Osteosarcoma is the most commonly occurring bone cancer in children and adolescents. Unfortunately, treatment failures are common due to the development of chemoresistance, for which the underlying molecular mechanisms remain unclear. In this study, we implicate the DNA-binding protein HMGB1, which also exerts immunoregulatory effects in its secreted form, in the development of drug resistance in osteosarcoma. Anticancer agents including doxorubicin, cisplatin, and methotrexate each induced HMGB1 upregulation in human osteosarcoma cells, and RNA interference-mediated knockdown of HMGB1 restored the chemosensitivity of osteosarcoma cells in vivo and in vitro. Mechanistic investigation revealed that HMGB1 increased drug resistance by inducing autophagy, an intracellular self-defense mechanism known to confer drug resistance. We found that HMGB1 bound to the autophagy regulator Beclin1 and regulated the formation of the Beclin1-PI3KC3 [PI3KC3, phosphatidylinositol 3-kinase class 3] complex that facilitates autophagic progression. In addition, we found that interaction between HMGB1 and Beclin1 relied upon the autophagic complex ULK1-mAtg13-FIP200. Therefore, through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance, and it offers a novel target for improving osteosarcoma therapy. Cancer Res; 72(1); 230-8. Ó2011 AACR.

A unique dataset obtained with combinations of minisodars and 915-MHz wind profilers at the Atmospheric Boundary Layer Experiments (ABLE) facility in Kansas was used to examine the detailed characteristics of the nocturnal low-level jet (LLJ). In contrast to instruments used in earlier studies, the ABLE instruments provide hourly, high-resolution vertical profiles of wind velocity from just above the surface to approximately 2 km above ground level (AGL). Furthermore, the 6-yr span of the dataset allowed the examination of interannual variability in jet properties with improved statistical reliability. It was found that LLJs occurred during 63% of the nighttime periods sampled. Although most of the observed jets were southerly, a substantial fraction (28%) was northerly. Wind maxima occurred most frequently at 200-400 m AGL, though some jets were found as low as 50 m, and the strongest jets tended to occur above 300 m. Comparison of LLJ heights at three locations within the ABLE domain and at one location outside the domain suggests that the jet is equipotential rather than terrain following. The occurrence of southerly LLJ varied annually in a way that suggests a connection between the tendency for jet formation and the large-scale circulation patterns associated with El Niño and La Niña, as well as with the Pacific decadal oscillation. Frequent and strong southerly jets that transport moisture downstream do not necessarily lead to more precipitation locally, however.

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BackgroundLncRNA small nucleolar RNA host gene 15 (SNHG15) was reported to play an oncogenic role in tumors. However, the role of SNHG15 and its molecular mechanism in osteosarcoma (OS) cells are largely unknown.MethodsqRT-PCR was performed to evaluate the expression levels of SNHG15 and miR-141 in OS tissues and cells. Cell transfection with different siRNAs, miRNAs or pcDNAs into U2OS and MG63 cells were carried out by Lipofectamine 2000. The effects of SNHG15 and miR-141 on OS cell proliferation, invasion and the levels of autophagy-related proteins were analyzed by MTT assay, Transwell invasion/migration assay and western blot, respectively. Luciferase reporter assay was used to confirm whether SNHG15 could directly interact with miR-141.ResultsWe found that up-regulation of SNHG15 was inversely correlated with miR-141 expression in OS tissues. SNHG15 knockdown and miR-141 overexpression significantly suppressed cell proliferation, invasion, migration and autophagy while SNHG15 overexpression and miR-141 repression exhibited the opposite effects on OS cells. Besides, SNHG15 could directly interact with miR-141 and regulate its expression. Furthermore, miR-141 suppressing significantly overturned the inhibition on proliferation, invasion, migration and autophagy mediated by SNHG15 knockdown while miR-141 overexpression remarkably attenuated SNHG15 overexpression-induced proliferation, invasion, migration and autophagy in OS cells.ConclusionOur data showed that SNHG15 contributes to proliferation, invasion, migration and autophagy in OS by negatively regulating miR-141, providing a new potential target and prognostic biomarker for the treatment of OS.

