Modeling epidemic in metapopulation networks with heterogeneous diffusion rates.

In this paper, the process of the infectious diseases among cities is studied in metapopulation networks. Based on the heterogeneous diffusion rate, the epidemic model in metapopulation networks is established. The factors affecting diffusion rate are discussed, and the relationship among diffusion rate, connectivity of cities and the heterogeneity parameter of traffic flow is obtained. The existence and stability of the disease-free equilibrium and the endemic equilibrium are analyzed, and epidemic threshold is also obtained. It is shown that the more developed traffic of the city, the greater the diffusion rate, which resulting in the large number of infected individuals; the stronger the heterogeneity of the traffic flow, the greater the threshold of the disease outbreak. Finally, numerical simulations are performed to illustrate the analytical results.

The Effect of Prescription on the Framework of Lipid Matrix and In Vitro Properties.

PURPOSE: To clarify the inner framework and relative properties in vitro of Lyotropic liquid crystal (LLC) based on various prescriptions by using hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) as model drugs. METHODS: Phase structures were checked by polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological studies and Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) analysis were carried out to reveal their molecular interactions. In vitro release and skin permeation were conducted by Franz diffusion cell. RESULTS: PLM and SAXS showed double diamond cubic crystal. All the samples displayed characteristics of non-Newtonian fluid, and the molecular interactions increased with the reducing water. ATRFTIR showed that the strongest strength of hydrogen bond emerged in the formulation with 32% water. Released SH of S2 and S3 arrived over 80%, while S1 only reached 45%, and that of CA was about 23%. Water-rich prescription gave higher percutaneous penetration for hydrophilic drugs, whereas no significant difference existed in CA permeation. CONCLUSION: Proportion of Phytantriol to water determined the LLC assembling and affected the dissolving status of hydrophilic substance, thereby impacting on the location sites of guest molecular interactions among the substances, rheology properties, and finally the release and penetration behavior in vitro. Adjusting the basic prescription was the key to obtain satisfactory percutaneous delivery and stability for LLC carrying multi-therapeutic agents.

On the Structure and Transdermal Profile of Liquid Crystals Based on Phytantriol.

BACKGROUND: There has been a growing concern in transdermal drug technology over the past several decades. As a novel transdermal delivery system, Lyotropic liquid crystals (LLC) still face challenges such as drug loading, limited drug permeation and instability of systems. LLC system is so sensitive that a very subtle change in composition may induce a phase transformation or conversion of spatial configuration, and result in a diverse percutaneous delivery subsequently. OBJECTIVE: To find out the effects of hydrophilic and lipophilic components on the structure and transdermal properties of LLCs, hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) was chosen as a model drug and a skin permeation enhancer, respectively, several formulations were prepared and compared. METHOD: The structure of LLC was evaluated by visual observation, Cross-polarizing light microscopy (CPLM) and Small angle X-ray diffraction (SAXS). The Franz diffusion cell was applied to investigate its skin penetration of SH across the rat skins. Fourier transform infrared spectroscopy (FTIR) was recorded to evaluate the intermolecular interaction between the LC samples and stratum corneum (SC). CONCLUSION: The results showed that a controlled transdermal process might be obtained by adjusting the ratios of different drugs or loading doses when LLCs with dual-components were applied.

[Rheological properties of sinomenine in situ liquid crystal as liquid embolic agent].

