LncRNA GAS5 Modulates the Progression of Glioma Through Repressing miR-135b-5p and Upregulating APC.

Purpose: The main purpose of this paper is to explore the interaction between GAS5 and miR-135b-5p to understand their function in the metastasis, invasion, and proliferation of glioma. This may provide new ideas for the pathogenesis and treatment of glioma. Patients and Methods: Western blotting assays and RT­qPCR were employed to investigate the expression of related genes in glioma tissues or cell lines. CCK-8 was used to examine the impact of GAS5 on cell viability. Motile activities were adopted by the transwell and wound healing experiments. A double luciferase experiment was performed to elucidate transcriptional regulation. Results: GAS5 showed low expression in glioma cells and tissues, and up-regulation of GAS5 could depress the invasion, proliferation, and metastasis of glioma. GAS5 negatively regulates miR-135b-5p, which can counteract the cellular effects caused by GAS5. APC was the target of miR-135b-5p, and GAS5 can regulate the expression of APC by sponging miR-135b-5p. APC overexpression reversed the effects of miR-135b-5p promotion on glioma cells, while miR-135b-5p has the opposite function. As a downstream target gene of GAS5, miR-135b-5p was negatively regulated by GAS5. The restoration of miR-135b-5p can remarkably reverse the impact of GAS5 on glioma cells. In addition, GAS5 increased the expression of APC in glioma cells by inhibiting miR-135b-5p. Conclusion: GAS5 increased APC expression by restraining miR-135b-5p and partially blocked the progression of glioma, suggesting that it could be an advantageous therapeutic target for glioma intervention.

Will economic development come at the cost of environmental pollution under fiscal pressure? evidence from resource-based cities in China.

The traditional view is that local governments are inclined to ease environmental regulations in response to fiscal pressure (FP) and alleviate FP by sacrificing the environment for economic development (ED). This paper takes Chinese Mainland resource-based cities (RBC) as the research sample but draws different conclusions. The research results are as follows: firstly, for RBC, although FP reduces environmental pollution (EP), it is not conducive to ED. Compared with non-resource-based cities (NRBC), the economic negative effect of FP in RBC is more obvious. Secondly, FP is detrimental to ED by reducing EP, and RBC have not sacrificed the environment to promote ED in the context of FP. This paper summarizes that the development path of RBC should be "optimizing government behavior → increasing FP → improving environmental quality → reducing ED level." Thirdly, the impact of FP on cities with slower economic growth and smaller economic gap is greater, and the impact of FP on cities with better environment is more obvious. This paper argues that facing FP, RBC in China will not trade EP for ED; at the same time, we suggest RBC in other countries in the face of the FP, not only thinking of promoting ED at the expense of the EP and ease the FP, but also the development of green ecological requirement, overall consideration of the relationship between EP and ED, and then achieve green and sustainable ED without degrading the environment as far as possible.

A study on the spatio-temporal evolutionary characteristics of OFDI in Chinese private enterprises and its influencing factors.

In the context of China's increasing openness to the global market, outward foreign direct investment (OFDI) has become an effective strategy for expanding overseas markets, and private enterprises have played a crucial role in driving China's economic development. This study utilizes data from the NK-GERC database of Nankai University to conduct a spatio-temporal analysis of the dynamic changes in OFDI by Chinese private enterprises from 2005 to 2020. The findings indicate that Chinese domestic private enterprises' OFDI exhibits a strong spatial pattern in the eastern regions and a weak one in the western regions. The main active investment regions include the Bohai Rim, Yangtze River Delta, and Pearl River Delta. Regarding destination countries for OFDI, traditional developed European economies such as Germany and the USA remain popular choices, but countries along the "Belt and Road" have become hotspots for investment. Non-manufacturing industries account for a higher proportion of investments, with private enterprises showing a preference for investing in foreign enterprises in the service sector. From a sustainable development perspective, the study finds that environmental factors play a significant role in the development of Chinese private enterprises. Moreover, the negative impact mechanism of environmental pollution on private enterprises' OFDI varies according to the enterprises' geographical location and time period. The negative effect is more significant in coastal areas and eastern regions compared to central and western regions, with the most significant impact observed from 2011 to 2015, followed by 2005 to 2010, and the weakest impact seen from 2016 to 2019. As China's ecological environment continues to improve, the negative impact of environmental pollution on enterprises gradually decreases, contributing to the improvement of the sustainability of private enterprises.

Downregulation of TET1 Promotes Glioma Cell Proliferation and Invasion by Targeting Wnt/ß-Catenin Pathway.

Glioma is the most common malignant tumor in adult brain characteristic with poor prognosis and low survival rate. Despite the application of advanced surgery, chemotherapy, and radiotherapy, the patients with glioma suffer poor treatment effects due to the complex molecular mechanisms of pathological process. In this paper, we conducted the experiments to prove the critical roles TET1 played in glioma and explored the downstream targets of TET1 in order to provide a novel theoretical basis for clinical glioma therapy. RT-qPCR was adopted to detect the RNA level of TET1 and ß-catenin; Western blot was taken to determine the expression of proteins. CCK8 assay was used to detect the proliferation of glioma cells. Flow cytometry was used to test cell apoptosis and distribution of cell cycle. To detect the migration and invasion of glioma cells, wound healing assay and Transwell were performed. It was found that downregulation of TET1 could promote the proliferation migration and invasion of glioma cells and the concomitant upregulation of ß-catenin, and its downstream targets like cyclinD1 and c-myc were observed. The further rescue experiments were performed, wherein downregulation of ß-catenin markedly decreases glioma cell proliferation in vitro and in vivo. This study confirmed the tumor suppressive function of TET1 and illustrated the underlying molecular mechanisms regulated by TET1 in glioma.

