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Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway performs a central role in tumorigenesis and is constitutively activated in many malignancies. As a novel dual PI3K/mTOR inhibitor currently undergoing evaluation in a phase I/II clinical trial, NVP-BEZ235 indicates a significant antitumor efficacy in diverse solid tumors, including colorectal cancer (CRC). Autophagy is a catabolic process that maintains cellular homeostasis and reduces diverse stresses through lysosomal recycling of the unnecessary and damaged cell components. This process is also observed to antagonize the antitumor efficacy of PI3K/mTOR inhibitor agents such as NVP-BEZ235, via apoptosis inhibition. In the present study, we investigated anti-proliferative and apoptosis-inducing ability of NVP-BEZ235 in SW480 cells and the crosstalk between autophagy and apoptosis in SW480 cells treated with NVP-BEZ235 in combination with an autophagy inhibitor. The results revealed that, NVP-BEZ235 effectively inhibit the growth of SW480 cells by targeting the PI3K/mTOR signaling pathway and induced apoptosis. The inhibition of autophagy with 3-methyladenine or chloroquine inhibitors in combination with NVP-BEZ235 in SW480 cells enhanced the apoptotic rate as componets to NVP-BEZ235 alone. In conclusion, the findings provide a rationale for chemotherapy targeting the PI3K/mTOR signaling pathway presenting a potential therapeutic strategy to enhance the efficacy of dual PI3K/mTOR inhibitor NVP-BEZ235 in combination with an autophagy inhibitor in CRC treatment and treatment of other tumors.

Full tetrahedron connected structures possess considerable potential as cathodes for lithium-ion batteries (LIBs) due to more lithium storage sites to obtain high specific capacity. However, different from the full octahedron and octahedron/tetrahedron hybrid structures with coplanar or collinear, the tetrahedron network is connected by common vertex, which provokes structural instability and poor electrochemistry performance. Here, using first principles calculations combined with experiments, we found that a heavy distortion and big volume expansion during delithiation for full tetrahedron (LiO4, FeO4 and SiO4 tetrahedra) Li2FeSiO4 nanocrystal lead to phase change or even structure fracture, and the optimized Ti(IV) doped in Fe sites can enhance the coupling effect among the tetrahedra by the strong d-orbital hybridization and like “spring” to hold these tetrahedra and prohibit structure fracture. Meanwhile, the Ti(IV) doping can also shorten the distance of two adjacent Li sites to decrease the activation barrier for Li-ion diffusion. Furthermore, the n-type doping effect increases the electronic conductivity. This discovery can be extended to other tetrahedron structures as well, providing a general approach to develop promising next-generation cathode materials for high-energy and long-life lithium-ion batteries.

Esophageal cancer is one of the leading causes of mortality worldwide. Although, surgery, radio- and chemotherapy are used to treat the disease, the identification of new drugs is crucial to increase the curative effect. The aim of the present study was to examine the chemotherapeutic sensitizing effect of nimotuzumab (h-R3) and cisplatin cytotoxic drugs cisplatin (DDP) and 5-fluorouracil (5-FU) on esophageal carcinoma cells with two different epidermal growth factor receptor (EGFR) expressions. The expression of EGFR was detected in the human EC1 or EC9706 esophageal squamous cell carcinoma cell line using immunohistochemistry. The inhibitory effect of DDP and 5-FU alone or combined with h-R3 on EC1 or EC9706 cell proliferation was detected using an MTT assay. Flow cytometry and the TUNEL assay were used to determine the effect of single or combined drug treatment on cell apoptosis. The results showed that the expression of EGFR was low in EC1 cells but high in EC9706 cells. The inhibitory effect of the single use of h-R3 on EC1 or EC9706 cell proliferation was decreased. The inhibitory effect between single use of h-R3 alone and combined use of the chemotherapy drugs showed no statistically significant difference (P>0.05) on the EC1 cell growth rate, but showed a statistically significant difference (a=0.05) on EC9706 cell growth rate. The results detected by flow cytometry and TUNEL assay showed that the difference between single use of h-R3 alone and the control group was statistically significant with regard to the EC1 apoptosis rate effect (P0.05). However, statistically significant differences were identified in the apoptotic rate of EC9706 cells between the h-R3 combined chemotherapy group and single chemotherapy group (P0.05). In conclusion, the sensitization effect of h-R3 on chemotherapy drugs is associated with the expression level of EGFR in EC1 or EC9706 cells. The cell killing effect of the combined use of h-R3 with DDP and 5-FU showed no obvious synergistic effect compared to the single-drug group, but only an additive effect.

