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Convolution neural network (CNN) has been widely used in the field of remaining useful life (RUL) prediction. However, the CNN-based RUL prediction methods have some limitations. The receptive field of CNN is limited and easy to happen gradient vanishing problem when the network is too deep. The contribution differences of different channels and different time steps to RUL prediction are not considered, and only use deep learning features or handcrafted statistical features for prediction. These limitations can lead to inaccurate prediction results. To solve these problems, this paper proposes an RUL prediction method based on multi-layer self-attention (MLSA) and temporal convolution network (TCN). The TCN is used to extract deep learning features. Dilated convolution and residual connection are adopted in TCN structure. Dilated convolution is an efficient way to widen receptive field, and the residual structure can avoid the gradient vanishing problem. Besides, we propose a feature fusion method to fuse deep learning features and statistical features. And the MLSA is designed to adaptively assign feature weights. Finally, the turbofan engine dataset is used to verify the proposed method. Experimental results indicate the effectiveness of the proposed method.

The newly found mesenchymal‐like endometrial regenerative cells (ERCs) have been proved to induce immune tolerance in cardiac allograft transplantation. However, the therapeutic mechanism is not clear. The present study was undertaken to investigate whether ecto‐5′‐nucleotidase (CD73) expression on ERCs is critical to cardiac allograft protection. C57BL/6 mouse recipients receiving BALB/c mouse cardiac allografts were treated with unmodified ERCs or anti‐CD73 monoclonal antibodies (mAb) pretreated ERCs, respectively. It has been found that CD73 expression was critical to ERC‐induced attenuation of graft pathology. The blockage of CD73 expression on ERCs was related to the percentage decline of tolerogenic dendritic cells (Tol‐DCs), macrophages type 2 (M2), and regulatory T cells (Tregs). As compared with anti‐CD73 mAb pretreated ERCs group, CD73 expressing ERCs significantly increased the level of anti‐inflammatory cytokine IL‐10 but decreased levels of pro‐inflammatory cytokines including IFN‐γ and TNF‐α. In addition, CD73 expressing ERCs showed tissue protective function via the regulation of adenosine receptor expression which was related to the infiltration of CD4+ and CD8+ cells in the allografts. Furthermore, significant increase of A2B receptors in the cardiac allograft was also associated with CD73 expressing ERC‐induced prolongation of cardiac allograft survival., Ecto‐5′‐nucleotidase (CD73) expression is critical to therapeutic effects of human endometrial regenerative cells in inhibition of cardiac allograft rejection in mice. The CD73 expression on human endometrial regenerative cells mainly affects three aspects: immune cells, cytokines, and the tissue expression of adenosine receptors.

Bombyx mori nucleopolyhedrovirus (BmNPV) infection causes a series of physiological and pathological changes in Bombyx mori (B. mori). Here, a metabolomic study of the innate immunity organs including hemolymph, fat body, and midgut of the silkworm strain Dazao following BmNPV challenge was conducted to reveal the metabolic variations in B. mori. Compared to the control, 4964 and 4942 features with 4077 and 4327 high-quality features were generated under positive and negative modes, respectively, from BmNPV-infected larvae. The principal component analysis and supervised learning method using partial least squares discrimination analysis demonstrated good analytical stability and experimental reproducibility of the metabolic profiles. Based on database annotations, a total of 296, 108, and 215 differential expressed metabolites (DEMs) were identified from BmNPV-infected group of hemolymph, fat body, and midgut, respectively, which were all mainly grouped into carboxylic acids and derivatives, fatty acyls, and glycerophospholipids. Kyoto Encyclopedia of Genes and Genomes Database enrichment analysis of the DEMs showed that amino acid metabolism was increased at 24 h after BmNPV infection. BmNPV induction was adopted to significantly alter a series of immune-related pathways including phospholipase D signaling pathway, FoxO signaling pathway, metabolism of xenobiotics by cytochrome P450, melanogenesis, membrane transport, carbohydrate metabolism, and lipid metabolism. The different levels of expression of several DEMs including l-glutamate, naphthalene, 3-succinoylpyridine 1-acyl-sn-glycerol 3-phosphate, and l-tyrosine which were involved in those pathways exhibited the immune responses of B. mori to BmNPV infection. Our findings are valuable for a better understanding of the antiviral mechanism of B. mori underlying the interaction between the silkworm and BmNPV.

