High Infiltration Research Articles

Immunological Tumor Microenvironment of Solitary Fibrous Tumors-Associating Immune Infiltrate with Variables of Prognostic Significance.

Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs). A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10-49, 2 = 50-99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round-oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS. Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round-oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1. SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores.

Evaluation and analysis of risk factors for adverse events of the fractured vertebra post-percutaneous kyphoplasty: a retrospective cohort study using multiple machine learning models

BackgroundAdverse events of the fractured vertebra (AEFV) post-percutaneous kyphoplasty (PKP) can lead to recurrent pain and neurological damage, which considerably affect the prognosis of patients and the quality of life. This study aimed to analyze the risk factors of AEFV and develop and select the optimal risk prediction model for AEFV to provide guidance for the prevention of this condition and enhancement of clinical outcomes.MethodsThis work included 383 patients with primary osteoporotic vertebral compression fracture (OVCF) who underwent PKP. The patients were grouped based on the occurrence of AEFV postsurgery, and data were collected. Group comparisons and correlation analysis were conducted to identify potential risk factors, which were then included in the five prediction models. The performance indicators served as basis for the selection of the best model.ResultsMultivariate logistic regression analysis revealed the following independent risk factors for AEFV: kissing spine (odds ratio (OR) = 8.47, 95% confidence interval (CI) 1.46–49.02), high paravertebral muscle fat infiltration grade (OR = 29.19, 95% CI 4.83–176.04), vertebral body computed tomography value (OR = 0.02, 95% CI 0.003–0.13, P < 0.001), and large Cobb change (OR = 5.31, 95% CI 1.77–15.77). The support vector machine (SVM) model exhibited the best performance in the prediction of the risk of AEFV.ConclusionFour independent risk factors were identified of AEFV, and five risk prediction models that can aid clinicians in the accurate identification of high-risk patients and prediction of the occurrence of AEFV were developed.

Larger shrubs can maintain high infiltration and evapotranspiration rates in experimental biofiltration systems impacted by high sediment loads

Biofiltration systems can fail over time due to clogging by fine sediments in stormwater. Infiltration can be maintained by plant roots, but species selection for biofiltration to date has largely been driven by pollutant removal efficiency and tolerance of conditions. As a result, plant species diversity in biofilters is typically low and dominated by sedges and rushes. Increased use of woody species could in theory improve plant diversity, aesthetic appeal, infiltration under high sediment loads and volumetric runoff reduction via higher evapotranspiration, without jeopardising nutrient pollutant removal. We tested whether shrubs could maintain infiltration and evapotranspiration in biofiltration profiles treated with a high sediment load, by comparing them with biofilters subjected to tap water without sediment. Following sediment application, biofilter columns planted with shrubs with high total biomass and total root length showed higher infiltration and evapotranspiration than those receiving tap water. These results indicate that shrub species are likely to alleviate clogging and increase stormwater retention in biofiltration systems. However, shrubs with a high root diameter also had low total biomass and total root length and showed 33–51 % lower infiltration rates after sediment application compared with those receiving tap water. As all shrubs had higher root diameters than typical sedges and rushes, we suggest that shrubs need a combination of higher total biomass, total root length and average root diameter to effectively maintain infiltration. While shrubs which maintained infiltration had traits associated with high nutrient removal, nutrient removal efficiency of shrubs needs to be quantified. Although root traits were related to maintenance of infiltration, above-ground stems likely created flow pathways through sediment which requires further investigation. Overall, selecting shrub species with high total biomass has the potential to maintain infiltration and increase evapotranspiration in biofiltration systems impacted by high sediment loads.

