Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Metabolic and proteostatic differences in quiescent and active neural stem cells

Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

Novel Investigation of Stochastic Fractional Differential Equations Measles Model via the White Noise and Global Derivative Operator Depending on Mittag-Leffler Kernel

Because of the features involved with their varied kernels,differential operators relying on convolution formulations have been acknowledged as effective mathematical resources for modeling real-world issues.In this paper,we constructed a stochastic fractional framework of measles spreading mechanisms with dual medication immunization considering the exponential decay and Mittag-Leffler kernels.In this approach,the overall population was separated into five cohorts.Furthermore,the descriptive behavior of the system was investigated,including prerequisites for the positivity of solutions,invariant domain of the solution,presence and stability of equilibrium points,and sensitivity analysis.We included a stochastic element in every cohort and employed linear growth and Lipschitz criteria to show the existence and uniqueness of solutions.Several numerical simulations for various fractional orders and randomization intensities are illustrated.

DNA methylation in poultry:a review

As an important epigenetic modification,DNA methylation is involved in many biological processes such as animal cell differentiation,embryonic development,genomic imprinting and sex chromosome inactivation.As DNA methylation sequencing becomes more sophisticated,it becomes possible to use it to solve more zoological problems.This paper reviews the characteristics of DNA methylation,with emphasis on the research and application of DNA methylation in poultry.

Present-day Upper-crustal Strain Rate Field in Southeastern Tibet and its Geodynamic Implications:Constraints from GPS Measurements with ABIC Method

The Earth’s surface kinematics and deformation are fundamental to understanding crustal evolution.An effective research approach is to estimate regional motion field and deformation fields based on modern geodetic networks.If the discrete observed velocity field is obtained,the velocity related fields,such as dilatation rate and maximum shear strain rate,can be estimated by applying varied mathematical approaches.This study applied Akaike's Bayesian Information Criterion(ABIC)method to calculate strain rate fields constrained by GPS observations in the southeast Tibetan Plateau.Comparison with results derived from other three methods revealed that our ABIC-derived strain rate fields were more precise.The maximum shear strain rate highlighted the Xianshuihe–Xiaojiang fault system as the main boundary for the outward migration of material in southeastern Tibet,indicating rotation of eastern Tibet material around the eastern Himalaya rather than whole extrusion along a fixed channel.Additionally,distinct dilatation rate patterns in the northeast and southwest regions of the fault system were observed.The northeast region,represented by the Longmenshan area,exhibited negative dilatational anomalies;while the southwest region,represented by the Jinsha River area north of 29°N,displayed positive dilatational anomalies.This indicates compression in the former and extension in the latter.Combined with deep geophysical observations,we believe that the upper and lower crusts of the Jinsha River area north of 29°N are in an entire expanding state,probably caused by the escape-drag effect of material.The presence of a large,low-viscosity region south of 29°N may not enable the entire escape of the crust,but instead result in a differential escape of the lower crust faster than the upper crust.

Imprinting at the KBTBD6 locus involves species-specific m ternal methylation and monoallelic expression in livestock animals

Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.

Spatiotemporal dynamics of the social structure of Indo-Pacific humpback dolphins(Sousa chinensis)in Xiamen waters from 2007 to 2019

As highly social animals,Indo-Pacific humpback dolphins(Sousa chinensis)exhibit community differentiation.Nevertheless,our understanding of the external and internal factors influencing these dynamics,as well as their spatiotemporal variations,is still limited.In the present study,variations in the social structure of an endangered Indo-Pacific humpback dolphin population in Xiamen Bay,China,were monitored over two distinct periods(2007–2010 and 2017–2019)to analyze the effects of habitat utilization and the composition of individuals within the population.In both periods,the population demonstrated a strikingly similar pattern of social differentiation,characterized by the division of individuals into two main clusters and one small cluster.Spatially,the two primary clusters occupied the eastern and western waters,respectively,although the core distribution area of the eastern cluster shifted further eastward between the two periods.Despite this distribution shift,the temporal stability of the social structure and inter-associations within the eastern cluster remained unaffected.A subset of 16individuals observed in both periods,comprising 51.6%and 43.2%of the population in each respective period,emerged as a foundational element of the social structure and may be responsible for sustaining social structure stability,especially during the 2007–2010 period.These observations suggest that the composition of dominant individuals,an internal factor,had a more substantial influence on the formation of the social network than changes in habitat use,an external factor.Consequently,the study proposes distinct conservation measures tailored to each of the two main clusters.

