Semicommutators and Zero Product of Block Toeplitz Operators with Harmonic Symbols

We completely characterize the finite rank semicommutators, commutators, and zero product of block Toeplitz operators TF and TG with F,G∈h∞⊗Mn×n on the vector valued Bergman space La2(,ℂn)

The Third-Generation EGFR Inhibitor, Osimertinib, Promotes c-FLIP Degradation, Enhancing Apoptosis Including TRAIL-Induced Apoptosis in NSCLC Cells with Activating EGFR Mutations

The third-generation EGFR inhibitor, osimertinib (AZD9291), selectively and irreversibly inhibits EGFR activating and T790 M mutants while sparing wild-type EGFR. Osimertinib is now an approved drug for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations (first-line) or those who have become resistant to 1st generation EGFR inhibitors through the T790 M mutation (second-line). Unfortunately, all patients eventually relapse and develop resistance to osimertinib. Hence, it is essential to fully understand the biology underlying the development of resistance to osimertinib in order to improve its therapeutic efficacy and overcome resistance. Cellular FLICE-inhibitory protein (c-FLIP) is a truncated form of caspase-8 and functions as a key inhibitor of the extrinsic apoptotic pathway. The current study has demonstrated that osimertinib reduces c-FLIP levels via facilitating its degradation and enhances apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) primarily in NSCLC with activating EGFR mutations. Moreover, modulation of c-FLIP expression levels, to some degree, also alters the sensitivities of EGFR mutant NSCLC cells to undergo osimertinib-induced apoptosis, suggesting that c-FLIP suppression is an important event contributing to the antitumor activity of osimertinib against EGFR mutant NSCLC

Projecting potential evapotranspiration change and quantifying its uncertainty under future climate scenarios: A case study in southeastern Australia

Projecting the likely change of potential evapotranspiration (ETp) under future climate scenarios is crucial for quantifying the impacts of climate change on the hydrologic cycle and aridity conditions. However, there are different sources of uncertainty in projecting future ETp that may arise from global climate models (GCMs), emission scenarios, and multiple ETp models used. In this study, we developed three random forest-based (RF-based) ETp models with solar radiation and air temperature at eight climatic stations in southeastern Australia. With Penman model as the benchmark, their performance was firstly compared with four empirical models (Jensen-Haise, Makkink, Abtew, and Hargreaves), which requires the same meteorological inputs. In general, the RF-based ETp models showed better performance in ETp estimates across all stations, with coefficients of determination (R2) ranging from 0.68 to 0.92, root mean square errors (RMSE) ranging from 0.58 mm day−1 to 1.46 mm day−1, and relative mean bias errors (rMBE) ranging from −16.10% to 9.73%. The RF-based and empirical models were then used to project future ETp for the eight stations based on statistically downscaled daily climatic data from 34 GCMs under two different representative concentration pathways (RCP4.5 and RCP8.5). All models indicated that ETp was likely to increase at the eight stations. The ensemble increases of mean ETp across eight stations ranged from 33 mm year−1 (2.1%, 2040s) to 129 mm year−1 (9.2%, 2090s) and from 43 mm year−1 (2.8%, 2040s) to 248 mm year−1 (17.6%, 2090s) under RCP4.5 and under RCP8.5, respectively. In addition, we also quantified uncertainties in ETp projections originating from ETp models, GCMs, RCPs, and their combined effects using the analysis of variance (ANOVA) method. Results showed that RCP-related uncertainty contributed the most to projected ETp uncertainty (around 40% for most stations) while GCM-related and ETp model-related uncertainties accounted for roughly equal amounts of projected ETp uncertainty (10%–30%). This study demonstrated the better performance of RF-based ETp models. It is advisable to use multiple ETp models driven by various GCMs under different RCPs to produce reliable projections of future ETp

