Insight into the spoilage heterogeneity of meat-borne bacteria isolates with high-producing collagenase

Chilled chicken is inevitably contaminated by microorganisms during slaughtering and processing,resulting in spoilage.Cutting parts of chilled chicken,especially wings,feet,and other skin-on products,are abundant in collagen,which may be the primary target for degradation by spoilage microorganisms.In this work,a total of 17 isolates of spoilage bacteria that could secrete both collagenase and lipase were determined by raw-chicken juice agar(RJA)method,and the results showed that 7 strains of Serratia,Aeromonas,and Pseudomonas could significantly decompose the collagen ingredients.The gelatin zymography showed that Serratia liquefaciens(F5)and(G7)had apparent degradation bands around 50 kDa,and Aeromonas veronii(G8)and Aeromonas salmonicida(H8)had a band around.65 and 95 kDa,respectively.The lipase and collagenase activities were detected isolate-by-isolate,with F5 showing the highest collagenase activity.For spoilage ability on meat in situ,F5 performed strongest in spoilage ability,indicated by the total viable counts,total volatile basic nitrogen content,sensory scores,lipase,and collagenase activity.This study provides a theoretical basis for spoilage heterogeneity of strains with high-producing collagenase in meat.

Individual dynamics and local heterogeneity provide a microscopic view of the epidemic spreading

The COVID-19 pandemic has caused severe global disasters,highlighting the importance of understanding the details and trends of epidemic transmission in order to introduce efficient intervention measures.While the widely used deterministic compartmental models have qualitatively presented continuous “analytical” insight and captured some transmission features,their treatment usually lacks spatiotemporal variation.Here,we propose a stochastic individual dynamical(SID)model to mimic the random and heterogeneous nature of epidemic propagation.The SID model provides a unifying framework for representing the spatiotemporal variations of epidemic development by tracking the movements of each individual.Using this model,we reproduce the infection curves for COVID-19 cases in different areas globally and find the local dynamics and heterogeneity at the individual level that affect the disease outbreak.The macroscopic trend of virus spreading is clearly illustrated from the microscopic perspective,enabling a quantitative assessment of different interventions.Seemingly,this model is also applicable to studying stochastic processes at the “meter scale”,e.g.,human society’s collective dynamics.

Editorial:Transcriptome analysis in tumor microenvironment and tumor heterogeneity

Cancer,a disease as intricate as it is devastating,continues to challenge the medical and scientific community[1].Its complex nature is epitomized by the tumor microenvironment and tumor heterogeneity.As we delve deeper into the realms of cancer research,the advent of transcriptome analysis has emerged as a powerful torchbearer,illuminating our understanding of these enigmatic facets of cancer biology[2].

Assessment and Visualization of Ki67 Heterogeneity in Breast Cancers through Digital Image Analysis

The Ki67 index (KI) is a standard clinical marker for tumor proliferation;however, its application is hindered by intratumoral heterogeneity. In this study, we used digital image analysis to comprehensively analyze Ki67 heterogeneity and distribution patterns in breast carcinoma. Using Smart Pathology software, we digitized and analyzed 42 excised breast carcinoma Ki67 slides. Boxplots, histograms, and heat maps were generated to illustrate the KI distribution. We found that 30% of cases (13/42) exhibited discrepancies between global and hotspot KI when using a 14% KI threshold for classification. Patients with higher global or hotspot KI values displayed greater heterogenicity. Ki67 distribution patterns were categorized as randomly distributed (52%, 22/42), peripheral (43%, 18/42), and centered (5%, 2/42). Our sampling simulator indicated analyzing more than 10 high-power fields was typically required to accurately estimate global KI, with sampling size being correlated with heterogeneity. In conclusion, using digital image analysis in whole-slide images allows for comprehensive Ki67 profile assessment, shedding light on heterogeneity and distribution patterns. This spatial information can facilitate KI surveys of breast cancer and other malignancies.

Effects of individual heterogeneity on social contagions

Despite having significant effects on social contagions,individual heterogeneity has frequently been overlooked in earlier studies.To better understand the complexity of social contagions,a non-Markovian model incorporating heterogeneous social influence and adoption thresholds is introduced.For theoretical analysis,a generalized edge-based compartmental theory which considers the heterogeneities of social influence and adoption thresholds is developed.Focusing on the final adoption size,the critical propagation probability,and the phase transition type,social contagions for adoption thresholds that follow normal distributions with various standard deviations,follow various distributions,and correlate with degrees are investigated.When thresholds follow normal distributions,a larger standard deviation results in a larger final adoption size when the information propagation probability is relatively low.However,when the information propagation probability is relatively high,a larger standard deviation results in a smaller final adoption size.When thresholds follow various distributions,crossover phenomena in phase transition are observed when investigating the relationship of the final adoption size versus the average adoption threshold for some threshold distributions.When thresholds are correlated with degrees,similar crossover phenomena occur when investigating the relationship of the final adoption size versus the degree correlation index.Additionally,we find that increasing the heterogeneity of social influence suppresses the effects of adoption threshold heterogeneity on social contagions in three cases.Our theory predictions agree well with the simulation results.

