Making waves: Power-to-X for the Water Resource Recovery Facilities of the future.

The wastewater industry and the energy system are undergoing significant transformations to address climate change and environmental pollution. Green hydrogen, which will be mainly obtained from renewable electricity water electrolysis (Power-to-Hydrogen, PtH), has been considered as an essential energy carrier to neutralize the fluctuations of renewable energy sources. PtH, or Power-to-X (PtX), has been allocated to multiple sectors, including industry, transport and power generation. However, considering its large potential for implementation in the wastewater sector, represented by Water Resource Recovery Facilities (WRRFs), the PtX concept has been largely overlooked in terms of planning and policymaking. This paper proposes a concept to implement PtX at WRRFs, where sourcing of water, utilization of the oxygen by-product, and PtX itself can be sustainable and diversified strategies. Potential value chains of PtX are presented and illustrated in the frame of a WWRF benchmark simulation model, highlighting the applications of oxygen from PtX through pure oxygen aeration and ozone disinfection. Opportunities and challenges are highlighted briefly, and so is the prospective outlook to the future. Ultimately, it is concluded that 'coupling PtX to WRRFs' is a promising solution, which will potentially bring sustainable opportunities for both WRRFs and the energy system. Apart from regulatory and economic challenges, the limitations in coupling PtX to WRRFs mainly come from energy efficiency concerns and the complexity of the integration of the water framework and the energy system.

Schlafen-5 inhibits LINE-1 retrotransposition.

Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in humans, and its retrotransposition may cause deleterious effects on the structure and function of host cell genomes and result in sporadic genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we demonstrated that IFN-inducible Schlafen5 (SLFN5) inhibits LINE-1 retrotransposition. Mechanistic studies revealed that SLFN5 interrupts LINE-1 ribonucleoprotein particle (RNP) formation, thus diminishing nuclear entry of the LINE-1 RNA template and subsequent LINE-1 cDNA production. The ability of SLFN5 to bind to LINE-1 RNA and the involvement of the helicase domain of SLFN5 in its inhibitory activity suggest a mechanism that SLFN5 binds to LINE-1 RNA followed by dissociation of ORF1p through its helicase activity, resulting in impaired RNP formation. These data highlight a new mechanism of host cells to restrict LINE-1 mobilization.

[Retracted] Silencing cyclin­dependent kinase inhibitor 3 inhibits the migration of breast cancer cell lines.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blotting data shown in Fig. 1C were strikingly similar to data appearing in different form in another article written by different authors at different research institutes [Chen Y, Guo Y, Yang H, Shi G, Xu G, Shi J, Yin N and Chen D: TRIM66 overexpression contributes to osteosarcoma carcinogenesis and indicates poor survival outcome. Oncotarget 6: 23708­23719, 2015]. Moreover, a pair of data panels showing the results from cell­cycle experiments purportedly performed under different experimental conditions in Fig. 4A appeared to be strikingly similar. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 14: 1523­1530, 2016; DOI: 10.3892/mmr.2016.5401].

Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis.

BACKGROUND: The value of human leukocyte antigen (HLA; also known as major histocompatibility complex) class I expression for the prediction of breast cancer survival outcomes remains unclear. We conducted a meta-analysis to explore the prognostic significance of this expression. MATERIALS AND METHODS: We searched electronic databases to identify reports on associations of HLA class I protein or mRNA expression with survival outcomes and clinicopathological factors in the breast cancer context. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to conduct a quantitative meta-analysis. RESULTS: The sample comprised eight studies involving 3590 patients. Only the classical HLA class Ia (HLA-ABC) molecules studies were included in this meta-analysis. Elevated HLA class I protein expression was found to be significantly related to better disease-free survival (DFS) (HR 0.58, 95% CI 0.35-0.95, P = 0.03), particularly among patients with triple-negative breast cancer (TNBC) (HR 0.31, 95% CI 0.18-0.52, P < 0.001), but not to overall survival. It was also associated with estrogen receptor (ER) negativity (OR 1.71, 95% CI 1.24-2.35, P = 0.001), progesterone receptor (PR) negativity (OR 1.49, 95% CI 1.22-1.81, P < 0.001), human epidermal growth factor receptor 2 (HER2) positivity (OR 1.51, 95% CI 1.18-1.94, P = 0.001), TNBC (OR 1.68, 95% CI 1.15-2.45, P < 0.01), high Ki-67 indices (OR 2.06, 95% CI 1.62-2.61, P < 0.001), and high nuclear grades (OR 2.67, 95% CI 2.17-3.29, P < 0.001). CONCLUSION: This meta-analysis demonstrated that enhanced HLA class I protein expression is significantly associated with the better DFS of patients with breast cancer, especially TNBC, as well as with ER and PR negativity, HER2 positivity, TNBC, and high Ki-67 indices and nuclear grades. The immune target HLA class I may serve as a prognostic indicator for breast cancer.

