To retrospectively analyze the relationship between preoperative blood parameters and postoperative clinical outcomes in patients with different molecular subtypes of breast cancer (BC), a cohort of ...601 patients with BC in the Third Affiliated Hospital, Sun Yat‐sen University, was retrospectively reviewed. They were categorized into four subtypes according to the expression of ER, PR, HER‐2, and KI‐67%. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts, the neutrophil‐to‐lymphocyte ratio (NLR), the neutrophil‐to‐monocyte ratio (NMR), the lymphocyte‐to‐monocyte ratio (LMR), and the platelet‐to‐lymphocyte ratio (PLR) were recorded. Univariate and multivariate analyses were performed to identify the relationship between parameters and ratios and disease‐free survival (DFS) and overall survival (OS). Luminal subtypes of BC had smaller tumor volume, better differentiation degree of invasive ductal carcinoma, less lymph node metastasis, and better clinical outcome than the HER‐2 overexpression and triple‐negative BC (TNBC) subtypes. In multivariate analysis, age and LMR were the independent prognostic factors of DFS in patients with luminal A (age, p = 0.005; LMR, P = 0.026); PLR in patients with luminal B (DFS; p = 0.032; OS, p= 0.012); LMR in patients with HER‐2 overexpression (DFS; p = 0.008; OS, p = 0.017); and NLR for DFS (p = 0.014); and WBC for OS (p = 0.008) in patients with TNBC. LMR was the benign predictor of luminal A and HER‐2 overexpression. PLR was the adverse predictor of luminal B. WBC and NLR were the adverse predictors of TNBC. Therefore, these peripheral blood parameters can play an important role in the diagnosis and treatment of patients with different molecular subtypes of BC.
This study was conducted to provide some evidence that immunocytes could influence the clinical prognosis of different molecular subtypes of breast cancer (BC), and we hoped that this could help the clinicians in the treatment of patients with BC.
Oxidative stress is the main factor responsible for the induction of diabetic renal fibrosis. Thus, improving the state of oxidative stress can effectively prevent the further deterioration of ...diabetic nephropathy (DN). Previous research has shown that formononetin (FMN), a flavonoid with significant antioxidant activity and Sirt1 activation effect, can improve diabetic renal fibrosis. However, the exact mechanisms underlying the effect of FMN on diabetic renal fibrosis have yet to be elucidated. In this study, we carried out
experiments in a db/db (diabetic) mouse model and demonstrated that FMN activated the nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway and improved oxidative stress by increasing levels of sirtuin-1 (Sirt1) protein level in renal tissue. We also found that this process reversed the up-regulation of fibronectin (FN) and intercellular adhesion molecule 1 (ICAM-1) and led to an improvement in renal insufficiency.
results further showed that FMN significantly reversed the upregulation of FN and ICAM-1 in glomerular mesangial cells (GMCs) exposed to high glucose. FMN also promoted the expression of Nrf2 and widened its nuclear distribution. Thus, our data indicated that FMN inhibited hyperglycemia-induced superoxide overproduction by activating the Nrf2/ARE signaling pathway. We also found that FMN up-regulated the expression of Sirt1 and that Sirt1 deficiency could block the activation of the Nrf2/ARE signaling pathway in GMCs induced by high glucose. Finally, we found that Sirt1 deficiency could reverse the down-regulation of FN and ICAM-1 induced by FMN. Collectively, our data demonstrated that FMN up-regulated the expression of Sirt1 to activate the Nrf2/ARE signaling pathway, improved oxidative stress in DN to prevent the progression of renal fibrosis. Therefore, FMN probably represents an efficient therapeutic option of patients with DN.
Firstly, a two-unit cold standby shock model with multiple adaptive vacations is introduced, in which the startup and replacement of repair facility are also considered. Secondly, using supplementary ...variable method and Laplace transform, some important reliability indices are derived, such as availability, failure frequency, mean vacation period, mean renewal cycle, mean startup period, and replacement frequency. Finally, a production line controlled by two cold-standby computers is modeled to present numerical illustration and its optimal part-time job policy at a maximum profit.
This paper develops a probabilistic decomposition method for an M ξ /G/1 repairable queueing system with multiple vacations, in which the customers who arrive during server vacations enter the system ...with probability p. Such a novel method is used to analyze the main performance indices of the server, such as the unavailability and the mean failure number during ( 0 , t . It is derived that the structures of server indices are two convolution equations. Further, comparisons with existing methods indicate that our method is effective and applicable for studying server performances in single-server M ξ /G/1 vacation queues and their complex variants. Finally, a stochastic order and production system with a multipurpose production facility is numerically presented for illustrative purpose.
