FOXQ1 inhibits breast cancer ferroptosis and progression via the circ_0000643/miR-153/SLC7A11 axis.

Dysregulation of ferroptosis is involved in breast cancer progression and therapeutic responses. Inducing ferroptosis can be a potential therapeutic strategy for breast cancer treatment. Forkhead box Q1 (FOXQ1) is an oncogenic transcription factor that highly expressed and related with poor outcomes in various tumors. However, the specific effects of FOXQ1 on ferroptosis in breast cancer is unclear. In this study, we intended to explore the functions and potential mechanisms of FOXQ1 in breast cancer ferroptosis. By CCK-8, colony formation, wound healing, transwell and ferroptosis related assays, we explored the functions of FOXQ1 in breast cancer ferroptosis and progression. Through bioinformatics analysis of public database, luciferase reporter assay, RIP and ChIP assay, we investigated the potential mechanisms of FOXQ1 in breast cancer ferroptosis and progression. We found that FOXQ1 was overexpressed in breast cancer and associated with worse survival. Additionally, inhibition of FOXQ1 suppressed breast cancer ferroptosis and progression. Mechanically, we confirmed that FOXQ1 could bind to the promoter of circ_0000643 host gene to increase the levels of circ_0000643, which could sponge miR-153 and enhance the expression of SLC7A11, leading to reduced cell ferroptosis in breast cancer cells. Targeting the FOXQ1/circ_0000643/miR-153/SLC7A11 axis could be a promising strategy in breast cancer treatment.

Inhibitor of glutamine metabolism V9302 promotes ROS-induced autophagic degradation of B7H3 to enhance antitumor immunity.

Despite the enormous successes of anti-PD-1/PD-L1 immunotherapy in multiple other cancer types, the overall response rates of breast cancer remain suboptimal. Therefore, exploring additional immune checkpoint molecules for potential cancer treatment is crucial. B7H3, a T-cell coinhibitory molecule, is specifically overexpressed in breast cancer compared with normal breast tissue and benign lesions, making it an attractive therapeutic target. However, the mechanism by which B7H3 contributes to the cancer phenotype is unclear. Here we show that the expression of B7H3 is negatively related to the number of CD8+ T cells in breast tumor sites. In addition, analysis of the differentially expressed B7H3 reveals that it is inversely correlated to autophagic flux both in breast cancer cell lines and clinical tumor tissues. Furthermore, block of autophagy by bafilomycin A1 (Baf A1) increases B7H3 levels and attenuates CD8+ T cell activation, while promotion of autophagy by V9302, a small-molecule inhibitor of glutamine metabolism, decreases B7H3 expression and enhances granzyme B (GzB) production of CD8+ T cells via regulation of reactive oxygen species (ROS) accumulation. We demonstrate that combined treatment with V9302 and anti-PD-1 monoclonal antibody (mAb) enhances antitumor immunity in syngeneic mouse models. Collectively, our findings unveil the beneficial effect of V9302 in boosting antitumor immune response in breast cancer and illustrate that anti-PD-1 together with V9302 treatment may provide synergistic effects in the treatment of patients insensitive to anti-PD-1 therapy.

Cost-effectiveness analysis of ovarian function preservation with GnRH agonist during chemotherapy in premenopausal women with early breast cancer.

