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The short survival time of transplanted adipose-derived mesenchymal stem cells (ASCs) is a problem for skin wound healing. Transplantation after the formation of cellular spheroids has been investigated as a promising method for prolonging cellular survival. However, there have been technical restrictions for transplantation of spheroids in clinical practice. Here, we show an effective method for transplantation of ASC spheroids onto skin wounds in order to efficiently cure refractory ulcers. To assist anchoring of spheroids onto skin wounds, we used a 120-nm-thick free-standing film (nanosheet) that has a highly adhesive property. Bioluminescence imaging showed that ASC spheroids carried by the nanosheet survived for 14 days, which is about two-times longer than that previously reported. Wounds treated with a nanosheet carrying ASC spheroids were 4-times smaller than untreated wounds on day 14. This method for transplantation of spheroids could be applied to cell therapy for various refractory skin wounds.

In general, it is common knowledge that people’s feelings are reflected in their voice and facial expressions. This research work focuses on developing techniques for diagnosing depression based on acoustic properties of the voice. In this study, we developed a composite index of vocal acoustic properties that can be used for depression detection. Voice recordings were collected from patients undergoing outpatient treatment for major depressive disorder at a hospital or clinic following a physician’s diagnosis. Numerous features were extracted from the collected audio data using openSMILE software. Furthermore, qualitatively similar features were combined using principal component analysis. The resulting components were incorporated as parameters in a logistic regression based classifier, which achieved a diagnostic accuracy of ~90% on the training set and ~80% on the test set. Lastly, the proposed metric could serve as a new measure for evaluation of major depressive disorder.

In modern society, evaluation and management of psychological stress may be important for the prevention of periodontal disease. The purpose of this study was to examine the relationship between psychological stress (vitality and mental activity) evaluated by Mind Monitoring System (MIMOSYS) and periodontal status. Forty students of Okayama University underwent the oral examination and self-reported questionnaire on the first day (baseline) and the 14th day (follow-up). Voice recording was performed every day with the MIMOSYS app during the whole study period. The participants completed the Patient Health Questionnaire (PHQ)-9 and Beck Depression Inventory (BDI) at baseline and at follow-up. Spearman’s rank correlation coefficient was used to determine the significance of correlations among variables. The PHQ-9 and BDI scores were negatively correlated with vitality in the morning. Change in vitality in the morning was significantly correlated with changes in periodontal inflammation. Mental activity was significantly correlated with change in mean probing pocket depth. This result shows that measurement of psychological stress using a voice-based tool to assess mental health may contribute to the early detection of periodontal disease.

In this report, we attempt to clarify the immune modulatory effects of Brazilian green propolis (BGP) and its major component, artepillin C, on the cytokine production of anti-CD3 antibody-stimulated mouse spleen cells. We also estimate the physiological mechanism affecting artepillin C's upon the cells.Male C3H/HeN mouse spleen cells stimulated by antiCD3 monoclonal antibody were co-cultured with BGP, artepillin C, and HC030031, a transient receptor potential ankyrin 1 (TRPA1) CaThe production of IL-2 was markedly enhanced, while that of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6, and IL-17 was significantly reduced in the antibody-stimulated spleen cells treated with BGP at a non-cytostatic concentration. These effects were reproduced in the cells treated with artepillin C. The expression of IL-2 mRNA was unaffected; however, that of the protein was significantly enhanced in the artepillin C-treated cells compared to untreated control cells. The enhancement of protein expression and the production of IL-2 by artepillin C was significantly alleviated by adding HC030031.Artepillin C is an important regulator of cytokine synthesis from activated spleen cells. The agent specifically augmented the expression of IL-2 via the Ca

Photothermal therapy (PTT) using a photo-absorbent in the near-infrared (NIR) region is an effective methodology for local cancer treatment. Before PTT using a NIR absorbent is executed, the operator generally determines the two parameters of fluence rate and irradiation time. However, even if the irradiation parameters are unchanged, the therapeutic effect of PTT is often different for individual tumors. Hence, we examined the therapeutic effect of PTT using a NIR absorbent (ICG lactosome) while changing two parameters (fluence rate and irradiation time) in various combinations. As a result, there was no robust correlation between those parameters and the therapeutic effect. Compared to those parameters, we found that a more reliable determinant was maintenance of the tumor temperature above 43 °C during NIR irradiation. To reconfirm the significance of the determinant, we developed a new system that can regulate the temperature at the NIR irradiation site at a constant level. By using the new system, we verified the treatment outcomes for tumors in which the NIR absorbent had accumulated. All of the tumors that had been kept at 43 °C during NIR irradiation were cured, while none of the tumors that had been kept at a temperature below 41 °C were cured. In conclusion, PTT using a NIR absorbent with thermal dosimetry is a highly reliable treatment for cancer.

Skin sensitization is an allergic reaction caused by certain chemical substances, and is an important factor to be taken into consideration when evaluating the safety of numerous types of products. Although animal testing has long been used to evaluate skin sensitization, the recent trend to regulate such testing has led to the development and use of alternative methods. Skin sensitization reactions are summarized in the form of an adverse outcome pathway consisting of four key events (KE), including covalent binding to skin proteins (KE1), keratinocyte activation (KE2), and dendritic cell activation (KE3). Equivalent alternative methods have been developed for KE1 to KE3, but no valid alternative has yet been developed for the evaluation of KE4 and T-cell activation. Current alternative methods rely on data from KE1 to KE3 to predict the effect of chemicals on skin sensitization. The addition of KE4 data is expected to improve the accuracy and reproducibility of such predictions. The aim of this study was to establish an assay to evaluate KE4 T-cell activation to supplement data on skin sensitization related to KE4. To evaluate T-cell activation, the Jurkat T-cell line stably expressing luciferase downstream of the pro-inflammatory cytokine interleukin-2 promoter was used. After exposure to known skin sensitizing agents and control substances, luciferase activity measurements revealed that this assay was valid for evaluating skin sensitization. However, two skin sensitizers known to have immunosuppressive effects on T-cells reacted negatively in this assay. The results revealed that this assay simultaneously allows for monitoring of the skin sensitization and immuno-suppressiveness of chemical substances and supplements KE4 T-cell activation data, and may thus contribute to reducing the use of animal experiments.

