Spatially resolved transcriptomic profiling of placental development in dairy cow

The placenta plays a crucial role in successful mammalian reproduction.Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons,essential for full-term fetal development.The cow placenta harbors at least two trophoblast cell populations:uninucleate(UNC)and binucleate(BNC)cells.However,the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches,and the molecular mechanisms governing trophoblast differentiation and functionalization.To fill this knowledge gap,we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation,attaining high-resolution,spatially resolved gene expression profiles.Based on clustering and cell marker gene expression analyses,key transcription factors,including YBX1 and NPAS2,were shown to regulate the heterogeneity of trophoblast cell subpopulations.Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment.Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation.Additionally,spatial modules and co-variant genes that help shape specific tissue structures were identified.Together,these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.

Dissecting the brain with spatially resolved multi-omics

Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.

Preface for Special Issue:Single-Cell and Spatially Resolved Omics

We are delighted to present you this special issue,which consists of a collection of articles focusing on the novel and rapidly evolving field of single-cell and spatially resolved omics.This encompasses epigenomics,transcriptomics,proteomics,and metabolomics.Recent technological advances,coupled with computational techniques,have advanced the scope of this discipline to allow the investigation of individual cells down to an unprecedented level of detail.Researchers can now explore the cellular heterogeneity and the intricate interplay among its multiple molecular elements comprehensively.

Preface for Special Issue: Single-Cell and Spatially Resolved Omics

In this special issue,we are excited to present a collection of articles focusing on the emerging and rapidly evolving field of singlecell and spatially resolved omics,including epigenomics,transcriptomics,proteomics,and metabolomics.In recent years,the developmentofadvanced,high-throughput technologiessand computational methods has enabled researchers to study individual cells at an unprecedented resolution,shedding light on their heterogeneity and the complex interplay between their various molecular components.The detailed exploration of these aspects is crucial not only for a better understanding of the fundamental biology underlying cell function and organization but also for identifying novel therapeutic targets and strategies in various disease contexts.

Promise of spatially resolved omics for tumor research

Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.

Enhanced THz Radiation from Spatially Inhomogeneous Fields

Nonlinear terahertz(THz)radiation from gas media usually relies on the asymmetric laser-induced current produced by ultra-intense two-color laser fields with a specific phase delay.Here a new scheme is proposed and theoretically investigated,in which the radiation is generated by spatially inhomogeneous fields induced by relatively low-intensity monochromatic lasers and an array of single triangular metallic nanostructures.Our simulations are based on the classical photocurrent model and the time-dependent Schrodinger equations separately.It is found that the collective motion of the ionized electrons can be efficiently controlled by the inhomogeneous field,resulting in strong residual currents.The intensity of the THz radiation could be enhanced by about two orders of magnitude by increasing the spatial inhomogeneity of the field.

Single-cell and spatially resolved omics:Advances and limitations

Recent advances in experimental and computational single-cell and spatially resolved omics have opened new avenues for research in biology and medicine.These technologies allow for the study of individual cells in unprecedented detail,providing insights into the heterogeneity within tissues and organs,and how different cells interact with each other.Humans and other eukaryotes are composed of billions of cells,each with vastly heterogeneous cell types and functional cell states determined by intrinsic and extrinsic factors.

Delayed response to the photovoltaic performance in a double quantum dots photocell with spatially correlated fluctuation

A viable strategy for enhancing photovoltaic performance is to comprehend the underlying quantum physical regime of charge transfer in a double quantum dots(DQD) photocell. This work explored the photovoltaic performance dependent spatially correlated fluctuation in a DQD photocell. The effects of spatially correlated fluctuation on charge transfer and output photovoltaic efficiency were explored in a proposed DQD photocell model. The results revealed that the charge transport process and the time to peak photovoltaic efficiency were both significantly delayed by the spatially correlated fluctuation, while the anti-spatially correlated fluctuation reduced the output peak photovoltaic efficiency. Further results revealed that the delayed response could be suppressed by gap difference and tunneling coefficient within two dots. Subsequent investigation demonstrated that the delayed response was caused by the spatial correlation fluctuation slowing the generative process of noise-induced coherence, which had previously been proven to improve the quantum photovoltaic performance in quantum photocells. And the reduced photovoltaic properties were verified by the damaged noise-induced coherence owing to the anti-spatial correlation fluctuation and a hotter thermal ambient environment. The discovery of delayed response generated by the spatially correlated fluctuations will deepen the understanding of quantum features of electron transfer, as well as promises to take our understanding even further concerning quantum techniques for high efficiency DQD solar cells.

