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Evapotranspiration (ET) is an important part of water cycle in nature, and the estimation of evapotranspiration on spatio-temporal scale has always been a hot issue. Remote sensing can estimate evapotranspiration on regional scale, but it is difficult to obtain evapotranspiration in continuous time series due to the limitation of satellite transit time. Soil moisture is an important controlling factor of evapotranspiration. Improving the remote sensing evapotranspiration model by combining soil moisture data is of great significance in improving the accuracy of remote sensing evapotranspiration estimation. However, most remote sensing methods give limited consideration to the characterization of soil moisture stress. This study used the evapotranspiration calculated by the vorticity correlation method as the actual evapotranspiration. combining with the single crop coefficient method recommended by FAO, the soil water content information was introduced into the Penman-Monteith formula to calculate the actual evapotranspiration. Based on Richards equation, the one-dimensional vertical soil water movement process under evaporation conditions was simulated to estimate the continuous daily evapotranspiration under soil water stress. Combining with remote sensing data, the regional scale evapotranspiration was estimated. The results show that the actual daily evapotranspiration calculated by the vorticity correlation method has a strong correlation with the potential daily evapotranspiration calculated by P-M formula, with the correlation coefficient of 0.918. With the introduction of soil water content information, the P-M formula improves the estimation accuracy of daily evapotranspiration significantly, and the RMSE reaches 0.133 mm/d. The estimated daily evapotranspiration under soil water stress based on Richards equation is close to the measured value, with the RMSE of 0.288 mm/d. The high value of daily evapotranspiration affected by the topography of the study area is concentrated in the water area and cultivated land area in the middle of the study area. The average daily evapotranspiration under different soil use types is water area > cultivated land > woodland > grassland > unused land, and the results on the regional scale show similar change with that measured in the the station in time series. This study provides basic information for understanding the influence mechanism of soil moisture on evapotranspiration and estimating regional evapotranspiration.

Abstract Nonreciprocal quantum transport effect is mainly governed by the symmetry breaking of the material systems and is gaining extensive attention in condensed matter physics. Realizing electrical switching of the polarity of the nonreciprocal transport without external magnetic field is essential to the development of nonreciprocal quantum devices. However, electrical switching of superconducting nonreciprocity remains yet to be achieved. Here, we report the observation of field-free electrical switching of nonreciprocal Ising superconductivity in Fe3GeTe2/NbSe2 van der Waals (vdW) heterostructure. By taking advantage of this electrically switchable superconducting nonreciprocity, we demonstrate a proof-of-concept nonreciprocal quantum neuronal transistor, which allows for implementing the XOR logic gate and faithfully emulating biological functionality of a cortical neuron in the brain. Our work provides a promising pathway to realize field-free and electrically switchable nonreciprocity of quantum transport and demonstrate its potential in exploring neuromorphic quantum devices with both functionality and performance beyond the traditional devices.

IntroductionEndometriosis (EMs) is characterized by ectopic growth of active endometrial tissue outside the uterus. The Luoshi Neiyi prescription (LSNYP) has been extensively used for treating EMs in China. However, data on the active chemical components of LSNYP are insufficient, and its pharmacological mechanism in EMs treatment remains unclear. This study aimed to explore the potential mechanism of LSNYP for EMs through network pharmacology based on the components absorbed into the blood.MethodsUltra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze blood components, and a series of network pharmacology strategies were utilized to predict targets of these components and EMs. Protein–protein interaction (PPI) network analysis, component–target–disease network construction, gene ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Additionally, molecular docking, molecular dynamics simulations, and in vitro and in vivo experiments were conducted to validate the HIF1A/EZH2/ANTXR2 pathway associated with hypoxic pathology in EMs.ResultsThirty-four absorbed components suitable for network pharmacology analysis were identified, and core targets, such as interleukin 6, EGFR, HIF1A, and EZH2, were founded. Enrichment results indicated that treatment of EMs with LSNYP may involve the regulation of hypoxia and inflammatory-related signaling pathways and response to oxidative stress and transcription factor activity. Experimental results demonstrated that LSNYP could decrease the expression of HIF1A, ANTXR2, YAP1, CD44, and β-catenin, and increased EZH2 expression in ectopic endometrial stromal cells and endometriotic tissues. Molecular docking and molecular dynamics simulations manifested that there was stable combinatorial activity between core components and key targets of the HIF1A/EZH2/ANTXR2 pathway.ConclusionLSNYP may exert pharmacological effects on EMs via the HIF1A/EZH2/ANTXR2 pathway; hence, it is a natural herb-related therapy for EMs.