Background Ulcerative colitis (UC) is a chronic, relapsing, and non-specific inflammatory bowel disease, and the current treatment strategies were mainly used to relieve symptoms or for maintenance. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and have been demonstrated to alleviate multiple immune-dysregulation diseases. Pro-inflammatory stimuli were reported to enhance the immunosuppressive functions of ERCs, but the mechanism underlined is not fully understood. Here, we have designed this study to investigate the therapeutic effects of IL-1β-primed ERCs in the attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. PBS (200 μL), ERCs, and IL-1β-primed ERCs (10ng/mL, 48 h) were injected (1 million/mouse/day, i.v.) on day 2, 5, and 8, respectively. Colonic and splenic samples were harvested on day 10 after DSS induction. Results It was found that IL-1β-primed ERC treatment markedly attenuated colonic damage, body weight loss, and colon length shortening in colitis mice. Compared with other treatments, cell populations of CD4+IL-4+Th2 cells, CD4+CD25+FOXP3+ regulatory T cells (Tregs), and CD68+CD206+ macrophages in spleens were also significantly upregulated in the IL-1β-primed ERC-treated group (p < 0.05). In addition, lower expression of pro-inflammatory (IFN-γ, IL-17, TNF-α, and IL-6), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) were detected in colons in the IL-1β-primed ERC-treated group (p < 0.05 vs. other groups). Importantly, we also found that different generations of ERCs had an overall lower secretion of Dickkopf-1 (DKK1) by IL-1β pre-stimulation (p < 0.05) and a higher expression of β-catenin in colonic and splenic tissues after the administration of IL-1β-primed ERCs. Conclusions This study has demonstrated that IL-1β pre-stimulation effectively downregulated DKK1 expression in ERCs, which in turn promoted the wnt/β-catenin pathway activation in colonic and splenic tissues. Consequently, IL-1β-primed ERCs exhibited an enhanced therapeutic effect in the attenuation of DSS-induced colitis.

Background We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1low-ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1low-ERCs) and glucocorticoid-treated ERCs (DKK1high-ERCs) were injected (1 million/mouse/day, i.v.) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction. Results It was found that DKK1low-ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4+IL-4+Th2, CD4+CD25+FOXP3+Treg, and CD68+CD206+macrophages in spleens were also significantly upregulated in DKK1low-ERC group (p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1low-ERC group (p < 0.01 vs. other groups). Conclusions DKK1low-ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.

Background. Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) shows some beneficial roles to ameliorate IRI, their effects are limited. In this study, the preventative effects of IL-37 gene-modified MSCs (IL-37-MSCs) on intestinal IRI are investigated. Methods. Intestinal IRI model was established by occluding the superior mesenteric artery for 30 minutes and then reperfused for 72 hours in rats. Forty adult male Sprague-Dawley rats were randomly divided into the sham control, IL-37-MSC-treated, MSC-treated, recombinant IL-37- (rIL-37-) treated, and untreated groups. Intestinal damage was assessed by H&E staining. The levels of gut barrier function factors (diamine oxidase and D-Lactate) and inflammation cytokine IL-1β were assayed using ELISA. The synthesis of tissue damage-related NLRP3 inflammasome and downstream cascade reactions including cleaved caspase-1, IL-1β, and IL-18 was detected by western blot. The mRNA levels of proinflammatory mediators IL-6 and TNF-α, which are downstream of IL-1β and IL-18, were determined by qPCR. Data were analyzed by one-way analysis of variance (ANOVA) after the normality test and followed by post hoc analysis with the least significant difference (LSD) test. Results. IL-37-MSCs were able to migrate to the damaged tissue and significantly inhibit intestinal IRI. As compared with MSCs or the rIL-37 monotherapy group, IL-37-MSC treatment both improved gut barrier function and decreased local and systemic inflammation cytokine IL-1β level in IRI rats. In addition, tissue damage-related NLRP3 and downstream targets (cleaved caspase-1, IL-1β, and IL-18) were significantly decreased in IRI rats treated with IL-37-MSCs. Furthermore, IL-1β- and IL-18-related proinflammatory mediator IL-6 and TNF-α mRNA expressions were all significantly decreased in IRI rats treated with IL-37-MSCs. Conclusion. The results suggest that IL-37 gene modification significantly enhances the protective effects of MSCs against intestinal IRI. In addition, NLRP3-related signaling pathways could be associated with IL-37-MSC-mediated protection.

