Physics-model-based neural networks for inverse design of binary phase planar diffractive lenses.

The inverse design approach has enabled the customized design of photonic devices with engineered functionalities through adopting various optimization algorithms. However, conventional optimization algorithms for inverse design encounter difficulties in multi-constrained problems due to the substantial time consumed in the random searching process. Here, we report an efficient inverse design method, based on physics-model-based neural networks (PMNNs) and Rayleigh-Sommerfeld diffraction theory, for engineering the focusing behavior of binary phase planar diffractive lenses (BPPDLs). We adopt the proposed PMNN to design BPPDLs with designable functionalities, including realizing a single focal spot, multiple foci, and an optical needle with size approaching the diffraction limit. We show that the time for designing single device is dramatically reduced to several minutes. This study provides an efficient inverse method for designing photonic devices with customized functionalities, overcoming the challenges based on traditional data-driven deep learning.

Separation and determination of triadimefon and its metabolites triadimenol enantiomers in fruit puree by supercritical fluid chromatography.

A method was established for the separation and determination of triadimefon and its metabolite triadimenol enantiomer residues in major complementary fruit puree for infants and young children (banana puree, pineapple puree, and grape puree) by supercritical fluid chromatography. After the samples were extracted with acetonitrile and purified with a solid phase extraction cartridge, Acquity Trefoil CEL2 chiral chromatographic column was adopted for separation, and gradient elution was conducted at the flow rate of 1.0 ml/min under the mobile phase of supercritical carbon dioxide - 0.5% ammonia methanol, the detection wavelength was 220 nm and quantification was conducted with the external standard method. The limits of quantitation of triadimefon and triadimenol enantiomers were both 0.05 mg/kg, the linear ranges were 0.5-50 mg/L, and the linear correlation coefficients were greater than 0.9993. The recoveries in the spiked samples at 0.05, 0.2, and 3.0 mg/kg were from 80.1 to 106%, and the relative standard deviation reached 3.3-7.6%. The method is efficient, rapid, reproducible, and environmentally friendly, enabling accurate analysis of pesticide enantiomers, which can detect the enantiomer residues of triadimefon and its metabolite triadimenol in major complementary fruit puree for infants and young children.

Determination of sugars and sugar alcohols in infant formula by high performance liquid chromatography with evaporative light-scattering detector.

A method was established for the simultaneous determination of five sugars (fructose, glucose, sucrose, lactose, maltose) and five sugar alcohols (erythritol, xylitol, sorbitol, mannitol, maltitol) in infant formula by high performance liquid chromatography-evaporative light scattering detector. After the samples were extracted with acetonitrile-water solution, precipitated by acetic acid, and purified with solid phase extraction cartridge, ALLChrom Rocksil Carbohydrate ES column was adopted for separation, and isocratic elution was conducted at the flow rate of 1.0 mL/min with acetonitrile-0.04 % ammonia solution as the mobile phase. The analytes were detected by an evaporative light-scattering detector, and quantified by external standard method. The linear ranges of the 10 components were 0.04-4.0 g/L with the correlation coefficients greater than 0.999, and the limits of quantification (S/N = 10) of the method were 0.08-0.4 g/100 g. The relative standard deviation of the lactose parallel samples reached 1.29 %, and the recoveries of the other 9 components ranged from 80.4 % to 99.4 % with the relative standard deviation of 2.8 %-7.1 %. The method performs well in sensitivity and separation, which is suitable for the simultaneous quantitative determination of sugars and sugar alcohols in infant formula.

Horizontal Tourism Coopetition Strategy for Marketing Performance - Evidence From Theme Parks.

Unprecedentedly impacted by COVID-19, tourism enterprises are pushed to adopt new strategic management to cope with the changes in tourists' consumer perception for sustainable development, such as corporate and compete simultaneously with their competitors. Our study aims to investigate the intermediate role of coopetition, including the three dimensions of resource similarity, market commonality, and willingness to cooperate in the marketing and performance relationships. Primary data on 360 observers were collected via questionnaire distribution to theme park managers in China with 85.3% accuracy in response rate. Structural equation modeling (SEM) was used to verify the intermediate effect of coopetition on marketing performance in tourism enterprises. The results of SEM indicate (1) the intermediate role of tourism coopetition, including the three dimensions existing in the relationship between tourism marketing and performance, (2) more significant positive impact on non-financial performance than that on financial performance, and (3) the mechanism of implementing coopetition. This study gives supportive evidence for tourism enterprises to implement coopetition and highlights the implications for appropriately developing coopetition strategies and tactics to achieve the synergy effect for the individual enterprises and the spillover effect for the destination regarding policy-making, mindset, and partner selection.

