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1.
Talanta ; 278: 126501, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38963978

ABSTRACT

In recent years, the development of spatial transcriptomic technologies has enabled us to gain an in-depth understanding of the spatial heterogeneity of gene expression in biological tissues. However, a simple and efficient tool is required to analyze multiple spatial targets, such as mRNAs, miRNAs, or genetic mutations, at high resolution in formalin-fixed paraffin-embedded (FFPE) tissue sections. In this study, we developed hydrogel pathological sectioning coupled with the previously reported Sampling Junior instrument (HPSJ) to assess the spatial heterogeneity of multiple targets in FFPE sections at a scale of 180 µm. The HPSJ platform was used to demonstrate the spatial heterogeneity of 9 ferroptosis-related genes (TFRC, NCOA4, FTH1, ACSL4, LPCAT3, ALOX12, SLC7A11, GLS2, and GPX4) and 2 miRNAs (miR-185-5p and miR522) in FFPE tissue samples from patients with triple-negative breast cancer (TNBC). The results validated the significant heterogeneity of ferroptosis-related mRNAs and miRNAs. In addition, HPSJ confirmed the spatial heterogeneity of the L858R mutation in 7 operation-sourced and 4 needle-biopsy-sourced FFPE samples from patients with lung adenocarcinoma (LUAD). The successful detection of clinical FFPE samples indicates that HPSJ is a precise, high-throughput, cost-effective, and universal platform for analyzing spatial heterogeneity, which is beneficial for elucidating the mechanisms underlying drug resistance and guiding the prescription of mutant-targeted drugs in patients with tumors.

2.
Sci Total Environ ; 946: 174323, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38955281

ABSTRACT

China's swift socioeconomic development has led to extremely severe ambient PM2.5 levels, the associated negative health outcomes of which include premature death. However, a comprehensive explanation of the socioeconomic mechanism contributing to PM2.5-related premature deaths has not yet to be fully elucidated through long-term spatial panel data. Here, we employed a global exposure mortality model (GEMM) and the system generalized method of moments (Sys-GMM) to examine the primary determinants contributing to premature deaths in Chinese provinces from 2000 to 2021. We found that in the research period, premature deaths in China increased by 46 %, reaching 1.87 million, a figure that decreased somewhat after the COVID-19 outbreak. 62 thousand premature deaths were avoided in 2020 and 2021 compared to 2019, primarily due to the decline in PM2.5 concentrations. Premature deaths have increased across all provinces, particularly in North China, and a discernible spatial agglomeration effect was observed, highlighting effects on nearby provinces. The findings also underscored the significance of determinants such as urbanization, import and export trade, and energy consumption in exacerbating premature deaths, while energy intensity exerted a mitigating influence. Importantly, a U-shaped relationship between premature deaths and economic development was unveiled for the first time, implying the need for vigilance regarding potential health impact deterioration and the implementation of countermeasures as the per capita GDP increases in China. Our findings deserve attention from policymakers as they shed fresh insights into atmospheric control and Health China action.