Formation of a PVP-protected C/UO2/Pt catalyst in a direct ethanol fuel cell.

In order to solve the problem that UO2 in direct ethanol fuel cell anode catalysts is easily lost in acidic solution, resulting in the degradation of catalytic performance, this paper prepared a C/UO2/PVP/Pt catalyst in three steps by adding polyvinylpyrrolidone (PVP). The test results by XRD, XPS, TEM and ICP-MS showed that PVP had a good encapsulation effect on UO2, and the actual loading rates of Pt and UO2 were similar to the theoretical values. When 10% PVP was added, the dispersion of Pt nanoparticles was significantly improved, which reduced the particle size of Pt nanoparticles and provided more ethanol electrocatalytic oxidation reaction sites. The test results by electrochemical workstation showed that the catalytic activity as well as the stability of the catalysts were optimized due to the addition of 10% PVP.

Pathological complete response and prognosis after neoadjuvant chemotherapy in patients with HER2-low breast cancer.

BACKGROUND: The development of novel human epidermal growth factor receptor 2 (HER2) antibody drug conjugates brings encouraging opportunities for the treatment of HER2-low breast cancer. In this study, we investigated the clinical factors and prognosis of HER2-low breast cancer after neoadjuvant chemotherapy (NAC). METHODS: Data from patients diagnosed with HER2-zero or HER2-low breast cancer at a single center between January 2017 and December 2021 who underwent NAC followed by surgery were retrospectively reviewed. HER2 status was detected by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), and classified as HER2-zero (IHC 0), HER2-low (IHC 1+ or IHC 2+ and FISH-), and HER2-positive (IHC 3+ or IHC 2+ and FISH+). Baseline characteristics were analyzed and compared between the HER2-low and HER2-zero groups. Survival outcomes were analyzed using the Kaplan-Meier method with the log-rank test and Cox proportional-hazards regression analysis. RESULTS: The sample comprised 132 patients with HER2-zero [n = 62 (47.0 %)] and HER2-low [n = 70 (53.0 %)] breast cancer. Relative to the HER2-zero group, the HER2-low group contained larger proportions of patients with hormone receptor (HR) positivity (37.1 % vs. 75.7 %, P < 0.001) and low nuclear grades and Ki-67 indices (both P < 0.05). The pathological complete response (pCR) rate was significantly lower in the HER2-low group than in the HER2-zero group (20.0 % vs. 37.1 %, P = 0.03). At the final follow-up [median 20 (range 4-66) months], patients with HER2-low status had significantly favorable disease-free survival (DFS) and overall survival (OS) outcomes relative to those with HER2-zero status (87.1 % vs. 71.0 %, P = 0.02 and 94.3 % vs. 82.3 %, P = 0.02, respectively). HER2-low status and pCR were independent prognostic factors for DFS [hazard ratio (HR) = 0.31, 95 % confidence interval (CI) 0.13-0.75, P = 0.009 and HR = 0.08, 95 % CI 0.01-0.67, P = 0.02, respectively]. CONCLUSION: This analysis revealed that HER2-low status is associated significantly with HR positivity and low nuclear grades, Ki-67 indices, and pCR rate. It is also associated with favorable DFS and OS outcomes after NAC. HER2-low status and pCR are independent prognostic factors for DFS.

Empathy and depression among a Chinese sample: The moderating role of rumination and attentional shift.

