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BACKGROUND: Ulna and radius segmentation of dual-energy X-ray absorptiometry (DXA) images is essential for measuring bone mineral density (BMD). OBJECTIVE: To develop and test a novel deep learning network architecture for robust and efficient ulna and radius segmentation on DXA images. METHODS: This study used two datasets including 360 cases. The first dataset included 300 cases that were randomly divided into five groups for five-fold cross-validation. The second dataset including 60 cases was used for independent testing. A deep learning network architecture with dual residual dilated convolution module and feature fusion block based on residual U-Net (DFR-U-Net) to enhance segmentation accuracy of ulna and radius regions on DXA images was developed. The Dice similarity coefficient (DSC), Jaccard, and Hausdorff distance (HD) were used to evaluate the segmentation performance. A one-tailed paired t-test was used to assert the statistical significance of our method and the other deep learning-based methods (P

Jin Chen,1,* Min Gong,1,* Zhuo Huang,1 Fang Wang,2 Yajing Wang,3 Zuquan Hu,1 Zhu Zeng,1 Yun Wang2 1Key Laboratory of Biology and Medical Engineering/Immune Cells and Antibody Engineering Research Center of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 2Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 3The Affiliated Stomatological Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhu Zeng, Key Laboratory of Biology and Medical Engineering/Immune Cells and Antibody Engineering Research Center of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, People’s Republic of China, Email zengzhu@gmc.edu.cn Yun Wang, Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, People’s Republic of China, Tel/Fax +86851-88174044, Email wangyun@gmc.edu.cnPurpose: Gastric injury is a major issue for long-term administration of aspirin. In this work, we tried to explore the possibility of using BLG to alleviate aspirin-induced gastric injury, because of excellent abilities of BLG in loading drug molecules.Methods: Various spectroscopic techniques and molecular docking methods were applied to investigate the interaction mechanism between BLG and aspirin. Animal experiments were performed to figure out the effects of taking aspirin-BLG on the stomach.Results: Our results demonstrate that aspirin could bind with BLG to form stable aspirin-BLG complex (the binding constant Kb= 2.051 × 103 M− 1). The formation process is endothermic (∆H> 0) and the main acting force is hydrophobic force. Our data also show that the aspirin-BLG complex is formed with a higher affinity in simulated gastric fluid and could remain stable for several hours, which might arise from its special binding mode under acidic condition and the resistance of BLG to gastric digestion. Furthermore, animal models (rats with aspirin-induced gastric damage) were built. The results of animal experiments reveal that the oral administration of aspirin-BLG could cause less damage to gastric tissue, and it also hardly triggers obvious inflammatory responses.Conclusion: This study would contribute to an in-depth understanding of the interaction mechanism between BLG and aspirin. It is reasonable to believe that using BLG to bind with aspirin would be a potential way to alleviate the aspirin-induced gastric injury.Graphical Abstract: Keywords: beta-lactoglobulin, aspirin, gastric injury, static quenching, molecular docking

Hematoporphyrin (HP) and protoporphyrin IX (PPIX) are useful porphyrin photosensitizers with significant application values in photodynamic therapy. Currently, many strategies have been developed to improve their clinical performance, such as incorporating them with nanoparticle (NP) carriers. In this work, we studied the possibility of using β-lactoglobulin (BLG) as a potential NP carrier due to their hydrophobic affinity, pH sensitivity, and low cost of extraction and preservation. The interaction mechanisms of BLG with HP and PPIX were investigated using spectroscopic techniques and molecular docking methods. The molecular docking results agree well with the experimental results, which demonstrate that the formations of HP-BLG and PPIX-BLG complexes are endothermic processes and the main acting force is hydrophobic force. Furthermore, the opening-closure states of EF loop have a great influence on the HP-BLG complex formation, where the central hydrophobic cavity of β-barrel is available for HP binding at pH 7.4 but not available at pH 6.2. However, the formation of the PPIX-BLG complex is less dependent on the states of the EF loop, and the binding sites of PPIX are both located on the external surface of BLG under both pH 7.4 and 6.2 conditions. All of our results would provide new insight into the mechanisms of noncovalent interactions between BLG and HP/PPIX. It is believed that this work indicated the potential application values of BLG in designing pH-sensitive carriers for the delivery of HP and PPIX, as well as other poorly soluble drugs.