3.
Parasit Vectors ; 17(1): 287, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956689

ABSTRACT

BACKGROUND: The emergence of pyrethroid resistance has threatened the elimination of Triatoma infestans from the Gran Chaco ecoregion. We investigated the status and spatial distribution of house infestation with T. infestans and its main determinants in Castelli, a municipality of the Argentine Chaco with record levels of triatomine pyrethroid resistance, persistent infestation over 2005-2014, and limited or no control actions over 2015-2020. METHODS: We conducted a 2-year longitudinal survey to assess triatomine infestation by timed manual searches in a well-defined rural section of Castelli including 14 villages and 234 inhabited houses in 2018 (baseline) and 2020, collected housing and sociodemographic data by on-site inspection and a tailored questionnaire, and synthetized these data into three indices generated by multiple correspondence analysis. RESULTS: The overall prevalence of house infestation in 2018 (33.8%) and 2020 (31.6%) virtually matched the historical estimates for the period 2005-2014 (33.7%) under recurrent pyrethroid sprays. While mean peridomestic infestation remained the same (26.4-26.7%) between 2018 and 2020, domestic infestation slightly decreased from 12.2 to 8.3%. Key triatomine habitats were storerooms, domiciles, kitchens, and structures occupied by chickens. Local spatial analysis showed significant aggregation of infestation and bug abundance in five villages, four of which had very high pyrethroid resistance approximately over 2010-2013, suggesting persistent infestations over space-time. House bug abundance within the hotspots consistently exceeded the estimates recorded in other villages. Multiple regression analysis revealed that the presence and relative abundance of T. infestans in domiciles were strongly and negatively associated with indices for household preventive practices (pesticide use) and housing quality. Questionnaire-derived information showed extensive use of pyrethroids associated with livestock raising and concomitant spillover treatment of dogs and (peri) domestic premises. CONCLUSIONS: Triatoma infestans populations in an area with high pyrethroid resistance showed slow recovery and propagation rates despite limited or marginal control actions over a 5-year period. Consistent with these patterns, independent experiments confirmed the lower fitness of pyrethroid-resistant triatomines in Castelli compared with susceptible conspecifics. Targeting hotspots and pyrethroid-resistant foci with appropriate house modification measures and judicious application of alternative insecticides with adequate toxicity profiles are needed to suppress resistant triatomine populations and prevent their eventual regional spread.


Subject(s)
Chagas Disease , Insecticide Resistance , Insecticides , Pyrethrins , Triatoma , Animals , Triatoma/drug effects , Triatoma/physiology , Pyrethrins/pharmacology , Argentina , Insecticides/pharmacology , Chagas Disease/transmission , Chagas Disease/epidemiology , Humans , Longitudinal Studies , Insect Vectors/drug effects , Insect Vectors/physiology , Housing , Ecosystem , Insect Control
4.
J Environ Manage ; 366: 121587, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981272

ABSTRACT

Nutrient loads in lakes are spatially heterogeneous, but current spatial analysis method are mainly zonal, making them subjective and uncertain. This study proposes a high-resolution model for assessing spatial differences in nutrient loads based on the lattice Boltzmann method. The model was applied to Dongping Lake in China. Firstly, the contribution rates of four influencing factors, including water transfer, inflow, wind, and internal load, were calculated at different locations in the lake. Then, their proportionate contributions during different intervals to the whole lake area were calculated. Finally, the cumulative load could be calculated for any location within the lake. The validation showed that the model simulated hydrodynamics and water quality well, with relative errors between the simulated and measured water quality data smaller than 0.45. Wind increased the nutrient loads in most parts of the lake. The loads tended to accumulate in the east central area where high-frequency circulation patterns were present. Overall, the proposed water quality model based on the lattice Boltzmann method was able to simulate seven indexes. Therefore, this model represents a useful tool for thoroughly assessing nutrient load distributions in large shallow lakes and could help refine lake restoration management.

5.
Math Biosci ; 375: 109243, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964670

ABSTRACT

Based on the distinctive spatial diffusion characteristics observed in syphilis transmission patterns, this paper introduces a novel reaction-diffusion model for syphilis disease dynamics, incorporating general incidence functions within a heterogeneous environment. We derive the basic reproduction number essential for threshold dynamics and investigate the uniform persistence of the model. We validate the model and estimate its parameters by employing the multi-objective Markov Chain Monte Carlo (MCMC) method, using real syphilis data from the years 2004 to 2018 in China. Furthermore, we explore the impact of spatial heterogeneity and intervention measures on syphilis transmission. Our findings reveal several key insights: (1) In addition to the original high-incidence areas of syphilis, Xinjiang, Guizhou, Hunan and Northeast China have also emerged as high-incidence regions for syphilis in China. (2) The latent syphilis cases represent the highest proportion of newly reported cases, highlighting the critical importance of considering their role in transmission dynamics to avoid underestimation of syphilis outbreaks. (3) Neglecting spatial heterogeneity results in an underestimation of disease prevalence and the number of syphilis-infected individuals, undermining effective disease prevention and control strategies. (4) The initial conditions have minimal impact on the long-term spatial distribution of syphilis-infected individuals in scenarios of varying diffusion rates. This study underscores the significance of spatial dynamics and intervention measures in assessing and managing syphilis transmission, which offers insights for public health policymakers.

