Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LM...Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LMRB's terrestrial water storage anomaly(TWSA)and its spatio-temporal dynamics during 2002–2020.Considering the effects of natural factors and human activities,the respective contributions of climate variability and human activities to terrestrial water storage change(TWSC)were separated.Results showed that:(1)LMRB's TWSA decreased by 0.3158 cm/a.(2)TWSA showed a gradual increase in distribution from southwest of MRB to middle LMRB and from northeast of LRB to middle LMRB.TWSA positively changed in Myanmar while slightly changed in Laos and China.It negatively changed in Vietnam,Thailand and Cambodia.(3)TWSA components decreased in a descending order of soil moisture,groundwater and precipitation.(4)Natural factors had a substantial and spatial differentiated influence on TWSA over the LMRB.(5)Climate variability contributed 79%of TWSC in the LMRB while human activities contributed 21%with an increasing impact after 2008.The TWSC of upstream basin countries was found to be controlled by climate variability while Vietnam and Cambodia's TWSC has been controlled by human activities since 2012.展开更多
The Healthy China Initiative is a major health strategy being pursued by the country.To prevent and control different types of diseases as well as their complex variants,research on the spatio-temporal differentiation...The Healthy China Initiative is a major health strategy being pursued by the country.To prevent and control different types of diseases as well as their complex variants,research on the spatio-temporal differentiation among and mechanisms of influence of epidemic diseases is growing worldwide.This study analyzed monthly data on the incidence of influenza by using different methods,including Moran’s I,the hotspot analysis model,concentration analysis,and correlation analysis,to determine the characteristics of spatiotemporal differentiation in the incidence of influenza across prefecture-level cities in China from 2004 to 2017,and to examine its relationship with air pollution.According to the results,the overall incidence of influenza in China exhibited a trend of increase from 2004 to 2017,with small peaks in 2009 and 2014.More cases of influenza were recorded in the first and fourth quarters of each year.Regions with higher incidences of influenza were concentrated in northwestern and northern China,and in the coastal areas of southeastern China.Over time,the distribution of regions with a higher incidence of influenza has shifted from the west to the east of the country.A significant relationship was observed between the incidence of influenza and factors related to air pollution.The contents of five air pollutants(PM_(2.5),PM10,SO_(2),NO_(2),and CO)were significantly positively correlated with the incidence of influenza,with a decreasing order of contribution to it of SO_(2)>CO>NO_(2)>PM_(2.5)>PM_(10).The content of O_(3) in the air was negatively correlated with the incidence of influenza.The influence of air pollution-related factors on the incidence of influenza in different regions and seasons showed minor differences.The large-scale empirical results provided here can supply a scientific basis for governmental disease control authorities to formulate strategies for regional prevention and control.展开更多
Based on the adaptive analysis paradigm,this paper constructs an evaluation index system and an evaluation model of the level of industrial ecology of a restricted development zone from the perspective of the industri...Based on the adaptive analysis paradigm,this paper constructs an evaluation index system and an evaluation model of the level of industrial ecology of a restricted development zone from the perspective of the industrial system and of the environmental system,and studies the spatial-temporal differentiation characteristics and the driving factors of the level of industrial ecology of the restricted development zone of the Shandong Province,China,by using a variety of measurement methods.The results show that:1)In the temporal dimension,the level of industrial ecology of the research area increased from 2005 to 2017,while in the regional dimension,it was higher in the eastern coastal areas,followed by the northwestern area and the southwestern area;2)In the spatial dimension,from 2005 to 2017 the level of industrial ecology of the research area had a clear spatial dependence,and the regional spatial agglomeration of the restricted development zones with similar industrial ecology levels become increasingly evident;3)On the whole,the industrial ecology level in the study area had a clear spatial differentiation pattern,as it was higher in the north and in the east and lower in the south and in the west.Moreover,its evolution model changed from a‘three-core driven model’to a‘spatial scattered mosaic distribution model’,and then to a‘single-core driven model’;4)Industrial ecology was positively correlated with economic development,foreign investment,science and technology,and negatively correlated with the government role,while industrial structure and environmental regulation failed to pass the statistical significance test.展开更多
In this study, we attempt to put forward a conception of landscape ecological niche, enlightened by international scholars on extending the ecological niche theory from spatial niche to functional niche. That is helpf...In this study, we attempt to put forward a conception of landscape ecological niche, enlightened by international scholars on extending the ecological niche theory from spatial niche to functional niche. That is helpful for comprehensively appraising landscape spatial patterns and ecological functions, also, presents a new method for analyzing landscape features from multidimensional aspects. The practice process is demonstrated by taking Yan＇an region in northwestern China as a case. Firstly, the indices system including spatial attribute and functional attribute is established for assessing landscape ecological niche. Additionally, two-dimensional figures are drawn for comparing the spatio-temporal features of landscape ecological niche in 1987 and 2000 among the 13 administrative counties. The results show that from 1987 to 2000, towards Yan＇an region, spatial attribute value of landscape ecological niche changes from 1.000 to 1.178 with an obvious increment, and functional attribute value changes from 0.989 to 1.069 with a little increment, both of which enhance the regional landscape ecological niche. Towards each county, spatial attribute value of landscape ecological niche increases to different extent while functional attribute value changes dissimilarly with an increment or a decrement.展开更多