Alternative splicing events are a major source of transcript and protein diversity in eukaryotes. Aberrant alternative splicing events have been increasingly reported in various cancers, including gastric cancer. To further explore the prognostic significance of alternative splicing events in gastric cancer patients, a comprehensive and systematic investigation was conducted by integrating alternative splicing event data and clinical information. Univariate Cox regression analysis identified 1383 alternative splicing events to be significantly associated with the overall survival of gastric cancer patients. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were performed for the development of prognostic signatures. The final prognostic signature based on all seven types of alternative splicing events can act as an independent prognostic indicator after multivariate adjustment of several clinical parameters. Furthermore, the correlation and function analysis identified CELF2, BAG2, RBFOX2, PTBP2 and QKI as hub splicing factors, and the focal adhesion signaling pathway was most significantly correlated with survival-associated alternative splicing events. The results of this study may establish a foundation for further research investigating the underlying mechanism of alternative splicing events in the progression of gastric cancer.

The tumor microenvironment is closely related to the progression and immune escape of tumor cells. Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) are indispensable components of the tumor microenvironment and have been demonstrated to be highly valuable in determining the prognosis of multiple cancers. To elucidate the prognostic value of TIICs and IRGs in gastric cancer, we conducted a comprehensive analysis focusing on the abundances of 22 types of TIICs and differentially expressed IRGs based on a dataset from The Cancer Genome Atlas (TCGA). The results showed that great composition differences in TIICs and immune cell subfractions were associated with survival outcomes in different stages. Additionally, 29 hub genes were characterized from 345 differentially expressed IRGs and found to be significantly associated with survival outcomes. Then, an independent prognostic indicator based on ten IRGs was successfully constructed after multivariate adjustment for some clinical parameters. Further validation revealed that these hub IRGs could reflect the infiltration levels of immune cells. Thus, our results confirmed the clinical significance of TIICs and IRGs in gastric cancer and may establish a foundation for further exploring immune cell and gene targets for personalized treatment.

Nonsmall cell lung cancer (NSCLC) is among the most prevalent malignant tumours threatening human health. In the tumour microenvironment (TME), cancer-associated fibroblasts (CAFs) induce M2-polarized macrophages, which strongly regulate tumour progression. However, little is known about the association between CAFs and M2 macrophages. CD248 is a transmembrane glycoprotein found in several cancer cells, tumour stromal cells, and pericytes. Here, we isolated CAFs from tumour tissues of NSCLC patients to detect the relationship between CD248 expression and patient prognosis. We knocked down the expression of CD248 on CAFs to detect CXCL12 secretion and macrophage polarization. We then examined the effects of CD248-expressing CAF-induced M2 macrophage polarization to promote NSCLC progression in vitro and in vivo. We found that CD248 is expressed mainly in NSCLC-derived CAFs and that the expression of CD248 correlates with poor patient prognosis. Blocking CXCL12 receptor (CXCR4) drastically decreased M2 macrophage chemotaxis. CD248 promotes CAFs secreting CXCL12 to mediate M2-polarized macrophages to promote NSCLC progression both in vitro and in vivo. Collectively, our data suggest that CD248-positive CAFs induce NSCLC progression by mediating M2-polarized macrophages.