Salinity Acclimation Induces Reduced Energy Metabolism,Osmotic Pressure Regulation and Transcriptional Reprogramming in Hypotrichida Ciliate Gastrostyla setifera

Coastal and estuarine protists are frequently exposed to salinity undulation.While the tolerance and stress responses of microalgae to salinity have been extensively studied,there have been scarce studies on the physiological response of heterotrophic protists to salinity stressing.In this study,we investigated the physiological response of the heterotrophic ciliate Gastrostyla setifera to a salinity of 3,via a transcriptomic approach.The first transcriptome of genus Gastrostyla was obtained utilizing a group of manually isolated ciliate individuals(cells)and RNA-seq technique.The completeness of the transcriptome was verified.Differentially expressed gene(DEG)analysis was performed among the transcriptomes of G.setifera acclimated in saline water(salinity 3)and those cultured in fresh water.The results demonstrated a significant alternation in gene transcription,in which the ciliate exhibits a transcripttomic acclimation in responding salinity stressing.The up-regulated DEGs were enriched in the pathways of cytoskeleton proteins,membrane trafficking,protein kinases and protein phosphatases.These may represent enhanced functions of ion transport,stress response and cell protections.Pathways involved in energy metabolism and biosynthesis were markedly down-regulated,reflecting decreased cell activity.Particularly,we detected significantly down-regulated genes involved in several pathways of amino acid catabolism,which may lead to accumulation of amino acids in the ciliate cell.Amino acid could act as compatible solutes in the cytoplasm to maintain the osmotic balance in saline water.Overall,this work is an initial exploration to the molecular basis of the heterotrophic protist responding to salinity stressing.The result sheds light on the mechanisms of enhancement of cell protection,reduction of cell activity,and osmotic pressure regulation in ciliates acclimated to salinity.

Nested Saturated Control of Uncertain Complex Cascade Systems Using Mixed Saturation Levels

This study addresses the problem of global asymptotic stability for uncertain complex cascade systems composed of multiple integrator systems and non-strict feedforward nonlinear systems. To tackle the complexity inherent in such structures, a novel nested saturated control design is proposed that incorporates both constant saturation levels and state-dependent saturation levels. Specifically, a modified differentiable saturation function is proposed to facilitate the saturation reduction analysis of the uncertain complex cascade systems under the presence of mixed saturation levels. In addition, the design of modified differentiable saturation function will help to construct a hierarchical global convergence strategy to improve the robustness of control design scheme. Through calculation of relevant inequalities, time derivative of boundary surface and simple Lyapunov function,saturation reduction analysis and convergence analysis are carried out, and then a set of explicit parameter conditions are provided to ensure global asymptotic stability in the closed-loop systems. Finally, a simplified system of the mechanical model is presented to validate the effectiveness of the proposed method.

