Boundary delineation and grading functional zoning of Sanjiangyuan National Park based on biodiversity importance evaluations.

Recently, China advanced a policy of establishing a protected area system with national parks as the main body, and so the development of protected areas has entered a transitional period. However, to promote the coordinated development of economic construction and ecological protection of protected areas, their management needs to be more comprehensive and refined. Therefore, a more quantitative and refined spatial planning and management method for protected areas is urgently needed. This study took Sanjiangyuan National Park as the research object and considered the three biodiversity elements of species, ecosystems and landscape. The maximum entropy (MaxEnt) model, Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, and Fragstats software were used to determine the areas with highly suitable species habitat, areas of high ecosystem service value and areas of high landscape diversity. Based on these areas, Marxan software was used to calculate the irreplaceability value, identify the boundary of Sanjiangyuan National Park and clarify the gaps of the existing Sanjiangyuan National Park in the space. We suggest that at least 18,569 km2 of the eastern part of the Sanjiangyuan Region with a high irreplaceability value should be included in the existing Sanjiangyuan National Park. Moreover, the first-level zones were also classified based on irreplaceability, and the second-level functional zones were classified by K-means clustering based on the evaluation of ecological vulnerability and economic construction suitability. The first-level zones include "core conservation zones" and "general control zones", which had areas of 71,758.20 km2 (57.99%) and 51,980.13 km2 (42.01%), respectively. The core conservation zones were further zoned into primary vulnerable zones and secondary vulnerable zones. The subzones of the general control zones are multifunctional and they are tourism-grazing-living zones, grazing-living zones, tourism-living zones, tourism zones and other areas.

An integrated assessment system for the carrying capacity of the water environment based on system dynamics.

Implementing an integrated assessment system for the carrying capacity of water environments should include recognizing and eliminating warning signs based on future predictions. However, existing methodologies tend to ignore the warning methods already in place, and current studies fail to quantify water ecology issues adequately. To help solve these problems, the ecological footprint that involves water uses a procedural indicator system, which adopts an early warning methodology system approach. This reconstruction has devised definitions, recognizes hazards, states forecasts status, analyses signs, judges situations, distinguishes levels, and eliminates risks. Based on these procedures, a dynamic system model has been developed, comprising five subsystems with an overarching parent system. These subsystems are population, ecology, water resources, water environment, and water ecology. The simulation involves carrying rates for the water environment, water resource, water ecology, and the level of harmony between society and the environment. All these serve to describe the water environment carrying capacity, i.e., the upper limit of the capacity to supply resources, remove pollutants, and offer sustainable ecological services. To properly quantify the carrying capacity, the water environment carrying rate was assessed by a comprehensive analysis of the water environment, water resources, and water ecological carrying rate. The carrying rates were calculated as the ratios of currently existing pressure to the maximum pressure that can be born. When values are greater than 1, they indicate overload because the actual pressure is greater than the pressure they can bear. The degree of coordination between economy and environment was standardized to range between 0 and 1. The larger the value, the more harmonious the relationship. For this research, the North Canal basin, a basin consisting of several rivers flowing through Beijing, Tianjin, and Hebei in northern China and its surrounding areas, was chosen. The results showed that water environment and resource carrying rates would decline to 2.60 and 0.94, respectively, while the water ecology carrying rate would remain high at 10.98 by the year 2025. In addition, the degree of coordination would increase from 0.65 to 0.79. These statistics mean that the overload statuses will be high for a long time, although they are expected to ease gradually. Besides, the relationship between society and the environment would become more stable. Considering both the overload statuses and the relationship between society and the environment, the warning signs would not vanish. Based on predictions, the measures used were explained from three perspectives, i.e., alleviating pressures, enhancing carrying capacities, and finding a balance between society and the environment. Finally, the effects of the measures were estimated quantitatively.

Identification of conflict between wildlife living spaces and human activity spaces and adjustments in/around protected areas under climate change：A case study in the Three-River Source Region.

Overlap between wildlife living spaces and human activity spaces represents one of the main causes of human-wildlife conflict. It is therefore necessary to identify and adjust the spatial distribution of conflicts because climate change will modify the ranges and locations of species. The MaxEnt model was used to simulate the distribution of wildlife living spaces under current and future climatic conditions (RCP4.5 scenario) based on species distribution data and environmental data from the Three-River Source Region. Furthermore, the logistic-cellular automata model was used to simulate the changes in human activity spaces (construction land and arable land) by 2050. Areas of overlap between wildlife living spaces and human activity spaces were determined by overlay analysis. Then, the areas of construction and arable land that would conflict with wildlife were redistributed outside highly suitable wildlife living spaces. In addition, ecological corridors connecting current and future living spaces were planned for the migration of certain species in response to climate change based on the minimum cumulative resistance model. The results showed that the areas of highly suitable wildlife living spaces will decrease under the influence of climate change if global warming occurs. In the future, the area of overlap between highly suitable wildlife living spaces and construction land will be 125 km2, and that between highly suitable wildlife living spaces and arable land will be 340 km2. The redistribution of these areas will cause human activity spaces to become more concentrated. Moreover, 110 ecological corridors should be constructed across roads in the Three-River Source Region.

Triptolide Promotes the Clearance of α-Synuclein by Enhancing Autophagy in Neuronal Cells.

