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Fractures play an important role in controlling the hydraulic conductivity of rock masses, and the aperture significantly influences the magnitude of fracture seepage. In this study, field measurements and experiments were conducted at a well-exposed granite fracture site in the Beishan area, China. Several types of single natural fractures were selected to remove the weathered surface and expose the fresh fractures. Subsequently, measuring ruler dispersion-tangent middle axis (MRD-TMA) method was developed to measure the fracture aperture and capture fracture geometry. Then, electrical resistivity tomography (ERT) technique was employed to investigate the seepage properties of these fractures. The results reveal that MRD-TMA method achieved good flexibility and accuracy in the current measurement of fracture aperture, and ERT is a useful tool for detecting the seepage properties of fractures in hard rock masses. Combined with field observations, the filling form of fractures can be categorized according to the ERT inversion results, as follows: open-weak filling, open filling, loose filling, and fully cemented-closed form, whose seepage properties decrease as the filling density increases. Generally, the open-weak filling is the main water channel in a fracture network, while the fully cemented-closed type is a water-blocking fracture and typically exhibits a pseudo-fracture with a large surface opening. In summary, the method for obtaining the morphological characteristics of the aperture can provide a low-cost and time-efficient approach for fracture logging in the field, and ERT technique provides a reference for the detection of potential hazards caused by connected water-conducting fractures in rock engineering.

Care dependence has been scarcely investigated in coronary heart disease patients after percutaneous coronary intervention. This study aimed to investigate the association between frailty, self-efficacy, combined effects of frailty and self-efficacy, mental health, and care dependence in coronary heart disease patients after percutaneous coronary intervention.Cross-sectional study.Data from 400 patients after percutaneous coronary intervention were collected from 2017-2020. Logistic regression model and mediating analysis were used to identify the association between frailty, self-efficacy, combined effects of frailty and self-efficacy, and care dependence.Patients with frailty and self-efficacy tended to have severe care dependence symptoms. There was no correlation between frailty symptoms, self-efficacy, and care dependence in patients without symptoms of anxiety or depression. But in patients with anxiety or depression symptoms, there is a strong correlation between frailty symptoms, lower self-efficacy, and care dependence. Mental health played an inhibitory effect on frailty and care dependence.

To explore the prognostic potential of AK021443 in non-small-cell lung carcinoma (NSCLC), AK021443 levels in NSCLC specimens were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between the AK021443 level and pathological factors in NSCLC patients was analyzed. Kaplan–Meier curves were plotted for assessing the prognostic value of AK021443 in NSCLC patients. Potential factors influencing NSCLC prognosis were analyzed by multivariable Cox regression test. AK021443 was upregulated in NSCLC specimens than normal ones. Its level was correlated to histological type, tumor differentiation, TNM staging, and lymphatic metastasis in NSCLC patients. AK021443 was the independent risk factor for the overall survival of NSCLC. AK021443 is highly expressed in NSCLC specimens, which is correlated to histological type, tumor differentiation, TNM staging, and lymphatic metastasis in NSCLC patients. It is the independent prognostic factor for NSCLC.

Background Lots of studies have shown that cyclin disorders can promote tumor development. This study aims to investigate the biological function and molecular mechanism of CCNB2 in lung adenocarcinoma (LUAD). Methods LUAD data were downloaded from GEO database and TCGA-LUAD database. Differential analysis was conducted to find the differentially expressed miRNAs and mRNAs, while targeted prediction was done for the access of potential target mRNAs. Gene expression level was detected by qRT-PCR and Western blot in human LUAD cell lines A-427, A549, Calu-3, PC-9 and human bronchial epithelial cell line BEAS-2B. MTT, colony formation, Transwell and flow cytometry assays were used to detect cell proliferation, metastasis, and cell cycle changes of PC-9 cell line. The dual-luciferase reporter gene was used to detect the targeted binding relationship of the target miRNA and mRNA. Results CCNB2 was highly expressed and served as a biomarker indicating poor prognosis in LUAD patients. Cell function experiments confirmed the inhibitory effects of silencing CCNB2 on the proliferation, migration and invasion of LUAD cells and cell cycle was blocked in the G0/G1 phase. In addition, with regard to the regulatory mechanism, we demonstrated that miR-335-5p had binding sites with 3'-UTR of CCNB2, indicating that miR-335-5p could target the regulation expression of CCNB2. In subsequent cell function tests, overexpression of miR-335-5p inhibited the proliferation and metastasis of cancer cells, and the rescue experiments also verified that miR-335-5p could reverse the promotion of CCNB2 overexpression on the progress of cancer cells. Conclusion In summary, our results revealed that miR-335-5p could target the down-regulation of CCNB2 to inhibit the occurrence and development of LUAD.