Remote sensing of air pollution incorporating integrated-path differential-absorption and coherent-Doppler lidar

An innovative complex lidar system deployed on an airborne rotorcraft platform for remote sensing of atmospheric pollution is proposed and demonstrated.The system incorporates integrated-path differential absorption lidar(DIAL) and coherent-doppler lidar(CDL) techniques using a dual tunable TEA CO_(2)laser in the 9—11 μm band and a 1.55 μm fiber laser.By combining the principles of differential absorption detection and pulsed coherent detection,the system enables agile and remote sensing of atmospheric pollution.Extensive static tests validate the system’s real-time detection capabilities,including the measurement of concentration-path-length product(CL),front distance,and path wind speed of air pollution plumes over long distances exceeding 4 km.Flight experiments is conducted with the helicopter.Scanning of the pollutant concentration and the wind field is carried out in an approximately 1 km slant range over scanning angle ranges from 45°to 65°,with a radial resolution of 30 m and10 s.The test results demonstrate the system’s ability to spatially map atmospheric pollution plumes and predict their motion and dispersion patterns,thereby ensuring the protection of public safety.

In situ forming injectable MSC-loaded GelMA hydrogels combined with PD for vascularized sweat gland regeneration

Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).

Transcriptome analysis reveals immune-related genes in tissues of Vibrio anguillarum-infected turbot Scophthalmus maximus

Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture industry.To understand the immune response of the turbot against V.anguillarum infection and to explore novel immune-related genes,the transcriptome analysis of turbot spleen and gills were conducted after V.anguillarum infection.Differentially expressed genes(DEGs)were identified in spleen and gill of the turbot amounted to 17261 and 16436,respectively.A large number of immunerelated DEGs were enriched in cytokine-cytokine receptor interaction signaling pathway,and the others by the kyoto encyclopedia of genes and genomes(KEGG)enrichment.The gene ontology(GO)classification analysis revealed that V.anguillarum infection had the greatest effect on biological processes and cellular components.Twelve immune-related DEGs were identified in the spleen(cstl.1,egfl6,lamb21,v2rx4,calcr,and gpr78a)and gills(ghra,sh3gl2a,cst12,inhbaa,cxcl8,and il-1b)by heat map.The proteinprotein interaction(PPI)networks were constructed to analyze the immune mechanism.The results demonstrate that the maturation and antigen processing of major histocompatibility complex(MHC)class II molecule,and calcitonin-or adrenomedullin-regulated physiological activity were important events in the immunity of turbot against V.anguillarum infection.In the gills,the protein interactions in TGF-βsignaling pathway,production of inflammatory factors,and endocytosis regulation were most significant.Our research laid a foundation for discovering novel immune-related genes and enriching the knowledge of immune mechanisms of turbot against V.anguillarum infection.

Identification and effective regulation of scarb1 gene involved in pigmentation change in autotetraploid Carassius auratus

The autotetraploid Carassius auratus(4nRR,4n=200,RRRR)is derived from whole-genome duplication of Carassius auratus red var.(RCC,2n=100,RR).In the current study,we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin(red in RCC,brownish-yellow in4nRR).To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR,we performed transcriptome profiling and molecular functional verification in RCC and 4nRR.Results revealed that scarb1,associated with carotenoid metabolism,underwent significant down-regulation in 4nRR.Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration.Subsequently,we identified four divergent scarb1 homeologs in 4nRR:two original scarb1 homeologs from RCC and two duplicated ones.Notably,three of these homeologs possessed two highly conserved alleles,exhibiting biased and allelespecific expression in the skin.Remarkably,after precise editing of both the original and duplicated scarb1homeologs and/or alleles,4nRR individuals,whether singly or multiply mutated,displayed a transition from brownishyellow skin to a cyan-gray phenotype.Concurrently,the proportional areas of the cyan-gray regions displayed a gene-dose correlation.These findings illustrate the subfunctionalization of duplicated scarb1,with all scarb1genes synergistically and equally contributing to the pigmentation of 4nRR.This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploidfish,substantiallyenrichingour understanding of coloration formation and change within this group of organisms.