Background: Although previous studies have explored the moderating role of emotional regulation strategies in the relationship between empathy and depression, no studies have studied the moderating role of attentional control in the relationship between empathy and depression. To address this research gap, the present study investigated the moderating roles of rumination and attentional control in the relationship between empathy and depression. Methods: 423 participants filled out questionnaires anonymously, including Interpersonal Reactivity Index, Attention Control Scale, Self-rating Depression Scale, and Rumination Response Scale. PROCESS macro for SPSS was used for moderating effect analysis. Results: Rumination and attentional shift moderated the relationship between emotional empathy and depression. Specifically, the lower rumination or the higher attentional shift, the stronger the negative association between emotional empathy and depression. Attentional shift moderated the relationship between cognitive empathy and depression, and cognitive empathy was significantly associated with depression only among participants whose attentional shift is high. Conclusion: The study showed that rumination and attentional shift play important roles in the relationship between empathy and depression. The findings implicated that the positive role of good emotional regulation strategies and executive function for individuals in the relationship between empathy and depression.

Are Perfectionists Always Dissatisfied with Life? An Empirical Study from the Perspective of Self-Determination Theory and Perceived Control.

Compared to non-perfectionists, perfectionists may not be satisfied with the growing needs in their lives to the same extent. To test whether perfectionists are dissatisfied with their lives, we investigated whether trait perfectionism attenuates the relationship between basic psychological needs, perceived control, and life satisfaction. A total of 574 college students self-reported basic psychological needs, perceived control, life satisfaction, and perfectionistic strivings and concerns, with a mean age of 19.53 (SD = 1.61), including 299 women and 275 men. A correlation analysis showed that perfectionistic strivings were significantly positively related to life satisfaction, while perfectionistic concerns were significantly negatively related to life satisfaction. The moderation analysis showed that perfectionistic strivings not only moderated the relationship between basic psychological needs and life satisfaction but also moderated the relationship between perceived control and life satisfaction. Individuals with high perfectionistic strivings generally reported high levels of life satisfaction. Perfectionistic strivings, however, reduced the positive relationship between perceived control and life satisfaction. Perfectionistic concerns moderated the relationship between perceived control and life satisfaction-the higher the perfectionistic concerns, the weaker the positive relationship between perceived control and life satisfaction. The study found that individuals with high perfectionistic tendencies are not always dissatisfied with life, but that perfectionism weakens the relationship between basic psychological needs, perceived control, and life satisfaction. We argue that one way to improve happiness is by coaching individuals who are highly perfectionistic to become self-aware of their personality so both their perfectionistic strivings and concerns are more coherent with their values and goals or character.

NCAPH promotes proliferation as well as motility of breast cancer cells by activating the PI3K/AKT pathway.

Objective: This study aimed to assess the expression of NCAPH in human breast cancer, and to investigate its effects on breast cancer cells. Methods: Bioinformation analysis was performed to analyze the expression of NCAPH in human breast cancer tissues and normal tissues in TCGA database. qPCR and Immunoblot assays were performed to clarify the expression of NCAPH in breast cancer tissues and cell lines, respectively. CCK-8, colony formation, FCM, transwell, and immunoblot assays were performed to reveal the effects of NCAPH on breast cancer proliferation, cell cycle, motility and EMT of breast cancer cells. Additionally, immunoblot assays were performed to investigate the effects of NCAPH on the PI3K/AKT pathway in breast cancer. Results: We found that NCAPH was highly expressed in human breast cancer cell lines. The depletion of NCAPH suppressed the viability of breast cancer cells. Further, we noticed that its downregulation restrained breast cancer cell migration as well as invasion, and the EMT process. Mechanically, we noticed that NCAPH mediated the PI3K/AKT pathway, and therefore contributed to breast cancer progression. Conclusion: In summary, NCAPH has the potential to serve as a breast cancer target.

A PRC2-independent function for EZH2 in regulating rRNA 2'-O methylation and IRES-dependent translation.

Dysregulated translation is a common feature of cancer. Uncovering its governing factors and underlying mechanism are important for cancer therapy. Here, we report that enhancer of zeste homologue 2 (EZH2), previously known as a transcription repressor and lysine methyltransferase, can directly interact with fibrillarin (FBL) to exert its role in translational regulation. We demonstrate that EZH2 enhances rRNA 2'-O methylation via its direct interaction with FBL. Mechanistically, EZH2 strengthens the FBL-NOP56 interaction and facilitates the assembly of box C/D small nucleolar ribonucleoprotein. Strikingly, EZH2 deficiency impairs the translation process globally and reduces internal ribosome entry site (IRES)-dependent translation initiation in cancer cells. Our findings reveal a previously unrecognized role of EZH2 in cancer-related translational regulation.