Infarct volume and outcome of cerebral ischaemia, a systematic review and meta-analysis.

BACKGROUND: Multiple studies have evaluated the accuracy of infarct volume (IV) as a predictor of outcome in patients with ischaemic stroke; however, no study has systematically reviewed the results of these studies. AIM: This systematic review and meta-analysis aim to sum up the results of the studies evaluating IV as the prognostic criteria for patients with cerebral ischaemia. METHODS: Human studies that reported the infarction volume and any prognostic outcome in patients with ischaemic stroke were collected from PubMed, Scopus, Embase and Cochrane library databases. Newcastle-Ottawa Quality Assessment Checklist was applied to evaluate the quality of the included articles. 90-day modified Rankin Scale (mRS) score was used as a meta-analysis outcome. The area under the curve, sensitivity and specificity among included studies was evaluated. The heterogeneity of the studies was assessed by Cochran test Egger and Begg test was used for assessing publication bias. RESULTS: Among the included studies, nine studies assessed the association between IV and outcome (90-day mRS score). The results of the meta-analysis revealed a significant association between IV with the unfavourable functional outcome (mRS score of 3-6) (OR = 0.80; 95% CI: 0.74-0.86 per 10 mL, P < .001; I2  = 98.1%, P < .001). The infarction volume cut of point between 20 and 50 mL showed the best sensitivity and specificity for the prediction of poor clinical outcomes in patients with ischaemic stroke. CONCLUSION: The results of the meta-analysis revealed a significant association between IV and unfavourable functional outcomes in patients with ischaemic stroke.

Hematoma Ventricle Distance on Computed Tomography Predicts Poor Outcome in Intracerebral Hemorrhage.

OBJECTIVE: To investigate the relationship between hematoma ventricle distance (HVD) and clinical outcome in patients with intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled consecutive patients with ICH in a tertiary academic hospital between July 2011 and April 2018. We retrospectively reviewed images for all patients receiving a computed tomography (CT) within 6 h after onset of symptoms and at least one follow-up CT scan within 36 h. The minimum distance of hematoma border to nearest ventricle was measured as HVD. Youden index was used to evaluate the cutoff of HVD predicting functional outcome. Logistic regression model was used to assess the HVD data and clinical poor outcome (modified Rankin Scale 4-6) at 90 days. RESULTS: A total of 325 patients were included in our final analysis. The median HVD was 2.4 mm (interquartile range, 0-5.7 mm), and 119 (36.6%) patients had poor functional outcome at 3 months. After adjusting for age, admission Glasgow coma scale, intraventricular hemorrhage, baseline ICH volume, admission systolic blood pressure, blood glucose, hematoma expansion, withdrawal of care, and hypertension, HVD ≤ 2.5 mm was associated with increased odds of clinical poor outcome [odd ratio, 3.59, (95%CI = 1.72-7.50); p = 0.001] in multivariable logistic regression analysis. CONCLUSION: Hematoma ventricle distance allows physicians to quickly select and stratify patients in clinical trials and thereby serve as a novel and useful addition to predict ICH prognosis.

scAAV9-VEGF-165 inhibits neuroinflammatory responses and invasion of macrophages into the peripheral nervous system of ALS transgenic mice.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to paralysis and death within 3-5 years. Although the vast majority of studies have focused on vulnerable neurons, growing evidence has shown that non-neuronal cells contribute to the pathogenesis and disease progression. Here, we showed that intrathecal injection of scAAV9-VEGF at 60 days of age significantly reduced the number of microglia and inhibited the neuroinflammatory response in the CNS. Meanwhile, we found that administration of VEGF inhibited the invasion of macrophages into the PNS, including ventral nerve roots, sciatic nerves and muscles. Overall, our study indicated the anti-inflammation effect of VEGF in the CNS and PNS of ALS mice when delivered by intrathecal injection.

The regulating role of mutant IkappaBalpha in expression of TIMP-2 and MMP-9 in human glioblastoma multiform.

BACKGROUND: Our previous studies demonstrated that mutant IkappaBalpha (IkappaBalphaM) inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform (GBM). However, the specific mechanism by which IkappaBalphaM regulates protein-degrading enzymes secreted from GBM to inhibit invasion and metastasis has remained unclear. The aim of the present study was to investigate the regulatory role and significance of IkappaBalphaM genes in the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in human GBM. METHODS: We established the following four GBM cell lines stably expressing IkappaBalphaM by plasmid construction, gene transfection and screening for IkappaBalphaM protein expression: mutant IkappaBalpha-transfected cells (G36Delta-M), wild-type IkappaBalpha-transfected cells (G36Delta-W), empty plasmid transfected cells (G36Delta-P) and untransfected cells (G36Delta). The TIMP-2 and MMP-9 expression was detected by RT-PCR and Western blotting. Tumor cells were then implanted subcutaneously into nude mice to establish an animal model of ectopic tumor growth, and TIMP-2 and MMP-9 expression was determined by immunohistochemical methods. RESULTS: The results showed that there was a significant increase in TIMP-2 expression and a significant decrease in MMP-9 expression in the G36Delta-M group at both the RNA and protein levels compared with the G36Delta-W group, G36Delta-P group and G36Delta group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36Delta-M group, TIMP-2 expression was significantly higher while MMP-9 expression was significantly lower than in the other three groups. CONCLUSIONS: Our findings indicate that IkappaBalphaM inhibits the activation of NF-kappaB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IkappaBalphaM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues.