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Complement aids in the construction of an immunosuppressive tumor microenvironment. Tumor cell–derived C3 has been previously reported, but whether and how it acts on antitumor immunity remains to be elucidated. Here, we describe a mechanism for tumor cell–derived C3 in suppressing antitumor immunity. Tumor cell–derived C3 was activated intracellularly, which results in generation of C3a. C3a modulated tumor-associated macrophages via C3a-C3aR-PI3Kγ signaling, thereby repressing antitumor immunity. Deletion of C3 in tumor cells that had high C3 expression enhanced efficacy of anti–PD-L1 treatment. Collectively, our results suggest tumor cell–derived C3 may be a useful target for cancer immunotherapy and that targeting C3 in tumor cells may enhance antitumor immunity.

International audience; The effect of Co, Pd and Pt ultrathin films on the kinetics of the formation of Ni-silicide by reactive diffusion is investigated. 50 nm Ni/1 nm X/ 50 nm Ni (X = Co, Pd, Pt) deposited on Si(100) substrates are studied using in-situ and ex-situ measurements by X-ray diffraction (XRD). The presence of Co, Pd or Pt thin films in between the Ni layers delays the formation of the metal rich phase compared to the pure Ni/Si system and thus these films act as diffusion barriers. A simultaneous silicide formation (δ-Ni2Si and NiSi phases) different from the classic sequential formation is found during the consumption of the top Ni layer for which Ni has to diffuse through the barrier. A model for the simultaneous growth in the presence of a barrier is developed, and simulation of the kinetics measured by XRD is used to determine the permeability of the different barriers. Atom probe tomography (APT) of the Ni/Pd/Ni system shows that the Pd layer is located between the Ni top layer and δ-Ni2Si during the silicide growth, in accordance with a silicide formation controlled by Ni diffusion through the Pd layer. The effect of the barrier on the silicide formation and properties is discussed.

Anti–PD-1/PD-L1 therapy, either by anti–PD-1 antibody or anti–PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8 + T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8 + T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200 + cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200 + T cells positively related to a favorable clinical outcome to anti–PD-1/PD-L1 therapy in three independent cohorts of patients with cancer. Using multiple mouse tumor models, we demonstrated that CD200 + CTLs are essential for efficacious anti–PD-L1 therapy. Mechanistically, we observed a unique chromatin landscape in CD200 + CTLs and found that these cells are enriched for tumor antigen–specific CTLs and have antitumor effector functions. Coinoculation of CD200 + CTLs with tumor cells led to robust tumor regression in two transplanted mouse models. Clinically, we found that infiltration of CD200 + CTLs into tumors could predict immunotherapy efficacy in six patient cohorts. Together, our findings reveal that CD200 + CTLs in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy and could serve as a predictor of successful immunotherapy in the clinic.

In-depth understanding of nickel (Ni) coarsening is helpful for improving the service life of Ni-yttria stabilized zirconia (YSZ) electrodes in solid oxide cells. Unfortunately, very few quantitative experimental/theoretical descriptions of Ni coarsening in Ni-YSZ electrodes during long-term operation exist. In this paper, quantitative modeling of Ni coarsening in Ni-YSZ electrodes was achieved through three-dimensional (3D) phase-field simulation supported by ex-situ ptychographic nano-tomography and input of reliable thermophysical parameters. A pragmatic procedure was proposed to refine and verify the materials parameters for the simulations. Moreover, the microstructures of the Ni-YSZ electrode in the pristine and annealed states obtained via the ex-situ ptychographic nano-tomography were used as the initial input and experimental validation for the phase-field simulations. After that, comprehensive comparison between the simulated and the experimental 3D microstructures was conducted, indicating the successful quantitative phase-field simulation of Ni coarsening in Ni-YSZ electrodes presented here. The success of this work is expected to pave the way for accurate prediction of the service life and even design of high-performance Ni-YSZ electrodes.

In this paper, an efficient design of a Ti-modified Al-Si-Mg-Sr casting alloy with simultaneously enhanced strength and ductility was achieved by integrating computational thermodynamics, machine learning, and key experiments within the Bayesian optimization framework. Firstly, a self-consistent Al-Si-Mg-Sr-Ti quinary thermodynamic database was established by the calculation of phase diagram method and verified by key experiments. Based on the established thermodynamic database, a high-throughput Scheil-Gulliver solidification simulation of the A356-0.005Sr alloy with different Ti contents was carried out to establish the “composition-microstructure” quantitative relationship of the alloy. Then, by combining the computational thermodynamic, machine learning, and experimental data within the Bayesian optimization framework, the relationship “composition/processing-microstructure-properties” of A356-0.005Sr with different Ti contents was constructed and validated by the key experiments. Furthermore, the optimum alloy composition of the Ti-modified A356-0.005Sr casting alloy was designed based on this integration method with the Bayesian optimization framework and verified by the experiments. It is anticipated that the present integration method may serve as a general one for the efficient design of casting alloys, especially in the high-dimensional composition space.