(1 − x)Li2FeSiO4·xLiFeBO3/C (x = 0, 0.02, 0.05, 0.08, 0.12, and 1.00) hetero-grains are successfully synthesized via an in situ citric acid-based sol–gel method and evaluated as cathode materials for lithium ion batteries. As a result, 0.92Li2FeSiO4·0.08LiFeBO3/C delivers an optimum discharge capacity of 251 mA h g−1 which corresponds to nearly 1.51 Li+ intercalation per molecule. Furthermore, a capacity retention of 104.5% after 5 cycles at 0.1 C is attained, and a value of 188.3 mA h g−1 (approaching 1.13 Li+ intercalation per molecule) remains even after one hundred cycles at 1 C. In particular, at a high-rate of 10 C, there is almost no capacity decline even after 500 cycles, indicating an excellent cycling stability. The greatly improved electrochemical lithium storage properties of the novel in situ hybridized materials can be attributed to the enhanced kinetics towards Li+ diffusion and electron transport compared with that of pure Li2FeSiO4/C electrodes.

The aim of the present study was to investigate the antitumor effects and possible mechanism of (-)-gossypol nanoparticles, loaded with vv polyethylene glycol-maleimide (mPEG-Mal), in vitro. Emulsification-volatilization was used to prepare the loaded (-)-gossypol nanoparticles. The toxicity of blank nanoparticles on human prostate cancer PC-3 cells and human prostate RWPE-1 cells was measured. The antitumor effects of the nanoparticles on PC-3 cells were evaluated by an MTT assay, acridine orange staining and transmission electron microscopy in vitro, and the results were compared with those of free (-)-gossypol. In addition, the mRNA expression levels of Bcl-2 and Bak were measured using semi-quantitative reverse transcription polymerase chain reaction. The growth inhibition activity of the loaded (-)-gossypol nanoparticles was found to be dose- and time-dependent, and similar to the activity of free (-)-gossypol. The nanoparticles induced apoptotic morphological changes on the PC-3 cells, downregulating the mRNA expression level of Bcl-2 and upregulating the mRNA expression level of Bak. Blank nanoparticles exhibited no evident toxicity on PC-3 and RWPE-1 cells at a high dose. Therefore, the mPEG-Mal loaded (-)-gossypol nanoparticles demonstrated a favorable antitumor activity and no toxicity. The nanoparticles were able to induce the apoptosis of prostate cancer cells; thus, may be a potential antitumor nanodrug.

Development of a cathode material with safety, low cost, high energy and power densities, long life and excellent abuse tolerance for Li-ion batteries is critical for hybrid electric vehicles (HEVs) and electric vehicles (EVs). Here, we developed graphene activated 3D-hierarchical flower-like Li2FeSiO4 with secondary nanopetals (G@3D-HFLFS), which exhibited a discharge capacity of 327.2 mA h g(-1) (specific energy of 879 W h kg(-1)) approaching the full theoretical capacity with large-current and long-life performance. The electrochemical reaction mechanism of G@3D-HFLFS was investigated by Mossbauer spectroscopy and parallel model X-band ESR. The high performance can be attributed to the secondary petal-like structures having an ultra-rapid Li-ion diffusion along the minimum length, the graphene coating layers facilitating double transport of electrons and Li-ions, and the special hierarchical structure with an optimal petal thickness possessing excellent structural stability. These results clearly demonstrate that our novel material is a promising cathode for commercial applications that require high energy and power densities, long operating life and excellent abuse tolerance.

Cyclin D1 polymorphism has been reported to be associated with risk of breast cancer, but the published studies have yielded controversial results. This study was undertaken to derive a precise risk estimate for the cyclin D1 polymorphism associated with breast cancer risk. We performed a search of EMBASE, PubMed, and Web of Science. In total, data from 18 publications were pooled and the association was assessed by odds ratios (ORs) with 95 % confidence intervals (CIs). This analysis showed that there was no obvious association between the cyclin D1 polymorphism and breast cancer risk in any of the analyzed genetic model. We found the same negative association in stratified analyses by ethnicity, source of controls, and sample size. Our meta-analysis provides an estimate that the presence of cyclin D1 polymorphism may not confer susceptibility to breast cancer.