Status Quo and Research Trends of Neurosurgical Departments in China: Bibliometric and Scientometric Analyses.

BACKGROUND: Modern neurosurgery is a relatively young discipline characterized by finesse and complexity. In recent years, neurosurgery in China has made continuous developments, with long-term progress and outstanding discoveries in many aspects of the field. OBJECTIVE: This scientometric investigation aimed to comprehensively provide insight into the development trends of neurosurgery in China, to demonstrate how the field has evolved. METHODS: PubMed database was searched to retrieve relevant papers published between 1988 and 2018 from neurosurgery institutions in China. The database of the National Natural Science Foundation of China was also retrieved for funding information. Information (eg, year of publication, journal, institute of origin) and keywords were collected from each paper after removing duplicates and filtering unintentional words. Co-word analysis was performed on the papers' keywords, and a time distribution matrix of coexisting keywords in a given paper (ie, termed co-words) was established. Co-words were clustered according to their growth rate within years and visually presented with a mountain plot and a heatmap. Trends and potential subspecialties were identified, and each topic, represented either by a co-word from publications or funding from the National Natural Science Foundation of China during the period from 2011 to 2018, was collected and analyzed. RESULTS: Within 15,972 publications on neurosurgery from institutions in China, diagnostic image was found to coexist the most with other keywords. Cluster 0, represented by diagnostic image with retrospective study, contained emerging topics with great developmental potential and demonstrated high growth rates in recent years. This finding suggests that the topics represented in Cluster 0 may represent future areas of important neurosurgical research. We also found that the developmental trend of China's neurosurgical research is highly correlated with National Natural Science Foundation of China funding acquisition. CONCLUSIONS: Co-word analysis and visualization results provided insight into the emerging research topics that are of vital importance, which can be used as a reference by neurosurgeons and researchers for future investigations. In this study, our analysis strategy based on co-word biclustering was able to clearly demonstrate current academic subject development; therefore, co-word biclustering is a reliable bibliometric analysis strategy.

MicroRNA-506 Is Involved in Regulation of the Occurrence of Lipopolysaccharides (LPS)-Induced Pulpitis by Sirtuin 1 (SIRT1).

BACKGROUND Toothache often occurs with pulpitis. Lipopolysaccharide (LPS) is produced by gram-negative bacteria, and its accumulation is related to clinical symptoms of pain. MicroRNAs (miRNAs) display anti-inflammatory potential due to their direct regulation of cellular protein expression, which can promote inflammatory changes in dental pulp tissues. However, the mechanism of LPS-induced pulpitis is still unclear. MATERIAL AND METHODS In this study, dental pulp stem cells (DPSCs) were separated and cultured from rat dental pulp tissues; then, LPS was administered to induce inflammation and activate the TLR4 pathway. RESULTS It was found that miR-506 was upregulated following LPS treatment in DPSCs. The inhibition of miR-506 in LPS-treated DPSCs led to attenuated inflammation and deactivation of the TLR4 pathway. Furthermore, the bioinformatic analysis and dual-luciferase reporter gene assay indicated that miR-506 could target the 3'-UTR of sirtuin 1 (SIRT1). Additionally, SIRT1 decreased in LPS-treated DPSCs, and miR-506 transfection resulted in SIRT1 upregulation. SIRT1 overexpression showed a similar inhibitory effect as that of miR-506 downregulation on inflammation and TLR4 activation in DPSCs. CONCLUSIONS In brief, miR-506 can protect dental pulp in LPS-induced inflammation by inhibiting the SIRT1-mediated TLR4 pathway.

[Comparative study with the effect of stromal cell derived factor-1 on osteogenic differentiation of human healthy and inflammatory periodontal ligament stem cells].