Innate immune cells remember Immunological memory is a phenomenon by which immune cells can quickly recognize an antigen that the host has previously encountered. Certain cells of the innate immune system exhibit memory-like responses know as trained immunity. Rapid, antigen-specific secondary (anamnestic) responses were long thought to be the domain of B and T cells. However, Dai et al. report that monocytes and macrophages can acquire memory specific for particular major histocompatibility complex I antigens using paired A-type immunoglobulin-like receptors (PIR-As) (see the Perspective by Dominguez-Andrés and Netea). This pathway contributes to recognition and rejection of allograft-transplanted tissue from a donor of the same species. Genetic depletion or blockade of PIR-As in mice diminished the rejection of kidney and heart allografts. This work, which expands immunological memory to include myeloid cells, points to targets that may improve organ transplantation outcomes in the future. Science , this issue p. 1122 ; see also p. 1052

Numerous studies have shown that the sustained release of ions from dental restorative materials have acid buffering capacity, prevents tooth enamel demineralization, and inhibits bacterial adhesion. Herein, the release behavior and bioresponsiveness of ions released from surface pre-reacted glass-ionomer (S-PRG) fillers were investigated in different types of media based on human dental pulp-derived stem cell (hDPSC) responses. The hDPSCs were cultured for 1-7 days in S-PRG eluates diluted with varying amounts of cell culture media. S-PRG released several types of ions, such as F-, Sr2+, Na+, Al3+, BO33-, and SiO32-. The balance of eluted ions differed depending on the dilution and solvent, which in turn affected the cytotoxicity, cell morphology, cell proliferation, and alkane phosphatase activity of hDPSCs, among other properties. The results suggest that tailored S-PRG filler eluates could be designed and prepared for application in dental practice.

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach. Keywords: Immune suppression, Tumor microenvironment (TME), IL-1α, IFN-γ, Programmed death (PD)1, Programmed death ligand (PD-L)1, Tumor associated macrophage (TAM), Cancer-associated fibroblast (CAF)

For high-critical-temperature (high-${T}_{\text{c}}$) superconductors, the normal state transport properties at low temperatures are of great importance to understand the Fermi surface structure and carrier profile. In this work we studied the doped ultrathin ${\mathrm{Ba}}_{0.57}{\mathrm{K}}_{0.43}{\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ system, a member of the optimally doped 122-type multigapped iron-based superconductors with complex superconducting gap structure. To explore the normal state resistivity below the zero-field superconducting ${T}_{\text{c}}$, both Co and Zn dopants were substituted into the superconducting ${\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ layer to suppress the superconductivity. The temperature dependence of in-plane resistivity below ${T}_{\text{c}}$ reveals a typical metallic behavior with the magnetic fields up to 45 T along $c$ axis. A linear dependence of Hall resistivity $({\ensuremath{\rho}}_{xy})$ is observed for ${\mathrm{Ba}}_{0.57}{\mathrm{K}}_{0.43}{\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ and ${\mathrm{Ba}}_{0.57}{\mathrm{K}}_{0.43}{({\mathrm{Fe}}_{0.96}{\mathrm{Zn}}_{0.04})}_{2}{\mathrm{As}}_{2}$ at high magnetic field, indicating a conventional metal profile. Nevertheless, the Co dopants lead to a decreasing $d{\ensuremath{\rho}}_{xy}/dH$ when the field is above 20 T. Such transformation of carrier transport properties may be contributed by band shift within a two-carrier model.

Objectives We have previously reported that mouse oral squamous carcinoma (OSCC), Sq-1979-1, produces interleukin (IL)-1α, which specifically enhances the immunosuppressive activity of co-cultured mesenchymal stromal 10T1/2 cells. This study assessed the conditions promoting the production of IL-1α in Sq-1979-1 cells, which could further enhance the immunosuppressive function of 10T1/2 cells, and evaluated its expression in OSCC tissues. Methods The expression of IL-1α was examined by RT-PCR, western blotting, and enzyme-linked immune sorbent assay (ELISA). The interferon (IFN)- γ-producing capability of anti-CD3 antibody-stimulated mouse spleen cells co-cultured with 10T1/2 cells and conditioned medium (CM) from Sq-1979-1 cells was examined by ELISA. The function of IL-1α was examined using an anti-IL1α antibody. Immunohistochemical analysis of the OSCC tissues was performed. Results The production of IL-1α from Sq-1979-1 cells was synergistically enhanced in lower serum (0.5% or 1.0% FBS) at the transcriptional level, and under hypoxia (1.0% oxygen) at the release level compared to that in the control medium supplemented with 10% FBS under normoxia. The IFN-γ-producing capability of stimulated spleen cells co-cultured with 10T1/2 cells was significantly reduced in the CMs prepared with the lower serum or under hypoxia. These functions of CMs were completely abolished by the anti-IL-1α antibody. The expression of IL-1α in OSCC tissues was prominent in the midst of a carcinomatous cellular lesion or a nearby necrotic lesion, where a supply deficiency could occur. Conclusion s: IL-1α production by Sq-1979-1 cells was synergistically augmented under low serum and hypoxic conditions, which could promote the immunosuppressive activity of mesenchymal cells.