Reduction of hydrogen content in deuterium-fueled fusion plasmas is important not only to avoid diluting reacting core deuterons but also so as to allow the optimization of hydrogen-minority-heating efficiency in those fusion devices which employ ion-cyclotron-radio-frequency heating systems. In EAST, the amount of hydrogen released from plasma-facing components has been shown to depend strongly on both their composition and their temperature. As measured by thermal desorption spectroscopy, the hydrogen inventory in graphite – used in EAST as lower divertor material – has been determined to be >25 times larger than that of tungsten which comprises the upper divertor. This difference in hydrogen inventory is attributed mostly to the intrinsically porous nature of bulk graphite. Thus the main source of hydrogen release into EAST discharges was identified as the graphite tiles used in the lower divertor. The hydrogen content in EAST plasmas were clearly reduced by first employing a high-temperature vacuum baking of all graphite tiles and then renewing a 100–200 μm thick SiC coating before an EAST experimental run campaign. Subsequent active surface conditioning of all wall components with elemental silicon and then with elemental lithium were seem to again reduce the plasma hydrogen content significantly – with lithium proving to be more effective than silicon. Combining these several techniques, H/(H + D) levels as low as ∼3% have been achieved in EAST discharges. Additionally, the effects of lithium thickness on H surface implantation and retention has been re-examined semi-quantitatively using data from a previous run campaign. These data suggest that relatively thick Li films coated on the first wall can effectively isolate the rich source of hydrogen stored in the porous bulk of the underlying graphite from the deuterium-fueled plasma so as to minimize hydrogen release. Finally an operational maneuver whereby a diverted plasma is repetitively switched from an upper single null configuration to a lower single null configuration is presented. This switching maneuver has been shown to suppress hydrogen influx into a 35s-long EAST discharge by alternately mitigating the rise in divertor temperature.

Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells, and their therapeutic potential has been tested in the prevention of renal ischemic reperfusion injury, acute liver injury, ulcerative colitis, and immunosuppression. However, their potential in the induction of transplant tolerance has not been investigated. The present study was undertaken to investigate the efficacy of ERCs in inducing cardiac allograft tolerance and the function of stromal cell-derived factor-1 (SDF-1) in the ERC-mediated immunoregulation. The inhibitory efficacy of human ERCs in the presence or absence of rapamycin was examined in both mouse cardiac allograft models between BALB/c (H-2d ) donors and C57BL/6 (H-2b ) recipients and in vitro cocultured splenocytes. AMD3100 was used to inhibit the function of SDF-1. Intragraft antibody (IgG and IgM) deposition and immune cell (CD4+ and CD8+ ) infiltration were measured by immunohistochemical staining, and splenocyte phenotypes were determined by fluorescence-activated cell sorting analysis. The results showed that ERC-based therapy induced donor-specific allograft tolerance, and functionally inhibiting SDF-1 resulted in severe allograft rejection. The negative effects of inhibiting SDF-1 on allograft survival were correlated with increased levels of intragraft antibodies and infiltrating immune cells, and also with reduced levels of regulatory immune cells including MHC class IIlow CD86low CD40low dendritic cells, CD68+ CD206+ macrophages, CD4+ CD25+ Foxp3+ T cells, and CD1dhigh CD5high CD83low IL-10high B cells both in vivo and in vitro. These data showed that human ERC-based therapy induces cardiac allograft tolerance in mice, which is associated with SDF-1 activity, suggesting that SDF-1 mediates the immunosuppression of ERC-based therapy for the induction of transplant tolerance. Stem Cells Translational Medicine 2017;6:1997-2008.