STUDY QUESTION: Is it economically worthwhile to use GnRH agonist (GnRHa) to prevent menopausal symptoms (MS) and protect fertility in premenopausal women with breast cancer (BC) during chemotherapy from the US perspective? SUMMARY ANSWER: It is cost-effective to administer GnRHa during chemotherapy in order to forefend MS in premenopausal patients with BC when the willingness-to-pay (WTP) threshold is $50 000.00 per quality-adjusted life-year (QALY), and to preserve fertility in young patients with BC who undergo oocyte cryopreservation (OC), or no OC, when the WTP thresholds per live birth are $71 333.33 and $61 920.00, respectively. WHAT IS KNOWN ALREADY: Chemotherapy often results in premature ovarian insufficiency (POI) in premenopausal survivors of BC, causing MS and infertility. Administering GnRHa during chemotherapy has been recommended for ovarian function preservation by international guidelines. STUDY DESIGN, SIZE, DURATION: Two decision-analytic models were developed, respectively, for preventing MS and protecting fertility over a 5-year period, which compared the cost-effectiveness of two strategies: adding GnRHa during chemotherapy (GnRHa plus Chemo) or chemotherapy alone (Chemo). PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were early premenopausal women with BC aged 18-49 years who were undergoing chemotherapy. Two decision tree models were constructed: one for MS prevention and one for fertility protection from the US perspective. All data were obtained from published literature and official websites. The models' primary outcomes included QALYs and incremental cost-effectiveness ratios (ICERs). The robustness of the models was tested by sensitivity analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the MS model, GnRHa plus Chemo resulted in an ICER of $17 900.85 per QALY compared with Chemo, which was greater than the WTP threshold of $50 000.00 per QALY; therefore, GnRHa plus Chemo was a cost-effective strategy for premenopausal women with BC in the USA. Probabilistic sensitivity analysis (PSA) results showed an 81.76% probability of cost-effectiveness in the strategy. In the fertility model, adding GnRHa for patients undergoing OC and those who were unable to undergo OC resulted in ICERs of $67 933.50 and $60 209.00 per live birth in the USA, respectively. PSA indicated that GnRHa plus Chemo was more likely to be cost-effective over Chemo when the WTP for an additional live birth exceed $71 333.33 in Context I (adding GnRHa to preserve fertility in young patients with BC after OC) and $61 920.00 in Context II (adding GnRHa to preserve fertility in young patients with BC who cannot accept OC). LIMITATIONS, REASONS FOR CAUTION: The indirect costs, such as disease-related mental impairment and non-medical costs (e.g. transportation cost) were not included. All data were derived from previously published literature and databases, which might yield some differences from the real world. In addition, the POI-induced MS with a lower prevalence and the specific strategy of chemotherapy were not considered in the MS model, and the 5-year time horizon for having a child might not be suitable for all patients in the fertility model. WIDER IMPLICATIONS OF THE FINDINGS: When considering the economic burden of cancer survivors, the results of this study provide an evidence-based reference for clinical decision-making, showing that it is worthwhile to employ GnRHa during chemotherapy to prevent MS and preserve fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of Fujian Province [2021J02038]; and the Startup Fund for Scientific Research, Fujian Medical University [2021QH1059]. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Long-term trend of future Cancer onset: A model-based prediction of Cancer incidence and onset age by region and gender.

OBJECTIVES: This study provided estimates of cancer incidence rate and onset age by Socio-demographic Index (SDI) regions and gender from 2020 to 2040, aiming to clarify the long-term patterns of future cancer onset. METHOD: Based on the incidence data from the Global Burden of Diseases (GBD) 2019 study, we constructed the Bayesian age-period-cohort model to calculate the age-standardized incidence rates (ASIR) of cancers from 2020 to 2040. Using the average annual percentage change (AAPC) to quantify the trends of ASIR and the onset age. In addition, the incidences in 2019 were fixed to distinguish the age onset changes caused by demographic and incidence from 2020 to 2040. RESULTS: Globally, two-thirds of cancers have escalating trends of incidence rate, and the proportion of cancer weighted average onset age above 60 years old will grow from 62% to 76% between 2020 and 2040. In five SDI regions, the proportion of weighted average onset age above 60 years old will rise above 10% in the next 20 years and increase sequentially with the rise of the SDI level. Preclude sex-specific cancers, the onset age is younger in men than in women in 2040. Rule out the influence of changing demographics, half of cancer's morbidity has a youth-oriented tendency globally, which is concentrated in hormone-related and digestive tract cancer. CONCLUSION: From 2020 to 2040, the incidence and onset age changes demonstrate marked geographic and gender variations in the cancer spectrum. Cancer incidence and onset age are predicted to continuously increase worldwide in the future.

