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Abstract Background Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, causing a major risk of liver disease and hepatocellular carcinoma (HCC). Many mouse models have been tried to establish HBV infection through injection with various HBV-containing plasmids. However, it is not well understood that different plasmids, all of which contain the similar HBV genome, even the same plasmids with different dose, results in opposite immune responses toward HBV. Methods In this study, we investigated the role of HBV-containing plasmid backbones and the HBcAg in determining the HBV persistence. C57BL/6 mice were injected hydrodynamically with 6 μg or 20 μg of WT pAAV/HBV1.2 plasmid, e/core-null pAAV/HBV1.2 plasmid, or none-HBV genome pAAV/control plasmid. Serum levels of HBV-related markers were measured by quantitative immunoradiometric assay (IRMA). Liver HBcAg expression was detected by immunohistochemical staining. The mRNA levels of cytokines and Th1-related immune factors were quantified by qRT-PCR. Results All mice injected with 6 μg of the pAAV/HBV1.2 plasmid shows HBsAg positive at week 6 after hydrodynamic injection (AHI) as previously investigated. However, the mice injected with 20 μg pAAV/HBV1.2 or 6μgpAAV/HBV1.2 plus 14μgpAAV/control plasmid results in HBV clearance within 4 weeks AHI, indicating the anti-HBV activity is induced by 20 μg plasmid DNA, but not by the inserted viral genome. This anti-HBV activity is independent of HBcAg and Toll like receptor (TLR) signaling pathway, since the lack of HBcAg in pAAV/HBV1.2 plasmid or stimulation with TLRs agonists does not influence the kinetics of serum HBsAg in mice. The mRNA levels of t-bet and cxcr3 were dramatically up-regulated in the liver of the mice injected with 20 μg plasmid DNA. Conclusion Our studies demonstrate that plasmid backbones are responsible for modulating immune responses to determine HBV persistence or clearance in our HBV mouse model by hydrodynamic injection of HBV-containing plasmid, and Th1 cells play key roles on HBV clearance.

DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus. Aberrantly methylated-DEGs were analyzed with R software. The Cancer Genome Atlas (TCGA) RNA sequencing and DNA methylation (Illumina HumanMethylation450) databases were utilized for validation. In total, 27 aberrantly methylated genes accompanied by altered expression were identified. After confirmation by The Cancer Genome Atlas (TCGA) database, 2 hypermethylated-low-expression genes (FAM135B and ZNF610) and 2 hypomethylated-high-expression genes (HOXA9 and DCC) were identified. A receiver operating characteristic (ROC) curve confirmed the diagnostic value of these four methylated genes for HNSCC. Multivariate Cox proportional hazards analysis showed that FAM135B methylation was a favorable independent prognostic biomarker for overall survival of HNSCC patients.

AIM: To explore feasibility and practicability of macula localization independent of macular morphological features. METHODS: A novel method was proposed to identify macula in fundus images by using structure label transfer. Its main idea was to match a processed image with the candidate images with known structures, and then transfer the structure label representing the macular to the processed image as a result of macula localization. In this way, macula localization couldn’t be influenced by lesion or other interference any more. RESULTS: The average success rate in four datasets was 98.18%. For accuracy, the average error distance in four datasets was 0.151 optic disc diameter (ODD). Even for severe lesion images, the proposed method can still maintain high success rate and high accuracy, e.g., 95.65% and 0.124 ODD in the case of STARE dataset, respectively, which indicated that the proposed method was highly robust and stable in the complicated situations. CONCLUSION: The proposed method can avoid the interference of lesion to macular morphological features in macula localization, and can locate macula with high accuracy and robustness, verifying its feasibility.

Listeria monocytogenes is a zoonotic food-borne pathogen. The production of food-borne pathogenic bacteria aggregates is considered to be a way to improve their resistance and persistence in the food chain. Ralstonia insidiosa has been shown to induce L. monocytogenes to form suspended aggregates, but induction mechanisms remain unclear. In the study, the effect of R. insidiosa cell-free supernatants cultured in 10% TSB medium (10% RIS) on the formation of L. monocytogenes suspended aggregates was evaluated. Next, the Illumina RNA sequencing was used to compare the transcriptional profiles of L. monocytogenes in 10% TSB medium with and without 10% RIS to identify differentially expressed genes (DEGs). The result of functional annotation analysis of DEGs indicated that these genes mainly participate in two component system, bacterial chemotaxis and flagellar assembly. Then the reaction network of L. monocytogenes suspended aggregates with the presence of 10% RIS was summarized. The gene-deletion strain of L. monocytogenes was constructed by homologous recombination. The result showed that cheA and cheY are key genes in the formation of suspended aggregates. This research is the preliminary verification of suspended aggregates’ RNA sequencing and is helpful to analyze the aggregation mechanisms of food-borne pathogenic bacteria from a new perspective.

To detect changes in human-to-human transmission of influenza A(H7N9) virus, we analyzed characteristics of 40 clusters of case-patients during 5 epidemics in China in 2013–2017. Similarities in number and size of clusters and proportion of clusters with probable human-to-human transmission across all epidemics suggest no change in human-to-human transmission risk.