Remdesivir is a broad-spectrum antiviral agent. With the rapid spread of Coronavirus disease 2019 (COVID-19) globally, remdesivir is taking the spotlight for COVID-19 treatment. Despite the promising signs of anti-CoV activity in several preclinical and clinical studies, more data of remdesivir in the treatment of COVID-19 is still needed for evaluating its efficacy.

Background: LncRNA PSMG3‑AS1 plays oncogenic role in breast cancer. However, its role in non-small cell lung cancer (NSCLC) is hardly known. We then studied the role of PSMG3‑AS1 in NSCLC.Methods: RT-qPCR was performed to determine the expression of PSMG3‑AS1 in NSCLC and non-tumor tissues from 60 NSCLC patients. A survival analysis was carried out to visit patients for 5 years to study the role PSMG3‑AS1 in prediction the survival of NSCLC. NSCLC cells were overexpressed with miR-340 or PSMG3‑AS1 to analyze the crosstalk between PSMG3‑AS1 and miR-340. MSP was performed to analyze the methylation of miR-340 miRNA gene. The invasion and migration abilities of cells were determind by Transwell assays.Results: PSMG3‑AS1 was highly expressed in NSCLC and was closely correlated poor survival. PSMG3‑AS1 and miR340 were inversely correlated. In NSCLC cells, PSMG3‑AS1 decreased the expression of miR-340 and increased methylation of miR-340 gene. However, miR-340 overexpression did not significantly affect the expression of PSMG3‑AS1. In addition, PSMG3‑AS1 overexpression resulted in upregulated expression of ROCK1. PSMG3‑AS1 and ROCK1 overexpression increased cell invasion and migration rates. MiR-340 overexpression suppressed cell behaviors and inhibited the role of PSMG3‑AS1.Conclusions: PSMG3‑AS1 may downregulate miR-340 through methylation to upregulate ROCK1 and promote cell invasion and migration in NSCLC.

Object. This study is aimed at evaluating the efficacy and safety of pemetrexed and gefitinib in the treatment of non-small-cell lung cancer (NSCLC). Methods. Databases, including PubMed, the Cochrane Library, Embase, CNKI, and Web of Science, were applied to search for randomized controlled trials (RCTs) about the use of pemetrexed and gefitinib in the second-line treatment of locally advanced and metastatic NSCLC from database foundation to April 2020. Meta-analysis was conducted using the RevMan 5.3 software. Primary outcomes included progression-free survival (PFS) and overall survival (OS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and all grades of drug-related adverse events (AEs). Results. Totally, 14 RCTs and 1,334 patients were involved in the study. The results of meta-analysis showed that compared with pemetrexed, gefitinib was not superior in improving ORR ( P = 0.21 ), DCR ( P = 0.52 ), PFS ( P = 0.41 ), and OS ( P = 0.79 ). Subgroup analysis showed that in patients with mutant EGFR ( P = 0.08 ) and wild-type EGFR ( P = 0.80 ), both pemetrexed and gefitinib produced a similar effect on PFS. In terms of safety, the incidence of rash ( P < 0.00001 ) and diarrhea ( P = 0.0005 ) in the gefitinib group was significantly higher than those in the pemetrexed group, while the occurrence of neutropenia ( P = 0.01 ) and fatigue ( P = 0.02 ) was significantly lower. Conclusion. Gefitinib and pemetrexed showed similar efficacy and safety, regardless of the type of EGFR. Both gefitinib and pemetrexed can be used as conventional drugs for the second-line treatment of locally advanced and metastatic NSCLC.

