A Study on Self-Translation of Eileen Chang’s Little Finger Up From Perspective of Translator’s Subjectivity

Based on both English and Chinese texts, this paper, with the help of corpus software, attempts to make a detailed analysis of translator’s subjectivity as revealed in Eileen Chang’s self-translation of Little Finger Up in terms of passivity, subjective initiative and purposefulness (self-benefiting) as well. Thereupon, the paper comes to the following conclusions. First, as the self-translator, Eileen Chang brings her subjective initiate into play in the self-translation in regard to sentence structure, proper nouns, culture-specific items, manifestation of the theme and way of expressing feelings. Second, privileged as she is, Eileen Chang is affected by both ideology and poetics. She deliberately eschews the sensitively political and warlike topic by way of omission and retains the heterogeneous elements of the source culture in the process of translation, reflecting her translator’s subjectivity in the self-translation while suffering the passivity imposed by ideology and poetics. Third, Eileen Chang usually adopts various strategies in the self-translation so as to fulfill her translation purposes, in which she deliberately deletes the plots and rewrites the title so as to highlight the problem of Chinese marriage and reveal her own pessimistic attitude towards marriage, indicating her self-benefiting in self-translation. In a nutshell, the self-translation seems to be concise and comprehensive as well as natural and unrestrained, indicating that the translator’s subjectivity is much more involved in self-translation, compared with that in conventional translation

Apoptosis Induction by MEK Inhibition in Human Lung Cancer Cells Is Mediated by Bim

AZD6244 (ARRY-142886) is an inhibitor of MEK1/2 and can inhibit cell proliferation or induce apoptosis in a cell-type dependent manner. The precise molecular mechanism of AZD6244-induced apoptosis is not clear. To investigate mechanisms of AZD6244 induced apoptosis in human lung cancer, we determined the molecular changes of two subgroups of human lung cancer cell lines that are either sensitive or resistant to AZD6244 treatment. We found that AZD6244 elicited a large increase of Bim proteins and a smaller increase of PUMA and NOXA proteins, and induced cell death in sensitive lung cancer cell lines, but had no effect on other Bcl-2 related proteins in those cell lines. Knockdown of Bim by siRNA greatly increased the IC50 and reduced apoptosis for AZD6244 treated cells. We also found that levels of endogenous p-Thr32-FOXO3a and p-Ser253-FOXO3a were lower in AZD6244-sensitive cells than in AZD6244-resistant cells. In the sensitive cells, AZD6244 induced FOXO3a nuclear translocation required for Bim activation. Moreover, the silencing of FOXO3a by siRNA abrogated AZD6244-induced cell apoptosis. In addition, we found that transfection of constitutively active AKT up-regulated p-Thr32-FOXO3a and p-Ser253-FOXO3a expression and inhibited AZD6244-induced Bim expression in sensitive cells. These results show that Bim plays an important role in AZD6244-induced apoptosis in lung cancer cells and that the PI3K/AKT/FOXO3a pathway is involved in Bim regulation and susceptibility of lung cancer cells to AZD6244. These results have implications in the development of strategies to overcome resistance to MEK inhibitors

Relationships Between Social Support, Loneliness, and Internet Addiction in Chinese Postsecondary Students: A Longitudinal Cross-Lagged Analysis

Using the Internet has become one of the most popular leisure activities among postsecondary students in China. Concern about the large number of students using the Internet has led to an increase in research on the influencing factors of Internet addiction and the negative consequences caused by it. This short-term longitudinal study examined the associations among three dimensions of social support [objective support (OS), subjective support (SS), and support utilization (SU)], loneliness, and the four dimensions of Internet addiction (compulsive Internet use [CIU] & withdrawal from Internet addiction [WIA], tolerance of Internet addiction [TIA], time-management problems [TMPs], and interpersonal and health problems [IHPs]) in a Chinese sample. A total of 169 postsecondary first-year students (88 girls and 81 boys; mean age = 18.31 years) participated in the study. The questionnaire measurements were taken at the beginning of the school year (T1), 6 months later (T2), and 1 year later (T3). Cross-lagged and structural equation modeling analyses indicated that (a) OS (T1) and SU (T1) negatively predicted loneliness (T2); and loneliness (T2) negatively predicted OS (T3) and SU(T3); (b) CIU & WIA (T1) and TMPs (T1) positively predicted loneliness (T2); and loneliness (T2) positively predicted CIU & WIA (T3), TIA (T3), TMP (T3), and IHP (T3); (c) SS (T1) directly affected TIA (T3) and TMP (T3); and (d) loneliness (T2) played a mediating role in the relationships between OS (T1) and CIU (T3), OS (T1) and TMP (T3), OS (T1) and IHP (T3), and SU (T1) and IHP (T3). Finally, interventions for Internet addiction and implications for future studies were discussed

Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo

AZD6244 and MK2206 are targeted small-molecule drugs that inhibit MEK and AKT respectively. The efficacy of this combination in lung cancer is unknown. Our previous work showed the importance of activated AKT in mediating resistance of non-small cell lung cancer (NSCLC) to AZD6244. Thus we hypothesized that dual inhibition of both downstream MEK and AKT pathways would induce synergistic antitumor activity. In this study, we evaluated the efficacy of AZD6244 and MK2206 individually on a large panel of lung cancer cell lines. Then, we treated 28 human lung cancer cell lines with a combination of AZD6244 and MK2206 at clinically applicable drug molar ratios. The AZD6244-MK2206 combination therapy resulted in a synergistic effect on inhibition of lung cancer cell growth compared to the results of single drug treatment alone. MK2206 enhanced AZD6244-induced Bim overexpression and apoptosis in A549 and H157 cells. When we tested the combination of AZD6244 and MK2206 at ratios of 8∶1, 4∶1, 2∶1, and 1∶8, we found that the synergistic effect of the combination therapy was ratio-dependent. At ratios of 8∶1, 4∶1, and 2∶1, the drug combination consistently demonstrated synergy, whereas decreasing the ratio to 1∶8 resulted in a loss of synergy and produced an additive or antagonistic effect in most cell lines. Furthermore, the AZD6244-MK2206 combination therapy showed synergy in the suppression of A549 and H157 xenograft tumor growth and increased mean animal survival time. The AZD6244-MK2206 combination therapy resulted in effective inhibition of both p-ERK and p-AKT expression in tumor tissue. In addition, a significant increase of apoptosis was detected in tumor tissue from mice treated with AZD6244-MK2206 compared with that from the single agent treated mice. Our study suggests that the combination of AZD6244 and MK2206 has a significant synergistic effect on tumor growth in vitro and in vivo and leads to increased survival rates in mice bearing highly aggressive human lung tumors

Dihydromyricetin Attenuates Diabetic Cardiomyopathy by Inhibiting Oxidative Stress, Inflammation and Necroptosis via Sirtuin 3 Activation

Dihydromyricetin (DHY), the main flavonoid component in Ampelopsis grossedentata, has important benefits for health. The present study aimed to investigate the exact effects and possible mechanisms of DHY on diabetic cardiomyopathy (DCM). Male C57BL/6 mice and sirtuin 3 (SIRT3) knockout (SIRT3-KO) mice were injected with streptozotocin (STZ) to induce a diabetic model. Two weeks later, DHY (250 mg/kg) or carboxymethylcellulose (CMC) were administrated once daily by gavage for twelve weeks. We found that DHY alleviated fasting blood glucose (FBG) and triglyceride (TG) as well as glycosylated hemoglobin (HbA1c) levels; increased fasting insulin (FINS); improved cardiac dysfunction; ameliorated myocardial hypertrophy, fibrosis and injury; suppressed oxidative stress, inflammasome and necroptosis; but improved SIRT3 expression in STZ-induced mice. Neonatal rat cardiomyocytes were pre-treated with DHY (80 μM) with or without high glucose (HG) stimulation. The results showed that DHY attenuated cell damage but improved SIRT3 expression and inhibited oxidative stress, inflammasome and necroptosis in cardiomyocytes with high glucose stimulation. Moreover, the above protective effects of DHY on DCM were unavailable in SIRT3-KO mice, implying a promising medical potential of DHY for DCM treatment. In sum, DHY improved cardiac dysfunction; ameliorated myocardial hypertrophy, fibrosis and injury; and suppressed oxidative stress, inflammation and necroptosis via SIRT3 activation in STZ-induced diabetic mice, suggesting DHY may serve as a candidate for an agent to attenuate diabetic cardiomyopathy

The tumor suppressor gene TUSC2 (FUS1) sensitizes NSCLC to the AKT inhibitor MK2206 in LKB1-dependent manner.