Abstract The spin Hall effect (SHE) allows efficient generation of spin polarization or spin current through charge current and plays a crucial role in the development of spintronics. While SHE typically occurs in non-magnetic materials and is time-reversal even, exploring time-reversal-odd (T-odd) SHE, which couples SHE to magnetization in ferromagnetic materials, offers a new charge-spin conversion mechanism with new functionalities. Here, we report the observation of giant T-odd SHE in Fe3GeTe2/MoTe2 van der Waals heterostructure, representing a previously unidentified interfacial magnetic spin Hall effect (interfacial-MSHE). Through rigorous symmetry analysis and theoretical calculations, we attribute the interfacial-MSHE to a symmetry-breaking induced spin current dipole at the vdW interface. Furthermore, we show that this linear effect can be used for implementing multiply-accumulate operations and binary convolutional neural networks with cascaded multi-terminal devices. Our findings uncover an interfacial T-odd charge-spin conversion mechanism with promising potential for energy-efficient in-memory computing.

Long-term exposure to PM2.5 pollution increases the risk of cardiovascular diseases, particularly ischemic heart disease (IHD). Current assessments of the health effects related to PM2.5 exposure are limited by sparse ground monitoring stations and applicable disease research cohorts, making accurate health effect evaluations challenging. Using satellite-observed aerosol optical depth (AOD) data and the XGBoost-PM25 model, we obtained 1 km scale PM2.5 exposure levels across China. We quantified the premature mortality caused by PM2.5-exposure-induced IHD using the Global Exposure Mortality Model (GEMM) and baseline mortality data. Furthermore, we employed the Gini coefficient, a measure from economics to quantify inequality, to evaluate the distribution differences in health impacts due to PM2.5 exposure under varying socioeconomic conditions. The results indicate that PM2.5 concentrations in China are higher in the central and eastern regions. From 2007 to 2022, the national overall level showed a decreasing trend, dropping from 47.41 μg/m3 to 25.16 μg/m3. The number of premature deaths attributable to PM2.5 exposure increased from 819 thousand in 2007 to 870 thousand in 2022, with fluctuations in certain regions. This increase is linked to population growth and aging because PM2.5 levels have decreased. The results also indicate disparities in premature mortality from IHD among different economic groups in China from 2007 to 2022, with middle-income groups having a higher cumulative proportion of IHD-related premature deaths compared with high- and low-income groups. Despite narrowing GDP gaps across regions from 2007 to 2022, IHD consistently “favored” the middle-income groups. The highest Gini coefficient was observed in the Northwest (0.035), and the lowest was in the South (0.019). Targeted policy interventions are essential to establish a more equitable atmospheric environment.

Personalized travel itinerary recommendation algorithms are the focus of research in smart tourism and tourism GIS. Aiming to address issues present in travel itinerary recommendations for the increasingly popular “self-drive tour” mode, this study proposes an algorithm based on comprehensive tourist satisfaction to mitigate problems such as the neglect of important relevant factors and low degree of personalization. First, we construct a model of tourist satisfaction for travel itineraries by comprehensively considering factors including time utilization, the attractiveness of attractions, itinerary feasibility, and the diversity of attraction types. Unlike previous studies, we consider dining and accommodation time during the itinerary, the physical condition of tourists, and the diversity of attraction types, and establish penalty functions to flexibly constrain deviations from the expected conditions in itinerary planning. Then, with the optimization of comprehensive tourist satisfaction as the objective, we design a new algorithm to address the itinerary recommendation problem, supporting tourists in selecting must-visit attractions, restaurants, and hotels, as well as personalized preferences such as the sightseeing sequence. The experimental results demonstrate that our proposed algorithm outperforms two baseline algorithms, providing higher comprehensive tourist satisfaction while also exhibiting greater feasibility in itinerary planning. The proposed algorithm effectively addresses the issue of personalized travel itinerary recommendation, presenting an efficient, feasible, and practical solution.

