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The deep learning-based change detection (CD) methods have achieved remarkable progress with remote sensing imagery. These methods mainly rely on complex feature extraction structures and numerous attention mechanisms to realize effective feature extraction and recognition. However, this results in a significant increase in the number of parameters and the training cost of the whole network. The increase in parameterization can also lead to the degradation of network performance when the amount of training data is insufficient. Thus, it is still promising and challenging to perform reliable CD results through light network design. In this article, we propose a lightweight full-scale hybrid network. The network is comprised of a convolutional neural network (CNN), multilayer perceptron (MLP), and transformer, and it is capable of achieving high performance in CD tasks with a lightweight structure. First, the MLP structures are integrated into the basic network to extract global feature information, compensating for the information loss caused by the convolutional operations of CNN. Second, a full-scale difference module is designed to sufficiently extract the feature information and ensure enough feedforward information. Third, a lightweight transformer is appended at the end of the network to accomplish the spatial-temporal correlation of features, which effectively enhances the quality of the final extracted features. Experimental results on three classical CD datasets show that the proposed method outperforms the state-of-the-art methods.

Abstract Background Alzheimer's disease presents an abnormal cognitive behavior. TgCtwh6 is one of the predominant T. gondii strains prevalent in China. Although T. gondii type II strain infection can cause host cognitive behavioral abnormalities, we do not know whether TgCtwh6 could also cause host cognitive behavioral changes. So, in this study, we will focus on the effect of TgCtwh6 on mouse cognitive behavior and try in vivo and in vitro to explore the underlying mechanism by which TgCtwh6 give rise to mice cognitive behavior changes at the cellular and molecular level. Methods C57BL/6 mice were infected orally with TgCtwh6 cysts. From day 90 post-infection on, all mice were conducted through the open field test and then Morris water maze test to evaluate cognitive behavior. The morphology and number of cells in hippocampus were examined with hematoxylin-eosin (H&E) and Nissl staining; moreover, Aβ protein in hippocampus was determined with immunohistochemistry and thioflavin S plaque staining. Synaptotagmin 1, apoptosis-related proteins, BACE1 and APP proteins and genes from hippocampus were assessed by western blotting or qRT-PCR. Hippocampal neuronal cell line or mouse microglial cell line was challenged with TgCtwh6 tachyzoites and then separately cultured in a well or co-cultured in a transwell device. The target proteins and genes were analyzed by immunofluorescence staining, western blotting and qRT-PCR. In addition, mouse microglial cell line polarization state and hippocampal neuronal cell line apoptosis were estimated using flow cytometry assay. Results The OFT and MWMT indicated that infected mice had cognitive behavioral impairments. The hippocampal tissue assay showed abnormal neuron morphology and a decreased number in infected mice. Moreover, pro-apoptotic proteins, as well as BACE1, APP and Aβ proteins, increased in the infected mouse hippocampus. The experiments in vitro showed that pro-apoptotic proteins and p-NF-κBp65, NF-κBp65, BACE1, APP and Aβ proteins or genes were significantly increased in the infected HT22. In addition, CD80, pro-inflammatory factors, notch, hes1 proteins and genes were enhanced in the infected BV2. Interestingly, not only the APP and pro-apoptotic proteins in HT22, but also the apoptosis rate of HT22 increased after the infected BV2 were co-cultured with the HT22 in a transwell device. Conclusions Neuron apoptosis, Aβ deposition and neuroinflammatory response involved with microglia polarization are the molecular and cellular mechanisms by which TgCtwh6 causes mouse cognitive behavioral abnormalities. Graphical Abstract

Abstract Background Toxoplasma gondii is a neurotropic single-celled parasite that can infect mammals, including humans. Central nervous system infection with T. gondii infection can lead to Toxoplasma encephalitis. Toxoplasma infection can cause endoplasmic reticulum (ER) stress and unfolded protein response (UPR) activation, which ultimately can lead to apoptosis of host cells. The dense granule protein GRA3 has been identified as one of the secretory proteins that contribute to the virulence of T. gondii; however, the mechanism remains enigmatic. Methods The expression of the GRA3 gene in RH, ME49, Wh3, and Wh6 strains was determined using quantitative real-time polymerase chain reaction (qRT–PCR). pEGFP-GRA3Wh6 was constructed by inserting Chinese 1 Wh6 GRA3 (GRA3Wh6) cDNA into a plasmid encoding the enhanced GFP. Mouse neuro2a (N2a) cells were transfected with either pEGFP or pEGFP-GRA3Wh6 (GRA3Wh6) and incubated for 24–36 h. N2a cell apoptosis and ER stress-associated proteins were determined using flow cytometry and immunoblotting. Furthermore, N2a cells were pretreated with GSK2656157 (a PERK inhibitor) and Z-ATAD-FMK (a caspase-12 inhibitor) before GRA3Wh6 transfection, and the effect of the inhibitors on GRA3Wh6-induced ER stress and apoptosis were investigated. Results GRA3 gene expression was higher in the less virulent strains of type II ME49 and type Chinese 1 Wh6 strains compared with the virulent strains of type I RH strain and type Chinese 1 Wh3 strain. Transfection with GRA3Wh6 plasmid induced neuronal apoptosis and increased the expression of GRP78, p-PERK, cleaved caspase-12, cleaved caspase-3, and CHOP compared with the control vector. Pretreatment with GSK2656157 and Z-ATAD-FMK decreased apoptosis in N2a cells, and similarly, ER stress- and apoptosis-associated protein levels were significantly decreased. Conclusion GRA3 induces neural cell apoptosis via the ER stress signaling pathway, which could play a role in toxoplasmic encephalitis. Graphical Abstract

