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Non-small cell lung cancer (NSCLC) is associated with high mortality rates worldwide. The costimulatory molecule, B7-H4, a member of the B7 family, plays an important role in immune regulation, mainly by inhibiting the proliferation of T cells to achieve a negative regulatory T cell immune response. The mechanism of action of B7-H4 in non-small cell lung cancer is unknown at present. Tumor tissues from 71 patients subjected to radical pneumonectomy were examined, along with NSCLC cells and BALB/c mice. Among the 71 NSCLC cases, overall and recurrence-free survival rates were significantly lower in those displaying high B7-H4 expression. Mechanistic analyses showed that B7-H4 promoted the growth and metastasis of non-small cell lung cancer tumor tissues in mice through effects on CD8+ T cell apoptosis. Data from western blot experiments further suggested that B7-H4 induced CD8+ T cell death, both in vitro and in vivo , and affecting the PD-1/Stat3 pathway and promoting immune escape of tumor cells. Our collective findings support the potential utility of B7-H4 gene expression as a marker of NSCLC prognosis and provide a novel strategy for targeted therapy. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a major cause of chronic liver disease, which affects 2–3% of the world population. Until now, the early detection of HCV has been a great challenge, especially for those who live in developing countries. In this study, we developed a novel and ultrasensitive assay for the detection of HCV RNA based on the reduced graphene oxide nanosheets (rGONS) and hybridization chain reaction (HCR) amplification technique. This detection system contains a pair of single fluorophore-labeled hairpin probes that can freely exist in the solution in the absence of target RNA. The introduction of target RNA can robustly trigger a HCR with the two probes and produce long nanowires containing a double-stranded structure. The weak adsorption to rGONS makes the long nanowires emit a strong fluorescence. Using this enzyme-free amplification strategy, we developed a new method for the HCV RNA assay with a detection limit of 10 fM, which is far more sensitive than the common GO-based fluorescence method. Furthermore, the new method exhibits high selectivity for the discrimination of perfectly complementary and mismatched sequences. Finally, the new method was successfully used as a HCV RNA assay in biological samples with a strong anti-interference capability in complicated environments. In summary, these remarkable characteristics of the new method highlight its potential use in a clinical sample primary screening. [ABSTRACT FROM AUTHOR]

Summary Neurogenesis is initiated by the transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators. Here, we discover a conserved post-translational switch governing the duration of proneural protein activity that is required for proper neuronal development. Phosphorylation of a single Serine at the same position in Scute and Atonal proneural proteins governs the transition from active to inactive forms by regulating DNA binding. The equivalent Neurogenin2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex. Using genome editing in Drosophila , we show that Atonal outlives its mRNA but is inactivated by phosphorylation. Inhibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expression dynamics and target gene expression resulting in neuronal number and fate defects. Strikingly, even a subtle change from Serine to Threonine appears to shift the duration of Atonal activity in vivo, resulting in neuronal fate defects. [ABSTRACT FROM AUTHOR]

The production of neurons, astrocytes and oligodendrocytes is regulated by a group of transcription factors, which determine cell fates and specify subtype identities in the nervous system. Here we focus on profiling the distinct roles of Neurogenin (Ngn or Neurog) family members during the neuronal development. Ngn proteins are tightly regulated to be expressed at defined times and positions of different progenitor cell pools. In addition to their well-elucidated proneural function, Ngn proteins play various critical roles to specify or maintain cell fate and regulate neurite outgrowth and targeting in the central nervous system. Finally, Ngns have been associated with neuronal disorders. Therefore understanding the function and regulation of Ngns will not only improve the understanding of the molecular mechanism underlying the development of nervous system, but may also provide insight into neuronal disease. [ABSTRACT FROM AUTHOR]

