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Ulcerative colitis (UC), one of the foremost common forms of inflammatory bowel disease, poses a serious threat to human health. Currently, safe and effective treatments are not available. This study investigated the protective effect of ginkgolide C (GC), a terpene lactone extracted from

Land consolidation has greatly altered land use patterns and the corresponding ecosystem services (ES) in China. However, the potential consequences of different consolidation measures for the interaction of ecosystem services are still largely unknown. Here, from a simulation perspective, we predict potential separate and joint influences of three land consolidation scenarios, i.e., reclamation of abandoned mining land, intensive construction land use and their integrated scenario, on the tradeoff/ synergic relationships of food production, carbon storage, habitat quality, and water conservation. Zhaoyuan city, one of China's top 100 counties at a green transformation stage of mining industry, is taken as a case study. Our results show that land consolidation will significantly mitigate the loss of farmland and vegetation while improving use efficiency of construction land. By 2035, food production is likely to present more trade-offs with other ES, whereas carbon storage, habitat quality, and water conservation will be highly synergic with each other. In contrast, consolidation of rural/urban construction land will be more feasible to coordinate multiple ecosystem services, as well as mitigating urban expansion and rural hollowing. This work enables us to identify the optimal combinations of multiple land consolidation measures towards sustainable ecosystem management.

Background Previous studies have shown a close association between an altered immune system and Parkinson's disease (PD). Neuroinflammation inhibition may be an effective measure to prevent PD. Recently, numerous reports have highlighted the potential of hydroxy-carboxylic acid receptor 2 (HCA2) in inflammation-related diseases. Notably, the role of HCA2 in neurodegenerative diseases is also becoming more widely known. However, its role and exact mechanism in PD remain to be investigated. Nicotinic acid (NA) is one of the crucial ligands of HCA2, activating it. Based on such findings, this study aimed to examine the effect of HCA2 on neuroinflammation and the role of NA-activated HCA2 in PD and its underlying mechanisms. Methods For in vivo studies, 10-week-old male C57BL/6 and HCA2−/− mice were injected with LPS in the substantia nigra (SN) to construct a PD model. The motor behavior of mice was detected using open field, pole-climbing and rotor experiment. The damage to the mice's dopaminergic neurons was detected using immunohistochemical staining and western blotting methods. In vitro, inflammatory mediators (IL-6, TNF-α, iNOS and COX-2) and anti-inflammatory factors (Arg-1, Ym-1, CD206 and IL-10) were detected using RT-PCR, ELISA and immunofluorescence. Inflammatory pathways (AKT, PPARγ and NF-κB) were delineated by RT-PCR and western blotting. Neuronal damage was detected using CCK8, LDH, and flow cytometry assays. Results HCA2−/− increases mice susceptibility to dopaminergic neuronal injury, motor deficits, and inflammatory responses. Mechanistically, HCA2 activation in microglia promotes anti-inflammatory microglia and inhibits pro-inflammatory microglia by activating AKT/PPARγ and inhibiting NF-κB signaling pathways. Further, HCA2 activation in microglia attenuates microglial activation-mediated neuronal injury. Moreover, nicotinic acid (NA), a specific agonist of HCA2, alleviated dopaminergic neuronal injury and motor deficits in PD mice by activating HCA2 in microglia in vivo. Conclusions Niacin receptor HCA2 modulates microglial phenotype to inhibit neurodegeneration in LPS-induced in vivo and in vitro models.

Social interaction has become one of the key factors affecting the spatial reconstruction of rural settlements (SRRS). However, most studies ignored the multi-scale impact of social networks on the identification of restructuring types of rural settlements. This paper, taking Ezhou City of Hubei Province, China as the case study area, developed a potential inter-settlement network through considering settlements as nodes, and inter-settlement interactions induced by the spatial disparity of public facilities as edges, divided towns in Ezhou City into three zones based on community structure at the town level, and then identified four types of rural settlements in light of the characteristics of cluster patterns and centrality at the patch level. The results show that the inter-settlement network in Ezhou City presents apparent disparities in terms of community structure, cluster patterns and centrality. In community analysis, high inter-community and intra-community interactions are concentrated in well-developed areas in the north and east, while weak interactions between communities occur in the southern areas dominated by traditional agricultural production. Accordingly, three zones are divided such as the urban-leading zone, urban-rural integration zone and rural-leading zone. For the network centrality and cluster patterns, high-level rural settlements are mainly distributed in the urban-leading zone, followed by the urban-rural integration zone and the rural-leading zone. Moreover, the lump cluster pattern is observed in each zone, but the chain pattern and dispersed pattern largely occur in the rural-leading zone. At same time, four types of rural settlements are identified, namely urbanized settlements, central settlements, grassroots settlements and relocated settlements. The corresponding plans are discussed in different zones regarding urbanization, integration and characteristics to provide meaningful insights for policymakers to guide SRRS. This study would contribute to our understanding of the impact of social network involved in daily life on rural settlement reconstruction, and expect to provide theoretical and methodological support for rural sustainable development in practice.

One of the key factors affecting rural settlements distribution is intervillage social connections. However, most of the current studies ignored the effects of social connections on the spatial distribution of rural settlements. This study proposed a multi-objective spatial reconstruction model for rural settlements based on the particle swarm optimization algorithm. The model considers intervillage social connections as one of the reconstruction objectives together with land-use quantity, spatial compactness, land-use suitability and relocation distance. Based on a questionnaire survey, the social connection strength between villages was measured from spatial and nonspatial aspects. The model was calibrated for the Chengui Township of Hubei Province in Central China. Five modeling scenarios for rural settlement reconstruction were designed according to potential development modes used in practice. A comparison of the reconstruction results of the different scenarios was performed to verify the applicability of the model and to analyze the joint interaction of the spatial objectives and social connections during the restructuring of rural settlements. The results indicated that five scenarios were effectively and robustly implemented using the proposed model. Social connections had a direct effect by guiding the restructuring direction of rural settlements. This study advances our understanding of the influence of social connections on rural settlement reconstruction and provides a useful exploratory tool for policymakers and rural planners in formulating reasonable reconstruction plans.

