Theoretical Prediction on Properties of 3,4-Bisnitrofurazanfuroxan (DNTF) Crystal and its Polymer Bonded Explosives (PBXs) Through Molecular Dynamics (MD) Simulation.

CONTEXT: 3,4-Bisnitrofurazanfuroxan (DNTF) is a typical high energy density compound (HEDC), it has high crystal density and detonation parameters, but also high mechanical sensitivity. To decrease its mechanical sensitivity, the DNTF based polymer bonded explosives (PBXs) was designed. The pure DNTF crystal and PBXs models were established. The stability, sensitivity, detonation performance and mechanical properties of DNTF crystal and PBXs models were predicted. Results show that PBXs models containing fluorine rubber (F2311) and fluorine resin (F2314) have higher binding energy, meaning that DNTF/F2311 and DNTF/F2314 is relatively more stable. PBXs models have higher value of cohesive energy density (CED) than pure DNTF crystal, DNTF/F2311 and DNTF/F2314 have the highest value of CED, implying that the sensitivity of PBXs is effectively decreased, DNTF/F2311 and DNTF/F2314 is more insensitive. PBXs have lower crystal density and detonation parameters than DNTF, the energy density is declined, DNTF/F2314 has higher energetic performance than other PBXs. Compared with pure DNTF crystal, engineering moduli (tensile modulus, shear modulus, bulk modulus) of PBXs models are obviously decreased, but Cauchy pressure is increased, implying that the mechanical properties of PBXs is superior to pure DNTF component, the PBXs containing F2311 or F2314 have more preferable mechanical properties. Consequently, DNTF/F2311 and DNTF/F2314 have the best comprehensive properties and is more attractive among the designed PBXs, indicating that F2311 and F2314 are more advantageous and promising in ameliorating properties of DNTF. METHODS: The properties of DNTF crystal and PBXs models were predicted through molecular dynamics (MD) method under Materials Studio 7.0 package. The MD simulation was performed with isothermal-constant volume (NVT) ensemble, and the force field was chosen as COMPASS force field. The temperature was set as 295 K, the time step was 1 fs and the total MD simulation time was 2 ns.

Designing and property prediction of a novel three-component CL-20/HMX/TNAD energetic cocrystal explosive by MD method.

CONTEXT: Cocrystallization technology can effectively regulate crystal structure, alter packing mode, and improve physicochemical performances of energetic materials at molecule level. CL-20/HMX cocrystal explosive has high energy density than HMX, but it also exhibits high mechanical sensitivity. To decrease the sensitivity and improve the properties of CL-20/HMX energetic cocrystal, the three-component energetic cocrystal CL-20/HMX/TNAD was designed. The properties of CL-20, CL-20/HMX, and CL-20/HMX/TNAD cocrystal models were predicted. The results show that CL-20/HMX/TNAD cocrystal models have better mechanical properties than CL-20/HMX cocrystal model, implying that the mechanical properties can be effectively improved. The binding energy of CL-20/HMX/TNAD cocrystal models is higher than CL-20/HMX cocrystal model, indicating that the three-component energetic cocrystal is more stable, and the cocrystal model with the ratio 3:4:1 is predicted to be the most stable phase. CL-20/HMX/TNAD cocrystal models have higher value of trigger bond energy than pure CL-20 and CL-20/HMX cocrystal models, meaning that the three-component energetic cocrystal is more insensitive. The crystal density and detonation parameters of CL-20/HMX and CL-20/HMX/TNAD cocrystal models are lower than CL-20, illustrating that the energy density is declined. The CL-20/HMX/TNAD cocrystal has higher energy density than RDX and can be regarded as a potential high energy explosive. METHODS: This paper was performed with molecular dynamics (MD) method with the software of Materials Studio 7.0 under COMPASS force field. The MD simulation was performed under isothermal-isobaric (NPT) ensemble, the temperature and pressure was 295 K and 0.0001 GPa, respectively.

Theoretical research on performances of CL-20/HMX cocrystal explosive and its based polymer bonded explosives (PBXs) by molecular dynamics method.