One-pot fabrication of magnetic adsorbent based on polymeric ionic liquid/aminated carbon nanotubes composite for efficient capture of synthetic auxins in complex samples prior to chromatographic analysis.

Efficient enrichment is a challenging and indispensable step in the quantification of polar synthetic auxins in complex samples. In the current study, a new magnetic adsorbent based on polymeric ionic liquid/aminated carbon nanotube composite was fabricated with a one-pot precipitation copolymerization strategy and employed as the extraction phase of magnetic solid phase extraction of synthetic auxins. Various characterization techniques were utilized to inspect the morphology, structure, magnetic property, and functional groups of the prepared adsorbent. Under the optimal conditions, the obtained adsorbent displayed satisfactory capture performance towards studied auxins through multiple interactions. Adsorption studies evidenced that the adsorption procedure of the developed method towards analytes was fit for the Freundlich adsorption model and pseudo-second-order kinetics. Combining with high-performance liquid chromatography, sensitive and reliable method for the identification and quantification of trace synthetic auxins in environmental water and fruit juice samples was developed. The obtained limits of detection for water and fruit juice samples located in the ranges of 0.0059-0.013 and 0.018-0.031 µg/L, respectively. Recoveries in actual samples with different fortified contents varied from 82.2% to 117%, with satisfactory reproducibility. The results will evidence that the introduced extraction technique is a useful alternative for the entrapment of trace synthetic auxins from complex samples.

Periostin drives extracellular matrix degradation, stemness, and chemoresistance by activating the MAPK/ERK signaling pathway in triple-negative breast cancer cells.

BACKGROUND: Adipose tissue, which is mainly composed of adipocytes, is a crucial component of the tumor microenvironment, particularly in breast cancer. Adipocytes surround breast cancer cells and may participate in cell‒cell interactions in the breast microenvironment. However, little is currently known about how adipocytes influence the biological behavior of the surrounding breast cancer cells. Hence, this study sought to investigate the role and underlying mechanisms of periostin in triple-negative breast cancer (TNBC) cells cocultured with adipogenic conditioned medium (ACM) and palmitic acid (PA). METHODS: Human TNBC cell lines (MDA‒MB‒231 and SUM159PT) were treated with ACM and PA, then the expression of periostin, matrix metalloproteinases (MMPs) and stemness-related molecules were assessed by Western blotting and RT‒qPCR. The cellular viability was assessed using CCK‒8 assay. Plasmid transfection, RNA sequencing, and pathway inhibitor were used to explore the specific mechanisms of periostin. RESULTS: ACM and PA elevated the expression of both MMPs and stemness-related molecules in TNBCs. MMPs can promote tumor cell infiltration and migration by degrading the extracellular matrix, and stemness expression increases the development of tumor chemoresistance. Additionally, ACM and PA increased periostin expression, while inhibiting periostin disrupted the involvement of ACM and PA in promoting extracellular matrix degradation, stemness, and chemoresistance in TNBCs. Furthermore, this study found that periostin promoted TNBC progression by activating the MAPK/ERK signaling pathway and that inhibition of MAPK/ERK signaling reduced the phenotype caused by periostin upregulation in TNBCs treated with ACM or PA. Finally, the present results showed that the high expression of POSTN, which encodes periostin, was substantially related to worse survival in TNBC patients. CONCLUSIONS: The results of the study elucidated for the first time how periostin is the key protein secreted in TNBCs in response to the adipocyte-regulated tumor microenvironment, while periostin-neutralizing antibodies may serve as potential therapeutic agents in relation to TNBC progression.

Long Non-Coding RNA LINC00052 Targets miR-548p/Notch2/Pyk2 to Modulate Tumor Budding and Metastasis of Human Breast Cancer.