Protein and fat oxidation are important factors that influence the quality of bovine liver. The objectives of this study were to investigate the degree of oxidation changes in bovine livers during 90d at different temperatures (−20°C, −10°C, 0°C, 10°C, and 20°C), and to develop Arrhenius models to predict its degree of oxidation.Carbonyl, thiobarbituric acid (TBA), peroxide value (POV) as oxidation attributes of bovine liver during storage were measured at different time and the changes were kinetically modeled using the Arrhenius equation. The activation energies of carbonyl, (TBA) and (POV) were 27.48, 55.48, and 58.94 KJ/mol, respectively. The determination coefficients (R2) were above 0.97 for all. In addition, volatile compounds in bovine liver and consumer acceptance of bovine liver pate with bovine liver as the final product were also measured. Among the volatile compounds, The content of aldehydes and ketones in bovine livers stored at different temperatures increased significantly (p

The development of low-cost, high-efficiency, and stable bifunctional electrocatalysts toward the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is of paramount importance for large-scale water splitting. Here, we develop a new strategy for the first design and synthesis of a NiO@Ni decorated WS2 nanosheet array on carbon cloth (NiO@Ni/WS2/CC) composite. This composite serves as a unique three-dimensional (3D) synergistic electrocatalyst that not only combines the intrinsic properties of individual NiO@Ni and WS2, but also exhibits significantly improved HER and OER activities when compared to that of pure NiO@Ni and WS2. This electrocatalyst possesses Pt-like activity for HER and exhibits better OER performance than that for commercial RuO2, as well as demonstrating superior long-term durability in alkaline media. Furthermore, it enables an alkaline electrolyzer with a current density of 10 mA cm–2 at a cell voltage as 1.42 V, which is the lowest one among all reported values to date. The excellent performance is mainly attributed to the unique 3D configuration and multicomponent synergies among NiO, Ni, and WS2. Our findings provide a new idea to design advanced bifunctional catalysts for water splitting.

Abstract This paper investigates data traffic offloading by considering a third-party cognitive small cell with wireless powered user equipments (UEs) providing data traffic offloading service to a primary macrocell. The cognitive small cell is assumed to use remaining resources for its own purpose provided that the quality of service (QoS) of the primary macrocell is satisfied. It is assumed that the small cell UEs (SUEs) are wirelessly powered and can harvest energy from the RF signals transmitted by the macrocell UEs (MUEs) as well as the RF signals transmitted by the small cell BS (SBS). Under the assumption that the successive interference cancellation (SIC) decoder is available or not available at the SBS, iterative optimization-based data traffic offloading schemes are proposed to maximize the SUE sum rate provided that the required minimum MUE sum rate is satisfied. It is shown that the proposed data traffic offloading schemes are effective in improving the performance of the MUEs and providing transmission opportunities for the wireless powered SUEs.

We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients.

Abstract Background Altered microRNAs expression mediates tumor development and progression in many type cancers including triple negative breast cancer (TNBC). Here we detected the effect of miR-454 on cell proliferation, migration and invasion of triple negative breast cancer cells. Results miR-454 promoted the proliferation of TNBC, and enhanced migration and invasion in TNBC cells. Meanwhile, miR-454 improved the survival of TNBC cells after ironizing radiation. miR-454 inhibited radiation-induced apoptosis in TNBC cells by regulation of caspase 3/7 and Bcl-2 expression. Furthermore, PTEN and pAKT levels in TNBC cells were changed after overexpression of miR-454. Conclusions miR-454 played an essential role in tumor development and progression in TNBC, and might be used as a potential biomarker to predict radiotherapy response and prognosis in TNBC.

Abstract The oriental armyworm Mythimna separate is an economically important insect with a wide distribution and strong migratory activity. However, knowledge about the molecular mechanisms regulating the physiological and behavioural responses of the oriental armyworm is scarce. In the present study, we took a transcriptomic approach to characterize the gene network in the adult head of M. separate. The sequencing and de novo assembly yielded 63,499 transcripts, which were further assembled into 46,459 unigenes with an N50 of 1,153 bp. In the head transcriptome data, unigenes involved in the ‘signal transduction mechanism’ are the most abundant. In total, 937 signal transduction unigenes were assigned to 22 signalling pathways. The circadian clock, melanin synthesis, and non-receptor protein of olfactory gene families were then identified, and phylogenetic analyses were performed with these M. separate genes, the model insect Bombyx mori and other insects. Furthermore, 1,372 simple sequence repeats of 2–6 bp in unit length were identified. The transcriptome data represent a comprehensive molecular resource for the adult head of M. separate, and these identified genes can be valid targets for further gene function research to address the molecular mechanisms regulating the migratory and olfaction genes of the oriental armyworm.

Breeding of rice with ideal plant architecture has increased rice yield worldwide. Here Zhanget al. show that, in the super rice variety YY12, this ideal plant architecture trait arose from three distal tandem repeats that are associated with an open chromatin state and increased expression of the IPA1gene.