Al-Si-Mg series alloys are the most common alloys available for additive manufacturing forming with low cracking tendency. However, there is no systematic study on the computational design of SLMed Al-Si-(Mg) alloys due to the huge parameter space of composition and processes. In this paper, a high-quality dataset of SLMed Al-Si-(Mg) alloys containing 176 pieces of data from 50 publications was first established, which recorded the information, including alloy compositions, process parameters, test conditions, and mechanical properties. A threshold value of 35 J/mm3 for energy density (Ed) was then proposed as a criterion to clean the data points with lower ultimate tensile strength (UTS) and elongation (EL). The cleaned dataset consists of a first training/testing dataset with 142 data for model construction and a second testing dataset with 9 data for model verification. After that, four machine learning models were applied to establish the quantitative relation of “composition-processes-properties” in SLMed Al-Si-(Mg) alloys. The MLPReg model was chosen as the optimal one considering its best performance and subsequently utilized to design novel compositions and process parameters for SLMed Al-Si-(Mg) alloys. The UTS and EL of the designed alloy with a maximum comprehensive mechanical property are 549 MPa and 16%, both of which are higher than all the available experimental data. It is anticipated that the present design strategy based on the machine learning method should generally be applicable to other SLMed alloy systems.

In this paper, the effect of different cooling media, i.e., water quenching, air cooling and furnace cooling, after solid solution treatment on the microstructure and yield strength of Ni-15.9Al at. pct alloy during aging at 800 °C was first experimentally investigated. It was found that the morphologies and the particle sizes of γ′ precipitates as well as the yield strength of the target alloys during aging were strongly affected by the cooling media after solid solution. The yield strengths of the target alloys after aging with water quenching and air cooling after solid solution are similar, and higher than that with furnace cooling. By further considering the cost and environment factors, the air cooling after solid solution treatment was thus proposed for industry alloys. Meanwhile, a quantitative simulation of the microstructure evolution in the target alloy during aging was realized by means of phase-field modeling coupling with CALPHAD thermodynamic and atomic mobility descriptions. Moreover, the extracted experimental microstructure of the Ni-15.9Al at. pct alloy with air cooling after solid solution was inputted as the initial microstructure of phase-field simulation. Subsequently, the microstructural features obtained from both phase-field simulations and experiments were imported into the strengthening models to predict the evolution of the total yield strengths during aging. The model-predicted total yield strengths in the Ni-15.9Al at. pct alloy were found to be in the excellent agreement with the experimental results from the tensile tests.

Introduction Whether the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors declines with senescence remains controversial for lung adenocarcinoma (LUAD). Responsiveness to anti–PD-1/PD-L1 therapy is thought to rely on neoantigen exposure and immune elements in the tumor microenvironment. In this study, we explored the features of the tumor immune microenvironment in elderly patients with treatment-naive LUAD. Methods Transcriptome profiles and clinical characteristics of patients with LUAD were retrieved from The Cancer Genome Atlas as a discovery cohort. Immune cell infiltration (quantified by a single-sample gene set enrichment analysis), immunoregulatory molecule expression, and mutational patterns (from The Cancer Immunome Atlas) were compared between young and elderly patients. Immune cell infiltration was verified by immunohistochemistry using a validation cohort including 105 treatment-naive patients with LUAD. A tissue microarray consisting of 120 LUAD patients was used in the immunohistochemistry validation. Results Activated CD8+ T cell numbers increased slightly with age, but cytolytic molecules in T cells (granzyme B [GZMB], perforin 1 [PRF1], granzyme A [GZMA], granzyme M [GZMM], and granulysin [GNLY]) gradually declined. PD-L1 expression was not associated with age; however, a number of immunosuppressive elements beyond PD-L1 were upregulated in aging patients, including regulatory T cells and co-inhibitory molecules, for example, TIM-3, TIGIT, and HHLA2. Finally, senescence was accompanied by a loss of clonal neoantigens, which is believed to be correlated with responsiveness to immune checkpoint inhibitors. Conclusions Elderly patients were characterized by increased numbers of CD8+ T cells and impaired cytolytic molecule expression. The observed immune signature was also associated with a loss of clonal neoantigens and the accumulation of immunosuppressive elements. These findings show a unique immune microenvironment in senescence and support biomarker-guided candidate identification for anti–PD-1/PD-L1 therapeutic strategies for elderly patients with LUAD.