Abnormal expression of long non-coding RNAs (lncRNAs) is involved in many pathological processes of cancers. However, the role of lncRNA LINC00052 in breast cancer progression is still unclear. Here, LINC00052 expression was detected by in situ hybridization and quantitative real-time PCR assays. Cell Counting Kit-8, wound healing, and transwell assays were used to investigate changes in the proliferation, migration, and invasion of breast cancer cells. MiR-548p was found associated with LINC00052 or Notch2 by RNA pull-down, dual-luciferase reporter, and qRT-PCR assays. The effect of LINC00052 on lung metastasis was explored through in vivo experiments. High LINC00052 expression was observed in breast cancer tissues and cells. LINC00052 silencing inhibited the proliferation, migration, and invasion of MCF7 cells, and LINC00052 overexpression produced the opposite results. MiR-548p, a target gene of LINC00052, partially rescued the effects of LINC00052 on proliferation, migration, and invasion of MCF7. Notch2 was the target of miR-548p and LINC00052 could promote Notch2 expression. Moreover, the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2), a downstream factor of Notch2, was increased by LINC00052, and a Pyk2 mutant could inhibit the cell migration and invasion induced by LINC00052 overexpression in MDA-MB-468 cells, which was similar to the function of the miR-548p mimic. We further demonstrated that LINC00052 exacerbated the metastases of breast cancer cells in vivo. Our research demonstrated that LINC00052 is highly expressed in breast cancer and promotes breast cancer proliferation, migration, and invasion via the miR-548p/Notch2/Pyk2 axis. LINC00052 could serve as a potential therapeutic target for breast cancer.

Fabrication of functional group-rich monoliths for magnetic field-assisted in-tube solid phase microextraction of inorganic selenium species in water samples followed by online chromatographic determination.

Efficient separation and enrichment is a crucial step in the analysis of Se(IV) and Se(VI). In the present study, for the first time, online monolith-based magnetic field-assisted in-tube solid phase microextraction (MFA/IT-SPME) was applied to capture inorganic selenium species in water samples. To this aim, porous monoliths mixed with magnetic nanoparticles were synthesized in a silica capillary and employed as a microextraction column (MEC) for MFA/IT-SPME. After that, a magnetic coil utilized to induce variable magnetic fields in adsorption and desorption steps was entwined around the MEC. Se(IV) was coordinated with o-phenylenediamine to form a coordination compound that was infused onto the MEC to be captured. Results evidenced that application of magnetic field during the extraction procedure assisted the capture of the Se(IV)-OPA complex, with an enhancement in the extraction efficiency from 83% to 97%. Under the optimized conditions, MFA/IT-SPME was online combined with HPLC equipped with a diode array detector (DAD) to perform quantification of Se(IV) and Se(VI) in environmental water samples. Total inorganic Se was quantified after pre-reduction of Se(VI) to Se(IV) prior to applying the established approach, and a subtraction method was adopted to calculate the Se(VI) and Se(IV) contents. The limit of detection for Se(IV) was as low as 0.012 µg L-1. The reliability of the suggested method was investigated by assaying Se(IV) and Se(VI) species in real-life water samples with satisfactory recoveries (81.1%-116%) and repeatability (RSDs below 9%).

Efficient entrapment of inorganic Se species in water and beer samples with functional groups-rich monolith-based adsorbent.