Objectives: It has been reported that Brazilian green propolis (BGP) possesses anti-tumor and chemo-preventive properties against prostate cancer (Szliszaka E, 2011). And bioactive components from propolis have been shown to have anti-cancerous effects upon hepatocellular carcinoma (Liu X, 2021). These observations revealed that propolis can be an anti-cancer drugs, however the immunological effects upon tumor microenvironments of these naturally occurring components has not been elucidated. In this report, we attempt to clarify immune modulatory effects of BGP and the major component, artepillin C, by observing cytokine production from activated T cells. Methods: The mouse spleen cell stimulated by anti-CD3 monoclonal antibody were co-cultured with BGP, artepillin C and HC030031, an antagonist of TRPA1 Ca2+ channel. The productions of IFN-γ, IL-6, IL-17, IL-4, IL-10 and IL-2 was assayed by ELISA. Results: Our results demonstrated the production of IL-2 was markedly enhanced, while the production of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6 and IL-17 were markedly reduced, in the highly viable stimulated spleen cells treated with BGP. These effects were also reproduced in the cells treated with artepillin C, a major component of BGP. The enhancement of IL-2 production by artepillin C was significantly alleviated by adding 10 HC030031, an antagonist of TRPA1 Ca2+ channel, suggesting the enhancement of the cytokine production by artepillin C could be mediated by Ca2+ influx. Conclusions: The artepillin C, a major component of BGP, is an important regulator of activated T lymphocytes and specifically augmented the expression of IL-2 vie Ca2+-permeable cation channel, TRPA1. These effects may exert immunomodulatory effects upon tumor microenvironments. Citation Format: Nobuo Kondoh, Masako Kamiya, Hanemi Tsuruta, Moe Takahashi, Kumiko Ikeno, Kyohei Ueno, Naoki Umemura, Eiji Takayama, Harumi Kawaki, Genjiro Nakamura, Toru Nikaido, Yasunori Muramatsu, Megumi Ando. Enhanced production of IL-2 from anti CD3-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5201.

This paper investigates the magnetic state of triangular antiferromagnets with metalic conductivity. The authors observe a slowing down of a spin fluctuation in the 3-sublattice partially disordered state and associate it to the magetic frustration on the two-dimensional triangular lattice.

Salivary peroxidase and myeloperoxidase are known to display antibacterial activity against oral microbes, and previous indications have pointed to the possibility that horseradish peroxidase (HRP) adsorbs onto the membrane of the major oral streptococci, Streptococcus mutans and Streptococcus sanguinis (S. sanguinis). However, the mechanism of interaction between HRP and the bacterial cell wall component is unclear. Dental plaques containing salivary glycoproteins and extracellular microbial products are visualized with 'dental plaque disclosing agent', and are controlled within dental therapy. However, current 'dental plaque disclosing agents' are difficult to evaluate with just dental plaques, since they stain and disclose not only dental plaques but also pellicle formed with salivary glycoproteins on a tooth surface. In this present study, we have demonstrated that HRP interacted with the cell wall component of the major gram-positive bacterial peptidoglycan, but not the major cell wall component of gram-negative bacteria lipopolysaccharide. Furthermore, we observed that the adsorbed HRP labeled with fluorescence was detected on the major oral gram-positive strains S. sanguinis and Streptococcus salivarius (S. salivarius), but not on a gram-negative strain, Escherichia coli (E. coli). Furthermore, we have demonstrated that the combination of HRP and chromogenic substrate clearly disclosed the dental plaques and the biofilm developed by S. sanguinis, S. salivarius and the major gram-postive bacteria Lactobacillus casei on tooth surfaces, and slightly disclosed the biofilm by E. coli. The combination of HRP and chromogenic substrate did not stain either the dental pellicle with the salivary glycoprotein mucin, or naked tooth surfaces. These results have suggested the possibility that the adsorption activity of HRP not only contributes to the evaluation of dental plaque, but that enzymatic activity of HRP may also contribute to improve dental hygiene.

The aim of this research was to investigate the value of autofluorescence imaging of oral cancer across different stages of tumor growth, to assist in detecting tumors. A xenograft mouse model was created with human oral squamous cell carcinoma cell line HSC‐3 being subcutaneously inoculated into nude mice. Tumor imaging was performed with an autofluorescence imaging method (Illumiscan®) using the luminance ratio, which was defined as the luminance of the tumor site over the luminance of normal skin tissue normalized to a value of 1.0. This luminance ratio was continuously observed postinoculation. Tumor and normal skin tissues were harvested, and differences in the concentrations of flavin adenine dinucleotide and nicotinamide adenine dinucleotide were examined. The luminance ratio of the tumor sites was 0.85 ± 0.05, and there was no significant change in the ratio over time, even if the tumor proliferated and expanded. Furthermore, flavin adenine dinucleotide and nicotinamide adenine dinucleotide were significantly lower in tumor tissue than in normal skin tissue. A luminance ratio under 0.90 indicates a high possibility of tumor, irrespective of the tumor growth stage. However, this cutoff value was determined using a xenograft mouse model and therefore requires further validation before being used in clinical diagnosis.