Based on SPOT5 satellite remote sensing images and land use data in five time phases covering the period 1988–2012, the distribution characteristics, spatial differentiation processes, and driving mechanisms affectin...Based on SPOT5 satellite remote sensing images and land use data in five time phases covering the period 1988–2012, the distribution characteristics, spatial differentiation processes, and driving mechanisms affecting the residential land of the Jinshitan Tourist Resort were studied. The work included a combination of GIS technology, adoption of the differentiation index D, and the multi-group differentiation-measure model D(m). The results provided a basis for the following conclusions: 1) From 1988 to 2012, the degree of differentiation of the rural residential land first decreased, and then increased. The general residential, commercial residential and garden-house land-types all showed declining trends, of which the garden-house type presented the most intense volatility. 2) The overall background of the traditional residential land type was gradually replaced by a new residential land type, and the total area of residential land increased year by year, significantly improving the overall residential conditions. The areas of the new residential land type showed growth, and were increasingly widely distributed in the coastal tourist resorts, transportation corridors, and scenic areas. 3) Government policy, social differentiation, market mechanisms, and individual choices(along with other factors) were mutually promoted, although still restrained. However, all of these factors interacted to constrain the developmental direction and the processes affecting tourism real estate in the Dalian Jinshitan Tourist Resort.展开更多
Large amounts of data accumulated in ecology and related environmental sciences arouses urgent need to explore useful patterns and information in it.Here we propose coclustering-based methods and a temperatures-photop...Large amounts of data accumulated in ecology and related environmental sciences arouses urgent need to explore useful patterns and information in it.Here we propose coclustering-based methods and a temperatures-photoperiod driven phenological model to explore spatio-temporal differentiation in long-term spring phenology in China.First,we created the first bloom date(FBD)dataset in China from 1979 to 2018 using the extended spring indices and China Meteorological Forcing Dataset.Then we analyzed the dataset using Bregman block average co-clustering algorithm with I-divergence(BBAC_I)and kmeans algorithm.Such analysis delineated the spatially-continuous phenoregions in China for the first time.Results showed three spatial patterns of FBD in China and their temporal dynamics for 40 years(1979–2018).More specifically,overall late spring onsets occur in 1979–1996,in which areas located in Jiangxi,northern Xinjiang and middle Inner Mongolia experienced constant changing spring onsets.Overall increasingly earlier spring onsets occur in 1997–2012,in which areas located in Fujian,Hunan and eastern Heilongjiang experienced the most variable spring onsets.Stable early spring onsets over China occur after 2012.Results also showed 15 temporal patterns of spring phenology over the study period and their spatial delineation in China.More specifically,most areas in China have the same FBD category for 40 years while northern Guizhou,Hunan and southern Hubei have the same category in 1979–1997 and then fluctuate between different categories.Finally,our results have certain directive significance on the design of existing observational sites in Chinese Phenological Network.展开更多
Green and plaza land(GPL)is one of the basic elements of urban construction,and is also the most basic public space to meet the needs of citizens for a better life.The exploration on its internal development laws can ...Green and plaza land(GPL)is one of the basic elements of urban construction,and is also the most basic public space to meet the needs of citizens for a better life.The exploration on its internal development laws can provide theoretical foundations for the planning of GPL and creating good human settlements.Taking 612 cities in China as the study area and from the"people-land"perspective,this paper selects the total GPL area,the per capita GPL area,and the land use proportion of per capita GPL as indicators to analyze the spatio-temporal differentiation characteristics and evolution rules of the construction level of GPL in China from 1996 to 2016,by using mathematical statistics and spatial analysis methods.The result shows:(1)from a national perspective,the construction level of GPL in China has been rapidly improved along with the temporal evolution,but there is still a big gap from the upper limit of the standard.In terms of the spatial distribution,regional differences have always been great,and the cities scoring below the standard are concentrated in the eastern and central regions,while high-scoring cities are more concentrated in the western region;the distribution of the land use proportion of per capita GPL is in a pattern that the eastern region has the highest proportion,followed by the western region,central region,and northeastern region successively.(2)From the perspective of scale,differences between cities of different sizes exist over a long period of time,and there is an obvious imbalance in the per capita GPL area as well as the land use proportion of per capita GPL between different cities.The construction level shows that small cities have the highest level,followed by medium-sized cities and then large cities.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Mountain area accounts for a high proportion of the land area in China,and it is the focal area to solve the contradiction of imbalanced regional development,as well as an important source of ecosystem services.Theref...Mountain area accounts for a high proportion of the land area in China,and it is the focal area to solve the contradiction of imbalanced regional development,as well as an important source of ecosystem services.Therefore,this area has been facing long-term pressure and challenges in economic development and ecological protection.In this paper,we selected a rocky desertification mountain area,an active mountain area of new tectonic movement and a typical northern earth-rock mountain area,as Qian-Gui karst Mountain area,Hengduan Mountain area and Taihang Mountain area,as examples to represent three main types of mountain areas.Three representative types of ecosystem services,including NPP(Net Primary Productivity)as a support service,water conservation as a regulation service,and agricultural produce as a supply service,were incorporated into this study.Linear regression,correlation analysis and other methods were then used to investigate the spatial-temporal characteristics of the trade-offs and synergies in each of the three kinds of mountain areas during 1990-2015 in China.The analysis yielded three main conclusions for the three mountainous areas.