An efficient multiple fibers solid-phase microextraction method based on porous monolith was established for Se(IV) and Se(VI) analysis. Poly(4-vinylphenylboronic acid/styrene-co-ethylene dimethacrylate/divinylbenzene) monolith was fabricated and employed as the extraction phase for efficient entrapment of Se(IV) complexed with o-phenylenediamine, followed by elution with a methanol/formic acid (99/1.0, v/v) mixture and quantification by high-performance liquid chromatography with diode array detector. The Se(VI) species was measured by the difference between total inorganic Se and Se(IV) after pre-reduction. Different characterization techniques were employed to inspect the structure and morphology of prepared adsorbent. A series of key extraction factors were optimized so as to achieve the expected extraction performance. Under the optimized separation and capture parameters, the linear range and limit of detection for Se(IV) in water sample were 0.050-200 and 0.013 µg/L, respectively. For beer sample, the corresponding values were 0.010-300 and 0.032 µg/L. The developed microextraction approach was successfully utilized to detect trace Se(IV) and Se(VI) in environmental water and beer samples with satisfactory fortified recovery and repeatability. Results well reveal the attractive merits of the established method in the analysis of Se species, including simple preparation of adsorbent, convenient extraction procedure, good sensitivity, high cost-effectiveness, and eco-friendliness.

Uncertainty quantification of PM2.5 concentrations using a hybrid model based on characteristic decomposition and fuzzy granulation.

The prediction of air pollution plays an important role in reducing the emission of air pollutants and guiding people to carry out early warning and control, so it attracts many scholars to conduct modeling and research on it. However, most of the current researches fail to quantify the uncertainty in prediction and only use traditional fuzzy information granulation to process data, resulting in the loss of much detail information. Therefore, this paper proposes a hybrid model based on decomposition and granular fuzzy information to solve these problems. The trend item and the Granulation fluctuation item are respectively predicted and the results are combined to obtain the change trend and fluctuation range of the sequence. This paper selects PM2.5 concentrations of 3 cities. The experimental results show that the evaluation index of the prediction model is significantly lower than other benchmark models, and a variety of statistical methods are used to further verify the effectiveness of the prediction model.

Development of magnetism-assisted in-tube solid phase microextraction of phenolic acids in fruit juices prior to high-performance liquid chromatography quantification.

Magnetism-assisted in-tube solid phase microextraction based on porous monolith mingled with Fe3 O4 nanoparticles was developed for capture of phenolic acids in fruit juices. First, poly (1-allyl-3-methylimidazolium bis [(trifluoro methyl) sulfonyl] imide-co-ethylene dimethacrylate) monolith embedded with Fe3 O4 nanoparticles was facile fabrication in a capillary and employed as microextraction column. Subsequently, a magnetic coil adopted to produce variable magnetic fields during extraction stage was twined on the microextraction column. The analytes contents in eluant were quantified by high performance liquid chromatogram with diode array detector. Various parameters affecting the extraction performance were inspected and optimized in detail. Results revealed that the exertion of magnetic fields in adsorption and desorption steps enhanced the extraction efficiencies of analytes from 44.9-64.0% to 78.6-87.1%. Under the optimal extraction factors, the limits of detection were between 0.012 and 0.061 µg/L, relative standard deviations for precision in terms of intra- and inter-day assay variability ranged from 1.9 to 9.8%. The introduced approach was successfully applied to simultaneously quantify the contents of five analytes in real fruit juices with satisfying fortified recoveries (80.1-116%). The obtained results well demonstrate the promising potential of the developed method in the highly sensitive quantification of trace phenolic acids in complex samples.

Development of monolith/aminated carbon nanotubes composite-based solid-phase microextraction of phenoxycarboxylic acids herbicides in water and soil samples.