Casting aluminum alloys are commonly used in industries due to their excellent comprehensive performance. Alloying/microalloying and post-solidification heat treatments are the most common measures to tune the microstructure for enhancing their mechanical properties. However, it is very challenging to achieve accurate and efficient development of novel casting aluminum alloys using the traditional trial-and-error method. With the rapid development of computer technology, the computational thermodynamics (CT) in the framework of the CALculation of PHAse Diagram approach, the data-driven machine learning (ML) technique, and also their combinations have been proved to be effective approaches for the design of casting aluminum alloys. In this review, the state-of-the-art computational alloy design approaches driven by CT and ML techniques, as well as their combinations, were comprehensively summarized. The current status of the thermodynamic database for aluminum alloys, as the core for CT, was also briefly introduced. After that, a variety of successful case studies on the design of different casting aluminum alloys driven by CT, ML, and their combinations were demonstrated, including common applications, CT-driven design of Sc-additional Al-Si-Mg series casting alloys, and design of Srmodified A356 alloys driven by combing CT and ML. Finally, the conclusions of this review were drawn, and perspectives for boosting the computational design approach driven by combining CT and ML techniques were pointed out.

Epigenetic modifications to histones dictate the differentiation of naive CD4+ T cells into different subsets of effector T helper (TH) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of TH1, TH2 and regulatory T (Treg) cells. However, whether and how EZH2 regulates follicular helper T (TFH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells. Ablation of EZH2 in LCMV-specific CD4+ T cells leads to a selective impairment of early TFH cell fate commitment, but not late TFH differentiation or memory TFH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs TFH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.

Complement aids in the construction of an immunosuppressive tumor microenvironment. Tumor cell–derived C3 has been previously reported, but whether and how it acts on antitumor immunity remains to be elucidated. Here, we describe a mechanism for tumor cell–derived C3 in suppressing antitumor immunity. Tumor cell–derived C3 was activated intracellularly, which results in generation of C3a. C3a modulated tumor-associated macrophages via C3a-C3aR-PI3Kγ signaling, thereby repressing antitumor immunity. Deletion of C3 in tumor cells that had high C3 expression enhanced efficacy of anti–PD-L1 treatment. Collectively, our results suggest tumor cell–derived C3 may be a useful target for cancer immunotherapy and that targeting C3 in tumor cells may enhance antitumor immunity.

Xinxin Wang,1 Diangang Chen,1 Jianbao Gao,1 Haixia Long,1 Haoran Zha,2 Anmei Zhang,1 Chi Shu,1 Li Zhou,1 Fei Yang,1 Bo Zhu,1 Wei Wu3 1Institute of Cancer, Xinqiao Hospital, Army Medical University, Chongqing, China; 2Department of Oncology, The General Hospital of the People’s Liberation Army Rocket Force, Beijing, China; 3Department of Cardiothoracic Surgery, Southwest Hospital, Army Medical University, Chongqing, China Purpose: Centromere protein U (CENPU) abnormally exhibits high expression in various types of human tumor tissues and participates in tumor progression; however, its expression pattern and biological function in lung cancer have not yet been elucidated. In the present study, we explored the clinical significance and biological function of CENPU in lung cancer.Materials and methods: The Cancer Genome Atlas (TCGA) data analyses, quantitative real-time PCR (RT-PCR), and Western blotting were performed to quantify CENPU and FOXM1 expression in non-small-cell lung cancer (NSCLC) samples. Survival data were obtained from Kaplan–Meier plotter or PROGgene V2 prognostic database. The function of CENPU in lung cancer cell proliferation was determined using 5-ethynyl-2′-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), and cell cycle assays, and the underlying mechanism was determined through bioinformatic analyses and validated by in vitro siRNA or plasmid transfection experiments.Results: CENPU was abnormally overexpressed in NSCLC samples compared with matched paired normal tissues. Higher expression of CENPU predicted worse overall survival (OS) and relapse-free survival (RFS) in NSCLC patients. Knockdown of CENPU expression by siRNA significantly inhibited proliferation and delayed cell cycle progression of lung cancer cells. To figure out the mechanism, bioinformatic analyses were performed and the results showed that the transcription factor, FOXM1, positively correlated with CENPU. Further in vitro experiments indicated that FOXM1 was the possible downstream transcription factor of CENPU as the knockdown of CENPU led to lower expression of FOXM1 and the overexpression of FOXM1 significantly reversed the inhibition of proliferation caused by CENPU knockdown. Furthermore, FOXM1 was highly expressed in NSCLC. The knockdown of FOXM1 also attenuated proliferation and induced G1 arrest in lung cancer cells.Conclusion: CENPU was highly expressed in NSCLC tissues, wherein it promoted lung cancer cell proliferation via the transcription factor, FOXM1, which could be a potential target for therapeutic strategies. Keywords: CENPU, NSCLC, proliferation, FOXM1

Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1-3. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia2, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+ T cell responses against pathogens in treatment-naive mice bearing large tumors. Specifically, we identify CD45+ erythroid progenitor cells (CD71+TER119+; EPCs) as robust immunosuppressors. CD45+ EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45+ EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45+ EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45+ EPC population was detected in patients with cancer who have anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in patients with advanced cancer.

The effect of different initial structures on the simulation of microstructure evolution during normal grain growth was comparatively studied by using a two-dimensional phase-field model. Three methods, standard Voronoi construction, weighted Voronoi construction, and hand drawing, were used to generate the initial structures. For the hand-drawn initial structure, different boundary conditions, including periodic and gradient boundary conditions, were also applied. The phase-field simulation of normal grain growth in the succinonitrile–coumarin152 system was chosen as the benchmark, and compared with the experimental microstructure evolution. The phase-field simulated results generally conformed to Hillert’s theory, Von Neumann–Mullins law, and the experimental results. Different initial structures with similar initial grain size distribution showed similar grain size evolution. The simulation results for the “experimental” initial structure constructed by hand drawing showed best agreement with the experimental results during the early stage of grain growth process. With the increased time, the accuracy of simulation appeared strongly dependent on the grain numbers, and thus the gradient boundary condition is more suitable for long-time grain growth simulation than the periodic boundary condition. Overall, the combination of phase-field simulation and “experimental” initial microstructures allows the study of the grain growth in arbitrary polycrystalline materials, as demonstrated here for comprehensive study of austenite grain growth in two commercial high-strength steels.

International audience; In this paper, the in-situ Scanning Electron Microscopy (in-situ SEM) technique and three-dimensional (3-D) phase-field simulation were combined to perform a comprehensive study on the kinetics and mechanisms of dewetting (or agglomeration) of a 30 nm NiSi films on Si(100) substrate at 600 °C. The evolution of texture during agglomeration of the polycrystalline NiSi thin film was also studied by ex-situ Electron BackScattered Diffraction (EBSD). The phase-field simulation results showed that abnormal grain growth plays an important role in the dewetting process of polycrystalline films, while the misorientations between the NiSi grains and the Si substrate are the main reason for the agglomeration of NiSi polycrystalline thin film on the monocrystal Si substrate. Moreover, 3-D phase-field simulations coupled with experimental information on misorientation distribution and initial grain size were also performed, and the simulated Ni silicide grain morphology is in good agreement with the in-situ SEM results during agglomeration. In order to slow down or to suppress the agglomeration, it is highly recommended to increase the volume fraction of low angle grains, and/or to decrease the misorientation between the NiSi grain and the Si substrate or between the NiSi grains.

Additional file 1: Table S1. Listing of primers used in this study. Figure S1. Breast cancer development in C3aR deficient mice. a 4 T1 cells were orthotopically injected into WT or C3aR−/− mice. Tumor volumes of WT and C3aR−/− mice were monitored at various time points after tumor inoculation. b On day 28 post tumor challenge, the tumor size and weight of these mice were investigated. c Tumors were harvested on day 15 after 4 T1 cell inoculation and single cell suspension was prepared for flow cytometry staining. The gating strategy for living cells is shown. d Percentage of Ki67+ cells in CD45− tumor cells in WT (n = 8) and C3aR−/− (n = 7) mice detected by FACs. Figure S2. The proliferation of CAF cells in C3aR−/− mice was comparable with that of WT mice. a Tumors were harvested on day 15 after 4 T1 cell inoculation and single cell suspension was prepared for flow cytometry staining. CAF was defined as PDGFRa+F4/80−. b Percentage of PDGFRα+F4/80− in total living cells from C3aR−/− and WT tumor-bearing mice. c Tumors were harvested on day 15 after 4 T1 cell inoculation and CAFs were sorted from FACS. The purity of sorted CAF was shown. Figure S3. C3aRA treatment has no effect on the breast cancer growth in 4 T1-bearing mice. a Tumor growth of 4 T1-bearing mice in C3aRA treated or PBS treated group. b Tumor weight of the two group of mice.