Abstract Background In addition to specifically inducing tumor cell apoptosis, recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has also been reported to influence the cancer immune microenvironment; however, its underlying effects and mechanisms remain unclear. Investigating the immunomodulatory effects and mechanisms of recombinant TRAIL in the tumor microenvironment (TME) may provide an important perspective and facilitate the exploration of novel TRAIL strategies for tumor therapy. Methods Immunocompetent mice with different tumors were treated with three doses of recombinant TRAIL, and then the tumors were collected for immunological detection and mechanistic investigation. Methodological approaches include flow cytometry analysis and single-cell sequencing. Results In an immunocompetent mouse model, recombinant soluble mouse TRAIL (smTRAIL) had dose-related immunomodulatory effects. The optimal dose of smTRAIL (2 mg/kg) activated innate immune cells and CD8+ T cells, whereas higher doses of smTRAIL (8 mg/kg) promoted the formation of a tumor-promoting immune microenvironment to counteract the apoptotic effects on tumor cells. The higher doses of smTRAIL treatment promoted M2-like macrophage recruitment and polarization and increased the production of protumor inflammatory cytokines, such as IL-10, which deepened the suppression of natural killer (NK) cells and CD8+ T cells in the tumor microenvironment. By constructing an HU-HSC-NPG.GM3 humanized immune system mouse model, we further verified the immunomodulatory effects induced by recombinant soluble human TRAIL (shTRAIL) and found that combinational administration of shTRAIL and trabectedin, a macrophage-targeting drug, could remodel the tumor immune microenvironment, further enhance antitumor immunity, and strikingly improve antitumor effects. Conclusion Our results highlight the immunomodulatory role of recombinant TRAIL and suggest promising therapeutic strategies for clinical application. Graphical Abstract

The timely monitoring of urban water bodies using unmanned aerial vehicle (UAV)-mounted remote sensing technology is crucial for urban water resource protection and management. Addressing the limitations of the use of satellite data in inferring the water quality parameters of small-scale water bodies due to their spatial resolution constraints and limited input features, this study focuses on the Zao River in Xi’an City. Leveraging UAV multispectral imagery, a feature selection method based on Relief Feature Ranking with Recursive Feature Elimination (Relief F-RFE) is proposed to determine the quality parameters of the typical urban pollution in water (dissolved oxygen (DO), total nitrogen (TN), turbidity, and chemical oxygen demand (COD). By constructing a potential feature set and utilizing optimal feature combinations, inversion models are developed for the four water quality parameters using three machine learning (ML) algorithms (Random Forest (RF), Support Vector Regression (SVR), Light Gradient Boosting Machine (LightGBM). The inversion accuracies of the different models are compared, and the spatial distribution of the four water quality parameters is analyzed. The results show that the models constructed based on UAV-based multispectral remote sensing imagery perform well in inferring the water quality parameters of the Zao River. The SVR algorithm, based on Relief F-RFE feature selection, achieves a higher accuracy, with RMSE values of 7.19 mg/L, 1.14 mg/L, 3.15 NTU, and 4.28 mg/L, respectively. The methods and conclusions of this study serve as a reference for research on the inversion of water quality parameters in urban rivers.

In wireless communication wiretap channel, for the eavesdropper to obtain the legitimate receiver decoding rules situation, this paper proposes a LT-SLT fountain code anti-eavesdropping channel coding design. This method targets the Luby Transform (LT) code transmission for some of the original symbols of the Shifted LT (SLT) code and utilizes the fountain code to receive the correct symbols in different noise channels with differential characteristics so that the decoding process of the eavesdropper changes and cannot be decoded in synchronization with the legitimate receivers, and then the partial symbols of the recovered source are different from those of the legitimate receivers. When these symbols continue to participate in SLT decoding, increasing the untranslated rate of the eavesdropper. Experimental results show that although the method proposed in this paper increases the number of decoded symbols by a small amount, the eavesdropper untranslated rate of this scheme gets improved by about 15% when the main channel or the wiretap channel is varied individually, compared with LT code and SLT code. When both the main channel and the wiretap channel are varied simultaneously, the untranslated rate of the eavesdropper in this scheme gets approximately 30% higher compared to LT code and SLT code, and the untranslated rate of the eavesdropper in this scheme gets approximately 14% higher compared to SLT-LT fountain code. When the main channel is worse or slightly better than the wiretap channel, the untranslated rate of eavesdroppers of this scheme is better than that of SLT-LT fountain code, which effectively ensures secure transmission of information.