Excellent electrochemical stability of Co3O4array with carbon hybridization derived from metal-organic framework.

Hybrid supercapacitors have attracted considerable attention for the use in the energy storage systems due to the simultaneous possession of high power and energy. Herein, Co3O4array with amorphous carbon on Ni foam has been derived from the Co-MOF. The electrochemical dynamics and energy storage mechanism of the prepared electrode have been investigated, which reveals the enhancement of the capacitive behavior with the scan rate. The electrochemically active specific surface area (ECSA) of our sample is calculated as 1416 cm2for per square centimeter of electrode. The prepared material exhibits an excellent electrochemical performance (3.17 F · cm-2at 1 mA · cm-2and 2.076 F · cm-2at 30 mA · cm-2). Further, the long-term life shows 96.7% capacity retention at 50 mV · s-1after 20 000 cycles in KOH aqueous electrolyte. The Coulomb efficiency is noted to range from 95% to 100% even after 20 000 cycles. Further, the symmetrical solid-state supercapacitor represents a wide operating voltage range and high scan rate for practical applications. Three charged solid-state supercapacitors are observed to lit 160 parallel green LEDs (20 mA, 2.2V) for approximately 50 s. These findings from this study confirm the potential of Co3O4array with carbon hybridization as an effective supercapacitor electrode material.

Demand response through reject water scheduling in water resource recovery facilities: A demonstration with BSM2.

The objective of this paper is to determine the importance of integrating peak demand mitigation and future energy pricing structures for process modelling of conventional water resource recovery facilities (WRRFs) when evaluating energy cost and control strategies. The well-established benchmark simulation model (BSM2) is used to monitor energy usage, and a detailed holistic study of different flow streams is performed in order to establish potential opportunities for flexible control of WRRF energy demand. Secondly, a detailed framework is introduced to optimize scheduling control strategies for the reject water stream while considering peak electricity demand avoidance as well as completing a comprehensive energy cost model based on current and anticipated future energy tariff structures. The reject water scheduling strategies, without other active controls (e.g. aeration), revealed 63.4% average peak demand mitigation and €10,755 cumulative annual energy cost savings on a 100k population equivalent WRRF without a deterioration in effluent quality. Analysis of different reject water scheduling control strategies shows that reject water scheduling can be an effective tool for energy cost optimisation under alternative electricity tariff structures. These strategies also deliver electricity peak demand mitigation.

Antihistamine Drug Ebastine Inhibits Cancer Growth by Targeting Polycomb Group Protein EZH2.

Enhancer of zester homolog 2 (EZH2), a histone lysine methyltransferase and the catalytic component of polycomb repressive complex 2, has been extensively investigated as a chromatin regulator and a transcriptional suppressor by methylating H3 at lysine 27 (H3K27). EZH2 is upregulated or mutated in most cancers, and its expression levels are negatively associated with clinical outcomes. However, the current developed small-molecule inhibitors targeting EZH2 enzymatic activities could not inhibit the growth and progression of solid tumors. Here, we discovered an antihistamine drug, ebastine, as a novel EZH2 inhibitor by targeting EZH2 transcription and subsequently downregulating EZH2 protein level and H3K27 trimethylation in multiple cancer cell lines at concentrations below 10 µmol/L. The inhibition of EZH2 by ebastine further impaired the progression, migration, and invasiveness of these cancer cells. Overexpression of Ezh2 wild-type and its mutant, H689A (lacking methyltransferase activity), rescued the neoplastic properties of these cancer cells after ebastine treatment, suggesting that EZH2 targeted by ebastine is independent of its enzymatic function. Next-generation RNA-sequencing analysis also revealed that C4-2 cells treated with 8 µmol/L ebastine showed a gene profiling pattern similar to EZH2-knockdown C4-2 cells, which was distinctively different from cells treated with GSK126, an EZH2 enzyme inhibitor. In addition, ebastine treatment effectively reduced tumor growth and progression, and enhanced progression-free survival in triple-negative breast cancer and drug-resistant castration-resistant prostate cancer patient-derived xenograft mice. Our data demonstrated that ebastine is a novel, safe, and potent anticancer agent for patients with advanced cancer by targeting the oncoprotein EZH2.

