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Dengue is the fastest spreading mosquito-transmitted disease in the world. In China, Guangzhou City is believed to be the most important epicenter of dengue outbreaks although the transmission patterns are still poorly understood. We developed an autoregressive integrated moving average model incorporating external regressors to examine the association between the monthly number of locally acquired dengue infections and imported cases, mosquito densities, temperature and precipitation in Guangzhou. In multivariate analysis, imported cases and minimum temperature (both at lag 0) were both associated with the number of locally acquired infections ( P < 0.05). This multivariate model performed best, featuring the lowest fitting root mean squared error (RMSE) (0.7520), AIC (393.7854) and test RMSE (0.6445), as well as the best effect in model validation for testing outbreak with a sensitivity of 1.0000, a specificity of 0.7368 and a consistency rate of 0.7917. Our findings suggest that imported cases and minimum temperature are two key determinants of dengue local transmission in Guangzhou. The modelling method can be used to predict dengue transmission in non-endemic countries and to inform dengue prevention and control strategies.

Dengue fever (DF) is the most prevalent and rapidly spreading mosquito-borne disease globally. Control of DF is limited by barriers to vector control and integrated management approaches. This study aimed to explore the potential risk factors for autochthonous DF transmission and to estimate the threshold effects of high-order interactions among risk factors. A time-series regression tree model was applied to estimate the hierarchical relationship between reported autochthonous DF cases and the potential risk factors including the timeliness of DF surveillance systems (median time interval between symptom onset date and diagnosis date, MTIOD), mosquito density, imported cases and meteorological factors in Zhongshan, China from 2001 to 2013. We found that MTIOD was the most influential factor in autochthonous DF transmission. Monthly autochthonous DF incidence rate increased by 36·02-fold [relative risk (RR) 36·02, 95% confidence interval (CI) 25·26–46·78, compared to the average DF incidence rate during the study period] when the 2-month lagged moving average of MTIOD was >4·15 days and the 3-month lagged moving average of the mean Breteau Index (BI) was ⩾16·57. If the 2-month lagged moving average MTIOD was between 1·11 and 4·15 days and the monthly maximum diurnal temperature range at a lag of 1 month was <9·6 °C, the monthly mean autochthonous DF incidence rate increased by 14·67-fold (RR 14·67, 95% CI 8·84–20·51, compared to the average DF incidence rate during the study period). This study demonstrates that the timeliness of DF surveillance systems, mosquito density and diurnal temperature range play critical roles in the autochthonous DF transmission in Zhongshan. Better assessment and prediction of the risk of DF transmission is beneficial for establishing scientific strategies for DF early warning surveillance and control.

We studied the evolution, genotypes, and the molecular clock of dengue virus serotype 1 (DENV-1), between 2001 and 2014 in Guangzhou, China. The analysis of the envelope (E) gene sequences of 67 DENV-1 strains isolated in Guangzhou, together with 58 representative sequences downloaded from NCBI, have shown shifts in viral genotypes. The genotype changed several times, from genotype I to IV in 2002, from IV to I in 2005, and from I to V in 2014. These genotype shifts may be the cause of DENV outbreaks. The diversity of genotypes and clades demonstrates a high risk of future outbreaks in Guangzhou. The mean rate of virus nucleotide substitution in Guangzhou was determined to be 7·77 × 10−4 per site per year, which represents a medium substitution rate compared to two other countries. Our research can point to different ancestors of the isolated strains, which may further reveal the different origins and transmission of DENV-1 strains in Guangzhou.

Aim： To evaluate the effect of neutral sulfate berberine on cardiac function, tumor necrosis factor α （TNF-α） release, and intracellular calcium concentration （[Ca^2＋]i） in cardiomyocytes exposed to lipopolysaccharide （LPS）. Methods： Primary cultured rat cardiomyocytes were prepared from ventricles of 3-4-day old Sprague-Dawley rats. TNF-α concentrations in cell-conditioned media were measured by using a Quantikine enzyme-linked immunosorbent assay kit, and cardiomyocyte [Ca^2＋]i was measured by using Fura-2/AM. The isolated rat hearts were perfused in the Langendorff mode. Results： LPS at doses of 1, 5, 10, and 20 μg/mL markedly stimulated TNF-α secretion from cardiomyocytes, and neutral sulfate berberine inhibited LPS-induced TNF-α production. Intracellular calcium concentration was significantly decreased after LPS stimulation for 1 h, and increased 2 h after LPS treatment. Pretreatment with neutral sulfate berberine reversed the LPS-induced [Ca^2＋]i alterations, although neutral sulfate berberine did not inhibit a rapid increase in cardiomyocyte [Ca^2＋]i induced by LPS. Perfusion of isolated hearts with LPS （100 μg/mL） for 20 min resulted in significantly impaired cardiac performance at 120 min after LPS challenge： the maximal rate of left ventricular pressure rise and fall （±dp/dtmax） decreased compared with the control. In contrast, ±dp/dtmax at 120 min in hearts perfused with neutral sulfate berberine （1μmol/L） for 10 min followed by 20 min LPS （100 μg/mL） was greater than the corresponding value in the LPS group. Conclusion： Neutral sulfate berberine inhibits LPS-stimulated myocardial TNF-α production, impairs calcium cycling, and improves LPS-induced contractile dysfunction in intact heart.