Recent reports have indicated that circular RNA (circRNA) may regulate Lung adenocarcinoma (LAC) development. Our previous studies showed that hsa_circ_0012673 was up-regulated in a circRNA microarray. However, its expression level in LAC has not been verified, and the underlying molecular mechanisms in LAC are unknown. In this study, we found that the expression of hsa_circ_0012673 was up-regulated in LAC tissues compared to pair-matched adjacent non-tumor tissues (P = 0.0079), and that the expression level was associated with tumour size (P = 0.015). Furthermore, hsa_circ_0012673 was primarily localized in the cytoplasm and promoted cell proliferation of LAC cells by sponging miR-22, which targeted erb-b2 receptor tyrosine kinase 3 (ErbB3) in LAC. Hsa_circ_0012673 promotes LAC proliferation by suppressing miR-22, which targets ErbB3.

Determining the statistically homogeneous regions is important for engineering geological modeling and promoting systematic research on regional rock mass characteristics and rock engineering designs. This study proposes a comprehensive framework considering multiple discontinuity geometry parameters (e.g., orientation, trace length, density, and cluster characteristics.) to distinguish statistical homogeneity of fractured rock masses. First, based on the equal-area plot method (Schmidt net), the quantitative judgment ability of the Miller method for determining the similarity between two discontinuity orientation populations was improved by optimizing block network division scheme and blank area merging principle. Then, considering the distribution characteristics of discontinuity in rock mass space and the variation features of discontinuity at different geographical locations, a three-dimensional fracture network model, established using the discontinuity geometry parameters obtained from field investigation, was combined with the fractal dimension method (called the network fractal dimension method; NFD) to further evaluate the statistical homogeneity of fractured rock mass. The proposed approaches were subsequently applied to the identification of the statistical homogeneity of several typical granite fracture outcrops in the Beishan area, which is a candidate site for high-level radioactive waste (HLW) repository of China. The case study reveals that the optimized Miller method is more flexible and applicable than the conventional orientation-based methods, especially in dealing with the complex situation of the coexistence of gentle dip angle and steep dip angle as well as clustering characteristics of discontinuity. The NFD method was used to unify the influence of the main discontinuity characteristic parameters for a logical and unbiased evaluation of the statistical homogeneity. The comprehensive framework developed herein integrates the advantages of the two methods and reduces the interference of subjective evaluation. Therefore, it can be employed to efficiently determine the statistical homogeneity of rock masses at different locations at a large scale without concern over the deviation caused by different directions and size of the compared areas.

Saussurea involucrata (Asteraceae) is a medicinal and second-degree national priority endangered plant that is mainly distributed in the high latitude region of the western Tianshan Mountains. The population is fragmented and isolated, and extensive human impact merits a suitable and specific conservation strategy, which can be compiled based on the genetic diversity, population structure, and demographic history. Phylogeographic studies were conducted on a total of five natural populations and 150 individuals were sampled. Data from three cpDNA intergenic spacer regions (trnL-F, matK, and ndhF-rpl32) and nrDNA ITS sequences showed that twelve haplotypes in cpDNA and five haplotypes in nrDNA indicated high genetic diversity among populations sampled (H T = 0.820 and 0.756) and within populations sampled (H S = 0.792 and 0.721). Additionally, the high genetic diversity did not mirror genetic structure in either cpDNA (F ST = 0.03153, G ST > N ST, p

Circular RNAs (circRNAs) are associated with cancer progression and metastasis, although little is known about their role in lung adenocarcinoma (LAC). In the present study, microarrays were first used to screen for tumour-specific circRNA candidates in LAC tissue. Thirty-nine circRNAs were found to be up-regulated and 20 were down-regulated (fold change > 2.0). Among them, hsa_circ_0013958 was further confirmed to be up-regulated in all of the LAC tissues, cells and plasma. In addition, hsa_circ_0013958 levels were associated with TNM stage (P = 0.009) and lymphatic metastasis (P = 0.006). The area under the receiver operating characteristic curve was 0.815 (95% confidence interval = 0.727-0.903; P < 0.001). In addition, to further illustrate the bioactivities of hsa_circ_0013958 in LAC, siRNA-mediated inhibition of hsa_circ_0013958 was performed in vitro. The results showed that hsa_circ_0013958 promoted cell proliferation and invasion and inhibited cell apoptosis in LAC. Moreover, hsa_circ_0013958 was identified as a sponge of miR-134, and thus it up-regulated oncogenic cyclin D1, which plays a pivotal role in the development of non-small cell lung cancer. In conclusion, our results suggested that hsa_circ_0013958 could be used as a potential non-invasive biomarker for the early detection and screening of LAC.

