Systems Pharmacology Strategy for the Investigation of Action Mechanisms of Qin Herb Libanotis Buchtormensis (Fisch.) DC. in Bone Diseases.

INTRODUCTION: Qin medicines are medicinal plants growing in habitat around the peak of Qinling Mountain. Their unique curative effects on bone metabolic diseases and pain diseases have been favoured by the local people in clinical trials for thousands of years. Libanotis buchtormensis (Fisch.) DC. (LBD), is one of the popular Qin herbs, which has been widely used for the treatment of various diseases, such as osteoporosis, rheumatic, and cardiovascular diseases. However, due to the multiple compounds in LBD, the underlying molecular mechanisms of LBD remain unclear. OBJECTIVE: This study aimed to systemically investigate the underlying mechanisms of LBD against bone diseases. METHODS: In this study, a systems pharmacology platform included the potential active compound screening, target fishing, and network pharmacological analysis was employed to decipher the action mechanisms of LBD. RESULTS: As a result, 12 potential active compounds and 108 targets were obtained. Furthermore, compound-target network and target-pathway network analysis showed that multi-components interacted with multi-targets and multi-pathways, i.e., MARK signalling pathway, mTORC1 signalling pathway, etc., involved in the regulation of the immune system and circulatory system. These results suggested the mechanisms of the therapeutic effects of LBD on various diseases through most compounds targeted by multiple targets. CONCLUSION: In conclusion, we successfully predicted the LBD bioactive compounds and potential targets, implying that LBD could be applied as a novel therapeutic herb in osteoporosis, rheumatic, and cardiovascular diseases. This work provides insight into the therapeutic mechanisms of LBD for treating various diseases.

Distinguishing the impact of tourism development on ecosystem service trade-offs in ecological functional zone.

Tourism in ecological functional zones (EFZs) is rapidly becoming an increasing trend; however, its impact on ecosystem services remains poorly understood owing to the absence of a consistent quantification framework. This study uses the Taihang Mountains (THM), an EFZ in China, as an example to develop a framework for evaluating the direct and indirect impact pathways of scenic spots on the trade-offs between multiple ecosystem services by identifying the linkages between scenic spot development, socioeconomic change, land use transitions, and ecosystem services. The results show that the continued conversion of agricultural land, grassland, and forest to constructed land around scenic spots in 2000-2020 was accompanied by a decline in water yield (WY) and habitat quality (HQ); while food production (FP), carbon storage (CS), and soil retention (SR) increased. Land use and ecosystem service changes around scenic spots in the THM also exhibited significant spatial gradient effects. In particular, a 10-km buffer area was identified as a distinct "influence zone" where the ecosystem services trade-offs and land use changes were the most pronounced. In 2010, scenic spot revenue was the dominant factor that increased the trade-offs between SR with FP and CS via direct pathways. However, in 2020, the dominant factor was scenic spot level, which shifted the impact toward the relationship between CS and WY and HQ by intensifying the trade-offs to facilitating synergies. This was accomplished in an indirect manner, such as the facilitation of local population growth, industrial restructuring, and infrastructure development. This study reveals the varying effects of scenic spot development via different pathways, thereby providing useful insights for global EFZs to more precisely design policies that can adequately balance human activities with ecosystem services.

Spatiotemporal effects of urban ecological land transitions to thermal environment change in mega-urban agglomeration.

Urban ecological land transitions (UELTs) have far-reaching effects on the thermal environment, but their dynamic effects in urban agglomerations remain poorly understood. This study defines the UELTs concept and quantifies its spatiotemporal effects and driving mechanisms on land surface temperature interdecadal variations (LSTIVs) in the Guangdong-Hong Kong-Macao Greater Bay Area using remote sensing, fuzzy overlay, shape-weighted landscape evolution index, and Geodetector methods. The results showed that UELTs shifted from degradation, increasing pressure, and decreasing vegetation proportion in the central city to scattered restoration, pressure relief, and increasing vegetation proportion in 2010-2020. LSTIVs simultaneously transitioned from rapid growth and contiguous expansion to reduction and dispersion. Moreover, the contribution of UELTs to LSTIVs increased by 19.49% from 2000 to 2020, and gradually shifted from being driven by dominant transition (isolating and adjacent degradation) (mean q = 0.58) to recessive transition (increased population and construction land pressure) (mean q = 0.62), where q is the determinant power. Interactions between edge-expansion and infilling restoration with the blue-green ratio (BGR; i.e., ratio of waterbodies to vegetation), habitat quality, and population layout had significant effects on LSTIVs. In addition, the relative magnitude of the effect of UEL restoration-degradation and BGR on LSTIVs was not fixed, but rather related to their interaction effect and the urban agglomeration development stage. Therefore, in addition to promoting an increase in UEL, optimizing the landscape structure of UEL (e.g., increasing aggregation and connectivity, adjusting BGR) and UEL distribution with other human factors are also crucial to reduce the urban thermal environment.

