(E)-N-{(E)-2-[(3,5-Dimethylbiphenyl-4-yl)imino]­acenaphthen-1-yl­idene}-2,6-di­methyl-4-phenyl­aniline

The title compound, C40H32N2, has crystallographic twofold rotation symmetry, with two C atoms lying on the axis. The dihedral angle between the two benzene rings of the 4-phenyl-2,6-dimethyl­phenyl group is 35.74 (17)°. The acenaphthene ring makes an angle of 76.93 (11)° with the benzene ring bonded to the N atom and an angle of 41.53 (13)° with the other benzene ring

U-Shaped Relationship Between Functional Outcome and Serum Uric Acid in Ischemic Stroke

Background/Aims: We sought to assess a consecutive number of patients with first-ever acute ischemic stroke (AIS), the clinical relevance in regard to functional outcome of the serum uric acid (SUA) measured at admission. Methods: In 2 prospective centers for observational study, serum concentrations of SUA were measured on admission in the serum of 710 consecutive patients with AIS. SUA concentrations were determined by high-performance liquid chromatography. SUA, NIH stroke scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcome within 3 months. Results: During the follow-up, an unfavorable functional outcome (defined as a mRS score > 2) was found in 219 (30.8%) patients. The unfavorable functional outcome distribution across the SUA quartiles ranged between 12.4% (third quartile) and 50.6% (first quartile). After adjusting for all other significant outcome predictors, SUA concentration remained an independent unfavorable outcome predictor with an adjusted OR of 0.996 (95% CI, 0.993-0.998; P< 0.001). Conclusions: The data show that the U-shaped nature of the exposure-risk relationship was more prominent when the data were assessed in deciles (based on the SUA values). This model predicted the lowest relative risk of unfavorable outcome in the 67th percentile (corresponding to 309 µmol/L). SUA was significantly associated with the risk of poor functional outcomes in Chinese patients with stroke

Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon’s antitumor activity based on our present study

Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort

Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, could reflect dynamic molecular changes. We evaluated the utility of ctDNA as a predictive and a prognostic marker in disease monitoring of advanced non-small cell lung cancer (NSCLC) patients.Methods: This is a multicenter prospective cohort study. We performed capture-based ultra-deep sequencing on longitudinal plasma samples utilizing a panel consisting of 168 NSCLC-related genes on 949 advanced NSCLC patients with driver mutations to monitor treatment responses and disease progression. The correlations between ctDNA and progression-free survival (PFS)/overall survival (OS) were performed on 248 patients undergoing various treatments with the minimum of 2 ctDNA tests.Results: The results of this study revealed that higher ctDNA abundance (P=0.012) and mutation count (P=8.5x10(-4)) at baseline are associated with shorter OS. We also found that patients with ctDNA clearance, not just driver mutation clearance, at any point during the course of treatment were associated with longer PFS (P=2.2x10(-1)6, HR 0.28) and OS (P=4.5x10(-6), HR 0.19) regardless of type of treatment and evaluation schedule.Conclusions: This prospective real-world study shows that ctDNA clearance during treatment may serve as predictive and prognostic marker across a wide spectrum of treatment regimens

Progesterone inhibits the migration and invasion of A549 lung cancer cells through membrane progesterone receptor α-mediated mechanisms

Lung cancer is the leading cause of cancer morbidity and mortality in the world. The incidence of lung cancer, particularly lung adenocarcinoma, is increasing in women compared to men. The role of sex hormones in the development of lung cancer has attracted substantial interest, but remains largely unknown. In this study, we demonstrated that membrane progesterone receptor α (mPRα) was expressed in a lung adenocarcinoma cell line, A549, and was located on the cell membrane. In additional experiments, we found that mPRα functioned as an essential mediator for progesterone (P4)-induced inhibitory effects on cell migration and invasion of A549 cells. Furthermore, PP1 (an Src pathway inhibitor), when co-incubated with P4, synchronously enhanced the inhibitory effects of P4 on cell migration and invasion. To explore the mechanisms of inhibition, we found that P4 and PP1 induced a cascade of molecular signaling events, such as dephosphorylation of focal adhesion kinase (FAK) and downregulation of matrix metalloproteinase 9 (MMP-9). Our study provides a mechanistic view on the effects of P4 through mPRα→Src/FAK relevant pathways in human lung adenocarcinoma cells and may aid in the development of novel therapeutic tools for the treatment of lung cancer

(A review of the research on the unsafe behavior of construction workers)

In order to make a systematical sort on the research system and explore the future research direction of construction worker's safety behavior, the present paper summarizes the related field journals, publishing date, author's country and the theme of the articles from 189 literatures, published from 1997 to 2016. Research shows that the domestic and foreign research on unsafe behavior of construction workers mainly concentrated in 7 journals, and the number of literature showed an increasing trend in recent years, the overall number increased at an annual rate of 20%. In addition, the number of the first author in developed countries are significantly higher than the developing countries and regions. The topics of present related articles are primarily around four aspects consisting of unsafe behavior interest subject, unsafe behavior influence factor analysis, unsafe behavior control management, unsafe behavior relationship variables. Furthermore, there also exists vacancy of present studies, such as unsafe behavior management from the group and environment perspective, mechanism of individual unsafe behavior, simulation of unsafe behavior

Lipidomics Revealed Aberrant Metabolism of Lipids Including FAHFAs in Renal Tissue in the Progression of Lupus Nephritis in a Murine Model

Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr mice in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the mice were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time