In the present paper, three Co-Al-W-Ni alloys (i.e., Co-9Al-10W-xNi with x=15, 25, 35 at. %) and their heat treatment mechanisms were carefully designed on the basis of the available phase equilibrium information. The temporal evolution of the microstructure and hardness in the Co-9Al-10W-xNi (x=15, 25, 35) alloys during aging process was measured, from which the effect of additional Ni contents, aging temperature and time on microstructure and hardness in the three Co-Al- W-Ni alloys was analyzed. Considering that the alloy compositions and heat treatment are not directly related with the hardness, the relationship between hardness and microstructure was then linked. It was found that the hardness of Co-based superalloys increases as the volume fraction of ?' precipitates increases, while decreases with the increase of the radius and interval of ?' precipitates. Moreover, the interfacial energy of ?/?' interface was also evaluated on the basis of the coarsening kinetics of ?' precipitates and the Philippe-Voorhees model in combination with the thermodynamic and atomic mobility databases. The results indicate that the interfacial energies of ?/?' interface reduce as the increase of additional Ni content and aging temperature.

A novel crack-free Ti-modified Al-Cu-Mg alloy for SLM was developed here, based on the thermodynamic calculations of the crack susceptibility index and growth-restriction factor. We found that the introduction of Ti into the Al-Cu-Mg alloy effectively promoted the grain refinement and columnar-to-equiaxed grain transition as a result of the heterogeneous nucleation provided by Al3Ti precipitates. The hot tearing cracks were eliminated after Ti modification due to the formation of the homogeneous and fine equiaxed microstructure. We created a new high-strength Al-Cu-Mg-Ti alloy with a tensile strength of 426.4 MPa, yield strength of 293.2 MPa and ductility of 9.1%. This novel Ti-modified Al alloy with fine equiaxed grains and highly-enhanced mechanical properties offers a new compositional space for the printable lightweight material categories specifically for the SLM technique.

In this paper, the effect of different casting means and heat treatment routines on the mechanical and corrosion resistance properties of A356-0.54Sc casting alloy was comprehensively studied. Three different molds, including graphite mold, steel mold, and copper mold, were employed. Both the grain size and secondary dendrite arm space of primary α-(Al) in the casting A356-0.54Sc alloy with copper mold are the finest. Three different heat treatments, i.e., T4, T5, and T6, were then applied. With the T4 treatment, the eutectic (Si) particles transferred from the as-cast fibrous structure to the isolated spherical one, leading to a significant increase in ductility. After aging, the alloys in the T6 state always own the best strength properties. The strong heredity of microstructures from the casting stage to the subsequent heat treatments was observed. Moreover, the corrosion resistance of alloys was studied by the salt-spray corrosion experiments. The experiments showed that the pitting corrosion mostly occurs in the interface between the eutectic (Si) and primary α-(Al). It was finally concluded that the alloys casted using the copper mold and treated with the T6 routine maintain the best comprehensive mechanical properties after corrosion, while the alloys casted using the graphite mold are with the best corrosion resistance.

T cells serve an important role in the destruction of tumor cells and clearing of foreign pathogens. Previous studies have suggested that the T cell immune response of tumor-bearing patients is significantly lower than that of healthy people, and the principal reason for this is lymphocytopenia, which is caused by repeated cycles of chemotherapy. In addition to lymphocytopenia, the present study revealed that cytotoxic chemotherapy also weakens the homing ability of T cells to the T-cell zone of the spleen, which decreases the possibility of encounters between antigen-specific T cells and dendritic cells presenting the appropriate antigen, thereby weakening the immune response of T cells. These changes are attributed to the lower expression of C-C motif chemokine ligand 21 (CCL21) and C-C motif chemokine ligand 19 (CCL19) in the spleen of secondary lymphoid organs (SLOs). Finally, the present study identified that chemotherapy affects the function and survival of fibroblastic reticular cells in SLOs, which are the main source of CCL21 and CCL19. These observations aid us in further understanding the mechanism that is responsible for the decreased T cell immune response following repeated cycles of chemotherapy.