Quantifying influences of administrative division adjustment on PM2.5 pollution in China's mega-urban agglomerations.

China's mega-urban agglomerations have experienced severe particulate matter pollution that is accompanied by rapid economic growth and extensive administrative division adjustment (ADA). However, the precise roles of ADA on the environmental quality are unknown. Using the geographical detector and evolution tree model, this study quantifies the effects and mechanisms of ADA on the changes in PM2.5 concentration in three mega-urban agglomerations: Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), and Pearl River Delta (PRD) during 2000-2017. Our results showed that: (1) ADA had strong positive effects on PM2.5 concentrations in the 0-6 years lag and negative effects in the 7-10 years lag; (2) During 2000-2009, ADA elevated PM2.5 concentration by 5.93% via stimulating the development and transfer of heavy industry and urban sprawl in the BTH; (3) YRD and PRD respectively reduced the ADA's exacerbating effect to 5.26% and 4.98% via reasonable industrial structures and comprehensive cooperation mechanisms; (4) During 2009-2017, BTH and YRD integrated industrial transformation and environmental protection services through ADA, which alleviated 9.51% and 8.49% of PM2.5 pollution. PRD, meanwhile, accomplished orderly population dispersal and urban expansion by combining ADA with urban planning, thus reducing the PM2.5 concentration by 8.01%. We located three agglomerations in the evolution tree, which provide a basis for formulating relevant policies and region-oriented air pollution joint prevention control strategies.

Ecological Risk Assessment and Protection Zone Identification for Linear Cultural Heritage: A Case Study of the Ming Great Wall.

Ecological risk assessment is an important part of the sustainable development of World Heritage. The Ming Great Wall Heritage (MGWH) plays an important role in World Heritage conservation as a representative of large linear heritage, yet its ecological risks have not received much attention. This study assessed the ecological risk of MGWH based on simultaneous consideration of spatial heterogeneity and autocorrelation of geographic factors, and four protection zones were further identified from the perspective of preservation status and risk by using GeoDetector, principal component analysis and bivariate autocorrelation. The results showed that there were statistically significant differences in the preservation status of MGWH at different elevations. Based on this assessed ecological risk, it was found that 63.49% of MGWH grids were in the low to medium risk, while the highest risk areas (16.61%) were mainly concentrated in lower (200-500 m) and medium (500-1000 m) elevation. As elevation increased, the dominant factor of ecological risk shifted from human factors to natural factors and the main ecological risk showed a trend of increasing and then decreasing with increasing elevation. In addition, four types of risk protection zones (i.e., Protection-Restricted, Restoration-Moderate exploited, Restoration-Restricted and Protection-Moderate exploited) and policy suggestions were identified in this study from the perspectives of conservation, restoration and development, respectively. Future ecological protection of the MGWH should be based on the principle of "cultural heritage protection first", with restricted development and use (e.g., tourism and education) and enhanced ecological restoration and environmental management of the surrounding area. This study provides references for the risk assessment of the cultural heritage at a large spatial scale, which is conducive to the maintenance and improvement of heritage value.

RNA Therapeutics - Research and Clinical Advancements.

RNA therapeutics involve the use of coding RNA such as mRNA as well as non-coding RNAs such as small interfering RNAs (siRNA), antisense oligonucleotides (ASO) to target mRNA, aptamers, ribozymes, and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR/Cas) endonuclease to target proteins and DNA. Due to their diverse targeting ability and research in RNA modification and delivery systems, RNA-based formulations have emerged as suitable treatment options for many diseases. Therefore, in this article, we have summarized different RNA therapeutics, their targeting strategies, and clinical progress for various diseases as well as limitations; so that it might help researchers formulate new and advanced RNA therapeutics for various diseases. Additionally, U.S. Food and Drug Administration (USFDA)-approved RNA-based therapeutics have also been discussed.

Spatial Coupling and Causal Effects between the Recreational Use of Ecological Land and Restoration: A Case Study of the Pearl River Delta Urban Agglomeration.

