Do environmental violations affect corporate loan financing? Evidence from China

This article reports an empirical study suggesting that environmental violations generally have a negative influence on the level of loans that the violating firms hold in China and that after a violation announcement involving waste water discharge, firms are forced to take secured loans. These effects are found to be mitigated for state-owned firms and the media coverage of a certain violation event has a negative effect on the level of loans that firms obtain. Our work presents the evidence of a penalty mechanism in the credit market that fines firms for their environmental violations in a transition economy, and has some implications for business management and governmental policy.     

高糖通过诱导HT22细胞衰老和凋亡抑制细胞生长

目的探讨高糖(High glucose,HG)对小鼠海马神经元细胞HT22细胞的生长抑制作用,分析其是否通过HG诱导细胞衰老以及凋亡而实现。方法采用台盼蓝染色计数法检测细胞生长状况并绘制生长曲线,β-半乳糖苷酶(Senescence associated acidic-β-galactosidas,SA-β-Gal)染色法检测衰老的HT22细胞,Hoechst 33258染色法检测HT22细胞凋亡形态。结果(1)HG(13.5、27、40.5mg/ml,48h)能显著抑制HT22细胞生长(P0.05,P0.01);(2)HG(13.5、27、40.5mg/ml)处理48h可明显诱导SA-β-Gal染色阳性率增加(P0.001);(3)HG(13.5、27、40.5mg/ml,48h)能诱导HT22细胞发生凋亡(P0.001),且呈浓度依赖性。结论 HG可通过诱导HT22细胞衰老和凋亡而抑制HT22细胞生长。     

Cucurbitacin I Induces Protective Autophagy in Glioblastoma in Vitro and in Vivo

There is an urgent need for new therapeutic avenues to improve the outcome of patients with glioblastoma multiforme (GBM). Current studies have suggested that cucurbitacin I, a natural selective inhibitor of JAK2/STAT3, has a potent anticancer effect on a variety of cancer cell types. This study showed that autophagy and apoptosis were induced by cucurbitacin I. Exposure of GBM cells to cucurbitacin I resulted in pronounced apoptotic cell death through activating bcl-2 family proteins. Cells treatment with cucurbitacin I up-regulated Beclin 1 and triggered autophagosome formation and accumulation as well as conversion of LC3I to LC3II. Activation of the AMP-activated protein kinase/mammalian target of rapamycin/p70S6K pathway, but not the PI3K/AKT pathway, occurred in autophagy induced by cucurbitacin I, which was accompanied by decreased hypoxia-inducible factor 1α. Stable overexpression of hypoxia-inducible factor 1α induced by FG-4497 prevented cucurbitacin I-induced autophagy and down-regulation of bcl-2. Knockdown of beclin 1 or treatment with the autophagy inhibitor 3-methyladenine also inhibited autophagy induced by cucurbitacin I. A coimmunoprecipitation assay showed that the interaction of Bcl-2 and Beclin 1/hVps34 decreased markedly in cells treated with cucurbitacin I. Furthermore, knockdown of beclin 1 or treatment with the lysosome inhibitor chloroquine sensitized cancer cells to cucurbitacin I-induced apoptosis. Finally, a xenograft model provided additional evidence for the occurrence of cucurbitacin I-induced apoptosis and autophagy in vitro. Our findings provide new insights into the molecular mechanisms underlying cucurbitacin I-mediated GBM cell death and may provide an efficacious therapy for patients harboring GBM.     

eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells

ObjectiveWe investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs).MethodsCortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.ResultsMdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.ConclusionseEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.     

混合菌群发酵秸秆合成菌体蛋白及其动力学分析

混合菌群发酵秸秆可有效提高秸秆纤维的降解率及菌体蛋白的转化率,对拓广蛋白饲料来源、减少环境污染起到积极的作用。本研究以小麦秸秆为原料,在纤维素酶水解预处理的基础上,以米曲霉作为先导菌,进一步分解残留的粗纤维,为后期发酵提供充足的碳源。根据不同微生物的代谢特征和协同机理,试验确定了发酵阶段混合菌群的组成为:米曲霉、产朊假丝酵母和枯草芽胞杆菌;接种顺序为:先接种米曲霉,再接种产朊假丝酵母,最后接种枯草芽胞杆菌。正交试验表明,影响发酵主要因素的主次顺序为:秸秆与麸皮配比>接种比例>发酵时间>接种量>发酵温度;发酵的最适条件为:米曲霉的接种量2.5%,发酵12h后接入5%的产朊假丝酵母,继续发酵8h后接入2.5%的枯草芽胞杆菌,发酵温度为28℃,秸秆与麸皮的配比为4∶1,尿素添加量为1.2%;结合动力学分析,将混合菌群的发酵时间优化为35h,发酵产物中粗蛋白含量由原来的5.47%提高到25%左右。对最适发酵条件下的动力学过程进行了探讨,建立了以Logistic方程为基础的数学模型和动力学方程。本研究表明,混合菌群发酵秸秆提高了发酵产物中的粗蛋白含量。动力学分析对于了解发酵机理、掌握整个发酵过程中混合菌群生长的动态变化、优化发酵工艺具有重要的指导意义。     