PurposeThe purpose of this study was to construct a multi-center cross-sectional study to predict self-regulated learning (SRL) levels of Chinese medical undergraduates.MethodsWe selected medical undergraduates by random sampling from five universities in mainland China. The classical regression methods (logistic regression and Lasso regression) and machine learning model were combined to identify the most significant predictors of SRL levels. Nomograms were built based on multivariable models. The accuracy, discrimination, and generalization of our nomograms were evaluated by the receiver operating characteristic curves (ROC) and the calibration curves and a high quality external validation.ResultsThere were 2052 medical undergraduates from five universities in mainland China initially. The nomograms constructed based on the non-overfitting multivariable models were verified by internal validation (C-index: learning motivation: 0.736; learning strategy: 0.744) and external validation (C-index: learning motivation: 0.986; learning strategy: 1.000), showing decent prediction accuracy, discrimination, and generalization.ConclusionComprehensive nomograms constructed in this study were useful and convenient tools to evaluate the SRL levels of undergraduate medical students in China.

INTRODUCTION:In many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18-24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition. METHODS:A longitudinal cohort and site development study in Mozambique between November 2013 and 2014 enrolled 505 participants between 18 to 35 years old. Samples from these healthy participants, were analyzed to determine reference values. All volunteers included in the analysis were clinically healthy and human immunodeficiency virus (HIV), hepatitis B and C virus, and syphilis negative. Median and reference ranges were calculated for the hematological, biochemical and immunological parameters. Ranges were compared with other African countries, the USA and the US National Institute of Health (NIH) Division of AIDS (DAIDS) toxicity tables. RESULTS:A total of 505 participant samples were analyzed. Of these, 419 participants were HIV, hepatitis B and C virus and syphilis negative including 203 (48.5%) females and 216 (51.5%) males, with a mean age of 21 years. In the hematological parameters, we found significant differences between sex for erythrocytes, hemoglobin, hematocrit, MCV, MCH and MCHC as well as white blood cells, neutrophils and platelets: males had higher values than females. There were also significant differences in CD4+T cell values, 803 cells/μL in men versus 926 cells/μL in women. In biochemical parameters, men presented higher values than women for the metabolic, enzymatic and renal parameters: total and direct bilirubin, ALT and creatinine. CONCLUSION:This study has established reference values for healthy adults with high-risk for HIV acquisition in Mozambique. These data are helpful in the context of future clinical research and patient care and treatment for the general adult population in the Mozambique and underline the importance of region-specific clinical reference ranges.

The residual deformation of a goaf is studied to improve the foundation stability assessment for metro lines passing through the subsidence area of steeply inclined extra-thick coal seams. The variable mining influence propagation angle is introduced to describe the special form of the rock movement. Based on the modified parameters in the traditional probability integral model, a subsidence prediction model is established. Then, based on the idea of an equivalent mining thickness, Kelvin model is introduced to analyze the creep characteristics of the old goaf, and the dynamic prediction function of the residual subsidence is constructed to realize the dynamic analysis of the residual deformation. Moreover, a case study is used to evaluate the predictive effectiveness of the prediction model, and the results are compared with the monitoring data and numerical simulation results. The results show that the values with a relative error between the predicted value and measured value are in the range of ±7%, indicating that the prediction model based on the mining influence propagation angle is feasible. Thus, the residual deformation prediction model based on the mining influence propagation angle is considered to be suitable for predicting the subsidence of engineering projects crossing a goaf.

Soil aggregation is closely related to the soil organic carbon sequestration, both of which plays an important role in the stability of the soil carbon pool. However, the results of the impact of yak grazing intensity on the soil carbon process in alpine meadows have been unclear. With the marsh meadow as the research object in the Gahai wetland of the east Qinghai-Tibet Plateau, we analyzed the influence of different grazing intensities on the allocation of mass, stability and aggregate-associated organic carbon content of aggregates in the surface soil (0-20cm) of pasture by the Le Bissonnais method. The results showed that the mass of aggregates in the particle size class of > 0.2-mm was the highest among the pastures with different grazing intensities. Compared with the no grazing grassland, light grazing promoted the formation of macro aggregates in the particle size class of > 1-mm and improved the stability of soil aggregates. The degree of soil agglomerations and stability of aggregates decreased, and the macro aggregates gradually transformed into micro aggregates (< 0.05-mm class) in moderately and heavily grazed pastures. The > 2-mm and < 0.05-mm classes of particle size had a strong fixation effect on organic carbon. Light grazing promoted the accumulation of organic carbon in this particle size aggregate, and moderate and heavy grazing accelerated the decomposition of organic carbon. There was no significant difference in organic carbon in other particle size aggregates among different grasslands (P > 0.05). This result shows that light grazing, which is a reasonable yak grazing intensity in the study area, is conducive to the formation of a good soil structure in the area and improves the soil carbon sequestration capacity.

