Achieving synergistic development of efficient urban land use and the natural environment is crucial in promoting green urbanization. The assessment of land use eco-efficiency (LUEE) and its temporal–spatial changes provides an effective means of quantifying the relationship between the urban ecological environment and land use. Targeting 55 selected cities in the Yellow River Basin (YRB), in this study, we utilize the Super-EBM method to gauge the LUEE. We explore the temporal patterns and the spatial convergence of LUEE utilizing kernel density estimation and spatial econometric methods. Considering the resource and environmental costs of land use, we assumed the industrial pollutant emissions generated during urban land use as the undesired outputs and designed a framework for measuring the level of LUEE under double constraints, which theoretically revealed the formation process and spatial convergence mechanism of LUEE. The results show the following: (1) Throughout the sample period, the LUEE of the YRB urban agglomeration decreased from 0.158 in 2009 to 0.094 in 2020, indicating a decreasing spatial disparity in LUEE over time. Notably, the Lanxi urban cluster exhibited the largest gap in LUEE, whereas the Guanzhong Plain urban agglomeration displayed the smallest gap. The hyper-variable density exceeded the inter-group gap as the main factor leading to the difference in LUEE. (2) Although the LUEE of urban agglomerations has increased, there still exists a noticeable polarization phenomenon. (3) The LUEE of YRB demonstrates a pattern of conditional convergence and exerts a significant spatial spillover effect. Over time, the LUEE of YRB will tend towards an individual steady state. The findings have implications for strengthening linkage and synergy among cities in YRB, promoting factor integration across administrative regions, and formulating heterogeneous policies.
Abstract Background: Estrogen metabolites play a role in breast cancer development. Previous studies have particularly focused on the two competing metabolism pathways which yield metabolites 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1). 2-OHE1 has been shown to have antiestrogenic effects, but 16-OHE1has strong estrogenic and even genotoxic activity. No study has investigated their biologically plausible role in predicting prognosis/mortality among women diagnosed with breast cancer. Methods: In the Long Island Breast Study Project, spot urine samples were obtained from 687 women diagnosed with first primary breast cancer (shortly after diagnosis) in 1996-1997. Urinary concentrations of estrogen metabolites 2-OHE1 and 16-OHE1 were measured using enzyme linked immuno-assay. Vital status was determined by the National Death Index through December 31, 2014; 244 deaths (84 breast cancer-specific and 80 cardiovascular diseases-specific) were identified. We used multivariable-adjusted Cox proportional hazards regression model to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause, breast cancer and cardiovascular diseases mortality as related to the two individual metabolites and their ratio (2-OHE1/16-OHE1). Multiplicative interactions with menopausal hormone therapy, body mass index, menopausal status, and breast cancer treatments were evaluated with likelihood ratio tests. Results: During a median follow-up of 18 years, urinary concentration of the 2-OHE1/16-OHE1 ratio (> median of 1.8 vs. ≤ median of 1.8) was associated with reduced risk of all-cause mortality (HR=0.74, 95% CI=0.56-0.98) among women with breast cancer. This inverse association with the 2-OHE1/16-OHE1 ratio was also observed for breast cancer mortality (HR=0.73, 95% CI=0.45-1.17) and cardiovascular diseases mortality (HR=0.76, 95% CI=0.47-1.23), although the 95%CIs included the null. The 2-OHE1/16-OHE1 ratio-mortality associations did not significantly differ by menopausal hormone therapy, body mass index, and menopausal status at the time of urine collection (Pinteration >0.05). Consistent patterns of association were not observed between the individual metabolites and mortality outcomes. Conclusion: To our knowledge, our study represents the first population-based epidemiologic evidence suggesting that the urinary concentration of the 2-OHE1/16-OHE1 ratio measured shortly after breast cancer diagnosis may be associated with improved overall mortality for breast cancer survivors. Future investigation is necessary to confirm our findings and to further understand the underlying biological mechanisms for estrogen metabolism–mortality relationships following breast cancer diagnosis. Citation Format: Tengteng Wang, Patrick B. Bradshaw, Sarah J. Nyante, Hazel B. Nichols, Patricia G. Moorman, Geoffrey C. Kabat, Susan L. Teitelbaum, Alfred I. Neugut, Marilie D. Gammon. Urinary estrogen metabolites and long-term all-cause and cause-specific mortality following breast cancer diagnosis: A population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3294.