Tumor hypoxia can seriously impede the effectiveness of photodynamic therapy (PDT). To address this issue, two approaches, termed in situ oxygen generation and oxygen delivery, were developed. The in situ oxygen generation method uses catalysts such as catalase to decompose excess H2O2 produced by tumors. It offers specificity for tumors, but its effectiveness is limited by the low H2O2 concentration often present in tumors. The oxygen delivery strategy relies on the high oxygen solubility of perfluorocarbon, etc., to transport oxygen. It is effective, but lacks tumor specificity. In an effort to integrate the merits of the two approaches, we designed a multifunctional nanoemulsion system named CCIPN and prepared it using a sonication-phase inversion composition–sonication method with orthogonal optimization. CCIPN included catalase, the methyl ester of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me), photosensitizer IR780, and perfluoropolyether. Perfluoropolyether may reserve the oxygen generated by catalase within the same nanoformulation for PDT. CCIPN contained spherical droplets below 100 nm and showed reasonable cytocompatibility. It presented a stronger ability to generate cytotoxic reactive oxygen species and consequently destroy tumor cells upon light irradiation, in comparison with its counterpart without catalase or perfluoropolyether. This study contributes to the design and preparation of oxygen-supplementing PDT nanomaterials.

Currently, many researches have developed several strategies to design the surface structures of hydroxyapatite (HA), and have proved that the surface structures are pivotal in guiding the adhesion of bone marrow mesenchymal stem cells (BMSCs) as well as subsequent cellular behaviours. Most of these strategies, such as altering roughness and constructing surface patterning of HA, involve the construction of geometric topographies at the micro/nanoscale. However, besides geometric topographies, crystal defects are also important characteristics of surface structures and would alter many local physicochemical properties, which is critical for contact between cells and bioceramic surfaces. For the practical applications of crystal defects, a major hindrance is that crystal defects are usually unstable and easily eliminated during crystallization, which limits the large-scale fabrication of materials with crystal defects. In this work, given that stepped structures contain massive stable crystal defects on their step edges and kinks, we proposed a feasible and efficient method to fabricate HA dishes with stepped structures on their surfaces. First, plate-like HA mesocrystals were prepared from CaHPO

Tobacco mosaic virus (TMV) is known to infect a wide range of plants, resulting in reduced yield and productivity. Novel, effective, and plant-based pesticides are required to protect plants against TMV infection. To identify novel anti-TMV agents from natural sources, we systematically studied the roots of Cynanchum paniculatum and isolated six new seco-pregnane C

Highlights • Combined therapy with MUC1 mRNA nanovaccine and anti-CTLA-4 mAb could reduce immunosuppressive TME, increase the infiltration of CD8+ T cells into tumor sites, and enhance anti-tumor cytotoxic T-lymphocyte activity when compared with each monotherapy. • Combination treatment with anti-CTLA-4 mAb and MUC1 mRNA nanovaccine could appear more effective than either nanovaccine or anti-CTLA-4 mAb alone at increasing level of apoptosis in tumor cells. • Combination immunotherapy could significantly downregulated the signal transducer and activator of transcription 3 (STAT3) signal pathway., The immunosuppressive tumor microenvironment (TME) is the main reason for the failure of many immunotherapies that directly stimulate anti-tumor immune response. Anti-CTLA-4 antibody may reduce effector regulatory T (Treg) cell numbers and their suppressive activity in the TME. We have previously reported that combination of anti-CTLA-4 antibody with MUC1 mRNA nanovaccine may mutually enhance each single treatment. But the enhancement mechanism of therapeutic efficacy of MUC1 mRNA nanovaccine plus anti-CTLA-4 monoclonal antibody (mAb) is unknown. In this study, anti-tumor CTL activity induced by combination of CTLA-4 Blockade with MUC1 mRNA nanovaccine and immunosuppressive factors in the TME of triple negative breast cancer were investigated. The results demonstrated that combined therapy with nanovaccine and anti-CTLA-4 mAb could induce stronger anti-tumor CTL response than each monotherapy, result in significantly decreased numbers of myeloid-derived suppressor cells (MDSC), Treg cells, tumor-associated fibroblasts (TAFs) and tumor vasculature in the TME, downregulated levels of interleukin-6, tumor necrosis factor-α and transforming growth factor-β, and significantly upregulated levels of IFN-γ and interleukin-12 as well as increased number of CD8+ T cell, and appear more effective than either nanovaccine or anti-CTLA-4 mAb alone at increasing level of apoptosis in tumor cells. In addition, combination immunotherapy could significantly downregulated the signal transducer and activator of transcription 3 (STAT3) signal pathway. Therefore, it can be concluded that combination of CTLA-4 blockade with MUC1 mRNA nanovaccine enhances anti-tumor cytotoxic T-lymphocyte activity by reducing immunosuppressive TME and inhibiting tumor-promoting STAT3 signaling pathway.