6.
Sci Rep ; 14(1): 16414, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014072

ABSTRACT

We present a methodology designed to study the spatial heterogeneity of climate change. Our approach involves decomposing the observed changes in temperature patterns into multiple trend, cycle, and seasonal components within a spatio-temporal model. We apply this method to test the hypothesis of a global long-term temperature trend against multiple trends in distinct biomes. Applying this methodology, we delve into the examination of heterogeneity of climate change in Brazil-a country characterized by a spectrum of climate zones. The findings challenge the notion of a global trend, revealing the presence of distinct trends in warming effects, and more accelerated trends for the Amazon and Cerrado biomes, indicating a composition between global warming and deforestation in determining changes in permanent temperature patterns.


Subject(s)
Climate Change , Ecosystem , Brazil , Temperature , Seasons , Conservation of Natural Resources , Global Warming
7.
Sci Total Environ ; 946: 174199, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38925385

ABSTRACT

Elucidating the spatial and temporal patterns of grassland ecosystem service value (ESV) changes under different karst geomorphic types (KGTs) is crucial for promoting regional sustainable development and enhancing human well-being. Karst ecosystems are characterized by high spatial heterogeneity. However, analyses of the drivers of spatial and temporal changes in ESV in karst grasslands at multiple scales are lacking. In this study, the South China Karst (SCK) region was selected as the focus area, the gross ecosystem product (GEP) accounting method was used to quantify the grassland ESV from 2000 to 2020, and the GeoDetector model was used to elucidate the spatial and temporal evolution of the GEP, the drivers, and their interactions in different KGTs. The results indicate the following: (1) Over the past 20 years, the grassland GEP of SCK has increased from ¥ 14,844.24 × 108 in 2000 to ¥ 17,174.90 × 108 in 2020. Among the various KGTs, the karst gorge exhibited the fastest GEP increase (24.93 %) and karst hilly depressions the slowest (6.22 %). (2) The karst grassland GEP showed a strong positive spatial correlation with significant clustering characteristics (p < 0.05). (3) There are significant differences in the factors influencing the GEP of grasslands with different KGT values, and although they are generally influenced by factors such as NPP, precipitation, and population density, anthropogenic factors are becoming increasingly important. In addition, the multifactor interaction explained GEP better than the single factor. Based on our findings, we propose targeted grassland ESV restoration approaches and management recommendations for various KGTs dominated by distinct factors. Our results provide a scientific basis for decision-making regarding karst ecosystem service enhancement and value realization.

8.
Front Public Health ; 12: 1297635, 2024.
Article in English | MEDLINE | ID: mdl-38827625

ABSTRACT

Background: In China, bacillary dysentery (BD) is the third most frequently reported infectious disease, with the greatest annual incidence rate of 38.03 cases per 10,000 person-years. It is well acknowledged that temperature is associated with BD and the previous studies of temperature-BD association in different provinces of China present a considerable heterogeneity, which may lead to an inaccurate estimation for a region-specific association and incorrect attributable burdens. Meanwhile, the common methods for multi-city studies, such as stratified strategy and meta-analysis, have their own limitations in handling the heterogeneity. Therefore, it is necessary to adopt an appropriate method considering the spatial autocorrelation to accurately characterize the spatial distribution of temperature-BD association and obtain its attributable burden in 31 provinces of China. Methods: A novel three-stage strategy was adopted. In the first stage, we used the generalized additive model (GAM) model to independently estimate the province-specific association between monthly average temperature (MAT) and BD. In the second stage, the Leroux-prior-based conditional autoregression (LCAR) was used to spatially smooth the association and characterize its spatial distribution. In the third stage, we calculate the attribute BD cases based on a more accurate estimation of association. Results: The smoothed association curves generally show a higher relative risk with a higher MAT, but some of them have an inverted "V" shape. Meanwhile, the spatial distribution of association indicates that western provinces have a higher relative risk of MAT than eastern provinces with 0.695 and 0.645 on average, respectively. The maximum and minimum total attributable number of cases are 224,257 in Beijing and 88,906 in Hainan, respectively. The average values of each province in the eastern, western, and central areas are approximately 40,991, 42,025, and 26,947, respectively. Conclusion: Based on the LCAR-based three-stage strategy, we can obtain a more accurate spatial distribution of temperature-BD association and attributable BD cases. Furthermore, the results can help relevant institutions to prevent and control the epidemic of BD efficiently.