Abstract Background Long non-coding RNA (LncRNA) plays important roles in physiological and pathological processes. Identifying LncRNA–protein interactions (LPIs) is essential to understand the molecular mechanism and infer the functions of lncRNAs. With the overwhelming size of the biomedical literature, extracting LPIs directly from the biomedical literature is essential, promising and challenging. However, there is no webserver of LPIs relationship extraction from literature. Results LPInsider is developed as the first webserver for extracting LPIs from biomedical literature texts based on multiple text features (semantic word vectors, syntactic structure vectors, distance vectors, and part of speech vectors) and logistic regression. LPInsider allows researchers to extract LPIs by uploading PMID, PMCID, PMID List, or biomedical text. A manually filtered and highly reliable LPI corpus is integrated in LPInsider. The performance of LPInsider is optimal by comprehensive experiment on different combinations of different feature and machine learning models. Conclusions LPInsider is an efficient analytical tool for LPIs that helps researchers to enhance their comprehension of lncRNAs from text mining, and also saving their time. In addition, LPInsider is freely accessible from http://www.csbg-jlu.info/LPInsider/ with no login requirement. The source code and LPIs corpus can be downloaded from https://github.com/qiufengdiewu/LPInsider .

Fountain code can significantly increase eavesdroppers’ untranslated efficiency in the wireless communication eavesdropping channel. The secondary LT coding anti-eavesdropping scheme with fountain code degree-1 is the subject of a theoretical investigation in this paper. The fact that its channel security capacity is greater than that of traditional LT code is first deduced from an information-theoretic standpoint, and the impact of source symbol length on decoding complexity and decoding overhead is then examined. The experimental results show that, compared with the traditional anti-eavesdropping twice fountain code, selecting long source symbols for double LT coding, when the main channel is better than the eavesdropping channel, can ensure that the eavesdropper has a higher untranslated efficiency, and can effectively reduce the fountain code decoding complexity and the number of encoded symbols sent by the source to improve the efficiency of information transmission.

Abstract Background Nicotine is an important risk factor and the main toxic component associated with periodontitis. However, the mechanism of nicotine induced periodontitis is not clear. To investigated the mechanism through which nicotine regulates autophagy of human periodontal ligament cells (hPDLCs) through the alpha7 nicotinic acetylcholine receptor (α7 nAChR) and how autophagy further regulates the release of IL-1β and IL-8 secretion in hPDLCs. Methods HPDLCs were obtained from root of extracted teeth and pre-incubated in alpha-bungarotoxin (α-BTX) or 3-Methyladenine (3-MA), followed by culturing in nicotine. We used a variety of experimental detection techniques including western blotting, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and RT-qPCR to assess the expression of the LC3 protein, autolysosome, and release of IL-1β and IL-8 from hPDLCs. Results Western blots, immunofluorescence and TEM results found that the nicotine significantly increased the autophagy expression in hPDLCs that was time and concentration dependent and reversed by α-BTX treatment (p < 0.05). RT-qPCR and ELISA results revealed a noticeable rise in the release of inflammatory factors IL-1β and IL-8 from hPDLCs in response to nicotine. RT-qPCR and ELISA results showed that nicotine can significantly up-regulate the release of inflammatory factors IL-1β and IL-8 in hPDLCs, and this effect can be inhibited by 3-MA (p < 0.05). Conclusions Nicotine regulated autophagy of hPDLCs through α7 nAChR and in turn the regulation of the release of inflammatory factors 1L-1β and 1L-8 by hPDLCs.