The performance of electrode materials depends intensively on the lithium (Li)‐ion storage mechanisms correlating ultimately with the Coulombic efficiency, reversible capacity, and morphology ...variation of electrode material upon cycling. Transition metal nitrides anode materials have exhibited high‐energy density and superior rate capability; however, the intrinsic mechanism is largely unexplored and still unclear. Here, a typical 3D porous Fe2N micro‐coral anode is prepared and, an intercalation–conversion–heterogeneity hybrid Li‐ion storage mechanism that is beyond the conventional intercalation or conversion reaction is revealed through various characterization techniques and thermodynamic analysis. Interestingly, using advanced in situ magnetometry, the ratio (ca. 24.4%) of the part where conversion reaction occurs to the entire Fe2N can further be quantified. By rationally constructing a Li‐ion capacitor comprising 3D porous Fe2N micro‐corals anode and commercial AC cathode, the hybrid full device delivers a high energy‐density (157 Wh kg−1) and high power‐density (20 000 W kg−1), as well as outstanding cycling stability (93.5% capacitance retention after 5000 cycles). This research provides an original and insightful method to confirm the reaction mechanism of material related to transition metals and a fundamental basis for emerging fast charging electrode materials to be efficiently explored for a next‐generation battery.
Combining various characterization techniques and thermodynamic analysis, the Li‐ion storage process in transition metal nitrides (TMNs) is reacquainted, showing an intercalation–conversion–heterogeneity hybrid mechanism, which may be one of the reasons for the fast charging and high energy output of TMNs electrode materials.
Acetic acid and furfural (AF) are two major inhibitors of microorganisms during lignocellulosic ethanol production. In our previous study, we successfully engineered Zymomonas mobilis 532 (ZM532) ...strain by genome shuffling, but the molecular mechanisms of tolerance to inhibitors were still unknown. Therefore, this study investigated the responses of ZM532 and its wild-type Z. mobilis (ZM4) to AF using multi-omics approaches (transcriptomics, genomics, and label free quantitative proteomics). Based on RNA-Seq data, two differentially expressed genes, ZMO_RS02740 (up-regulated) and ZMO_RS06525 (down-regulated) were knocked out and over-expressed through CRISPR-Cas technology to investigate their roles in AF tolerance. Overall, we identified 1865 and 14 novel DEGs in ZM532 and wild-type ZM4. In contrast, 1532 proteins were identified in ZM532 and wild-type ZM4. Among these, we found 96 important genes in ZM532 involving acid resistance mechanisms and survival rates against stressors. Furthermore, our knockout results demonstrated that growth activity and glucose consumption of mutant strains ZM532∆ZMO_RS02740 and ZM4∆ZMO_RS02740 decreased with increased fermentation time from 42 to 55 h and ethanol production up to 58% in ZM532 than that in ZM532∆ZMO_RS02740. Hence, these findings suggest ZMO_RS02740 as a protective strategy for ZM ethanol production under stressful conditions.
Our previous study proved that paeonol (Pae) could lower blood glucose levels of diabetic mice. There are also a few reports of its potential use for diabetes treatment. However, the role of Pae in ...regulating glucose and lipid metabolism in diabetes remains largely unknown. Considering the critical role of serine/threonine kinase B (Akt) in glucose and lipid metabolism, we explored whether Pae could improve glucose and lipid metabolism disorders via Akt. Here, we found that Pae attenuated fasting blood glucose, glycosylated serum protein, serum cholesterol and triglyceride (TG), hepatic glycogen, cholesterol and TG in diabetic mice. Moreover, Pae enhanced glucokinase (GCK) and low-density lipoprotein receptor (LDLR) protein expressions, and increased the phosphorylation of Akt. In insulin-resistant HepG2 cells, Pae increased glucose uptake and decreased lipid accumulation. What's more, Pae elevated LDLR and GCK expressions as well as Akt phosphorylation, which was consistent with the
results. Knockdown and inhibition experiments of Akt revealed that Pae regulated LDLR and GCK expressions through activation of Akt. Finally, molecular docking assay indicated the steady hydrogen bond was formed between Pae and Akt2. Experiments above suggested that Pae ameliorated glucose and lipid metabolism disorders and the underlying mechanism was closely related to the activation of Akt.