Subject(s)
Dysentery, Bacillary , Temperature , China/epidemiology , Humans , Dysentery, Bacillary/epidemiology , Incidence , Spatial Analysis , Models, Statistical
9.
Article in English | MEDLINE | ID: mdl-38837060

ABSTRACT

PURPOSE: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity. METHODS: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated. RESULTS: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance. CONCLUSION: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future.

10.
Front Microbiol ; 15: 1340575, 2024.
Article in English | MEDLINE | ID: mdl-38919496

ABSTRACT

Introduction: Knowledge on spatiotemporal heterogeneity of plant root microbiomes is lacking. The diversity of the root microbiome must be revealed for understanding plant-microbe interactions and the regulation of functionally crucial microbial taxa. Methods: We here investigated the dynamics of microbial group characteristics within each soil ecological compartment [rhizoplane (B), rhizosphere (J), and bulk soil (T)] across different cultivation years (year 4: F4 and year 5: F5) by using high-throughput sequencing (16S and ITS). Results: According to the species diversity, microbiome diversity and the ASV (amplified sequence variant) number in the rhizoplane ecotone increased significantly with an increase in the planting years. By contrast, the microbiome diversity of the rhizosphere soil remained relatively stable. PCoA and PERMANOVA analyses revealed that microbial taxa among different planting years and ecological compartments varied significantly. Planting years exerted the least effect on the rhizosphere microbiome, but their impact on fungi in the rhizoplane and bacteria in the bulk soil was the most significant. Discussion: Planting years influenced the microbial community composition in various ecological compartments of ginseng root soil. Potentially harmful fungi such as Cryptococcus (2.83%), Neonectria (0.89%), llyonectria (0.56%), Gibberella (0.41%), Piloderma (4.44%), and Plectosphaerella (3.88%) were enriched in F5B with an increase in planting years, whereas the abundance of potentially beneficial Mortierella increased. Correlation analysis indicated associations between bacterial taxa and soil pH/S-CAT, and between fungal taxa and soil moisture content/total potassium. Our study highlights the significance of changes in rhizoplane fungi and the stability of the rhizosphere microbial community in comprehending plant ecological sustainability.

11.
Article in English | MEDLINE | ID: mdl-38922937

ABSTRACT

OBJECTIVE: To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs). METHODS AND RESULTS: Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli-extra-stimulus (S1-S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol-12-myristate-13-acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p < .05) and decreased the thresholds of the VA and APD alternans (p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch-clamp, peak amplitude of L-type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p < .05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans. CONCLUSION: PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.

12.
J Neuroeng Rehabil ; 21(1): 102, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877589

ABSTRACT

BACKGROUND: Investigating the spatial distribution of muscle activity would facilitate understanding the underlying mechanism of spasticity. The purpose of this study is to investigate the characteristics of spastic muscles during passive stretch and active contraction by high-density surface electromyography (HD-sEMG). METHODS: Fourteen spastic hemiparetic subjects and ten healthy subjects were recruited. The biceps brachii (BB) muscle activity of each subject was recorded by HD-sEMG during passive stretch at four stretch velocities (10, 60, 120, 180˚/s) and active contraction at three submaximal contraction levels (20, 50, 80%MVC). The intensity and spatial distribution of the BB activity were compared by the means of two-way analysis of variance, independent sample t-test, and paired sample t-test. RESULTS: Compared with healthy subjects, spastic hemiparetic subjects showed significantly higher intensity with velocity-dependent heterogeneous activation during passive stretch and more lateral and proximal activation distribution during active contraction. In addition, spastic hemiparetic subjects displayed almost non-overlapping activation areas during passive stretch and active contraction. The activation distribution of passive stretch was more distal when compared with the active contraction. CONCLUSIONS: These alterations of the BB activity could be the consequence of deficits in the descending central control after stroke. The complementary spatial distribution of spastic BB activity reflected their opposite motor units (MUs) recruitment patterns between passive stretch and active contraction. This HD-sEMG study provides new neurophysiological evidence for the spatial relationship of spastic BB activity between passive stretch and active contraction, advancing our knowledge on the mechanism of spasticity. TRIAL REGISTRATION: ChiCTR2000032245.