Objectives; We have already reported that mouse oral squamous carcinoma (OSCC), Sq-1979-1, cells produce IL-1α which specifically enhances the immunosuppressive activity of co-cultured mesenchymal stromal, 10T1/2, cells (Morimoto-Ito, Open Dent J. 2019). In this report, we evaluated conditions promoting the expression of IL-1α of Sq-1979-1 cells to further enhance immunosuppressive function of the 10T1/2 cells, and also examined the expression in OSCC tissues. Methods; Expression of IL-1α in Sq-1979-1 cells was evaluated by RT-PCR, western blots and enzyme-linked immune sorbent assay (ELISA). Conditioned mediums (CMs) from Sq-1979-1 cells were co-cultured with 10T1/2 cells and anti-CD3 antibody-stimulated mouse spleen cells. The production of interferon (IFN)- γ and IL-1α was evaluated using ELISA. The function of IL-1α in CM was examined by anti- IL-1α antibody. Immunohistochemical analysis of OSCC tissues was performed. Results; The production of IL-1α from Sq-1979-1 cells was specifically enhanced in lower serum (0.5% or 1.0%FBS), or under hypoxia (1.0% oxygen) compared to that in the standard growth condition supplemented with 10% FBS under normoxia. Compared to standard CM, the CMs prepared in 0.5% and 1.0% FBS, or under hypoxia significantly reduced IFN-γ production from stimulated spleen cells co-cultured with 10T1/2 cells. These functions of the CMs completely abolished by anti- IL-1α antibody. Expression of IL-1α in OSCC tissues was prominent in the midst of carcinomatous cellular lesion, or nearby necrotic lesion, where the supply deficiency could be occurred. Conclusions; The promotion of immunosuppressive activity of mesenchymal cells by Sq-1979-1 cells was specifically augmented in lower serum and hypoxic conditions, mediated by increased IL-1α production. Citation Format: Nobuo Kondoh, Akihiro Matsunami, Masako Mizuno-Kamiya, Naoki Umemura, Eiji Takayama, Harumi Kawaki, Kyouhei Ueno, Hiroe Morimoto-Ito, Yasunori Muramatsu, Shinichiro Sumitomo. Augmented secretion of IL-1α from mouse oral squamous cell carcinoma (OSCC) cells caused by the serum deprivation and hypoxia promotes immune-suppressive activity of mesenchymal stromal cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1910.

We report NMR experiments on heavily electron-doped Fe-based superconductor in comparison with the results on the parent Fe-based compounds. The typical parent Fe-based compound LaFe(As1-x′P x′)O exhibits the re-emergent antiferromagnetic (AFM) order at x′ ~ 0.6 (AFM2) separated from the parent AFM order at x′ =0 (AFM1). Systematic 31P-NMR study on [Sr4Sc2O6]Fe2(As1−x P x )2 (SrSc42622), which has local lattice parameters of iron-pnictogen (FePn) layer similar to the series of LaFe(As1−x′/P x′)O, also revealed that the presence of AFM1 order is universal for most of parent Fe-based compounds. In contrast, the static AFM2 order was absent in this series, however, the dynamical low-energy AFM spin fluctuations are enhanced at around x ~ 0.8, indicating that the onset of the static AFM2 is quite sensitive to the local lattice parameters of FePn layer. In order to elucidate the further universality and diversity, we have carried out 77Se-NMR measurement on Li x (NH3)yFe2−δ Se2 (Tc = 44 K) in heavily electron-doped regime. Although the spin fluctuations at low energies does not significantly develops upon cooling, the moderate spin fluctuations were extracted at high temperatures from comparison of the temperature (T) dependences of Knight shift and nuclear relaxation rate (1/T 1 T). We discuss the universality and diversity of the relationship between the Tc and the characteristics of the spin fluctuations in the Fe-based compounds from a microscopic point of the NMR measurements.

Myeloid derived suppressor cells (MDSCs) localize to hematopoietic organs and peripheral blood during inflammation or tumor tissues and lymph nodes in the presence of a tumor. However, whether there are differences in MDSCs found in the primary tumor and metastases is unknown. In the present study, we established a cell line of metastasized tumor cells to a lymph node, L5-11, which were derived from the Sq-1979 mouse buccal mucosa squamous cell carcinoma cell line. We then analyzed tumor immunogenicity, especially with regard to MDSCs, to clarify the differences between the primary tumor and metastases, using an isogenic heterotopic tumor transplantation model. Our data showed that the population of intratumoral MDSCs, especially polymorphonuclear MDSCs in the lymph node metastasis model were significantly increased compared with syngeneic grafts from the primary cell line Sq-1979 after 21 days. Furthermore, we identified that the lymph node metastasis cell line had increased expression of genes that promote the expansion of MDSCs, tumor growth and metastasis. Hence, these data suggest that tumor immunosuppression can occur via activation of MDSCs. However, further examination is required to clarify whether all or a subset of these factors from the lymph node metastasis tumor cells are required to induce intratumoral MDSCs.

To evaluate systemic immunity associated with tumor growth limited to a subcutaneous site versus growth proceeding at multiple tumor sites, we established syngeneic mouse subcutaneous and pulmonary tumor models by local subcutaneous and intravenous injection of colon carcinoma CT26 cells. We found that splenic myeloid-derived suppressor cell (MDSC) levels were significantly increased in the subcutaneous tumor model but not in the pulmonary tumor model. Furthermore, both CD4(+) and CD8(+) T cells as well as CD4(+) Foxp3(+) T cells were significantly decreased in the subcutaneous tumor model and were largely unchanged in the pulmonary tumor model. In addition, the subcutaneous model, but not the pulmonary model, displayed a Th1 polarization bias. This bias was characterized by decreased IL-4, IL-9, and IL-10 production, whereas the pulmonary model displayed increased production of IL-10. These results suggest that the mode of tumor development has differential effects on systemic immunity that may, in turn, influence approaches to treatment of cancer patients.

We report a systematic NMR study on [Sr4Sc2O6]Fe-2(As1-xPx)(2), for which the local lattice parameters of the iron-pnictogen (FePn) layer are similar to those of the series LaFe(As1-x'Px')O, which exhibits two segregated antiferromagnetic (AFM) order phases, AFM1 at x' = 0 - 0.2 and AFM2 at x' = 0.4 - 0.7. Our results reveal that the parent AFM1 phase at x = 0 disappears at x = 0.3 - 0.4, corresponding to a pnictogen height (h(pn)) from the Fe plane of 1.3-1.32 angstrom, which is similar to that of LaFe(As1-x'Px')O and various parent Fe pnictides. By contrast, the AFM2 order reported for LaFe(As0.4P0.6)O does not appear at x similar to 0.8, although the local lattice parameters of the FePn layer and the microscopic electronic states are quite similar. Despite the absence of the static AFM2 order, reemergent dynamical AFM spin fluctuations were observed at approximately x similar to 0.8, which can be attributed to the instability of the AFM2 phase. We suggest this re-enhancement of AFM spin fluctuations plays a significant role in enhancing the T-c to 17 K for x = 0.8 - 1. Finally, we discuss the universality and diversity of the complicated magnetic ground states from a microscopic point of view, including the difference in the origins of the AFM1 and AFM2 phases, and their relations with the high superconducting transitions in Fe pnictides.