Interleukin-7 (IL-7) is a non-hematopoietic cell-derived cytokine with a central role in the adaptive immune system. It promotes lymphocyte development in the thymus and maintains survival of naive and memory T cell homeostasis in the periphery. Moreover, it is important for the organogenesis of lymph nodes (LN) and for the maintenance of activated T cells recruited into the secondary lymphoid organs (SLOs). The immune capacity of cancer patients is suppressed that is characterized by lower T cell counts, less effector immune cells infiltration, higher levels of exhausted effector cells and higher levels of immunosuppressive cytokines, such as transforming growth factor β (TGF-β). Recombinant human IL-7 (rhIL-7) is an ideal solution for the immune reconstitution of lymphopenia patients by promoting peripheral T cell expansion. Furthermore, it can antagonize the immunosuppressive network. In animal models, IL-7 has been proven to prolong the survival of tumor-bearing hosts. In this review, we will focus on the mechanism of action and applications of IL-7 in cancer immunotherapy and the potential restrictions for its usage.

TNF-alpha plays an important role in the development of secondary lymphoid tissues. Earlier studies showed that fibroblastic reticular cells express TNF-alpha receptor, suggesting that TNF-alpha may affect the development of FRCs. To test this, we analyzed the development and function of FRCs in wild-type or TNF-alpha knockout mice. We found that GP38 expression was down-regulated in the spleen of TNF-alpha knockout mice. Chemokines, mainly secreted by GP38(+) FRCs, were also down-regulated. Additionally, we found that absence of TNF-alpha decreased the homing ability to direct T cells to the spleen. However, absence of TNF-alpha did not affect the development of lymph nodes FRCs. These data reveal that TNF-alpha plays an important role in the development of spleen FRCs. Absence of TNF-alpha could cause abnormality of spleen FRCs, thereby weakening the homing ability of T cells to localize to the spleen T cell zone.

s All the experimental phase equilibria and thermodynamic properties in the Si–Sr and Al–Si–Sr systems were critically reviewed. Based on the reviewed experimental data, the thermodynamic descriptions of the Si–Sr binary system were updated by using the CALculation of PHAse Diagram (CALPHAD) technique, resulting in better agreement with the experimental data, especially for the standard enthalpies of formation, than those in the previous assessment. After that, the thermodynamic assessment of the Al–Si–Sr ternary system was carried out using the CALPHAD approach. Comprehensive comparisons indicate a good agreement between the calculated phase equilibria/thermodynamic properties and the experimental/first-principles data in Al–Si–Sr ternary system. Moreover, the as-cast microstructures of 4 Sr-additional Al–Si alloys were experimentally investigated by using the scanning electron microscope and electron probe microanalysis techniques. The solidification sequence and volume fractions of precipitated phases in the 4 alloys predicated from Scheil-Gulliver solidification simulations agree reasonably with the presently measured data, which further validates the reliability of the present thermodynamic descriptions.

The adsorption, desorption and anti-ultraviolet light characteristics of the protoxin from Bacillus thuringiensis strain WG-001 on montmorillonite, kaolinite, zinc oxide and rectorite were studied. The protoxin was easily adsorbed onto minerals and the adsorption reached equilibrium within 0.5–1.0 h (except for rectorite). The adsorption isotherms of protoxin at different concentrations in sodium carbonate buffer (pH 9) followed the Langmuir (R 2 >0.97) and Freundlich (R 2 >0.95) equations. The maximum amounts of protoxin adsorbed were in the order: montmorillonite>rectorite>znic oxide>kaolinite. In the range of pH from 9 to 11 (carbonate buffer), the protoxin adsorbed decreased with increasing pH. The adsorption was not significantly affected by the temperature between 5 and 45°C. Both free and adsorbed protoxin were toxic to larvae of Heliothis armigera. The LC50 value of free and adsorbed protoxin on montmorillonite, rectorite, zinc oxide and kaolinite were 14±1.16, 1.76±0.31, 2.94±0.71, 4.78±...