In this article, the CL-20/HMX cocrystal model was established and its based polymer bonded explosives (PBXs) were designed. The static performances, including mechanical properties, stability and detonation performance of CL-20/HMX cocrystal model and PBXs models, were predicted by molecular dynamics (MD) method. The mechanical parameters, binding energy, and detonation parameters of PBXs models were calculated and compared with that of pure CL-20/HMX cocrystal model. The influence of polymer binders on performances of CL-20/HMX cocrystal explosive was evaluated. Results show that the polymer binders make the engineering moduli (tensile modulus, shear modulus, and bulk modulus) of PBXs declined and Cauchy pressure increased, meaning that the polymer binder can obviously improve mechanical properties of CL-20/HMX cocrystal explosive, and the PBXs model with fluorine rubber (F2311) has the best mechanical properties. In different PBXs models, the binding energy between CL-20, HMX molecules and F2311 is higher than other polymer binders, indicating that the CL-20/HMX/F2311 model is more stable. The PBXs models have lower value of crystal density and detonation parameters compared with pure CL-20/HMX cocrystal and the energetic performance of PBXs is weakened. The PBXs model with fluorine resin (F2314) has the highest energetic performance and it is higher than pure HMX. Therefore, the CL-20/HMX/F2311 and CL-20/HMX/F2314 models have more favorable comprehensive properties, proving that F2311 and F2314 are more preferable and promising to design CL-20/HMX cocrystal based PBXs.

Highly sensitive fluorescent detection of EDIL3 overexpressed exosomes for the diagnosis of triple-negative breast cancer.

EDIL3 is a strong and highly accurate diagnostic marker for breast cancer, meanwhile, EDIL3 overexpressed exosomes are novel biomarkers for the early diagnosis of triple-negative breast cancer (TNBC). Here, we proposed a fluorescent detection method for EDIL3 overexpressed exosomes, which is simple and sensitive. Basically, we utilized a magnetic nanospheres (MNS) based liquid sandwich immunoassay strategy. MNS were modified with CD63 aptamers, which can immunologically bound to the CD63 protein on the surface of exosomes. Alexa Fluor 647 labeled anti-EDIL3 antibodies (Anti-EDIL3/AF647) were used as the fluorescent probes to recognize the EDIL3 on exosomes derived from a TNBC cell line (MDA-MB-231). With the target TNBC exosomes present, sandwich structures containing MNS, exosomes and fluorescent probes were formed. After magnetic purification, optical super resolution imaging of the products was conducted to check the specificity of the assay. In addition, fluorescence signals of the products were detected to quantitatively analyze the EDIL3 overexpressed exosomes. The linear range was found to be 7.78 × 101to 7.78× 106particlesµl-1. The detection limit was approximately 10 particlesµl-1. The feasibility of the method for the detection of exosomes in complex biological samples was also demonstrated. Such a simple and sensitive detection method for EDIL3 overexpressed exosomes holds a great potential in clinical diagnosis of TNBC.

Real-World Prescription Patterns For Patients With Young-Onset Parkinson's Disease in China: A Trend Analysis From 2014 to 2019.

Introduction Pharmacotherapy is one of the main treatments for patients with young-onset Parkinson's disease (YOPD). Although numerous studies on the treatment of YOPD have been published, the real-world prescription patterns of these populations remain unclear in China. Methods A national comprehensive evaluation was performed to reveal the pharmacological treatment patterns in Chinese patients with Parkinson's disease from 1 January 2014 to 31 December 2019, with patients aged 21-50 years classified as having YOPD for the subgroup analysis. Information on patients and drugs was extracted to analyse the demographic characteristics, prescription patterns, and levodopa equivalent daily dose (LED) during disease progression. Results A total of 1,134 patients with YOPD were included, and the majority were aged 41-50 years. Prescription of L-DOPA/benserazide and pramipexole accounted for more than 30 and 20%, respectively, in each year from 2014 to 2019. There was no difference in prescription patterns in terms of age, sex and geographical areas. Half of the patients with YOPD were on monotherapy, but the proportion decreased from 2016. Correspondingly, the proportion of patients receiving polytherapy increased, especially those who were prescribed more than two anti-Parkinson's disease drugs. During the disease course, LED showed high variability, which increased over time. Conclusion L-DOPA/benserazide and pramipexole were the most frequently prescribed anti-PD drugs for patients with YOPD in China. There was a slight trend in the transition from monotherapy to polytherapy. LED increased with disease duration. Thus, we provided an overview of the prescription patterns for patients with YOPD in China.

