Rothahmad8915

BACKGROUND We performed a retrospective study on the efficacy and safety of sirolimus (an mTOR inhibitor) in hormone receptor (HR)-positive advanced breast cancer and searched for biomarkers to predict its efficacy. METHODS All patients with HR-positive metastatic breast cancer treated with sirolimus plus endocrine therapy between December 2017 and July 2018 at the Cancer Hospital, Chinese Academy of Medical Sciences were consecutively and retrospectively reviewed. Mutations in circulating tumour DNA (ctDNA) were assayed for 1021 tumour-related genes via gene panel target capture-based next-generation sequencing. RESULTS Thirty-six patients with metastatic breast cancer treated with sirolimus plus endocrine therapy were included. The progression-free survival (PFS) rates between the sirolimus group and everolimus group were similar, and the median PFS was 4.9 months and 5.5 months, respectively (hazard ratio 1.56, 95% CI 0.86-2.81, P = 0.142). The objective response rate in the 36 patients was 19.4%, and the clinical benefit rate was 41.7%. Lipid metabolism disorder was the most common adverse event (69.4%), and 13.9% of patients had stomatitis. Most (94.4%) adverse events were grade 1-2. Twenty patients (55.6%) underwent ctDNA analysis before receiving sirolimus therapy. For patients who received less than 3 lines of chemotherapy, those with PI3K/Akt/mTOR pathway alterations had a better response to sirolimus than those without alterations, with a median PFS of 7.0 months vs 4.3 months (hazard ratio = 0.01, 95% CI 0.00-0.34, P = 0.010). CONCLUSIONS Sirolimus is a potentially effective treatment option for patients with HR-positive advanced breast cancer. INTRODUCTION Increasing evidence demonstrates the relevant association between Parkinson's disease (PD) and vascular diseases/risk factors, as well as a worse clinico-pathological progression in those patients with vascular comorbidity. The mechanisms underlying this relationship have not been clarified yet, although their comprehension is critical in a perspective of disease-modifying treatments development or prevention. METHODS We performed an experimental protocol of ischemic injury (glucose-oxygen deprivation, OGD) on PTEN-induced kinase 1 knockout (PINK1-/-) mice, a well-established PD model, looking at both electrophysiological and morphological changes in basal ganglia. In addition, 253 PD patients were retrospectively analysed, to estimate the prevalence of vascular risk factors. RESULTS In PINK1-/- mice, the OGD protocol induced electrophysiological (prolonged depolarization) and morphological alterations (picnotic cells, cellular loss and swelling, thickening of nuclear chromatin) in striatal medium spiny neurons and nigral dopaminergic neurons. Vascular comorbidity occurred in 75% of PD patients. CONCLUSIONS The ischemic injury precipitates neuronal vulnerability in basal ganglia of PINK1-/- mice, probably through an impairment of mitochondrial metabolism and higher oxidative stress. These experimental data may provide a potential mechanistic explanation for both the association between vascular diseases and PD and their reciprocal interactions in determining the clinico-pathological burden of PD patients. Levoglucosan is served as a significant versatile product to generate high value-added chemicals and pharmaceutical additives. Levoglucosan was predominately produced from pyrolysate of cellulose. However, the direct fast pyrolysis of waste biomass produces a small quantity of levoglucosan in comparison with the theoretical value of cellulose. This study explored Fenton pretreatment as a possible route to enhance levoglucosan yield during the fast pyrolysis of the waste corncob. The experimental results showed that different Fenton pretreated conditions and pyrolytic temperatures played vital roles in the formation of levoglucosan. The levoglucosan yield from fast pyrolysis at 500 °C of corncob pretreated by Fenton reaction of 14 mL/g H2O2 and 16 mM FeSO4 was about 95% higher than that of the untreated corncob. Additionally, Fenton pretreated corncob was capable of obtaining the levoglucosan at a low pyrolytic temperature (300 °C). It was mainly attributed to the effective disrupting of biomass structures and the selective degradation of lignin and hemicellulose during pretreatment. Furthermore, the powerful removal of alkali and alkaline earth metals during Fenton pretreatment was beneficial to increasing the levoglucosan yield. These findings demonstrate that Fenton pretreatment can provide a novel effective method to enhance levoglucosan yield during biomass fast pyrolysis. Char, a solid product obtained from carbonization of waste Poly(Ethylene) Terephthalate (PET), has high potential to solve the current plastic waste problem through the synthesis of new carbon-based adsorbents. However, thermal degradation reaction of polymer involves multiple series of complex reaction pathways and the formation of char is not clarified. In this study, the phase behavior of PET carbonization and the mechanism of char formation was studied in detail. Based on the van Krevelen diagram, it is evident that rapid thermal decomposition of PET occurs through decarbonylation to form char and decarboxylation to form wax. Based on the analysis of cross-linking behavior, a correlation between the degree of cross-linking as a function of CO and CO2 and dependent parameters based on the experimental operation was obtained. The findings validified the assumption that scission of CO bond in the carbonyl group through decarbonylation and decarboxylation to release CO and CO2 leads to the formation of char. The cross-linking behavior was further clarified by studying the distribution of cross-linking structure in char and wax. It was confirmed that decarbonylation reaction to release CO is highly associated with the formation of cross-linking to form char in the solid residue, whereas decarboxylation reaction to release CO2 is highly associated with the formation of cross-linking to form aromatic compounds in the wax residue. In the present study, the treatment of synthetic landfill leachate was carried out using a lab-scale anaerobic hybrid membrane bioreactor (An-HMBR). The reactor was operated for 250 days at two days of hydraulic retention time (HRT). click here Average chemical oxygen demand (COD) removal efficiency was ≥ 88% at steady-state conditions at 100% raw leachate. As organic loading rate (OLR) increased from 1.6 to 13.9 Kg COD m-3 d-1, flux gradually declined from 70 to 52 L/m2 h (LMH) within 250 days. Chemical membrane cleaning enhanced the flux up to 75% of the initial flux at the final stage of the reactor. Reversible fouling (>90%) dominated over irreversible fouling ( SMP (soluble microbial products). A nonlinear regression model developed for prediction of membrane resistance at different OLR can predict with an error of ±7%.