Three different kinds of sinomenine in situ liquid crystal were prepared for different prescriptions, to investigate the rheological properties before and after in situ treatment and evaluate its feasibility for embolization. Rheological experiments were carried out with cone plate fixtures. Both the steady-state rheological and non-steady-state rheological properties of in-situ gels and the swelling gels were studied and compared. Steady-state rheological study results showed that all the three liquid embolic agents were non-newtonian fluid before and after in situ treatment, which would become less ropy when they were pressed with shear stress; their viscosities differed by 2-5 orders of magnitude. It had a yield value of about 10 Pa before in situ treatment and about 4 500 Pa after in situ treatment. All the six systems had thixotropy while their dynamic viscosities were not influenced by the shear rate, all less than 0.3 Pa·s before in situ treatment more than 1 Pa·s after in situ treatment, differing by an order of magnitude. The results of temperature sweeping showed a slight decrease with a steady rate in viscosity within the range of 10-50 °C, differing by 3-4 orders of magnitude. The results of unsteady rheology showed that there was no obvious linear viscoelastic region in the three kinds of agents, indicating the properties of liquid. After in situ treatment, their linear viscoelastic range γ<1% (No.3 was 5%), and their elastic modulus G' was larger than the viscous modulus G", indicating the properties of solid. Frequency scanning results showed that for the systems at low frequencies, G">G', system viscosity in a dominant position; while at high frequencies, G'>G", system elasticity in a dominant position. The results of compound viscosity test also proved that the liquid embolic agent in situ can form a cubic liquid crystal (the structure of No. 3 was destroyed after in situ treatment). The DHR-2 rheometer was used to investigate the rheological properties of in situ gels with three different prescriptions. The method is simple and the result is reliable, which can provide more theoretical reference for the in vitro evaluation and practical application of the product.

ROR1 is a novel prognostic biomarker in patients with lung adenocarcinoma.

Currently, there is no reliable biomarker to clinically predict the prognosis of lung adenocarcinoma (ADC). The receptor-tyrosine-kinase like orphan receptor 1 (ROR1) is reported to be overexpressed and associated with poor prognosis in several tumors. This study aimed to examine the expression of ROR1 and evaluate its prognostic significance in human lung ADC patients. In this present study, Western blot analysis and immunohistochemistry were performed to characterize expression of ROR1 protein in lung ADC patients. The results revealed that ROR1 protein expression was significantly higher in lung ADC tissues than that in their adjacent non-tumor tissues. Patients at advanced stages and those with positive lymph node metastasis expressed higher level of ROR1 (P < 0.001). Moreover, Chi-square test showed that ROR1 expression was correlated to gender (P = 0.028), the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) staging system and lymph node metastasis (P < 0.001). Kaplan-Meier survival analysis indicated an association of high ROR1 expression with worse overall survival (OS) in lung ADC patients (P < 0.001). Multivariate COX regression analysis further confirmed that ROR1 is an independent prognostic predictor (P < 0.001, HR = 4.114, 95% CI: 2.513-6.375) for OS. Therefore, ROR1 expression significantly correlates with malignant attributes of lung ADC and it may serve as a novel prognostic marker in lung ADC patients.

Annoyance and activity disturbance induced by high-speed railway and conventional railway noise: a contrastive case study.

BACKGROUND: High-speed railway (HR, Electrified railway with service speed above 200 km/h.) noise and conventional railway (CR, Electrified railway with service speed under 200 km/h.) noise are different in both time and frequency domain. There is an urgent need to study the influence of HR noise and consequently, develop appropriate noise evaluation index and limits for the total railway noise including HR and CR noise. METHODS: Based on binaural recording of HR and CR noises in a approximate semi-free field, noise annoyance and activity disturbance induced by maximal train pass-by events in China were investigated through laboratory subjective evaluation. 80 students within recruited 102 students, 40 males and 40 females, 23.9 ± 2.1 years old, were finally selected as the subjects. After receiving noise stimulus via headphone of a binaural audio playback system, subjects were asked to express the annoyance or activity disturbance due to railway noise at a 0-100 numerical scale. RESULTS: The results show that with the same annoyance rating (A) or activity disturbance rating (D), the A-weighted equivalent sound pressure level (LAeq) of CR noise is approximately 7 dB higher than that of HR noise. Linear regression analysis between some acoustical parameters and A (or D) suggests that the coefficient of determination (R2) is higher with the instantaneous fast A-weighted sound pressure level (LAFmax) than that with LAeq. A combined acoustical parameter, LHC = 1.74LAFmax + 0.008LAFmax(Lp-LAeq), where Lp is the sound pressure level, was derived consequently, which could better evaluate the total railway noise, including HR and CR noise. More importantly, with a given LHC, the noise annoyance of HR and CR noise is the same. CONCLUSIONS: Among various acoustical parameters including LHC and LAeq, A and D have the highest correlation with LHC. LHC has been proved to be an appropriate index to evaluate the total railway noise, including both HR and CR. However, it should be pointed out that this study provides suggestive evidence, rather than a final proof. Further study is expected to elucidate conclusions above by additional measurements.