Cisplatin has been widely used in the treatment of a various types of cancers including triple-negative breast cancer (TNBC) by damaging DNA and inducing apoptosis. However, its anti-cancer effects are often limited due to chemo-resistance, which is one of the main reasons causing cancer relapse and metastasis. To overcome resistance, cisplatin is often used in combination with other drugs or molecules. Our study found that the targeted inhibition of miR-221/222 in MDA-MB-231 cells promoted cisplatin-induced cell apoptosis, and increased the cell sensitivity to cisplatin in vitro. Much higher expression levels of miR-221/222 were detected in the cisplatin-resistant MDA-MB-231 cells and in cisplatin-resistant breast cancer patients. The combination chemotherapy of cisplatin with anti-miR-221/222 showed much higher efficiency in suppressing tumor growth in the mice transplanted with MDA-MB-231 cells. In addition, anti-miR-221 and anti-miR-222 showed synergetic effects on improving sensitivity to cisplatin in MDA-MB-231 cells. Suppression of SOCS1-STAT3-Bcl-2 pathway and activation of p53-Pten signaling both contribute to anti-miR-221/222-induced sensitivity to cisplatin in MDA-MB-231 cells. These findings suggest the potential of a novel approach for the combination chemotherapy of cisplatin with small non-coding RNA in treatment of human TNBC.

For some ferromagnetic metallic materials, measurable influence of strong external magnetic field on their fracture properties has been observed experimentally, i.e., an external magnetic field of large intensity can promote the propagation of the crack. In order to clarify the mechanism of this phenomenon, a fracture model is put forward in this paper based on reversal magnetic domain theory and minimum free energy algorithm and verified through observations of magnetic domains structure. Compact tensile (CT) specimens which were stretched in strong magnetic field are adopted to observe their magnetic domains structure with the powder grain method in practice. It is found that the crack in the CT specimen propagated mainly along the magnetic domain wall rather than passing through the domain body. Together with the experimental results, the fracture model for the rupture and propagation mechanism under strong magnetic field was discussed.

Monoacylglycerol lipase (MAGL) hydrolyzes monoacylglycerol, producing free fatty acid and glycerol. Although this enzyme has been shown to play important roles in mammal, its potential function in plants remains poorly understood. In a survey of the MAGL genes in Brassica napus, we found tapetal expression of BnaC.MAGL8.a, a homolog of AtMAGL8, results in male sterility in Arabidopsis thaliana. Retarded tapetal PCD and defective pollen wall were observed in the transgenic plants. The tapetal cells became vacuolated at stage 9, and then degenerated at stage 11. Most microspores degenerated with the tapetal cells, and only few pollen grains with an irregular-shaped exine layer were produced in the transgenic plants. Transcriptome analysis identified 398 differentially expressed genes. Most of them are involved in pollen development and stress response. ABORTED MICROSPORES and its downstream pollen wall biosynthesis genes were down-regulated, but genes related with reactive oxygen species homeostasis and jasmonates signaling were up-regulated in the transgenic plants. These results suggest that expression of BnaC.MAGL8.a in tapetum invokes stress response and impairs pollen development. The apparent phenotypic similarity between atgpat1 mutant and BnA9::BnaC.MAGL8.a transgenic plants lead us to propose a role for monoacylglycerol (MAG) in pollen development in Arabidopsis. Our study provides insights on not only the biological function of plant MAGL genes but also the role of MAG in pollen development.

4-hydroxyderricin (4-HD), as a natural flavonoid compound derived from Angelica keiskei, has largely unknown inhibition and mechanisms on liver cancer. Herein, we investigated the inhibitory effects of 4-HD on hepatocellular carcinoma (HCC) cells and clarified the potential mechanisms by exploring apoptosis and cell cycle arrest mediated via the PI3K/AKT/mTOR signaling pathway. Our results show that 4-HD treatment dramatically decreased the survival rate and activities of HepG2 and Huh7 cells. The protein expressions of apoptosis-related genes significantly increased, while those related to the cell cycle were decreased by 4-HD. 4-HD also down-regulated PI3K, p-PI3K, p-AKT, and p-mTOR protein expression. Moreover, PI3K inhibitor (LY294002) enhanced the promoting effect of 4-HD on apoptosis and cell cycle arrest in HCC cells. Consequently, we demonstrate that 4-HD can suppress the proliferation of HCC cells by promoting the PI3K/AKT/mTOR signaling pathway mediated apoptosis and cell cycle arrest.

The mode-1 semidiurnal internal tides that emanate from multiple sources in the Sulu-Sulawesi Seas are investigated using multi-satellite altimeter data from 1993–2020. A practical plane-wave analysis method is used to separately extract multiple coherent internal tides, with the nontidal noise in the internal tide field further removed by a two-dimensional (2-D) spatial band-pass filter. The complex radiation pathways and interference patterns of the internal tides are revealed, showing a spatial contrast between the Sulu Sea and the Sulawesi Sea. The mode-1 semidiurnal internal tides in the Sulawesi Sea are effectively generated from both the Sulu and Sangihe Island chains, forming a spatially inhomogeneous interference pattern in the deep basin. A cylindrical internal tidal wave pattern from the Sibutu passage is confirmed for the first time, which modulates the interference pattern. The interference field can be reproduced by a line source model. A weak reflected internal tidal beam off the Sulawesi slope is revealed. In contrast, the Sulu Island chain is the sole energetic internal tide source in the Sulu Sea, thus featuring a relatively consistent wave and energy flux field in the basin. These energetic semidiurnal internal tidal beams contribute to the frequent occurrence of internal solitary waves (ISWs) in the study area. On the basis of the 28-year consistent satellite measurements, the northward semidiurnal tidal energy flux from the Sulu Island chain is 0.46 GW, about 25% of the southward energy flux. For M2, the altimetric estimated energy fluxes from the Sulu Island chain are about 80% of those from numerical simulations. The total semidiurnal tidal energy flux from the Sulu and Sangihe Island chains into the Sulawesi Sea is about 2.7 GW.