A geochemical perspective on the genesis of Cenozoic basic volcanism in northeastern Turkey:an overview of metasomatism and heterogeneity of the sub-continental lithospheric mantle in a post-collisional setting

The post-collisional Cenozoic basic volcanic rocks in NE Turkey show temporal variations in whole-rock lithophile element and highly siderophile element(HSE)systematics that are mainly associated with the nature of sub-continental lithospheric mantle(SCLM)sources and parental melt generation.So far,the traditional whole-rock lithophile geochemical data of these basic volcanic rocks have provided important constraints on the nature of SCLM sources.Integrated lithophile element and HSE geochemical data of these basic volcanic rocks also reveal the heterogeneity of the SCLM source,which is principally related to variable metasomatism resulting from previous subduction(s)and post-collisional mantle-crust interactions in an extensional setting.Lithophile element geochemical features suggest that the parental magmas have derived from metasomatized spinel-to garnet-bearing SCLM sources for Eocene and Miocene basic volcanic rocks with subduction signatures whereas originated from spinel-to garnet-bearing SCLM sources for Mio-Pliocene and Plio-Quaternary basaltic volcanic rocks without the subduction signature.Lithophile element and HSE geo-chemistry also reveal that Eocene and Miocene basic vol-canic rocks were affected by more pronounced crustal contamination than the basaltic volcanic rocks of Mio-Pliocene and Quaternary.Furthermore,the integrated lithophile element and HSE compositions of these basic volcanic rocks,together with the regional asymmetric lithospheric delamination model,reveal that the compositional variation(especially due to metasomatism)was significant temporally in the heterogeneity of the SCLM sources from which parental magmas formed during the Cenozoic era.

Pumping-induced Well Hydraulics and Groundwater Budget in a Leaky Aquifer System with Vertical Heterogeneity in Aquitard Hydraulic Properties

In groundwater hydrology,aquitard heterogeneity is often less considered compared to aquifers,despite its significant impact on groundwater hydraulics and groundwater resources evaluation.A semi-analytical solution is derived for pumping-induced well hydraulics and groundwater budget with consideration of vertical heterogeneity in aquitard hydraulic conductivity(K)and specific storage(S_(s)).The proposed new solution is innovative in its partitioning of the aquitard into multiple homogeneous sub-layers to enable consideration of various forms of vertically heterogeneous K or S_(s).Two scenarios of analytical investigations are explored:one is the presence of aquitard interlayers with distinct K or S_(s) values,a common field-scale occurrence;another is an exponentially depth-decaying aquitard S_(s),a regional-scale phenomenon supported by statistical analysis.Analytical investigations reveal that a low-K interlayer can significantly increase aquifer drawdown and enhance aquifer/aquitard depletion;a high-S_(s) interlayer can noticeably reduce aquifer drawdown and increase aquitard depletion.Locations of low-K or high-S_(s) interlayers also significantly impact well hydraulics and groundwater budget.In the context of an exponentially depth-decaying aquitard S_(s),a larger decay exponent can enhance aquifer drawdown.When using current models with a vertically homogeneous aquitard,half the sum of the geometric and harmonic means of exponentially depth-decaying aquitard S_(s) should be used to calculate aquitard depletion and unconfined aquifer leakage.

Effect of Modulus Heterogeneity on the Equilibrium Shape and Stress Field ofαPrecipitate in Ti-6Al-4V

For media with inclusions(e.g.,precipitates,voids,reinforcements,and others),the difference in lattice parameter and the elastic modulus between the matrix and inclusions cause stress concentration at the interfaces.These stress fields depend on the inclusions’size,shape,and distribution and will respond instantly to the evolving microstructure.This study develops a phase-field model concerningmodulus heterogeneity.The effect of modulus heterogeneity on the growth process and equilibrium state of theαplate in Ti-6Al-4V during precipitation is evaluated.Theαprecipitate exhibits strong anisotropy in shape upon cooling due to the interplay of the elastic strain and interfacial energy.The calculated orientation of the habit plane using the homogeneous modulus ofαphase shows the smallest deviation fromthat of the habit plane observed in the experiment,compared to the case where the homogeneous modulus ofβphase is adopted.In addition,the equilibrium volume ofαphase within the systemusing homogeneousβmodulus exhibits the largest dependency on the applied stresses.The stress fields across theα/βinterface are further calculated under the assumption of modulus heterogeneity and compared to those using homogeneous modulus of eitherαorβphase.This study provides an essential theoretical basis for developing mechanics models concerning systems with heterogeneous structures.