Due to powerful drug resistance and fatal toxicity of methicillin-resistant Staphylococcus aureus (MRSA), therapeutic strategies against virulence factors present obvious advantages since no evolutionary pressure will induce bacterial resistance. Alpha-hemolysin (Hla) is an extracellular toxin secreted by Staphylococcus aureus and contributes to bacterial pathogenicity. Herein, we identified a natural product 2,3-dehydrokievitone (2,3-DHKV) for inhibiting Hla activity of MRSA strain USA300 but not affecting bacteria growth. 2,3-DHKV significantly decreased hemolysin expression in a dose-dependent manner, but it did not potently neutralize hemolysin activity. Subsequently, cellular thermal shift and heptamer formation assays confirmed that 2,3-DHK affects hemolytic activity through indirect binding to Hla. RT-qPCR and western blot revealed that 2,3-DHKV suppressed Hla expression at the mRNA and protein levels, and further decreased accessory gene regulator A (agrA) transcription levels. We also observed that 2,3-DHK significantly attenuated the damage of A549 cells by S. aureus and reduced the release of lactate dehydrogenase (LDH). Moreover, in the MRSA-induced pneumonia mouse model, 2,3-DHK treatment prolonged the life span of mice and reduced the bacterial load in the lungs, which significantly alleviated the damage to the lungs. In summary, this study proved that 2,3-DHK as a Hla inhibitor is a potential antivirulence agent against MRSA infection.

Severe tropospheric O3 pollution has swept across China in recent years. Consequently, investigation of tropospheric O3 concentration influencing mechanism is of significance for O3 pollution control in China. Previous studies have rarely detected combined impacts of natural factors and anthropogenic activities behind tropospheric O3 concentration in China at a national scale. Moreover, there is significant spatiotemporal heterogeneity of O3 pollution distribution in China due to the temporal and regional differences of socioeconomic and natural environmental condition in the vast territory. The targeted O3 control recommendations for different regions and seasons should be put forward in terms of the spatiotemporal heterogeneity of O3 concentration determinants. In this context, a three-level regression model integrating multi-scale biophysical and socioeconomic variables was proposed to explore the determinants of O3 pollution in China. The results showed that the tropospheric O3 concentration in the eastern and southeastern regions of China was strongly affected by meteorological conditions. In contrast, tropospheric O3 pollution concentrated in inland areas mainly depended on the emission intensity from anthropogenic sources. Supplementary Information The online version contains supplementary material available at 10.1007/s10653-020-00797-8.

Farmland reforestation can contribute substantially to ecological restoration. Previous studies have extensively examined the ecological effects of farmland reforestation, but few of them have investigated the spatiotemporal responses of broad-scale landscape connectivity to reforestation. By using a typical agro-pastoral ecotone in northern China as a case study, we addressed this issue based on an innovative integration of circuit theory approach and counterfactual analysis. The forest connectivity through multiple dispersal pathways was measured using the circuit theory approach, and its spatiotemporal changes after reforestation were evaluated by counterfactual analysis. The results showed that from 2000–2015, the reforested farmland occupied 2095 km2, and 12.5% was on steeply sloped land. Farmland reforestation caused a greater increase in ecological connectivity by adding new ecological corridors and stepping stones in scattered forest areas rather than in areas with dense forest distributions. The newly added corridors and stepping stones were fragmented, short and narrow and thus deserve powerful protection. Future reforestation to improve landscape connectivity should highlight pinch point protection and obstacle removal as well as the tradeoff between farmland loss and farmer survival. Our findings are expected to inform the optimization of the Grain for Green policy from the perspective of broad-scale biodiversity conservation.

Background Galangin has been extensively studied as the antitumor agent in various cancers. However, the effect of galangin in hepatocellular carcinoma (HCC) remains elusive. Methods Using RNA sequencing, the differential expression of lncRNA in human HCC cell line with highly metastatic potential (MHCC97H) cells treated with galangin was investigated. Furthermore, H19 expression pattern was also determined in MHCC97H cells following treatment with galangin. In addition, knockdown and overexpression of H19 was performed to analyze the effect of the expression pattern of H19 on cell apoptosis, cell cycle, migration, and invasion in HCC cells. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. In order to analyze loss expression of H19 in vivo, clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) was used. Results Total of 50 lncRNAs were significantly differentially expressed in MHCC97H cells treated with galangin. Besides, the expression of H19 was markedly reduced following treatment with galangin in MHCC97H cells. Compared to the Control group, the galangin‐treated group inhibited cell migration and invasion. Knockdown of H19 expression showed increased cell apoptosis and decreased invasion. In addition, RNA‐seq data also identified 161 mRNA which was significantly differentially expressed following treatment with galangin. To further determine the underlying mechanism, p53 protein was analyzed. Notably, the results indicated that knockdown of H19 and miR675 induced the expression of p53, eventually promoting cell apoptosis in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through reduced the expression of H19 and miR675 in MHCC97H cells. The in vivo result showed that compared to the Con, tumor growth was remarkably suppressed with loss expression of H19. Conclusion Our data suggested that galangin has a crucial role in hepatocarcinogenesis through regulating the expression pattern of H19., Amount 50 lncRNAs were differentially expressed in galangin‐treated by RNA‐Seq. H19 induced cell apoptosis through p53 protein after galangin treatment. Target knock out H19 expression using CRISPR/Cas9.