Mesoscale eddies are ubiquitous in the world ocean and well researched both globally and regionally, while their properties and distributions across the whole Indonesian Seas are not yet fully understood. This study investigates for the first time the spatiotemporal variations and generation mechanisms of mesoscale eddies across the whole Indonesian Seas. Eddies are detected from altimetry sea level anomalies by an automatic identification algorithm. The Sulu Sea, Sulawesi Sea, Maluku Sea and Banda Sea are the main eddy generation regions. More than 80% of eddies are short-lived with a lifetime below 30 days. The properties of eddies exhibit high spatial inhomogeneity, with the typical amplitudes and radiuses of 2–6 cm and 50–160 km, respectively. The most energetic eddies are observed in the Sulawesi Sea and Seram Sea. Eddies feature different seasonal cycles between anticyclonic and cyclonic eddies in each basin, especially given that the average latitude of the eddy centroid has inverse seasonal variations. About 48% of eddies in the Sulawesi Sea are highly nonlinear, which is the case for less than 30% in the Sulu Sea and Banda Sea. Instability analysis is performed using high-resolution model outputs from Bluelink Reanalysis to assess mechanisms of eddy generation. Barotropic instability of the mean flow dominates eddy generation in the Sulu Sea and Sulawesi Sea, while baroclinic instability is slightly more in the Maluku Sea and Banda Sea.

Acinetobacter baumannii, a non-fermenting Gram-negative bacterium, is a common pathogen in intensive care units (ICU) that is easily spread through contact and can cause nosocomial outbreaks. This study investigated the risk factors associated with outbreaks of pan-drug resistant Acinetobacter baumannii (PDR-Ab) infection by studying a suspected nosocomial outbreak in a comprehensive ICU in a teaching hospital in China, and discusses the effectiveness of current prevention and control measures.

Since the first outbreak of avian influenza A(H7N9) virus in humans was identified in 2013, there have been five seasonal epidemics observed in China. An earlier start and a steep increase in the number of humans infected with H7N9 virus was observed between September and December 2016, raising great public concern in domestic and international societies. The epidemiological characteristics of the recently reported confirmed H7N9 cases were analysed. The results suggested that although more cases were reported recently, most cases in the fifth epidemic were still highly sporadically distributed without any epidemiology links; the main characteristics remained unchanged and the genetic characteristics of virus strains that were isolated in this epidemic remained similar to earlier epidemics. Interventions included live poultry market closures in several cities that reported more H7N9 cases recently.

Abstract Background Concurrent chemoradiotherapy (CCRT) significantly increases the survival rate of esophageal squamous cell carcinoma (ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long-term survival. Methods We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat-sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were retrospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening (NRS) before, during, and after treatment. Twenty-two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT. Results With a median follow-up of 18 months (range, 3–39 months), patients’ 1-year overall survival (OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score (P = 0.003), increase in NRS score (P = 0.024), fistula closure (P = 0.011), and response to treatment (P

Different factors that influence the alkaline degradation of cellulose in the pulping process were considered in this study. The factors were the reaction temperature, reaction time, dosage of NaOH, and metal ions. Microcrystal cellulose (MCC) was applied as the model compound. To measure the influence of different metal ions on the alkaline degradation of cellulose, K+ and Mg2+ were added into the reaction system. The Fourier transform infrared (FTIR) spectra of the MCC in the solution with and without K+ and Mg2+ were analyzed to clarify the reaction mechanism of the alkaline degradation of cellulose and MCC. Alkaline degradation increased with increasing reaction temperature, reaction time, and alkali concentration. When the reaction temperature was above 80 °C, the reaction time was above 2 h, or the alkali content was below 5 g/L, the degradation ratio of MCC decreased. The amount of degraded MCC and the concentration of glucose in the reaction solution exhibited a nearly linear relationship when the alkali quantity increased from 0 g/L to 5 g/L. K+ and Mg2+ had an opposite impact on the alkaline degradation. While the K+ promoted the alkaline degradation of cellulose, the Mg2+ inhibited it, along with an increase of the dosage of the two metal ions.

Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis and metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, and survive during starvation. Autophagy exerts an anticarcinogenic role in normal cells and inhibits the malignant transformation of cells. On the other hand, aberrations in autophagy are involved in gene derangements, cell metabolism, the process of tumor immune surveillance, invasion and metastasis, and tumor drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have anticarcinogenic properties, including those relating to cellular proliferation inhibition, the induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, the impairment of cell migration, invasion, tumor angiogenesis, and the reduction of multidrug resistance in tumor cells. Flavonoids, which are a group of natural polyphenolic compounds characterized by multiple targets that participate in multiple pathways, have been widely studied in different models for autophagy modulation. However, flavonoid-induced autophagy commonly interacts with other mechanisms, comprehensively influencing the anticancer effect. Accordingly, targeted autophagy may become the core mechanism of flavonoids in the treatment of tumors. This paper reviews the flavonoid-induced autophagy of tumor cells and their interaction with other mechanisms, so as to provide a comprehensive and in-depth account on how flavonoids exert tumor-suppressive effects through autophagy.