Synthetic aperture radar (SAR) imagery has the advantages of all-day and all-weather observation. However, due to the imaging mechanism of microwaves, it is difficult for nonexperts to interpret SAR images. Transferring SAR imagery into optical imagery can better improve the interpretation of SAR data and support the further fusion research of multi-source remote sensing. Methods based on generative adversarial networks (GAN) have been proven to be effective in SAR-to-optical translation tasks. To further improve the translation results of SAR data, we propose a method of an adjacent dual-decoder UNet (ADD-UNet) based on conditional GAN (cGAN) for SAR-to-optical translation. The proposed network architecture adds an adjacent scale of the decoder to the UNet, and the multi-scale feature aggregation of the two decoders improves structures, details, and edge sharpness of generated images while introducing fewer parameters compared with UNet++. In addition, we combine multi-scale structure similarity (MS-SSIM) loss and L1 loss as loss functions with cGAN loss together to help preserve structures and details. The experimental results demonstrate the superiority of our method compared with several state-of-the-art methods.

Abstract Background The predominant genotype of Toxoplasma in China is the Chinese 1 (ToxoDB#9) lineage. TgCtwh3 and TgCtwh6 are two representative strains of Chinese 1, exhibiting high and low virulence to mice, respectively. Little is known regarding the virulence mechanism of this non-classical genotype. Our previous RNA sequencing data revealed differential mRNA levels of TgMIC1 in TgCtwh3 and TgCtwh6. We aim to further confirm the differential expression of TgMIC1 and its significance in this atypical genotype. Methods Quantitative real-time PCR was used to verify the RNA sequencing data; then, polyclonal antibodies against TgMIC1 were prepared and identified. Moreover, the invasion and proliferation of the parasite in HFF cells were observed after treatment with TgMIC1 polyclonal antibody or not. Results The data showed that the protein level of TgMIC1 was significantly higher in high-virulence strain TgCtwh3 than in low-virulence strain TgCtwh6 and that the invasion and proliferation of TgCtwh3 were inhibited by TgMIC1 polyclonal antibody. Conclusion Differential expression of TgMIC1 in TgCtwh3 and TgCtwh6 may explain, at least partly, the virulence mechanism of this atypical genotype.

Interferon-γ (IFN-γ)-activated macrophages restrain the replication of intracellular parasites and disrupt the integrity of vacuolar pathogens. The growth of the less virulent type II strain of Toxoplasma gondii (such as ME49) was strongly inhibited by IFN-γ-activated murine macrophages. However, the mechanism of resistance is poorly understood. Immunity-related GTPases (IRGs) as well as guanylate-binding proteins (GBPs) contributed to this antiparasitic effect. Previous studies showed the cassette of autophagy-related proteins including Atg7, Atg3, and Atg12-Atg5-Atg16L1 complex, plays crucial roles in the proper targeting of IFN-γ effectors onto the parasitophorous vacuole (PV) membrane of Toxoplasma gondii and subsequent control of parasites. TgCDPK3 is a calcium dependent protein kinase, located on the parasite periphery, plays a crucial role in parasite egress. Herein, we show that the less virulent strain CDPK3 (ME49, type II) can enhance autophagy activation and interacts with host autophagy proteins Atg3 and Atg5. Infection with CDPK3-deficient ME49 strain resulted in decreased localization of IRGs and GBPs around PV membrane. In vitro proliferation and plaque assays showed that CDPK3-deficient ME49 strain replicated significantly more quickly than wild-type parasites. These data suggested that TgCDPK3 interacts with the host Atg3 and Atg5 to promote the localization of IRGs and GBPs around PV membrane and inhibits the intracellular proliferation of parasites, which is beneficial to the less virulent strain of Toxoplasma gondii long-term latency in host cells.