Boron-bearing magnetite concentrate is typically characterized by low grade of iron and boron （wTFe = 51%- 54%, WB2O3 =6%-8%）, as well as the close intergrowth of ascharite phase and magnetite phase. A promising technology was proposed to separate iron and boron by coupling the direct reduction of iron oxides and Na activation of boron minerals together. The influence of Na2CO3 as additive on the direct reduction of boron-bearing magnetite was studied by chemical analysis, kinetic analysis, XRD analysis and SEM analysis. The results showed that the ad- dition of Na2CO3 not only activated boron minerals, but also reduced the activation energy of the reaction and pro- moted the reduction of iron oxides. Besides, the addition of Na2CO3 changed the composition and melting point of non-ferrous phase, and then promoted the growth and aggregation of iron grains, which was conducive to the subse- quent magnetic separation. Thus, the coupling of the two processes is advantageous,

By virtue of Cauchy’s integral formula in the theory of complex functions,the authors establish an integral representation for the weighted geometric mean,apply this newly established integral representation to show that the weighted geometric mean is a complete Bernstein function,and find a new proof of the well-known weighted arithmetic-geometric mean inequality.

Aim： Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods： The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine （TCM） network pharmacology platform. The anti- tumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results： The nuciferine target profile was enriched with signaling pathways and biological functions, including ＂regulation of lipase activity＂, ＂response to nicotine＂ and ＂regulation of cell proliferation＂. Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine （0.8 mg/mL） markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine （0.05 mg/mL） significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine （9.5 mg/mL, ip, 3 times a week for 3 weeks） significantly decreased the weight of SYSY and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion： By using a TCM network pharmacology method, nuciferine is neuroblastoma and mouse colorectal cancer in vitro and in vivo, through dentified as an anti-tumor agent against human nhibiting the PI3K-AKT signaling pathways and IL-1 levels

Aim： Pseudolaric acid B （PAB）, a diterpene acid isolated from the root bark of Pseudolarix kaempferi Gordon, has shown to exert antitumor effects via inducing cell cycle arrest followed by apoptosis in several cancer cell lines. Here we reported that PAB induced a mitotic catastrophe in human lung cancer A549 cells, which resulted in senescence without apoptosis or necrosis. Methods： Three human lung cancer cell lines （A549, H460 and H1299 cells） were examined. Cell growth inhibition was assessed with MTT assay. Cell cycle distribution was determined using a flow cytometer. Cell nuclear morphology was observed under a fluorescence microscope. Senescent cells were detected using SA-β-Gal staining. Apoptotic and senescent protein expression was examined using Western blot analysis. The expression of p53 and p21 in the cells was downregulated by siRNAs. Results： Treatment with PAB （5-80 pmol/L） inhibited the growth of A549 cells in dose- and time-dependent manners. Prolonged treatment with PAB （20 pmol/L） caused G2/M arrest at day i followed by mitotic catastrophe from day 2, which eventually resulted in cell senescence between days 3 and 4 without cell death （apoptosis or necrosis）. Knockdown of p53 expression with siRNA significantly suppressed PAB-induced senescence in A549 cells （p53 wild）. Furthermore, PAB-induced senescence was also observed in human lung cancer H460 cells （p53 wild）, but not in human lung cancer H1299 cells （p53 null）. Conclusion： The anti-tumor action of PAB against human lung cancer A549 cells in vitro involves the induction of senescence through activation of the p53 pathway.

Aim： Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans （Gardn ＆ Champ） Benth, is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain. Methods： Mice were subjected to partial sciatic nerve ligation （PSNL）. After the mice were injected with gelsemine or pregabalin （the positive control） intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram （EEG）/ electromyogram （EMG） recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining. Results： In PSNL mice, gelsemine （2 and 4 mg/kg） increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine （4 mg/kg, administered at 6：30 AM） increased non-rapid eye movement （non-REM, NREM） sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine （4 mg/kg） did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine （4 mg/kg） decreased c-Fos expression by 58%. Gelsemine （4 mg/kg, administered at either 6：30 AM or 8：30 PM） did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice. Conclusion： Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.