Many enzymes are known to change conformations during their catalytic cycle, but the role of these protein motions is not well understood. Escherichia coli dihydrofolate reductase (DHFR) is a small, flexible enzyme that is often used as a model system for understanding enzyme dynamics. Recently, native tryptophan fluorescence was used as a probe to study micro- to millisecond dynamics of DHFR. Yet, because DHFR has five native tryptophans, the origin of the observed conformational changes could not be assigned to a specific region within the enzyme. Here, we use DHFR mutants, each with a single tryptophan as a probe for temperature jump fluorescence spectroscopy, to further inform our understanding of DHFR dynamics. The equilibrium tryptophan fluorescence of the mutants shows that each tryptophan is in a different environment and that wild-type DHFR fluorescence is not a simple summation of all the individual tryptophan fluorescence signatures due to tryptophan–tryptophan interactions. Additionally, each mutant exhibits a two-phase relaxation profile corresponding to ligand association/dissociation convolved with associated conformational changes and a slow conformational change that is independent of ligand association and dissociation, similar to the wild-type enzyme. However, the relaxation rate of the slow phase depends on the location of the tryptophan within the enzyme, supporting the conclusion that the individual tryptophan fluorescence dynamics do not originate from a single collective motion, but instead report on local motions throughout the enzyme.

Emotion recognition is of great significance to computational intelligence systems. In order to improve the accuracy of emotion recognition, electroencephalogram (EEG) signals and external physiological (EP) signals are adopted due to their perfect performance in reflecting the slight variations of emotions, wherein EEG signals consist of multiple channels signals and EP signals consist of multiple types of signals. In this paper, a multimodal emotion recognition method based on convolutional auto-encoder (CAE) is proposed. Firstly, a CAE is designed to obtain the fusion features of multichannel EEG signals and multitype EP signals. Secondly, a fully connected neural network classifier is constructed to achieve emotion recognition. Finally, experiment results show that the proposed method can improve the accuracy of emotion recognition obviously compared with other similar methods.

Experimental non-human primate models of obesity are induced through the introduction of atypically calorically rich diets. Studies in captive-bred macaques show the development of obesity and diabetes with similar complications to humans including eye and kidney diseases, nerve damage associated with pain and blood vessel damage. Diets differ in outcomes and here we document inflammation of the gastrointestinal tract that can be exacerbated through these dietary interventions. Following baseline physiological evaluation of body composition, Southern pigtail macaques were given a high-fat diet (HFD) for three months. This HFD consisted of lard, grains (including gluten), dairy and fructose that was otherwise omitted from a standard macaque diet (Chow). Physiological parameters were then reassessed before animals were reverted back to standard Chow for a further three months (remission). Consumption of the HFD resulted in food-mediated hypersensitivity marked by chronic weight loss, alopecia, malabsorption, protein-losing enteropathy and gross diffuse intestinal villi atrophy and lamina propria hypertrophy. Physiological changes were more highly pronounced in female macaques suggesting sex-specific differences but could be fully reversed through change of diet. Care should be taken in choosing non-human primate HFD diets for creating experimental models of obesity because they can induce severe food-driven chronic inflammation of the gastrointestinal tract that can eventuate to diet-induced chronic wasting and mortality.

Introduction: Initiation of pulpal pain begins with the release of bacterial toxins and inflammatory mediators that either activate or sensitize nociceptors thereby activating the trigeminal pain pathway. In addition, pain perception quickly triggers inhibitory signals that are often mediated by endogenously produced analgesic substances such as opioid peptides. The balance between inflammatory mediators and endogenously released analgesics may contribute to clinical conditions such as symptomatic versus asymptomatic pulpitis. We hypothesized that patients with asymptomatic periradicular pathosis have increased levels of the opioid peptides compared to patients with symptomatic periradicular pathosis. In addition, we also proposed to study the immune cell type that is responsible for the release the opioid peptides in periradicular lesions. Material and method: Fifty tissue biopsy samples obtained from patients who have received endodontic microsurgery and assigned to either symptomatic and asymptomatic groups (n = 25/group) based on their pre-operative clinical periradicular testings. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Fluorescence-Activated Cell Sorting (FACS) were performed to determine the expressions, levels and the cellular sources of opioid peptides, namely; β-endorphin (END), met-enkephalin (ENK) and dynorphin A (DYN), respectively. Radioimmunoassay (RIA) was performed to determine the functional role of conditioned media (CM) from asymptomatic and symptomatic patients on regulation of trigeminal (TG) neuronal activity in vitro. Results: Compared to symptomatic group, patients with asymptomatic lesions showed 3-fold increase in END levels only. Macrophages showed the highest expression of END, DYN and ENK. This study shows that the application of CM from asymptomatic and symptomatic patients triggered differential regulation of TG neuronal activity. Conclusion: Endogenous opioid peptides are present in periapical lesions. The higher level of endogenous opioid peptides in asymptomatic periapical lesions could explain the lack of symptoms in asymptomatic lesions.

IntroductionMozambique continues to have a significant burden of HIV. Developing strategies to control the HIV epidemic remains a key priority for the Mozambican public health community. The primary aim of this study was to determine HIV prevalence and risk behavior among males and females screened for a HIV vaccine preparedness study in Maputo, Mozambique.MethodsMale and female participants between 18-35 years old were recruited from the general community and from female sex worker (FSW) and lesbian, gay, bisexual, and transgender (LGBT) associations in Maputo. All participants were screened for HIV and a questionnaire was administered to each participant to assess HIV risk behavior.ResultsA total of 1125 adults were screened for HIV infection, among whom 506 (45%) were male. Among men, 5.7% reported having had sex with men (MSM) and 12% of female participants reported having exchanged sex for money, goods or favors in the past 3 months. The overall HIV prevalence was 10.4%; 10.7% of women, and 10.1% of men were HIV infected; 41.4% of MSM were seropositive. HIV infection was associated with older age (25-35 years old) (OR: 6.13, 95% CI: 3.01, 12.5), MSM (OR: 9.07, 95% CI: 3.85, 21.4), self-perception of being at high-risk for HIV (OR: 3.99, 95% CI: 1.27, 12.5) and self-report of a history of a diagnosis of sexually transmitted infection (OR: 3.75, 95% CI: 1.57, 8.98).ConclusionIn our cohort, HIV prevalence was much higher among MSM compared to the overall prevalence. Behavioral factors were found to be more associated with HIV prevalence than demographic factors. The study findings demonstrate the critical importance of directing services to minority communities, such as MSM, when prevention strategies are being devised for the general population.

Objective. To explore the role of purine family member P2Y6 receptors in regulating neuropathic pain (NP) via neuroinflammation in the spinal cord. Methods. Chronic constriction injury of the sciatic nerve (CCI) of NP was classic in setting up models on Sprague-Dawley (SD) rats. Experiments were performed on rats with sham surgery, CCI, CCI + MRS2578 (a P2Y6 receptor antagonist), and UDP (a P2Y6 receptor agonist). The hyperalgesia intensity was mirrored by paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL). Immunofluorescence staining and western blot were used to evaluate activated microglial marker Iba-1. Enzyme-linked immunosorbent assay (ELISA) was used to access levels of IL-6. Conventional reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the expression of P2Y6 mRNA and activation of JAK/STAT signaling. Results. Among all groups, CCI caused decreased PWT and TWL compared to sham surgery, meaning a successful establishment of the NP model. These decreased values of PWT and TWL tests could be prevented by intraperitoneally injected MRS2578 and enhanced by UDP administration. Similarly, CCI induced increase of Iba-1 protein, P2Y6 mRNA expression, and circulating IL-6 secretion, as well as increased JAK2/STAT3 mRNA expression and phosphorylating modification in spinal cord tissues could also be diminished by MRS2578 treatment and exacerbated by UDP. Conclusions. These findings indicated the crucial role of the P2Y6 receptor in modulating the microglial and inflammatory responses in the process of NP in vivo. Results from this study would provide insights into targeting the P2Y6 receptor to treat NP in the near future.

Today, graphene nanomaterials are produced on a large-scale and applied in various areas. The toxicity and hazards of graphene materials have aroused great concerns, in which the detection and quantification of graphene are essential for environmental risk evaluations. In this study, we developed a fast identification and quantification method for graphene oxide (GO) in aqueous environments using Raman spectroscopy. GO was chemically reduced by hydrazine hydrate to form partially reduced GO (PRGO), where the fluorescence from GO was largely reduced, and the Raman signals (G band and D band) were dominating. According to the Raman characteristics, GO was easily be distinguished from other carbon nanomaterials in aqueous environments, such as carbon nanotubes, fullerene and carbon nanoparticles. The GO concentration was quantified in the range of 0.001–0.6 mg/mL with good linearity. Using our technique, we did not find any GO in local water samples. The transport of GO dispersion in quartz sands was successfully quantified. Our results indicated that GO was conveniently quantified by Raman spectroscopy after partial reduction. The potential applications of our technique in the environmental risk evaluations of graphene materials are discussed further.

In practical engineering application, trial method is widely used to determine the control value of unified power flow controller (UPFC in short). Since the calculation is based on offline typical data, the trial method is inefficient and less accurate, which could not adjust to the changing operating conditions. In order to make up for the deficiency, this paper proposes a novel UPFC control strategy based on power transfer distribution factors. First, the anticipated line tripping fault throughout the grid is scanned and the N − 1 overload lines are marked. Then, in regard to each overload condition, a certain UPFC control value is calculated based on power transfer distribution factors. The anticipated control list could be formed and updated according to online EMS data. When a line tripping fault is detected, simply by searching the control list, a condition could be matched and the UPFC could immediately be activated to eliminate the line overload. This method mentioned above could provide decision-making support to power-grid dispatching institutions. The results of a simulation example shows that the method is efficient and utilisable.