Further insight into systemic sclerosis from the vasculopathy perspective

Systemic sclerosis (SSc) is an autoimmune disease characterized by immune dysfunction, vascular system dysfunction, and tissue fibrosis. Vascular injury, vascular remodeling, and endothelial dysfunction are the hallmark pathological changes of the disease. In the early stages of SSc development, endothelial cell injury and apoptosis can lead to vascular and perivascular inflammation, oxidative stress, and tissue hypoxia, which can cause clinical manifestations in various organs from the skin to the parenchymal organs. Early diagnosis and rational treatment can improve patient survival and quality of life. Ancillary examinations such as nailfold capillaroscopy as well as optical coherence tomography can help early detect vascular injury in SSc patients. Studies targeting the mechanisms of vascular lesions will provide new perspectives for treatment of SSc

Gene polymorphism of cytochrome P450 significantly affects lung cancer susceptibility

Abstract Background Cytochrome P450 (CYPs) are heme proteins involved in the metabolism of a variety of endogenous and exogenous substances and play an important role in the carcinogenesis mechanisms of environmental and hereditary factors. The objective of this study was to investigate how polymorphisms of CYPs correlate with lung cancer (LC) susceptibility. Methods Six single nucleotide polymorphisms (SNPs) were genotyped in this study. The chi‐square test and unconditional logistic regression model were used to evaluate the correlation between SNPs and LC susceptibility. The expressions and survival data of genes in patients with LC were mined using Oncomine and Kaplan‐Meier Plotter database. Results Four SNPs were found to be significantly associated with the risk of LC development (P < 0.05). The most significant correlation was that the A allele and AA genotype of CYP2D6 rs1065852 were associated with increased risk of LC development (adjusted odds ratio [OR] = 1.35, 95% confidence interval [95%CI] = 1.13‐1.60, P = 9.04e‐4; OR = 1.83, 95%CI = 1.29‐2.59, P = 0.001 respectively). Similar association of this variant was also found in the subgroups of male patients, cases in III‐IV stages, positive lymph node, squamous cell carcinomas and adenocarcinomas. Whereas rs1065852 was considered as protective factor in females (adjusted OR = 0.33, 95% CI = 0.16‐0.70, P = 0.004). In stratified analyses, the association of CYP24A1 rs2762934, CYP24A1 rs6068816, CYP20A1 rs2043449 polymorphism with LC risk appeared stronger in some subgroups. CYP2D6, CYP24A1 and CYP20A1 are overexpressed in some pathological types of LC (P < 0.05), and high levels of CYP2D6 and CYP20A1 indicate poor and good prognosis of LC, respectively. Conclusion This study revealed that rs1065852, rs2043449, rs2762s934, and rs6068816 of CYPs were associated with LC susceptibility in the Northwestern Chinese Han population; CYP2D6 and CYP20A1 were overexpressed and correlated with prognosis of LC

Effects of Adult Male Circumcision on Premature Ejaculation: Results from a Prospective Study in China

The purpose of this study is to investigate the effects of adult male circumcision on premature ejaculation (PE). Therefore, between December 2009 and March 2014, a total of 575 circumcised men and 623 uncircumcised men (control group) were evaluated. Detailed evaluations (including circumcision and control groups) on PE were conducted before circumcision and at the 3-, 6-, 9-, and 12-month follow-up visits after circumcision. Self-estimated intravaginal ejaculatory latency time (IELT), Patient-Reported Outcome measures, and 5-item version of the International Index of Erectile Function were used to measure the ejaculatory and erectile function for all subjects. The results showed that, during the one-year follow-up, men after circumcision experienced higher IELT and better scores of control over ejaculation, satisfaction with sexual intercourse, and severity of PE than men before circumcision (P<0.001 for all). Similarly, when compared with the control group, the circumcised men reported significantly improved IELT, control over ejaculation, and satisfaction with sexual intercourse (P<0.001 for all). These findings suggested that circumcision might have positive effects on IELT, ejaculatory control, sexual satisfaction, and PE severity. In addition, circumcision was significantly associated with the development of PE