Endometrial regenerative cells (ERCs) are a new type of mesenchymal-like stromal cells, and their therapeutic potential has been tested in a variety of disease models. SDF-1/CXCR4 axis plays a chemotaxis role in stem/stromal cell migration. The aim of the present study was to investigate the role of SDF-1/CXCR4 axis in the immunomodulation of ERCs on the experimental colitis. The immunomodulation of ERCs in the presence or absence of pretreatment of SDF-1 or AMD3100 was examined in both in vitro cell culture system and dextran sulphate sodium-induced colitis in mice. The results showed that SDF-1 increased the expression of CXCR4 on the surface of ERCs. As compared with normal ERCs, the SDF-1-treated, CXCR4 high-expressing ERCs more significantly suppressed dendritic cell population as well as stimulated both type 2 macrophages and regulatory T cells in vitro and in vivo. Meanwhile, SDF-1-pretreated ERCs increased the generation of anti-inflammatory factors (e.g., IL-4, IL-10) and decreased the pro-inflammatory factors (e.g., IL-6, TNF-α). In addition, SDF-1-pretreated CM-Dil-labeled ERCs were found to engraft to injured colon. Our results may suggest that an SDF-1-induced high level of CXCR4 expression enhances the immunomodulation of ERCs in alleviating experimental colitis in mice.

Endometrial regenerative cells (ERCs) are easily isolated from menstrual blood, and can be cultured in large amounts. Although, ERCs can ameliorate DSS-induced colitis in mice, the molecular mechanism underlying ERCs-mediated immunosuppression is unclear. This study was aimed to assess the function of PD-L1 expressed on ERCs in colitis attenuation. ERCs with and without anti-PD-L1 mAb-pretreatment were administered to mice by injection at 2, 5 and 8 days after colitis induction by DSS treatment. Blood, spleen and colon samples were obtained 15 days post-DSS-induction. Then, clinicopathological alterations, cytokine levels, immune cell types and cell tracking were assessed. ERCs or ERCs preincubated with anti-PD-L1 antibody were co-cultured with splenocytes, whose phenotypes was analyzed by flow cytometry. We found that PD-L1 on ERCs was upregulated by IFN-γ stimulation. The transplanted PKH26-labeled ERCs were engrafted to the lung, liver, spleen and injured colon. Interestingly, ERC-based therapy markedly attenuated mouse colitis, but blockade of PD-L1 on ERCs with a specific monoclonal antibody conferred severe colitis to the animals. These effects of PD-L1 inhibition on colitis were associated with reduced amounts of pro-inflammatory cytokines and infiltrated immune cells, including CD3(+)CD4(+) T lymphocytes, CD3(+)CD8(+) T lymphocytes, CD11c(+)MHC-II(+) Dendritic cells and F4/80(+) macrophages, both in vivo and in vitro, as well as with elevated levels of anti-inflammatory cytokines and regulatory immune cells, including CD4(+)CD25(+)Foxp3(+) Tregs and F4/80(+)CD206(+) macrophages. These findings demonstrated that ERCs-based treatment promotes immune tolerance in mouse colitis, in association with PD-L1, thus indicating that PD-L1 modulates immunosuppression by ERCs.

Sleep deprivation is reported to cause oxidative stress and is hypothesized to induce subsequent aging-related diseases including chronic inflammation, Alzheimer’s disease, and cardiovascular disease. However, how sleep deprivation contributes to the pathogenesis of sleep deficiency disorder remains incompletely defined. Accordingly, more effective treatment methods for sleep deficiency disorder are needed. Thus, to better understand the detailed mechanism of sleep deficiency disorder, a sleep deprivation mouse model was established by the multiple platform method in our study. The accumulation of free radicals and senescence-associated secretory phenotype (SASP) was observed in the sleep-deprived mice. Moreover, our mouse and human population-based study both demonstrated that telomere shortening and the formation of telomere-specific DNA damage are dramatically increased in individuals suffering from sleeplessness. To our surprise, the secretion of senescence-associated cytokines and telomere damage are greatly improved by folic acid supplementation in mice. Individuals with high serum baseline folic acid levels have increased resistance to telomere shortening, which is induced by insomnia. Thus, we conclude that folic acid supplementation could be used to effectively counteract sleep deprivation-induced telomere dysfunction and the associated aging phenotype, which may potentially improve the prognosis of sleeplessness disorder patients.

Determination of tritium production in the liquid blanket of fusion reactor is necessary for the nuclear material accounting system. In this paper, an equivalent measurement method is proposed, which is based on measuring the isotope abundance of lithium before and after irradiation. Theoretical analysis of the feasibility of the method is carried out, including complex nuclear reactions of neutron and lithium, the influence of the lead matrix, and the influence of gradient of the lithium isotope abundance before and after irradiation.