In this study, a new adsorbent based on monolith/aminated carbon nanotubes composite was facilely prepared and employed as the extraction phase of multiple monolithic fibers solid-phase microextraction for the capture of phenoxycarboxylic acids herbicides. The adsorbent was fabricated by mingling aminated carbon nanotubes in the poly (allylthiourea-co-ethylene glycol dimethacrylate) monolith. Various techniques were employed to characterize the morphology, structure, and pore size of the prepared adsorbent. The proposed microextraction method displayed satisfactory capture performance towards studied analytes through multi-interactions such as hydrogen-bonding, hydrophobic and π-π interactions. Under the optimized conditions, a sensitive and reliable method to quantify trace analytes in water and soil samples was developed. The limits of detection were in the ranges of 0.13-0.25 µg/L and 0.20-0.61 µg/kg for water and soil samples, respectively. The practicality of the introduced method was demonstrated by applying it to monitor the contents of studied analytes in environmental water and soil samples. Satisfactory fortified recoveries (76.4-119%) and reproducibility were obtained. The achieved results well demonstrated that the suggested microextraction technique can efficiently extract phenoxycarboxylic acids and the developed method exhibits a promising potential for reliable and sensitive quantification of trace analytes in complex samples.

A Fructan Exohydrolase from Maize Degrades Both Inulin and Levan and Co-Exists with 1-Kestotriose in Maize.

Enzymes with fructan exohydrolase (FEH) activity are present not only in fructan-synthesizing species but also in non-fructan plants. This has led to speculation about their functions in non-fructan species. Here, a cell wall invertase-related Zm-6&1-FEH2 with no "classical" invertase motif was identified in maize. Following heterologous expression in Pichia pastoris and in Nicotiana benthamiana leaves, the enzyme activity of recombinant Zm-6&1-FEH2 displays substrate specificity with respect to inulin and levan. Subcellular localization showed Zm-6&1-FEH2 exclusively localized in the apoplast, and its expression profile was strongly dependent on plant development and in response to drought and abscisic acid. Furthermore, formation of 1-kestotriose, an oligofructan, was detected in vivo and in vitro and could be hydrolyzed by Zm-6&1-FEH2. In summary, these results support that Zm-6&1-FEH2 enzyme from maize can degrade both inulin-type and levan-type fructans, and the implications of the co-existence of Zm-6&1-FEH2 and 1-kestotriose are discussed.

Highly Permeable Monolith-based Multichannel In-Tip Microextraction Apparatus for Simultaneous Field Sample Preparation of Pesticides and Heavy Metal Ions in Environmental Waters.

A portable multichannel in-tip microextraction-based field sample preparation (FSP) apparatus was developed using polymer-based monoliths as an extraction phase. The construction of the FSP device is quite facile and convenient. More specifically, according to the chemical properties of studied analytes, functional-rich and high-permeability monoliths were in situ synthesized in pipet tips. After that, three tips containing the sorbents were mounted to three syringes, which were connected to a screw motor employed to drive the syringes and accurately regulate the flow rates in the adsorption and desorption stages. Because of the multifunction groups in the monoliths, the sorbents displayed satisfactory coextraction performance for pesticides (carbamates and triazoles) and heavy metal ions (Cd2+, Pb2+, and Cu2+) under the optimized conditions. The practicability of the proposed apparatus was demonstrated by the quick and simultaneous FSP of studied analytes in various environmental waters and combined with high-performance liquid chromatography/diode-array detection (for pesticides) and atomic absorption spectrometry (for metal ion) analysis. The results indicated that the limits of detection for the pesticides and metal ions were in the range of 0.36 to 1.2 ng/L and 0.061 to 0.40 ng/L, respectively, with ideal coefficients of determination. Furthermore, the results obtained with the constructed device were quite comparable to those obtained with the traditional laboratory extraction process, which demonstrated that the newly developed apparatus possesses the expected application in the high-throughput FSP of pesticides and heavy metal ions in water samples.

Endothelial Hypoxia-Inducible Factor-1α Is Required for Vascular Repair and Resolution of Inflammatory Lung Injury through Forkhead Box Protein M1.

