association between the Systolic Blood Pressure Trajectory and Risk of Stroke in a Health-Management Population in Jiaozuo, China.

The trajectories of systolic blood pressure (SBP) in a screening population in Jiaozuo were examined, and the association between the different types of SBP trajectories and the risk of stroke was evaluated. Data of a fixed cohort population from the Jiaozuo Stroke Prevention and Control Project Management Special Database System that underwent community screening in 2015, 2017, 2019, and 2021 were collected. Ultimately, a total of 1,451 participants who met the inclusion criteria for this study were included in the analysis, which was performed using group trajectory modeling. The baseline SBP for each trajectory subgroup was characterized at follow-up. Kaplan-Meier analysis for each trajectory group was also performed, and the relationship between the SBP trajectory and risk of stroke onset during follow-up was validated using a Cox proportional hazards model. Based on the SBP from 2015 to 2021, this cohort population was divided into three groups based on the trajectory development patterns: the low-stable group (37.6%), the moderate-increasing group (53.4%), and the high-acutely increasing group (9%). Gender, age, body mass index, diastolic blood pressure, and fasting blood glucose level were predictive factors for the SBP trajectory group. The cumulative survival risk in the high-acutely increasing group was higher than that of the other two groups. After adjusting for potential confounding factors and using the low-stable group as a reference, the hazard ratios (95% confidence interval) for the risk of stroke onset in the moderate-increasing and high-acutely increasing groups were 1.38 (0.91-2.07) and 1.51 (0.82-2.76), respectively. The results of the analysis demonstrate that higher blood pressure trajectories are associated with a higher risk of stroke and that the risk of stroke can be reduced by better control and management of the SBP.

Phage Selective Pressure Reduces Virulence of Hypervirulent Klebsiella pneumoniae Through Mutation of the wzc Gene.

Hypervirulent Klebsiella pneumoniae (hvKp), one of the major community-acquired pathogens, can cause invasive infections such as liver abscess. In recent years, bacteriophages have been used in the treatment of K. pneumoniae, but the characteristics of the phage-resistant bacteria produced in the process of phage therapy need to be evaluated. In this study, two Podoviridae phages, hvKpP1 and hvKpP2, were isolated and characterized. In vitro and in vivo experiments demonstrated that the virulence of the resistant bacteria was significantly reduced compared with that of the wild type. Comparative genomic analysis of monoclonal sequencing showed that nucleotide deletion mutations of wzc and wcaJ genes led to phage resistance, and the electron microscopy and mucoviscosity results showed that mutations led to the loss of the capsule. Meanwhile, animal assay indicated that loss of capsule reduced the virulence of hvKp. These findings contribute to a better understanding of bacteriophage therapy, which not only can kill bacteria directly but also can reduce the virulence of bacteria by phage screening.

MicroRNA-598 inhibits the growth of triple negative breast cancer cells by targeting JAG1.

Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor outcome. The discovery that dysregulated microRNAs (miRNAs) play an important role in tumor progression has led to the suggestion that miRNAs (miRs) could be a potential target for the treatment of TNBC. In the present study, it was demonstrated that miR-598 expression was significantly decreased in TNBC tissues and was related to the degree of lymph node metastasis of patients with TNBC. Ectopic expression of miR-598 suppressed viability and colony formation, as well as increased the apoptosis of TNBC cells. To further understand the functional mechanism of action underlying miR-598 in TNBC, targets of miR-598 were predicted with the miRDB bioinformatics tool. Jagged 1 (JAG1) was identified as a direct target of miR-598, possessing a binding site for miR-598 in its 3'-untranslated region. Overexpression of miR-598 inhibited the expression of JAG1 in TNBC cells. In addition, JAG1 was highly expressed in TNBC tissues and its expression was negatively correlated with the expression of miR-598. Overexpression of JAG1 significantly attenuated the inhibitory effects of miR-598 on the proliferation and colony formation of TNBC cells. Collectively, these results provided novel insights into the functional mechanism of action for the miR-598/JAG1 pathway in the development of TNBC.

Chidamide suppresses the glycolysis of triple negative breast cancer cells partially by targeting the miR­33a­5p­LDHA axis.