The existing physical layer security technology based on fountain codes needs to ensure that the legal channel is superior to the eavesdropping channel; when the quality of the legal channel and the eavesdropping channel are close, the information security cannot be guaranteed. Aiming at this problem, this paper proposes a shifted Luby transform (SLT) code security scheme for partial information encryption, which is mainly divided into two stages, partial information encryption transfer and degree distribution adjustment. The main idea is that the source randomly extracts part of the information symbols, and performs XOR encryption with the random sequence containing the main channel noise sent by the legitimate receiver. Afterward, the degree distribution is adjusted using the number of transfer information symbols received by the legitimate receiver to improve the average degree of the encoded codewords. Since the eavesdropper can only obtain fewer information symbols in the initial stage, it is difficult to decode the generated coded symbols after the degree distribution adjustment, thereby ensuring the safe transmission of information. The experimental results show that, compared with other LT anti-eavesdropping schemes, even if the legitimate channel is not dominant, the proposed scheme still has better security performance and less decoding overhead.

Moonlighting proteins (MPs) are a special type of protein with multiple independent functions. MPs play vital roles in cellular regulation, diseases, and biological pathways. At present, very few MPs have been discovered by biological experiments. Due to the lack of data sample, computation-based methods to identify MPs are limited. Currently, there is no de-novo prediction method for MPs. Therefore, systematic research and identification of MPs are urgently required. In this paper, we propose a multimodal deep ensemble learning architecture, named MEL-MP, which is the first de novo computation model for predicting MPs. First, we extract four sequence-based features: primary protein sequence information, evolutionary information, physical and chemical properties, and secondary protein structure information. Second, we select specific classifiers for each kind of feature. Finally, we apply the stacked ensemble to integrate the output of each classifier. Through comprehensive model selection and cross-validation experiments, it is shown that specific classifiers for specific feature types can achieve superior performance. For validating the effectiveness of the fusion-based stacked ensemble, different feature fusion strategies including direct combination and a multimodal deep auto-encoder are used for comparative purposes. MEL-MP is shown to exhibit superior prediction performance (F-score = 0.891), surpassing the existing machine learning model, MPFit (F-score = 0.784). In addition, MEL-MP is leveraged to predict the potential MPs among all human proteins. Furthermore, the distribution of predicted MPs on different chromosomes, the evolution of MPs, the association of MPs with diseases, and the functional enrichment of MPs are also explored. Finally, for maximum convenience, a user-friendly web server is available at: http://ml.csbg-jlu.site/mel-mp/.

Therapeutic cancer vaccines aim to induce an effective immune response against cancer, and the effectiveness of these vaccines is influenced by the choice of immunogen, vaccine type, and immunization strategy. Although treatment with cancer vaccines can improve tumor burden and survival, in most animal studies, it is challenging to achieve a complete response against tumor growth and recurrence, without the use of other therapies in combination. Here, we present a novel approach where dual antigens (survivin and MUC1) are co-targeted using three DNA vaccines, followed by a single booster of a recombinant modified vaccinia Ankara (MVA) vaccine. This heterologous vaccination strategy induced higher levels of interferon (IFN)-γ-secretion and stronger antigen-specific T-cell responses than those induced individually by the DNA vaccines and the MVA vaccine in mice. This strategy also increased the number of active tumor-infiltrating T cells that efficiently inhibit tumor growth in tumor-bearing mice. Heterologous DNA prime-MVA boost immunization was capable of inducing a robust antigen-specific immune-memory, as seen from the resistance to subsequent survivin- and MUC1-expressing tumors. Moreover, the therapeutic effects of DNA prime-MVA boost and DNA prime-adenovirus boost strategies were compared. DNA prime-MVA boost immunization performed better, as indicated by the T effector ratio and the induction of Th1 immunity. This study provides the basis for the use of heterologous DNA prime-MVA boost vaccination regime targeting two antigens simultaneously as a promising immunotherapeutic strategy against cancer.

Lipids are key factors in nutrition, structural function, metabolic features, and other biological functions. In this study, the lipids from the heads of four species of shrimp (Fenneropenaeus chinensis (FC), Penaeus japonicus (PJ), Penaeus vannamei (PV), and Procambarus clarkia (PCC)) were compared and characterized based on UPLC–Q–Exactive Orbitrap/MS. We compared the differences in lipid composition of four kinds of shrimp head using multivariate analysis. In addition, a zebrafish model was used to evaluate pro-angiogenic, anti-inflammatory, anti-thrombotic, and cardioprotective activities of the shrimp head lipids. The lipids from the four kinds of shrimp head had different degrees of pro-angiogenic activities, and the activities of PCC and PJ shrimp lipids were more significant than those of the other two species. Four lipid groups displayed strong anti-inflammatory activities. For antithrombotic activity, only PCC (25 μg/mL) and PV (100 μg/mL) groups showed obvious activity. In terms of cardioprotective activity, the four kinds of lipid groups significantly increased the zebrafish heart rhythms. The heart distances were shortened, except for those of the FC (100 μg/mL) and PJ (25 μg/mL) groups. Our comprehensive lipidomics analysis and bioactivity study of lipids from different sources could provide a basis for the better utilization of shrimp.