A series of shaking table tests were conducted on unreinforced and micropiles-reinforced soil landslides to investigate the seismic response of micropiles-reinforced landslide and the dynamic mechanical behaviour of micropiles in landslide under earthquake. The test results indicate that: (1) The micropiles can raise the anti-seismic performance of landslide, and it can efficiently delay the development of earthquake landslide hazards. (2) After earthquake, the flexural failure of micropile mainly occurs in the area that 1.4–4 times pile diameter above the sliding surface and the area that 1.4–3.4 times pile diameter below the sliding surface. (3) After reinforced by micropiles, the acceleration response on the slope surface of landslide can be decreased, especially the slope toe. (4) Both thrust of sliding mass and resistance of sliding bed are mainly concentrated near the sliding surface. The dynamic bending moment distributions of the three rows of micropiles present as reverse 'S'. The maximum bending moment of the pile above sliding surface is located at the point that 3.7 times pile diameter above sliding surface, and the maximum bending moment of the pile below sliding surface is located to the point that 1.43 times pile diameter below sliding surface. [ABSTRACT FROM AUTHOR]

It has been certified that long noncoding RNAs (lncRNAs) are crucial regulators in the progression of various human cancers. snoRNA host gene 6 (SNHG6) has been uncovered to affect the initial stage and tumorigenesis of hepatocellular carcinoma. Nevertheless, the expression pattern and biological role of SNHG6 in glioma still need to be investigated. The study aims to investigate the expression pattern, biological role and the potential mechanism of SNHG6 in glioma. In this study, the high expression of SNHG6 was tested in both glioma tissues and glioma cells. The correlation between expression levels of SNHG6 and the overall survival of glioma patients was demonstrated by using Kaplan Meier method analysis. Next, gain of function assays revealed that overexpression of SNHG6 can promote the formation of malignant phenotype of 1800 cell. However, results of loss-of-function assays revealed that silenced SNHG6 exerted the inhibitory function on glioma cell growth. Flow cytometric analysis was performed in glioma cells to detect the anti-oncogenic effects of silenced SNHG6 on cell cycle and apoptosis. Finally, we identified that p21 was involved in glioma cell proliferation after SNHG6 was downregulated. Taken together, we concluded that SNHG6 is a regulator and a potential therapeutic target in glioma. [ABSTRACT FROM AUTHOR]

Microwave-assisted crushing and grinding can improve efficiency and reduce energy consumption. This paper takes rock grains with galena and calcite as the research object to establish a two-dimensional computational model through the finite difference software FLAC2D. It analyzes the process and law of mineral boundary failure under microwave irradiation, and assesses the effects of four factors, namely, microwave irradiation time, power density, mineral crystal size, and mineral content, on mineral boundary failure. Results indicate an optimal microwave irradiation period for the rapid failure of mineral boundary. Moreover, irradiation time and energy consumption can be reduced by increasing the microwave power density. However, irradiation time and energy consumption are basically unchanged when the microwave power density is above a certain threshold. Mineral content slightly affects the microwave irradiation time, whereas mineral crystal size significantly affects the microwave irradiation time. In addition, a larger-sized mineral crystal requires less irradiation time and energy consumption to reach the same failure rate. However, irradiation time and energy consumption slightly change when the crystal size is larger than a certain value. [ABSTRACT FROM AUTHOR]

Objective The aim of this research was to compare the functional outcome and safety between supraorbital keyhole approach (SKA) and pterional keyhole approach (PKA) for clipping intracranial aneurysms. Methods This is a retrospective study involving 318 patients with a total of 365 aneurysms who underwent keyhole surgery, comprising 195 cases in SKA group and 123 cases in PKA group. The outcome measures include Glasgow Outcome Scale, complete clipping rate, adverse events incidence, operation view angle, working distance, and surgical incision condition. Results Of a total of 356 aneurysms that were clipped and 9 trapped, no significant difference was observed in Glasgow Outcome Scale score, adverse events incidence, or complete clipping rate between the SKA and PKA groups. The distance from skin incision to anterior clinoid process was 5.87 ± 0.24 cm in SKA and 5.12 ± 0.27 cm in PKA. The operation view angle (from midline to the operating channel in sagittal plane) was 30°–40° in the SKA group and 60°–68° in the PKA group. Conclusions Our research demonstrates that both SKA and PKA are safe and effective for most anterior circulation aneurysms and parts of posterior circulation aneurysms. The SKA exposures aneurysm better on deep and sagittal directions and is more suitable for clipping aneurysms by the contralateral approach due to the short distance. The PKA has a good exposure on the neck of aneurysm with dorsal direction of parent artery and can be used to evacuate hematoma in the temporal lobe when clipping the aneurysm. Integrating multimodal 3-dimensional images could help neurosurgeon in selecting an appropriate and effective approach. [ABSTRACT FROM AUTHOR]