[Study on the soil salinization monitoring based on synthetical hyperspectral index].

The present paper selected the spectral reflectivity of saline soil and vegetation of Weigan-Kuqa River Delta Oasis in the northern margin of the Tarim Basin in Xinjiang as objects, and used various spectral transforms to process the data with continum removed methods, derivate spectra, reciprocal, first order differential and root mean square etc, then analyzed the spectrum features and decided the most sensitive band ranges most relevant to salinization, and used field hyperspectral vegetation index, soil salinity index and measured synthetical spectral index to respectively establish hyperspectral quantitative models which could evaluate the soil salinization degrees. By comparing various spectral transformations of hyperspectral data the result showed that the first derivative of measured soil and vegetation hyperspectral were most sensitive to soil salinization degrees. The hyperspectral quantitative model based on measured synthetical spectral index could monitor soil salinization accurately and was better than the models simply based on vegetation index or soil salinity index. The research provided some scientific basis with soil salinization detection.

Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe.

In order to investigate the physiological effects of airport noise exposure on organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d. For comparison, we also used unexposed control rats. Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (L(WECPN)) of 75 and 80 dB for the two experimental groups. We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD). We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM). Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals. After 29 d of airport noise exposure, the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05). We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe.

Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer.

Metastatic breast cancers are hard to treat and almost always fatal. Chloroquine diphosphate, a derivative of quinine, has long been used as a potent and commonly used medicine against different human diseases. We therefore investigated the effects of chloroquine diphosphate on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of 4T1 mouse breast cancer cells with chloroquine diphosphate resulted in significant inhibition of cellular proliferation and viability, and induction of apoptosis in 4T1 cells in a time- and dose-dependent manner. Further analysis indicated that induction of apoptosis was associated with the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase. The effect of chloroquine diphosphate was then examined using a mice model in which 4T1 cells were implanted subcutaneously. Chloroquine diphosphate (25mg/kg and 50mg/kg, respectively) significantly inhibited the growth of the implanted 4T1 tumor cells and induced apoptosis in the tumor microenvironment. Moreover, the metastasis of tumor cells to the lungs was inhibited significantly and the survival of the mice enhanced. These data suggested that chloroquine diphosphate might have chemotherapeutic efficacy against breast cancer including inhibition of metastasis.

Barbigerone, a natural isoflavone, induces apoptosis in murine lung-cancer cells via the mitochondrial apoptotic pathway.

Barbigerone is a naturally occurring isoflavone with antioxidant activity. In present study, we investigated the antitumor activity of barbigerone against murine lung cancer cells LL/2 and the possible mechanism in vitro. Our results showed that barbigerone inhibited LL/2 cells proliferation in a concentration- and time-dependent manner and caused apoptotic death of LL/2 cells. Barbigerone-induced apoptosis was characterized by enhanced mitochondrial cytochrome c release, activation of caspase-3,-9, but not caspase-8. Exposure of LL/2 cells to barbigerone resulted in upregulation of Bcl-2-associated protein (Bax) and down-regulation of Bcl-2. In addition, proliferation inhibitory effect of barbigerone was associated with decreased level of phosphorylated p42/44 mitogen-activated protein kinase (p42/44 MAPK) and phosphorylated Akt. Moreover, barbigerone exhibit less toxicity to non-cancer cells than tumor cells. In conclusion, our results indicated that barbigerone can inhibit murine lung cancer cell proliferation by inducing apoptosis via mitochondrial apoptotic pathway and by decreasing phosphorylated p42/44 MAPK and Akt. Its potential to be a candidate of anti-cancer agent is worth being further investigated.

