Prognostic analysis of cT1-3N1M0 breast cancer patients who have responded to neoadjuvant therapy undergoing various axillary surgery and breast surgery based on propensity score matching and competitive risk model

BackgroundSentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT).MethodsPatients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model.ResultsThe PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey’s test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey’s test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05).ConclusionFor cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes

Protective Role of Nuclear Factor-Erythroid 2-Related Factor 2 Against Radiation-Induced Lung Injury and Inflammation

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. Inflammatory cell infiltration, imbalance of inflammatory cytokines, and oxidative damage were reported to be involved during RILI pathogenesis, especially in the early phase of RILI. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidative cascades, and regulates life span of mice after administration of thoracic irradiation. We investigated the effects of Nrf2 on RILI and inflammation using Nrf2-knockout, Nrf2-overexpression and wild-type mice with or without 15 Gy ionizing radiation to thorax. Our results showed that Nrf2 deficiency aggravated radiation-induced histopathological changes, macrophage and neutrophil infiltration, serum levels of pro-inflammatory cytokines (IL-6, MCP-1, IFN-γ, TNF, and IL-12p70), and the levels of peroxidation products in the mouse lung. Moreover, loss of Nrf2 reduced radiation-induced serum levels of anti-inflammatory cytokine, IL-10, and antioxidative proteins. Nrf2 overexpression significantly alleviated radiation-induced histopathological changes, macrophages and neutrophils infiltration, serum levels of pro-inflammatory cytokines, and the levels of peroxidation products in lung tissues. Nrf2 overexpression also increased the serum levels of IL-10 and antioxidative proteins. These results indicated that Nrf2 had a protective role against radiation-induced acute lung injury and inflammation, and that antioxidative therapy might be a promising treatment for RILI

An immune-related prognostic model predicts neoplasm-immunity interactions for metastatic nasopharyngeal carcinoma

BackgroundThe prognosis of nasopharyngeal carcinoma (NPC) has been recognized to improve immensely owing to radiotherapy combined with chemotherapy. However, patients with metastatic NPC have a poor prognosis. Immunotherapy has dramatically prolonged the survival of patients with NPC. Hence, further research on immune-related biomarkers is imperative to establish the prognosis of metastatic NPC.Methods10 NPC RNA expression profiles were generated from patients with or without distant metastasis after chemoradiotherapy from the Fujian Cancer Hospital. The differential immune-related genes were identified and validated by immunohistochemistry analysis. The method of least absolute shrinkage and selection operator (LASSO)was used to further establish the immune-related prognostic model in an external GEO database (GSE102349, n=88). The immune microenvironment and signal pathways were evaluated in multiple dimensions at the transcriptome and single-cell levels.Results1328 differential genes were identified, out of which 520 were upregulated and 808 were downregulated. Notably, most of the immune genes and pathways were down-regulated in the metastasis group. A prognostic immune model involving nine hub genes. Patients in low-risk group were characterized by survival advantage, hot immune phenotype and benefit from immunotherapy. Compared with immune cells, malignant cell exhibited the most active levels of risk score by ssGSEA. Accordingly, intercellular communications including LT, CD70, CD40 and SPP1, and the like, between high-risk and low-risk were explored by the R package “Cellchat”.ConclusionWe have constructed a model based on immunity of metastatic NPC and determined its prognostic value. The model identified the level of immune cell infiltration, cell-cell communication, along with potential immunotherapy for metastatic NPC

An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation

The exocyst/aPKC complex controls the spatiotemporal activation of the kinases JNK and ERK at the leading edge of migrating cells and thereby controls the dynamic behaviour of the adhesion protein paxillin during cell migration

Direct and indirect effects of climate on richness drive the latitudinal diversity gradient in forest trees

Data accessibility statement: Full census data are available upon reasonable request from the ForestGEO data portal, http://ctfs.si.edu/datarequest/ We thank Margie Mayfield, three anonymous reviewers and Jacob Weiner for constructive comments on the manuscript. This study was financially supported by the National Key R&D Program of China (2017YFC0506100), the National Natural Science Foundation of China (31622014 and 31570426), and the Fundamental Research Funds for the Central Universities (17lgzd24) to CC. XW was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB3103). DS was supported by the Czech Science Foundation (grant no. 16-26369S). Yves Rosseel provided us valuable suggestions on using the lavaan package conducting SEM analyses. Funding and citation information for each forest plot is available in the Supplementary Information Text 1.Peer reviewedPostprin

2011): The role of EDTA on Cadmium phytoextraction in a Cadmiumhyperaccumulator Rorippa globosa

Enhanced phytoextraction technologies have been proposed as an effective approach to the decontamination of heavy metals in soils. In this study, the application of ethylene diamine tetraacetic acid (0.5 and 1.0 g/kg EDTA) at preflowering stage depressed Rorippa globosa growth and Cd uptake, the dry biomass, Cd concentration and total metal accumulation (TMC) of shoots at the concentration of 1.0 g/kg EDTA resulted in 39.6, 3.1 and 41.0% reduction, respectively, relative to the control. In contrast, when EDTA was added at flowering and mature stages, it facilitated plant production and Cd absorption. Especially for 1.0 g/kg EDTA applied at mature stage, the maximum of shoot dry biomass, Cd concentration, TMC and remediation ratio (RR) were obtained, which were 4.7 g/pot, 210.3 mg/kg, 982.4 µg/pot and 1.6, respectively. Therefore, the moderate concentration of EDTA (1.0 g/kg) applied at optimal growing stage (mature stage) of R. globosa was more effective in increasing phytoextraction of Cd from contaminated soils