(1)The agricultural produce supply service decreased relatively,while the support and regulation services of NPP and hydrological regulation increased significantly.(2)There was a synergistic relationship between NPP and the hydrological regulation services in the three mountainous areas.The synergistic relation in Qian-Gui karst Mountain area became enhanced,while those in Hengduan and Taihang Mountain areas became weakened,and the former was weakened to a greater extent.There was a trade-off between NPP,the hydrological regulation service and the agricultural produce supply service among the three mountainous areas.In particular,the trade-off between NPP and the agricultural produce supply service in Qian-Gui karst Mountain area became weaker,while those in Hengduan and Taihang Mountain areas were enhanced,and the latter was enhanced to a greater degree.(3)Significant spatial differentiation was evident in the trade-offs and synergies of ecosystem services among the three mountain areas.展开更多
Cultivated land pressure is often used to reflect the shortage of cultivated land resources. By using the methods of the Cultivated Land Pressure Index, coefficient of variation and cold-hot spot analysis, this paper ...Cultivated land pressure is often used to reflect the shortage of cultivated land resources. By using the methods of the Cultivated Land Pressure Index, coefficient of variation and cold-hot spot analysis, this paper analyzes the spatial-temporal differentiation pattern and dynamic change processes of cultivated land pressure in the counties of the Pearl River-Xijiang Economic Zone from 2008 to 2017, and measures the factors which influence cultivated land pressure by using Principal Component Analysis. The results show that the cultivated land pressure in the Pearl River-Xijiang Economic Zone has been in a “high pressure” state, and the Cultivated Land Pressure Index has been rising continuously from 2008 to 2017. The coefficient of variation of the Cultivated Land Pressure Index in the Pearl River-Xijiang Economic Zone and various prefecture-level cities is fluctuating and rising, which indicates that the overall spatial differences in the cultivated land pressure in this region are expanding and polarization is obvious. In addition, the area where the municipal district of the provincial capital city is located is the core area of urban development and also the area with the greatest cultivated land pressure. The spatial pattern of cultivated land pressure cold-hot spots in the Pearl River-Xijiang Economic Zone is obviously heterogeneous, in which the Pearl River Economic Zone is the main hot spot gathering area and the Xijiang Economic Zone is the main cold spot gathering area. Farmers’ income, investment in fixed assets, GDP, population and other socio-economic factors are the main factors driving the changes in the cultivated land pressure in the Pearl River-Xijiang Economic Zone. Furthermore, farming production factors, such as the multiple cropping index and grain yield per unit area,will also have an important impact on the changes in the cultivated land pressure.展开更多
Sloping farmland,particularly in mountainous and hilly areas,constitutes a significant component of regional farmland resources.An investigation into the spatio-temporal pattern of sloping farmland and its influencing...Sloping farmland,particularly in mountainous and hilly areas,constitutes a significant component of regional farmland resources.An investigation into the spatio-temporal pattern of sloping farmland and its influencing factors in China is imperative for the efficient utilization of farmland and the optimization of land space.We used land use transfer matrix,geographically weighted regression model and geographical detector to conduct this study.Results showed that sloping farmland in China firstly decreased and then increased from 2000 to 2020.The proportion of sloping farmland decreased radially outward from Sichuan basin to the surrounding areas.Change rates of sloping farmland with different slopes varied and the slope with 6°-15°underwent the fastest changes.The influencing factors of farmland at various slope degrees were different.For sloping farmland below 15°,land use intensity and elevation had the greatest contribution.For sloping farmland between 15°and 25°,elevation,land use intensity,and population density were the main influencing factors.Sloping farmland above 25°was mostly affected by natural factors.This study can provide scientific basis for rational development and protection of sloping farmland.展开更多
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
The ability to accurately predict urban traffic flows is crucial for optimising city operations.Consequently,various methods for forecasting urban traffic have been developed,focusing on analysing historical data to u...The ability to accurately predict urban traffic flows is crucial for optimising city operations.Consequently,various methods for forecasting urban traffic have been developed,focusing on analysing historical data to understand complex mobility patterns.Deep learning techniques,such as graph neural networks(GNNs),are popular for their ability to capture spatio-temporal dependencies.However,these models often become overly complex due to the large number of hyper-parameters involved.In this study,we introduce Dynamic Multi-Graph Spatial-Temporal Graph Neural Ordinary Differential Equation Networks(DMST-GNODE),a framework based on ordinary differential equations(ODEs)that autonomously discovers effective spatial-temporal graph neural network(STGNN)architectures for traffic prediction tasks.The comparative analysis of DMST-GNODE and baseline models indicates that DMST-GNODE model demonstrates superior performance across multiple datasets,consistently achieving the lowest Root Mean Square Error(RMSE)and Mean Absolute Error(MAE)values,alongside the highest accuracy.On the BKK(Bangkok)dataset,it outperformed other models with an RMSE of 3.3165 and an accuracy of 0.9367 for a 20-min interval,maintaining this trend across 40 and 60 min.Similarly,on the PeMS08 dataset,DMST-GNODE achieved the best performance with an RMSE of 19.4863 and an accuracy of 0.9377 at 20 min,demonstrating its effectiveness over longer periods.The Los_Loop dataset results further emphasise this model’s advantage,with an RMSE of 3.3422 and an accuracy of 0.7643 at 20 min,consistently maintaining superiority across all time intervals.These numerical highlights indicate that DMST-GNODE not only outperforms baseline models but also achieves higher accuracy and lower errors across different time intervals and datasets.展开更多
The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with t...The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with the advantage of being environmental-friendly.As one of the organic acids produced by biological metabolism,citric acid was used to leach REEs and explore the performance and process.The results demonstrate that citric acid exhibits higher leaching efficiency(96.00%)for REEs at a relatively low concentration of 0.01 mol/L compared with(NH_(4))_(2)SO_(4)(84.29%,0.1 mol/L)and MgSO_(4)(83.99%,0.1 mol/L).Citric acid shows a preference for leaching heavy rare earth elements,with 99%leaching efficiency in IAREO,which shows higher capacity than(NH_(4))_(2)SO_(4)and MgSO_(4)(as inorganic leaching agents).Kinetic analysis indicates that the leaching process of REEs with citric acid is controlled by both the internal diffusion kinetics and chemical reaction kinetics,which is different from inorganic leaching agents.Visual Minteq calculations confirm that RE-Citrate is the main constituent of the extract solution in the leaching process of the IAREO,thereby enhancing the leaching efficiency of REEs from the IAREO.It suggests that citric acid may be used as a promising organic leaching agent for the environmentalfriendly extraction of REEs from IAREO.展开更多
Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infr...Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,...The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.展开更多
Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characteri...Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.展开更多
The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic fu...The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.展开更多
Objective To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis(TB)in the Guangdong Province between 2010 and 2019.Method Spatial and temporal variations in TB ...Objective To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis(TB)in the Guangdong Province between 2010 and 2019.Method Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering.Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive(ST-CAR)model.Results Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000in 2019.Spatial hotspots were found in northeastern Guangdong,particularly in Heyuan,Shanwei,and Shantou,while Shenzhen,Dongguan,and Foshan had the lowest rates in the Pearl River Delta.The STCAR model showed that the TB risk was lower with higher per capita Gross Domestic Product(GDP)[Relative Risk(RR),0.91;95%Confidence Interval(CI):0.86–0.98],more the ratio of licensed physicians and physician(RR,0.94;95%CI:0.90-0.98),and higher per capita public expenditure(RR,0.94;95%CI:0.90–0.97),with a marginal effect of population density(RR,0.86;95%CI:0.86–1.00).Conclusion The incidence of TB in Guangdong varies spatially and temporally.Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection.Strategies focusing on equitable health resource distribution and economic development are the key to TB control.展开更多
基金National Natural Science Foundation of China,No.42161006Yunnan Fundamental Research Projects No.202201AT070094,No.202301BF070001-004+1 种基金Special Project for High-level Talents of Yunnan Province for Young Top Talents,No.C6213001159European Research Council(ERC)Starting-Grant STORIES,No.101040939。
文摘Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LMRB's terrestrial water storage anomaly(TWSA)and its spatio-temporal dynamics during 2002–2020.Considering the effects of natural factors and human activities,the respective contributions of climate variability and human activities to terrestrial water storage change(TWSC)were separated.Results showed that:(1)LMRB's TWSA decreased by 0.3158 cm/a.(2)TWSA showed a gradual increase in distribution from southwest of MRB to middle LMRB and from northeast of LRB to middle LMRB.TWSA positively changed in Myanmar while slightly changed in Laos and China.It negatively changed in Vietnam,Thailand and Cambodia.(3)TWSA components decreased in a descending order of soil moisture,groundwater and precipitation.(4)Natural factors had a substantial and spatial differentiated influence on TWSA over the LMRB.(5)Climate variability contributed 79%of TWSC in the LMRB while human activities contributed 21%with an increasing impact after 2008.The TWSC of upstream basin countries was found to be controlled by climate variability while Vietnam and Cambodia's TWSC has been controlled by human activities since 2012.
基金Under the auspices of Key Program of National Natural Science Foundation of China(No.41630749)Program of the National Social Science Fund of China(No.17BJL051)Fundamental Research Funds for the Central Universities(No.1709103,2412020FZ001)。
文摘The Healthy China Initiative is a major health strategy being pursued by the country.To prevent and control different types of diseases as well as their complex variants,research on the spatio-temporal differentiation among and mechanisms of influence of epidemic diseases is growing worldwide.This study analyzed monthly data on the incidence of influenza by using different methods,including Moran’s I,the hotspot analysis model,concentration analysis,and correlation analysis,to determine the characteristics of spatiotemporal differentiation in the incidence of influenza across prefecture-level cities in China from 2004 to 2017,and to examine its relationship with air pollution.According to the results,the overall incidence of influenza in China exhibited a trend of increase from 2004 to 2017,with small peaks in 2009 and 2014.More cases of influenza were recorded in the first and fourth quarters of each year.Regions with higher incidences of influenza were concentrated in northwestern and northern China,and in the coastal areas of southeastern China.Over time,the distribution of regions with a higher incidence of influenza has shifted from the west to the east of the country.A significant relationship was observed between the incidence of influenza and factors related to air pollution.The contents of five air pollutants(PM_(2.5),PM10,SO_(2),NO_(2),and CO)were significantly positively correlated with the incidence of influenza,with a decreasing order of contribution to it of SO_(2)>CO>NO_(2)>PM_(2.5)>PM_(10).The content of O_(3) in the air was negatively correlated with the incidence of influenza.The influence of air pollution-related factors on the incidence of influenza in different regions and seasons showed minor differences.The large-scale empirical results provided here can supply a scientific basis for governmental disease control authorities to formulate strategies for regional prevention and control.
