BackgroundReprogrammed energy metabolism as an emerging hallmark of cancer has recently drawn special attention since it facilitate cell growth and proliferation. Recently, long noncoding RNAs (lncRNAs) have been served as key regulators implicated in tumor development and progression by promoting proliferation, invasion and metastasis. However, the associations of lncRNAs with cellular energy metabolism in lung cancer (LC) need to be clarified.MethodsHere, we conducted bioinformatics analysis and found insulin-like growth factor binding protein 4–1 (IGFBP4–1) as a new candidate lncRNA located in the upstream region of IGFBP4 gene. The expression levels of lnc-IGFBP4–1, mRNA levels of IGFBP4 in 159 paired lung cancer samples and adjacent, histological normal tissues by qRT-PCR. Over-expression and RNA interference (RNAi) approaches were adopted to investigate the biological functions of lnc-IGFBP4–1. The intracellular ATP level was measured using the Cell Titer-Glo Luminescent Cell Viability Assay kit, and changes in metabolic enzymes were examined in cancer cells and normal pulmonary epithelial cells with qRT-PCR.ResultsOur results showed that lnc-IGFBP4–1 was significantly up-regulated in LC tissues compared with corresponding non-tumor tissues (P < 0.01), and its expression level was significantly correlated with TNM stage (P < 0.01) and lymph node metastasis (P < 0.05). Further investigation showed that overexpression of lnc-IGFBP4–1 significantly promoted LC cell proliferation in vitro and in vivo, while downregulation of endogenous lnc-IGFBP4–1 could inhibited cell proliferation and induce apoptosis. Moreover, we found lnc-IGFBP4–1 could influences ATP production levels and expression of enzymes including HK2, PDK1 and LDHA, in addition, decline in both ATP production and these enzymes in response to 2-DG and 2-DG-combined Rho123, respectively, was observed in lnc-IGFBP4–1-overespressing LC cells, indicative of an enhanced aerobic glycolysis rate. Finally, lnc-IGFBP4–1 was observed to negatively correlate with gene IGFBP4, and lower expression level of IGFPB4 was found after lnc-IGFBP4–1-overexpression was transfected into PC9 cells, higher expression level of IGFPB4 was also found after lnc-IGFBP4–1-downregulation was transfected into GLC-82 cells, which indicates that IGFBP4 may exert its targeting function regulated by lnc-IGFBP4–1.ConclusionsTaken together, these findings provide the first evidence that lnc-IGFBP4–1 is significantly up-regulated in LC tissues and plays a positive role in cell proliferation and metastasis through possible mechanism of reprogramming tumor cell energy metabolism, which suggests that lnc-IGFBP4–1 may be a promising biomarker in LC development and progression and as a potential therapeutic target for LC intervention.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0722-8) contains supplementary material, which is available to authorized users.