The heterogeneity of tumor-associated macrophages and strategies to target it

Tumor-associated macrophages(TAMs)are emerging as targets for tumor therapy because of their primary role in promoting tumor progression.Several studies have been conducted to target TAMs by reducing their infiltration,depleting their numbers,and reversing their phenotypes to suppress tumor progression,leading to the development of drugs in preclinical and clinical trials.However,the heterogeneous characteristics of TAMs,including their ontogenetic and functional heterogeneity,limit their targeting.Therefore,in-depth exploration of the heterogeneity of TAMs,combined with immune checkpoint therapy or other therapeutic modalities could improve the efficiency of tumor treatment.This review focuses on the heterogeneous ontogeny and function of TAMs,as well as the current development of tumor therapies targeting TAMs and combination strategies.

Quantifying the impact of earthquakes and geological factors on spatial heterogeneity of debris-flow prone areas:A case study in the Hengduan Mountains

Understanding the spatial heterogeneity of debris-flow-prone areas holds significant implications for regional risk management, particularly in seismically active regions with geological faults. Despite the significance of this knowledge, a comprehensive quantification of the influence of regional topographical and geological factors on the spatial heterogeneity of debris-flow-prone areas has been lacking. This study selected the Hengduan Mountains, an earthquake-prone region characterized by diverse surface conditions and complex landforms, as a representative study area. An improved units zoning and objective factors identification methodology was employed in earthquake and fault analysis to assess the impact of seismic activity and geological factors on spatial heterogeneity of debrisflow prone areas. Results showed that the application of GIS technology with hydrodynamic intensity and geographical units analysis can effectively analyze debris-flow prone areas. Meanwhile, earthquake and fault zones obviously increase the density of debrisflow prone catchments and make them unevenly distributed. The number of debris-flow prone areas shows a nonlinear variation with the gradual increase of geomorphic factor value. Specifically, the area with 1000 m-2500 m elevation difference, 25°-30° average slope, and 0.13-0.15 land use index is the most favorable conditions for debris-flow occurrence;The average annual rainfall from 600 to 1150 mm and landslides gradient from 16° to 35° are the main causal factors to trigger debris flow. Our study sheds light on the quantification of spatial heterogeneity in debris flow-prone areas in earthquake-prone regions, which can offer crucial support for post-debris flow risk management strategies.

Influence of Transportation Accessibility on Urban-rural Income Disparity and Its Spatial Heterogeneity

Transportation accessibility has been treated as an important means of reducing the urban-rural income disparity.However,only a few studies have examined the effects of different types of transportation accessibility on urban-rural income disparity and their spatial heterogeneity.Based on data from 285 prefecture-level(and above)Chinese cities in 2000,2005,2010,2015,and 2020,this study uses spatial econometric models to examine how highway accessibility and railway accessibility influence the urban-rural income disparity and to identify their spatial heterogeneity.The result reveals that highway accessibility and railway accessibility have‘coreperiphery’ring-like circle structures.The urban-rural income disparity exhibits strong spatial clustering effects.Both highway accessibility and railway accessibility are negatively associated with urban-rural income disparity,and the former having a greater effect size.Moreover,there is a substitution effect between highway accessibility and railway accessibility in the whole sample.Furthermore,these associations differ in geographic regions.In the central region,highway accessibility is more important in reducing the urban-rural income disparity,but its effect is weakened with the increase of railway accessibility.In the western region,railway accessibility has a larger effect on narrowing the urban-rural income disparity,and this effect is strengthened by the increase of highway accessibility.We conclude that improving transportation accessibility is conducive to reducing the urban-rural income disparity but its effect is spatial heterogenetic.Highways and railways should be developed in a coordinated manner to promote an integrated transport network system.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Prediction of Porous Media Fluid Flow with Spatial Heterogeneity Using Criss-Cross Physics-Informed Convolutional Neural Networks