The Yingpan cemetery is situated in the Lop Nor region of the Tarim Basin in southern Xinjiang, China, and it has been dated to the Eastern Han and Jin dynasties (∼25–420 AD). Macrofossil and microfossil analyses were undertaken to investigate the associated plant and food remains. The results indicated that the principal cereal crops of Yingpan people were Panicum miliaceum, Triticum aestivum, and Hordeum vulgare var. coeleste, moreover flour of Triticum aestivum was also processed into cakes. Meanwhile, plant remains of Vitis vinifera suggested grape cultivation and utilization in this region. Apart from the agricultural and horticultural remains, two taxa of wild plants were also identified. This study presents the first systematic archaeobotanical data about the cereal cultivation and plant utilization in ancient Xinjiang during the Eastern Han and Jin dynasties in the Tarim Basin.

Platinum-based chemotherapy is recommended as the first-line treatment regimen for patients with advanced non-small-cell lung cancer (NSCLC). Lobaplatin (LBP), a third-generation platinum anti-neoplastic agent, has shown an improved efficacy. This study is aimed to investigate the mechanisms of LBP-induced apoptosis in the A549 p53 wild-type cell line. The Cell Counting Kit-8 assay (CCK-8), flow cytometry (FCM), Western blot, xenograft tumor models, terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), and RNA interference were used in this study. Our results showed that the proliferation of A549 cells could be inhibited by LBP. At lower concentrations, LBP triggered cell cycle arrest at the G1 phase in A549 cells. LBP could also induce apoptosis of A549 cells. LBP also increased the expression of PARP and Bax and the cleavage of caspase-3, caspase-8, and caspase-9 and reduced Bcl-2 expression. In vivo experiment confirmed that LBP could inhibit tumor growth in the A549 xenograft models and induce apoptosis. Apoptosis of A549 cells was decreased after transfected with p53 shRNA or treated with reactive oxygen species inhibitor NAC and p38MAPK inhibitor SB203580, suggesting that the p53/ROS/p38MAPK pathway appeared to mediate the LBP-induced apoptosis of A549 cells. Our data demonstrate that LBP could be a promising candidate for the treatment of NSCLC with wild-type p53.

Background Circular RNA (circRNA), as a covalently closed circular RNA molecule, is widely present, which is recognized as a competing endogenous RNA. A large number of differentially expressed circRNAs have been identified and are recognized as potential biomarkers for the diagnosis of tumors. Main body CircRNAs play an important role in the regulation of cell signaling pathways. The main biological functions of circRNAs include acting as miRNA sponges, regulating the transcription of the parental genes, and acting as adapters to regulate the interactions between proteins and encoding proteins. Compared with normal tissues, there are differentially expressed circRNAs in lung cancer tissue, and the expression levels of circRNAs are correlated with clinicopathological features of lung cancer. Their roles in pathway regulation are described, and the diagnostic and prognostic values are further evaluated. Conclusion In lung cancer, circRNAs participate in the proliferation, migration, and invasion, acting as a competitive endogenous RNA. Differentially expressed circRNAs may serve as non-invasive diagnostic markers for lung cancers. Further investigation of the roles of circRNAs in the pathogenesis and regulatory pathways is conducive to the development of novel approaches for the diagnosis and accurate treatment of lung cancers.