China low activation martensitic (CLAM) steel has been chosen as the primary structural material in the designs of dual function lithium-lead (DFLL) blanket for fusion reactors, China helium cooled ceramic breeder (HCCB) test blanket module (TBM) for ITER and China fusion engineering test reactor (CFETR) blanket. The cooling components of the blankets are designed with high density cooling channels (HDCCs) to remove the high nuclear thermal effectively. Hence, the welding spacing among the channels are small. In this paper, the welded joints of CLAM steel with different weld spacings have been fabricated with electron beam welding (EBW). The weld spacing was designed to be 2 mm, 3 mm, 4 mm, 6 mm and 8 mm. The microstructure and mechanical properties such as microhardness, impact and tensile were investigated at different welding spacing for both conditions of as-welded and post weld heat treatment (PWHT). The PWHT is tempering at 740 °C for 120 min. The results showed that the grain size in the heat affected zone (HAZ) increased with the increasing weld spacing, and the joint with small weld spacing had a better performance after PWHT. This work would give useful guidance to improve the preparation of the cooling components of blanket.

The thermal aging effects on mechanical properties and microstructures in China low-activation martensitic steel have been tested by aging at 550 °C for 2,000 hours, 4,000 hours, and 10,000 hours. The microstructure was analyzed by scanning and transmission electron microscopy. The results showed that the grain size and martensitic lath increased by about 4 μm and 0.3 μm, respectively, after thermal exposure at 550 °C for 10,000 hours. MX type particles such as TaC precipitated on the matrix and Laves-phase was found on the martensitic lath boundary and grain boundary on aged specimens. The mechanical properties were investigated with tensile and Charpy impact tests. Tensile properties were not seriously affected by aging. Neither yield strength nor ultimate tensile strength changed significantly. However, the ductile–brittle transition temperature of China low-activation martensitic steel increased by 46 °C after aging for 10,000 hours due to precipitation and grain coarsening.

Two newly developed integrated infrared and visible tangential wide-angle (WA) viewing systems (VS) have been mounted in the Experimental Advanced Superconducting Tokamak (EAST) to provide temperature measurement and hot spot monitoring of the plasma facing components (PFC) for machine protection and further physics studies of various plasma parameters such as the scrap-off layer power fall-off length λ q , the peak heat flux on the divertor target q p e a k etc. The systems use endoscopes with reflective optics to obtain a wide-angle view (49.5°×62°). Via endoscope, the 3-5 μm middle wave infrared camera and the visible camera with spectral range of 400−700 nm, the WAVS could provide simultaneous real time infrared and visible image data of the first wall components in the same field of view (FOV). Some key components e.g. the 4.6 GHz lower hybrid wave (LHW) antenna, the ion cyclotron resonance frequency (ICRF) antenna, the high field side region of neutral beam injection in port F, and approximately 78° more toroidal coverage of outer divertor regions with 27° more toroidal coverage of inner divertor regions are firstly covered by the camera system. This paper presents the diagnostic description of the newly developed WAVS and preliminary experimental results observed including fast-ion losses to the inner wall during neutral beam injection (NBI), single edge localized mode (ELM) observation on upper outer divertor, hot spots on antenna guide limiters and temperature and heat flux distribution on the tungsten and graphite divertor targets in EAST.

INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b) donors to BALB/c (H-2d) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 × 106 cells) at the same time. The tumor size and pathological changes, cell populations and cytokine profiles were evaluated at day 14 post-transplantation. RESULTS: The results showed that as compared to non-transplant group, the allogenic immune response in the skin-grafting group inhibited the growth of tumors, which was significantly associated with increased numbers of intra-tumor infiltrating lymphocytes, increased populations of CD11c+MHC-classII+CD86+ DCs, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, as well as decreased percentage of CD4+CD25+Foxp3+ T cells in the spleens. In addition, the levels of serum IgM and IgG, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were significantly higher within the tumor in skin transplant groups than that in non-transplant group. CONCLUSIONS: Allogenic skin transplantation suppresses the tumor growth through activating the allogenic immune response, and it may provide a new immunotherapy option for the clinical refractory tumor treatment.

