Structural Connectivity Enhanced Anisotropic 3D Network for Brain Midline Delineation

Brain midline delineation can facilitate the clinical evaluation of brain midline shift,which has a pivotal role in the diagnosis and prognosis of various brain pathology.However,there are still challenges for brain midline delineation:1)the largely deformed midline is hard to localize if mixed with severe cerebral hemorrhage;2)the predicted midlines of recent methods are not smooth and continuous which violates the structural priority.To overcome these challenges,we propose an anisotropic three dimensional(3D)network with context-aware refinement(A3D-CAR)for brain midline modeling.The proposed network fuses 3D context from different two dimensional(2D)slices through asymmetric context fusion.To exploit the elongated structure of the midline,an anisotropic block is designed to balance the difference between the adjacent pixels in the horizontal and vertical directions.For maintaining the structural priority of a brain midline,we present a novel 3D connectivity regular loss(3D CRL)to penalize the disconnectivity between nearby coordinates.Extensive experiments on the CQ dataset and one in-house dataset show that the proposed method outperforms three state-of-the-art methods on four evaluation metrics without excessive computational burden.

Digital Construction of Rural Landscape Based on DEM:A Case Study of Xiangyu Village of West Beijing

[Objective]The paper uses Geographic Information System(ArcGIS)as a platform to discuss the study of DEM data on the digital construction of rural landscape databases and the coupling relationship in geographic space of rural landscape.The aim is to further expand the coverage of China's land space digitization and provide practical theoretical basis and development possibility of quantitative planning for village level administrative zoning research.[Method]In this paper,Xiangyu Village,Junzhuang Town,Mentougou,West Beijing,is selected as the research object,and the document space database of the study area is constructed by building digital elevation model(DEM),ArcGIS stacked map weighting and visual interpretation methods.Moreover,its elevation equivalence,slope direction,and water flow direction are visually analyzed.[Result]The mountainous terrain and hydrological characteristics of Xiangyu Village are roughly consistent with the village layout;the living environment of Xiangyu Village is consistent with the terrain and texture,and it belongs to the rural landscape system of mountains,valleys and small watersheds.[Conclusion]The results obtained through data visualization analysis are basically consistent with the traditional village planning pattern of Xiangyu Village;the rural landscape based on village level administrative divisions is still in the traditional planning stage,and there is great development space for village level geographic spatial survey.Therefore,it is necessary for relevant practitioners to make more contributions to fill the full coverage of China's land space digitization.

ABM-based emergency evacuation modelling during urban pluvial floods:A“7.20”pluvial flood event study in Zhengzhou,Henan Province

Increasing urban pluvial flood disasters due to climate change and rapid urbanisation have been a great challenge worldwide.Timely and effective emergency evacuation is important for reducing casualties and losses.This has become a bottleneck for emergency management.This study aimed to develop a commonly used Agent-Based Mode(ABM)for pluvial flood emergency evacuation at the city scale,exploring the cascading impacts of pluvial flooding on human behaviour and emergency evacuation.The July 2021 pluvial flood event in Zhengzhou,Henan Province,claiming 380 lives and 40.9 billion yuan in direct losses,was selected as this case study.A raster-based hydraulic model(ECNU Flood-Urban)was used to predict flood inundation(extent and depth)during an event in Zhengzhou’s centre.Moreover,a comparative analysis of emergency evacuations was conducted before and after the pluvial flood event.The results showed that crowd behaviour plays an important role in an emergency evacuation,and extensive flooding leads to an 11-83%reduction in the number of evacuees.This study highlights the importance of risk education and contingency plans in emergency response.The ABM model developed in this study is proven to be effective and practical and will provide support for decision-making in urban flood emergency management.

TNF-α suppresses sweat gland differentiation of MSCs by reducing FTO-mediated m^6 A-demethylation of Nanog mRNA

An effect of inhibition of tumor necrosis factor-α(TNF-α)on differentiation of mesenchymal stromal cells(MSCs)has been demonstrated,but the exact mechanisms that govern MSCs differentiation remain to be further elucidated.Here,we show that TNF-αinhibits the differentiation of MSCs to sweat glands in a specific sweat gland-inducing environment,accompanied with reduced expression of Nanog,a core pluripotency factor.We elucidated that fat mass and obesity-associated protein(FTO)-mediated m^6 A demethylation is involved in the regulation of MSCs differentiation potential.Exposure of MSCs to TNF-αreduced expression of FTO,which demethylated Nanog m RNA.Reduced expression of FTO increased Nanog m RNA methylation,decreased Nanog m RNA and protein expression,and significantly inhibited MSCs capacity for differentiation to sweat gland cells.Our finding is the first to elucidate the functional importance of m^6 A modification in MSCs,providing new insights that the microenvironment can regulate the multipotency of MSCs at the post-transcriptional level.Moreover,to maintain differentiation capacity of MSCs by regulating m^6 A modification suggested a novel potential therapeutic target for stem cellmediated regenerative medicine.

