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Abstract Background Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated. Methods In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests. Results We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects. Conclusions This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.

ABSTRACTIn the context of global warming and the increasing water shortage in dry areas, it is necessary to find a sustainable pathway for utilization of land resources (ULR) to solve these problems. For this purpose, using socioeconomic and environmental indicators from 2006 to 2018 and taking the Tarim Basin, China as an example, this study employed an integrated approach composed of the indicator evaluation system (IES) and the System Dynamics (SD) model to evaluate the possibility of sustainable ULR in the basin. During the simulation, three scenarios namely traditional development (TD), economic priority (EP) and harmonious development (HD) were designed, and different thresholds were set for each indicator of potential ULR in each sub-region to predict their future development status. The IES was established to derive the sustainable utilization degree (SUD) of ULR. The results show that the SUD in Tarim in 2030 is likely be 0.60 (TD), 0.62 (EP) and 0.68 (HD), indicating that only in HD scenario is it possible to find pathway to solve water scarcity problem and achieve sustainable ULR. This study provides a supportive idea for decision-making on sustainable ULR in Tarim and also an approach for similar sustainability assessment in other dry areas.

Abstract Mitochondria morphology and function, and their quality control by mitophagy, are essential for heart function. We investigated whether these are influenced by time of the day (TOD), sex, and fed or fasting status, using transmission electron microscopy (EM), mitochondrial electron transport chain (ETC) activity, and mito-QC reporter mice. We observed peak mitochondrial number at ZT8 in the fed state, which was dependent on the intrinsic cardiac circadian clock, as hearts from cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit different TOD responses. In contrast to mitochondrial number, mitochondrial ETC activities do not fluctuate across TOD, but decrease immediately and significantly in response to fasting. Concurrent with the loss of ETC activities, ETC proteins were decreased with fasting, simultaneous with significant increases of mitophagy, mitochondrial antioxidant protein SOD2, and the fission protein DRP1. Fasting-induced mitophagy was lost in CBK mice, indicating a direct role of BMAL1 in regulating mitophagy. This is the first of its kind report to demonstrate the interactions between sex, fasting, and TOD on cardiac mitochondrial structure, function and mitophagy. These studies provide a foundation for future investigations of mitochondrial functional perturbation in aging and heart diseases.

Abstract To better implement the Strategy of Rural Revitalization, it is essential to characterize the rural settlements and understand their roles in the socio-environmental interactive system. This paper is hence aimed at achieving such a study using different spatial analysis such as kernel density and spatial autocorrelation (SA) and modeling approaches, e.g., simple and multiple linear regression analyses taking Jiangxi, a province in China as an example. Remote sensing, topographic and socioeconomic data were employed for this purpose. Through these analyses, it is found that the rural settlements in the study area appear to have a spatial distribution pattern of “dense north and sparse south” as an “F” type, and are quantitatively characterized as low elevations, flat terrain, high river and road densities, rich cultivated land resources and susceptible to the impact of urban radiation with a R2 of 0.520–0.748. Based on this understanding, a new inequality evaluation indicator of rural development, i.e., socio-environmental evaluation index (SEI), was developed. Areas with SEI lower than 0.40 should be given a priority to implement the revitalization strategy in the province. This index can also be extended to study of the imbalance of rural development in other regions and countries.

As geographic environment is an expression of the geological settings, it is the objective of this research to explore the roles of geological background in society development, in particular, city development. Based on field trips, geological and tectonic maps, digital elevation model (DEM) and Google Earth images were utilized for this study. Simple linear and binary logistic regression (BLR) and a set of spatial analysis were applied to explore the impacts of environmental factors on city distribution and its relationship with the geological factors taking Jiangxi, China as an example. Here we show that distribution of all level of cities is surprisingly consistent with the lithospheric faults, deep-and-large faults which constitute the fundamental framework for developing the open valleys, rivers and plains that host in turn cities. This finding may provide scientists with deeper understanding and rethinking on the human-environmental interaction and decision-makers an idea where to urbanize in future.