Indocyanine green (ICG) is a near-infrared light-absorbing substance. Thus, when a tumor in which ICG has accumulated is irradiated with a near-infrared (NIR) laser, only the tumor can be heated by a photothermal reaction. We developed ICG lactosome, a novel drug delivery system (DDS) composed of polymeric micelles and ICG that shows selective accumulation in tumor based on an enhanced permeability and retention (EPR) effect. We showed that ICG lactosome accumulated in a tumor by using an intradermal tumor mouse model of a murine colon cancer cell line (Colon26) transfected with Nano lantern luminescent protein (NLC26). Two days after the administration of ICG lactosome, the tumor was irradiated with an 808-nm diode-laser while monitoring tumor temperature. The results showed that the treated tumors were cured when the peak of tumor temperature during NIR irradiation reached 43°C or higher. To verify these results, photothermal therapy (PTT) using ICG lactosome was carried out using a newly developed system that can control the temperature at the NIR irradiation site at a constant level. All of the tumors that had been kept at 43°C during irradiation were cured, while 2 of 5 tumors that had been kept at 42°C were not cured, and none of tumors that had been kept at a temperature below 41°C were cured. ICG lactosome-assisted PTT combined with thermal dosimetry is a highly reliable method for cancer treatment and may afford further clinical opportunities for PTT.

The compound $\mathrm{BaIrS}{\mathrm{i}}_{2}$ was successfully synthesized under high pressure at 6 GPa. $\mathrm{BaIrS}{\mathrm{i}}_{2}$ crystalizes in an orthorhombic symmetry with the noncentrosymmetric space group $C{222}_{1}$ and the lattice parameters $a=15.0492(1)\phantom{\rule{0.16em}{0ex}}\AA{}, b=8.0311(1)\phantom{\rule{0.16em}{0ex}}\AA{}$, and $c=8.0314(1)\phantom{\rule{0.16em}{0ex}}\AA{}$. $\mathrm{BaIrS}{\mathrm{i}}_{2}$ shows superconductivity below a critical temperature ${T}_{c}\ensuremath{\sim}6\phantom{\rule{0.16em}{0ex}}\mathrm{K}$ and an upper critical field ${\ensuremath{\mu}}_{0}{H}_{c2}(0)\ensuremath{\sim}6\phantom{\rule{0.16em}{0ex}}\mathrm{T}$ with a Ginzburg-Landau parameter ${\ensuremath{\kappa}}_{\mathrm{GL}}\ensuremath{\sim}87$. Specific-heat measurements suggest that $\mathrm{BaIrS}{\mathrm{i}}_{2}$ is an intermediate-coupling superconductor with a moderate electron-phonon coupling constant ${\ensuremath{\lambda}}_{ep}\ensuremath{\sim}0.8$. The Sommerfeld constant is ${\ensuremath{\gamma}}_{n}\ensuremath{\sim}5.5\phantom{\rule{0.16em}{0ex}}\mathrm{mJ}/\mathrm{mole}\phantom{\rule{0.16em}{0ex}}{\mathrm{K}}^{2}$. Phonon mediation seems to be dominant for Cooper pairing in $\mathrm{BaIrS}{\mathrm{i}}_{2}$. The ab initio calculations revealed that $\mathrm{BaIrS}{\mathrm{i}}_{2}$ has four Fermi surfaces split by spin-orbit coupling. The Cooper pairing seems to occur between electrons without spin degeneracy.

Background/Objective: Lipopolysaccharides (LPS) promote allergic responses to nickel (Ni) both in the sensitization and elicitation steps. In this study, we examine the effect of pre-sensitization to LPS on the occurrence of Ni allergy using a mouse model. Method: A 100 mg of LPS was injected into C57BL/6J mice intraperitoneally (ip). Three weeks later, the mice were subsequently injected with 0.3 μ moles of nickel dichloride (NiCl2) and 100 μg of CpG-DNA, which acted as an adjuvant. The mice were repeatedly immunized with the 0.3 μg of nickel sulfate (NiSO4), along with 300 μl of the adjuvant, Inject Alum (Pierce, USA). Then we examined the producing capabilities of T helper type 1 (Th1) and 2 (Th2) cytokines (interferon-gamma- (IFN)-γ and interleukin (IL)-10, respectively) from anti CD3 antibody-stimulated spleen cells. Results: Pre-treatment with LPS, followed by repeated challenges with Ni2+ and adjuvants significantly enhanced the IFN-γ-producing capability of spleen cells (n=5, p2+ and adjuvants (n=5). In contrast, without LPS treatment, single or even repeated challenges by Ni2+ could not enhance the IFN-γ-producing capability. On the other hand, the IL-10-producing capability of spleen cells was not enhanced even by LPS and repeated challenges with Ni2+ and adjuvants. Conclusion: The solitary pre-sensitization to LPS is essential for the onset of Ni allergy by shifting the Th1/Th2 immune balance toward a Th1 dominant.