OBJECTIVE: This study aims to compare the osteogenic differentiation capability of stem cells derived from human inflammatory periodontal ligament tissues (iPDLSCs) with those of stem cells derived from healthy periodontal ligament tissues (hPDLSCs). Both types of tissues were induced by stromal cell derived factor (SDF-1) in vitro. METHODS: iPDLSCs and hPDLSCs were primarily cultured by tissue digestion method and purified by limited dilution cloning. The cells were passaged and identified by stem cell surface marker expression through flow cytometry. Then, we used thiazolyl blue tetrazolium bromide to detect and compare the proliferation capabilities of the iPDLSCs and hPDLSCs. Express of bone volumes were detected by alizarin red staining after SDF-1 was added to the cells. Using alkaline phosphatase, we evaluated the osteogenic differentiation capability of the cells induced by SDF-1. The expression levels of the osteogenesis-related genes of the cells induced by SDF-1 were determined by reverse transcription-polymerase chain reaction. RESULTS: After purification, both iPDLSCs and hPDLSCs expressed stem cell markers. hPDLCSs had a higher proliferation capability than iPDLSCs. Osteogenesis-related genes had higher expression levels in the cells induced by SDF-1 than in those without induction (P<0.05). SDF-1 at 50 and 200 ng·mL⁻¹ concentration greatly affected the differen-tiation capabilities of iPDLSCs and hPDLSCs respectively. CONCLUSIONS: iPDLSCs and hPDLSCs had osteogenic differentia-tion capability. The level of osteogenic differentiation in normal and inflamed periodontal ligament stem cells increases after SDF-1 induction.

The Competition of Homophily and Popularity in Growing and Evolving Social Networks.

Previous studies have used several models to investigate the mechanisms for growing and evolving real social networks. These models have been widely used to simulate large networks in many applications. In this paper, based on the evolutionary mechanisms of homophily and popularity, we propose a new generation model for growing and evolving social networks, namely, the Homophily-Popularity model. In this new model, new links are added, and old links are deleted based on the link probabilities between every node pair. The results of our simulation-based experimental studies provide evidence that the proposed model is capable of modelling a variety of real social networks.

Microbial Biofertilizer Decreases Nicotine Content by Improving Soil Nitrogen Supply.

Biofertilizers have been widely used in many countries for their benefit to soil biological and physicochemical properties. A new microbial biofertilizer containing Phanerochaete chrysosporium and Bacillus thuringiensis was prepared to decrease nicotine content in tobacco leaves by regulating soil nitrogen supply. Soil NO3--N, NH4+-N, nitrogen supply-related enzyme activities, and nitrogen accumulation in plant leaves throughout the growing period were investigated to explore the mechanism of nicotine reduction. The experimental results indicated that biofertilizer can reduce the nicotine content in tobacco leaves, with a maximum decrement of 16-18 % in mature upper leaves. In the meantime, the total nitrogen in mature lower and middle leaves increased with the application of biofertilizer, while an opposite result was observed in upper leaves. Protein concentration in leaves had similar fluctuation to that of total nitrogen in response to biofertilizer. NO3--N content and nitrate reductase activity in biofertilizer-amended soil increased by 92.3 and 42.2 %, respectively, compared to those in the control, whereas the NH4+-N and urease activity decreased by 37.8 and 29.3 %, respectively. Nitrogen uptake was improved in the early growing stage, but this phenomenon was not observed during the late growth period. Nicotine decrease is attributing to the adjustment of biofertilizer in soil nitrogen supply and its uptake in tobacco, which result in changes of nitrogen content as well as its distribution in tobacco leaves. The application of biofertilizer containing P. chrysosporium and B. thuringiensis can reduce the nicotine content and improve tobacco quality, which may provide some useful information for tobacco cultivation.

Incentive effect of bentonite and concrete admixtures on stabilization/solidification for heavy metal-polluted sediments of Xiangjiang River.

Solidification is a very effective way to alleviate heavy metal impacts to the environment. In this paper, an improved method was adopted herein for the solidification/stabilization (S/S) of sediments with cement-based additives and low content of cement in S/S materials. Sediments in Xiangjiang River, containing high concentrations of Cu, Cd, and Pb, were solidified/stabilized by binders of cement, fly ash, and bentonite. Admixtures such as sodium lignosulfonate, sodium lauryl sulfate, and triethanolamine were used to improve the bonding properties of S/S, which had never been investigated before. Results demonstrated that the addition of concrete admixtures had significant effects on the S/S of sediments. Sequential extraction method indicates that the concentrations of heavy metals changed significantly after solidification and were more stable over time, with the exception of Pb. In addition, SEM images indicated that the main hydrated product was ettringite. Large quantities of calcium silicate hydrates (CSH) formed and filled the solidified sediment in 60 days. The results provide further insights into the transformation of heavy metals during S/S.