Reconstructing in vivo spatially offset Raman spectroscopy of human skin tissue using a GPU-accelerated Monte Carlo platform

As one type of spatially offset Raman spectroscopy(SORS), inverse SORS is particularly suited to in vivo biomedical measurements due to its ring-shaped illumination scheme. To explain inhomogeneous Raman scattering during in vivo inverse SORS measurements, the light–tissue interactions when excitation and regenerated Raman photons propagate in skin tissue were studied using Monte Carlo simulation. An eight-layered skin model was first built based on the latest transmission parameters. Then, an open-source platform, Monte Carlo e Xtreme(MCX), was adapted to study the distribution of 785 nm excitation photons inside the model with an inverse spatially shifted annular beam. The excitation photons were converted to emission photons by an inverse distribution method based on excitation flux with spatial offsets Δs of 1 mm, 2 mm, 3 mm and 5 mm. The intrinsic Raman spectra from separated skin layers were measured by continuous linear scanning to improve the simulation accuracy. The obtained results explain why the spectral detection depth gradually increases with increasing spatial offset, and address how the intrinsic Raman spectrum from deep skin layers is distorted by the reabsorption and scattering of the superficial tissue constituents. Meanwhile, it is demonstrated that the spectral contribution from subcutaneous fat will be improved when the offset increases to 5 mm, and the highest detection efficiency for dermal layer spectral detection could be achieved when Δs = 2 mm. Reasonably good matching between the calculated spectrum and the measured in vivo inverse SORS was achieved, thus demonstrating great utility of our modeling method and an approach to help understand the clinical measurements.

Non-parametric machine learning methods for interpolation of spatially varying non-stationary and non-Gaussian geotechnical properties

Spatial interpolation has been frequently encountered in earth sciences and engineering.A reasonable appraisal of subsurface heterogeneity plays a significant role in planning,risk assessment and decision making for geotechnical practice.Geostatistics is commonly used to interpolate spatially varying properties at un-sampled locations from scatter measurements.However,successful application of classic geostatistical models requires prior characterization of spatial auto-correlation structures,which poses a great challenge for unexperienced engineers,particularly when only limited measurements are available.Data-driven machine learning methods,such as radial basis function network(RBFN),require minimal human intervention and provide effective alternatives for spatial interpolation of non-stationary and non-Gaussian data,particularly when measurements are sparse.Conventional RBFN,however,is direction independent(i.e.isotropic)and cannot quantify prediction uncertainty in spatial interpolation.In this study,an ensemble RBFN method is proposed that not only allows geotechnical anisotropy to be properly incorporated,but also quantifies uncertainty in spatial interpolation.The proposed method is illustrated using numerical examples of cone penetration test(CPT)data,which involve interpolation of a 2D CPT cross-section from limited continuous 1D CPT soundings in the vertical direction.In addition,a comparative study is performed to benchmark the proposed ensemble RBFN with two other non-parametric data-driven approaches,namely,Multiple Point Statistics(MPS)and Bayesian Compressive Sensing(BCS).The results reveal that the proposed ensemble RBFN provides a better estimation of spatial patterns and associated prediction uncertainty at un-sampled locations when a reasonable amount of data is available as input.Moreover,the prediction accuracy of all the three methods improves as the number of measurements increases,and vice versa.It is also found that BCS prediction is less sensitive to the number of measurement data and outperforms RBFN and MPS when only limited point observations are available.

Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.