Transplantation of hematopoietic stem and progenitor cells (HSCs) i.e., self-renewing cells that retain multipotentiality, is now a widely performed therapy for many hematopoietic diseases. However, these cells are present in low number and are subject to replicative senescence after extraction; thus, the acquisition of sufficient numbers of cells for transplantation requires donors able to provide repetitive blood samples and/or methods of expanding cell numbers without disturbing cell multipotentiality. Previous studies have shown that HSCs maintain their multipotentiality and self-renewal activity if TCF3 transcription function is blocked under B cell differentiating conditions. Taking advantage of this finding to devise a new approach to HSC expansion in vitro, we constructed an episomal expression vector that specifically targets and transiently represses the TCF3 gene. This consisted of a vector encoding a transcription activator-like effector (TALE) fused to a Krüppel-associated box (KRAB) repressor. We showed that this TALE-KRAB vector repressed expression of an exogenous reporter gene in HEK293 and COS-7 cell lines and, more importantly, efficiently repressed endogenous TCF3 in a human B lymphoma cell line. These findings suggest that this vector can be used to maintain multipotentiality in HSC being subjected to a long-term expansion regimen prior to transplantation.

Administration of bone marrow-derived mesenchymal stem cells (MSCs) is a possible treatment for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation and other inflammatory conditions. To address the mechanism of immunosuppression by MSCs, in particular those derived from adipose tissue (AMSCs), AMSCs were isolated from three different mouse strains, and the suppressive capacity of the AMSCs thus obtained to suppress interferon (IFN)-γ generation in mixed lymphocyte reaction cultures serving as an in vitro model of GVHD were assessed. It was revealed that the AMSCs had a potent capacity to suppress IFN-γ production regardless of their strain of origin and that such suppression was not associated with production of interleukin-10. In addition, the results demonstrated that β2-microglobulin (β2m)-deficient AMSCs from β2m−/− mice were also potent suppressor cells, verifying the fact that the mechanism underlying the suppression by AMSCs is independent of major histocompatibility complex (MHC) class I expression or MHC compatibility. As AMSCs appear to have immunosuppressive properties, AMSCs may be a useful source of biological suppressor cells for the control of GVHD in humans.

Mental health disorders have become a social problem, and countermeasures are thus required. Previously, the authors developed the MIMOSYS (Mind Monitoring System) algorithm to evaluate an individual’s mental health state using their voice. An individual’s mental health state is detected using aspects of emotions that are present in their voice; however, since emotions change subtly, influence to emotions will be concerned owing to voice acquisition methods such as a natural conversation with someone else or reading fixed phrases. The aim of this research was to evaluate the influence of the type of voice acquisition method on the estimation of emotion and mental health state using the vocal analysis in MIMOSYS. In the experiments, we collected emotions and MIMOSYS analysis results from voice recordings during calls and during readings of fixed phrases from the application for over two weeks. In addition, the Beck’s Depression Inventory (BDI) test was used to evaluate participants’ subjective depression levels at the beginning of the experiment. In the evaluation, we analyzed recordings of calls and readings of fixed phrases for the participants in the normal range of the BDI test. Results indicated that the expression of emotions was suppressed in the recordings of readings of fixed phrases when compared to the recordings of calls, and the analysis result by MIMOSYS tended to be lower. Consequently, when measuring an individual’s mental health state from their voice, it may be necessary to match the type of voice acquisition methods or correct the estimations according to acquisition method.

Introduction:In order to survive, cancers control immune systems and evade immune detection using mediators consisting of immune checkpoint molecules and cellular systems associated with immune suppression.Methodology:During the development of cancer and chronic infections, the immune checkpoints and cellular components including regulatory T cells, myeloid derived suppressor cells and cancer associated fibroblasts are often enhanced as a mechanism of immune subversion and have therefore become very important therapeutic targets.Conclusion:In this review, we will discuss the complexity of immune-suppressive mechanisms in the tumor milieu of cancers, including oral malignancy.

T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments regulates cancer progression. Nude mice are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The tumor microenvironment in a xenograft, comprising human and mouse cells, exhibits more complex bidirectional signaling and function than that of allograft. Here, we evaluated the differences of myeloid cells between them. Plasma interferon-γ and interleukin-18 concentrations in the xenograft tumor model after lipopolysaccharide (LPS) administration were significantly higher than those in the allograft tumor model. MHC class I, II, and CD80 expression levels were increased in CD11b+ and MDSC populations after LPS administration in the spleen of a xenograft tumor model but not in that of an allograft tumor model. Additionally, the number of CD80- and mannose receptor C type 1 (MRC1)-expressing cells was decreased upon LPS administration in the tumor of the xenograft tumor. These results suggest that functions of macrophages and DCs are sustained in the xenograft, whereas their functions in response to LPS were suppressed in the allograft. The findings will encourage the consideration of the effects of myeloid cells in the xenograft for drug development.

In order to evaluate the Th1 and Th2 responses of Oral Squamous Cell Carcinoma (OSCC) patients, we investigated the cytokine producing capability of peripheral blood (PB), and compared it with clinicopathological appearances of OSCC patients. The production of a Th1-type cytokine, interferon (IFN)-γ, from lipopolysaccharide (LPS)-stimulated PB correlated positively with the frequency of lymph node metastasis. We also investigated the production of a Th2-type cytokine, IL-10, however, no significant correlation was observed with the clinicopathological appearances. Our results suggested that the IFN-γ producing capability was specifically regulated and dependent on the regional metastatic potencies of OSCCs.

Nematic order often breaks the tetragonal symmetry of iron-based superconductors. It arises from regular structural transition or electronic instability in the normal phase. Here, we report the observation of a nematic superconducting state, by measuring the angular dependence of the in-plane and out-of-plane magnetoresistivity of Ba0.5K0.5Fe2As2 single crystals. We find large twofold oscillations in the vicinity of the superconducting transition, when the direction of applied magnetic field is rotated within the basal plane. To avoid the influences from sample geometry or current flow direction, the sample was designed as Corbino-shape for in-plane and mesa-shape for out-of-plane measurements. Theoretical analysis shows that the nematic superconductivity arises from the weak mixture of the quasi-degenerate s-wave and d-wave components of the superconducting condensate, most probably induced by a weak anisotropy of stresses inherent to single crystals., Nematic electronic order is rare and its onset often indicates a phase transition. Here, Li et al. report a nematic superconducting state in Ba0.5K0.5Fe2As2 by measuring the angular dependence of the in-plane and out-of-plane magnetoresistivity.