Subject(s)
Electromyography , Muscle Contraction , Muscle Spasticity , Muscle, Skeletal , Stroke , Humans , Male , Muscle Spasticity/physiopathology , Muscle Spasticity/etiology , Female , Middle Aged , Stroke/physiopathology , Stroke/complications , Muscle, Skeletal/physiopathology , Muscle Contraction/physiology , Adult , Aged
13.
Int J Environ Health Res ; : 1-15, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851885

ABSTRACT

A notable finding is that Kerala's capital Thiruvananthapuram has shown an increasing trend in lung cancer (LC) incidence. Long-term exposure to air pollution is a significant environmental risk factor for LC. This study investigated the spatial association between LC and exposure to air pollutants in Thiruvananthapuram, using Spatial Lag Model (SLM), Spatial Error Model (SEM), and Geographically Weighted Regression (GWR). The results showed that overall LC incidence rate was 111 per 105 males (age >60 years), whereas spatial distribution map revealed that 48% of the area had an incidence rate greater than 150. The results revealed a significant association between PM2.5 and LC. SLM was identified as the best model that predicted 62% variation in LC. GWR model improved model performance and made better local predictions in the southeastern parts of the study area. This study explores the effectiveness of spatial regression techniques for dealing spatial effects and pinpointing high-risk areas.

14.
Environ Pollut ; 357: 124465, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942280

ABSTRACT

The microbial community colonized on microplastics (MPs), known as the 'plastisphere', has attracted extensive concern owing to its environmental implications. Coastal salt marshes, which are crucial ecological assets, are considered sinks for MPs. Despite their strong spatial heterogeneity, there is limited information on plastisphere across diverse environments in coastal salt marshes. Herein, a 1-year field experiment was conducted at three sites in the Yancheng salt marsh in China. This included two sites in the intertidal zone, bare flat (BF) and Spartina alterniflora vegetation area (SA), and one site in the supratidal zone, Phragmites australis vegetation area (PA). Petroleum-based MPs (polyethylene and expanded polystyrene) and bio-based MPs (polylactic acid and polybutylene succinate) were employed. The results revealed significant differences in bacterial community composition between the plastisphere and sediment at all three sites examined, and the species enriched in the plastisphere exhibited location-specific characteristics. Overall, the largest difference was observed at the SA site, whereas the smallest difference was observed at the BF site. Furthermore, the MP polymer types influenced the composition of the bacterial communities in the plastisphere, also exhibiting location-specific characteristics, with the most pronounced impact observed at the PA site and the least at the BF site. The polybutylene succinate plastisphere bacterial communities at the SA and PA sites were quite different from the plastispheres from the other three MP polymer types. Co-occurrence network analyses suggested that the bacterial community network in the BF plastisphere exhibited the highest complexity, whereas the network in the SA plastisphere showed relatively sparse interactions. Null model analyses underscored the predominant role of deterministic processes in shaping the assembly of plastisphere bacterial communities across all three sites, with a more pronounced influence observed in the intertidal zone than in the supratidal zone. This study enriches our understanding of the plastisphere in coastal salt marshes.

15.
Sci Total Environ ; 946: 174190, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38936731

ABSTRACT

Ecological security (ES) is a crucial indicator for assessing the sustainable development of a region. Currently, most studies on ES primarily focus on process analysis, and the integration of environmental variability into the development of tailored control strategies for regions with varying ecological quality is overlooked. Therefore, in this study, we identified regional ES change processes, employed an optimized system to calculate the ecological security index (ESI), and identified ecological corridors (ECs) through the Minimum Constrained Resource (MCR) model to determine zoning strategies for typical arid regions, using the Ningxia region in the Yellow River Basin of China as an example. The findings showed that (1) from 2006 to 2020, the ESI values of most regions were between 0.2 and 0.4, with small but consistent increases in the ESI values over the years. (2) The proportion of regions with high ES ratings increased by 9.08 % across all districts and counties, and the center of gravity of ES shifted in a north-south and east-west direction. (3) The ESI exhibited a strong positive spatial correlation, characterized by spatial diffusion and spillover effects in most regions. (4) The ECs were predominantly distributed in a north-south direction, involving a total of 20 districts and counties. Based on the principles of sustainable development, we developed a model for the dynamic identification and zoning control of regional ES, aiming to provide a practical framework for effective ecological restoration and protection measures. Additionally, the strategies and methodologies presented in this study serve as important references for similar regions worldwide to facilitate the zoning control of ES, highlighting the broader significance and applicability of the study.

