Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due ...to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP‐seq and RNA‐seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.
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ZIC family members regulate neural development but have also been implicated in the development of various tumors. Here the authors report downregulation of ZIC2 in breast cancer cells. Low expression of ZIC2 correlated with poor outcome in breast cancer patients and served as an independent prognostic marker. The transcription factor STAT3 was identified as a potential target for ZIC2, and inhibition of STAT3 abrogated the oncogenic effects induced by decreased ZIC2 expression. STAT3 inhibitors might provide an alternative option for women with breast cancer showing ZIC2 downregulation.
Over the past decade, sustainable finance has been a topic of burgeoning significance for investors, and ESG ratings have become commonly used to implement ESG investment strategies in practice. ...Strikingly, it is widely documented in both academic literature and investment practices that ESG ratings of a given firm can be extremely different across rating providers. However, despite the disagreement in ESG ratings being subject to a lot of criticism, only few studies have examined the sources and determinants of rating divergence. This study examines whether quantitative ESG disclosure is conducive to rating convergence among agencies. Based on ESG rating data of Chinese A-share listed companies, the author finds that greater quantitative ESG disclosure, especially disclosure on environmental and social pillars, results in greater divergence of ESG ratings. When employing a difference-in-differences design with a quasi-experiment of disclosure guidance introduced by Hong Kong Exchange, the results show that if ESG disclosure is standardized and comparable, more numerical information reduces agencies' rating disagreement instead. Further analyses show that the lack of agreement is related to a low rating in the future. The author also finds that the effect of quantified ESG disclosure on rating divergence is more pronounced when firms are single businesses rather than diversified businesses with poor ESG performance rather than good ESG performance. The results are robust to alternative measures of ESG rating divergence, alternative sample, two-way clustering, and additional control variables. Taken together, the results indicate that quantitative ESG disclosure degenerates rating disagreement.
Background To date, coronavirus disease 2019 (COVID-19) becomes increasingly fierce due to the emergence of variants. Rapid herd immunity through vaccination is needed to block the mutation and ...prevent the emergence of variants that can completely escape the immune surveillance. We aimed to systematically evaluate the effectiveness and safety of COVID-19 vaccines in the real world and to establish a reliable evidence-based basis for the actual protective effect of the COVID-19 vaccines, especially in the ensuing waves of infections dominated by variants. Methods We searched PubMed, Embase and Web of Science from inception to July 22, 2021. Observational studies that examined the effectiveness and safety of SARS-CoV-2 vaccines among people vaccinated were included. Random-effects or fixed-effects models were used to estimate the pooled vaccine effectiveness (VE) and incidence rate of adverse events after vaccination, and their 95% confidence intervals (CI). Results A total of 58 studies (32 studies for vaccine effectiveness and 26 studies for vaccine safety) were included. A single dose of vaccines was 41% (95% CI: 28-54%) effective at preventing SARS-CoV-2 infections, 52% (31-73%) for symptomatic COVID-19, 66% (50-81%) for hospitalization, 45% (42-49%) for Intensive Care Unit (ICU) admissions, and 53% (15-91%) for COVID-19-related death; and two doses were 85% (81-89%) effective at preventing SARS-CoV-2 infections, 97% (97-98%) for symptomatic COVID-19, 93% (89-96%) for hospitalization, 96% (93-98%) for ICU admissions, and 95% (92-98%) effective for COVID-19-related death, respectively. The pooled VE was 85% (80-91%) for the prevention of Alpha variant of SARS-CoV-2 infections, 75% (71-79%) for the Beta variant, 54% (35-74%) for the Gamma variant, and 74% (62-85%) for the Delta variant. The overall pooled incidence rate was 1.5% (1.4-1.6%) for adverse events, 0.4 (0.2-0.5) per 10 000 for severe adverse events, and 0.1 (0.1-0.2) per 10 000 for death after vaccination. Conclusions SARS-CoV-2 vaccines have reassuring safety and could effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world. In the context of global pandemic and the continuous emergence of SARS-CoV-2 variants, accelerating vaccination and improving vaccination coverage is still the most important and urgent matter, and it is also the final means to end the pandemic. Graphical Keywords: SARS-CoV-2, Vaccine, Effectiveness, Safety, Meta-analysis
► A new dynamic increase factor (DIF) is proposed for nonlinear static analysis. ► The new DIF is a function of the level of residual capacity of the damaged frame. ► A nonlinear static alternative ...path analysis procedure using new DIFs is outlined. ► Empirical DIF formulas are derived from curve fitting data of model steel frames.
This paper presents a new empirical method for calculating the dynamic increase factor (DIF) that is used to amplify the gravity loads on the affected bays of a building frame, when the nonlinear static alternate path analysis is carried out to predict the peak dynamic responses to sudden column removal. The new method defines the DIF as a function of max(Mu/Mp), where the maximum operator is applied to all beams within the affected bays immediately adjacent to and above the removed column, and Mu and Mp are the factored moment demand under original unamplified static gravity loads and the factored plastic moment capacity, respectively, of an affected beam. Therefore, 1–max(Mu/Mp) directly, albeit approximately, measures the percentage level of the overall residual capacity of a building frame to remain essentially elastic while withstanding the dynamic effect of gravity loads upon sudden column removal, after the static effect of gravity loads has been resisted by the damaged frame. A step-by-step nonlinear static analysis procedure using the new DIF is described. As an illustration, empirical DIF formulas are derived from curve fitting data points generated by the nonlinear static alternate path analysis of three model steel moment frames originally designed to resist different levels of earthquake. It is found from the numerical examples that the new DIF is well correlated with max(Mu/Mp) for different column removal scenarios. Hence, the new DIF can be used with nonlinear static analysis in lieu of nonlinear dynamic analysis to assess the potential of building frames for progressive collapse.
Single atom catalysts exhibit particularly high catalytic activities in contrast to regular nanomaterial-based catalysts. Until recently, research has been mostly focused on single atom catalysts, ...and it remains a great challenge to synthesize bimetallic dimer structures. Herein, we successfully prepare high-quality one-to-one A-B bimetallic dimer structures (Pt-Ru dimers) through an atomic layer deposition (ALD) process. The Pt-Ru dimers show much higher hydrogen evolution activity (more than 50 times) and excellent stability compared to commercial Pt/C catalysts. X-ray absorption spectroscopy indicates that the Pt-Ru dimers structure model contains one Pt-Ru bonding configuration. First principle calculations reveal that the Pt-Ru dimer generates a synergy effect by modulating the electronic structure, which results in the enhanced hydrogen evolution activity. This work paves the way for the rational design of bimetallic dimers with good activity and stability, which have a great potential to be applied in various catalytic reactions.
Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman’s syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant ...impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate–carboxymethylcellulose or polyethylene oxide–sodium carboxymethylcellulose as anti-adhesive barrier.
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