Phytotoxicity and Accumulation of Copper-Based Nanoparticles in Brassica under Cadmium Stress

The widespread use of copper-based nanoparticles expands the possibility that they enter the soil combined with heavy metals, having a toxic effect and posing a threat to the safety of vegetables. In this study, single and combined treatments of 2 mg/L Cd, 20 mg/L Cu NPs and 20 mg/L CuO NPs were added into Hoagland nutrient solution by hydroponics experiments. The experimental results show that copper-based Nanoparticles (NPs) can increase the photosynthetic rate of plants and increase the biomass of Brassica. Cu NPs treatment increased the Superoxide Dismutase (SOD), Peroxidase (POD) and catalase (CAT) activities of Brassica, and both NPs inhibited ascorbate peroxidase (APX) activity. We observed that Cd + Cu NPs exhibited antagonistic effects on Cd accumulation, inhibiting it by 12.6% in leaf and 38.6% in root, while Cd + CuO NPs increased Cd uptake by 73.1% in leaves and 22.5% in roots of Brassica. The Cu content in the shoots was significantly negatively correlated with Cd uptake. The Cd content of each component in plant subcellular is soluble component > cytoplasm > cell wall. Cu NPs + Cd inhibited the uptake of Zn, Ca, Fe, Mg, K and Mn elements, while CuO NPs + Cd promoted the uptake of Mn and Na elements. The results show that copper-based nanoparticles can increase the oxidative damage of plants under cadmium stress and reduce the nutritional value of plants

Unexpected C–H Bond Activation Promoted by Bimetallic Lanthanide Amido Complexes Bearing a META-Phenylene-Bridged Bis(β-diketiminate) Ligand

Treatment of META-[Na­(THF)₂]₂ (<b>1</b>; META = {[2,6-^<i>i</i>Pr₂C₆H₃NC­(Me)­C­(H)­C­(Me)­N]⁻}₂-(<i>m-</i>phenylene)] with 1 equiv of {Ln­[N­(SiMe₃)₂]₂(μ-Cl)­(THF)}₂ (Ln = Y, Yb) in toluene at 110 °C afforded bimetallic lanthanide amido complexes bridged by a chloride and a phenyl group, {Ln­[N­(SiMe₃)₂]}₂(META′)­(μ-Cl) (Ln = Y (<b>2</b>), Yb (<b>3</b>)), which formed via unexpected C–H bond activation of the arene ring. However, the same reactions carried out in both THF and toluene at room temperature gave the bimetallic lanthanide amido–chloro complexes {Ln­[N­(SiMe₃)₂]₂}­META­{Ln­[N­(SiMe₃)₂]­Cl­(THF)} (Ln = Y (<b>4</b>), Yb (<b>5</b>)). When they were heated to 110 °C in toluene, complexes <b>4</b> and <b>5</b> were converted to complexes <b>2</b> and <b>3</b> via amine elimination. All of these complexes were confirmed by elemental analysis, FT-IR, and X-ray structure analysis and by NMR analysis in the cases of complexes <b>1</b>, <b>2</b>, and <b>4</b>

Analysis on Characteristics of Surrounding Rocks of Roadway and Bearing Structure Based on Stress Regulation

To address the prominent status of great deformation and difficult maintenance of the roadway under high stresses, this study investigated the mechanical characteristics of surrounding rocks and bearing structural stability in a roadway under adjustment and redistribution of stresses through theoretical analysis, numerical simulation, and engineering field test. Stability forms of the bearing structure of roadway surrounding rocks were analyzed by using the axis-changing theory from the perspectives of surrounding rock, mechanical properties of roadways, surrounding rock stress distribution, and mechanical mechanism of the bearing structure. It is suggested that the surrounding rock stress distribution state is improved and the bearing structure is optimized through unloading and reinforcement construction. A mechanical model of roadway excavation was constructed to analyze the influences of excavation spatial effect on the stress releasing and bearing structure of surrounding rocks. A rock postpeak strain softening and dilatation model was introduced to investigate the mechanical characteristics of the surrounding rock mass in the rupture residual zone and plastic softening zone in a roadway. Moreover, we analyzed the influences of unloading and reinforcement construction on the stress path and mechanical characteristics of the rock unit model, which disclosed the adjustment mechanism of the bearing structure of surrounding rocks by the failure development status of rocks. A numerical simulation on the distribution of surrounding rock stress fields and adjustment features of the bearing structure after roadway excavation and unloading and reinforcement construction was carried out by using the FLAC3D program. Results demonstrate that the unloading construction optimizes the axial ratio of spatial excavation in a roadway and the reinforcement zones on both sides are the supporting zones of the bearing structure. Moreover, the ratio between the distance from two side peaks to the roadway sides and the distance from the roof and floor peaks to the excavation space is equal to the coefficient of horizontal pressure. In other words, the final collapse failure mode of surrounding rock is that the long axis of the excavation unloading space points to the same direction with the maximum principal stress of the primary rock. Reinforcement forces the surrounding rocks to form a “Ω-shaped” bearing structure, which is in favor of the long-term maintenance of the roadway