Spatial evolution and spatial production of traditional villages from "backward poverty villages" to "ecologically well-off villages": Experiences from the hinterland of national nature reserves in China

With the rapid urbanization process,the space of traditional villages in China is undergoing significant changes.Studying the spatial evolution of traditional villages is significant in promoting rural spatial transformation and realizing rural revitalization and sustainable rural development.Based on the traceability analysis of spatial production theory,this paper constructed an analytical framework for the spatial production evolution of traditional villages,analyzed the spatial evolution process and characteristics of traditional villages by using buffer analysis,spatial syntax,and other research methods,and revealed the characteristics of the spatial production evolution of traditional villages and the driving mechanism.The results show that:(1)The village spatial formation and development follow the village life cycle theory and usually develop from embryonic villages to diversified and integrated villages;(2)The evolution of village spatial production is characterized by the diversity of material space,the sublimation of daily life space,and the integration of social system space and generalization of emotional space;(3)The evolution of village spatial production from backward and poor village to ecologically well-off village is influenced by a combination of factors;(4)The village has formed a spatial structure of"people-land-scape-culture-industry",realized comprehensive reconstruction and spatial reproduction.The study results reflect the spatial evolution characteristics of traditional villages in mountainous areas in a more comprehensive way,which helps to promote the protection and development of traditional villages in mountainous areas and,to a certain extent,provides a reference for the development of rural revitalization.

Dynamics of Advantageous Mutant Spread in Spatial Death-Birth and Birth-Death Moran Models

The spread of an advantageous mutation through a population is of fundamental interest in population genetics. While the classical Moran model is formulated for a well-mixed population, it has long been recognized that in real-world applications, the population usually has an explicit spatial structure which can significantly influence the dynamics. In the context of cancer initiation in epithelial tissue, several recent works have analyzed the dynamics of advantageous mutant spread on integer lattices, using the biased voter model from particle systems theory. In this spatial version of the Moran model, individuals first reproduce according to their fitness and then replace a neighboring individual. From a biological standpoint, the opposite dynamics, where individuals first die and are then replaced by a neighboring individual according to its fitness, are equally relevant. Here, we investigate this death-birth analogue of the biased voter model. We construct the process mathematically, derive the associated dual process, establish bounds on the survival probability of a single mutant, and prove that the process has an asymptotic shape. We also briefly discuss alternative birth-death and death-birth dynamics, depending on how the mutant fitness advantage affects the dynamics. We show that birth-death and death-birth formulations of the biased voter model are equivalent when fitness affects the former event of each update of the model, whereas the birth-death model is fundamentally different from the death-birth model when fitness affects the latter event.

Enhancing transboundary natural tourism resources governance:unveiling the spatial pattern and its influencing factors

Tourism resources that span provincial boundaries in China play a pivotal role in regional development,yet effective governance poses persistent challenges.This study addresses this issue by constructing a comprehensive database of transboundary natural tourism resources(TNTR)through amalgamation of diverse data sources.Utilizing the Getis-Ord Gi^(*),kernel density estimation,and geographical detectors,we scrutinize the spatial patterns of TNTR,focusing on both named and unnamed entities,while exploring the influencing factors.Our findings reveal 7883 identified TNTR in China,with mountain tourism resources emerging as the predominant type.Among provinces,Hunan boasts the highest count,while Shanghai exhibits the lowest.Southern China demonstrates a pronounced clustering trend in TNTR distribution,with the spatial arrangement of biological landscapes appearing more random compared to geological and water landscapes.Western China,characterized by intricate terrain,exhibits fewer TNTR,concurrently unveiling a significant presence of unnamed natural tourism resources.Crucially,administrative segmentation influences TNTR development,generating disparities in regional goals,developmental stages and intensities,and management approaches.In response to these variations,we advocate for strengthening the naming of the unnamed transboundary tourism resources,constructing a geographic database of TNTR for government and establishing a collaborative management mechanism based on TNTR database.Our research contributes to elucidating the intricate landscape of TNTR,offering insights for tailored governance strategies in the realm of cross-provincial tourism resource management.