Endothelial barrier dysfunction is a central factor in the pathogenesis of persistent lung inflammation and protein-rich edema formation, the hallmarks of acute respiratory distress syndrome. However, little is known about the molecular mechanisms that are responsible for vascular repair and resolution of inflammatory injury after sepsis challenge. Herein, we show that hypoxia-inducible factor-1α (HIF-1α), expressed in endothelial cells (ECs), is the critical transcriptional factor mediating vascular repair and resolution of inflammatory lung injury. After sepsis challenge, HIF-1α but not HIF-2α expression was rapidly induced in lung vascular ECs, and mice with EC-restricted disruption of Hif1α (Hif1af/f/Tie2Cre+) exhibited defective vascular repair, persistent inflammation, and increased mortality in contrast with the wild-type littermates after polymicrobial sepsis or endotoxemia challenge. Hif1af/f/Tie2Cre+ lungs exhibited marked decrease of EC proliferation during recovery after sepsis challenge, which was associated with inhibited expression of forkhead box protein M1 (Foxm1), a reparative transcription factor. Therapeutic restoration of endothelial Foxm1 expression, via liposomal delivery of Foxm1 plasmid DNA to Hif1af/f/Tie2Cre+ mice, resulted in reactivation of the vascular repair program and improved survival. Together, our studies, for the first time, delineate the essential role of endothelial HIF-1α in driving the vascular repair program. Thus, therapeutic activation of HIF-1α-dependent vascular repair may represent a novel and effective therapy to treat inflammatory vascular diseases, such as sepsis and acute respiratory distress syndrome.

SOX8 acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer.

The molecular mechanisms underlying triple-negative breast cancer (TNBC) pathology are not fully understood. Here, we reviewed the SOX8 transcript level in 24 types of cancer and normal tissues and the SOX8 expression pattern in breast cancer from the TCGA and METABRIC data sets and found that SOX8 was highly expressed in TNBC. We investigated the effect of SOX8 on tumorigenicity, migration and apoptosis in TNBC cell lines and xenografts models. We identified SOX8 as a functional oncogene that involved in the maintenance of stem-like capacities in TNBC cells. Through a promoter truncation experiment and ChIP experiment, we verified zinc finger E-box binding homeobox 1 (ZEB1) as a transcriptional activator of SOX8 that enhanced SOX8 expression by binding to its promoter. We evaluated the ZEB1 and the SOX8 levels in 240 TNBC patients and high expression of ZEB1 and SOX8 were significantly associated with poor prognosis. We demonstrated the significance of the ZEB1-SOX8 axis in regulating TNBC cancer stem-like cells (CSCs) and its connection with poor prognosis. Due to its vital role in TNBC CSCs, the ZEB1-SOX8 regulatory axis could be a promising therapeutic target for TNBC.

Metformin mediates induction of miR-708 to inhibit self-renewal and chemoresistance of breast cancer stem cells through targeting CD47.

Breast cancer stem cells (BCSCs) have been considered responsible for cancer progression, recurrence, metastasis and drug resistance. However, the mechanisms by which cells acquire self-renewal and chemoresistance properties are remaining largely unclear. Herein, we evaluated the role of miR-708 and metformin in BCSCs, and found that the expression of miR-708 is significantly down-regulated in BCSCs and tumour tissues, and correlates with chemotherapy response and prognosis. Moreover, miR-708 markedly inhibits sphere formation, CD44+ /CD24- ratio, and tumour initiation and increases chemosensitivity of BCSCs. Mechanistically, miR-708 directly binds to cluster of differentiation 47 (CD47), and regulates tumour-associated macrophage-mediated phagocytosis. On the other hand, CD47 is essential for self-renewal, tumour initiation and chemoresistance of BCSCs, and correlates with the prognosis of breast cancer patients. In addition, the anti-type II diabetes drug metformin are found to be involved in the miR-708/CD47 signalling pathway. Therefore, our study demonstrated that miR-708 plays an important tumour suppressor role in BCSCs self-renewal and chemoresistance, and the miR-708/CD47 regulatory axis may represent a novel therapeutic mechanism of metformin in BCSCs.

circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer.