Vasculopathy is one of the primary pathological changes in chronic rejection of vascularized allograft transplantation. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells with immunosuppressive effect. B7-H1 is a negative costimulator that mediates active immune suppression. The aim of this study was to investigate the requirement of B7-H1 in the immunoregulation of ERCs in preventing transplant vasculopathy of aorta allografts. The results showed that B7-H1 expression on ERCs was upregulated by IFN-γ in a dose-dependent manner and it was required for ERCs to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro. ERCs could alleviate transplant vasculopathy, as the intimal growth of transplanted aorta was limited, and the preventive effects were correlated with an increase in the percentages of CD11c+MHC class IIlowCD86low dendritic cells, CD68+CD206+ macrophages, and CD4+CD25+Foxp3+ T cells, as well as a decrease in the percentages of CD68+ macrophages, CD3+CD4+ T cells, CD3+CD8+ T cells, and donor-reactive IgM and IgG antibodies. Moreover, overexpression of B7-H1 by IFN-γ can promote the immunosuppressive effect of ERCs. These results suggest that overexpression of B7-H1 stimulated by IFN-γ is required for ERCs to prevent the transplant vasculopathy, and this study provides a theoretical basis for the future clinical use of human ERCs.

Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studies of ERCs in idiopathic pulmonary fibrosis (IPF) have not been reported. The present study was designed to examine the effects of ERCs on bleomycin-induced pulmonary fibrosis. All IPF models in C57BL/6 mice were induced by administrating 5 mg/kg bleomycin in PBS intratracheally. ERCs were isolated from healthy female menstrual blood and were injected (1 million/mouse, i.v.) 24 hours after induction. Wet/dry weight ratio assay, hydroxyproline content, pathological and immunohistological changes, MDA content, T-SOD activity, cytokine profiles, and RT-qPCR analysis were assessed 2 weeks after disease induction. The results showed that ERC treatment significantly decreased the wet/dry ratio and reduced collagen deposition. Histological analyses, Masson staining, and hydroxyproline content analysis indicated that ERCs could reduce collagen fiber production. Immunohistochemical staining revealed lower expression of TGF-βafter ERC treatment. Furthermore, mice treated with ERCs had lower levels of IL-1βand TNF-α, but a higher level of IL-10 in both the lung and serum. Gene expression analysis demonstrated that ERCs potently suppressed the proapoptotic gene Bax, while increasing the antiapoptotic gene Bcl-2 and antifibrosis genes HGF and MMP-9. Our results indicate that human ERCs protected the lung from pulmonary fibrosis in mice through immunosuppressive and antifibrosis effects. Moreover, these findings formed a foundation for the further use of ERCs in clinical treatment.

Background: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by chronic inflammation of colon. It is commonly believed that the imbalance of immune system and overwhelming production of cytokines are involved in the pathogenesis of UC. Recent studies demonstrated that interleukin-35 (IL-35), a key player in the regulation of inflammation, has been identified as potential therapeutic target to treat UC. However, conventional intravenous administration is costly and inconvenient. The present study was designed to establish a novel IL-35 delivery system and investigate its therapeutic effects on dextran sulfate sodium (DSS)-induced experimental colitis in mice for the first time. Methods: An engineered Escherichia coli (E. coli/IL-35) expressing IL-35 was constructed. Adult male BALB/c mice randomly got the oral administration of E. coli/IL-35, empty plasmid-transformed E. coli (E. coli0) or PBS for treatment following ingestion of 3% DSS solution for 5 days. Normal mice were used as control group. Colonic and splenic tissues were collected on day 10 post-DSS-induction. Clinical signs, disease activity index (DAI), pathological and immunohistological changes, cytokine profiles and cell populations were evaluated. Results: Intragastric administration of E. coli/IL-35 effectively protected the colitis mice from DSS assimilation including weight loss and colon shortening. Pathological analysis showed significantly lower DAI score and much less intra-colon infiltration of neutrophils and CD3+ cells in the IL-35 treated group. Moreover, E. coli/IL-35-treated mice demonstrated much less CD4+ IL-17A+ Th17 cells and a higher level of CD4+CD25+Foxp3+ Tregs in spleen and mesenteric lymph nodes, as well as increased colon and serum level of IL-10 and IL-35 and decreased levels of IL-6. Conclusions: Our study showed that E. coli/IL-35 as a novel oral IL-35 delivery system alleviated inflammatory damage of colonic tissue in the colitic mice. Genetic therapeutic strategies using engineered E. coli encoding immunoregulatory cytokines may provide a potential approach for the treatment of IBD.