Spatial-temporal differentiation and influencing factors of rural settlements in mountainous areas: an example of Liangshan Yi Autonomous Prefecture, Southwestern China

Rural settlement is the basic spatial unit for compact communities in rural area. Scientific exploration of spatial-temporal differentiation and its influencing factors is the premise of spatial layout rationalization. Based on land use data of Liangshan Yi Autonomous Prefecture(hereinafter referred to as Liangshan Prefecture) in Sichuan Province, China from 1980 to 2020, compactness index, fractal dimension, imbalance index, location entropy and the optimal parameters-based geographical detector(OPGD) model are used to analyze the spatial-temporal evolution of the morphological characteristics of rural settlements, and to explore the influence of natural geographical factors, socioeconomic factors, and policy factors on the spatial differentiation of rural settlements. The results show that:(1) From 1980 to 2020, the rural settlements area in Liangshan Prefecture increased by 15.96 km^(2). In space, the rural settlements are generally distributed in a local aggregation, dense in the middle and sparse around the periphery. In 2015, the spatial density and expansion index of rural settlements reached the peak.(2) From 1980 to 2020, the compactness index decreased from 0.7636 to 0.7496, the fractal dimension increased from 1.0283 to 1.0314, and the fragmentation index decreased from 0.1183 to 0.1047. The spatial morphological structure of rural settlements tended to be loose, the shape contour tended to be complex, the degree of fragmentation decreased, and the spatial distribution was significantly imbalanced.(3) The results of OPGD detection in 2015 show that the influence of each factor is slope(0.2371) > traffic accessibility(0.2098) > population(0.1403) > regional GDP(0.1325) > elevation(0.0987) > poverty alleviation(0). The results of OPGD detection in 2020 show that the influence of each factor is slope(0.2339) > traffic accessibility(0.2198) > population(0.1432) > regional GDP(0.1219) > poverty alleviation(0.0992) > elevation(0.093). Natural geographical factors(slope and elevation) are the basic factors affecting the spatial distribution of rural settlements, and rural settlements are widely distributed in the river valley plain and the second half mountain area. Socioeconomic factors(traffic accessibility, population, and regional GDP) have a greater impact on the spatial distribution of rural settlements, which is an important factor affecting the spatial distribution of rural settlements. Policy factors such as poverty alleviation relocation have an indispensable impact on the spatial distribution of rural settlements. The research results can provide decisionmaking basis for the spatial arrangement of rural settlements in Liangshan Prefecture, and optimize the implementation of rural revitalization policies.

Metabolic profiles and morphological characteristics of leaf tips among different sweet potato(Ipomoea batatas Lam.)varieties

Sweet potato leaf tips have high nutritional value,and exploring the differences in the metabolic profiles of leaf tips among different sweet potato varieties can provide information to improve their qualities.In this study,a UPLC-Q-Exactive Orbitrap/MS-based untargeted metabolomics method was used to evaluate the metabolites in leaf tips of 32 sweet potato varieties.Three varieties with distinct overall metabolic profiles(A01,A02,and A03),two varieties with distinct profiles of phenolic acids(A20 and A18),and three varieties with distinct profiles of flavonoids(A05,A12,and A16)were identified.In addition,a total of 163 and 29 differentially expressed metabolites correlated with the color and leaf shape of sweet potato leaf tips,respectively,were identified through morphological characterization.Group comparison analysis of the phenotypic traits and a metabolite-phenotypic trait correlation analysis indicated that the color differences of sweet potato leaf tips were markedly associated with flavonoids.Also,the level of polyphenols was correlated with the leaf shape of sweet potato leaf tips,with lobed leaf types having higher levels of polyphenols than the entire leaf types.The findings on the metabolic profiles and differentially expressed metabolites associated with the morphology of sweet potato leaf tips can provide useful information for breeding sweet potato varieties with higher nutritional value.