Parkinson's disease (PD) is a progressive and age-associated neurodegenerative disorder. Patients at different stages of the disease course have distinguished features, mainly in the number of dopaminergic neurons. Cerebral dopamine neurotrophic factor (CDNF) is a recently discovered neurotrophic factor, being deemed as a hopeful candidate for PD treatment. Here, we evaluated the efficacy of CDNF in protecting dopaminergic function using the 6-OHDA-induced PD rat model suffering from different levels of neuronal loss and the recombinant adeno-associated virus 8 (AAV8) as a carrier for the CDNF gene. The results showed that AAV8-CDNF administration significantly improved the motor function and increased the tyrosine hydroxylase (TH) levels in PD rats with mild lesions (2 weeks post lesion), but it had limited therapeutic effects in rats with severe lesions (5 weeks post lesion). To better improve the recovery of motor function in severely lesioned PD rats, we employed a strategy using the CDNF gene along with the aromatic amino acid decarboxylase (AADC) gene. This combination therapeutic strategy indeed showed an enhanced benefit in restoring the motor function of severely lesioned PD rats by providing the neuroprotective effect of CDNF and dopamine enhancing effect of AADC as expected. This study may provide a basis for future clinical application of CDNF in PD patients at different stages and offer a new alternative strategy of joint use of CDNF and AADC for advanced PD patients in clinical trials.

Background/Aims: Tobacco smoking is a major risk factor for the occurrence and progression of periodontitis. We previously demonstrated that nicotine could induce the expression of a7 nicotinic acetylcholine receptors (a7 nAChR) in human and rat periodontal tissues. To further examine the signal pathways mediated by a7 nAChR in periodontal ligament (PDL) cells, we investigated whether nicotine affects interleukin-1ß (IL-1ß) and interleukin-8 (IL-8) via the a7 nAChR/NF-κB pathway in human PDL cells. Methods: Human PDL cells were pre-incubated with alpha-bungarotoxin (a-BTX) or pyrrolidine dithiocarbamate (PDTC), then cultured with nicotine. Then, we used western blotting, a dual-luciferase reporter, real-time quantitative PCR and an enzyme-linked immunoassay to assess expression of the NF-κB p65 subunit, NF-κB activity and production of IL-1ß and IL-8 in human PDL cells. Results: Compared with the control group, nicotine could significantly induce production of IL-1ß and IL-8 in human PDL cells and cause the similar effects on the expression of the NF-κB p65 subunit and NF-κB activity. Conclusion: This study demonstrates that nicotine could induce production of IL-1ß and IL-8 via the a7 nAChR/NF-κB pathway in human PDL cells, providing data for a better understanding of the relationships among smoking, nicotine, and periodontitis.

PURPOSE: Activation of Toll like receptors (TLRs) signaling has been implicated in promoting malignant cell invasion and metastatic potential. Previously we demonstrated that increased TLR-9 expression predicted poor survival in oral cancer patients. The objective of this study is to further investigate the roles and potential molecular mechanisms of TLR-9 signaling in human oral cancer cell invasion. METHODS: Cell migration, invasion and protein expression were detected by wound healing assay, Transwell chambers model and western blot. The secretion and activity levels of metalloproteinases-2/9 were quantified by ELISA and Gelatin zymography. EMSA and ChIP assays were employed to detect the activity of AP-1signal pathway. TLR-9 siRNA transfection was used to regulate the expression and activity of TLR-9 in oral cancer cell line HB cells. RESULT: The results of both wound healing assay and in vitro Transwell assay revealed that activation of TLR-9 induced dose- and time- dependent migration and invasion of HB cells. An increased expression, secretion and activity of MMP-2 were observed upon the treatment of CpG-ODN. The TLR-9 signaling-mediated MMP-2 expression appeared to be a consequence of AP-1 activation, because that their DNA binding activity was enhanced by CpG-ODN treatment. All these influences were efficiently repressed by the knockdown of TLR-9 through siRNA or pretreatment of an AP-1 inhibitor. CONCLUSION: Activation of TLR-9 signaling could promote human oral cancer HB cells invasion with the induction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel anti-metastatic application for TLR-9 targeted therapy in oral cancer in the future.