Parkinson's disease (PD) is an aging-associated neurodegenerative disease with a characteristic feature of α-synuclein accumulation. Point mutations (A53T, A30P) that increase the aggregation propensity of α-synuclein result in familial early onset PD. The abnormal metabolism of α-synuclein results in aberrant level changes of α-synuclein in PD. In pathological conditions, α-synuclein is degraded mainly by the autophagy-lysosome pathway. Triptolide (T10) is a monomeric compound isolated from a traditional Chinese herb. Our group demonstrated for the first time that T10 possesses potent neuroprotective properties both in vitro and in vivo PD models. In the present study, we reported T10 as a potent autophagy inducer in neuronal cells, which helped to promote the clearance of various forms of α-synuclein in neuronal cells. We transfected neuronal cells with A53T mutant (A53T) or wild-type (WT) α-synuclein plasmids and found T10 attenuated the cytotoxicity induced by pathogenic A53T α-synuclein overexpression. We observed that T10 significantly reduced both A53T and WT α-synuclein level in neuronal cell line, as well as in primary cultured cortical neurons. Excluding the changes of syntheses, secretion, and aggregation of α-synuclein, we further added autophagy inhibitor or proteasome inhibitor with T10, and we noticed that T10 promoted the clearance of α-synuclein mainly by the autophagic pathway. Lastly, we observed increased autophagy marker LC3-II expression and autophagosomes by GFP-LC3-II accumulation and ultrastructural characterization. However, the lysosome activity and cell viability were not modulated by T10. Our study revealed that T10 could induce autophagy and promote the clearance of both WT and A53T α-synuclein in neurons. These results provide evidence of T10 as a promising mean to treat PD and other neurodegenerative diseases by reducing pathogenic proteins in neurons.

EP2-PKA signaling is suppressed by triptolide in lipopolysaccharide-induced microglia activation.

BACKGROUND: Microglia are key players for the inflammatory responses in the central nervous system. Suppression of microglial activation and the resulting production of proinflammatory molecules are considered a promising strategy to alleviate the progression of neurodegenerative disorders. Triptolide was demonstrated as a potent anti-inflammatory compound both in vitro and in vivo. The present study explored potential signal pathways of triptolide in the lipopolysaccharide (LPS)-induced inflammatory response using primary rat microglial cells. FINDINGS: Microglial cells were pretreated with triptolide and stimulated with LPS. To investigate the anti-inflammatory effect of triptolide, we used Griess reagent and Western blot for NO release and iNOS expression, respectively. Moreover, we applied microglia-conditioned medium to neuronal cells and used the MTS assay to test cell viability. We found that triptolide inhibited LPS-induced NO and iNOS synthesis in microglial cells, which in turn protected neurons. To evaluate the involvement of the EP2 pathway, we used real-time PCR and Western blot to determine EP2 expression. We found that LPS induced a large increase in EP2 expression in microglia, and triptolide almost completely inhibited LPS-induced EP2 expression. Using the selective EP2 agonist butaprost and the EP2 antagonist AH6809, we determined that triptolide inhibited LPS-stimulated NO production in microglia mainly through the EP2 pathway. Additionally, by further treating triptolide-treated microglia with the downstream PKA-specific activator 6-Bnz-cAMP or the Epac-specific activator 8-pCPT-2-O-Me-cAMP, we found that 6-Bnz-cAMP but not 8-pCPT-2-O-Me-cAMP increased NO production in triptolide-LPS treated microglia. These results indicate that the EP2-PKA pathway is very important for triptolide's effects. CONCLUSIONS: Triptolide inhibits LPS-stimulated NO production in microglia via a signaling mechanism involving EP2 and PKA. This finding may help establish the pharmacological function of triptolide in neurodegenerative disorders. Moreover, the observation of inflammatory EP2 signaling in primary microglia provides important evidence that EP2 regulates innate immunity in the central nervous system.

Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.

The complex pathogenesis of Alzheimer's disease (AD) involves multiple contributing factors, including amyloid ß (Aß) peptide accumulation, inflammation and oxidative stress. Effective therapeutic strategies for AD are still urgently needed. Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases. The 5-month-old 5XFAD mice, which carry five familial AD mutations in the ß-amyloid precursor protein (APP) and presenilin-1 (PS1) genes, were treated with triptolide for 8 weeks. We observed enhanced spatial learning performances, and attenuated Aß production and deposition in the brain. Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of ßAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro. In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain. Triptolide therefore confers protection against the effects of AD in our mouse model and is emerging as a promising therapeutic candidate drug for AD.

AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model.

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder with progressive pathology involving the loss of midbrain dopaminergic neurons. Neurotrophic factors are promising for PD gene therapy; they are integrally involved in the development of the nigrostriatal system. Cerebral dopamine neurotrophic factor (CDNF) was recently discovered to be more selective and potent on preserving dopaminergic neurons than other known trophic factors. The present study examined the neuroprotective and functional restorative effects of CDNF overexpression in the striatum via recombinant adeno-associated virus type 2 (AAV2.CDNF) in 6-hydroxydopamine (6-OHDA) injected rats. Striatal delivery of AAV2.CDNF was able to recover 6-OHDA-induced behavior deficits and resulted in a significant restoration of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and TH-ir fiber density in the striatum. PET analyses with [(11)C]-2ß-carbomethoxy-3ß-(4-fluorophenyl)-tropane ([(11)C]ß-CFT) probes suggested functional recovery of dopaminergic (DA) neurons. Our results indicate that striatal administration of AAV2.CDNF was able to provide effective neuro-restoration in the 6-OHDA-lesioned nigrostriatal system and that it may be considered for future clinical applications in PD therapy.