Height estimation from a single Synthetic Aperture Radar (SAR) image has demonstrated a great potential in real-time environmental monitoring and scene understanding. The projection of a single 2D SAR image from multiple 3D height maps is an ill-posed problem in mathematics. Although Unet has been widely used for height estimation from a single image, the ill-posed problem cannot be completely resolved, and it leads to deteriorated performance with limited training data. This paper tackles the problem by Unet with the help of supplementary sparse height information and proxyless neural architecture search (PDPNAS) for Unet. The sparse height, which can be accepted from low-resolution SRTM or LiDAR products, is included as the supplementary information and is helpful to improve the accuracy of the estimated height map, especially in mountain areas with a wide range of elevations. In order to explore the effect of sparsity of sparse height on the estimated height map, a parameterized method is proposed to generate sparse height with a different sparse ratio. In order to further improve the accuracy of the estimated height map from a single SAR imagery, PDPNAS for Unet is proposed. The optimal architecture for Unet can be searched by PDPNAS automatically with the help of a depth-aware penalty term p. The effectiveness of our approach is evaluated by visual and quantitative analysis on three datasets from mountain areas. The root mean squared error (RMSE) is reduced by 90.30% through observing only 0.0109% of height values from a low-resolution SRTM product. Furthermore, the RMSE is reduced by 3.79% via PDPNAS for Unet. The research proposes a reliable method for estimating height and an alternative method for wide-area DEM mapping from a single SAR image, especially for the implementation of real-time DEM estimation in mountain areas.

Synthetic aperture radar (SAR) has been widely applied in oil spill detection on the sea surface due to the advantages of wide area coverage, all-weather operation, and multi-polarization characteristics. Sentinel-1 satellites can provide dual-polarized SAR data, and they have high potential for successful application to oil spill detection. However, the characteristics of the sea surface and oil film on different images are not the same when imaging at different locations and in different conditions, which leads to the inconsistent accuracy of these images with the application of the current oil spill detection methods. In order to avoid the above limitation, we propose an oil spill detection method using image stretching based on superpixels and a convolutional neural network. Experiments were carried out on eight Sentinel-1 dual-pol data, and the optimal superpixel number and image stretching parameters are discussed. Mean intersection over union (MIoU) was used to evaluate classification accuracy. The proposed method could effectively improve the classification accuracy; when the expansion and inhibition coefficients of image stretching were set to 1.6 and 1.2 respectively, the experiments achieved a maximum MIoU of 85.4%, 7.3% higher than that without image stretching.

Investigation of subsidence situations is important for the design of railway lines. Traditional geological investigations are expensive. Multi-temporal InSAR (MT-InSAR) analysis has shown great potential for detecting subsidence areas along large-scale manmade linear features (LMLFs). The disadvantage of applying high-resolution SAR data such as that from TerraSAR-X and COSMO-SkyMed data is the high cost. By contrast, the free and open data from Sentinel-1 A/B offer an unprecedented opportunity for InSAR applications. Despite these advantages, research investigating the potential for monitoring subsidence along LMSFs using multi-temporal Sentinel-1 InSAR data at the design stage of LMSFs is limited. This paper explores the monitoring ability of MT-InSAR analysis with Sentinel-1 A/B multi-temporal data in an experiment along the planned Jakarta-Bandung high-speed railway in Bandung, Indonesia. Subsidence patterns along the route of the planned high-speed railway were analyzed in detail. By means of validation using 12 leveling points, the root mean square error (RMSE) of the average displacement velocity that was obtained from the MT-InSAR results was found to be 10.31 mm/yr. This paper demonstrates the potential of Sentinel-1 multi-temporal INSAR data to detect potential subsidence areas along planned LMLFs (e.g., the planned high-speed railway that is the focus of this study), serving as a reference for further planning of monitoring subsidence over planned LMLFs.

Imbalance of Th1 and Th2 response at the maternal–fetal interface is considered as a radical event in the pathogenesis of immunity-related pregnant diseases. It has been demonstrated that the ROP16I, a rhoptry protein of Toxoplasma gondii, and the viable parasite with ROP16I may induce M2 macrophage polarization in host innate immunity and may be involved in the adverse pregnant outcomes. However, the mechanisms by which T. gondii-derived effectors subvert the immune tolerance in the pathology of pregnancy remain unclear. Here, we constructed the RH strain with ROP16I deletion (RHΔrop16) to explore the pathogenesis of abnormal pregnancy. We found that C57BL/6 mice infected with RHΔrop16 exhibited the increased resorption of fetuses and more severe adverse pathology of placentae at the early phase of gestation, as compared to the mice infected with RH wild type (RH WT) parasite. Additionally, RHΔrop16 strain infection significantly promoted M1 macrophage phenotypes of CD80 and CD86, and decreased CD206 expression of M2 macrophages, with upregulation of the iNOS and downregulation of the Arg-1 expression in placental homogenates. Simultaneously, the pro-inflammatory cytokines of IL-12 and TNF-α were elevated whereas the anti-inflammatory cytokine of TGF-β1 was dampened. Moreover, the p38α mitogen-activated protein kinase (p38α MAPK) was notably phosphorylated in placental macrophages infected with both RHΔrop16 and RH WT strains compared with the control. Taken together, our findings indicated that ROP16I deletion of type I RH strain may cause exacerbated adverse pregnant outcomes, which is attributable to subversion of the maternal immune tolerance due to the increased pro-inflammatory cytokines in the pregnant animals. The results also suggest that ROP16I might be a protective factor and other T. gondii-derived molecules might be involved in the M1–Th1 biased pathological process in aberrant pregnancy at the early phase of gestation.