Objective Ten-eleven translocation (TET) enzymes that oxidize a 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) have been responsible for fine-tuning methylation patterns and exhibit role in epigenetic modifications. Chrysin, a natural flavone frequently present in honey, has been recognized to exhibit anti-tumor properties. In this study, we investigated the effects of Chrysin in the expression pattern of TET proteins in gastric cancer (GC) cells. Materials and Methods Using qRT-PCR and Western blot analysis, we analyzed the expression of TET1 in GC cells in vitro following treatment with Chrysin. Immunofluorescence staining detected the expression levels of 5mC and 5hmC. Flow cytometry, wound healing, and Matrigel invasion assays were performed to determine cell proliferation, cell cycle, apoptosis, and migration and invasion of GC cells following treatment with Chrysin, si-TET1, and TET1-KO. Furthermore, a xenograft model was developed to analyze the expression pattern of TET1 on tumor development in vivo. Results qRT-PCR and Western blot assays indicated that treatment with Chrysin significantly promoted the expression of TET1 in GC cells. Immunofluorescence study further confirmed that TET1 and 5hmC levels were significantly enhanced following treatment with Chrysin in MKN45 cells. Moreover, our results suggested that Chrysin could noticeably induce cell apoptosis and inhibit cell migration and invasion. Further, knockdown and overexpression of TET1 were conducted to investigate whether TET1 expression affected cell apoptosis, and cell migration and invasion in MKN45 cells. The results indicated that overexpression of TET1 markedly promoted cell apoptosis and inhibited cell migration and invasion. Furthermore, the TET1 gene knocked out was generated using the CRISPR/Cas9 system. Our data suggested that TET1 expression was associated with GC tumor growth in vivo. Conclusion This study indicated that Chrysin exerted anti-tumor effects through the regulation of TET1 expression in GC and presented TET1 as a novel promising therapeutic target for GC therapy.

Due to powerful drug resistance and fatal toxicity of methicillin-resistant

A better understanding of regional differences in ecosystem health and its driving factors is conducive to ecosystem management and restoration. Although various studies on ecosystem health have been carried out in different regions, few studies have been devoted to the insightful exploration of the spatial heterogeneity of ecosystem health and its driving forces at a national scale. In this study, we used an evaluation framework in terms of vigor, organization, resilience, and ecosystem service functions to assess the ecosystem health level in China from 2000 to 2015. Then, spatial agglomeration and regional differences in ecosystem health were examined using the spatial autocorrelation method and K-means clustering analysis, and the factors driving the regional differences of ecosystem health were explored based on the geographical detector model. Our results showed the following: (1) the ecosystem health level in China spatially increases from the northwest to the southeast, exhibiting significant global spatial autocorrelation and local spatial agglomeration; (2) eleven zones with three types were identified to indicate the regional differences of ecosystem health; (3) In terms of the driving factors, the moisture index and land use intensity contributed 24.5% and 20.7% to the variation in ecosystem health at the national scale. The ecosystem health changes were influenced by the interaction of meteorological and socio-economic factors in most regions with high ecosystem health types. Socio-economic factors act as a bridge that linked and reinforced the other factors in most regions with low and medium ecosystem health types. Ecologically protected factors were found to exert a remarkable impact in the southwestern region and the Loess Plateau region. Our findings can provide more effective and detailed decision-making support for ecosystem conservation and management in China.

Ten-eleven translocation (TET) proteins have been shown to be abnormally expressed in different cancers. To investigate the expression pattern of TET proteins in HepG2 cells, sodium ascorbate was used to treat HepG2 cells. Our results showed that TET1, TET2 and TET3 expression was increased after sodium ascorbate treatment. The TET proteins catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thus, 5mC and 5hmC levels were examined. The results suggested that 5hmC was increased after sodium ascorbate treatment. To further determine the biological function of the TET proteins, si-TET1, si-TET2 and si-TET3 were transfected into HepG2 cells. The results showed that a knock down of TET3 expression stimulated cell proliferation of HepG2 cells. To further understand the effects of TET3 expression on cell proliferation, sodium ascorbate was added to the cells after transfection with si-TET3. The results demonstrated that sodium ascorbate could rescue TET3 expression and inhibit cell proliferation. Taken together, these results indicate that TET3 expression regulated cell proliferation, which is associated with 5hmC in HepG2 cells.

China has been under threat of severe haze in recent years, particularly that caused by fine particulate matter (PM2.5). Exploring the determinants of PM2.5 concentration is critical for improving air quality. The influencing mechanism of smog pollution is a comprehensive and systematic process affected by multiple driving factors. In this research, we collected PM2.5 monitoring data from 292 cities across China in 2015 and employed multilevel regression models constructed using three levels to detect the physical and socioeconomic driving forces behind the PM2.5 concentration at monthly, seasonal and spatial scales, which captured random effects both varied by season and region. The results indicated significant spatiotemporal heterogeneity in the PM2.5 distribution, with the pollution core located in central China and northern China. The most severely haze episodes occurred in winter. Multilevel models showed that 46.40% of the variance was derived from the seasonal and spatial levels, and the models could explain a maximum of 90.7% of the PM2.5 concentration variance. The multilevel model identified more determinant influences varying by time and region. The outcomes suggested that the impacts of temperature and relative humidity on PM2.5 were of significant spatiotemporal heterogeneity due to the influencing mechanism differing from season and station. The variation of anthropogenic activities led to the socioeconomic influences featured a significant spatiotemporal heterogeneity. This research revealed the spatiotemporal characteristic of PM2.5 pollution influencing mechanism from physical and perspective and provided effective strategies for restricting air pollution.

Parkinson’s disease (PD) is a neurodegenerative disease in which neuronal apoptosis and associated inflammation are involved in its pathogenesis. However, there is still no specific treatment that can stop PD progression. Isoalantolactone (IAL) plays a role in many inflammation-related diseases. However, its effect and mechanism in PD remain unclear. In this study, results showed that IAL administration ameliorated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-related pathological impairment and decreased motor activity in mice. Results from in vitro mechanistic studies showed that IAL regulated apoptosis-related proteins by activating the AKT/Nrf2 pathway, thereby suppressing the apoptosis of SN4741 cells induced by N-methyl-4-phenylpyridinium Iodide (MPP+). On the other hand, IAL inhibited LPS-induced release of pro-inflammatory mediators in BV2 cells by activating the AKT/Nrf2/HO-1 pathway and inhibiting the NF-κB pathway. In addition, IAL protected SN4741 from microglial activation-mediated neurotoxicity. Taken together, these results highlight the beneficial role of IAL as a novel therapy and potential PD drug due to its pharmacological profile.