基金Under the auspices of National Natural Science Foundation of China(No.41801105,41771138)National Natural Science Foundation of Shandong(No.ZR2018BD002)Social Science Planning Research Project of Shandong(No.18DJJJ14)。
文摘Based on the adaptive analysis paradigm,this paper constructs an evaluation index system and an evaluation model of the level of industrial ecology of a restricted development zone from the perspective of the industrial system and of the environmental system,and studies the spatial-temporal differentiation characteristics and the driving factors of the level of industrial ecology of the restricted development zone of the Shandong Province,China,by using a variety of measurement methods.The results show that:1)In the temporal dimension,the level of industrial ecology of the research area increased from 2005 to 2017,while in the regional dimension,it was higher in the eastern coastal areas,followed by the northwestern area and the southwestern area;2)In the spatial dimension,from 2005 to 2017 the level of industrial ecology of the research area had a clear spatial dependence,and the regional spatial agglomeration of the restricted development zones with similar industrial ecology levels become increasingly evident;3)On the whole,the industrial ecology level in the study area had a clear spatial differentiation pattern,as it was higher in the north and in the east and lower in the south and in the west.Moreover,its evolution model changed from a‘three-core driven model’to a‘spatial scattered mosaic distribution model’,and then to a‘single-core driven model’;4)Industrial ecology was positively correlated with economic development,foreign investment,science and technology,and negatively correlated with the government role,while industrial structure and environmental regulation failed to pass the statistical significance test.
基金National Natural Science Foundation of China, No.40371003 Innovation Foundation of Shaanxi Normal University
文摘In this study, we attempt to put forward a conception of landscape ecological niche, enlightened by international scholars on extending the ecological niche theory from spatial niche to functional niche. That is helpful for comprehensively appraising landscape spatial patterns and ecological functions, also, presents a new method for analyzing landscape features from multidimensional aspects. The practice process is demonstrated by taking Yan＇an region in northwestern China as a case. Firstly, the indices system including spatial attribute and functional attribute is established for assessing landscape ecological niche. Additionally, two-dimensional figures are drawn for comparing the spatio-temporal features of landscape ecological niche in 1987 and 2000 among the 13 administrative counties. The results show that from 1987 to 2000, towards Yan＇an region, spatial attribute value of landscape ecological niche changes from 1.000 to 1.178 with an obvious increment, and functional attribute value changes from 0.989 to 1.069 with a little increment, both of which enhance the regional landscape ecological niche. Towards each county, spatial attribute value of landscape ecological niche increases to different extent while functional attribute value changes dissimilarly with an increment or a decrement.
基金Under the auspices of National Natural Science Foundation of China(No.41471140)Outstanding Youth Program of Liaoning Province(No.LJQ2015058)
文摘Based on SPOT5 satellite remote sensing images and land use data in five time phases covering the period 1988–2012, the distribution characteristics, spatial differentiation processes, and driving mechanisms affecting the residential land of the Jinshitan Tourist Resort were studied. The work included a combination of GIS technology, adoption of the differentiation index D, and the multi-group differentiation-measure model D(m). The results provided a basis for the following conclusions: 1) From 1988 to 2012, the degree of differentiation of the rural residential land first decreased, and then increased. The general residential, commercial residential and garden-house land-types all showed declining trends, of which the garden-house type presented the most intense volatility. 2) The overall background of the traditional residential land type was gradually replaced by a new residential land type, and the total area of residential land increased year by year, significantly improving the overall residential conditions. The areas of the new residential land type showed growth, and were increasingly widely distributed in the coastal tourist resorts, transportation corridors, and scenic areas. 3) Government policy, social differentiation, market mechanisms, and individual choices(along with other factors) were mutually promoted, although still restrained. However, all of these factors interacted to constrain the developmental direction and the processes affecting tourism real estate in the Dalian Jinshitan Tourist Resort.
基金supported by the National Key R&D Program of China(Grant No.2019YFA0606901)the National Natural Science Foundation of China(Grant No.41901317)the China Postdoctoral Science Foundation(Grant No.2018M641246)。
文摘Large amounts of data accumulated in ecology and related environmental sciences arouses urgent need to explore useful patterns and information in it.Here we propose coclustering-based methods and a temperatures-photoperiod driven phenological model to explore spatio-temporal differentiation in long-term spring phenology in China.First,we created the first bloom date(FBD)dataset in China from 1979 to 2018 using the extended spring indices and China Meteorological Forcing Dataset.Then we analyzed the dataset using Bregman block average co-clustering algorithm with I-divergence(BBAC_I)and kmeans algorithm.Such analysis delineated the spatially-continuous phenoregions in China for the first time.Results showed three spatial patterns of FBD in China and their temporal dynamics for 40 years(1979–2018).More specifically,overall late spring onsets occur in 1979–1996,in which areas located in Jiangxi,northern Xinjiang and middle Inner Mongolia experienced constant changing spring onsets.Overall increasingly earlier spring onsets occur in 1997–2012,in which areas located in Fujian,Hunan and eastern Heilongjiang experienced the most variable spring onsets.Stable early spring onsets over China occur after 2012.Results also showed 15 temporal patterns of spring phenology over the study period and their spatial delineation in China.More specifically,most areas in China have the same FBD category for 40 years while northern Guizhou,Hunan and southern Hubei have the same category in 1979–1997 and then fluctuate between different categories.Finally,our results have certain directive significance on the design of existing observational sites in Chinese Phenological Network.