Icariin is a main component of the Chinese medicinal plant Epimedium brevicornu Maxim, exhibits potent activity against inflammatory diseases. Our previous data demonstrated the valid bioactivity of icariin on mitigating rodent asthma. Endoplasmic reticulum (ER) stress and nuclear factor-κB (NF-κB) pathway were involved in the pathogenesis of asthma. However, it remains poorly defined that whether icariin could inhibit ER stress and NF-κB mediated apoptosis in asthma and further influence the central neural system. Herein, we investigated the effects of icariin on primary cultured fetal rat hippocampal neurons and OVALPS-OVA induced asthma rat model. Asthma rat models were established by ovalbumin (OVA) and lipopolysaccharide (LPS) intraperitoneal injection and OVA inhalational challenge. Airway resistance was analyzed to evaluate lung function after last challenge and pathological changes were detected on lung tissues. Assessment of inflammatory cells counts in bronchoalveolar lavage fluids (BALF) were performed and ELISA was used to determine levels of interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and interferon-γ in serum. Protein expression of BiP and IRE-1α, XBP-1s and phosphorylation-IκBα (p-IκBα), IκBα, and p65 as well as cytochrome c, caspase-3 (cleaved caspase-3), and caspase-9 (cleaved caspase-9) were tested by Western blot. We found that icariin could remarkably improve pulmonary function and reduce inflammatory cells in the lung, levels of inflammatory cytokines, and ER stress related proteins as well as NF-κB were prominently suppressed by icariin. Our results suggested that icariin had an inhibitory effect on airway inflammation and neuroprotective effect on ER stress and NF-κB mediated apoptosis in asthma rats and cultured fetal rat hippocampal neurons, which may provide new mechanistic insights into the asthma prevention and treatment of icariin.

Abstract Background Toxoplasma gondii, a single-celled parasite commonly found in mammals, has been shown to induce trophoblast cell apoptosis and subsequently cause fetal damage and abortion. Although dense granule protein 15 (GRA15) has been identified as a key component in innate immunity to T. gondii infection and its pathogenesis, its role in host cell apoptosis remains unclarified. Methods Type II GRA15 (GRA15II) cDNA was inserted into a plasmid encoding enhanced green fluorescent protein (pEGFP). Choriocarcinoma JEG-3 cells were transfected with either pEGFP or pEGFP-GRA15II and cultured for 24 h. Cell apoptosis and endoplasmic reticulum stress (ERS) responses were assessed. Inhibitors targeting inositol-requiring kinase 1α (IRE1α; 4μ8C, 100 nM) or c-Jun N-terminal kinase (JNK; SP6000125, 20 μM) were added 12 h after plasmid transfection, followed by testing the effect of GRA15II on ERS. Results When compared to pEGFP, pEGFP-GRA15II transfection facilitated cell apoptosis (P < 0.05), increased mRNA expression of caspase-3, caspase-4, 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP) and X-box binding protein-1 (XBP1) (all P < 0.05), and promoted protein expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax, CHOP, GRP78, phospho-JNK, and phospho-IRE1α (all P < 0.05). The 4μ8C and SP6000125 decreased apoptosis and protein expression of XBP1s, CHOP, TNF receptor-associated factor 2 (TRAF2), phosphorylated apoptosis signal-regulating kinase 1 (ASK1), cleaved caspase-3, phospho-JNK, and Bax (all P < 0.05) in pEGFP-GRA15II transfected cells. Conclusions Toxoplasma GRA15II induced ERS and subsequently caused apoptosis of choriocarcinoma JEG-3 cells.

Abstract Background Toxoplasma gondii is an opportunistic protozoan apicomplexan and obligate intracellular parasite that infects a wide range of animals and humans. Rhoptry proteins 5 (ROP5), ROP16, ROP18 and dense granules 15 (GRA15) are the important effectors secreted by T. gondii which link to the strain virulence for mice and modulate the host’s response to the parasite. Little has been known about these molecules as well as GRA3 in type Chinese 1 strains that show polymorphism among strains of archetypical genotypes. This study examined the genetic diversity of these effectors and its correlated virulence in mice among T. gondii isolates from China. Results Twenty-one isolates from stray cats were detected, of which 15 belong to Chinese 1, and 6 to ToxoDB #205. Wh6 isolate, a Chinese 1 strain, has an avirulent phenotype. PCR-RFLP results of ROP5 and ROP18 presented few variations among the strains. Genotyping of GRA15 and ROP16 revealed that all the strains belong to type II allele except Xz7 which carries type I allele. ROP16 amino acid alignment at 503 locus demonstrated that 17 isolates are featured as type I or type III (ROP16I/III), and the other 4 as type II (ROP16II). The strains investigated may be divided into four groups based on GRA3 amino acid alignment, and all isolates of type Chinese 1 belong to the μ-1 allele except Wh6 which is identical to type II strain. Conclusions PCR-RFLP and sequence alignment analyses of ROP5, ROP16, ROP18, GRA3, and GRA15 in T. gondii revealed that strains with the same genotype may have variations in some of their key genes. GRA3 variation exhibited by Wh6 strain may be associated with the difference in phenotype and pathogenesis.

