Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.

A Novel Method for Identifying Recursive Systematic Convolutional Encoders Based on the Cuckoo Search Algorithm

The existing methods for identifying recursive systematic convolutional encoders with high robustness require to test all the candidate generator matrixes in the search space exhaustively.With the increase of the codeword length and constraint length,the search space expands exponentially,and thus it limits the application of these methods in practice.To overcome the limitation,a novel identification method,which gets rid of exhaustive test,is proposed based on the cuckoo search algorithm by using soft-decision data.Firstly,by using soft-decision data,the probability that a parity check equation holds is derived.Thus,solving the parity check equations is converted to maximize the joint probability that parity check equations hold.Secondly,based on the standard cuckoo search algorithm,the established cost function is optimized.According to the final solution of the optimization problem,the generator matrix of recursive systematic convolutional code is estimated.Compared with the existing methods,our proposed method does not need to search for the generator matrix exhaustively and has high robustness.Additionally,it does not require the prior knowledge of the constraint length and is applicable in any modulation type.

Study on the effect of PET/CT-guided nasopharyngeal carcinoma target delineation on the dose received by endangered organs

Objective:To compare the differences of radiation-induced doses between 18F-FDG-PET/CT and CT/MRI-guided target delineation in nasopharyngeal carcinoma in intensity-modulated radiotherapy.Methods:A total of 31 patients with locally advanced nasopharyngeal carcinoma receiving treatment in our hospital from December 2016 to December 2017 were studied in this research,and 18F-FDG-PET/CT and CT/MRI were used to guide the target delineation to develop an intensity-modulated radiotherapy plan(experimental group and control group).The dose differences between GTV and endangered organs in the two groups were compared.Results:Comparison of primary tumor volume:PET/CT was smaller than CT/MRI,and volumes of T3 and T4 were significantly different(P<0.001).Comparison of the two delineation plans,in terms of PGTV in Dmin,Dmean,and D95,the data of experimental group was smaller than that of the control group;in Dmax,the PGTV of the experimental group was larger than that of the control group with P<0.001 considered as a significant difference.In Dmin and Dmax,doses of experimental groups of the spinal cord were lower than those of the control group,showing a significant difference(P=0.022,0.042);In Dmean,there was no difference between the two groups.In Dmax doses of an experimental group of the brainstem and parotid gland were significantly smaller than the control group(P=0.001,0.047)while there was no difference between Dmin and Dmean.There was no difference between the two groups of Dmin,Dmean,and Dmax in the doses received by chiasm and temporal lobe.Conclusion:PET/CT guided target delineation is applied in the simultaneous dose adjustment of intensity-modulated radiation therapy in patients with advanced nasopharyngeal carcinoma.In primary lesion targets shown by MRI/CT,the tumor tissue of PET/CT concentration zone was given a higher dose with relatively smaller average dose and minimum dose in the overall tumor target area.Statistics also showed that the doses received by the spinal cord,brain stem,and parotid gland were reduced with no effect on the optic chiasm and temporal lobe.In the future,more studies should probe into the long-term effects of dose changes on lesion control and endangered organs.

High safety separators for rechargeable lithium batteries

Lithium-ion batteries(LIBs)are presently dominant mobile power sources due to their high energy density,long lifespan,and low self-discharging rates.The safety of LIBs has been concerned all the time and become the main problem restricting the development of high energy density LIBs.As a significant part of LIBs,the properties of separators have a significant effect on the capacity and performances of batteries and play an important role in the safety of LIBs.In recent years,researchers devoted themselves to the development of various multi-functional safe separators from different views of methods,materials,and practical requirements.In this review,we mainly focus on the recent progress in the development of high-safety separators with high thermal stability,good lithium dendritic resistance,high mechanical strength and novel multifunction for high-safety LIBs and have in-depth discussions regarding the separator's significant contribution to enhance the safety and performances of the batteries.Furthermore,the future directions and challenges of separators for the next-generation high-safety and high energy density rechargeable lithium batteries are also provided.

Design and synthesis of biotinylated dimethylation of alkannin oxime derivatives

DMAKO-05,a novel dimethylation of alkannin oxime derivative,exhibits remarkable anticancer activity as well as excellent cellular selectivity and thus has been considered as a promising antineoplastic agent for colorectal carcinoma and melanoma.However,its potent cytotoxicity is not closely associated with reactive oxygen species（ROS） and bioreductive alkylation.Its specific antitumor target（s） has still remained elusive.To recognize the molecular target（s） of DMAKO-05 and its analogs,four biotinylated DMAKO derivatives were designed and prepared.The biotin moiety was successfully introduced in the molecule through a modified Mitsunobu reaction,which kept its anticancer activity.Moreover,the cellbased investigation demonstrated that replacement of the linker C4 chain with another alkyl chain（C6 or C8） gave rise to the enhancement of cytotoxicity.Among these biotinyl derivatives,both compound 16 and 8c exhibited more potent anticancer activity than DMAKO-05 against MCF-7 cells and were comparatively effective to alkannin toward HCT-15 cells.As expected,they might be thought as ideal chemical probes.Collectively,our present work could provide an available approach for the identification of the potential antineoplastic target（s） of DMAKO derivatives.

Trigger and response mechanisms for controlled release of corrosion inhibitors from micro/nanocontainers interpreted using endogenous and exogenous stimuli:A review

Metallic corrosion can lead to both economic losses and environmental pollution due to undesired chemical and biochemical reactions.Furthermore,there are a number of drawbacks associated with different corrosion prevention and mitigation techniques.In view of these challenges,corrosion inhibitor-based smart micro/nanocontainers(CISCs)with stimuli-responsive functionality emerge as an important alternative technical approach in dealing with metallic corrosion.The development of CISCs involves controlled release corrosion inhibitors and self-healing coatings.This review focuses on the trigger and response mechanisms of controlling the discharge of corrosion inhibitors from micro/nanocontainers(a core-shell or layered structure)into aqueous solution under endogenous(pH,redox,and ion-exchange).exogenous(temperature,magnetic field,and light),and multiple stimuli.When these CISCs are embedded into coating materials,the self-healing effect of the coating can manifest to protect various types of metals.In this review effort,different types of CISCs are classified for the first time into the following three categories:inorganic,organic,and organic-inorganic hybrid.We also discuss application scope,future perspectives,and research strategies for CISCs in the hopes of increasing the life of corrosion protection and providing inspiration in related fields.

Cerium(Ⅳ)ammonium nitrate(CAN)-mediated regioselective synthesis and anticancer activity of 6-substituted 5,8-dimethoxy-1,4-naphthoquinone

6-Substituted 5,8-O-dimethyl-1,4-naphthoquinones（6-DMNQ）,the promising anticancer scaffolds,were selectively generated by oxidative demethylation of 2-substituted 1,4,5,8-tetramethoxynaphthalenes with CAN in EtOAc/H2O in comparatively high yields.An interesting finding was that apart from the reported electron-withdrawing effects of substituents on position 2 of naphthalene ring,regioselective synthesis of 6-DMNQ was largely dependent on the steric effects in CAN-mediated oxidation.The selective cytotoxicities of 6-DMNQ from the in vitro cell-based assays were exhibited between the cancer cells and normal cells.Moreover,most of sulfur-containing 6-DMNQ derivatives displayed better anticancer activities than the corresponding oxygen-containing ones,which could provide an available strategy for the design of 6-DMNQ derivatives as potential anticancer agents.