Centrosome aberrations have been implicated in the development and progression of breast cancer. Our previous worked show that centrosomal protein 70 (Cep70) regulates breast cancer growth and metastasis. However, it remains elusive whether Cep70 is implicated in the sensitivity of the anti-microtubule drug paclitaxel in breast cancer. Here we provide evidence that Cep70 is a mediator of paclitaxel sensitivity in breast cancer. Cell proliferation assays show that Cep70 expression correlates with paclitaxel sensitivity in breast cancer cell lines. In addition, paclitaxel sensitivity varies when altering Cep70 expression level. Mechanistic studies reveal that Cep70 interacts with tubulin, and promotes the ability of paclitaxel to stimulate microtubule assembly. These data demonstrate that Cep70 mediates paclitaxel sensitivity in breast cancer. Full article

Thermoelectric materials which can convert energies directly between heat and electricity are used for solid state cooling and power generation. There is a big challenge to improve the efficiency of energy conversion which can be characterized by the figure of merit (ZT). In the past two decades, the introduction of nanostructures into bulk materials was believed to possibly enhance ZT. Nanocomposites is one kind of nanostructured material system which includes nanoconstituents in a matrix material or is a mixture of different nanoconstituents. Recently, nanocomposites have been theoretically proposed and experimentally synthesized to be high efficiency thermoelectric materials by reducing the lattice thermal conductivity due to phonon-interface scattering and enhancing the electronic performance due to manipulation of electron scattering and band structures. In this review, we summarize the latest progress in both theoretical and experimental works in the field of nanocomposite thermoelectric materials. In particular, we present various models of both phonon transport and electron transport in various nanocomposites established in the last few years. The phonon-interface scattering, low-energy electrical carrier filtering effect, and miniband formation, etc., in nanocomposites are discussed. Full article

The vibration control of a construction vehicle must be carried out in order to meet the aims of sustainable environmental development and to avoid the potential human health hazards. In this paper, based on market feedback, the driver seat vibration of a type of wheel loader in the left and right direction, is found to be significant over a certain speed range. In order to find abnormal vibration components, the order tracking technique (OTT) and transmission path analysis (TPA) were used to analyze the vibration sources of the wheel loader. Through this analysis, it can be seen that the abnormal vibration comes from the interaction between the tire tread and the road, and this is because the vibration was amplified by the cab mount, which was eventually transmitted to the cab seat. Finally, the seat vibration amplitudes were decreased by up to 50.8%, after implementing the vibration reduction strategy. Full article

The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene. Full article

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157—an inhibitor of PERK—effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy. Full article

To evaluate the mercury (Hg) exposure level of children located in a Hg mining area, total Hg concentrations and speciation were determined in hair and urine samples of children in the Wanshan Hg mining area, Guizhou Province, China. Rice samples consumed by these same children were also collected for total mercury (THg) and methyl-mercury (MeHg) analysis. The geometric mean concentrations of THg and MeHg in the hair samples were 1.4 (range 0.50–6.0) μg/g and 1.1 (range 0.35–4.2) μg/g, respectively, while the geometric mean concentration of urine Hg (UHg) was 1.4 (range 0.09–26) μg/g Creatinine (Cr). The average of the probable daily intake (PDI) of MeHg via rice consumption was 0.052 (0.0033–0.39) µg/kg/day, which significantly correlated with the hair MeHg concentrations (r = 0.55, p < 0.01), indicating that ingestion of rice is the main pathway of MeHg exposure for children in this area. Furthermore, 18% (26/141) of the PDIs of MeHg exceeded the USEPA Reference Dose (RfD) of 0.10 µg/kg/day, indicating that children in this area are at a high MeHg exposure level. This paper for the first time evaluates the co-exposure levels of IHg and MeHg of children living in Wanshan mining area, and revealed the difference in exposure patterns between children and adults in this area. Full article

Selenium is an essential micronutrient for humans. Much of selenium’s beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on D-galactose-induced apoptosis in hLE cells were studied. The results showed that both D-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to D-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by D-galactose, implying that selenium as a micronutrient may play important roles in hLE cells. Full article

A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC₅₀ values ranging from 0.49 to 6.70 μM, which is more potent than the control drugs etoposide and cisplatin. Compound 21a is characterized by a perbutyrylated α-D(+)-galactosyl residue, the absence of an additional linking spacer between the sugar residue and the triazole ring, as well as a 4'-OH group on the E ring of the podophyllotoxin scaffold. Full article

A series of 4β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC₅₀ values ranging from 0.59 to 2.90 μM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue. Full article

The Xiemisitai area, West Junggar, Xinjiang, China, is situated at a potential copper mineralization zone in association with small granitic intrusions. In order to identify the alteration zones and mineralization characteristics of the intrusions, Landsat Enhanced Thematic Mapper (ETM+) and Quickbird data of the study area were evaluated in mapping lithological units, small intrusions, and alteration zones. False color composites of the first principal component analyses (PCA1), PCA2, and PCA4 in red (R), green (G), and blue (B) of the ETM+ image, and relevant hue-saturation-intensity (HSI) color model transformations, were performed. This led to the identification of lithologic units and discrimination of granitic intrusions from wall-rocks. A new geological map was generated by integrating the remote sensing results with two internally published local geologic maps and field inspection data. For the selected region, false color composites from PCA and relevant HSI-transformed images of the Quickbird data delineated the details of small intrusions and identified other unknown similar intrusions nearby. Fifteen separate potash-feldspar granites and three separate hornblende biotite granites were identified using ETM+ and Quickbird data. The principal component analysis-based Crosta technique was employed to discriminate alteration minerals. Some of the mapped alteration zones using the Crosta technique agreed very well with the known copper deposits. Field verification led to the discovery of three copper mineralizations and two gold mineralizations for the first time. The results show that the PCA and HSI transformation techniques proved to be robust in processing remote sensing data with moderate to high spatial resolutions. It is concluded that the utilized methods are useful for mapping lithology and the targeting of small intrusion-type mineral resources within the sparsely vegetated regions of Northwest China. Full article

A novel co-polymer based on 2-hydroxypropyl-α-cyclodextrin cross-linked by low molecular weight polyethylenimine was synthesized as a gene delivery vector. The copolymer could bind and condense DNA tightly. It showed lower cytotoxicity than PEI 25kDa in SK-BR-3 cells. Transfection efficiency was increased over 5.5-fold higher than PEI 25 kDa in SK-BR-3 cells in complete serum medium. It is a potential candidate vector for gene therapy. Full article