Determination of collective behavior of the financial market.

In this paper, we adopt the network synchronization to measure the collective behavior in the financial market, and then analyze the factors that affect the collective behavior. Based on the data from the Chinese financial market, we find that the clustering coefficient, the average shortest path length and the volatility fluctuation have a positive effect on the collective behavior respectively, while the average return has a negative effect on it; the effect of the average shortest path length on the collective behavior is the greatest in the above four variables; the above results are robust against the window size and the time interval between adjacent windows of the stock network; the effect of network structures and stock market properties on the collective behavior during the financial crisis is the same as those during other periods.

ColoFinder: a prognostic 9-gene signature improves prognosis for 871 stage II and III colorectal cancer patients.

Colorectal cancer (CRC) is a heterogeneous disease with a high mortality rate and is still lacking an effective treatment. Our goal is to develop a robust prognosis model for predicting the prognosis in CRC patients. In this study, 871 stage II and III CRC samples were collected from six gene expression profilings. ColoFinder was developed using a 9-gene signature based Random Survival Forest (RSF) prognosis model. The 9-gene signature recurrence score was derived with a 5-fold cross validation to test the association with relapse-free survival, and the value of AUC was gained with 0.87 in GSE39582(95% CI [0.83-0.91]). The low-risk group had a significantly better relapse-free survival (HR, 14.8; 95% CI [8.17-26.8]; P < 0.001) than the high-risk group. We also found that the 9-gene signature recurrence score contributed more information about recurrence than standard clinical and pathological variables in univariate and multivariate Cox analyses when applied to GSE17536(p = 0.03 and p = 0.01 respectively). Furthermore, ColoFinder improved the predictive ability and better stratified the risk subgroups when applied to CRC gene expression datasets GSE14333, GSE17537, GSE12945and GSE24551. In summary, ColoFinder significantly improves the risk assessment in stage II and III CRC patients. The 9-gene prognostic classifier informs patient prognosis and treatment response.

Impact of systemic risk in the real estate sector on banking return.

In this paper, we measure systemic risk in the real estate sector based on contingent claims analysis, and then investigate its impact on banking return. Based on the data in China, we find that systemic risk in the real estate sector has a negative effect on banking return, but this effect is temporary; banking risk aversion and implicit interest expense have considerable impact on banking return.

SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials.

[Efficacies of using modified oral appliance after uvulopalatopharyngoplasty in the treatment of moderate to severe obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To evaluate the efficacies of a modified oral appliance (MOA) for residual obstruction after uvulopalatopharyngoplasty (UPPP) in the treatment of moderate-to-severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: The patients with residual airway obstruction on polysomnography (PSG) at four weeks post-UPPP were selected from the Sleep Medicine Center, Gansu Provincial People's Hospital from October 2013 to February 2014. As of week 5 post-UPPP, all subjects wore MOA for 4 weeks. Before and 4 weeks after treatment, questionnaires were distributed to evaluated the improvement of subjective and objective sleep. The average apnea hyponea index (AHI) and sleep patterns were examined by PSG. The sagittal diameter in minimal region of retropalatal and retroglossal patency and the volume of orophary were measured by cone beam computed tomography (CBCT) scans. And the correlation between the outcomes of CBCT and AHI were analyzed. RESULTS: A total of 10 male OSAHS patients were enrolled. The average age was (42.4 ± 9.2) (31-55) years, body mass index (BMI) (25.0 ± 4.8) (22.8-29.4) kg/m² and AHI was (26.0 ± 7.5) (15.8-35.9)/h. After wearing MOA for 4 weeks, the symptoms of snoring, daytime somnolence and suffocated waking during sleep improved as compared with that pre-treatment. All adapted to sleep with MOA. Average AHI decreased from (26.0 ± 7.5)/h to (6.0 ± 0.7)/h (P < 0.001). And the lowest average oxygen saturation value (SaO2) increased from (79.6 ± 3.9)% to (87.6 ± 1.6)% (P < 0.001). PSG indicated that the percentage of awakening time and sleep time in nonrapid eye movement (NREM) stage 1 decreased from (11.0 ± 2.3)% and (26.1 ± 4.3)% to (6.8 ± 1.6)% and (11.1 ± 1.5)% respectively in total sleep time (TST). The percentage of NREM stage3 sleep time and rapid eye movement (REM) sleep time in TST increased on average from (10.2 ± 2.2)% and (11.6 ± 1.4)% to (17.7 ± 3.1)% and (21.3 ± 3.1)% respectively (all P < 0.001). CBCT measurements showed that the sagittal diameter in minimal region of retropalatal and retroglossal patency increased on average by (0.64 ± 0.04) and (1.51 ± 0.18) mm respectively. The average volume of orophary increased by (2 446 ± 963) mm³ (all P < 0.05). Negative correlations existed between AHI and sagittal diameter of minimal region of retroglossal patency, AHI and volume of orophary (all P < 0.05). CONCLUSION: The application of MOA after UPPP can significantly increase the sagittal diameter of minimal region of retroglossal patency and the volume of orophary and improve effectively hyperpnoea and disordered sleep patterns.