BACKGROUND: Increasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. But the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear. METHODS: We used a circRNA microarray to explore the circRNA expression profile of TNBC. The expression of the top upregulated circRNA, circKIF4A, was confirmed by qRT-PCR in breast cancer cell lines and tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of circKIF4A on TNBC. A series of experiments was performed to explore the functions of circKIF4A in TNBC progression, such as cell proliferation and migration. We investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC. RESULTS: qRT-PCR analyses verified that circKIF4A was significantly upregulated and positively associated with poorer survival of TNBC. The inhibition of circKIF4A suppressed cell proliferation and migration in TNBC. Luciferase reporter assay and RNA immunoprecipitation assay revealed that circKIF4A and KIF4A could bind to miR-375 and that circKIF4A regulated the expression of KIF4A via sponging miR-375. CONCLUSIONS: The circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the competitive endogenous RNA (ceRNA) mechanism. circKIF4A may therefore serve as a prognostic biomarker and therapeutic target for TNBC.

Fabrication of boron-rich multiple monolithic fibers for the solid-phase microextraction of carbamate pesticide residues in complex samples.

To enrich carbamate pesticides from complex matrices, an adsorbent based on poly (vinylboronic anhydride pyridine complex-co-ethylenedimethacrylate) monolith was fabricated and utilized as the extraction phase of multiple monolithic fiber solid-phase microextraction. Due to the abundant boron atoms in the monolith, the B-N coordination interaction between adsorbent and analytes play a key role in the efficient extraction of analytes. Under the optimized conditions, the monolithic fibers were combined with high-performance liquid chromatography for the quantify trace levels of carbamate pesticides in environmental water and orange juice samples. For water sample, the limit of detection and limit of quantification were in the range of 0.017-0.29 and 0.057-0.96 µg/L, respectively. The related values in orange juice samples were 0.038-0.39 and 0.12-1.36 µg/kg, respectively. Besides, the proposed method also exhibits wide linearity, satisfactory coefficients of determination, and good precision. The introduced approach was successfully applied to determine trace target analytes in real-life samples. The spiked recoveries with different fortified concentrations were in the range of 80.4-117% for water samples and 83.7-119% for fruit juice samples. The relative standard deviations were below 10%. The results evidence that the suggested method was convenient, reliable, and eco-friendly for the monitoring of trace levels of carbamate pesticides in complex samples such as waters and juices.

Allylthiourea functionalized magnetic adsorbent for the extraction of cadmium, copper and lead ions prior to their determination by atomic absorption spectrometry.

A quick and sensitive method was developed for the trace determination of Cd(II), Pb(II) and Cu(II) ions in water and bean samples. It is based on a combination of magnetic solid phase extraction (MSPE) and graphite furnace atomic absorption spectrometry (GFAAS). Allylthiourea (which contains abundant sulfur and nitrogen atoms) was copolymerized with ethylene dimethacrylate on the surface of magnetite (Fe3O4) nanoparticles to prepare a new adsorbent for use in MSPE. Various technologies were used to characterize the morphology, spectroscopic and magnetic properties of the adsorbent, and several parameters that affect the extraction performance were optimized. The adsorbent can enrich Cd(II), Pb(II) and Cu(II) ions via chelation interaction. Following elution with 0.1 mol·L-1 HNO3, the ions were quantified by GFAAS. Under the most favorable conditions, the limits of detection are from 3.3-7.2 ng·L-1 for water samples, and 1.1-1.5 µg·kg-1 for beans. The method displays wide linear analytical ranges and good precision. It was successfully applied to the determination of the metal ions in water and bean samples. The recoveries from spiked samples ranged between 80.5 and 114% in water, and from 82.2 to 118% in bean samples. The relative standard deviations of reproducibility were < 10%. Graphical abstract Schematic presentation of the magetic solid phase extraction (MSPE) for the analysis of Cd(II), Pb(II) and Cu(II). MNP: magnetic nanoparticles; ATED: allylthiourea ethylene dimethacrylate copolymer.