Survival of spores of Bacillus thuringiensis was determined under various processing conditions for spray drying. The results indicated that the viable spores number of B. thuringiensis decreased with increased inlet air temperature, outlet air temperature and atomising air pressure. When the inlet air temperature ranged from 170 °C to 250 °C, the outlet air temperature (75 °C) and atomising air pressure (0.15 MPa) were fixed, the pseudo- z value (one logarithmic cycle reduction) was 238.1 °C; when the outlet air temperature ranged from 65 °C to 95 °C, the inlet air temperature (200 °C) and atomising air pressure (0.15 MPa) were fixed, the pseudo- z value was 85.5 °C, the activation energy calculated according to the outlet air temperature was 59.96 kJ mol −1 ; when the atomising air pressure ranged from 0.10 MPa to 0.25 MPa, the inlet air temperature (200 °C) and outlet air temperature (75 °C) were fixed, the pseudo- z value was 3.49 MPa, the variance analysis showed that the atomising air pressure has no significant influence to the spores. The diluting solutions between Tween-80 solution and phosphate buffer have significant influence on the plate count of spores. The B. thuringiensis powder prepared by spray drying with inlet air temperature 250 °C, outlet air temperature 97 °C, the spores count of powder decreased obviously. But when the inlet air temperature of 155–165 °C, outlet air temperature of 66–70 °C were employed, the spores count of powder approaches to that of freeze drying powder. The spores count of oven drying powder was lower than that of the freeze drying powder, but close to the spray drying powder which inlet air temperature was 200 °C, outlet air temperature was 75 °C.

The immune system of patients with cancer is usually in an inhibitory state. Lymph node (LN) draining of pathological sites provides a suitable microenvironment where adaptive immune responses mainly occur. However, the microenvironment in the tumor draining lymph nodes (TDLNs) of patients with cancer appears to be in favor of tolerance. The effects of tumor cells on TDLNs have not been elaborated clearly. The present results have indicated that tumor cells may directly affect TDLNs by decreasing the fibroblastic reticular cell population that led to less interleukin-7 secretion. As a result, the number of T cells in TDLNs declined with reduced survival signals. A decreased number of T cells in TDLNs means weakened ability of immune surveillance. Clinically, these results were also confirmed in LN biopsies from patients with colon cancer at different clinical stages. Results of the present study showed that tumor cells may directly inhibit the immunological function of TDLNs.

In online education, course evaluation is a key element to improve the teaching quality, and the education managers have to attach importance to evaluate the course. In this paper, we propose a Fuzzy Synthetic Evaluation based method to evaluate the course, the different factors are considered in the evaluation process. On the basis of principles of online course evaluation, Fuzzy Synthetic Evaluation is used to evaluate the course, which can evaluate the online course from different aspects, thus providing teachers with clear and actionable feedback to enhance their practice. Introduction Online education is learner-centered system, the teacher can provide the course materials, such as curriculum plans, courseware and related information on the learning Website, the students can get those network courses and related services via computer and network [1]. In the learning process, the students can communicate with their teachers and students by using E-mail, discussion boards and chat rooms, the teachers can provide the guidance and help. The advantage of online education is [2]: (1) The student can learn the related courses at any time and place. (2) It is more effective for some special learners, such as the distance learner, the learner with physical disabilities, learners have the talent in certain areas as well as those who love contemplative and good at writing to express their idea. (3) The teaching ways can be more personalized and flexible. Online education course, it is the course used for the network education [3]. First of all, it is the course, secondly, we emphasize that it must have the network characteristics. Therefore, the online education is teaching activities that use to realize the teaching content of course and its enforcement. It consists of two parts: (1) the teaching content is organized by using a certain teaching objectives and teaching strategies. (2) The network teaching supporting environment, network teaching environment is the software tools using to support online teaching, teaching resources, and the teaching activity running on the network teaching platform. At present, the form of online education is flourishing and different. The quality of online course is a key part that restricts the whole network education, how to evaluate the online education course is a hot topic in the education field [4, 5]. And how to use the new teaching ideas and new educational perspective to construct the new training objectives that meet the actual requirement, system integrity and reasonable structure of online course evaluation system has a positive meaning for improving the network teaching management and the teaching quality. The evaluation of online course refers that the development of scientific criteria and use a series of feasible controlled technologies, methods and means to measure and evaluate the teaching process based on the teaching objectives. The evaluation of online course can timely feedback the related information in order to regulate the teaching activities between teacher and student, thus ensuring the effectiveness of teaching [6]. For the students, the evaluation of online course mainly enhances the learning autonomy through the self-evaluation feedback and self-understanding. For the teachers, it can help find the strengths and weaknesses in the teaching process by timely getting the information about the various aspects of the network teaching in the enforcement process, and the teacher can adjust and improve teaching based on the feedback. 2nd International Conference on Education, Management and Information Technology (ICEMIT 2015) © 2015. The authors Published by Atlantis Press 429 In order to satisfy these requirements, the evaluation of online course must be adequately funded and staffed, and fully developed and validated. This paper proposes a Fuzzy Synthetic Evaluation based method to evaluate online course. Below summarizes our main contributions: We evaluate the quality of online course from various aspects related to learning, and involve various objects associated with the learners. Then we use the Fuzzy Synthetic Evaluation, which can evaluate the teacher ability from different aspects, thus providing teachers with clear and actionable feedback to enhance their practice. The rest of this paper is organized as follows. Section 2 presents the evaluation index of online education courses, and Section 3 describes the Fuzzy Synthetic Evaluation and its construction steps. Next, we give the case study to illustrate the evaluation process. Finally, Section VII concludes. Evaluation Index of Online Education Courses This paper divides the teaching objects into two levels by decomposing the goals and analyzing the main factors and their properties of online education courses, thereby forming the index system. The first index is divided into four indicators: teaching, scientific, technology and teaching activities, which is shown in the Table 1. The second level will get based on the first level. Table 1 Course Evaluation Index Primary index Secondary index Evaluation Excellent Good Ordinary Poor Very poor Technology Innovation 0.5 0.15 0.2 0.15 0 Learning support tools 0.2 0.6 0.1 0.1 0 Teaching support tools 0.4 0.4 0.1 0 0.1 Course management 0.1 0.3 0.5 0.05 0.05 Teaching Purpose 0.3 0.5 0.15 0.05 0 Structure 0.4 0.2 0.2 0.1 0.1 Content 0.4 0.4 0.1 0.1 0 Means 0.1 0.3 0.3 0.2 0.1 Resource 0.1 0.2 0.5 0.2 0.1 Scientific Political thought 0.1 0.3 0.3 0.2 0.1 Courseware design 0.2 0.3 0.3 0.1 0.1 Innovation 0.2 0.4 0.2 0.15 0.05 Information carrier 0.1 0.3 0.4 0.1 0.1 Teaching activity Teaching interactivity 0.1 0.3 0.4 0.1 0.1 Student interactivity 0.3 0.4 0.2 0.1 0 Training 0.2 0.3 0.4 0.1 0 Others 0.4 0.3 0.2 0.1 0