基金co-funded by the National Natural Science Foundation of China(No.51778389)the“Qing Lan Project”of Colleges and Universities of Jiangsu Province+1 种基金the Enterprise-Postgraduate Studio of Jiangsu Provincethe Project of Disciplinary Construction of Landscape Architecture at Suzhou University of Science and Technology。
文摘Green and plaza land(GPL)is one of the basic elements of urban construction,and is also the most basic public space to meet the needs of citizens for a better life.The exploration on its internal development laws can provide theoretical foundations for the planning of GPL and creating good human settlements.Taking 612 cities in China as the study area and from the"people-land"perspective,this paper selects the total GPL area,the per capita GPL area,and the land use proportion of per capita GPL as indicators to analyze the spatio-temporal differentiation characteristics and evolution rules of the construction level of GPL in China from 1996 to 2016,by using mathematical statistics and spatial analysis methods.The result shows:(1)from a national perspective,the construction level of GPL in China has been rapidly improved along with the temporal evolution,but there is still a big gap from the upper limit of the standard.In terms of the spatial distribution,regional differences have always been great,and the cities scoring below the standard are concentrated in the eastern and central regions,while high-scoring cities are more concentrated in the western region;the distribution of the land use proportion of per capita GPL is in a pattern that the eastern region has the highest proportion,followed by the western region,central region,and northeastern region successively.(2)From the perspective of scale,differences between cities of different sizes exist over a long period of time,and there is an obvious imbalance in the per capita GPL area as well as the land use proportion of per capita GPL between different cities.The construction level shows that small cities have the highest level,followed by medium-sized cities and then large cities.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金The National Natural Science Foundation of China(41771115)National Key Basic Research and Development Program(2015CB452706)Guizhou Science and Technology Fund(Guizhou Technology Cooperation Basis 20181116)。
文摘Mountain area accounts for a high proportion of the land area in China,and it is the focal area to solve the contradiction of imbalanced regional development,as well as an important source of ecosystem services.Therefore,this area has been facing long-term pressure and challenges in economic development and ecological protection.In this paper,we selected a rocky desertification mountain area,an active mountain area of new tectonic movement and a typical northern earth-rock mountain area,as Qian-Gui karst Mountain area,Hengduan Mountain area and Taihang Mountain area,as examples to represent three main types of mountain areas.Three representative types of ecosystem services,including NPP(Net Primary Productivity)as a support service,water conservation as a regulation service,and agricultural produce as a supply service,were incorporated into this study.Linear regression,correlation analysis and other methods were then used to investigate the spatial-temporal characteristics of the trade-offs and synergies in each of the three kinds of mountain areas during 1990-2015 in China.The analysis yielded three main conclusions for the three mountainous areas.(1)The agricultural produce supply service decreased relatively,while the support and regulation services of NPP and hydrological regulation increased significantly.(2)There was a synergistic relationship between NPP and the hydrological regulation services in the three mountainous areas.The synergistic relation in Qian-Gui karst Mountain area became enhanced,while those in Hengduan and Taihang Mountain areas became weakened,and the former was weakened to a greater extent.There was a trade-off between NPP,the hydrological regulation service and the agricultural produce supply service among the three mountainous areas.In particular,the trade-off between NPP and the agricultural produce supply service in Qian-Gui karst Mountain area became weaker,while those in Hengduan and Taihang Mountain areas were enhanced,and the latter was enhanced to a greater degree.(3)Significant spatial differentiation was evident in the trade-offs and synergies of ecosystem services among the three mountain areas.
基金The Guangdong Education Science Planning Project(2019GXJK080)The Guangdong Philosophy and Social Science Planning Project(GD19YYJ03)The Guangdong Coastal Economic Belt Development Research Institute 2020 Special Project(YJY202002).
文摘Cultivated land pressure is often used to reflect the shortage of cultivated land resources. By using the methods of the Cultivated Land Pressure Index, coefficient of variation and cold-hot spot analysis, this paper analyzes the spatial-temporal differentiation pattern and dynamic change processes of cultivated land pressure in the counties of the Pearl River-Xijiang Economic Zone from 2008 to 2017, and measures the factors which influence cultivated land pressure by using Principal Component Analysis. The results show that the cultivated land pressure in the Pearl River-Xijiang Economic Zone has been in a “high pressure” state, and the Cultivated Land Pressure Index has been rising continuously from 2008 to 2017. The coefficient of variation of the Cultivated Land Pressure Index in the Pearl River-Xijiang Economic Zone and various prefecture-level cities is fluctuating and rising, which indicates that the overall spatial differences in the cultivated land pressure in this region are expanding and polarization is obvious. In addition, the area where the municipal district of the provincial capital city is located is the core area of urban development and also the area with the greatest cultivated land pressure. The spatial pattern of cultivated land pressure cold-hot spots in the Pearl River-Xijiang Economic Zone is obviously heterogeneous, in which the Pearl River Economic Zone is the main hot spot gathering area and the Xijiang Economic Zone is the main cold spot gathering area. Farmers’ income, investment in fixed assets, GDP, population and other socio-economic factors are the main factors driving the changes in the cultivated land pressure in the Pearl River-Xijiang Economic Zone. Furthermore, farming production factors, such as the multiple cropping index and grain yield per unit area,will also have an important impact on the changes in the cultivated land pressure.