Intersection management for autonomous vehicles with vehicle-to-infrastructure communication.

This paper proposes an intersection management strategy for autonomous vehicles under the vehicle-to-infrastructure circumstance. All vehicles are supposed to be fully autonomous and can communicate with the intersection management unit to check the traffic situation. Priority of passing the intersection is decided by a static conflict matrix which represents the potential conflict between lanes of different directions and a dynamic information list which could capture the real-time occupation of each lane in the intersection. Compared with the existing approaches in the literature, the intersection management unit in our strategy is more like a database rather than a computational center, and therefore, requires less computational resource and more likely satisfies the real-time requirement in heavy traffic situations. Simulations are conducted using SUMO (Simulation of Urban MObility), in which the proposed strategy is compared with both fixed and adaptive traffic light methods. The results indicate that the proposed strategy could significantly reduce the average time delay caused by the intersection and the corresponding variance, which shows the efficiency and fairness of the proposed strategy in intersection management.

Protective Effects of Lixisenatide against Lipopolysaccharide-Induced Inflammation Response in MAC-T Bovine Mammary Epithelial Cells: A Therapeutic Implication in Mastitis.

Mastitis is acute inflammation caused by microbial infections in the mammary glands. This disease is extremely harmful to lactating mothers. The preferred clinical strategy is antibiotic treatment, but this method results in resistance and side effects. Lixisenatide, a kind of glucagon-like peptide-1 (GLP-1) receptor agonist, is typically used for the treatment of type II diabetes. It is unknown whether lixisenatide possesses a beneficial role in mastitis. In the current study, we assessed the protective effects of lixisenatide against lipopolysaccharide (LPS) stimulation in MAC-T bovine mammary epithelial cells (MECs). Our findings show that lixisenatide attenuated LPS-induced oxidative stress by reducing reactive oxygen species (ROS) production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases-1 (NOX-1) expression in MAC-T MECs. Additionally, lixisenatide inhibited LPS-induced expression and secretion of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß). We also found that lixisenatide suppressed LPS-induced expression of matrix metalloproteinase 2 (MMP-2) and metalloproteinase 9 (MMP-9), and reduced the expression of toll-like receptor 4 (TLR4) (a typical receptor of LPS), its downstream molecule myeloid differentiation factor 88 (MyD88), and the phosphorylation of TGF ß-activated kinase 1 (TAK1). Notably, lixisenatide decreased the nuclear levels of nuclear factor-κB (NF-κB) and its transcriptional activity. These findings suggest that lixisenatide might become a possible therapeutic agent for the treatment of mastitis by weakening oxidative stress and the inflammatory response in MECs.

Benchmarking leachate co-treatment strategies in municipal wastewater treatment plants under dynamic conditions and energy prices.

Combined leachate treatment at municipal wastewater treatment plants (WWTPs) is applicable to a certain extent depending on the leachate composition, treatment plant configuration and its capacity. Co-treatment of leachate at WWTPs has several advantages, but due to increasingly stringent discharge standards applied in WWTPs, it has become more problematic. This study was undertaken to investigate the impact of leachate feeding strategies on effluent quality and the aeration energy costs of WWTPs. A modified version of Benchmark Simulation Model No.1 was used to develop, test and compare several leachate feeding and WWTP control strategies in the context of dynamic pollutant loads and energy prices. The results highlighted that combined leachate treatment led to a deterioration in the quality of discharged wastewater, as indicated by a 12-20% increase in effluent quality index. Additionally, it adversely affected aeration energy demand and cost of the plant by increasing them 1.7-2.3% and 0.8-2.5%, respectively. The impacts could be mitigated by adjusting leachate flow based on effluent ammonium concentrations and by using advanced process control, i.e. feedback ammonium control for dissolved oxygen regulation in aerobic reactors. The study demonstrates that modeling can be used as a valuable tool to assess the potential impacts of leachate co-treatment and develop better management strategies.