Background Although a lot is known about how Fibroblastic Reticular Cells (FRCs) can regulate T lymphocytes (T cells), little is understood about whether or how T cells can regulate FRCs. Results This study shows that the absence of T cells inhibited the secretion of ER-TR7 by splenic FRCs, induced the structural disorder of FRCs, down-regulated the expression of the chemokine ligands CCL21 and CCL19, and weakened the homing ability of T cells to the spleen of nude mice. Transfusion of T cells from BALB/c mice restored the structure and functions of FRCs and recovered them. The expression of lymphotoxin (LT)-B was significantly downregulated in the absence of T cells from nude mice and was recovered after the transfusion of T cells. After the occlusion of the LT-B receptor, the FRCs’ structure and functions were not restored by transfusion of T cells. Conclusions These data reveal that the absence of T cells will subject spleen FRCs to structural and functional abnormality, and weaken the homing ability of T cells to the spleen. These changes are attributed to the T-cell- derived LT-B.

The adsorption thermodynamics of toxin (65 kDa) and protoxin (130 kDa) from Bacillus thuringiensis (Bt) by several minerals (montmorillonite, kaolinite and silica) were investigated. The adsorption of toxin and protoxin by minerals was a spontaneous process in the range of temperature from 278K to 318K. The ?G0ads values of the toxin adsorption by above minerals ranged from -35.30 to -43.81 kJ mol-1, and the protoxin adsorption ranged from -35.87 to -44.83 kJ mol-1. The adsorption isotherms of both proteins followed Langmuir equation and the maximum adsorbed amount (Nadsmax) of protoxin were lower than those of toxin. The adsorption of Bt proteins on minerals was exothermic process, companying a negative value of ?H0ads. The ?H0ads values of the adsorption of toxin were between -3.85 and -4.98 kJ mol-1 and the protoxin were between -2.60 and -4.53 kJ mol-1. The standard adsorption entropy changes (?S0ads) of toxin ranged from 110.73 to 122.16 J mol-1 K-1, and of protoxin ranged from 122.57 to 132.77 J mol-1 K-1. The positive standard entropy (?S0ads) indicated that the freedom increased when the insecticidal proteins from B. thuringiensis adsorbed minerals. The Kads, ?G0ads and ?S0ads of toxin in value were lower than those of protoxin, suggesting that the spontaneous trend and the affinity between protoxin and minerals were larger than those of toxin.