Parkinson's disease (PD) is a usual disease caused by degeneration of the central nervous system, which features the denaturation and death of dopaminergic neurons in the substantia nigra compact (SNc) of the midbrain. Neuroinflammation casts a consequential role in its pathogenesis, and the excessive activation of microglia as a major part of neuroinflammation cannot be ignored. Studies have indicated that Hordenine (HOR) functioned widely as an anti-oxidant and anti-inflammatory substance, but there are no reports on neuroinflammation effects. Therefore, this study is devoted to exploring the effect of HOR on neuroinflammation and its specific mechanism. In vivo, results revealed that HOR depressed the activation of microglia in SNc and protected dopaminergic neurons in the 6-hydroxydopamine (6-OHDA)-induced PD rat model, which terminally reduced movement disorders and weight loss. In vitro, studies have shown that HOR can inhibit inflammatory responses triggered by lipopolysaccharide (LPS) in BV-2 cells. More profound studies have discovered that the specific anti-inflammatory mechanism is intimately associated with the NF-κB and MAPK signaling pathways. All in it together, HOR acts as a significant role in preserving dopaminergic neurons by restraining neuroinflammation mediated by activation of microglia. This may provide a potential drug for Parkinson's treatment.

Microglia, the main immune cells in the brain, participate in the innate immune response in the central nervous system (CNS). Studies have shown that microglia can be polarized into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Accumulated evidence suggests that over-activated M1 microglia release pro-inflammatory mediators that damage neurons and lead to Parkinson’s disease (PD). In contrast, M2 microglia release neuroprotective factors and exert the effects of neuroprotection. Camptothecin (CPT), an extract of the plant Camptotheca acuminate, has been reported to have anti-inflammation and antitumor effects. However, the effect of CPT on microglia polarization and microglia-mediated inflammation responses has not been reported. In our study we found that CPT improved motor performance of mice and reduced the loss of neurons in the substantia nigra (SN) of the midbrain in LPS-injected mice. In the mechanism study, we found that CPT inhibited M1 polarization of microglia and promotes M2 polarization via the AKT/Nrf2/HO-1 and NF-κB signals. Furthermore, CPT protected the neuroblastoma cell line SH-SY5Y and dopaminergic neuron cell line MN9D from damage mediated by microglia activation. In conclusion, our results demonstrate that CPT regulates the microglia polarization phenotype via activating AKT/Nrf2/HO-1 and inhibiting NF-κB pathways, inhibits neuro-inflammatory responses, and exerts neuroprotective effects in vivo and in vitro.

Background Parkinson's disease (PD), the second largest neurodegenerative disease seriously affects human health. Microglia, the main immune cells in the brain participate in the innate immune response in the central nervous system (CNS). Studies have shown that microglia can be polarized into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Accumulated evidences suggest that over-activated M1 microglia release pro-inflammatory mediators that damage neurons and lead to Parkinson's disease (PD). In contrast, M2 microglia release neuroprotective factors and exert the effects of neuroprotection. Camptothecin (CPT), an extract of the plant Camptotheca acuminate, has been reported to have anti-inflammation and antitumor effects. However the effect of CPT on microglia polarization and microglia-mediated inflammation responses has not been reported. Therefore, we aim to explore the effect of CPT on microglia polarization and its underlying mechanism on neuroinflammation. Methods C57BL/6 mice (25–30 g) were injected LPS or PBS into the substantia nigra (SN). Open-Field Test and Immunohistochemistry were performed to test the dyskinesia of mice and the loss of neurons in the substantia nigra (SN). Microglia cell line BV-2, the neuroblastoma SH-SY5Y and dopaminergic neuron MN9D cell were cultured. Cytotoxicity assay, reverse transcription quantitative real-time polymerase chain reaction (RT-PCR), Western blot, ELISA and Immunofluorescence staining were performed. All results were presented with mean ± SD. Results In vivo, CPT improved dyskinesia of mice, reduced the loss of neurons in the substantia nigra (SN) and inhibited neuro-inflammatory responses in LPS-injected mice. In vitro, CPT inhibited M1 polarization of microglia and promotes M2 polarization via the AKT/Nrf2/HO-1-NF-κB signal axis. Furthermore, CPT protected the neuroblastoma cell line SH-SY5Y and dopaminergic neuron cell line MN9D from neurotoxicity of mediated by microglia activation. Conclusion CPT regulates the microglia polarization phenotype via the AKT/Nrf2/HO-1-NF-κB signal axis, inhibits neuro-inflammatory responses and exerts neuroprotective effects in vivo and in vitro.

Maintaining biodiversity is vital for ecological processes. Yet, present static protected areas seem to be inefficient in biodiversity conservation. In this study, we use a set of indicators to evaluate topological features, landscape connectivity and resilience of the current habitat conservation institution, and apply the node addition method to prioritize habitats that play roles in improving connectivity and resilience outside the protected areas. Wanzhou District, Chongqing (SW China) is selected as the study area as it is a biodiversity hotspot in Three Gorges Reservoir Area. The results show that, in current conservation institution, average clustering coefficient and average weighted degree rise with the increasing dispersal distance of species; besides, landscape connectivity is rather low, while long dispersers have larger connectivity degree and resilience compared with short ones. Furthermore, how those patches could function as connectivity providers in different aspects (e.g. stepping-stone effect) is also presented by partitioning the connectivity indicator into three parts. However, it is interesting to find that, patches with good performance in improving connectivity may not have the equal efficiency in enhancing resilience, and the possible reasons are elaborately discussed. Prioritized patches are suggested to be placed under protection, and to update the habitat conservation institution. Our indicators and method can extend the knowledge of the importance of linking protected areas with surrounding habitats, and it can serve as a supporting tool for conservation planning or land use planning.