AIMS: Cigarette smoking is one of the high risk factors of adult chronic periodontitis and nicotine is the well established toxic substance in cigarette. However, the mechanism of nicotine induced periodontitis is still unknown. Here we studied whether nicotine impaired the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) through activating α7 nicotinic acetylcholine receptor (α7 nAChR). METHODS: hPDLSCs with multi differentiation potential and surface makers for mesenchymal stem cells were harvested by limiting dilution technique. The level of mineralized nodule formation was assessed by alizarin red S staining. Expression level of ostegenic related genes and proteins were detected by real-time PCR and western blot analysis. The expression of α7 nAChR and its downstream signaling pathway were examined by western blot. The role of the receptor and related signaling pathway in nicotine impairing the osteogenic potential of hPDLSCs were also studied in different levels. RESULTS: Nicotine deteriorated the ostegenic differentiation of hPDLSCs in a dose dependent manner. Activation of α7 nAChR by nicotine treatment activated wnt/β-catenin signaling pathway, leading to osteogenic deficiency of hPDLSCs. Blockage of α7 nAChR and wnt pathway inhibitor treatment rescued nicotine induced osteogenic differentiation deficiency. CONCLUSIONS: These data suggested that nicotine activated α7 nAChR expressed on PDLSCs and further activated wnt signaling downstream, thus deteriorating the osteogenic potential of PDLSCs. The impairment of osteogenic differentiation of PDLSCs by nicotine might lead to cigarette smoking related periodontitis.

Objective: To explore the effect of nicotine on the autophagy level of human periodontal ligament cells (hPDLCs)., Methods: Periodontal tissues collected from premolars for orthodontic treatment reasons were used to culture hPDLCs. Western blot analysis was performed to test the most optimal time and concentration of nicotine on the autophagy level of the hPDLCs. Transmission electron microscope and immunofluorescence observation were carried out to detect the form of autophagosomes and expression of autophagy related protein LC3 in hPDLCs under this optimal condition., Results: Protein expression of LC3Ⅱ was up regulated with the 12 h nicotine stimulating. Besides that, the up regulation of the protein expression of LC3Ⅱ was concentration dependent and nicotine with a concentration of 1×10⁻⁵ mol·L⁻¹ was the most optimal condition. Transmission electron microscope and immunofluorescence observations indicated that nicotine would activate the autophagy level of hPDLCs by increasing the number of autophagosomes and up regulating the expression of autophagy related protein LC3., Conclusions: Nicotine could increase autophagy level of hPDLCs, thus affecting the occurrence and development of smoking related periodontitis.