Abstract Background Congenital infection of Toxoplasma gondii is an important factor causing birth defects. The neural stem cells (NSCs) are found to be one of the target cells for the parasite during development of the brain. As a key virulence factor of the parasite that hijacks host cellular functions, ROP18 has been demonstrated to mediate the inhibition of host innate and adaptive immune responses through specific binding different host immunity related molecules. However, its pathogenic actions in NSCs remain elusive. Results In the present study, ROP18 recombinant adenovirus (Ad-ROP18) was constructed and used to infect C17.2 NSCs. After 3d- or 5d–culture in differentiation medium, the differentiation of C17.2 NSCs and the activity of the Wnt/β-catenin signaling pathway were detected. The results showed that the protein level of βIII-tubulin, a marker of neurons, in the Ad-ROP18-transfected C17.2 NSCs was significantly decreased, indicating that the differentiation of C17.2 NSCs was inhibited by the ROP18. The β-catenin level in the Ad-ROP18-transfected C17.2 NSCs was found to be lower than that in the Ad group. Also, neurogenin1 (Ngn1) and neurogenin2 (Ngn2) were downregulated significantly (P

Bu-Shen-Yi-Qi formula (BSYQF) could suppress chronic airway inflammation according to previous studies. However, there is relatively little direct experimental evidence to evaluate the effects of BSYQF treatment on airway remodeling in chronic asthma. Recent evidence suggests that oxidative stress is involved in airway inflammation and airway remodeling in chronic asthma. BSYQF which includes various of chemical components having antioxidant effects, could be beneficial in attenuating airway remodeling in chronic asthma. The purpose of this study was to elucidate the effect of BSYQF treatment on airway remodeling and investigate its potential mechanisms in chronic asthma. To develop the murine models of chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 8 weeks. BSYQF (5, 10, 20 g raw herbs/kg body weight) or tiotropium bromide (0.1 mM) were administered orally and intranasal instillation, respectively. The effect of BSYQF on pulmonary inflammation and remodeling was evaluated. The parameters of oxidative stress in the lung were analyzed. BSYQF treatment reduced airway hyperresponsiveness (AHR), Th2 response including IL-4, IL-13, and OVA-specific IgE and IgG1, transforming growth factor-β (TGF-β), vascular endothelium growth factor (VEGF), airway inflammation and airway remodeling including smooth muscle thickening and peribronchial collagen deposition. As for oxidative stress, BSYQF treatment reduced reactive oxygen species (ROS), Malondialdehyde (MDA), NO, and the expression of inducible nitric oxide synthase (iNOS), but increased significantly glutathione (GSH) /Oxidized glutathione(GSSH) ratios in the lung, restored mitochondrial ultrastructural changes of bronchial epithelia and ATP levels in the lung.In summary, this study suggested that BSYQF treatment ameliorated airway remodeling and alleviated asthmatic features in chronic asthma models. Anti-inflammatory and antioxidant effect of BSYQF may explain why BSYQF has effects on preventing airway remodeling.

Oil spill detection plays an important role in marine environment protection. Quad-polarimetric Synthetic Aperture Radar (SAR) has been proved to have great potential for this task, and different SAR polarimetric features have the advantages to recognize oil spill areas from other look-alikes. In this paper we proposed an oil spill detection method based on convolutional neural network (CNN) and Simple Linear Iterative Clustering (SLIC) superpixel. Experiments were conducted on three Single Look Complex (SLC) quad-polarimetric SAR images obtained by Radarsat-2 and Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR). Several groups of polarized parameters, including H/A/Alpha decomposition, Single-Bounce Eigenvalue Relative Difference (SERD), correlation coefficients, conformity coefficients, Freeman 3-component decomposition, Yamaguchi 4-component decomposition were extracted as feature sets. Among all considered polarimetric features, Yamaguchi parameters achieved the highest performance with total Mean Intersection over Union (MIoU) of 90.5%. It is proved that the SLIC superpixel method significantly improved the oil spill classification accuracy on all the polarimetric feature sets. The classification accuracy of all kinds of targets types were improved, and the largest increase on mean MIoU of all features sets was on emulsions by 21.9%.