Abstract Background Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. Methods We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses’ Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952). Results Early menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferation (e.g. Myc, PI3K/AKT/mTOR, cell cycle), oxidative stress (e.g. oxidative phosphorylation, unfolded protein response), and inflammation (e.g. pro-inflammatory cytokines IFN $$\alpha$$ α and IFN $$\gamma$$ γ ). Replication in TCGA confirmed these trends. Early menarche was associated with significantly higher PAM50 proliferation scores (β = 0.082 [0.02–0.14]), odds of aggressive molecular tumor subtypes (basal-like, OR = 1.84 [1.18–2.85] and HER2-enriched, OR = 2.32 [1.46–3.69]), and PAM50 risk of recurrence score (β = 4.81 [1.71–7.92]). Our NHS-derived early menarche gene expression signature was significantly associated with worse 10-year disease-free survival in METABRIC (N = 952, HR = 1.58 [1.10–2.25]). Conclusions Early menarche is associated with more aggressive molecular tumor characteristics and its gene expression signature within tumors is associated with worse 10-year disease-free survival among women with breast cancer. As the age of onset of menarche continues to decline, understanding its relationship to breast tumor characteristics and prognosis may lead to novel secondary prevention strategies.
The aim of the present study was to compare pathological diagnoses, as determined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, with conventional radiological features. In addition, the present study aimed to evaluate the correlation among clinical characteristics, computed tomography (CT) images and gene mutation status in patients with stage IA adenocarcinoma of the lung. A total of 212 patients with stage IA lung adenocarcinoma were included in the study. The patients were classified into pure ground-glass opacity (pGGO), mixed GGO (mGGO) and solid GGO (sGGO) by CT imaging. Histological subtype was classified according to the IASLC/ATS/ERS classification of lung adenocarcinoma. In addition, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) mutation assays were performed, and 36.8% of patients (78/212) were determined to have an EGFR mutation, while 8.5% of patients (18/212) were found to have a KRAS mutation. According to the IASLC/ATS/ERS classification, 44 cases were diagnosed as adenocarcinoma in situ (AIS; 20.8%), 62 cases were diagnosed as minimally invasive adenocarcinoma (MIA; 29.2%) and 106 cases were classified as invasive adenocarcinoma (IAC; 50.0%). pGGO image patterns were observed in 39.2% of patients (n=83), while mGGO and sGGO patterns were observed in 28.8% (n=61) and 32.0% (n=68) of patients, respectively. From pGGO to sGGO, cases of AIS and MIA were shown to have a decreasing trend, while IAC cases exhibited an increasing trend (P=0.036). Analysis of the correlation between CT image patterns and gene mutations demonstrated that L858R point mutations, exon 19 deletions and KRAS mutations were more common in lesions with a lower GGO proportion (P=0.029, 0.027 and 0.018, respectively). Therefore, according to the IASLC/ATS/ERS classification, GGO imaging patterns were shown to correlate with subtypes of adenocarcinomas. In addition, EGFR and KRAS mutations were found to be associated with lesions with a low GGO proportion. Therefore, analysis of GGO lesions may offer useful indications of the histological subtype of an adenocarcinoma in patients with stage IA lung adenocarcinoma, and predictive value for EGFR and KRAS mutations.