Theoretical investigations on stability, sensitivity, energetic performance, and mechanical properties of CL-20/TNAD cocrystal explosive by molecular dynamics method.

The crystal models of trans-1,4,5,8-tetranitro-1,4,5,8-tetraazadecalin (TNAD), hexanitrohexaazaisowurtzitane (CL-20), and CL-20/TNAD cocrystal explosive with different component ratios were established. Molecular dynamics (MD) method was applied to predict the stability, sensitivity, energetic properties, and mechanical properties. The effect of component ratio on properties of CL-20/TNAD cocrystal explosive was investigated and estimated. Results show that the cocrystal model with component ratio in 1:1 exhibits the highest binding energy and it is more stable. In CL-20/TNAD cocrystal explosive, the interaction energy of trigger bond is increased by 0.8 ~ 15.0 kJ/mol, implying that the mechanical sensitivity of CL-20/TNAD cocrystal explosive is lower than CL-20 and the safety is effectively improved. Compared with raw CL-20, the crystal density of cocrystal explosive is declined by 0.014 ~ 0.193 g/cm3, detonation velocity is declined by 39 ~ 755 m/s, and detonation pressure is declined by 0.95 ~ 11.40 GPa; namely the energy density of CL-20/TNAD cocrystal explosive is lower than CL-20. The cocrystal explosives with component ratio in 10:1 ~ 1:1 still exhibit desirable detonation performance and can be regarded as high energy density explosives. The values of tensile modulus, shear modulus, and bulk modulus of CL-20/TNAD cocrystal explosive are decreased by 0.448 ~ 10.285 GPa, 0.195 ~ 4.189 GPa, and 0.194 ~ 6.292 GPa, respectively, Cauchy pressure is increased by 0.990 ~ 5.704 GPa, meaning that the rigidity, fracture strength, and hardness of cocrystal explosive are declined, while the plastic property and ductility are increased and the mechanical properties are improved. The cocrystal model with component ratio in 1:1 has the best mechanical properties. Consequently, the CL-20/TNAD cocrystal explosive with component ratio in 1:1 is more stable and insensitive; it also has high energy density and the best mechanical properties and may be an attractive candidate for high energy explosives.

Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line.

AIM: To investigate the apoptosis-inducing effect of oridonin, a diterpenoid isolated from Rabdosia rubescens, in the human cervical carcinoma HeLa cell line. METHODS: A morphological analysis, nuclear condensation, and fragmentation of chromatin were monitored using Hoechst 33342 staining. Cell viability was assessed using the 3-(4, 5-dimethylthiazol-(2)-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and the apoptosis-related activation in the HeLa cell line were evaluated by flow cytometry and Western blotting. RESULTS: Oridonin suppressed the proliferation of the HeLa cell line in a dose- and time-dependent fashion. Oridonin treatment downregulated the activation of protein kinase B (Akt), the expression of forkhead box class O (FOXO) transcription factor, and glycogen synthase kinase 3 (GSK3). Oridonin also induced the release of cytochrome c accompanied by the activation of caspase-3 and poly-adenosine diphosphate- ribose polymerase cleavage. In addition, Z-D(OMe)-E(OMe)-V-D(OMe)- FMK (z-DEVD-fmk), an inhibitor of caspases, prevented caspase-3 activation and abrogated oridonin-induced cell death. Finally, oridonin treatment of the HeLa cell line downregulated the expression of the inhibitor of the apoptosis protein. CONCLUSION: Our results showed that oridonin-induced apoptosis involved several molecular pathways. Oridonin may suppress constitutively activated targets of phosphatidylinositol 3-kinase (Akt, FOXO, and GSK3) in the HeLa cell line, inhibiting the proliferation and induction of caspase-dependent apoptosis.