Objectives: Squamous cell carcinoma in a thyroglossal duct cyst is exceedingly rare with only 26 reported cases in the literature so far, which only account for 6% of the patients. Methods: We report a unique case of squamous cell carcinoma arising from a thyroglossal duct cyst in a 49-year-old male who was primarily diagnosed as a thyroglossal duct cyst with inflammation. The patient underwent Sistrunk procedure with wide local excision and radiation therapy as well as chemotherapy post-operatively and had no evidence of recurrence or metastasis for 24 months. In addition, we reviewed the relevant literatures. Results: Whether squamous cell carcinoma actually arises from thyroglossal duct cyst is still controversial; however, carcinoma originating from metaplasia of columnar and squamous epithelium in thyroglossal duct cyst has been well accepted. The gold-standard diagnostic method is fine needle aspiration biopsy with ultrasound guidance. Sistrunk procedure alone or with wide excision is likely to be beneficial. Neck dissection is necessary in patients with positive cervical lymphadenopathy. Radiation therapy and chemotherapy have not yet been clearly defined. Conclusion: Squamous cell carcinoma arising from thyroglossal duct cyst is really a rare disease, whose origin, treatments and prognosis still remain uncertain. These are solely based on case reports, case series and expert opinions. Hence, more investigations about squamous cell carcinoma will be conducted in the near future.

We estimated the incubation period and serial interval for human-to-human–transmitted avian influenza A(H7N9) virus infection using case-patient clusters from epidemics in China during 2013–2017. The median incubation period was 4 days and serial interval 9 days. China’s 10-day monitoring period for close contacts of case-patients should detect most secondary infections.

Quercus fenchengsis is a rare Chinese oak species sporadically recorded in Fengcheng, Liaoning, Yuntai Mountain, Henan, and Qinling Mountains, Shaanxi. Here, the complete chloroplast (cp) genome of Q. fenchengensis was first reported. The cp genome is 161,296 bp in length with a GC content of 36.81%, and encodes 134 genes (86 protein-coding genes, 40 tRNA genes and eight rRNA genes). The phylogenetic tree based on the cp genome confirmed that Q. fenchengensis has a close relationship with Quercus aliena acutiserrata and Quercus dentata, consistent with the previous morphology-based suggestion that it would be a hybrid of Q. aliena acutiserrata and Q. dentata.

Data from four ice-tethered buoys deployed in 2010 were used to investigate sea-ice motion and deformation from the Central Arctic to Fram Strait. Seasonal and long-term changes in ice kinematics of the Arctic outflow region were further quantified using 42 ice-tethered buoys deployed between 1979 and 2011. Our results confirmed that the dynamic setting of the transpolar drift stream (TDS) and Fram Strait shaped the motion of the sea ice. Ice drift was closely aligned with surface winds, except during quiescent conditions, or during short-term reversal of the wind direction opposing the TDS. Meridional ice velocity south of 85°N showed a distinct seasonal cycle, peaking between late autumn and early spring in agreement with the seasonality of surface winds. Inertia-induced ice motion was strengthened as ice concentration decreased in summer. As ice drifted southward into the Fram Strait, the meridional ice speed increased dramatically, while associated zonal ice convergence dominated the ice-field deformation. The Arctic atmospheric Dipole Anomaly (DA) influenced ice drift by accelerating the meridional ice velocity. Ice trajectories exhibited less meandering during the positive phase of DA and vice versa. From 2005 onwards, the buoy data exhibit high Arctic sea-ice outflow rates, closely related to persistent positive DA anomaly. However, the long-term data from 1979 to 2011 do not show any statistically significant trend for sea-ice outflow, but exhibit high year-to-year variability, associated with the change in the polarity of DA.

The unified power flow controller (UPFC) based on modular multilevel converter (MMC) is the most creative flexible ac transmission system (FACTS) device. In theory, the output voltage of the series MMC in MMC-UPFC can be regulated from 0 to the rated value. However, there would be relatively large harmonics in the output voltage if the voltage modulation ratio is small. In order to analyze the influence of MMC-UPFC on the harmonics of the power grid, the theoretical calculation method and spectra of the output voltage harmonics of MMC are presented. Subsequently, the calculation formulas of the harmonics in the power grid with UPFC are proposed. Based on it, the influence of UPFC on the grid voltage harmonics is evaluated, when MMC-UPFC is operated with different submodular numbers and voltage modular ratios. Eventually, the proposed analysis method is validated using digital simulation. The study results would provide guideline for the design and operation of MMC-UPFC project.

Wind farms can affect the power quality (PQ) of the power supply grid, with subsequent impacts on the safe and stable operation of other electrical equipment. A novel PQ prediction, early warning, and control approach for the common coupling points between wind farms and the network is proposed in this paper. We then quantify PQ problems and provide rational support measures. To obtain predicted PQ data, we first establish a trend analysis model. The model incorporates a distance-based cluster analysis, probability distribution analysis based on polynomial fitting, pattern matching based on similarity, and Monte Carlo random sampling. A data mining algorithm then uses the PQ early warning flow to analyze limit-exceeding and abnormal data, quantify their severity, and output early warning prompts. Finally, PQ decision support is applied to inform both the power suppliers and users of anomalous changes in PQ, and advise on corresponding countermeasures to reduce relevant losses. Case studies show that the proposed approach is effective and feasible, and it has now been applied to an actual PQ monitoring platform.