With the increasingly serious environmental pollution and intensified energy crisis, exploitation and utilization of new kinds of clean energy resources are imperative. Among them, thermoelectric (TE) conversion technology based on highperformance TE materials enables direct energy conversion between heat and electricity through the movement of internal phonons and charge carriers. [1][2][3][4] It has shown extensive and important prospects in power generation using industrial waste heat and electronic refrigeration. [5] The energy conversion efficiency of a TE material is mainly determined by its dimensionless figure of merit, defined as zT = σS 2 T/(κ L + κ e ), where σ, S, T, κ L , and κ e are the electrical conductivity, Seebeck coefficient, absolute temperature, lattice thermal conductivity, and electronic thermal conductivity, respectively. The general criteria for high zTs require high crystal symmetry for materials, many valleys (carrier pockets) near the Fermi level, heavy elements with small electronegativity differences between the constituent elements, or complex crystal structure, etc. [6][7][8][9][10] For the constituent elements in the same group such as S, Se, and Te, the heavy one (Te and Se) always has large atomic mass for low κ L and more covalent bonding character for large carrier mobility (µ H ) and thus outstanding electrical transports. [10] Therefore, the zTs are usually high in tellurides and selenides, but they are low in sulfides. This is the general phenomenon that has been observed in those well-known TE materials such as Bi 2 X 3 -, SnX-, and PbX-based compounds (X = S, Se, and Te). As shown in Figure 1, the zT values gradually improve as the anion element change from S to Se and then to Te. However, the case is different in Cu 2 X-based liquidlike TE materials that are among the hottest materials in recent TE study. They possess exceptionally low thermal conductivity and excellent zTs with the values of 1.7-1.9 for Cu 2 S, 1.5-2.3 for Cu 2 Se, and 0.4-1.1 for Cu 2 Te (see Figure 1). [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] It is quite abnormal and interesting that the zT in Cu 2 Te is lower than those in Cu 2 S and Cu 2 Se. As we known, tellurium is less electronegative, thus the chemical bonds between Cu and Te should be less ionic as compared with those in Cu 2 S and Cu 2 Se, which is beneficial for large µ H and electrical transports. Besides, the κ L in Cu 2 Te is expected lower than or similar to those in Cu 2 S and Cu 2 Se because tellurium is much heavier than sulfur and Most of the state-of-the-art thermoelectric (TE) materials exhibit high crystal symmetry, multiple valleys near the Fermi level, heavy constituent elements with small electronegativity differences, or complex crystal structure. Typically, such general features have been well observed in those well-known TE materials such as Bi 2 X 3 -, SnX-, and PbX-based compounds (X = S, Se, and Te). The performance is usually high in the materials with heavy constituent elements such as Te and Se, bu...

The aim of this study was to investigate the treatment of Kümmell’s disease with neurological deficits and to determine whether intravertebral clefts are a pathognomonic sign of Kümmell’s disease. A total of 17 patients who had initially been diagnosed with Kümmell’s disease were admitted, one patient was excluded from this study. Posterior decompression and vertebroplasty for the affected vertebrae were conducted. Pedicle screw fixation and posterolateral bone grafts were performed one level above and one level below the affected vertebrae. Vertebral tissue was extracted for histopathological examination. The mean time of follow-up was 22 months (range, 18 to 42 months). The anterior and middle vertebral heights were measured on standing lateral radiographs prior to surgery, one day postoperatively and at final follow-up. The Cobb angle, the visual analog scale (VAS) and the Frankel classification were used to evaluate the effects of the surgery. The VAS, anterior and middle vertebral heights and the Cobb angle were improved significantly one day postoperatively and at the final follow-up compared with the preoperative examinations (P<0.05). No significant differences were observed between the one-day postoperative results and those at final follow-up (P>0.05). The neurological function of all patients was improved by at least one Frankel grade. All patients in this study exhibited intravertebral clefts, and postoperative pathology revealed bone necrosis. One patient (not included in this study) showed an intravertebral cleft, but the pathology report indicated a non-Hodgkin’s lymphoma. The intravertebral cleft sign is not pathognomonic of Kümmell’s disease. Posterior decompression with short-segment fixation and fusion combined with vertebroplasty is an effective treatment for Kümmell’s disease with neurological deficits.

Recent studies have reported that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and progression. LncRNA-LET, a recently identified lncRNA, has been shown to be a tumor suppressor in hepatocellular carcinoma. However, the expression and functional of lncRNA-LET in other type of cancers remain largely unknown. In this study, we found that lncRNA-LET was significantly downregulated in nasopharyngeal carcinoma (NPC) tissues compared with corresponding normal tissues. Decreased LET expression is significantly correlated with advanced clinical stage, larger tumor size, increased lymph node tumor burden, and poor survival of NPC patients. Gain- and loss-of-function experiments demonstrated that enhanced LET expression inhibited NPC cells proliferation and induced cell apoptosis. By contrast, the knockdown of LET promoted NPC cells proliferation and inhibited cell apoptosis. Importantly, we found lncRNA-LET is transcriptional repressed by EZH2-mediated H3K27 histone methylation on the LET promoter. The expressions of EZH2 and lncRNA-LET are significantly inversely correlated in NPC tissues. Collectively, these findings indicate a pivotal role for lncRNA-LET in NPC cell proliferation and apoptosis, and reveal an epigenetic mechanism for lncRNA-LET dysregulation.