We have successfully synthesized the single crystal of $\mathrm{A}{\mathrm{g}}_{2}\mathrm{P}{\mathrm{d}}_{3}\mathrm{S}$, which exhibits superconductivity with the transition temperature of ${T}_{\mathrm{c}}=2.25\phantom{\rule{0.16em}{0ex}}\mathrm{K}$. $\mathrm{A}{\mathrm{g}}_{2}\mathrm{P}{\mathrm{d}}_{3}\mathrm{S}$ crystallizes in the space group $P{4}_{1}32$ with the filled $\ensuremath{\beta}\ensuremath{-}\mathrm{Mn}$ structure, which has no inversion symmetry. The value of the Ginzburg-Landau parameter ${\ensuremath{\kappa}}_{\mathrm{GL}}$ indicates that $\mathrm{A}{\mathrm{g}}_{2}\mathrm{P}{\mathrm{d}}_{3}\mathrm{S}$ is a type-II superconductor. $\mathrm{\ensuremath{\Delta}}C({T}_{\mathrm{c}})/{\ensuremath{\gamma}}_{\mathrm{n}}{T}_{\mathrm{c}}=1.50$ and $2\mathrm{\ensuremath{\Delta}}/{k}_{B}{T}_{\mathrm{c}}=3.48$ from the heat-capacity analyses indicate that $\mathrm{A}{\mathrm{g}}_{2}\mathrm{P}{\mathrm{d}}_{3}\mathrm{S}$ is a weak-coupling Bardeen-Cooper-Schrieffer (BCS) superconductor with an isotropic superconducting gap. On the other hand, the violation of the Werthamer-Helfand-Hohenberg curve in the $H\ensuremath{-}T$ phase diagram implies $\mathrm{A}{\mathrm{g}}_{2}\mathrm{P}{\mathrm{d}}_{3}\mathrm{S}$ is not a typical BCS superconductor.

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune "natural" and antigen-induced "immune" IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcμR). We have recently identified a bona fide FcμR in both humans and mice. In this article we briefly review what we have learned so far about FcμR.

A novel strontium–gold silicide (SrAuSi3) was successfully synthesized for the first time using a high-pressure technique, at ∼6 GPa. X-ray Rietveld analysis and scanning transmission electron microscopy studies clearly revealed that SrAuSi3 crystallizes in a BaNiSn3-type structure, in space group I4mm with the following lattice parameters: a = 4.4090(1) A, and c = 9.9475(3) A. The structure was found not to have inversion symmetry in real space. From direct measurements of polycrystalline SrAuSi3, the electrical resistivity was zero, the static magnetic susceptibility was almost a full volume Meissner diamagnetic signal, and the specific heat exhibited a sharp jump, all of which were accompanied by a phase transition due to bulk superconductivity at a critical temperature (TC) of 1.54 K. The SrAuSi3 compound is the first noncentrosymmetric superconductor that includes Au as a principal constituent element.

Structural phase transitions in BiMnO3 were studied by means of energy-dispersive X-ray diffraction in the pressure 0–4 GPa and temperature 300–900 K ranges, and also by means of angle-dispersive X-ray diffraction and Raman spectroscopy at high pressures up to 50 GPa and ambient temperature. The P–T phase diagram of BiMnO3 was constructed. A suppression of the transition temperatures between monoclinic C2/c and orthorhombic Pnma phases was observed under pressure. The temperature and pressure dependencies of lattice parameters were obtained. A new orthorhombic Imma phase was observed at P > 20 GPa. The lattice dynamics calculations were performed for the analysis of the Raman spectra of BiMnO3.

Polycrystals of Ba0.5K0.5Fe1.9M0.1As2 (M = Fe, Co, Ni, Cu, and Zn) synthesized at high pressures show quasi-periodic spikes in the magnetization loop at 2 K owing to successive flux jumps, while the single crystals are observed as absence of jumps. The Zn-doped crystal indicates higher frequency flux jumps than that of Zn-free samples, because of the reduction of grain size and enhancement of grain boundary effect. However, the Co-, Ni- and Cu-doped crystals show less jumps duo to the increased granularity. Our present results suggest that the flux jump in the textured polycrystals is controlled largely by the grain boundary as the flux pining effect rather than the intrinsic dopants.

The mechanisms of immunomodulation by mesenchymal stromal cells remain poorly understood. In this study, the effects of mouse adipose tissue-derived mesenchymal stromal cells (ASCs) on mouse spleen cells alloreactively stimulated by anti-CD3 and anti-CD28 antibody-coated (anti-CD3/CD28) beads were observed. Production of interferon-γ by the anti-CD3/CD28 bead-stimulated spleen cells was significantly suppressed in co-culture with ASCs. However, an augmented intensity of CD69 on the stimulated spleen cells was not suppressed in the presence of ASCs. The immunosuppressive effects of ASCs were partially mediated by one or more soluble factors (26% suppression). However, the ASCs require cell-cell contact in order to maximally exert suppression (88%). The suppressive effect of ASCs mediated by direct cell contact was partially reversed following knockdown of β2 microglobulin, a component of the major histocompatibility complex (MHC) class I molecule, with siRNA. The results of the study demonstrated that ASCs have significant immune modulatory effects on alloreactively stimulated spleen cells. The effects of ASCs on spleen cells are dependent on soluble factor(s) and cell contact, which is mediated by the MHC class I complex on ASCs.