Rapid urbanization evidently affected ecosystem service provisions. Although numerous models have incorporated ecosystem services into land use decisions, most of them typically ignored the interactions between multiple ecosystem services (MES), as well as their impact on future urban expansion. Here, we propose a novel urban simulation model based on the integration of the coupling coordination evaluation of MES and cellular automata. The Wuhan Metropolitan Area was selected to test the model. Six conservation scenarios at different ecological coupling coordination levels were designed to predict urban expansion in 2030 and examine how ES interactions impact urban expansion modes. The results showed that the proposed model has an accuracy of 84.01% and can better capture the changes in MES interactions caused by urban expansion. A significantly negative correlation exists between the coupling coordination degree of MES and urban expansion, with a decreased coefficient from -0.924 to -0.945 during the period of 2010-2015. Our results also suggest that single conservation scenario may be inadequate to coordinate MES and urban expansion, which necessitates a comprehensive ecological protection mechanism in spatial planning. The proposed model can provide better understanding of relationships between MES interactions and urban expansion, and help planners to generate sustainable urban development policies.

Accumulating evidence has shown that activated microglia cause inflammatory immune response, which could lead to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. α-Cyperone, one of the main ingredients of Cyperus rotundus oil, has been reported to possess anti-inflammatory activity in activated macrophages. In this study, we found that α-cyperone markedly decreased the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in LPS-induced BV-2 cells. Moreover, α-cyperone inhibited NF-κB activation and enhanced heme oxygenase-1 (HO-1), nuclear factor-E2-related factor 2 (Nrf2) and Akt expression. Furthermore, we found that α-cyperone could upregulate HO-1 expression and enhance nuclear translocation of Nrf2 via activating the Akt signaling pathway, and inhibition of Akt, Nrf2 or HO-1 attenuated LPS-induced expression of proinflammatory cytokines in BV-2 cells. Moreover, the toxicities of conditioned medium from activated microglia toward dopaminergic neuronal SH-SY5Y cells and hippocampal neuronal HT22 cells were significantly inhibited by pretreatment with α-cyperone. Taken together, our results indicate that α-cyperone exerts neuroprotective effects by inhibiting the production of inflammatory cytokines in BV-2 cells through activating Akt/Nrf2/HO-1 and suppressing the NF-κB pathway.

Cropland conversion is a significant theme of the influence of human activities on ecological systems and global food security. Conventionally, cropland conversion in China has been deemed to match the dynamic balance of cropland resources well and to ensure food security for the whole country. However, local studies have presented some conflicting signs that call for an integrated analysis from a national viewpoint. In this paper, by considering the significance of slope in cropland-related natural and socioeconomic issues, we explore the slope features of China’s cropland conversion during 2000–2015 and endeavor to identify some potential risks hidden in the process. High-resolution remotely sensed images, digital elevation model and spatial analytical methods are adopted to conduct the analysis. The results show that, the features of cropland conversion in diverse slope division areas are all distinct. Some risks indicated by these conversion features can be identified as follows: (1) unsuitable reclamation of cropland in flat areas causes ecological damage, (2) the invasion of sparsely populated construction land on cropland in steep areas has a dramatic impact on the local area, (3) excessive greening in Northwest and Northeast China, and insufficient greening in Southwest China are not healthy for regional sustainability, (4) cropland’s upslope reclamation and downslope loss pose potential risks for food security. In the context of dynamic balance management and other related national policies, cropland conversion in China is not as optimistic as former surveys have indicated, and promoted measures should be elaborately adjusted based on local conditions.

Rural land use development is experiencing a transition stage of socioeconomic and land use development in China. Historic land use transition process and policy interventions have key influence on the applicability of land use allocation solutions in future land use management. Strategic land use allocation is therefore required to possess a good adjustment capability to the transition process. Although heuristic optimization methods have been promising to solve land use allocation problems, most of them ignored the spatially explicit effect of historic land use transition and policies. To help resolve this issue, this study aims to optimize future land use pattern in the context of rural land use development. We took Yunmeng County, one of the typical major grain producing and rapidly urbanizing areas in central China, as a case study and solved the sustainable land use allocation problem by using an improved heuristic optimization model. The model was constructed based on the integration of a spatial discrete particle swarm optimization and cellular automata-Markov simulation approach. The spatiotemporal land use patterns and policy interventions were represented by the CA-Markov as in spatially explicit transition rules, and then incorporated into the discrete PSO for optimal land use solutions. We examined the influence of the joint effect of spatiotemporal land use patterns and policy interventions on the land use allocation outcome. Our results demonstrate the robustness and potential of the proposed model, and, more importantly, indicate the significance of incorporating the spatiotemporal land use patterns and policy interventions into rural land use allocation.

In neurodegenerative diseases, neuronal damage caused by neuroinflammation is very important. Many studies have suggested that the activation of microglia is critical for the neuroinflammatory process. Therefore, inhibiting neuroinflammation is considered to be a hopeful target for curing neurodegenerative diseases. In this study, we aimed to explore whether menthol can protect the dopaminergic neurons by exerting anti-inflammatory effects in vivo or in vitro. The results showed that menthol had an inhibitory effect on impaired dopaminergic neurons and LPS-induced microglial activation. Further, menthol can inhibit the expression of related pro-inflammatory enzymes and pro-inflammatory factors. Both in vitro and in vivo mechanistic studies showed that menthol inhibited the neuroinflammatory response through the MAPK, NF-κB and AKT signaling pathways.