A novel multifunctional nano-drug delivery system based on reversal of peptide charge was successfully developed for anticancer drug delivery and imaging. Mesoporous silica nano-particles (MSN) ~50 nm in diameter were chosen as the drug reservoirs, and their surfaces were modified with HIV-1 transactivator peptide-fluorescein isothiocyanate (TAT-FITC) and YSA-BHQ1. The short TAT peptide labeled with FITC was used to facilitate intranuclear delivery, while the YSA peptide tagged with the BHQ1 quencher group was used to specifically bind to the tumor EphA2 membrane receptor. Citraconic anhydride (Cit) was used to invert the charge of the TAT peptide in neutral or weak alkaline conditions so that the positively charged YSA peptide could combine with the TAT peptide through electrostatic attraction. The FITC fluorescence was quenched by the spatial approach of BHQ1 after the two peptides bound to each other. However, the Cit-amino bond was unstable in the acidic atmosphere, so the positive charge of the TAT peptide was restored and the positively charged YSA moiety was repelled. The FITC fluorescence was recovered after the YSA-BHQ1 moiety was removed, and the TAT peptide led the nano-particles into the nucleolus. This nano-drug delivery system was stable at physiological pH, rapidly released the drug in acidic buffer, and was easily taken up by MCF-7 cells. Compared with free doxorubicin hydrochloride at an equal concentration, this modified MSN loaded with doxorubicin molecules had an equivalent inhibitory effect on MCF-7 cells. This nano-drug delivery system is thus a promising method for simultaneous cancer diagnosis and therapy.

// Xiaobo Fan 1, 2, * , Fengfeng Zhao 2, * , Xiyong Wang 2 , Guoqiu Wu 1, 2 1 Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University, Nanjing, 210009, China 2 Medical School, Southeast University, Nanjing, 210009, China * These authors have contributed equally to this work Correspondence to: Guoqiu Wu, email: nationball@163.com Keywords: matrilin-1 C-terminal peptide, self-assembly, nanosphere, drug delivery, cancer therapy Received: May 16, 2016 Accepted: July 19, 2016 Published: August 11, 2016 ABSTRACT In this study, we designed and fabricated self-assembly nanospheres, which consisted of a P45 peptide and doxorubicin (Dox). P45 is a hybrid peptide composed of an Arg-Gly-Asp motif linked to the human matrilin-1 C-terminal domain by a serine linker. The fabricated nanospheres had a uniform mulberry-like spherical shape, a diameter of 63 nm, excellent polydispersity, and high Dox drug-loading efficiency. In the presence of the RGD motif, the Dox/P45 nanospheres could specifically target A549 cells, which have high integrin α v β 3 expression. Confocal laser scanning microscopy and flow cytometry results showed the enhanced cellular uptake of Dox/P45, and the CCK8 assay indicated the low cytotoxicity of the nanospheres to normal human embryonic kidney 293 cells. Furthermore, the fabricated nanospheres were stable in a physiological environment, but they disassembled and exhibited a rapid Dox release in an acidic atmosphere, allowing for a specific pH-sensitive release into cytosol after cellular uptake. These results suggest that natural amphiphilic peptides can be used as carriers of nanodrugs for targeting delivery as well as controlled drug release for cancer therapy.

e21036 Background: Micropapillary adenocarcinoma (MPC) is one of the most aggressive histologic subtypes of lung adenocarcinoma (ADC). Although the incidence of MPC predominant ADC is low, nearly half of ADCs contain a minor proportion of MPC, which could contribute to poor prognosis in these patients. Comprehensive analysis of genetic and immunological features of ADC with different MPC contents would help better understand cancer biology of this ADC subtype and direct future treatments. Methods: We performed panel next-generation sequencing (NGS) of 425 cancer-related genes for a discovery cohort of 43 ADC patients whose tumors were microdissected to separate MPC and non-MPC regions and a reference cohort of 113 ADC patients with unknown ADC histologic subtypes. MPC-enriched mutations were identified by comparing tumors with different original MPC contents within these cohorts, which was then confirmed using a validation cohort of 183 ADC patients. Staining of immunological markers was also conducted for MPC samples from the discovery cohort to investigate their tumor microenvironment. Results: We found that ADC tumors with higher MPC contents/similarities tended to harbor more tumor mutation burdens (TMBs) and chromosome instability (CIN). In addition, genetic alterations in transcription termination factor 1 ( TTF1), brain-specific angiogenesis inhibitor 3 ( BAI3), mammalian target of rapamycin ( MTOR), cyclin-dependent kinase inhibitor 2A ( CDKN2A), and CDKN2A were found to be enriched in MPC using the discovery and reference cohorts, which could then be cross-validated using the validation cohort. Tumors with higher MPC content were associated with elevated infiltration of CD4+, CD8+ and FOXP3+ T cells, especially at the peritumor regions. Higher percentage of PD-L1+ tumor cells were also found to be correlated with higher MPC content, suggesting of more immunosuppression in MPC predominant tumors than low MPC tumors. Conclusions: We identified multiple novel MPC-enriched genetic changes that could help understand the nature of MPC. MPC predominant tumors tended to have higher levels of TMBs, T cell infiltration, and immunosuppression than low MPC tumors, making it a potential candidate for immunotherapy, especially the combination therapy of anti-PD-1/PD-L1 drugs and anti-CTLA-4 drugs, which could inhibit PD-1/PD-L1 pathway and FOXP3+ Treg cells simultaneously.