16.
Breast Cancer Res ; 26(1): 104, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918836

ABSTRACT

BACKGROUND: Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune checkpoint blockade (ICB) in immunologically "hot" tumors. However, immune dynamics in the low T-cell infiltrating "cold" tumor immune microenvironment during ICB remain poorly understood. This study uses molecular imaging to evaluate changes in CD4 + T cells and CD8 + T cells during ICB in breast cancer models and examines biomarkers of response. METHODS: [89Zr]Zr-DFO-CD4 and [89Zr]Zr-DFO-CD8 radiotracers were used to quantify changes in intratumoral and splenic CD4 T cells and CD8 T cells in response to ICB treatment in 4T1 and MMTV-HER2 mouse models, which represent immunologically "cold" tumors. A correlation between PET quantification metrics and long-term anti-tumor response was observed. Further biological validation was obtained by autoradiography and immunofluorescence. RESULTS: Following ICB treatment, an increase in the CD8-specific PET signal was observed within 6 days, and an increase in the CD4-specific PET signal was observed within 2 days in tumors that eventually responded to immunotherapy, while no significant differences in CD4 or CD8 were found at the baseline of treatment that differentiated responders from nonresponders. Furthermore, mice whose tumors responded to ICB had a lower CD8 PET signal in the spleen and a higher CD4 PET signal in the spleen compared to non-responders. Intratumoral spatial heterogeneity of the CD8 and CD4-specific PET signals was lower in responders compared to non-responders. Finally, PET imaging, autoradiography, and immunofluorescence signals were correlated when comparing in vivo imaging to ex vivo validations. CONCLUSIONS: CD4- and CD8-specific immuno-PET imaging can be used to characterize the in vivo distribution of CD4 + and CD8 + T cells in response to immune checkpoint blockade. Imaging metrics that describe the overall levels and distribution of CD8 + T cells and CD4 + T cells can provide insight into immunological alterations, predict biomarkers of response to immunotherapy, and guide clinical decision-making in those tumors where the kinetics of the response differ.


Subject(s)
Breast Neoplasms , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Disease Models, Animal , Immune Checkpoint Inhibitors , Positron-Emission Tomography , Tumor Microenvironment , Animals , Tumor Microenvironment/immunology , Female , Mice , CD8-Positive T-Lymphocytes/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Positron-Emission Tomography/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/immunology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Cell Line, Tumor , Zirconium , Radiopharmaceuticals , Radioisotopes
17.
Huan Jing Ke Xue ; 45(6): 3318-3328, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38897754

ABSTRACT

Ecosystem services (ESs) and their changes are complex processes driven by multiple factors. Understanding the trade-off and synergy between ESs and their driving factors is essential for achieving effective management of ESs and human well-being. Taking the Yangtze River Economic Belt as the research area, this study analyzed the temporal and spatial variation characteristics of four ESs including water yield, soil conservation, carbon sequestration, and food supply from 2000 to 2020. Correlation analysis and geographically weighted regression were used to identify and quantify the trade-off and synergy between ESs. On this basis, the partial least squares structural equation model was used to explore the impact of natural and human activities on ESs, and then the driving mechanism of ESs relationship change was analyzed via GeoDetector. The results showed that:① During the 20 years, the average annual carbon sequestration increased from 946.14 t·km-2 to 1 202.73 t·km-2, and the average food supply increased from 32.73×104 Yuan·km-2 to 127.22×104 Yuan·km-2. Water yield and soil conservation increased to a lesser degree. ② On the whole, carbon sequestration and soil conservation and food supply and water yield showed synergy, and other ESs were trade-offs. The relationship between ESs varied in different regions. ③ Terrain and climate were important driving factors for ESs and the trade-off and synergy of multiple ESs. Among them, structural equation model results showed that climate had a positive impact on water yield (S=0.73), and terrain had a negative impact on food supply (S=-0.57). GeoDetector results revealed that the main driving factors affecting the spatial relationship between carbon sequestration and water yield were elevation (q=0.38) and precipitation (q=0.19). The results of this study can provide a scientific reference for the sustainable management of ESs in the Yangtze River Economic Belt and the realization of the coordinated development of ecological environment protection and social economy in the region.