基金supported by the Key Laboratory of Natural Resources Monitoring and Supervision in Southern Hilly Region,Ministry of Natural Resources(NRMSSHR2023Y02)Yunnan Key Laboratory of Plateau Geographic Processes and Environmental Changes,Faculty of Geography,Yunnan Normal University(PGPEC2304)China Scholarship Council。
文摘Sloping farmland,particularly in mountainous and hilly areas,constitutes a significant component of regional farmland resources.An investigation into the spatio-temporal pattern of sloping farmland and its influencing factors in China is imperative for the efficient utilization of farmland and the optimization of land space.We used land use transfer matrix,geographically weighted regression model and geographical detector to conduct this study.Results showed that sloping farmland in China firstly decreased and then increased from 2000 to 2020.The proportion of sloping farmland decreased radially outward from Sichuan basin to the surrounding areas.Change rates of sloping farmland with different slopes varied and the slope with 6°-15°underwent the fastest changes.The influencing factors of farmland at various slope degrees were different.For sloping farmland below 15°,land use intensity and elevation had the greatest contribution.For sloping farmland between 15°and 25°,elevation,land use intensity,and population density were the main influencing factors.Sloping farmland above 25°was mostly affected by natural factors.This study can provide scientific basis for rational development and protection of sloping farmland.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
文摘The ability to accurately predict urban traffic flows is crucial for optimising city operations.Consequently,various methods for forecasting urban traffic have been developed,focusing on analysing historical data to understand complex mobility patterns.Deep learning techniques,such as graph neural networks(GNNs),are popular for their ability to capture spatio-temporal dependencies.However,these models often become overly complex due to the large number of hyper-parameters involved.In this study,we introduce Dynamic Multi-Graph Spatial-Temporal Graph Neural Ordinary Differential Equation Networks(DMST-GNODE),a framework based on ordinary differential equations(ODEs)that autonomously discovers effective spatial-temporal graph neural network(STGNN)architectures for traffic prediction tasks.The comparative analysis of DMST-GNODE and baseline models indicates that DMST-GNODE model demonstrates superior performance across multiple datasets,consistently achieving the lowest Root Mean Square Error(RMSE)and Mean Absolute Error(MAE)values,alongside the highest accuracy.On the BKK(Bangkok)dataset,it outperformed other models with an RMSE of 3.3165 and an accuracy of 0.9367 for a 20-min interval,maintaining this trend across 40 and 60 min.Similarly,on the PeMS08 dataset,DMST-GNODE achieved the best performance with an RMSE of 19.4863 and an accuracy of 0.9377 at 20 min,demonstrating its effectiveness over longer periods.The Los_Loop dataset results further emphasise this model’s advantage,with an RMSE of 3.3422 and an accuracy of 0.7643 at 20 min,consistently maintaining superiority across all time intervals.These numerical highlights indicate that DMST-GNODE not only outperforms baseline models but also achieves higher accuracy and lower errors across different time intervals and datasets.
基金Project supported by the Thousand Talents Program of Jiangxi Province,China(JXSQ2023201003)National Natural Science Foundation of China(42107254)+4 种基金Science and Technology Major Program of Ordos City(2022EEDSKJZDZX014-2)Technological Innovation Guidance Program of Jiangxi Province(20212BDH81029)Rare Earth Industry Fund(IAGM2020DB06)Selfdeployed Projects of Ganjiang Innovation Academy,Chinese Academy of Sciences(E055A01)the Key Research Program of the Chinese Academy of Sciences(ZDRW-CN-2021-3-3)。
文摘The rare earth elements(REEs)extraction by chemical leaching from ion-adsorption type rare earth ores(IAREO)has led to serious ecological and environmental risks.Conversely,demand for bioleaching is on the rise with the advantage of being environmental-friendly.As one of the organic acids produced by biological metabolism,citric acid was used to leach REEs and explore the performance and process.The results demonstrate that citric acid exhibits higher leaching efficiency(96.00%)for REEs at a relatively low concentration of 0.01 mol/L compared with(NH_(4))_(2)SO_(4)(84.29%,0.1 mol/L)and MgSO_(4)(83.99%,0.1 mol/L).Citric acid shows a preference for leaching heavy rare earth elements,with 99%leaching efficiency in IAREO,which shows higher capacity than(NH_(4))_(2)SO_(4)and MgSO_(4)(as inorganic leaching agents).Kinetic analysis indicates that the leaching process of REEs with citric acid is controlled by both the internal diffusion kinetics and chemical reaction kinetics,which is different from inorganic leaching agents.Visual Minteq calculations confirm that RE-Citrate is the main constituent of the extract solution in the leaching process of the IAREO,thereby enhancing the leaching efficiency of REEs from the IAREO.It suggests that citric acid may be used as a promising organic leaching agent for the environmentalfriendly extraction of REEs from IAREO.
基金supported by the National Research Foundation(NRF)S&F-Scarce Skills Postdoctoral Fellowship,No.120752(to AC)the Global Excellence and Stature,Fourth Industrial Revolution(GES 4.0)Postgraduate Scholarship(to MJR)the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa(SARChI/NRF-DST),No.146290(to DDS and HA).