The performance of implanted biomaterials is largely determined by their interaction with the host immune system. As a fibrous-like 3D network, fibrin matrix formed at the interfaces of tissue and material, whose effects on dendritic cells (DCs) remain unknown. Here, a bone plates implantation model was developed to evaluate the fibrin matrix deposition and DCs recruitment

Dendritic cells (DCs) are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses against cancer. Tumor cells can escape from immune attack by secreting suppressive cytokines that solely or cooperatively impair the immune function of DCs. However, the underlying mechanisms are not fully defined. Vascular endothelial growth factor (VEGF) has been identified as a major cytokine in the tumor microenvironment. To elucidate the effects of VEGF on the motility and immune function of mature DCs (mDCs), the cells were treated with 50 ng/mL VEGF and investigated by proteomics and molecular biological technologies. The results showed that VEGF can impair the migration capacity and immune function of mDCs through the RhoA‐cofilin1 pathway mediated by the VEGF receptor 2, suggesting impaired motility of mDCs by VEGF is one of the aspects of immune escape mechanisms of tumors. It is clinically important to understand the biological behavior of DCs and the immune escape mechanisms of tumor as well as how to improve the efficiency of antitumor therapy based on DCs.

The tumor immune microenvironment is of crucial importance in cancer progression and anticancer immune responses. Thus, systematic exploration of the expression landscape and prognostic significance of immune-related genes (IRGs) to assist in the prognosis of colon cancer is valuable and significant. The transcriptomic data of 470 colon cancer patients were obtained from The Cancer Genome Atlas database and the differentially expressed genes were analyzed. After an intersection analysis, the hub IRGs were identified and a prognostic index was further developed using multivariable Cox analysis. In addition, the discriminatory ability and prognostic significance of the constructed model were validated and the characteristics of IRGs associated overall survival were analyzed to elucidate the underlying molecular mechanisms. A total of 465 differentially expressed IRGs and 130 survival-associated IRGs were screened. Then, 46 hub IRGs were identified by an intersection analysis. A regulatory network displayed that most of these genes were unfavorable for the prognosis of colon cancer and were regulated by transcription factors. After a least absolute shrinkage and selection operator regression analysis, 14 hub IRGs were ultimately chose to construct a prognostic index. The validation results illustrated that this model could act as an independent indicator to moderately separate colon cancer patients into low- and high-risk groups. This study ascertained the prognostic significance of IRGs in colon cancer and successfully constructed an IRG-based prognostic signature for clinical prediction. Our results provide promising insight for the exploration of diagnostic markers and immunotherapeutic targets in colon cancer.

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In this study, we describe a novel mycovirus isolated from Ustilaginoidea virens strain GZ-2, which was designated "Ustilaginoidea virens nonsegmented virus 2" (UvNV-2). The genome of UvNV-2 contains two overlapping open reading frames (ORFs). ORF1 encodes an unknown protein, and ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp), which is most closely related to that of Purpureocillium lilacinum nonsegmented virus 1 (PINV-1) and is likely to be expressed by a + 1 ribosomal frameshift within the sequence CCC_UUU_UAG. A phylogenetic analysis of the RdRp of UvNV-2 showed that UvNV-2 is an unclassified mycovirus.