The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain metastasis in patients with non-small cell lung cancer

Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (BM) in NSCLC patients. We genotyped 16 single nucleotide polymorphisms (SNPs) in 7 autophagy-related (ATG) genes (ATG3, ATG5, ATG7, ATG10, ATG12, ATG16L1, and MAP1LC3/LC3) by using DNA from blood samples of 323 NSCLC patients. Further, we evaluated the potential associations of these genes with subsequent BM development. Lung cancer cell lines stably transfected with ATG16L1: rs2241880 (T300A) were established. Mouse models of brain metastasis were developed using cells transfected with ATG16L1–300T or ATG16L1–300A. ATG10: rs10036653 and ATG16L1: rs2241880 were significantly associated with a decreased risk of BM (respective hazard ratios [HRs]=0.596, 95% confidence interval [CI] 0.398–0.894, P = 0.012; and HR = 0. 655, 95% CI 0.438–0.978, P = 0.039, respectively). ATG12: rs26532 was significantly associated with an increased risk of BM (HR=1.644, 95% CI 1.049–2.576, P = 0.030). Invasion and migration assays indicated that transfection with ATG16L1–300T (vs. 300A) stimulated the migration of A549 cells. An in vivo metastasis assay revealed that transfection with ATG16L1–300T (vs. 300A) significantly increased brain metastasis. Our results indicate that genetic variations in autophagy-related genes can predict BM and that genome analysis would facilitate stratification of patients for BM prevention trials.     

JSI-124 Suppresses Invasion and Angiogenesis of Glioblastoma Cells In Vitro

Glioblastoma multiforme (GBM) is one of the utmost malignant tumors. Excessive angiogenesis and invasiveness are the major reasons for their uncontrolled growth and resistance toward conventional strategies resulting in poor prognosis. In this study, we found that low-dose JSI-124 reduced invasiveness and tumorigenicity of GBM cells. JSI-124 effectively inhibited VEGF expression in GBM cells. In a coculture study, JSI-124 completely prevented U87MG cell–mediated capillary formation of HUVECs and the migration of HUVECs when cultured alone or cocultured with U87MG cells. Furthermore, JSI-124 inhibited VEGF-induced cell proliferation, motility, invasion and the formation of capillary-like structures in HUVECs in a dose-dependent manner. JSI-124 suppressed VEGF-induced p-VEGFR2 activity through STAT3 signaling cascade in HUVECs. Immunohistochemistry analysis showed that the expression of CD34, Ki67, p-STAT3 and p-VEGFR2 protein in xenografts was remarkably decreased. Taken together, our findings provide the first evidence that JSI-124 effectively inhibits tumor angiogenesis and invasion, which might be a viable drug in anti-angiogenesis and anti-invasion therapies.     

A Postspinel Anode Enabling Sodium‐Ion Ultralong Cycling and Superfast Transport via 1D Channels

Sodium‐ion batteries are intensively investigated for large‐scale energy storage due to the favorable sodium availability. However, the anode materials have encountered numerous problems, such as insufficient cycling performance, dissatisfactory capacity, and low safety. Here, a novel post‐spinel anode material, i.e., single‐crystalline NaVSnO₄, is presented with the confined 1D channels and the shortest diffusion path. This material delivers an ultra long cycling life (84% capacity retention after 10 000 cycles), a high discharging capacity (163 mA h g^?1), and a safe average potential of 0.84 V. Results indicate that the post‐spinel structure is well maintained over 10 000 cycles, surprisingly, with 0.9% volume change, the Sn⁴⁺/Sn²⁺ based redox enables two sodium ions for reversible release and uptake, and the diffusion coefficient of sodium ions is characterized by 1.26 × 10^?11 cm² s^?1. The findings of this study provide a new insight into design of new frameworks with polyelectronic transfers for full performance electrode materials of sodium‐ion batteries.     

EMAP-II sensitize U87MG and glioma stem-like cells to temozolomide via induction of autophagy-mediated cell death and G2/M arrest

Despite the fact that temozolomide (TMZ) has been widely accepted as the key chemotherapeutic agent to prolong the survival of patients with glioblastoma, failure and recurrence cases can still be observed in clinics. Glioma stem-like cells (GSCs) are thought to be responsible for the drug resistance. In this study, we investigate whether endothelial monocyte-activating polypeptide-II (EMAP-II), a pro-inflammatory cytokine, can enhance TMZ cytotoxicity on U87MG and GSCs or not. As described in prior research, GSCs have been isolated from U87MG and maintained in the serum-free DMEM/F12 medium containing EGF, b-FGF, and B27. TMZ and/or EMAP-II administration were performed for 72 h, respectively. The results showed that TMZ combined with EMAP-II inhibit the proliferation of U87MG and GSCs by a larger measure than TMZ single treatment by decreasing the IC₅₀. EMAP-II also enhanced TMZ-induced autophagy-mediated cell death and G2/M arrest. Moreover, we found that EMAP-II functioned a targeted suppression on mTOR, which may involve in the anti-neoplasm mechanism. The results suggest that EMAP-II could be considered as a combined chemotherapeutic agent against glioblastoma by sensitizing U87MG and GSCs to TMZ.