Spatial analysis of the osteoarthritis microenvironment: techniques, insights, and applications

Osteoarthritis(OA)is a debilitating degenerative disease affecting multiple joint tissues,including cartilage,bone,synovium,and adipose tissues.OA presents diverse clinical phenotypes and distinct molecular endotypes,including inflammatory,metabolic,mechanical,genetic,and synovial variants.Consequently,innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches.Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints,causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues.This issue has led to standardization difficulties and hindered the success of clinical trials.Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues,encompassing DNA,RNA,metabolites,and proteins,as well as their chemical properties,elemental composition,and mechanical attributes,can contribute to a more comprehensive understanding of the disease subtypes.Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment,providing a more holistic view of cellular function.Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various-omics lenses,such as genomics,transcriptomics,proteomics,and metabolomics,with spatial data.This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates.Furthermore,advanced imaging techniques,including high-resolution microscopy,hyperspectral imaging,and mass spectrometry imaging,enable the visualization and analysis of the spatial distribution of biomolecules,cells,and tissues.Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes.This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis.It explores their applications,challenges,and potential opportunities in the field of OA.Additionally,this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.

Spatial and temporal evolution of electromagnetic pulses from solid target irradiated with multi-hundred-terawatt laser pulse inside target chamber

Giant electromagnetic pulses(EMPs) induced by high-power laser irradiating solid targets interfere with various experimental diagnoses and even damage equipment,so unveiling the evolution of EMPs inside the laser chamber is crucial for designing effective EMP shielding.In this work,the transmission characteristics of EMPs as a function of distances from the target chamber center(TCC) are studied using B-dot probes.The mean EMP amplitude generated by picosecond laser-target interaction reaches 561 kV m^(-1),357 kV m^(-1),395 kV m^(-1),and 341 kV m^(-1)at 0.32 m,0.53 m,0.76 m,and 1 m from TCC,which decreases dramatically from 0.32 m to 0.53 m.However,it shows a fluctuation from 0.53 m to 1 m.The temporal features of EMPs indicate that time-domain EMP signals near the target chamber wall have a wider full width at half maximum compared to that close to TCC,mainly due to the echo oscillation of electromagnetic waves inside the target chamber based on simulation and experimentation.The conclusions of this study will provide a new approach to mitigate strong electromagnetic pulses by decreasing the echo oscillation of electromagnetic waves inside the target chamber during laser coupling with targets.

Adaptive interaction driven by the learning effect in the spatial prisoner's dilemma

We propose a computing model in which individuals can automatically adjust their interaction intensity with their mentor according to the learning effect.This model is designed to investigate the cooperative dynamics of the spatial prisoner's dilemma.More specifically,when the cumulative payoff of a learner is more than his reference earning,he will strengthen his interaction with his mentor;otherwise,he will reduce it.The experimental results indicate that this mechanism can improve the emergence of cooperation in a networked population and that the driving coefficient of interaction intensity plays an important role in promoting cooperation.Interestingly,under a certain social dilemma condition,there exists a minimal driving coefficient that leads to optimal cooperation.This occurs due to a positive feedback effect between the individual's satisfaction frequency and the number of effective neighbors.Moreover,we find that the experimental results are in accord with theoretical predictions obtained from an extension of the classical pair-approximation method.Our conclusions obtained by considering relationships with mentors can provide a new perspective for future investigations into the dynamics of evolutionary games within structured populations.