Microglia are the brain's immune cells and play an important role in regulating the microenvironment in the central nervous system. Activated microglia are capable of acquiring the pro-inflammatory (M1) phenotype and anti-inflammatory (M2) phenotype. Overactivation of microglia is neurotoxic and may lead to neuroinflammatory brain disorders. Neuroinflammation in the brain plays a crucial role part in the pathophysiology of many psychiatric and neurological diseases. The inhibition of M1 microglia and promotion of M2 microglia was demonstrated to treat and prevent these diseases through reduced neuroinflammation. Isovitexin (IVX) has anti-inflammatory properties and passes through the blood-brain barrier; however, the molecular mechanism that modulates IVX-mediated microglial polarization remains unclear. In BV-2 cells and mouse primary microglia, IVX suppressed the expression of M1 microglial markers, enhanced the expression of M2 microglial markers, and enhanced the release of interleukin 10 (IL-10). IVX promoted the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) in LPS-induced microglial activation. The inhibition of PPARγ and PGC-1α attenuated the regulatory effect of IVX in LPS-induced microglial polarization. IVX increased the expression of p-CaMKKβ, p-AMPK, and PGC-1α in BV-2 cells. Inhibition of CaMKKβ with STO-609 or knockdown of CaMKKβ with CaMKKβ siRNA attenuated IVX-mediated M2 microglial polarization in LPS-treated cells. In LPS-treated mice, the inhibition of CaMKKβ and PGC-1α attenuated the IVX-mediated prevention of sickness behavior and enhanction of IVX-mediated M2 microglial polarization. IVX promoted M2 microglial polarization which exerted anti-inflammatory effects on LPS-induced neuroinflammation via the activation of the CaMKKβ/AMPK-PGC-1α signaling axis.

The present study abstracts the land consolidation project site selection (LCPSS) problem to a multi-objective spatial optimization problem. In view of the shortcomings of traditional site selection methods in coordinating multiple objectives, the present study, considering the scale-related constraint conditions and general site selection rules of land consolidation, proposes a multi-objective LCPSS model (MOLCPSSM) based on an ant colony optimization algorithm with social, economic and ecological benefits as the optimization objectives. In addition, the present study focuses on the investigation of the mapping and coding relationships between the artificial ants and vector patches and also improves the ants’ spatial unit selection scheme and pheromone update mechanism. Furthermore, the present study verifies the MOLCPSSM through a case study of Jiayu County, Hubei Province, China. The results demonstrate the operability of the MOLCPSSM in solving practical land consolidation problems.

Neuroinflammation is caused by excessive activation of microglia and plays an essential role in neurodegenerative diseases. After activation, microglia produce several kinds of inflammatory mediators, trigger an excessive inflammatory response, and ultimately destroy the surrounding neurons. Therefore, agents that inhibit neuroinflammation may be potential drug candidates for neurodegenerative diseases. Evodiamine (EV) has anti-inflammatory functions in peripheral tissues. However, whether EV exerts the same function in neuroinflammation is not known. In the present study, the aim was to explore whether EV attenuates microglial overactivation and therefore suppresses the development of neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. It was found that EV effectively inhibited expression of proinflammatory mediators (cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) via AKT/Nrf2/HO-1 activation and suppressed NF-κB p65 phosphorylation. In addition, EV could suppress LPS-induced inflammatory response and loss of dopaminergic neuron in mouse mesencephalic neuron--glia cells. Hence, these findings demonstrate that EV suppresses neuroinflammation caused by overactivated microglia via regulating the AKT/Nrf2/HO-1/NF-κB signaling axis.

Against the background of rapid social and economic reform, urban space systems are unceasingly reconstituted. Population migration, which is a popular social phenomenon, has become an impo...

Ecosystem health assessment is vital for regional ecological restoration and management. Although many studies have improved the framework of ecosystem health assessment at the regional scale, most of them primarily focus on the single measurements of the natural states of ecosystems or external disturbances. However, there is a lack of comprehensive evaluation methods based on the ecological integrity and human demand for ecosystem services from the perspective of coupled human and ecological systems. In this study, we proposed an improved method that considers the ecological integrity and ecosystem services demand, which comprises four aspects of indicators: vigor, organization, resilience and ecosystem services (ES) supply-demand ratio. We used the Middle Reaches of the Yangtze River Economic Belt in China as a case study to apply the evaluation method. Our results indicate that (1) the level of ecosystem health is low in the middle of the study area and high on the periphery from 2000 to 2015. The moderate and good health levels dominate throughout the study area in 2000 and 2015. (2) The ES supply-demand ratio can objectively measure the actual status of ES, and the strong ES deficit aggravated dramatically the deterioration of regional ecosystems. (3) Urbanization exhibited a significant negative correlation with the ecosystem health index, and the greatest impact was observed in the urban agglomeration regions. Our framework extend the ecosystem health assessment methodology, and the research results can provide significant references for regional ecological protection and management.

The sexually dimorphic expression of H19/IGF2 is evolutionarily conserved. To investigate whether the expression of H19/IGF2 in the female porcine eye is sex-dependent, gene expression and methylation status were evaluated using quantitative real-time PCR (qPCR) and bisulfite sequencing PCR (BSP). We hypothesized that H19/IGF2 might exhibit a different DNA methylation status in the female eye. In order to evaluate our hypothesis, parthenogenetic (PA) cells were used for analysis by qPCR and BSP. Our results showed that H19 and IGF2 were over-expressed in the female eye compared with the male eye (3-fold and 2-fold, respectively). We observed a normal monoallelic methylation pattern for H19 differentially methylated regions (DMRs). Compared with H19 DMRs, IGF2 DMRs showed a different methylation pattern in the eye. Taken together, these results suggest that elevated expression of H19/IGF2 is caused by a specific chromatin structure that is regulated by the DNA methylation status of IGF2 DMRs in the female eye.

Traditional dual clustering algorithms cannot adaptively perform clustering well without sufficient prior knowledge of the dataset. This article aims at accommodating both spatial and non-spatial attributes in detecting clusters without the need to set parameters by default or prior knowledge. A novel adaptive dual clustering algorithm (ADC+) is proposed to obtain satisfactory clustering results considering the spatial proximity and attribute similarity with the presence of noise and barriers. In this algorithm, Delaunay triangulation is utilized to adaptively obtain spatial proximity and spatial homogenous patterns based on particle swarm optimization (PSO). Then, a hierarchical clustering method is employed to obtain clusters with similar attributes. The hierarchical clustering method adopts a discriminating coefficient to adaptively control the depth of the hierarchical architecture. The clustering results are further refined using an optimization approach. The advantages and practicability of the ADC+ algorithm are illustrated by experiments on both simulated datasets and real-world applications. It is found that the proposed ADC+ algorithm can adaptively and accurately detect clusters with arbitrary shapes, similar attributes and densities under the consideration of barriers.