Alteration of culture fluid proteins by cadmium induction in Phanerochaete chrysosporium.

Microorganisms need to resist the hazards posed by heavy metals during the process of metal adsorption. Phanerochaete chrysosporium is a fungus that is efficiently used for heavy-metal biosorption in wastewater treatment. Extraction and analysis of proteins induced by heavy metals can help to understand the regulatory mechanisms of P. chrysosporium in wastewater treatment. In this study, P. chrysosporium was exposed to 50 µM cadmium nitrate. A maximum cadmium adsorption capability of 77.1 mg/g dry biomass was found after 65 h, which was accompanied by a relatively higher protein concentration. After separation of the culture fluid proteins by two-dimensional difference gel electrophoresis (2D-DIGE), three differentially expressed proteins were detected from 17 spots. By using 2D-DIGE, followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF MS), glutathione S-transferase, glyceraldehyde-3-phosphate dehydrogenase, and malate dehydrogenase were identified. All three enzymes play important roles in the oxidative stress caused by cadmium.

Prevalence and burden of headache disorders in two neighboring provinces of China.

To our knowledge, studies concerning the prevalence and burden of primary headache in China are limited to specific regions without comparison of different districts. A survey in a different area with similar climate and culture may enhance our knowledge of the factors causing primary headache and the burden of headache. We conducted a 1 year survey on the prevalence and burden of primary headache in the Chinese provinces of Guangdong and Guangxi. Our study also evaluated the factors behind similarities and differences affecting prevalence in the two regions of study. The survey methodology, which was used in an Expanded Program on Immunization by the World Health Organization, was adopted to investigate the prevalence and burden of headache patients. Random samples of 372 local residents in Guangdong and 182 local residents in Guangxi aged 18-65 years were invited to a face-to-face interview. The education level and mean household income were higher in Guangdong (p<0.05). The 1 year prevalence of primary headache was 22.6% (84/372) in Guangdong and 41.2% (75/182) in Guangxi (p<0.001). The average financial burden of primary headache is 2.1% and 3.7% of the mean household income in Guangdong and Guangxi, respectively (p=0.001). The district with lower economic status had a higher prevalence of primary headache, and inevitably bears a heavier burden even with the same disease cost.

[Anti-tumor effect of Sendai virus Tianjin strain defective interfering particles on tumor-bearing mice].