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer and has a poor prognosis. Therefore, the development of novel drugs and understanding the molecular mechanisms that may contribute to the initiation and development of TNBC are urgently required. Chidamide, a histone deacetylase inhibitor, has been reported as possessing anti­cancer properties in several cancers, however, the function of chidamide in TNBC remains to be elucidated. The present study revealed that chidamide inhibited the proliferation, colony formation and migration of TNBC cells. Experiments investigating the underlying mechanism revealed that chidamide upregulated the expression of microRNA (miR)­33a­5p in TNBC cells via RT­qPCR. Luciferase reporter assay demonstrated that miR­33a­5p was bound to the 3'­untranslated region of lactate dehydrogenase A (LDHA) and decreased the expression of LDHA in TNBC cells. In addition, chidamide suppressed the expression of LDHA and significantly decreased the glycolysis of TNBC cells. Collectively, the results of the present study demonstrated that chidamide reprogramed glucose metabolism, partially by targeting the miR­33a­5p/LDHA pathway, in TNBC. These findings indicate that chidamide may be a promising novel drug in the treatment of patients with TNBC.

MiRNA-20a-5p promotes the growth of triple-negative breast cancer cells through targeting RUNX3.

Increasing evidence showed that microRNAs (miRNAs) were abnormally expressed in cancers and made effects on the tumorigenesis. Aberrant expression of miR-20a-5p has been reported in human breast carcinoma. However, the functional mechanism of miR-20a-5p in human breast carcinoma, particularly in triple-negative breast cancer (TNBC), required further investigations. Here, firstly, we determined that miR-20a-5p was highly expressed in both TNBC tissues and cell lines. Then, we explored that the overexpression of miR-20a-5p promoted the migration and invasion of TNBC cells in vitro. The tendency was significantly reversed after the depletion of miR-20a-5p. Consistent result could be obtained with the in vivo nude mice tumorigenesis. Thirdly, the underlying molecular mechanism was investigated. The Runt-related transcription factor 3 (RUNX3) was identified as a target of miR-20a-5p in TNBC cells. High expression of miR-20a-5p significantly decreased both the mRNA and protein levels of RUNX3, as well as its direct downstream targets Bim and p21. These results verified the significance of miR-20a-5p and explored its functional mechanisms in TNBC, suggesting the potential clinical applications of miR-20a-5p in TNBC.

Investigation of DC hybrid circuit breaker based on high-speed switch and arc generator.

A new design of DC hybrid circuit breaker based on high-speed switch (HSS) and arc generator (AG), which can drastically profit from low heat loss in normal state and fast current breaking under fault state, is presented and analyzed in this paper. AG is designed according to the magnetic pinch effect of liquid metal. By utilizing the arc voltage generated across AG, the fault current is rapidly commutated from HSS into parallel connected branch. As a consequence, the arcless open of HSS is achieved. The post-arc conducting resume time (Δ tc) of AG and the commutation original voltage (Uc), two key factors in the commutation process, are investigated experimentally. Particularly, influences of the liquid metal channel diameter (Φ) of AG, fault current rate of rise (di/dt) and Uc on Δ tc are focused on. Furthermore, a suitable Uc is determined during the current commutation process, aiming at the reliable arcless open of HSS and short breaking time. Finally, the fault current breaking test is carried out for the current peak value of 11.8 kA, and the validity of the design is confirmed by the experimental results.

[Analysis of predictors of axillary node metastases in 787 breast cancer patients].

OBJECTIVE: To explore the predictors of axillary nodal metastass in patients with breast cancer. METHODS: A retrospective study was performed using the clinicopathological data of breast cancer cases diagnosed and treated in our Hospital between Dec 2006 and Nov 2008. Logistic regression analysis was used to determine the predictors of axillary node positivity. RESULTS: The total number of patients was 1133. 69.5% of them (787) had complete clinical and pathological data. The median age was 49 years old (range 20-85). The average number of lymph nodes removed was 14.6 per person. The average number of involved nodes was 3.5 per person. Increasing tumor size was associated with increased risk of lymph node metastases. Assessed by multivariate analysis, the tumor size, age, ER status, and pathological type were significantly associated with node metastasis. CONCLUSIONS: Axillary nodal metastases are significantly affected by the tumor size, ER status, age, and pathological type in breast cancer patients.