Most breast cancers are estrogen dependent and were sensitive to endocrine therapy, and genistein (GEN) shows strong affinity with human oestrogen receptor beta (ERβ).
The present study aimed to ...investigate the anticancer activity of GEN in breast cancer cell lines that constitutively expressing ERβ1 in vitro and in vivo.
MCF-7/ERβ1 and MDA-MB-231/ERβ1 cell sub-lines were established through lentiviral infection. Then, cells were treated with increasing concentrations of GEN (10
mol/l, 10
mol/l and 10
mol/l) for 48 h, and cell proliferation, cell cycle analyses were performed to investigate different biological characteristics of ERβ1-overexpressing cell lines. Studies in vivo were also performed to investigate the effects of dietary GEN on MCF-7/ERβ1 and MDA-MB-231/ERβ1 cells implanted mice.
Results showed that compared to parental cells, GEN inhibited the proliferation ability of MCF-7/ERβ1 cells to a greater extent, especially at high concentrations. MDA-MB-231 cells were also inhibited by high doses of GEN, but the overexpressed ERβ1 did not enhance the anti-proliferative effect on MDA-MB-231 cells. ERβ1 arrested cells in G2/M phase, and GEN arrested cells in G0/G1, which led to a combinatorial effect on cell cycle blockade. Furthermore, ERβ1 increased the anti-tumour activity of dietary GEN in MCF-7/ERβ1 subcutaneous tumour models. Our data indicated that ERβ1 increased the anticancer efficacy of GEN in MCF-7 cells by affecting cell cycle transition.
As a result, GEN could be a potential therapeutic agent for ERβ1-positive cancer.
To gain better knowledge of the effects of residual chlorothalonil on soil characteristics and soil microbial communities, we evaluated the dissipation of chlorothalonil and the effects of different ...chlorothalonil concentrations on soil respiration, enzyme activities, and microbial community structure in yellow–brown loam soils. Bacterial and fungal soil communities were examined using traditional plate counting and polymerase chain reaction–denaturing gradient gel electrophoresis (PCR–DGGE) methods. Soil properties and the results of DGGE band analysis were both used to estimate the status of the soil microbial ecosystem. The results show that residual chlorothalonil has considerable effects on soil respiration, enzymatic activities, and microbial community structure. In particular, soil respiration and phosphatase activities were increased, while saccharase activity, microbial biomass, and microbial community diversity were decreased by increasing levels of chlorothalonil treatment. Correlation analyses revealed that the application of chlorothalonil was significantly correlated with the change of the soil respiration, urease activity, sucrase activity, soil culturable bacteria, and culturable fungi biomass. We conclude that residual chlorothalonil is directly related to soil respiration, enzyme activities, and microbial community structure.
Lowering cost will prompt the sustainable development of sugarcane‐based ethanol industry. In this work, we developed a low‐cost process for ethanol production from sugarcane by a genetically ...engineered Zymomonas mobilis. Fermentation media were first optimized, resulting in a 15.54% increase in ethanol fermentation efficiency as compared to control media. To further reduce the byproduct levan formation, a levansucrase‐encoding gene of Z. mobilis, sacB, was deleted through the type I‐F CRISPR‐Cas system, which resulted in a further elevation of both ethanol conversion ratio and productivity comparing with the starting strain ZMS912 (87.50% vs. 76.77%, 1.95 g/L/h vs. 1.71 g/L/h). Moreover, we conducted fed‐batch fermentation for ethanol production using sugarcane juice in 5 L bioreactors and employing the optimized media and engineered strain. The results showed that maximum ethanol titer of 81.59 g/L and productivity of 5.83 g/L/h were achieved. Finally, preliminary techno‐economic assessment demonstrated that our efforts to modify media and strain could reduce the processing cost of ethanol production from sugarcane juice, which provides the feasibility for economic ethanol production in the future.
Bioethanol is the primary force in future energy supply and carbon reduction. In this work, we developed a low‐cost process for ethanol production from sugarcane by a genetically engineered Zymomonas mobilis. The effective combination of two nitrogen sources can shorten the fermentation time and increase ethanol production. Gene mutation in Z. mobilis may further improve ethanol concentration and eliminated the formation of by‐products. Furthermore, higher ethanol titer and shorter fermentation time are achieved by fed‐batch fermentation in fermentor scale. The techno‐economic assessment demonstrated that this study provides the feasibility for the profitable production of sugarcane‐based ethanol.
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