Equilibrium Strategy of the Pursuit-Evasion Game in Three-Dimensional Space

The pursuit-evasion game models the strategic interaction among players, attracting attention in many realistic scenarios, such as missile guidance, unmanned aerial vehicles, and target defense. Existing studies mainly concentrate on the cooperative pursuit of multiple players in two-dimensional pursuit-evasion games. However, these approaches can hardly be applied to practical situations where players usually move in three-dimensional space with a three-degree-of-freedom control. In this paper,we make the first attempt to investigate the equilibrium strategy of the realistic pursuit-evasion game, in which the pursuer follows a three-degree-of-freedom control, and the evader moves freely. First, we describe the pursuer's three-degree-of-freedom control and the evader's relative coordinate. We then rigorously derive the equilibrium strategy by solving the retrogressive path equation according to the Hamilton-Jacobi-Bellman-Isaacs(HJBI) method, which divides the pursuit-evasion process into the navigation and acceleration phases. Besides, we analyze the maximum allowable speed for the pursuer to capture the evader successfully and provide the strategy with which the evader can escape when the pursuer's speed exceeds the threshold. We further conduct comparison tests with various unilateral deviations to verify that the proposed strategy forms a Nash equilibrium.

THE EXACT MEROMORPHIC SOLUTIONS OF SOME NONLINEAR DIFFERENTIAL EQUATIONS

We find the exact forms of meromorphic solutions of the nonlinear differential equations■,n≥3,k≥1,where q,Q are nonzero polynomials,Q■Const.,and p_(1),p_(2),α_(1),α_(2)are nonzero constants withα_(1)≠α_(2).Compared with previous results on the equation p(z)f^(3)+q(z)f"=-sinα(z)with polynomial coefficients,our results show that the coefficient of the term f^((k))perturbed by multiplying an exponential function will affect the structure of its solutions.

KSKV:Key-Strategy for Key-Value Data Collection with Local Differential Privacy

In recent years,the research field of data collection under local differential privacy(LDP)has expanded its focus fromelementary data types to includemore complex structural data,such as set-value and graph data.However,our comprehensive review of existing literature reveals that there needs to be more studies that engage with key-value data collection.Such studies would simultaneously collect the frequencies of keys and the mean of values associated with each key.Additionally,the allocation of the privacy budget between the frequencies of keys and the means of values for each key does not yield an optimal utility tradeoff.Recognizing the importance of obtaining accurate key frequencies and mean estimations for key-value data collection,this paper presents a novel framework:the Key-Strategy Framework forKey-ValueDataCollection under LDP.Initially,theKey-StrategyUnary Encoding(KS-UE)strategy is proposed within non-interactive frameworks for the purpose of privacy budget allocation to achieve precise key frequencies;subsequently,the Key-Strategy Generalized Randomized Response(KS-GRR)strategy is introduced for interactive frameworks to enhance the efficiency of collecting frequent keys through group-anditeration methods.Both strategies are adapted for scenarios in which users possess either a single or multiple key-value pairs.Theoretically,we demonstrate that the variance of KS-UE is lower than that of existing methods.These claims are substantiated through extensive experimental evaluation on real-world datasets,confirming the effectiveness and efficiency of the KS-UE and KS-GRR strategies.

A Coupled Thermomechanical Crack Propagation Behavior of Brittle Materials by Peridynamic Differential Operator

This study proposes a comprehensive,coupled thermomechanical model that replaces local spatial derivatives in classical differential thermomechanical equations with nonlocal integral forms derived from the peridynamic differential operator(PDDO),eliminating the need for calibration procedures.The model employs a multi-rate explicit time integration scheme to handle varying time scales in multi-physics systems.Through simulations conducted on granite and ceramic materials,this model demonstrates its effectiveness.It successfully simulates thermal damage behavior in granite arising from incompatible mineral expansion and accurately calculates thermal crack propagation in ceramic slabs during quenching.To account for material heterogeneity,the model utilizes the Shuffle algorithm andWeibull distribution,yielding results that align with numerical simulations and experimental observations.This coupled thermomechanical model shows great promise for analyzing intricate thermomechanical phenomena in brittle materials.