BackgroundRadiation brain necrosis (RBN) is a serious complication in patients receiving radiotherapy for intracranial disease. Many studies have investigated the efficacy and safety of bevacizumab in patients with RBN. In the present study, we systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab, as well as for studies comparing bevacizumab with corticosteroids.Materials and MethodsWe searched PubMed, Cochrane library, EMBASE, and ClinicalTrials.gov from their inception through 1 March, 2020 for studies that evaluated the efficacy and safety of bevacizumab in patients with RBN. Two investigators independently performed the study selection, data extraction, and data synthesis.ResultsOverall, the present systematic review included 12 studies (eight retrospective, two prospective, and two randomized control trials [RCTs]) involving 236 patients with RBN treated who were treated with bevacizumab. The two RCTs also had control arms comprising patients with RBN who were treated with corticosteroids/placebo (n=57). Radiographic responses were recorded in 84.7% (200/236) of patients, and radiographic progression was observed in 15.3% (36/236). Clinical improvement was observed in 91% (n=127) of responding patients among seven studies (n=113). All 12 studies reported volume reduction on T1 gadolinium enhancement MRI (median: 50%, range: 26%–80%) and/or T2 FLAIR MRI images (median: 59%, range: 48%–74%). In total, 46 responding patients (34%) had recurrence. The two RCTs revealed significantly improved radiographic response in patients treated with bevacizumab (Levin et al.: p = 0.0013; Xu et al.: p &lt; 0.001). Both also showed clinical improvement (Levin et al.: NA; Xu et al.: p = 0.039) and significant reduction in edema volume on both T1 gadolinium enhancement MRI (Levin et al.: p=0.0058; Xu et al.: p=0.027) and T2 FLAIR MRI (Levin et al.: p=0.0149; Xu et al.: p &lt; 0.001). Neurocognitive improvement was significantly better after 2 months of treatment in patients receiving bevacizumab than in those given corticosteroids, as assessed by the MoCA scale (p = 0.028). The recurrence rate and side effects of the treatments showed no significant differences.ConclusionsPatients with RBN respond to bevacizumab, which can improve clinical outcomes and cognitive function. Bevacizumab appears to be more efficacious than corticosteroid-based treatment. The safety profile was comparable to that of the corticosteroids.

BackgroundConsiderable controversy exists regarding the association between dietary calcium intake and risk of mortality from cardiovascular disease and all causes. Therefore, we performed a meta-analysis of prospective cohort studies to examine the controversy.MethodsWe identified relevant studies by searching MEDLINE, Embase, and the Cochrane Library databases between 1 September 2013 and 30 December 2013. Reference lists of relevant articles were also reviewed. Observational prospective studies that reported relative risks and 95% confidence intervals for the association of calcium intake with cardiovascular and all-cause mortality were eligible. Study-specific relative risks were pooled using a random-effects model.ResultsIn this meta-analysis, 11 prospective studies with 12 independent cohorts, involving 757,304 participants, were eligible. There was evidence of a non-linear association between dietary calcium intake and risk of mortality from cardiovascular disease (P for non-linearity <0.01) and all causes (P for non-linearity <0.01). A dose-response analysis showed a U-shaped relationship between dietary calcium intake and cardiovascular mortality. Intakes that were lower and higher than around 800 mg/day were gradually associated with a higher risk of cardiovascular mortality. For all-cause mortality, we also observed a threshold effect at intakes around 900 mg/day. The risk of all-cause mortality did not decrease further at intakes above 900 mg/day.ConclusionsThis meta-analysis of prospective cohort studies suggests that dietary calcium intake is associated with cardiovascular mortality in a U-shaped manner and that high dietary calcium intake (>900 mg/day) is not associated with a decreased risk of all-cause mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0158-6) contains supplementary material, which is available to authorized users.

We perform Raman spectroscopy studies on α-RuCl3 at room temperature to explore its phase transitions of magnetism and chemical bonding under pressures. The Raman measurements resolve two critical pressures, about p1 = 1.1 GPa and p2 = 1.7 GPa, involving very different intertwining behaviors between the structural and magnetic excitations. With increasing pressures, a stacking order phase transition of α-RuCl3 layers develops at p1 = 1.1 GPa, indicated by the new Raman phonon modes and the modest Raman magnetic susceptibility adjustment. The abnormal softening and splitting of the Ru in-plane Raman mode provide direct evidence of the in-plane dimerization of the Ru-Ru bonds at p2 = 1.7 GPa. The Raman susceptibility is greatly enhanced with pressure increasing and sharply suppressed after the dimerization. We propose that the system undergoes Mott collapse at p2 = 1.7 GPa and turns into a dimerized correlated band insulator. Our studies demonstrate competitions between Kitaev physics, magnetism, and chemical bondings in Kitaev compounds.arXiv:1807.08211v1 [cond-mat.str-el]