Redirecting differentiation of mammary progenitor cells by 3D bioprinted sweat gland microenvironment

Background:Mammary progenitor cells(MPCs)maintain their reproductive potency through life,and their specific microenvironments exert a deterministic control over these cells.MPCs provides one kind of ideal tools for studying engineered microenvironmental influence because of its accessibility and continually undergoes postnatal developmental changes.The aim of our study is to explore the critical role of the engineered sweat gland(SG)microenvironment in reprogramming MPCs into functional SG cells.Methods:We have utilized a three-dimensional(3D)SG microenvironment composed of gelatin-alginate hydrogels and components from mouse SG extracellular matrix(SG-ECM)proteins to reroute the differentiation of MPCs to study the functions of this microenvironment.MPCs were encapsulated into the artificial SG microenvironment and were printed into a 3D cell-laden construct.The expression of specific markers at the protein and gene levels was detected after cultured 14 days.Results:Compared with the control group,immunofluorescence and gene expression assay demonstrated that MPCs encapsulated in the bioprinted 3D-SG microenvironment could significantly express the functional marker of mouse SG,sodium/potassium channel protein ATP1a1,and tend to express the specific marker of luminal epithelial cells,keratin-8.When the Shh pathway is inhibited,the expression of SG-associated proteins in MPCs under the same induction environment is significantly reduced.Conclusions:Our evidence proved the ability of differentiated mouse MPCs to regenerate SG cells by engineered SG microenvironment in vitro and Shh pathway was found to be correlated with the changes in the differentiation.These results provide insights into regeneration of damaged SG by MPCs and the role of the engineered microenvironment in reprogramming cell fate.

Stiffness-mediated mesenchymal stem cell fate decision in 3D-bioprinted hydrogels

Background:Hydrogels with tuneable mechanical properties are an attractive material platform for 3D bioprinting.Thus far,numerous studies have confirmed that the biophysical cues of hydrogels,such as stiffness,are known to have a profound impact on mesenchymal stem cell(MSC)differentiation;however,their differentiation potential within 3D-bioprinted hydrogels is not completely understood.Here,we propose a protocol for the exploration of how the stiffness of alginate–gelatin(Alg-Gel)composite hydrogels(the widely used bioink)affects the differentiation of MSCs in the presence or absence of differentiation inducing factors.Methods:Two types of Alg-Gel composite hydrogels(Young’s modulus:50 kPa vs.225 kPa)were bioprinted independently of porosity.Then,stiffness-induced biases towards adipogenic and osteogenic differentiation of the embedded MSCs were analysed by co-staining with alkaline phosphatase(ALP)and oil red O.The expression of specific markers at the gene level was detected after a 3-day culture.Results:Confocal microscopy indicated that all tested hydrogels supported MSC growth and viability during the culture period.Higher expression of adipogenic and osteogenic markers(ALP and lipoprotein lipase(LPL))in stiffer 3D-bioprinted matrices demonstrated a more significant response of MSCs to stiffer hydrogels with respect to differentiation,which was more robust in differentiation-inducing medium.However,the LPL expression in stiffer 3D-bioprinted constructs was reduced at day 3 regardless of the presence of differentiation-inducing factors.Although MSCs embedded in softer hydrogels to some extent proceeded toward adipogenic and osteogenic lineages within a few days,their differentiation seemed to be slower and more limited.Interestingly,the hydrogel itself(without differentiation-inducing factors)exhibited a slight effect on whether MSCs differentiated towards an adipogenic or an osteogenic fate.Considering that the mechanoregulated protein Yes-associated protein(YAP)is involved in MSC fate decisions,we further found that inhibition of YAP significantly downregulated the expression of ALP and LPL in MSCs in stiffer constructs regardless of the induced growth factors present.Conclusions:These results demonstrate that the differentiation of MSCs in 3D-bioprinted matrices is dependent on hydrogel stiffness,which emphasizes the importance of biophysical cues as a determinant of cellular behaviour.