OBJECTIVE: To explore the anti-tumor effect and its mechanism of Sendai virus Tianjin strain defective interfering particles (DIP) on mouse models of colon carcinoma. METHODS: CT26 cells (5×10(6)/0.1 ml) were subcutaneously injected into the back of Bal B/c mice to establish murine colon carcinoma model. After the tumors reached 5 mm in diameter, the mice were randomly divided into Tianjin strain DIP group and saline control group. The former was intratumorally injected with Tianjin strain DIP (0.1 ml) once a day on day 4, 7, 10 and 13 after CT26 cell inoculation. The latter was intratumorally injected with the same volume of saline. Tumor volume and survival rate of the mice were calculated to confirm the anti-tumor effect of DIP. Flow cytometry and ELISA were used to examine the maturation and release of cytokines IL-6, IFN-α and TNF-α from murine myeloid dendritic cells (DCs) induced by Tianjin strain DIP. Moreover, real-time RT-PCR and immunohistochemistry were performed to identify whether the Tianjin strain DIP could induce infiltration of CD11c(+) DCs, CD4(+) and CD8(+) T cells in the tumors. RESULTS: On day 22 after CT26 cell inoculation, the average tumor volume of the Tianjin strain DIP group was (33.2 ± 2.0) mm(3), significantly smaller than that of the control group [(2 376.0 ± 130.8)mm(3), P < 0.01]. On day 50 after CT26 cell inoculation, the survival rate of mice was 90.0% in the Tianjin strain DIP group, much higher than that of the control group (30.0%, P < 0.01). Flow cytometry analysis showed that the expression of markers of DCs maturation, including CD40, CD80 and CD86, was dose-dependently increased by DIP or intact virus. No statistically significant difference was found betweent the DIP and intact virus groups. ELISA results showed that DIP could stimulate the secretion of IL-6, IFN-α and TNF-α from mouse DCs. The secretion of all of the cytokines was dose-dependently increased by DIP or intact virus. Real-time RT-PCR revealed that the expression of CD4, CD8 and CD11c mRNAs was increased in tumors treated with DIP compared with that of the saline group at all time points. Moreover, the expression level of all of them remained maximal at 120 h after the last treatment. Immunohistochemical staining revealed that the ratios of CD4(+), CD8(+) T cells or CD11c(+) DCs to total cells were (21.60 ± 1.49)%, (22.12 ± 2.84)% and (23.05 ± 2.91)%, respectively, in the DIP-treated tumors. In the tumors treated by saline, the ratios were (2.62 ± 0.60)%, (4.05 ± 0.12)% and (3.10 ± 0.09)%, respectively. The difference between experimental group and control group had statistical significance. CONCLUSIONS: Tianjin strain DIP may exert anti-tumor effect on tumor-bearing mice. The mechanism is related with the antitumor immunity induced by DCs and T cells.

Three new diterpenoid alkaloids from the roots of Aconitum duclouxii.

Three new C19-diterpenoid alkaloids, ducloudines C (1), D (2), and E (3), were isolated from the roots of Aconitum duclouxii. Their structures were established on the basis of extensive spectroscopic analyses. Ducloudine C (1) is the first aconitine-type C19-diterpenoid alkaloid with a C=O group at C-3 and a C=C bond between C-1 and C-2. All compounds were tested for their biological activities against one pathogenic fungi and two pathogenic bacteria.

Inactivated Sendai virus strain Tianjin, a novel genotype of Sendai virus, inhibits growth of murine colon carcinoma through inducing immune responses and apoptosis.

BACKGROUND: Ultraviolet-inactivated, replication-defective Sendai virus particles (Z strain) have displayed antitumor effect through enhancing the immune responses or inducing apoptosis in a variety of carcinomas. Sendai virus strain Tianjin was isolated from the lungs of marmoset and proved to be a novel genotype of Sendai virus. In this study, we explored the antitumor effect and its mechanism of ultraviolet-inactivated, replication-defective Sendai virus strain Tianjin (UV-Tianjin) in mice bearing CT26 colon carcinoma. METHODS: Three injections of UV-Tianjin were delivered into CT26 tumors growing on the back of BALB/c mice. Tumor size was measured in a blinded manner and survival rate of mice was calculated. In order to make clear antitumor mechanism of UV-Tianjin, the maturation and interleukin-6 (IL-6) release from murine myeloid dendritic cells (DCs) was examined by flow cytometry or ELISA assay after induced by UV-Tianjin and compared with those of live virus. Moreover, real-time RT-PCR and immunohistochemistry was performed to identify whether UV-Tianjin could induce infiltration of DCs, CD4⁺ and CD8⁺ T cells into tumors. The TUNEL assay was done to observe the apoptosis of CT26 tumor cells after UV-Tianjin injection. RESULTS: In animal model, UV-Tianjin could obviously inhibit the growth of CT26 tumors and prolong the survival of the tumor-bearing mice compared with control group (P < 0.01). In vitro murine DCs stimulated by UV-Tianjin underwent dose-dependent maturation, similar to that elicited by live virus. And the secretion amount of IL-6 from DCs induced by UV-Tianjin was a little lower than that released in the presence of live virus. Real-time RT-PCR and immunohistochemistry revealed that UV-Tianjin induced a remarkable infiltration of DCs, CD4⁺ and CD8⁺ T cells into tumors. The TUNEL assay showed that the apoptosis index of tumor tissues injected with UV-Tianjin was significantly higher than that of control group (P < 0.01). CONCLUSIONS: Our results have demonstrated that UV-Tianjin alone could inhibit the growth of CT26 tumor in mice through enhancing host antitumor immunity and inducing apoptosis of tumor cells. Therefore, UV-Tianjin shows its prospect as a novel drug for carcinoma therapy.