Pseudopodium-enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine kinase, has been demonstrated to act as an oncogenic regulator in breast and pancreatic cancers. However, the role of PEAK1 in the progression and metastasis of lung cancer is still unknown. Here, we observed that ectopic PEAK1 expression promoted lung cancer cell migration and invasion, while PEAK1 knockout resulted in suppressed cell migration and invasion. Interestingly, cell proliferation did not significantly increase or decrease in either the PEAK1 overexpression or knockout groups compared with the corresponding control cells. In addition, PEAK1 overexpression could induce epithelial-to-mesenchymal transition (EMT) and the expression of matrix metalloproteinase-2 (MMP2) and MMP9 both in vitro and in vivo, whereas PEAK1 knockout had the opposite effects. Then, we had confirmed that PEAK1 was significantly upregulated in lung cancer tissues, and correlated with a higher tumor node metastasis stage. Moreover, PEAK1 upregulation markedly enhanced the activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and Janus kinase-2 (JAK2) signaling in lung cancer cells. Further work demonstrated that the combination of PD98059 with AZD1480 could reverse the effects of PEAK1-induced EMT, cell migration and invasion. Our findings highlight a newer mechanism for PEAK1 in regulating EMT and metastasis in lung cancer, which might serve as a therapeutic target for lung cancer patients.

Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors. CCK8 assay and colony formation assay were used to detect the cell proliferation and colony formation. We measured the IC50 value of 5-FU alone and in combination with BZA by cell viability inhibition. Cell migration and invasion ability were tested by scratch migration assays and transwell invasion assays. Flow cytometric analysis for cell apoptosis and cell cycle. Quantitative real-time PCR was used to detect Bad, Bcl-2 and Ki-67 mRNA expression and western blotting (WB) assay analyzed protein expression of Bad/Bcl-2 signaling pathway. Further mechanism study, WB analysis detected the key proteins level in IL-6/GP130 targets and JAK/STAT3, Ras/Raf/MEK/ERK, and PI3K/AKT/mTOR signaling pathway. A colon cancer xenograft model was used to further confirm the efficacy of 5-FU and BZA in vivo. The GP130, P-STAT3, P-AKT, and P-ERK expression levels were detected by immunohistochemistry in the xenograft tumor. BZA markedly potentiates the anti-tumor function of 5-FU in vitro and in vivo. Conversely, 5-FU activation is reduced following exogenous IL-6 treatment in cells. Further mechanistic studies determined that BZA treatment enhanced 5-FU anti-tumor activation by inhibiting the IL-6/GP130 signaling pathway and the phosphorylation status of the downstream effectors AKT, ERK and STAT3. In contrast, IL-6 can attenuate 5-FU function via activating IL-6R/GP130 signaling and the P-AKT, P-ERK and P-STAT3 levels. This study firstly verifies that targeting IL-6/GP130 signaling can increase the anti-tumor function of 5-FU; in addition, this strategy can sensitize cancer cell drug sensitivity, implying that blocking IL-6/GP130 targets can reverse chemoresistance. Therefore, combining 5-FU and IL-6/GP130 target inhibitors may be a promising approach for cancer treatment.