Highly Selective Adsorption on SiSe Monolayer and Effect of Strain Engineering: A DFT Study.

The adsorption types of ten kinds of gas molecules (O2, NH3, SO2, CH4, NO, H2S, H2, CO, CO2, and NO2) on the surface of SiSe monolayer are analyzed by the density-functional theory (DFT) calculation based on adsorption energy, charge density difference (CDD), electron localization function (ELF), and band structure. It shows high selective adsorption on SiSe monolayer that some gas molecules like SO2, NO, and NO2 are chemically adsorbed, while the NH3 molecule is physically adsorbed, the rest of the molecules are weakly adsorbed. Moreover, stress is applied to the SiSe monolayer to improve the adsorption strength of NH3. It has a tendency of increment with the increase of compressive stress. The strongest physical adsorption energy (-0.426 eV) is obtained when 2% compressive stress is added to the substrate in zigzag direction. The simple desorption is realized by decreasing the stress. Furthermore, based on the similar adsorption energy between SO2 and NH3 molecules, the co-adsorption of these two gases are studied. The results show that SO2 will promote the detection of NH3 in the case of SO2-NH3/SiSe configuration. Therefore, SiSe monolayer is a good candidate for NH3 sensing with strain engineering.

BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer.

B lymphoma Mo-MLV insertion region 1 (BMI1) has been reported to be an oncoprotein. BMI1 represses tumor suppressors to promote cell proliferation, epithelial-mesenchymal transition (EMT), and cancer progression. Although it is known that the expression of BMI1 is increased in many cancer types, the mechanism of BMI1 upregulation is not yet clear. We performed integrative analysis for 3 sets of prostate cancer (PCa) genomic data, and found that BMI1 and androgen receptor (AR) were positively correlated, suggesting that AR might regulate BMI1. Next, we showed that dihydrotestosterone (DHT) upregulated both mRNA and protein levels of BMI1 and that BMI1 was increased in castration-resistant prostate cancer (CRPC) from both human patients and a mouse xenograph model. We further identified an AR binding site in the promoter/enhancer region of BMI1, and confirmed BMI1 as the direct target of AR using gene-editing technology. We also demonstrated that high expression of BMI1 is critical for the development of castration-resistance. Our data also suggest that BMI1-specific inhibitors could be an effective treatment of CRPC.

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for breast cancer patients: An updated meta-analysis of 17079 individuals.

AIMS: This study aimed to evaluate the prognostic effect of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for patients with breast cancer (BC). METHODS: A literature search was performed by searching medical databases. Basic characteristics and prognostic data were extracted from included studies. Primary outcomes, such as overall survival (OS) and disease-free survival (DFS), were synthesized and compared. Subgroup analyses were performed according to pathology, geographical region, cut-off value, and tumor progression. RESULTS: A total of 39 studies comprising 17079 BC patients were included in this meta-analysis. Among them, 28 studies with 142 64 BC patients investigated predicting role of NLR for OS, showing elevated NLR were associated poor prognosis (hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.49-2.13, P < 0.001). Twenty-seven studies containing 115 04 patients explored the role of NLR in predicting DFS, showing elevated NLR was associated with poor DFS with HR of 1.60 (95% CI: 1.42-1.96, P < 0.001). Twelve studies explored the role of PLR in predicting OS, showing patients with higher PLR were associated with a significantly worse prognosis with a pooled HR of 1.32 (95% CI: 1.11-1.57, P = 0.002). Eleven studies with 5013 patients shown patients with elevated PLR were associated shorter DFS (HR: 1.43, 95% CI: 1.09-1.86, P = 0.009). Subgroup analyses shown a greater magnitude of association between NLR and OS in triple-negative BC patients than in HER2-positive ones. CONCLUSIONS: Our study suggested that elevated NLR and PLR were associated with poor OS as well as high risk of recurrence for BC patients. Subgroup analyses confirmed the prognostic effect of NLR and PLR in HER2-positive BC patients. As easily accessible parameters, NLR and PLR should be identified as useful biomarkers in the management of BC.

Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer.

Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In our study, we report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, we demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities. These results collectively suggest that pharmacologically targeting EZH2 might be a promising strategy for advanced prostate cancer.