Abstract Background: Experimental evidence suggests that aspirin may inhibit breast tumor growth and reduce invasiveness of breast cancer cells. In large population-based studies (including our own), post-diagnostic aspirin use was associated with reduced breast cancer-specific and all-cause mortality. Here, we have extended our prior study with an additional 10 years of follow-up (3,785 more breast cancer cases) and investigation of the molecular underpinnings of the role of aspirin in breast cancer prognosis. Methods: Our study included 7,949 women diagnosed with stage I, II or III breast cancer from the Nurses’ Health Study (NHS) and NHSII. Cox proportional hazards regression was used to compute the multivariate hazard ratio (HR) for death, adjusting for tumor characteristics, treatment information and lifestyle factors. Post-diagnostic aspirin use was obtained at least 12 months after diagnosis and updated at every 2-year follow-up interval. We also evaluated the association between post-diagnostic aspirin use and survival according to tumor characteristics. Estrogen receptor (ER), insulin receptor (IR), PTEN, and Ki67 protein expression was evaluated by immunohistochemistry. PIK3CA mutation status was determined via polymerase chain reaction and pyrosequencing. In an exploratory analysis to identify functional enrichment of biologic pathways associated with long-term pre-diagnostic aspirin use (ever use of aspirin for ≥10 years with >2d/wk), we used a competitive gene-set testing procedure in a subgroup of cases with gene expression data (N=453). In this subset, we also computed the abundance of immune cell infiltration (B cell, CD4+ T cell, CD8+T cell, macrophage, neutrophil and dendritic cell) using Tumor IMmune Estimation Resource (TIMER). Results: During a median follow-up of 12 years after breast cancer diagnosis, we documented 2,502 deaths, including 1,373 from breast cancer. Compared with nonusers, women who regularly used aspirin after diagnosis had lower breast cancer-specific mortality: HR for 1, 2-5, 6-7 days of aspirin use per week were 0.65 (95% CI: 0.49, 0.86), 0.41 (95% CI: 0.29, 0.57) and 0.61 (95% CI: 0.47, 0.78) for, respectively (p-trend<0.0001). The association did not differ statistically by PTEN loss, PIK3CA mutation, or expression of IR (PI3K—AKT—mTOR), ER or Ki67 expression (proliferation pathways), or immune cell infiltration of the primary tumors (p-heterogeneity>0.05). Long-term regular aspirin use before diagnosis was associated with the downregulation of pathways related to inflammation (INF-α, INF-γ, and TNF-α), PI3K—AKT—mTOR signaling (mTOR and PI3K—AKT), and other proliferation (E2F and myc targets) in primary breast tumors and/or normal-adjacent tissues (FDR≤0.05). Long-term regular aspirin use prior to diagnosis was also associated with higher CD8+T cell (mean±SD=0.20±0.02 for non-users and 0.21±0.02 for users, p=0.01) and macrophage (mean±SD=0.05±0.03 for non-users and 0.06±0.02 for users, p=0.0002) relative abundance in primary tumors. Conclusion: Regular aspirin use after breast cancer diagnosis was associated with lower risk of breast cancer-specific and total mortality. The association between aspirin and mortality did not differ by molecular characteristics of primary tumors. Long-term aspirin use prior to breast cancer diagnosis was associated with downregulation of inflammatory and proliferation pathways and higher immune cell infiltration of CD8+ T cells and macrophages in breast tumors. Taken together, our large-scale population-based analysis with long-term of follow-up highlight the potential benefit of aspirin as a secondary prevention strategy across different tumor molecular characteristics. Citation Format: Cheng Peng, Michelle D. Holmes, Tengteng Wang, Alexandra Harris, Wendy Chen, Kristen Brantley, Yujing J Heng, Vanessa C. Bret-Mounet, Gabrielle M Baker, Bernard Rosner, Walter Willett, Rulla Tamimi, A. Heather Eliassen. Regular aspirin use, breast tumor characteristics and long-term breast cancer survival [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-01.
Baby Boom(BBM) gene is a key regulatory factor in embryonic development and regeneration, cell proliferation, callus growth, and differentiation promotion. Since the genetic transformation system of Panax quinquefolius is unstable with low efficiency and long period, this study attempted to transfer BBM gene of Zea mays to P. quinquefolius callus by gene gunship to investigate its effect on the callus growth and ginsenoside content, laying a foundation for establishing efficient genetic transformation system of P. quinquefolius. Four transgenic callus of P. quinquefolius with different transformation events were obtained by screening for glufosinate ammonium resistance and molecular identification by PCR. The growth state and growth rate of wild-type and transgenic callus were compared in the same growth period. The content of ginsenoside in transgenic callus was determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The results showed that transgenic callus growth rate was significantly higher than that of wild-type callus. In addition, the content of ginsenoside Rb_1, Rg_1, Ro, and Re was significantly higher than that in wild-type callus. The paper preliminarily proved the function of BBM gene in promoting growth rate and increasing ginsenoside content, which provided a scientific basis to establish a stable and efficient genetic transformation system for Panax plants in the future.
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