As the urbanization and industrialization of China's urban agglomerations reach increasingly high levels, residents are voicing a growing demand for improved green public sport and recreational space. The coordination of ecological land restoration (ELR) and recreational use at the regional level is therefore urgent. This study demonstrates the spatiotemporal evolution of coupled ELR and the recreational use of ecological land (RUoEL) in the Pearl River Delta urban agglomeration based on spatial interpretation, remote sensing mapping, and spatial statistical analysis. A geographical and temporally weighted regression is used to test the spatial effects of the RUoEL on the evolution of the ELR patterns. The results show that the RUoEL (mainly greenways and ecological recreational spaces) and ELR exert a certain degree of coupled spatial characteristics, and that the former significantly impacts the latter. These spatial differences are more notable in areas with high-level ecological recreational spaces, or which are located near densely populated built-up areas. Recreation-oriented ELR is therefore relatively easy to develop in these areas. The results provide important guidelines for the development of ecosystem service patterns in urban agglomerations that include the coexistence of ELR and recreational use, which will strengthen the academic support for regional ELR planning and improve public health.

Urban ecological land and natural-anthropogenic environment interactively drive surface urban heat island: An urban agglomeration-level study in China.

The surface urban heat island effect (SUHI) that occurs during rapid urbanization increases the health risks associated with high temperatures. Urban ecological land (UEL) has been shown to play an important role in improving urban heat stress, however, the impact of UEL interactions with the natural-anthropogenic environment on SUHI at the urban agglomeration-scale is less explored. In this study, the Google Earth Engine and GeoDetector were applied to characterize the spatiotemporal patterns of UEL and SUHI in the Guangdong-Hong Kong-Macao Greater Bay Area from 2000 to 2020 by extracting major built-up urban areas and quantifying the impacts of UEL and its interactions with the natural-anthropogenic factors on SUHI. The results show that the evolution of the UEL landscape structure exhibits clear spatiotemporal coupling with SUHI. Specifically, the UEL underwent a dispersion and degradation process in 2000-2015 and a convergence and restoration process in 2015-2020, the SUHI correspondingly transitioned from intensification and continuity to mitigation and contraction. The UEL landscape structure showed a notable impact on the SUHI reduction, and the dominance and richness of the patches explained an average of 19.95% and 16.03% of the SUHI, respectively. Moreover, the interaction between UEL and land urbanization rate and anthropogenic heat release had a dominant effect on SUHI, but this effect significantly declined from 2015 to 2020. With the implementation of ecological restoration projects, the interaction of UEL with topography rapidly increased and the SUHI gradually dominated by the joint interaction of UEL and natural-anthropogenic factors. A synthesis of the varying effects of several factors showed that the dynamic relationship between the development stages of the urban agglomeration's regional system and SUHI may conform to the Environmental Kuznets Curve. SUHI reduction strategies should therefore comprehensively optimize the rational allocation of UEL landscape structures and natural-human elements to promote the well-being of residents.

Spatial-temporal patterns and influencing factors of ecological land degradation-restoration in Guangdong-Hong Kong-Macao Greater Bay Area.

Despite the fact that urban agglomerations have undergone extensive ecological land coverage modifications, exploration of the patterns and driving mechanisms associated with ecological land degradation (ELD) and ecological land restoration (ELR) in urban agglomerations is still limited. This study combined remote sensing technology, as well as landscape index and geographical detector to characterize the spatiotemporal patterns of ELD (isolating, adjacent, and enclosing degradation) and ELR (outlying, edge-expansion, and infilling restoration) in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 1990 to 2019. Subsequently, the contributions, interactions, and driver changes were quantified. The results showed an ecological land shift from over-exploitation to balanced co-existence, which was facilitated by a spatiotemporal pattern transition from adjacent degradation-led (1990-2010) to edge-expansion restoration-led (2010-2019). Land urbanization rate and population density showed a stronger promoting effect on ELD than natural factors, while tertiary industry, topography, and soil conditions were more significant in ELR. The factors' nonlinear interaction enhanced the degradation-restoration pattern evolution and continued to increase over time-particularly the interaction between construction land expansion and other drivers. Additionally, from 2010 to 2019, 80% of the ELR socio-economic factors turned from negative to positive and gradually became to play a significant role. This study is expected to help ecological protection and restoration planners/managers recognize the factors' interactions and variations, and ultimately improve the ecological network structure that is designed to integrate the city with the ecosystem.