Our previous investigations indicated that in vitro polarization of mouse macrophages by Toxoplasma gondii type II strain dense granule protein 15 (GRA15II), one of the genotype-associated effectors of T. gondii, induced the phenotypes of classically activated macrophage (M1). Transfusion of the cells to mice may effectively alleviated hepatic fibrosis caused by schistosomiasis. The purpose of the study was to identify whether liver macrophages can be in vivo driven to M1 macrophages by lentiviral vector (LV) carrying GRA15II gene (LV-gra15II) and to explore the potential mechanism by which the LV-gra15II-activated liver macrophage (LV-gra15II-M) ameliorates the hepatic fibrosis in schistosomiasis. The mice were treated with LV-gra15II by hydrodynamic injection via the tail vein followed by challenge of Schistosoma japonicum (S. japonicum). Our experiments showed that LV-gra15II was successfully delivered to liver macrophages and GRA15II was persistently expressed in the macrophages of mice for at least 2 months. Furthermore, the LV-gra15II infected macrophages were polarized to M1 macrophages in vivo. Consequently, mice with schistosomiasis receiving LV-gra15II injection displayed a remarkable amelioration of liver granuloma formation and collagen deposition in association with downregulated expression of transforming growth factor-beta1, arginase 1 (Arg-1), α-smooth muscle actin, and an increased expression of matrix metalloproteinase 13 (MMP13). Simultaneously, no negative effects of liver function and vitality of mice were noted. The in vitro experiments indicated that the C-C motif chemokine ligand 2 and nitric oxide level were elevated in LV-gra15II-M cultural supernatants; hepatocyte growth factor expression was enhanced in LV-gra15II-M. In addition, LV-gra15II-M not only secreted MMP13, which greatly degraded type I collagen, but also induced murine hepatic stellate cell (HSC) line (JS1) apoptosis in the co-culture system. Taken together, we identified for the first time that LV-gra15II may in vivo drive liver macrophages to M1 macrophage phenotypes, which helps for alteration of the liver fibrotic microenvironment with collagen dissolution, HSC deactivation, apoptosis and hepatocyte protection. Our study gives an insight into the use of gene delivery with parasite-derived immunomodulatory factor as a potential immune cell activating agent to re-equilibrate the other pathogen-induced immune response in some chronic diseases.

Toxoplasma gondii infection evokes a strong Th1-type response with interleukin (IL)-12 and interferon (IFN)-γ secretion. Recent studies suggest that the infection of pregnant mice with T. gondii may lead to adverse pregnancy results caused by subversion of physiological immune tolerance at maternofetal interface rather than direct invasion of the parasite. Genotype-associated dense granule protein GRA15II tends to induce classically activated macrophage (M1) differentiation and subsequently activating NK, Th1, and Th17 cells whereas rhoptry protein ROP16I/III drives macrophages to alternatively activated macrophage (M2) polarization and elicits Th2 immune response. Unlike the archetypal strains of types I, II, and III, type Chinese 1 strains possess both GRA15II and ROP16I/III, suggesting a distinct pathogenesis of Toxoplasma-involved adverse pregnancies. We constructed T. gondii type Chinese 1 strain of WH3Δrop16 based on CRISPR/Cas9 technology to explore the ROP16I/III-deficient/GRA15II-dominant parasites in induction of trophoblast apoptosis in vitro and abnormal pregnant outcomes of mice in vivo. Our study showed that Toxoplasma WH3Δrop16 remarkably induced apoptosis of trophoblasts. C57BL/6 pregnant mice injected with the tachyzoites of WH3Δrop16 presented increased absorptivity of fetuses in comparison with the mice infected with WH3 wild type (WH3 WT) parasites although no remarkable difference of virulence to mice was seen between the two strains. Additionally, the mice inoculated with WH3Δrop16 tachyzoites exhibited a notable expression of both IL-17A and IFN-γ, while the percentage of CD4+CD25+FoxP3 [T regulatory cells (Tregs)] were diminished in splenocytes and placenta tissues compared to those infected with WH3 WT parasites. Accordingly, expressions of IL-4, IL-10, and transforming growth factor beta 1, the pivotal cytokines of Th2 and Tregs response, were significantly dampened whereas IFN-γ and IL-12 expressions were upregulated in WH3Δrop16-infected mice, which gave rise to more prominent outcomes of abnormal pregnancies. Our results indicated that the WH3Δrop16 parasites with gra15II background of T. gondii type Chinese 1 strains may cause miscarriage and stillbirth due to subversion of the maternal immune tolerance and system immunity of the animals and the GRA15II effector contributes to the process of adverse pregnant consequences.

Abstract Background Toxoplasma gondii, an obligate intracellular pathogen, has a strong affinity for the nervous system. TgCtwh3, a representative Chinese 1 Toxoplasma strain prevalent in China, has the polymorphic features of the effectors ROP16I/III with type I and GRA15II with type II Toxoplasma strains. The interaction of this atypical strain with host cells remains extremely elusive. Methods Using a transwell system, neural stem cells C17.2 were co-cultured with the tachyzoites of TgCtwh3 or standard type I RH strain. The apoptosis levels of C17.2 cells and the expression levels of related proteins in the endoplasmic reticulum stress (ERS)-mediated pathway were detected by flow cytometry and Western blotting. Results The apoptosis level of C17.2 cells co-cultured with TgCtwh3 had a significant increase compared to the negative control group; however, the apoptosis level in the TgCtwh3 group was significantly lower than that in the RH co-culture group. Western blotting analyses reveal that, after the C17.2 cells were co-cultured with TgCtwh3 and RH tachyzoites, the expression levels of caspase-12, CHOP and p-JNK in the cells increased significantly when compared to the control groups. After the pretreatment of Z-ATAD-FMK, an inhibitor of caspase-12, the apoptosis level of the C17.2 cells co-cultured with TgCtwh3 or RH tachyzoites had an apparent decline, and correspondingly, the expression levels of those related proteins were notably decreased. Conclusions Our findings suggest that TgCtwh3 may induce the apoptosis of the C17.2 cells by up-regulation of caspase-12, CHOP, and p-JNK, which are associated with ERS signaling pathways. This work contributes to better understanding the possible mechanism of brain pathology induced by T. gondii Chinese 1 isolates prevalent in China, and also reveals the potential value of ERS inhibitors to treat such related diseases in the future.