TUSC2-defective gene expression is detected in the majority of lung cancers and is associated with worse overall survival. We analyzed the effects of TUSC2 re-expression on tumor cell sensitivity to the AKT inhibitor, MK2206, and explored their mutual signaling connections, in vitro and in vivo. TUSC2 transient expression in three LKB1-defective non-small cell lung cancer (NSCLC) cell lines combined with MK2206 treatment resulted in increased repression of cell viability and colony formation, and increased apoptotic activity. In contrast, TUSC2 did not affect the response to MK2206 treatment for two LKB1-wild type NSCLC cell lines. In vivo, TUSC2 systemic delivery, by nanoparticle gene transfer, combined with MK2206 treatment markedly inhibited growth of tumors in a human LKB1-defective H322 lung cancer xenograft mouse model. Biochemical analysis showed that TUSC2 transient expression in LKB1-defective NSCLC cells significantly stimulated AMP-activated protein kinase (AMPK) phosphorylation and enzymatic activity. More importantly, AMPK gene knockdown abrogated TUSC2-MK2206 cooperation, as evidenced by reduced sensitivity to the combined treatment. Together, TUSC2 re-expression and MK2206 treatment was more effective in inhibiting the phosphorylation and kinase activities of AKT and mTOR proteins than either single agent alone. In conclusion, these findings support the hypothesis that TUSC2 expression status is a biological variable that potentiates MK2206 sensitivity in LKB1-defective NSCLC cells, and identifies the AMPK/AKT/mTOR signaling axis as an important regulator of this activity

pH-Responsive Graphene Oxide-Based 2D/3D Composite for Enhancing Anti-Corrosion Properties of Epoxy Coating

The functionalized graphene oxide (GO)-based composites as fillers added into organic coatings are desired for realizing the longstanding corrosion protection of carbon steel. Here, the pH-responsive two-dimensional/three-dimensional (2D/3D) GO-based composite (ZIF–90–AAP/GO) was developed by environmentally friendly corrosion inhibitor 4-aminoantipyrine (AAP) anchored on the in situ growth of zeolite imidazolate framework–90 (ZIF–90) on the GO surface (ZIF–90/GO) through the Schiff base reaction. The active filler (ZIF–90–AAP/GO) was incorporated into an epoxy coating (EP) to obtain a high-performance self-healing coating on the surface of carbon steel. ZIF–90–AAP can greatly improve dispersion and compatibility of GO in EP. The low-frequency impedance modulus of ZIF–90–AAP/GO–EP can still reach up to 1.35 × 1010 Ω⋅cm2 after 40 days, which is about three orders of magnitude higher than that of the EP containing GO (GO–EP) relying on its passive and active corrosion protection. Meanwhile, ZIF–90–AAP/GO–EP exhibits excellent self-healing performance. The self-healing rate of ZIF–90–AAP/GO changes from negative to positive after 24 h, which results from the effective corrosion inhibition activity of ZIF–90–AAP for carbon steel based on the pH-triggered controlled release of AAP. The developed pH-responsive 2D/3D GO-based composite coating is very attractive for the corrosion protection of carbon steel

Elevated estradiol levels on hCG trigger day adversely effects on the clinical pregnancy rates of blastocyst embryo transfer but not cleavage-stage embryo transfer in fresh cycles: a retrospective cohort study

Background Elevated estradiol (E2) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E2 at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles. Methods This study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E2 levels when hCG was administered: set 1 (E2 ≤ 2,000 pg/ml), set 2 (E2 = 2,001–3,000 pg/ml), set 3 (E2 = 3,001–4,000 pg/ml), and set 4 (E2 > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses. Results The multivariate regression model in the cleavage group showed that patients’ CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P = 0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P = 0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E2 levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E2 (adjusted OR = 0.83, 95% CI [0.72–0.96], P = 0.012). Conclusions Elevated E2 levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET

Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

Myocardial ischemia or hypoxia can induce myocardial fibroblast proliferation and myocardial fibrosis. Hydrogen sulfide (H2S) is a gasotransmitter with multiple physiological functions. In our present study, primary cardiac fibroblasts were incubated with H2S donor sodium hydrosulfide (NaHS, 50 μM) for 4 h followed by hypoxia stimulation (containing 5% CO2 and 1% O2) for 4 h. Then, the preventive effects on cardiac fibroblast proliferation and the possible mechanisms were investigated. Our results showed that NaHS reduced the cardiac fibroblast number, decreased the hydroxyproline content; inhibited the EdU positive ratio; and down-regulated the expressions of α-smooth muscle actin (α-SMA), the antigen identified by monoclonal antibody Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), collagen I, and collagen III, suggesting that hypoxia-induced cardiac fibroblasts proliferation was suppressed by NaHS. NaHS improved the mitochondrial membrane potential and attenuated oxidative stress, and inhibited dynamin-related protein 1 (DRP1), but enhanced optic atrophy protein 1 (OPA1) expression. NaHS down-regulated receptor interacting protein kinase 1 (RIPK1) and RIPK3 expression, suggesting that necroptosis was alleviated. NaHS increased the sirtuin 3 (SIRT3) expressions in hypoxia-induced cardiac fibroblasts. Moreover, after SIRT3 siRNA transfection, the inhibitory effects on cardiac fibroblast proliferation, oxidative stress, and necroptosis were weakened. In summary, necroptosis inhibition by exogenous H2S alleviated hypoxia-induced cardiac fibroblast proliferation via SIRT3