Climate and land use change (CLUC) have a far-reaching influence on the ecosystem. Regional ecosystem health, which is the direct and comprehensive reflection of evaluating regional ecosystem quality, has been significantly affected by these changes. However, existing studies mainly focused on the influences of climate or land use change on ecosystem structure, functions, or services, few studies have explored and predicted their joint impacts on regional ecosystem health. In this study, to fill this gap, we proposed a simulation framework to predict the joint impact of future climate and land use change on ecosystem health under the different representative concentration pathways (RCP) scenarios based on the integration of FLUS (Future Land Use Simulation) model and ecosystem health assessment model. The Middle Reaches of the Yangtze River Economic Belt was taken as the study area to examine the prediction framework and identify relationships between future climate and land use change and ecosystem health index (EHI) during the period of 2015–2030. The prediction results show that the EHI in the north of the study area and urban agglomeration areas would suffer marked decrease under the joint influence of future climate and land use changes, indicating that these areas will likely to become the key conservation areas for future ecological protection and management. Additionally, predicted the future CLUC will result in a significant increase in EHI in more than 58% regions under the RCP 2.6 and RCP 4.5 scenarios from 2015 to 2030, whereas 74.87% areas would suffer the decrease of EHI under the RCP 8.5. From the perspective of regional development, the RCP 4.5 scenario can provide a compromise solution for tackling future climate and land use change to ensure the ecological conservation and economic development. Moreover, the direct impact of future climate change on ecosystem health will not be significant in the short term, while the indirect impact of future land use change will play a leading role in the joint influence. Furthermore, the flexible multi-model coupled prediction framework of this study provides a promising method for better predicting the joint impact of future climate and land use changes on regional ecosystem health, it can also be applied to explore the joint impact of these change on other ecological environment. Most importantly, the prediction results can provide scientific suggestions for ecological conservation, management and regional development.

Rapid land use/cover changes (LUCC) have triggered severe habitat degradation over recent decades. Existing studies mainly focus on how LUCC per se affects habitat quality, while less attention is paid to the integration of LUCC, socio-economic development and climate change as a land use system, and to investigate their synergistic impacts on habitat quality. This study addresses this issue by incorporating a top-down system dynamic model, a bottom-up cellular automata and a habitat quality assessment model. The potential impacts of urban growth, socio-economic development and climate change on habitat quality of Hubei Province, China, were predicted under the four IPCC RCP scenarios. Overall, construction land was predicted to expand fast whereas forested land and cultivated land to shrink significantly from 2015 to 2030, but RCP 2.6 and 4.5 scenarios may maintain higher habitat quality compared with RCP 6.0 and 8.5 scenarios. Severe habitat degradation is likely to occur in the megacity’s surrounding ecosystems under RCP 2.6 and 8.5 scenarios, while the degradation is more likely to occur in middle-sized and small cities under RCP 4.5 and 6.0 scenarios. Further, our findings suggest that fixed asset investments and technology innovation play important roles in mitigating the negative impacts of urban and socio-economic development on habitat quality. This study should provide a useful approach for decision makers to design alternative development scenarios and to strike a balance between regional development and habitat conservation.

The unsustainable and rapid economy development brings air pollution prominently in China. In the last decade, the haze weather and its influencing mechanism across China have received increasingly attention. Although previous research has extensively focused on the characteristics of aerosols, better understanding of long-term variation in aerosols and their determinants since the Reform and Opening-up still lack in China. Furthermore, the previous studies exploring the influencing mechanism behind haze episodes by using statistical method only reflect correlation between pollutant concentration and indicators at single station, which cannot consider the remote influences resulting from atmosphere transport. In this research, we investigated the spatiotemporal pattern of aerosol optical depth (AOD) and aerosol species in China during 1980–2018 and explored the spatially heterogeneous response of AOD and aerosol component to meteorological conditions and urbanization based on singular value decomposition (SVD) method. The results indicated that AOD exhibited an upward trend in nearly 40 years, especially in eastern China with the fastest growth of sulfate aerosol. The heterogeneity of determinants revealed a great gap in anthropogenic activities and meteorological influences on aerosol varing regions. In eastern China, anthropogenic activities should be closely monitored. Besides, scientific desert governance and urban construction exert positive impact on air pollution in Xinjiang province.

Numerous studies have shown that over-activation of microglia could cause neuroinflammation and release pro-inflammatory mediators, which could result in neurodegenerative diseases, like Parkinson's disease, Alzheimer's disease etc. Beta-naphthoflavone (BNF) has anti-oxidant and anti-inflammatory effects in borderline tissues, but BNF has not been reported the effect associated with neuroinflammation. Therefore, the purpose of this experiment is to inquiry the impact and mechanism of BNF on neuroinflammation. The results indicated that BNF significantly inhibited the production of pro-inflammatory mediators (inducible nitric-oxide synthase (iNOS), Cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) andinterleukin-6 (IL-6)) in LPS-exposed BV-2 cells. Analysis of western blot results found that BNF accelerated the activation of AKT/Nrf-2/HO-1 signaling pathway and suppressed NF-κB pathway activation. Further study showed that BNF inhibited activation of NF-κB pathway via promoting HO-1, and SnPP IX (a HO-1 inhibitor) could inhibit anti-inflammatory function of BNF. We also found that BNF reduced the apoptosis rate of Human neuroblastoma cells (SHSY5Y) and mouse hippocampal neuron cell line (HT22) by inhibiting release of inflammatory mediators in LPS-exposed BV2 cells. In a word, our results suggested that BNF could inhibit inflammatory response via AKT/Nrf-2/HO-1-NF-κB signaling axis in BV-2 cells and exerts neuroprotective impact via inhibiting the activation of BV2 cells.