Most simulation-based noise maps are important for official noise assessment but lack local noise characteristics. The main reasons for this lack of information are that official noise simulations only provide information about expected noise levels, which is limited by the use of large-scale monitoring of noise sources, and are updated infrequently. With the emergence of smart cities and ubiquitous sensing, the possible improvements enabled by sensing technologies provide the possibility to resolve this problem. This study proposed an integrated methodology to propel participatory sensing from its current random and distributed sampling origins to professional noise simulation. The aims of this study were to effectively organize the participatory noise data, to dynamically refine the granularity of the noise features on road segments (e.g., different portions of a road segment), and then to provide a reasonable spatio-temporal data foundation to support noise simulations, which can be of help to researchers in understanding how participatory sensing can play a role in smart cities. This study first discusses the potential limitations of the current participatory sensing and simulation-based official noise maps. Next, we explain how participatory noise data can contribute to a simulation-based noise map by providing (1) spatial matching of the participatory noise data to the virtual partitions at a more microscopic level of road networks; (2) multi-temporal scale noise estimations at the spatial level of virtual partitions; and (3) dynamic aggregation of virtual partitions by comparing the noise values at the relevant temporal scale to form a dynamic segmentation of each road segment to support multiple spatio-temporal noise simulations. In this case study, we demonstrate how this method could play a significant role in a simulation-based noise map. Together, these results demonstrate the potential benefits of participatory noise data as dynamic input sources for noise simulations on multiple spatio-temporal scales.

When synthetic aperture radar interferometry (InSAR) technology is applied in the monitoring of land subsidence, the sensor band plays an important role. An X-band SAR system as TerraSAR-X (TSX) provides high resolution and short revisit time, but it has no capability of global coverage. On the other side, an L-band sensor as Advanced Land Observing Satellite-Phased Array L-band Synthetic Aperture Radar (ALOS-PALSAR) has global coverage and it produces highly coherent interferograms, but it provides much less details in time and space. The characteristics of these two satellites from different bands can be regarded as complementary. In this paper, we firstly present a possible strategy for X-band optimized acquisition planning combining with L-band. More importantly, we also present the multi-temporal InSAR (MT-InSAR) analysis results from 23 ALOS-PALSAR images and 37 TSX data, which show the complementarity of L- and X-band allows measuring deformations both in urban and non-urban areas. Furthermore, the validation between MT-INSAR and leveling/GPS has been carried out. The combination analysis of L- and X-band MT-InSAR results effectively avoids the limitation of X-band, providing a way to define the shape and the borderline of subsiding center and helps us to understand the subsidence mechanism. Finally, the geological interpretation of the detected subsidence center is given.

Point-like targets are useful in providing surface deformation with the time series of synthetic aperture radar (SAR) images using the multi-temporal interferometric synthetic aperture radar (MTInSAR) methodology. However, the spatial density of point-like targets is low, especially in non-urban areas. In this paper, a hierarchical MTInSAR method is proposed to increase the spatial density of deformation measurements by tracking both the point-like targets and the distributed targets with the temporal steadiness of radar backscattering. To efficiently reduce error propagation, the deformation rates on point-like targets with lower amplitude dispersion index values are first estimated using a least squared estimator and a region growing method. Afterwards, the distributed targets are identified using the amplitude dispersion index and a Pearson correlation coefficient through a multi-level processing strategy. Meanwhile, the deformation rates on distributed targets are estimated during the multi-level processing. The proposed MTInSAR method has been tested for subsidence detection over a suburban area located in Tianjin, China using 40 high-resolution TerraSAR-X images acquired between 2009 and 2010, and validated using the ground-based leveling measurements. The experiment results indicate that the spatial density of deformation measurements can be increased by about 250% and that subsidence accuracy can reach to the millimeter level by using the hierarchical MTInSAR method.