The P21/n structured nanocrystalline-Li2FeSiO4 is prepared by a confinement effect of three-dimensional conductive carbon frameworks, which are formed through a chelating reaction and subsequent pyrolysis. As a benefit of enhanced electronic conductivity by carbon frameworks and Li-ion diffusion kinetics by nanocrystalline-Li2FeSiO4 architectures, the novel nanocomposite shows a 1.28 Li-ion storage capacity (211.3 mA h g−1) at 0.1 C, corresponding to two successive steps of oxidation and reduction of Fe2+/Fe3+/Fe4+. Furthermore, the discharge capacity is 189.8, 175.6, 148.9, 125.7 and 106.6 mA h g−1 at a variable rate of 0.5, 1, 2, 5 and 10 C, respectively, and then easily returns to 175 mA h g−1 at 1 C. It is a surprise that the initial capacity is 90.9 mA h g−1 at 10 C, and 97.7% is retained after 1000 cycles. Thus, we believe that the nanocrystalline-Li2FeSiO4 with carbon frameworks, possessing high-capacity and high-rate performance, is a promising next-generation cathode material for high-power lithium-ion batteries.

We successfully synthesized the novel hierarchical shuttle-like Li2FeSiO4 using one step hydrothermal method with ethylene glycol assisted. The growth mechanism of the shuttle-like Li2FeSiO4 constructed of nanosingle crystals was discussed and its electrochemical performance as a cathode material for lithium ion battery was investigated. Astonishingly, the 1st discharge specific capacity of the new material without carbon coating was 180.6 mA h g−1 at 0.1 C with a remarkably high Coulombic efficiency of 97.5%, and an improved high-rate capability (71.0 mA h g−1 at 2 C) was offered which is comparable to the commonly carbon-coated Li2FeSiO4. Moreover, it exhibited a very stable discharge specific capacity at current densities from 0.1 to 2 C. Its excellent electrochemical performance can be ascribed to the significantly improved diffusion coefficient of lithium ions (5.6421 * 10−11 cm2 s−1), which was greatly larger than the reported carbon-coated Li2FeSiO4 nanocomposites and diatomic metallic ions (Ni2+, Cu2+, Zn2+) doped Li2FeSiO4. These indicate the shuttle-like Li2FeSiO4 is a very promising cathode material for lithium-ion batteries.

Li 2 FeSiO 4 /C/carbon nanosphere (CNS) composites as cathode materials for lithium-ion batteries were synthesized by a simple hydro-chemical method. The double-carbon structural design of glucose pyrolysis-carbon (C) and CNS improved electrochemical performance of the composite where the CNS can build conductivity belts to connect the Li 2 FeSiO 4 /C particles and to favor electronic transmission. The exchange current density and the diffusion coefficient of lithium ions with the composite were 0.208 mA cm −2 and 1.06E−11 cm 2 S −1 , respectively, which were much larger than that of conventional Li 2 FeSiO 4 /C composite cathode materials ( i = 0.131 mA cm −2 , D Li = 4.69E−12 cm 2 S −1 ). The electrochemical test results showed that the discharge capacity of 164.7 mA h g −1 could be obtained, and especially, after 60 cycles, 98.4% of the initial discharge capacity remained at 0.1 C of galvanostatic discharge in the potential range of 1.5–4.8 V (vs. Li/Li + ). In addition, the discharge capacity of 92.4 mA h g −1 at 5 C was easily recovered to 159.8 mA h g −1 at 0.1 C.

This study was devised to investigate the genetic effect modification of the BsmI polymorphism associated with the susceptibility to breast cancer. Case-control studies of the BsmI polymorphism and breast cancer were searched. A total of 17 eligible publications were included in our final analysis. Pooled ORs and 95 % CIs were obtained by means of fixed effects model. The general and stratified analyses according to ethnicity showed that the association between the BsmI polymorphism and the risk of breast cancer was not statistically significant. However, the subgroup of the hospital-based studies was found to confer protection against the disease (ORBBvs.bb = 0.83, 95 % CI = 0.71-0.97, P h = 0.571; OR BBvs.Bb+bb = 0.86, 95 % CI = 0.74-1.00, P h = 0.903; OR allele B vs. allele b = 0.92, 95 % CI = 0.86-0.99, P h = 0.337). Our results suggested that the presence of the BsmI polymorphism may contribute to the susceptibility of breast cancer. It is necessary that future large-scale studies should be conducted to further confirm the association between the BsmI polymorphism and breast cancer risk.