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Bisphenol-A (BPA), one of endocrine-disrupting chemicals, is a male reproductive toxicant. Previous studies have revealed the direct cytotoxicity of BPA in many cultured cells, such as mitotic aneuploidy in embryonic cells and somatic cells, and apoptosis in neurons and testicular Sertoli cells. To understand the action of BPA and assess its risk, the Pten/Akt pathway was investigated in cultured Sertoli cells to elucidate the mechanism of the reproductive effects of BPA. The results showed that over 50 μM BPA treatment could decrease the viability of Sertoli cells and cause more apoptosis. In addition, BPA could induce the increase in mRNA levels of Pten and Akt. The protein level of Pten was increased; however, the protein levels of phospho-Akt and procaspase-3 were decreased after BPA exposure. Taken together, observed results suggested that the Pten/Akt pathway might be involved in the apoptotic effects of BPA on Sertoli cells.

Psycholinguistic research has long established that focus-marked words have a processing advantage over other words in an utterance, e.g., they are recognized more quickly and remembered better. More recently, studies have shown that listeners infer contextual alternatives to a focused word in a spoken utterance, when marked with a contrastive accent, even when the alternatives are not explicitly mentioned in the discourse. This has been shown by strengthened priming of contextual alternatives to the word, but not other non-contrastive semantic associates, when it is contrastively accented, e.g., after hearing “The customer opened the window," salesman is strongly primed, but not product . This is consistent with Rooth's ( 1992 ) theory that focus-marking signals the presence of alternatives to the focus. However, almost all of the research carried out in this area has been on Germanic languages. Further, most of this work has looked only at one kind of focus-marking, by contrastive accenting (prosody). This paper reports on a cross-modal lexical priming study in Mandarin Chinese, looking at whether focus-marking heightens activation, i.e., priming, of words and their alternatives. Two kinds of focus-marking were investigated: prosodic and syntactic. Prosodic prominence is an important means of focus-marking in Chinese, however, it is realized through pitch range expansion, rather than accenting. The results showed that focused words, as well as their alternatives, were primed when the subject prime word carried contrastive prosodic prominence. Syntactic focus-marking, however, did not enhance priming of focused words or their alternatives. Non-contrastive semantic associates were not primed with either kind of focus-marking. These results extend previous findings on focus and alternative priming for the first time to Chinese. They also suggest that the processing advantages of focus, including priming alternatives, are particularly related to prosodic prominence, at least in Chinese and Germanic languages. This research sheds light on what linguistic mechanisms listeners use to identify important information, generate alternatives, and understand implicature necessary for successful communication.

To control vibration-induced white finger among workers performing the fine grinding of golf club heads, the aims of this study are to clarify the major vibration sources in the grinding process, to identify and understand the basic characteristics of the club head vibration, and to propose potential approaches for reducing the vibration exposure. The vibrations on two typical club heads and two belt grinding machines were measured at a workplace. A simulated test station was also constructed and used to help examine some influencing factors of the club head vibration. This study found that the club head vibration was the combination of the vibration transmitted from the grinding machines and that generated in the grinding process. As a result, any factor that affects the machine vibration, the grinding vibration, and/or the dynamic response of the club head can influence the vibration exposure of the fingers or hands holding the club head in the grinding process. The significant influencing factors identified in the study include testing subject, grinding machine, machine operation speed, drive wheel condition, club head model, mechanical constraints imposed on the club head during the grinding, and machine foot pad. These findings suggest that the vibration exposure can be controlled by reducing the grinding machine vibration, changing the workpiece dynamic properties, and mitigating the vibration transmission in its pathway. Many potential methods for the control are proposed and discussed. Relevance to industry: Vibrations on handheld workpieces can be effectively transmitted to the hands, especially the fingers. As a result, a major component of the hand-arm vibration syndrome - vibration-induced white finger - has been observed among some workers performing the grinding and/or polishing tasks of the handheld workpieces such as golf club heads. The results of this study can be used to develop more effective methods and technologies to control the vibration exposure of these workers. This may help effectively control this occupational disease.