Based on the smooth blasting method, the blasting parameters of the Beishan exploration tunnel have been designed. According to the principle of blasting parameters design, three kinds of cutting methods have been laid out, which are straight parallel hole cutting, single-wedge cutting, and double-wedge cutting. The other parameters such as the borehole number, the detonator segment, and the charge amount of each hole are also designed. Then, the blasting tests under different cutting methods were carried out in the field. The results show that all the three cutting methods can achieve good utilization ratio of blasting holes. The blasting effect of straight parallel hole cutting is good. The rock slag size of single-wedge and double-wedge cutting is uniform, which is beneficial to slag extraction. Moreover, the blasting vibration velocity and blasting energy have been analyzed. It is found that the energy distribution of single-wedge and double-wedge cutting is more uniform, mainly concentrated in the high-frequency part, while the energy of straight parallel hole cutting is more concentrated in the low-frequency part. Among many factors affecting blasting vibration velocity, besides the explosive quantity, it would also be easily influenced by the cutting way. It should be noticed that the blasting method includes numerous blasting parameters, which interact with each other. Those blasting parameters obtained were just limited to the cutting method, and the result and the theoretical knowledge could be applied to the blasting and excavation of the deep geoengineering and the HLW geo-disposal.

Based on the slit charge technology, the blasting progress and the blasting theory have been studied in detail. Combined with the high-level radioactive waste geological disposal, in which the excavation damaged zone of the surrounding rock is required as small as possible, the testing of the Beishan exploration tunnel (BET) has been studied, and the blasting parameters have been designed using the slit charge technology. Theoretically, the rock failure criterion has been proposed, which adopted the dynamic mechanical parameters, such as the dynamic compress strength, dynamic tensile strength, dynamic modulus, dynamic passion ratio, dynamic fracture toughness, and dynamic stress intensity factor. Furthermore, the blasting test has been carried out under the same tunnel face with left and right sides simultaneously, and it can be found that the blasting effect with the slit charge technology is better than another side, which verified the useful and scientific meaning of this technology. It should be noticed that the blasting method includes numerous blasting parameters, which interact with each other. Those blasting parameters obtained just limited the slit charge, and the result and the theoretical knowledge could be applied to the blasting and excavation of the deep geoengineering and HLW geodisposal.

Gambogenic acid (GNA), which is an important active compound present in gamboge, exerts anticancer activity in various types of tumor cells. However, the effect of GNA on small-cell lung cancer (SCLC) cell lines and the underlying mechanism involved still remain unclear. In the present study, GNA inhibited the proliferation and cell cycle progression of SCLC cells. GNA also promoted the apoptosis of SCLC cells in a dose-dependent manner, which is associated with modulating the levels of proteins involved in apoptosis pathways in NCI-H446 and NCI-H1688 cells. The results demonstrated that GNA increased the level of cleaved caspase-3, −8 and −9, and Bax but decreased the expression of anti-apoptotic protein, Bcl-2. Furthermore, similar results were obtained in a mouse tumor xenograft model. Additionally, GNA exhibit low toxicity in tissues when administered to mice in the SCLC xenograft models. Collectively, our findings demonstrated that GNA significantly inhibited the proliferation of SCLC cells and promoted cell apoptosis via cell cycle arrest and induction of apoptosis.