18.
Heliyon ; 10(7): e28659, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38689999

ABSTRACT

Based on the perspective of spatial economy, this paper focuses on the primary effects and spatial characteristics of Digital Financial Inclusion (DFI) on the upgrading of rural consumption structure (URCS) in China, conducting a literature review and theoretical analysis. It then uses statistical data collected over the years and the Digital Financial Inclusion Index (DFII) of Peking University to prepare panel data for 31 provinces in China (aside from Hong Kong, Macao, and Taiwan) from 2011 to 2020 for empirical testing. The results are as follows: DFI can considerably boost URCS, and there is a strong spatial neighbor impact, that is, it is affected by random shocks in surrounding provinces via its spatial effect; DFI has nonlinear characteristics in the process of fostering URCS, with the threshold variables of income level and family sizes; the impact of DFI on URCS is spatially heterogeneous, and the promotion of the eastern region is better than other zones. These results can inform policymakers about rural development and provide valuable references to push forward rural vitalization.

19.
J Math Biol ; 88(6): 76, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38691213

ABSTRACT

Most water-borne disease models ignore the advection of water flows in order to simplify the mathematical analysis and numerical computation. However, advection can play an important role in determining the disease transmission dynamics. In this paper, we investigate the long-term dynamics of a periodic reaction-advection-diffusion schistosomiasis model and explore the joint impact of advection, seasonality and spatial heterogeneity on the transmission of the disease. We derive the basic reproduction number R 0 and show that the disease-free periodic solution is globally attractive when R 0 < 1 whereas there is a positive endemic periodic solution and the system is uniformly persistent in a special case when R 0 > 1 . Moreover, we find that R 0 is a decreasing function of the advection coefficients which offers insights into why schistosomiasis is more serious in regions with slow water flows.


Subject(s)
Basic Reproduction Number , Epidemics , Mathematical Concepts , Models, Biological , Schistosomiasis , Seasons , Basic Reproduction Number/statistics & numerical data , Schistosomiasis/transmission , Schistosomiasis/epidemiology , Humans , Animals , Epidemics/statistics & numerical data , Epidemiological Models , Computer Simulation , Water Movements
20.
Environ Sci Technol ; 58(20): 8724-8735, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38717952

ABSTRACT

Building and protecting soil organic carbon (SOC) are critical to agricultural productivity, soil health, and climate change mitigation. We aim to understand how mechanisms at the organo-mineral interfaces influence SOC persistence in three contrasting soils (Luvisol, Vertisol, and Calcisol) under long-term free air CO2 enrichment conditions. A continuous wheat-field pea-canola rotation was maintained. For the first time, we provided evidence to a novel notion that persistent SOC is molecularly simple even under elevated CO2 conditions. We found that the elevated CO2 condition did not change the total SOC content or C forms compared with the soils under ambient CO2 as identified by synchrotron-based soft X-ray analyses. Furthermore, synchrotron-based infrared microspectroscopy confirmed a two-dimensional microscale distribution of similar and less diverse C forms in intact microaggregates under long-term elevated CO2 conditions. Strong correlations between the distribution of C forms and O-H groups of clays can explain the steady state of the total SOC content. However, the correlations between C forms and clay minerals were weakened in the coarse-textured Calcisol under long-term elevated CO2. Our findings suggested that we should emphasize identifying management practices that increase the physical protection of SOC instead of increasing complexity of C. Such information is valuable in developing more accurate C prediction models under elevated CO2 conditions and shift our thinking in developing management practices for maintaining and building SOC for better soil fertility and future environmental sustainability.


Subject(s)
Carbon Dioxide , Carbon , Soil , Carbon Dioxide/chemistry , Soil/chemistry , Climate Change
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