Objective of this paper is to excavate the siderophore synthesis gene from Brevibacillus brevis GZDF3 and verify its type and antibacterial effects. The method is using genome mining technology to analyze the siderophore synthesis genes and the phylogenetic tree of each synthesis gene was constructed separately. Iron free medium was utilized to induce the synthesis of siderophore and CAS liquid detection method was used for qualitative and quantitative analysis on siderophore. The type of siderophore was preliminaries identified by Arnow and its antibacterial effects were analyzed according to the agar punching method. The results show that a siderophore synthesis gene cluster with 83% similarity to Petrobactin was found in Brevibacillus brevis GZDF3 genome. Iron free medium could induce siderophore synthesis and the optimal incubation time cultured in iron free medium was 30 h and 48 h. Antagonistic strain GZDF3 had the capacity to synthesize catechol-type siderophore. Also, GZDF3 had a powerful antibacterial effect on pathogenic fungus Fusarium oxysporum of rotted root on Pinellia ternata. Therefore, Brevibacillus brevis GZDF3 can produce catechol-type siderophore in an iron-deficient culture medium, which was also a main antifungal active substance.

Fumonisin B1 (FB1) is an important mycotoxin in nature and is a serious threat to human and animal health, but its specific target and molecular mechanism of the toxicity and potential carcinogenicity remain unclear. In this study, we first detected the effects of FB1 on the cell viability, biophysical properties, migration ability, and reactive oxygen species (ROS) of human umbilical vein endothelial cells (HUVECs). Subsequently, changes in the cytoskeletal structure and its binding proteins were analyzed by immunofluorescence and real-time PCR, respectively. The results showed that FB1 could inhibit the viability of HUVECs in a dose-dependent manner. After treatment of HUVECs with FB1, the hypotonic resistance, cell surface charges, cell membrane fluidity, and migration ability were weakened, whereas the ROS levels were significantly increased. Moreover, the cytoskeletal structure of the HUVECs was significantly changed, and the mRNA expression of some important actin-binding proteins was altered. Therefore, this study revealed that FB1 can affect the migration and cytoskeletal structure of HUVECs, which provides a new perspective for further understanding the molecular mechanisms of FB1 toxicity.

The immune infiltration of tumors is closely related to clinical outcomes. The composition of tumor-infiltrating immune cells (TIICs) can serve as biomarkers for predicting response to treatment and survival in different patient subgroups in terms of chemotherapy and immunotherapy. This study is focused on investigating the clinical implications of TIICs in breast cancer patients. We performed several in silico analyses of gene expression profiles in 2976 nonmetastatic tumor samples. CIBERSORT was used to estimate the proportion of 22 immune cell types to analyze their correlation with overall survival (OS) and disease-free survival (DFS) in different breast cancer subtypes and stages. Our results showed that a higher fraction of plasma cells in estrogen receptor (ER)-positive breast cancer patients indicated an increase in DFS (hazard ratio [HR]=0.66, 95% confidence interval [CI] 0.54~0.82, p