Recent advances in deep neural networks have shed new light on physics,engineering,and scientific computing.Reconciling the data-centered viewpoint with physical simulation is one of the research hotspots.The physicsinformedneural network(PINN)is currently the most general framework,which is more popular due to theconvenience of constructing NNs and excellent generalization ability.The automatic differentiation(AD)-basedPINN model is suitable for the homogeneous scientific problem;however,it is unclear how AD can enforce fluxcontinuity across boundaries between cells of different properties where spatial heterogeneity is represented bygrid cells with different physical properties.In this work,we propose a criss-cross physics-informed convolutionalneural network(CC-PINN)learning architecture,aiming to learn the solution of parametric PDEs with spatialheterogeneity of physical properties.To achieve the seamless enforcement of flux continuity and integration ofphysicalmeaning into CNN,a predefined 2D convolutional layer is proposed to accurately express transmissibilitybetween adjacent cells.The efficacy of the proposedmethodwas evaluated through predictions of several petroleumreservoir problems with spatial heterogeneity and compared against state-of-the-art(PINN)through numericalanalysis as a benchmark,which demonstrated the superiority of the proposed method over the PINN.

Optimal Insurance with Background Risk under the Ambiguity and Belief Heterogeneity Structure

In this paper, we discuss the optimal insurance in the presence of background risk while the insured is ambiguity averse and there exists belief heterogeneity between the insured and the insurer. We give the optimal insurance contract when maxing the insured’s expected utility of his/her remaining wealth under the smooth ambiguity model and the heterogeneous belief form satisfying the MHR condition. We calculate the insurance premium by using generalized Wang’s premium and also introduce a series of stochastic orders proposed by [1] to describe the relationships among the insurable risk, background risk and ambiguity parameter. We obtain the deductible insurance is the optimal insurance while they meet specific dependence structures.

Type 2 diabetes in children and adolescents:Exploring the disease heterogeneity and research gaps to optimum management

Over the past 20 years,the incidence and prevalence of type 2 diabetes mellitus(T2DM)in children and adolescents have increased,particularly in racial and ethnic minorities.Despite the rise in T2DM in children and adolescents,the pathophysiology and progression of disease in this population are not clearly understood.Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM.Furthermore,the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients,mostly due to the challenges of implementing clinical trials.A better understanding of the mechanisms underlying the development and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies.This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.

A semi-analytical rate-transient analysis model for light oil reservoirs exhibiting reservoir heterogeneity and multiphase flow

Rate-transient analysis(RTA)has been widely applied to extract estimates of reservoir/hydraulic fracture properties.However,the majority of RTA techniques can lead to misdiagnosis of reservoir/fracture information when the reservoir exhibits reservoir heterogeneity and multiphase flow simultaneously.This work proposes a practical-yet-rigorous method to decouple the effects of reservoir heterogeneity and multiphase flow during TLF,and improve the evaluation of reservoir/fracture properties.A new,general,semi-analytical model is proposed that explicitly accounts for multiphase flow,fractalbased reservoir heterogeneity,anomalous diffusion,and pressure-dependent fluid properties.This is achieved by introducing a new Boltzmann-type transformation,the exponent of which includes reservoir heterogeneity and anomalous diffusion.In order to decouple the effects of reservoir heterogeneity and multiphase flow during TLF,the modified Boltzmann variable allows the conversion of three partial differential equations(PDE's)(i.e.,oil,gas and water diffusion equations)into ordinary differential equations(ODE's)that are easily solved using the Runge-Kutta(RK)method.A modified time-power-law plot is also proposed to estimate the reservoir and fracture properties,recognizing that the classical square-root-of-time-plot is no longer valid when various reservoir complexities are exhibited simultaneously.Using the slope of the straight line on the modified time-power-law plot,the linear flow parameter can be estimated with more confidence.Moreover,because of the new Boltzmann-type transformation,reservoir and fracture properties can be derived more efficiently without the need for defining complex pseudo-variable transformations.Using the new semi-analytical model,the effects of multiphase flow,reservoir heterogeneity and anomalous diffusion on rate-decline behavior are evaluated.For the case of approximately constant flowing pressure,multiphase flow impacts initial oil rate,which is a function of oil relative permeability and well flowing pressure.However,multiphase flow has a minor effect on the oil production decline exponent.Reservoir heterogeneity/anomalous diffusion affect both the initial oil production rate and production decline exponent.The production decline exponent constant is a function of reservoir heterogeneity/anomalous diffusion only.The practical significance of this work is the advancement of RTA techniques to allow for more complex reservoir scenarios,leading to more accurate production forecasting and better-informed capital planning.