Cell growth inhibition, G2/M cell cycle arrest, and apoptosis induced by chloroquine in human breast cancer cell line Bcap-37.

Chloroquine is an antimalarial drug that has been used in the treatment and prophylaxis of malaria since the 1950s. The present study was undertaken to examine the effects of chloroquine on Bcap-37 human breast cancer cells' growth, cell cycle modulation, apoptosis induction, and associated molecular alterations in vitro. The chloroquine treatment decreased the viability of Bcap-37 cells in a concentration- and time-dependent manner, which correlated with G(2)/M phase cell cycle arrest. The chloroquine-mediated cell cycle arrest was associated with a decrease in protein levels/activity of polo-like kinase 1 (Plk1), phosphorylated cell division cycle 25C (Cdc25C), phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated Akt. The chloroquine-treated Bcap-37 cells exhibited a marked decrease in the level of mitochondrial transmembrane potential (DeltaPsim), which was accompanied by the activation of caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Exposure of Bcap-37 cells to chloroquine also resulted in the induction of spindle abnormalities. In conclusion, the findings in this study suggested that chloroquine might have potential anticancer efficacy, which could be attributed, in part, to its proliferation inhibition and apoptosis induction of cancer cells through modulation of apoptosis and cell cycle-related proteins expressions, down-regulation of mitochondrial transmembrane potential (DeltaPsim), and induction of spindle abnormalities.

[Optimally control urban railway noise by sound propagation path].

In order to control railway noise pollution in urban areas, the residential district located near the Zhegan railway in Hangzhou urban was taken for example, and some controlling measures were proposed based on the investigation in railway noise impact as well as the planning of the district, the environmental scene and the project devises. The measures included setting man-made soil slopes, noise barriers and virescence. Combining some of them could be a typical noise reduction scheme. The professional software Cadna/A was used to predict the noise reduction results of every scheme. Results show that the maximal difference of noise reduction is 19.4 dB and the noise reduction effect of the second scheme is best. However, if only railway noise influence is considered, the first scheme is best. The research results can provide reference for residential districts planning and noise control near the railway in urban areas.

[Effects of chloroquine diphosphate on proliferation and apoptosis of human leukemic K562 cells].

The purpose of this study was to investigate the effects of chloroquine diphosphate on the proliferation and apoptosis of human leukemic K562 cells, and to elucidate its possible mechanism of activity. The inhibitory effect of chloroquine diphosphate with different concentrations on K562 cell proliferation was detected by MTT method. Apoptosis was measured by flow cytometry (FCM); morphological analysis of apoptosis was performed after staining with propidium iodide (PI) under fluorescence microscope; cell apoptosis was assessed by the DNA ladder shown agarose gel electrophoresis. After treatment with chloroquine diphosphate, K562 cells were stained by Rhodamine 123 to detect changes in mitochondrial transmembrane potential (DeltaPsim) by FCM. The results showed that the cell viability decreased in dose-dependent manner, following chloroquine diphosphate treatment at different concentrations (1.5625, 3.125, 6.25, 12.5, 25, 50 and 100 micromol/L) for 24, 48 and 72 hours. By FCM analysis, the significant increases of sub-G(1) were observed. DNA ladder was detected and apoptotic nuclei were observed. DeltaPsim decreased in K562 cells after chloroquine diphosphate treatment. It is concluded that the chloroquine diphosphate can inhibit the proliferation of K562 cells and induce cell apoptosis, which may relate to down-regulation of mitochondrial transmembrane potential (DeltaPsim).