Maize (Zea mays L.), an important food and feed crop worldwide, can be infected by Fusarium pathogens that can contaminate grain with mycotoxins. From August to October in 2018 and 2019, a field survey for maize ear rot was conducted in 76 counties of Guizhou province. The incidence ranged from 3% to 15% at individual fields in different areas. A total of 175 diseased maize ears with similar symptoms, including kernels covered with white, pink or salmon-colored mold or exhibiting a white streaking ("starburst") symptom, were collected from fields. Symptomatic kernels were surface-sterilized by soaking for 30 s in 70% alcohol and for another 2 min in 2% sodium hypochlorite solution, followed by five rinses with sterile water. Each kernel was cut into half and placed on potato dextrose agar (PDA). After incubation at 28 °C in the dark for 5 days, colonies displaying morphological characteristics of Fusarium were transferred to fresh PDA (Leslie and Summerell 2006). Single-sporing was conducted to purify the putative Fusarium colonies. A total of 120 isolates belonged to 16 Fusarium species were determined and F. meridionale was the dominant species. Five isolates from Huaxi district of Guiyang City were identified as F. miscanthi (Gams et al. 1999). Colonies on PDA were white and floccose, and pigmentation as viewed from the underside of the Petri dish was violet. The average growth rate was 7.5-8.0 mm/day at 28 °C in the dark. In cultures grown on PDA, 0-1-septate microconidia were produced in slimy heads. Microconidia were clavate to fusiform with a truncate base and a broadly rounded tip, 4.8-13.3 μm × 1.8-3.3 μm (n=110). In cultures grown on half-strength CMC broth (Xu et al. 2010), macroconidia were mostly 3-septate, almost straight for most of the length, with a slightly foot-shaped basal cell and curved apical cell that gradually tapered, 17.8-71.3 μm × 2.0-4.3 μm (n=78). The identity of the fungus was confirmed by sequence comparison of the partial translation elongation factor-1α (TEF-1α), RNA polymerase II subunit (RPB2), mitochondrial small subunit rDNA (mtSSU) and β-tubulin genes (Mirete et al. 2004; O'Donnell et al. 2010; O'Donnell and Cigelnik 1997). BLASTn searches of GenBank, using the partial TEF-1α (MN750829), RPB2 (MN750834), mtSSU (MT594104) and β-tubulin (MT584781) sequences of representative isolate GYHXB03 as the queries, revealed 99.84%, 99%, 100% and 100% sequence identity, respectively, to F. miscanthi NRRL 26231 accessions AF324331, JX171634, AF060371 and AF060384. Inoculum of isolate GYHXB03 was prepared (Xu et al. 2010), and a pathogenicity test was conducted on maize hybrid "Shundan7" and repeated twice. A 106/mL spore suspension (2 mL) or sterile water was injected into each of 8 maize ears through the silk channel at the blister stage of reproductive development in field (Duan et al. 2019). After three weeks, typical Fusarium kernel rot symptoms the same as those previously shown in the field was observed on all pathogen-inoculated plants, while the controls were asymptomatic. The pathogens re-isolated from two diseased kernels were identified as F. miscanthi based on morphology and TEF-1α and mtSSU analyses. F. miscanthi was first isolated from Miscanthus sinensis in Denmark (Gams et al. 1999), and also identified from M. × giganteus rhizomes in Belgium (Scauflaire et al. 2013). To our knowledge, this is the first report of F. miscanthi causing maize ear rot in China. This disease should be monitored in Guizhou due to its threat to maize production.

Dendritic cells (DCs) are the most potent specialized antigen-presenting cells as now known, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. Immunologically, the motilities and T cell activation capabilities of DCs are closely related to the resulting immune responses. However, due to the complexity of the immune system, the dynamic changes in the number of cells during the peripheral tissue (e.g. skin and mucosa) immune response induced by DCs are still poorly understood. Therefore, this study simulated dynamic number changes of DCs and T cells in this process by constructing several ordinary differential equations and setting the initial conditions of the functions and parameters. The results showed that these equations could simulate dynamic numerical changes of DCs and T cells in peripheral tissue and lymph node, which was in accordance with the physiological conditions such as the duration of immune response, the proliferation rates and the motilities of DCs and T cells. This model provided a theoretical reference for studying the immunologic functions of DCs and practical guidance for the clinical DCs-based therapy against immune-related diseases.