Spatial distribution of shallow landslides caused by Typhoon Lekima in 2019 in Zhejiang Province, China

In recent years, the coastal region of Southeast China has witnessed a significant increase in the frequency and intensity of extreme rainfall events associated with landfalling typhoons. The hilly and mountainous terrain of this area, combined with rapid rainfall accumulation, has led to a surge in flash floods and severe geological hazards. On August 10, 2019, Typhoon Lekima made landfall in Zhejiang Province, China, and its torrential rainfall triggered extensive landslides, resulting in substantial damage and economic losses. Utilizing high-resolution satellite images, we compiled a landslide inventory of the affected area, which comprises a total of 2,774 rainfallinduced landslides over an area of 2965 km2. The majority of these landslides were small to mediumsized and exhibited elongated, clustered patterns. Some landslides displayed characteristics of high-level initiation, obstructing or partially blocking rivers, leading to the formation of debris dams. We used the inventory to analyze the distribution pattern of the landslides and their relationship with topographical, geological, and hydrological factors. The results showed that landslide abundance was closely related to elevation, slope angle, faults, and road density. The landslides were predominantly located in hilly and low mountainous areas, with elevations ranging from 150 to 300 m, slopes of 20 to 30 degrees, and a NE-SE aspect. Notably, we observed the highest Landslide Number Density(LND) and Landslide Area Percentage(LAP) in the rhyolite region. Landslides were concentrated within approximately 4 km on either side of fault zones, with their size and frequency negatively correlated with distances to faults, roads, and river systems. Furthermore, under the influence of typhoons, regions with denser vegetation cover exhibited higher landslide density, reaching maximum values in shrubland areas. In areas experiencing significantly increased concentrated rainfall, landslide density also showed a corresponding rise. In terms of spatial distribution, the rainfall-triggered landslides primarily occurred in the northeastern part of the study area, particularly in regions characterized by complex topography such as Shanzao Village in Yantan Town, Xixia Township, and Shangzhang Township. The research findings offer crucial data on the rainfallinduced landslides triggered by Typhoon Lekima, shedding light on their spatial distribution patterns. These findings provide valuable references for mitigating risks and planning reconstruction in typhoon-affected area.

Understanding the spatial interaction of ultrasounds based on three-dimensional dual-frequency ultrasonic field numerical simulation

A transient 3D model was established to investigate the effect of spatial interaction of ultrasounds on the dual-frequency ultrasonic field in magnesium alloy melt.The effects of insertion depth and tip shape of the ultrasonic rods,input pressures and their ratio on the acoustic field distribution were discussed in detail.Additionally,the spacing,angle,and insertion depth of two ultrasonic rods significantly affect the interaction between distinct ultrasounds.As a result,various acoustic pressure distributions and cavitation regions are obtained.The spherical rods mitigate the longitudinal and transversal attenuation of acoustic pressure and expand the cavitation volume by 53.7%and 31.7%,respectively,compared to the plate and conical rods.Increasing the input pressure will enlarge the cavitation region but has no effect on the acoustic pressure distribution pattern.The acoustic pressure ratio significantly affects the pressure distribution and the cavitation region,and the best cavitation effect is obtained at the ratio of 2:1(P15:P20).

FPGA-based position reconstruction method for neutron beam flux spatial distribution measurement in BNCT

A new measurement method for the spatial distribution of neutron beam flux in boron neutron capture therapy(BNCT)is being developed based on the two-dimensional Micromegas detector.To address the issue of long processing times in traditional offline position reconstruction methods,this paper proposes a field programmable gate array based online position reconstruction method utilizing the micro-time projection chamber principle.This method encapsulates key technical aspects:a self-adaptive serial link technique built upon the dynamical adjustment of the delay chain length,fast sorting,a coordinate-matching technique based on the mapping between signal timestamps and random access memory(RAM)addresses,and a precise start point-merging technique utilizing a circular combined RAM.The performance test of the selfadaptive serial link shows that the bit error rate of the link is better than 10-12 at a confidence level of 99%,ensuring reliable data transmission.The experiment utilizing the readout electronics and Micromegas detector shows a spatial resolution of approximately 1.4 mm,surpassing the current method’s resolution level of 5 mm.The beam experiment confirms that the readout electronics system can obtain the flux spatial distribution of neutron beams online,thus validating the feasibility of the position reconstruction method.The online position reconstruction method avoids traditional methods,such as bubble sorting and traversal searching,simplifies the design of the logic firmware,and reduces the time complexity from O(n2)to O(n).This study contributes to the advancement in measuring neutron beam flux for BNCT.