Synthetic Aperture Radar Interferometry (InSAR), widely applied for the monitoring of land subsidence, has the advantage of high accuracy and wide coverage. High-resolution SAR data offers a chance to reveal impressive details of large-scale man-made linear features (LMLFs) with Multi-temporal InSAR (MT-InSAR) analysis. Despite these advantages, research validating high-resolution MT-InSAR results along high-speed railways with high spatial and temporal density leveling data is limited. This paper explored the monitoring ability of high-resolution MT-InSAR in an experiment along Jingjin Inter-City Railway, located in Tianjin, China. Validation between these MT-InSAR results and a high spatial/temporal density leveling measurement was conducted. A total of 37 TSX images spanning half a year were processed for MT-InSAR analysis. The distance between two consecutive leveling points is 60 m along Jingjin Inter-City railway and the time interval of the study was about one month. The Root Mean Square Error (RMSE) index of average subsidence rate comparison between MT-InSAR results and leveling data was 3.28 mm/yr, with 34 points, and that of the displacement comparison was 2.90 mm with 464 valid observations. The experimental results along Jingjin Inter-City railway showed a high correlation between these two distinct measurements. These analyses show that millimeter accuracy can be achieved with MT-InSAR analysis when monitoring subsidence along a high-speed railway. We discuss the possible reason for the subsiding center, and the characteristics of both leveling and MT-InSAR results. We propose further planning for the monitoring of subsidence over LMLFs.

The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD.A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol.A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P0.05) among three groups.BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general.Chinese Clinical Trial Register center ChiCTR-TRC-09000530.

BACKGROUND: Recent population structure studies of T. gondii revealed that a few major clonal lineages predominated in different geographical regions. T. gondii in South America is genetically and biologically divergent, whereas this parasite is remarkably clonal in North America and Europe with a few major lineages including Types I, II and III. Information on genotypes and mouse virulence of T. gondii isolates from China is scarce and insufficient to investigate its population structure, evolution, and transmission. METHODOLOGY/PRINCIPAL FINDINGS: Genotyping of 23 T. gondii isolates from different hosts using 10 markers for PCR-restriction fragment length polymorphism analyses (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) revealed five genotypes; among them three genotypes were atypical and two were archetypal. Fifteen strains belong to the Chinese 1 lineage, which has been previously reported as a widespread lineage from swine, cats, and humans in China. Two human isolates fall into the type I and II lineages and the remaining isolates belong to two new atypical genotypes (ToxoDB#204 and #205) which has never been reported in China. Our results show that these genotypes of T. gondii isolates are intermediately or highly virulent in mice except for the strain TgCtwh6, which maintained parasitemia in mice for 35 days post infection although it possesses the uniform genotype of Chinese 1. Additionally, phylogenetic network analyses of all isolates of genotype Chinese 1 are identical, and there is no variation based on the sequence data generated for four introns (EF1, HP2, UPRT1 and UPRT7) and two dense granule proteins (GRA6 and GRA7). CONCLUSION/SIGNIFICANCE: A limited genetic diversity was found and genotype Chinese 1 (ToxoDB#9) is dominantly circulating in mainland China. The results will provide a useful profile for deep insight to the population structure, epidemiology and biological characteristics of T. gondii in China.

Cancer is one of the leading causes of deaths worldwide. Compounds derived from traditional Chinese medicines have been an important source of anticancer drugs and adjuvant agents to potentiate the efficacy of chemotherapeutic drugs and improve the side effects of chemotherapy. Herba Epimedii is one of most popular herbs used in China traditionally for the treatment of multiple diseases, including osteoporosis, sexual dysfunction, hypertension and common inflammatory diseases. Studies show Herba Epimedii also possesses anticancer activity. Flavonol glycosides icariin and icariside II are the main bioactive components of Herba Epimedii. They have been found to possess anticancer activities against various human cancer cell lines in vitro and mouse tumor models in vivo via their effects on multiple biological pathways, including cell cycle regulation, apoptosis, angiogenesis, and metastasis, and a variety of signaling pathways including JAK2-STAT3, MAPK-ERK, and PI3k-Akt-mTOR. The review is aimed to provide an overview of the current research results supporting their therapeutic effects and to highlight the molecular targets and action mechanisms.

This paper proposes a novel rigorous transformation model for 2D-3D registration to address the difficult problem of obtaining a sufficient number of well-distributed ground control points (GCPs) in urban areas with tall buildings. The proposed model applies two types of geometric constraints, co-planarity and perpendicularity, to the conventional photogrammetric collinearity model. Both types of geometric information are directly obtained from geometric building structures, with which the geometric constraints are automatically created and combined into the conventional transformation model. A test field located in downtown Denver, Colorado, is used to evaluate the accuracy and reliability of the proposed method. The comparison analysis of the accuracy achieved by the proposed method and the conventional method is conducted. Experimental results demonstrated that: (1) the theoretical accuracy of the solved registration parameters can reach 0.47 pixels, whereas the other methods reach only 1.23 and 1.09 pixels; (2) the RMS values of 2D-3D registration achieved by the proposed model are only two pixels along the x and y directions, much smaller than the RMS values of the conventional model, which are approximately 10 pixels along the x and y directions. These results demonstrate that the proposed method is able to significantly improve the accuracy of 2D-3D registration with much fewer GCPs in urban areas with tall buildings.