α-Cyperone, extracted from Cyperus rotundus, has been reported to inhibit microglia-mediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson’s disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neuroprotective effects of α-cyperone against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells. Neurotoxicity was assessed by MTT assay and the measurement of lactic dehydrogenase (LDH) release. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The apoptosis of SH-SY5Y cells was evaluated by annexin-V-FITC staining. The translocation of NF-E2-related factor 2 (Nrf2) was determined by western blot and immunofluorescence staining. Western blot analysis was conducted to determine the expression level of cleaved-caspase-3, the pro-apoptotic factor Bax, and the anti-apoptotic factor, Bcl-2. The results showed that α-cyperone substantially decreased H2O2-induced death, release of LDH, and the production of ROS in SH-SY5Y cells. In addition, we found that α-cyperone attenuated H2O2-induced cellular apoptosis. Moreover, α-cyperone remarkably reduced the expression of cleaved-caspase-3 and Bax, and upregulated Bcl-2. Furthermore, α-cyperone enhanced the nuclear translocation of Nrf2. Pretreatment with brusatol (BT, an Nrf2 inhibitor) attenuated α-cyperone-mediated suppression of ROS, cleaved-caspase-3, and Bax, as well as α-cyperone-induced Bcl-2 upregulation in H2O2-treated SH-SY5Y cells. α-cyperone neuroprotection required Nrf2 activation. In conclusion, α-cyperone attenuated H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells via the activation of Nrf2, suggesting the potential of this compound in the prevention and treatment of PD.

Ecosystem services (ESs) are facing challenges from urbanization processes globally. Exploring how ESs respond to urbanization provides valuable information for ecological protection and urban landscape planning. Previous studies mainly focused on the global and single-scaled responses of ESs but ignored the spatially heterogenous and scale-dependent characteristics of these responses. This study chose Wuhan City in China as the study area to explore the spatially varying and scale-dependent responses of ESs, i.e., grain productivity, carbon sequestration, biodiversity potential and erosion prevention, to urbanization using geographically weighted regression (GWR). The results showed that the responses of ESs were spatially nonstationary evidenced by a set of local parameter estimates in GWR models, and scale-dependent indicated by two kinds of scale effects: effect of different bandwidths and effect of grid scales. The stationary index of GWR declined rapidly as the bandwidth increased until reaching to a distance threshold. Moreover, GWR outperformed ordinary least square at both grid scales (i.e., 5 km and 10 km scales) and behaved better at finer scale. The spatially non-stationary and scale-dependent responses of ESs to urbanization are expected to provide beneficial guidance for ecologically friendly urban planning.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downregulation of microglial activation may aid in the treatment of PD. Polydatin (PLD) has been reported to pass through the blood-brain barrier and protect against motor degeneration in the SN. However, the molecular mechanisms underlying the effects of PLD in the treatment of PD remain unclear. The present study aimed to determine whether PLD protects against dopaminergic neurodegeneration by inhibiting the activation of microglia in a rat model of lipopolysaccharide (LPS)induced PD. Our findings indicated that PLD treatment protected dopaminergic neurons and ameliorated motor dysfunction by inhibiting microglial activation and the release of pro-inflammatory mediators. Furthermore, PLD treatment significantly increased levels of p-AKT, pGSK-3βSer9, and Nrf2, and suppressed the activation of NF-κB in the SN of rats with LPS-induced PD. To further explore the neuroprotective mechanism of PLD, we investigated the effect of PLD on activated microglial BV-2 cells. Our findings indicated that PLD inhibited the production of pro-inflammatory mediators and the activation of NF-κB pathways in LPS-induced BV-2 cells. Moreover, our results indicated that PLD enhanced levels of p-AKT, p-GSK-3βSer9, and Nrf2 in BV-2 cells. After BV-2 cells were pretreated with MK2206 (an inhibitor of AKT), NP-12 (an inhibitor of GSK-3β), or Brusatol (BT; an inhibitor of Nrf2), treatment with PLD suppressed the activation of NF-κB signaling pathways and the release of pro-inflammatory mediators in activated BV-2 cells via activation of the AKT/GSK3β-Nrf2 signaling axis. Taken together, our results are the first to demonstrate that PLD prevents dopaminergic neurodegeneration due to microglial activation via regulation of the AKT/GSK3β-Nrf2/NF-κB signaling axis. Funding Sources: This work was funded by National Nature Science Foundation of China (project No. 31772547, 31672509), Jilin Scientific and Technological Development Program (project No. 20170623029TC, 20170623083-04TC). Conflicts of Interest: The authors report no conflicts of interest. The study design was approved by the appropriate ethics review board.

China has been under threat of severe haze in recent years, particularly that caused by fine particulate matter (PM

In this paper, a stochastic equilibrium chance-constrained programming (SECCP) model was developed for tackling the municipal waste management issue under uncertainty. The main advantage of this model is that it effectively reflected the dual-random characteristics of uncertain parameters through incorporating the opinions and judgments from various respondents into the parameter identification processes. This will lead to birandom variables, where their mean values and standard deviations are allowed to be the random variables, instead of the fixed values. The generation of birandom variables will enrich the stochastic optimization theory and improve the accuracy and rationality of parameters design and estimation. The equilibrium chance-constrained programming algorithm was used to solve the SECCP model, which is capable of tackling birandom variables and is overcoming limitations of traditional stochastic chance-constrained programming while parameters with normal distribution are required strictly. Currently, the application of SECCP model in the environmental management fields was limited. As the first attempt, the regional waste management of the City of Dalian, China, was used as a study case for demonstration. A variety of solutions are beneficial in providing decision space to the local managers through designing and adjusting the constraints-violation levels. This solution process also reflected trade-off between system economy and reliability. The successful application in regional waste management system is expected to be a good example for tackling other similar problems.

Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn’s disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice, then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis, however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.