Single-cell analysis of cellular heterogeneity and interactions in the ischemia-reperfusion injured mouse intestine

Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion(II/R)injury by single-cell RNA sequencing.For enterocyte cells,11 subclusters were found,in which enterocyte cluster 1(EC1),enterocyte cluster 3(EC3),and enterocyte cluster 8(EC8)were newly discovered cells in ischemia 45 min/reperfusion 720 min(I 45 min/R 720 min)group.EC1 and EC3 played roles in digestion and absorption,and EC8 played a role in cell junctions.For TA cells,after ischemia 45 min/reperfusion 90 min(I 45 min/R 90 min),many TA cells at the stage of proliferation were identified.For Paneth cells,Paneth cluster 3 was observed in the resting state of normal jejunum.After I 45 min/R 90 min,three new subsets were found,in which Paneth cluster 1 had good antigen presentation activity.The main functions of goblet cells were to synthesize and secrete mucus,and a novel subcluster(goblet cluster 5)with highly proliferative ability was discovered in I 45 min/R 90 min group.As a major part of immune system,the changes in T cells with important roles were clarified.Notably,enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells,TA cells,Paneth cells,and goblet cells to elicit intercellular communication.One marker known as glutathione S-transferase mu 3(GSTM3)affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases(MAPK)signaling during II/R injury.The data on the heterogeneity of intestinal cells,cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.

Risk assessment of fault reactivation considering the heterogeneity of friction strength in the BZ34-2 Oilfield,Huanghekou Sag,Bohai Bay Basin,China

The hazards of fault reactivation caused by fluid injection are a growing concern.However,traditional evaluation methods of fault stability are likely to underestimate the risk in fault segments with a high clay content.Therefore,an extended evaluation method of fault stability(ECPP)incorporating the heterogeneity in friction strength caused by variation in the clay content within the fault zone is established in this study.After characterizing the current stress field of the BZ34-2 Oilfield in the Huanghekou Sag,Bohai Bay Basin,the reactivation potential of faults is evaluated using both traditional and ECPP methods.Traditional evaluation of fault stability shows that all faults are stable in the present stress field.Faults oriented ENE have a relatively high risk.The maximum sustainable fluid pressure Δp is approximately 8.8-8.9 MPa and 9.3-9.9 MPa.When considering the heterogeneity in fault friction strength,the fault stability is clearly controlled by the clay content of the faults.The high-risk fault segments assessed using traditional methods are no longer obvious,which reflects the importance of incorporating friction strength heterogeneity in the process of fault evaluation.Moreover,the results also show that most fault segments are activated when the fault zone is dominated by montmorillonite,reflecting the strong influence of clay mineral types on fault stability.The factors influencing the heterogeneity of fault friction strength are very complicated in actual situations.Therefore,future work should focus on establishing a database through a large number of experiments and investigating the relationship between the friction coefficient and the main controlling factors.

Spatial patterns of Picea crassifolia driven by environmental heterogeneity and intraspecifi c interactions

Research on the spatial patterns of tree populations is critical for understanding the structure and dynamic processes of forests.However,little is known about how the underlying drivers shape these patterns and species interactions in forest systems.In this study,spatial point pattern analysis investigated the combined eff ects of intraspecifi c interactions and environmental heterogeneity on the spatial structure and internal maintenance mechanisms of Picea crassifolia in the Qilian Mountain National Nature Reserve,China.Data were obtained from a 10.2-ha dynamic monitoring plot(DMP)and sixteen 0.04-ha elevation gradient plots(EGPs).Under complete spatial randomness,both mature trees and saplings in the DMP demonstratedlarge-scale aggregation with negative correlations.In EGPs,saplings were clustered in small mesoscales,mature trees were randomly distributed,and the interactions of saplingstrees at all elevations were not correlated.By eliminating the interference of environmental heterogeneity through the inhomogeneous Poisson process,saplings in the DMP and EGPs were clustered in small scales and trees randomly distributed.Intraspecifi c associations were negatively correlated,in the DMP and at low elevations,and no correlations in high elevations of EGPs.In the vertical scale,saplings showed a small-scale aggregation pattern with increase in elevation,and the aggregation degree fi rst decreased and then increased.The interactions of saplings-trees and saplings–saplings showed inhibitions at small scales,with the degree of inhibition gradually decreasing.Spatial patterns and associations of adults–adults did not change signifi-cantly.The results revealed that intraspecifi c interactions and environmental heterogeneity regulated the spatial patterns of P.crassifolia at small and large scales,respectively.Environmental heterogeneity might be the most decisive factor aff ecting the spatial patterns of saplings,while trees were more aff ected by intraspecifi c interactions.Moreover,competition between trees in this area could be more common than facilitation for the growth and development of individuals.