Background The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)–induced acute liver injury (ALI). Methods An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction. Results ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver. Conclusions Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.

To investigate the effect of transfection of 5-aza cytidine (5-aza) induced BMSCs that were transfected with Ad. ANG ex vivo into infarcted myocardium.Lewis rat BMSCs were cultured in vitro and incubated together with 5-aza (3 micro mol/l) for 24 hours, and the induced BMSCs were transfected with Ad. ANG with a infection multiple of 50. ELISA method was applied to assay the expression and secretion of ANG in the medium. Then such BMSCs expressing ANG were transplanted into the ischemic myocardium of 14 Lewis rats whose left descending branch of coronary artery had been ligated 4 weeks ago (Group I). Eight rats with infarcted myocardium were transplanted with such BMSCs too (group II). Another eight rats received only Ad. ANG injection (group III). Twelve rats receiving serum-free medium injection were used as controls (Group IV). Four weeks after the ligation of LDA (for group I) and 4 weeks after the beginning of experiment (for all groups), the parameters of heart function, such as ejection fraction (EF) and end-diastole volume of left heart (EDLV), were examined by echocardiography. Four weeks after the beginning of experiment, the rats were killed, and the survival and differentiation of transplanted BMSCs and angiogenesis were observed by immunohistochemistry and transmission electron micrography.One day after the beginning of experiment, the concentration of ANG in the supernatant of medium was 162 +/- 10 pg/ml, significantly higher than that in the supernatant of medium in control group (86 +/- 5 pg/ml, P0.01). The concentration of ANG gradually increased and reached its peak at the 4th to 7th day; ANG could still be assayed 15 days later. 4 weeks after the transplantation, most of the 5-aza-induced BMSCs in group I and group II had differentiated into cardiomyogenic cells in the transplanted area. The EF value was 0.42 +/- 0.114 weeks after ligation of LAD, and was 0.69 +/- 0.034 weeks after the transplantation in group I. The EF value was 0.46 +/- 0.06 at the beginning of experiment and was 0.64 +/- 0.144 weeks after the transplantation in group II. The improvement of EF in Group I was significantly than that in other 3 groups (P0.05 or P0.01). The number of new vessels in group I was 36.3/high-power field (HPF), significantly higher than those in the other three groups (10.5/HPF in Group II, 23.1/HPF in Group III, and 0.9/HPF in Group IV).Induced by 5-aza, BMSCs differentiate into cardiomyogenic cells in infracted myocardium. ANG-expressing BMSCs transplantation is one of the safe and beneficial new strategies for repairing damaged myocardium and enhancing angiogenesis in ischemic myocardium.

To study the morphologic classification and its clinical significance of giant left atrium (GLA) combined with mitral valvular disease.Between January 1993 and December 1999, a total of 62 consecutive patients with mitral valvular disease, whose preoperative left atrial endodiastolic volume index/= 300 ml/m(2) or endosystolic diameter/= 6.0 cm, were enrolled as research candidates. Morphologically, GLA was classified by Q Hierarchical cluster analysis according to the right or left side cardiothoracic ratio of the left atrium (r- or l-LATR) on an anteroposterior chest roentgenogram and the ratio of the distant diameter of the left main bronchus to the approximate diameter of the left main bronchus (LBDd/Dp) or to the trachea (LB/TR) on an left anterior oblique chest roentgenogram.According to r-LATR and l-LATR, the morphology of GLA was classified clinically into three types: type L (l-LATR/= 0.6 and r-LATR0.58), type R (r-LATR/= 0.58 and l-LATR0.6) and type B (r-LATR/= 0.58 and l-LATR/= 0.6). According to LBDd/Dp and LB/TR, GLA in type L and B was further classified into two subtypes, respectively: left posterior downward type (L(I) and B(I)), in which LBDd/Dp is equal or exceeds 0.38 or LB/TR is equal or exceeds 0.33, and left posterior upward type (L(II) and B(II)), in which LBDd/Dp is less than 0.38 or LB/TR less than 0.33.The morphologic classification of GLA may represent the main pathophysiological changes of GLA and might be a guideline for the selection of the optimal plication procedures of GLA in patients with valve diseases.