We have investigated the magnetic properties of the new colossal magnetoresistance oxide NaCr2O4 with the calcium-ferrite-type structure by using 23Na, 53Cr nuclear magnetic resonance (NMR) and magnetization measurements. This chromate is found to show an antiferromagnetic order with the spin moments slightly canted from the b axis at temperatures below T N=125 K. The spin structure may be governed by the competition between double-exchange ferromagnetic and superexchange antiferromagnetic interactions in the double chains. The origin of the large magnetoresistance is discussed for several scenarios such as phase separation, rearrangement of the spin structure induced by the magnetic field, and domain walls.

Correction for 'New layered cobalt oxyfluoride, Sr

To elucidate the genetic events that occur during the development of OSCC, the present study established a model of oral malignancy using a mouse oral squamous cell carcinoma (OSCC) Sq-1979 cell line. Sq-1979 cells were implanted into syngeneic C3H mice. Subsequently, 233 cells and metastatic sub-clones (L cells) from primary OSCC, as well as the metastasized lymph node tissues of Sq-1979-implanted mice were established. Compared with parental Sq-1979 and 233 cells, the majority of L cells exhibited a higher proliferation rate and transplantability, and conferred a lower survival rate on the implanted mice. To investigate the genetic background of L cells, preferentially expressed genes in L cells were identified by cDNA microarray and reverse transcription-polymerase chain reaction analyses. The expression of FYN-binding protein (Fyb), solute carrier family 16 member 13 (Slc16a13), keratin 7, transmembrane portion 173 and Slc44a3 mRNAs was significantly elevated in L cells compared with that in Sq1979 and 233 cells. The mRNA expression was also evaluated in human OSCC and leukoplakia (LP) tissues. Among the 5 aforementioned mRNAs, the expression of FYB and SLC16A13 was significantly higher in OSCC than in LP tissues. Furthermore, the expression of SLC16A13 mRNA was significantly elevated in highly invasive OSCCs, which were classified as grades 3 and 4 by the Yamamoto-Kohama (YK) classification of invasion, compared with those in lower grades (YK-1 and -2). The model proposed in the present study could thus describe essential marker genes for the diagnosis of oral malignancies.

The lack of MHC molecules on red blood cells (RBCs) has led to questions regarding the immunological function of CD8(+) T cells against malarial blood-stage (MBS). However, several recent reports contradicting with this concept have suggested that they play an important role in the course of MBS infection. The present study generated genetically engineered murine malaria, Plasmodium yoelii, which expresses a well-defined Trypanosoma cruzi-derived, H-2K(b)-restricted CD8(+) T cell epitope, ANYNFTLV. Prime/boost vaccination by the use of recombinant adenovirus and recombinant modified vaccinia virus Ankara (MVA), which induced an enhanced number of ANYNFTLV-specific CD8(+) T cells, failed to prevent a pathological outcome to occur upon ANYNFTLV-expressing murine MBS infection. This outcome did not change even with the combination of passive transfer of an appreciable number of in vitro-expanded ANYNFTLV-specific CD8(+) T cells. In contrast, the pre-infection of mice with T. cruzi, which intrinsically bears the same CD8(+) T cell epitope significantly improved the survival of ANYNFTLV-expressing malaria-infected mice but not that of control malaria-infected ones. This protective effect was abrogated by the use of a CD8(+) T cell-depleting monoclonal antibody. Although the protective effect was observed only in certain situations, the actively induced antigen-specific CD8(+) T cells could ameliorate the pathologies caused by the MBS. This is the first study to implicate that the active induction of antigen-specific CD8(+) T cells should be included in the development of a vaccine against MBS.

Solid solutions of BiGaxM1–xO3 (M = Cr, Mn, and Fe) were prepared using the high-pressure high-temperature method at 6 GPa and 1700 K (M = Cr and Fe) and 1300 K (M = Mn). The formation of a large family of polar materials with R3c and Cm symmetries was found. Crystal structures were studied with laboratory X-ray powder diffraction: space group Cm, a = 5.3150(1) A, b = 5.2960(1) A, c = 4.6965(1) A, and β = 92.556(2)° for BiGa0.4Fe0.6O3; space group Cm, a = 5.2798(1) A, b = 5.2577(1) A, c = 4.6465(1) A, and β = 91.974(2)° for BiGa0.7Mn0.3O3; space group R3c, a = 5.51623(8) A and c = 13.61391(17) A for BiGa0.4Cr0.6O3. Samples with the Cm symmetry have square-pyramidal coordination of (Ga,M)3+ ions, and their structure is very similar with the structure of supertetragonal PbVO3, BiCoO3, and Bi2ZnTiO6 materials. Samples with the R3c symmetry are isostructural with BiFeO3 and have comparable calculated (based on the point-charge model) spontaneous polarization (58 μC/cm2 for BiGa0.4Cr0.6O3). The calculated pola...

Toll-like receptors (TLRs) serve as the major innate immune sensors for detection of specific molecular patterns on various pathogens. TLRs activate signaling events mainly by utilizing ubiquitin-dependent mechanisms. Recent research advances have provided evidence that TLR signaling is linked to induction of autophagy. Autophagy is currently known to affect both of the immune defense and suppression of inflammatory responses. In TLR-associated immune responses, autophagic lysis of intracellular microbes (called xenophagy) contributes to the former mechanism, while the latter seems to be mediated by the control of the mitochondrial integrity or selective autophagic clearance of aggregated signaling proteins (called aggrephagy). Several autophagy-related ubiquitin-binding proteins, such as SQSTM1/p62 and NDP52, mediate xenophagy and aggrephagy. In this review, we summarize the expanded knowledge regarding TLR signaling and autophagy signaling. After that, we will focus on autophagy-associated signaling downstream of TLRs and the effect of autophagy on TLR signaling, thus highlighting the signaling crosstalk between the TLR-associated innate immune responses and the regulation of innate immunity by xenophagy and aggrephagy.