文摘Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
基金supported by National Natural Science Foundation of China(grant numbers 82072523 to Zhiyong Hou)Postdoctoral program of Clinical medicine of Hebei Medical University(grant numbers PD2023012 to Sujuan Xu)+2 种基金Excellent postdoctoral research funding project of Hebei Province(grant numbers B2023005011 to Sujuan Xu)The 16th special grant of China Postdoctoral Science Foundation(grant numbers 2023T160182 to Sujuan Xu)Natural Science Foundation of Hebei Province,China(grant numbers H2023206230 to Yingchao Yin,H2024206186 to Sujuan Xu).
文摘The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
基金supported by grants from the Liaoning Province Excellent Talent Program Project(XLYC1902031)Dalian Science and Technology Talent Innovation Plan Grant(2022RG18)Basic Research Project of the Department of Education of Liaoning Province(LJKQZ20222395)。
文摘Objective Cerebral palsy(CP)is a prevalent neurodevelopmental disorder acquired during the perinatal period,with periventricular white matter injury(PWMI)serving as its primary pathological hallmark.PWMI is characterized by the loss of oligodendrocytes(OLs)and the disintegration of myelin sheaths,leading to impaired neural connectivity and motor dysfunction.Neural stem cells(NSCs)represent a promising regenerative source for replenishing lost OLs;however,conventional twodimensional(2D)in vitro culture systems lack the three-dimensional(3D)physiological microenvironment.Microfluidic chip technology has emerged as a powerful tool to overcome this limitation by enabling precise spatial and temporal control over 3D microenvironmental conditions,including the establishment of stable concentration gradients of bioactive molecules.Catalpol,an iridoid glycoside derived from traditional medicinal plants,exhibits dual antioxidant and anti-apoptotic properties.Despite its therapeutic potential,the capacity of catalpol to drive NSC differentiation toward OLs under biomimetic 3D conditions,as well as the underlying molecular mechanisms,remains poorly understood.This study aims to develop a microfluidic-based 3D biomimetic platform to systematically investigate the concentration-dependent effects of catalpol on promoting NSCs-to-OLs differentiation and to elucidate the role of the caveolin-1(Cav-1)signaling pathway in this process.Methods We developed a novel multiplexed microfluidic device featuring parallel microchannels with integrated gradient generators capable of establishing and maintaining precise linear concentration gradients(0-3 g/L catalpol)across 3D NSCs cultures.This platform facilitated the continuous perfusion culture of NSC-derived 3D spheroids,mimicking the dynamic in vivo microenvironment.Real-time cell viability was assessed using Calcein-AM/propidium iodide(PI)dual staining,with fluorescence imaging quantifying live/dead cell ratios.Oligodendrocyte differentiation was evaluated through quantitative reverse transcription polymerase chain reaction(qRT-PCR)for MBP and SOX10 gene expression,complemented by immunofluorescence staining to visualize corresponding protein changes.To dissect the molecular mechanism,the Cav-1-specific pharmacological inhibitor methyl‑β‑cyclodextrin(MCD)was employed to perturb the pathway,and its effects on differentiation markers were analyzed.Results Catalpol demonstrated excellent biocompatibility,with cell viability exceeding 96%across the entire tested concentration range(0-3 g/L),confirming its non-cytotoxic nature.At the optimal concentration of 0-3 g/L,catalpol significantly upregulated both MBP and SOX10 expression(P<0.05,P<0.01),indicating robust promotion of oligodendroglial differentiation.Intriguingly,Cav-1 mRNA expression was progressively downregulated during NSC differentiation into OLs.Further inhibition of Cav-1 with MCD further enhanced this effect,leading to a statistically significant increase in OL-specific gene expression(P<0.05,P<0.01),suggesting Cav-1 acts as a negative regulator of OLs differentiation.Conclusion This study established an integrated microfluidic gradient chip-3D NSC spheroid culture system,which combines the advantages of precise chemical gradient control with physiologically relevant 3D cell culture.The findings demonstrate that 3 g/L catalpol effectively suppresses Cav-1 signaling to drive NSC differentiation into functional OLs.This work not only provides novel insights into the Cav-1-dependent mechanisms of myelination but also delivers a scalable technological platform for future research on remyelination therapies,with potential applications in cerebral palsy and other white matter disorders.The platform’s modular design permits adaptation for screening other neurogenic compounds or investigating additional signaling pathways involved in OLs maturation.
基金Supported by Natural Science Foundation of Guangdong Province in China(2018KTSCX161)。
文摘The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.
基金supported by the Guangdong Provincial Clinical Research Center for Tuberculosis(No.2020B1111170014)。
文摘Objective To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis(TB)in the Guangdong Province between 2010 and 2019.Method Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering.Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive(ST-CAR)model.Results Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000in 2019.Spatial hotspots were found in northeastern Guangdong,particularly in Heyuan,Shanwei,and Shantou,while Shenzhen,Dongguan,and Foshan had the lowest rates in the Pearl River Delta.The STCAR model showed that the TB risk was lower with higher per capita Gross Domestic Product(GDP)[Relative Risk(RR),0.91;95%Confidence Interval(CI):0.86–0.98],more the ratio of licensed physicians and physician(RR,0.94;95%CI:0.90-0.98),and higher per capita public expenditure(RR,0.94;95%CI:0.90–0.97),with a marginal effect of population density(RR,0.86;95%CI:0.86–1.00).Conclusion The incidence of TB in Guangdong varies spatially and temporally.Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection.Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