Purpose: High-grade mucoepidermoid carcinoma (MEC) is an infrequent malignant neoplasm originates most commonly in the salivary glands with poor prognosis. Thus far, there is little knowledge on MUC-1 expression in high-grade MEC or how it may relate to patient survival. The aim of this study was to determine the extent of MUC-1 expression in high-grade MEC and correlate expression with clinic outcome., Methods: Surgical specimens from 62 cases of primary high-grade MEC and 10 cases of normal salivary gland tissue were examined by immunohistochemistry. The relationship between MUC-1 expression and the clinicopathological data and patient survival was analyzed., Results: The disease-free survival rates were 54.6% (3 years) and 37.7% (5 years) for high-grade MEC patients. Patient who with primary location at submandibular gland have the worst prognosis (P = 0.042) in comparing with other sites. High expression of MUC-1 in high-grade MEC was significantly correlated with lymphatic/regional metastasis (P = 0.003) and clinic stage (P = 0.02), and high expression of MUC-1 (>75%) was confirmed to be significant independent prognostic factors in high-grade MEC patients [HR 2.929 (95% CI 1.246-6.881); P < 0.0137]., Conclusions: The findings suggest that high levels of MUC-1 expression may be a potential marker for worse outcome in high-grade MEC and could be used as a new molecule target to improve outcomes for these patients in the future., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Increasing evidence suggests that malignant transformation can result from chronic infection, and Toll-like receptors (TLRs) may play an important role in this process. We have previously reported that the increased expression of TLR-9 is associated with tumor cell proliferation in oral cancer. However, the mechanisms involved have not been elucidated. The aim of this study was to investigate whether CpG-oligodeoxynucleotides (CpG-ODN), a special TLR-9 agonist, is able to exert the proliferation-promoting effect in human oral squamous cell carcinoma (OSCC), and to explore the possible underlying molecular mechanism. Flow cytometry, MTT, and colony formation assay were used to evaluate cell proliferation and cell cycle distribution. The mRNA and protein levels were analyzed by quantitative RT-PCR and Western blot assay. Luciferase reporter gene, EMSA, and ChIP assays were used to detect the activity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) in HB cells. Results showed that CpG-ODN could stimulate proliferation of HB cells in a dose- and time-dependent manner with a promoted G(1) /S cell cycle progression. Increased cyclin D1 expression was detected in the nuclear region after CpG-ODN treatment. Moreover, CpG-ODN promoted nuclear translocation and activation of AP-1, which appeared to be required for TLR-9-mediated cyclin D1 expression and subsequently cell proliferation, but seemed to have little impact on NF-κB activity. Our results indicate that CpG-ODN stimulates tumor cell proliferation through TLR-9-mediated AP-1-activated cyclin D1 expression in OSCC HB cells. Pharmacologic inhibition of the TLR-9/AP-1/cyclin D1 pathway may be a new therapeutic approach for prevention as well as treatment of OSCC., (© 2012 Japanese Cancer Association.)

Objective: Toll-like receptor-9 (TLR-9), a new member of the interleukin-1 receptor superfamily, was recently found to have a high level of expression in many carcinoma specimens. The objective of this study was to examine the TLR-9 expression and its role in tumour cell proliferation in oral squamous cell carcinoma., Materials and Methods: Western blot and immunohistochemistry were used to detect TLR-9 protein in oral squamous cell carcinoma (OSCC) Tca-8113 cell lines and clinical specimens (n=60). The relationship between TLR-9 expression and clinicopathologic features was analysed. Cell proliferation and inflammatory chemokines secretion were tested by MTT and ELISA methods respectively., Results: Results showed that TLR-9 expression level was higher in OSCC tissues than in paired adjacent normal tissues (P<0.01), and the expression level of TLR-9 was significantly associated with tumour size (P=0.001), tumour clinical stage (P=0.003) and Ki-67 expression (P<0.01). In vitro results also suggested that stimulation of Tca-8113 cells with TLR-9 agonist CpG-ODN could significantly increase tumour cell proliferation as well as subsequent IL-1α and IL-6 secretions (P<0.01), which could be partially inhibited by usage of anti-TLR-9 protein., Conclusions: It was therefore hypothesized that increased expression of TLR-9 may be of great value in assessing the development of OSCC, and could be used as a new target for OSCC prevention and therapy in future., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Primary desmoid-type fibromatoses arising from the oral and maxillofacial region are uncommon and hold the character of local invasion and regional recurrence. The purpose of this study was to analyze the clinicoepidemiologic characteristics of this rare disease in an eastern Chinese population., Study Design: Epidemiological and clinicopathological data on 20 patients were reviewed from the hospital records and analyzed accordingly., Results: Twelve males and 8 females with a ratio of 3:2 were involved. The mandible was the most common site of presentation. Suspected malignant change was found in 6 cases and an extremely high recurrence rate was also found in up to 53%. Abnormally high blood levels of alkaline phosphatase were found in 65% of patients, which had a close relation with tumor malignant change., Conclusion: Chinese people are more susceptible to desmoid-type fibromatoses and are at an extremely high risk of regional malignant change. Elevated serum alkaline phosphatase levels may be taken as an indicator for malignant transformation., (Copyright © 2011 Mosby, Inc. All rights reserved.)