Objective To obtain in vitro transcription of mouse mucin 1(MUC1) mRNA and express it in NIH/3T3 cells. Methods The MUC1 gene was amplified from mouse 4T1 cells by reverse transcription PCR (RT-PCR), and then inserted into the eukaryotic expression vector pcDNA3.1(+) to construct the recombinant vector pcDNA3.1(+)-MUC1. After identification by restriction enzyme cutting, the recombinant plasmid was used as a PCR template for the amplification of the MUC1-HA TAG fusion gene fragment with the reverse primer containing hemagglutinin tag (HA TAG) sequence. Subsequently, the MUC1-HA TAG fusion gene was cloned into the expression vector pcDNA3.1(+). After double restriction enzyme digestion and DNA sequence identification, the recombinant plasmid encoding MUC1-HA TAG was used as a PCR template for the amplification of a PCR product containing T7 promoter and the MUC1-HA TAG fusion gene fragment as an in vitro transcription template to obtain the modified MUC1-HA TAG mRNA by in vitro transcription, tailing and purification. The resulting MUC1-HA TAG mRNA was transfected into NIH/3T3 cells by various transfection reagents and the expression of the fusion protein MUC1-HA TAG was detected by Western blot analysis. Results The MUC1 gene amplified by RT-PCR was about 1 900 bp in length. The restriction enzyme digestion and sequence analysis confirmed that the MUC1-HA TAG fusion gene had been successfully inserted into pcDNA3.1(+), and the insertion sequence was identical to the MUC1 gene sequence of the mouse in GenBank database. HA TAG was correctly inserted in the downstream of MUC1 gene and the reading frame was correct. Western blot analysis indicated that the in vitro transcriptionally modified MUC1-HA TAG mRNA could be expressed in NIH/3T3 cells. Conclusion In vitro transcriptionally modified mouse MUC1-HA TAG mRNA can be translated and expressed in mammalian NIH/3T3 cells.

Dendritic cells (DCs), the most potent antigen-presenting cells, play a central role in the initiation, regulation, and maintenance of the immune responses. Vascular endothelial growth factor (VEGF) is one of the important cytokines in the tumor microenvironment (TME) and can inhibit the differentiation and functional maturation of DCs. To elucidate the potential mechanisms of DC dysfunction induced by VEGF, the effects of VEGF on the biophysical characteristics and motility of human mature DCs (mDCs) were investigated. The results showed that VEGF had a negative influence on the biophysical properties, including electrophoretic mobility, osmotic fragility, viscoelasticity, and transmigration. Further cytoskeleton structure analysis by confocal microscope and gene expression profile analyses by gene microarray and real-time PCR indicated that the abnormal remodeling of F-actin cytoskeleton may be the main reason for the deterioration of biophysical properties, motility, and stimulatory capability of VEGF-treated mDCs. This is significant for understanding the biological behavior of DCs and the immune escape mechanism of tumors. Simultaneously, the therapeutic efficacies may be improved by blocking the signaling pathway of VEGF in an appropriate manner before the deployment of DC-based vaccinations against tumors.

A fluid theory of void formation in dusty plasmas taking into account ionization is proposed. It is shown that if the ionization rate is larger than a threshold, an initial steady-state dust-density distribution can evolve into a stable distribution containing a void. As the ionization rate is further increased, the time required for void formation decreases. The void size first increases, but then decreases. However, for still larger ionization rates, the dusty region of the plasma becomes ringlike, including the convection term in dust momentum equation. The results are in agreement with existing experiments and theories.

The lower-hybrid drift instability (LHDI) in a thin current sheet in the intermediate-wavelength (kyρiρe∼1, where ky, ρe, and ρi are the wave vector and the electron and ion gyroradii, respectively) regime for particles with κ velocity distribution is studied. The latter is more suitable for describing nonthermal distributions with an enhanced high-energy tail and includes the Maxwellian as a limiting case. It is shown that linear electromagnetic LHDI can be excited near the center of the current sheet. The growth rate decreases, but the electromagnetic component of the LHD mode increases with increase in hot particles.

Using fluid theory, the properties of voids in collision-dominated plasmas containing negative ions are studied. The profiles of the charged-particle densities in the void region are obtained. It is also shown that with an increase of the negative-ion concentration, the electric field, the ion drift velocity, the dust charge at the void edge, as well as the void size decrease.

The steady structures of dust voids in electronegative plasmas for different ionization rates are investigated using fluid theory. The effects of the concentration of negative ions in plasmas on the distributions of the electric field and the potential in the region of voids as well as Mach number are analyzed numerically. The results show that when the ionization rate is lower, the steady structures do not appear. With an increase of the ionization rate, the steady structures can be formed. The latter are affected by the concentration of the negative ions. With increasing negative ions, the potential decays, and the Mach number as well as the electric field increases. It is also found that increasing both the concentration of the negative ions and the ionization rate can gives rise to contraction of the steady void structures.