Abstract: Wilms tumor (WT) is a genetically heterogeneous childhood kidney tumor. Several genetic mutations have been identified in WT patients, including inactivation of WTX, somatic stabilizing CTNNB1, and p53 mutations. However, the molecular mechanisms in tumorigenesis remain largely unexplored. Stat3 is a transcription factor that can promote oncogenesis. Stat3 activation is commonly viewed as crucial for multiple tumor proliferation and metastasis. We show that Stat3 is highly activated in Wilms tumor tissues compared to those in adjacent tissues. IL-6 treatment or transfection of a constitutively activated Stat3 in G401 cells promotes cell proliferation. At the molecular level, we further elucidate that Stat3 inhibits WTX expression through up-regulation of microRNA-370. Our results suggest that Stat3/miR-370/WTX regulatory axis might be a critical mechanism in Wilms tumor cells. [Copyright &y& Elsevier]

• The micro-pore structure of ECC is refined after exposed to sub-elevated temperature. • The high fly ash content in ECC favors its tensile performance under sub-elevated temperature. • The underlying mechanism was discussed at micro-scale level. In this paper, the mechanical properties of Engineered Cementitious Composites (ECC) with two different fly ash contents after sub-elevated temperature exposure were investigated systematically at multiple scales. At composite level, uniaxial compressive and tensile tests were performed on specimens underwent 20 °C, 50 °C, 100 °C, and 200 °C exposure. The results indicate that, as temperature rise from 20 °C to 200 °C, the compressive strength of both ECC mixtures increased due to the refinement of the matrix pore structure. In term of tensile properties, after exposed to 100 °C and 200 °C, ECC M1 with relatively lower fly ash content shows a substantial reduction in strain capacity, but still retaining strain-hardening behavior, whereas ECC M2 with higher fly ash content exhibits a comparable or even enhanced tensile strength and strain capacity. At micro-scale, ECC matrix toughness was increased and PVA fiber strength was degraded under 200 °C exposure, which deteriorates the tensile properties of ECCs. However, the above negative effects are diminished due to the reduced fiber/matrix interfacial bond. Furthermore, the rather low matrix toughness and fiber/matrix interfacial bond associated with high fly ash content are the main reasons for the highly remained ductility in ECC M2 after sub-elevated temperature exposure. [ABSTRACT FROM AUTHOR]

A new fluorometric method is delineated for the detection of RNase H activity by combining DNAzyme with reduced graphene oxide (rGO). In the absence of RNase H, the fluorescence of FAM-labeled probe is quenched due to the strong adsorption on the rGO. The presence of RNase H can release the active DNAzyme from the DNA-RNA chimeric strand. This triggers the cleavage of the signal probe at the rA site with the help of the cofactor Mg2+. The recycle cleavage can directly result in the amplified signal emitted by the FAM-labeled short fragment. The method allows the activity of RNase H to be detected in a linear range of 0.01 to 5 U·mL−1. The detection limit of 0.018 U·mL−1 is calculated by the principle of three-time standard deviation over the blank signal. Then, RNase H-targeting natural compounds were screened for their inhibitory action. Among the investigated compounds, five were screened as RNase H inhibitors in a concentration-dependent manner, and 4 compounds were identified as activators. Finally, the method was reliably used for discriminating the difference of RNase H activity in human serum. It is found that RNase H activity was upregulated in patients with hepatitis C virus infection. [ABSTRACT FROM AUTHOR]