Land use/cover change (LUCC) detection and modeling play an important role in global environmental change research, in particular, policy-making to mitigate climate change, support land spatial planning, and achieve sustainable development. For the time being, a couple of hybrid models, such as cellular automata–Markov (CM), logistic–cellular automata-Markov (LCM), multicriteria evaluation (MCE), and multicriteria evaluation–cellular automata–Markov (MCM), are available. However, their disadvantages lie in either dependence on expert knowledge, ignoring the constraining factors, or without consideration of driving factors. For this purpose, we proposed in this paper a new hybrid model, the logistic–multicriteria evaluation–cellular automata–Markov (LMCM) model, that uses the fully standardized logistic regression coefficients as impact weights of the driving factors to represent their importance on each land use type in order to avoid these defects but is able to better predict the future land use pattern with higher accuracy taking Hefei, China as a study area. Based on field investigation, Landsat images dated 2010, 2015, and 2020, together with digital elevation model (DEM) data, were harnessed for land use/cover (LUC) mapping using a supervised classification approach, which was achieved with high overall accuracy (AC) and reliability (AC > 95%). LUC changes in the periods 2010–2015 and 2015–2020 were hence detected using a post-classification differencing approach. Based on the LUC patterns of the study area in 2010 and 2015, the one of 2020 was simulated by the LMCM, CM, LCM, and MCM models under the same conditions and then compared with the classified LUC map of 2020. The results show that the LMCM model performs better than the other three models with a higher simulation accuracy, i.e., 1.72–5.4%, 2.14–6.63%, and 2.78–9.33% higher than the CM, LCM, and MCM models, respectively. For this reason, we used the LMCM model to simulate and predict the LUC pattern of the study area in 2025. It is expected that the results of the simulation may provide scientific support for spatial planning of territory in Hefei, and the LMCM model can be applied to other areas in China and the world for similar purposes.

Intravascular transplantation of human-induced pluripotent stem cells (hiPSCs) demonstrated a significant therapeutic effect in the treatment of restenosis by the paracrine function of extracellular vesicles (EVs). However, the risk of tumorigenicity and poor cell survival limits its clinical applications. In this study, we for the first time applied a highly efficient and robust three-dimensional (3D) protocol for hiPSC differentiation into endothelial cells (ECs) with subsequent isolation of EVs from the derived hiPSC-EC (ECs differentiated from hiPSCs), and validated their therapeutic effect in intimal hyperplasia (IH) models. We found that intravenously (iv) injected EVs could accumulate on the carotid artery endothelium and significantly alleviate the intimal thickening induced by the carotid artery ligation. To elucidate the mechanism of this endothelial protection, we performed miRNA expression profiling and found out that among the most conserved endothelial miRNAs, miR-126 was the most abundant in hiPSC-EC-produced EVs (hiPSC-EC-EV). MiR-126 depletion from hiPSC-EC-EV can hinder its protective effect on human umbilical vein endothelial cells (HUVECs) in an inflammatory process. A variety of functional in vitro studies revealed that miR-126 was able to prevent endothelial apoptosis after inflammatory stimulation, as well as promote EC migration and tube formation through autophagy upregulation. The latter was supported by in vivo studies demonstrating that treatment with hiPSC-EC-EV can upregulate autophagy in mouse carotid artery ECs, thereby preventing IH and modulating vascular homeostasis via remodeling of the vascular intima. Our findings suggest a regulatory mechanism for the therapeutic effect on arterial restenosis by autophagy regulation, and provide a potential strategy for clinical treatment of the disease.

Mesenchymal stem cells (MSCs) have been proven capable of differentiating into endothelial cells (ECs) and increasing vascular density in mouse ischemia models. However, the therapeutic potential of MSCs in neointimal hyperplasia after vascular injury is still not fully understood. In this study, we proposed that sustained release of miR-217 inhibitor encapsulated by nanoparticles in MSCs can enhance the therapeutic effects of MSCs on alleviating neointimal hyperplasia in a standard mouse wire injury model. We intravenously administered MSCs to mice with injured arteries and examined neointimal proliferation, endothelial differentiation and senescence. We demonstrated that MSCs localized to the luminal surface of the injured artery within 24 h after injection and subsequently differentiated into endothelial cells, inhibited neointimal proliferation and migration of vascular smooth muscle cells. Transfection of MSCs with poly lactic-co-glycolic acid nanoparticles (PLGA-NP) encapsulating an miR-217 agomir abolished endothelial differentiation as well as the therapeutic effect of MSCs. On the contrary, silencing of endogenous miR-217 improved the therapeutic efficacy of MSCs. Our study provides a new strategy of augmenting the therapeutic potency of MSCs in treatment of vascular injury.

The first successful sand-control was achieved in the Mu Us Desert by local people in the 1950–1960s, and their experience and approach have been extended to the whole Ordos and Northern China since then. The objective of this paper is to assess comprehensively the effectiveness of sand-control in 15 counties in and around Mu Us using multitemporal satellite images and socioeconomic data. After atmospheric correction, Landsat TM and OLI images were harnessed for land cover classification based on the ground-truth data and for derivation of the GDVI (generalized difference vegetation index) to extract the biophysical changes of the managed desert and desertification. Climatic, socioeconomic, environmental and spatial factors were selected for coupling analysis by multiple linear and logistic regression models to reveal the driving forces of desertification and their spatial determinants. The results show that from 1991 to 2020, 8712 km2 or 63% of the desert has been converted into pastures and shrublands with a greenness increase of 0.3509 in GDVI; the effectiveness of sand-control is favored by the rational agropastoral activities and policies; though desertification occurs locally, it is associated with both climatic and socioeconomic factors, such as wind speed, precipitation, water availability, distance to roads and animal husbandry.