Copper foils for flexible printed circuit boards were prepared by double rolling, and the matt surface of double-rolled copper foil was characterized by atomic force microscope, scanning electron microscope, 3D optical interferometer, optical microscope and surface profiler. The morphology characteristics of matt surface were studied, and the formation mechanism of matt surface was discussed. The results showed that the matt surface of the double-rolled copper foil presented rough and relatively homogeneous morphology, and the morphologies of upper and lower matt surfaces were practically coincident. As the copper strips just entered into the deforming zone, the roughening of laminated surface occurred, but the roughness was relatively small. When the copper strips passed through the neutral plane, the roughness of the laminated surface increased significantly. In the backward slip zone, the initial micro-dimples between the two laminated surfaces were connected in the rolling direction, which led to the formation of larger and airtight dimples; when the copper strips moved toward the neutral plane and entered into the forward slip zone, the pressure of fluid in the airtight dimples increased rapidly, which enhanced the depths of the dimples; meanwhile, the depression corrugations with certain depth and larger width were formed on the laminated surface because of the dimple connection in the width direction. The copper foils with thickness of 36–54 μm were fabricated by double rolling, and the R z value of their matt surfaces was 1.0–1.3 μm, which meet the requirements for directly using as adhesive surface of resin substrate, and therefore multiple roughening treatments during the traditional production process of flexible printed circuit board might be omitted. The formation mechanism of the matt surface of double-rolled copper foil proposed on the basis of the metal flow and deformation mechanics theory could explain the representative characteristics of the length direction of corrugations on matt surface being perpendicular to the rolling direction, several corrugations within a grain on the matt surface and the coincident morphologies of the upper and lower matt surfaces.

Purpose: To develop a qPCR method to examine the 202 isoform of excision repair cross-complementation group 1 (ERCC1_202) and to evaluate its clinical utility as a predictive biomarker for platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Methods: The relative complementary DNA (cDNA) quantification for ERCC1_202 was conducted using a fluorescence-based, real-time detection method and β-actin was used as a reference gene. Results: A strong correlation was observed between ERCC1_202 mRNA and ERCC1 mRNA levels in NSCLC cells (P < 0.001). 28 patients completed this research. Our results implied that as ERCC1_202 levels increased, the risk of progression (HR = 4.296, P = 0.011) and death (HR = 6.503, P = 0.001) increased. At multivariate analysis, high expression of ERCC1_202 was shown to be an independent predictive factor for time to progression (P = 0.047), and progression-free survival (P = 0.014). However, the high expression of ERCC1_202 was not an independent predictive factor for response (P = 0.324). Conclusions: This study suggests that the efficacy of platinum-based chemotherapy can be improved when customized according to the expression of ERCC1_202.

We tested the effectiveness of four DNA barcoding markers (rbcL, matK, ITS and trnLF region) for land plants in identifying Calligonum species. High quality sequences were obtained for rbcL, matK and trnLF with the universal primers whereas ITS sequences were of poor quality. RbcL and matK were highly conservative and failed in species discrimination. When rbcL, matK and trnLF were combined, the species resolution was up to 6.25%. Low sequence variation resulted in poorly resolved tree topologies. Among the sixteen sampled species, only three were recovered as a monophyletic group. Our results show that although DNA barcoding is an important tool for species identification, it fails in discriminating Calligonum species. Further research will be needed to develop markers capable to discriminate species in this taxonomy complicated and recently diverged genus.

Developing ultra-thin copper foils with different surface roughness and microstructure has important significance for improving the service performance and reducing the production cost of high-end circuit boards. In this paper, pure copper strips with initial cube texture were subjected to a double rolling process (deformation amount ranges from 50% to 95%), and the surface textures evolution law and mechanism of double-rolled strips were studied by an X-ray diffraction technique. The results show that when a deformation amount increased from 50% to 70%, the grains of two surfaces rotate away from the cube orientation, and the formed textures of two surfaces mainly consisted of C, S and B orientation components. The orientation density values for these three components on bright surface only had slight difference; the orientation density values for C and S components were much larger than that for B components on a matt surface. When the deformation amount increased to 90%, the increase extents of orientation density values for C and S components were obviously larger than that for B components on a bright surface; the increase extents of orientation density values for these three components were almost the same on the matt surface. It has been found that when deformation amount reaches 95%, the grains orientation of bright surface were relatively concentrated, and the orientation density value for C texture obviously increased to 11.68 and that for B texture was only 3.15; the grains orientation of matt surface were relatively dispersed, and the orientation density value for C texture increased to 9.26 and that for B texture obviously increased to 6.35, and the density values of these two textures had less difference. For the condition of strong compressive and shear stress on the bright surface, grains were mainly rotating to C texture orientation; compared with the bright surface, “semi-free” deformation condition on the matt surface is beneficial to promote much more grains to rotate to the B texture orientation.