Contribution of root and soil properties on soil infiltration capacity of gramineous and leguminous forages during root decomposition

Soil properties are generally altered during root decomposition, which impacts soil water infiltration. Gramineous and leguminous plants present distinct root properties, but it remains unclear whether the root or soil properties are primarily responsible for the soil infiltration capability during root decomposition. To identifythe differences in the contributions of root and soil properties to soil infiltration capability between these two species during root decomposition, a potted plant in situ decomposition experiment was conducted using Bothriochloa. ischaemum (Gramineae) and Lespedeza. davurica (Leguminosae) during three root decomposition times (the 90th, 270th and 450th day). The results revealed that all the root properties (root length, root volume, average root diameter and root biomass) gradually decreased during root decomposition, especially the root length (RL) and root volume (RV) of L. davurica in 0–40 cm soil layer, with reductions of 55.35% and 58.73% at the 450th day compared with the 90th day. The reverse was true for the soil porosity and mean weight diameter of the soil aggregates. Compared to B. ischaemum, L. davurica presented relatively high initial infiltration rate (IIR), steady infiltration rate (SIR), and average infiltration rate (AIR) values at three root decomposition times. A great increase in the soil infiltration rate was observed for both species at the late decomposition stage (450th day), especially for L. davurica, with increases of 38.32%, 267.7%, and 137.1% in IIR, SIR, and AIR. The GLM analysis results revealed that root properties had a greater contribution to the soil infiltration capability. The key factors controlling the soil water infiltration process have been quantified as RL and RV. The present study indicates that leguminous forage presented greater soil infiltration capability during root decomposition. A great decrease in RL and RV within the upper soil layers increased the soil porosity and facilitated the formation of soil aggregates, thereby promoting water flow and ultimately improving the soil infiltration capability.

A case of eosinophilic granulomatosis with polyangiitis preceded by allergic bullous lesions.

A 62-year-old man with a history of diabetes mellitus was hospitalised with numbness of lower limbs, bullous lesions of the whole body, kidney dysfunction, presence of eosinophils, and elevated antineutrophil cytoplasmic antibodies to myeloperoxidase and anti-bullous pemphigoid 180 antibodies and was diagnosed with mononeuritis multiplex. Kidney and muscle biopsies showed vasculitis with fibrinoid necrosis, whereas skin biopsies showed only blister formation between the epidermis and dermis; a high eosinophilic infiltrate was present in all three tissues. These findings led to a diagnosis of eosinophilic granulomatosis with polyangiitis combined with allergic bullous lesions. Immunohistological examination indicated cytolytic eosinophils and extracellular traps, suggesting the presence of eosinophil extracellular trap cell death (eosinophil ETosis) in diseased tissue.

Disruptions in antigen processing and presentation machinery on sarcoma

BackgroundThe antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.MethodsWe investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001–2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.ResultsAll investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.ConclusionSarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.

Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function

Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic, proteomic and spatial single-cell approaches. Resolution of immune lineages indicates high infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoint markers, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M mouse models tested. We show these myeloid populations communicate with H3-mutant cells, mediating immunosuppression and sustaining tumor formation and maintenance. Dual inhibition of myeloid cells and immune checkpoint pathways show significant therapeutic benefits in pre-clinical syngeneic mouse models. Our findings provide a valuable characterization of the TME of oncohistone-mutant gliomas, and insight into the means for modulating the myeloid infiltrate for the benefit of patients.

Identifying CDCA3 as a pivotal biomarker for predicting outcomes and immunotherapy efficacy in pan-renal cell carcinoma.

Renal cell carcinoma (RCC) is a heterogeneous disease. Identifying effective biomarkers is crucial for improving prognostic accuracy and therapy outcomes. This study investigates cell division cycle-associated 3 (CDCA3) as a novel biomarker for prognostic assessment and immunotherapy response in RCC. This study analyzed multi-omics data from The Cancer Genome Atlas (TCGA) for kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe (KICH) subtypes to evaluate CDCA3 expression and its clinical implications. Functional enrichment and immune infiltration analyses were performed using bioinformatics tools gene set enrichment analysis (GSEA) and xCell. The prognostic value of CDCA3 was assessed through Cox regression and Kaplan-Meier survival analysis. Immunohistochemistry (IHC) was employed to confirm CDCA3 expression at the protein level in RCC samples. Higher CDCA3 expression correlated with poor survival outcomes and reduced response to programmed cell death protein 1 (PD-1) blockade therapies. Statistical analysis indicated that CDCA3 was an independent prognostic factor for poor survival in RCC. CDCA3 was consistently overexpressed in RCC tissues compared to normal tissues and was associated with adverse clinical features, including high Th2 cell infiltration and suppression of immune pathways. CDCA3 is a promising biomarker for RCC, offering insights into the tumor's prognosis and potential response to immunotherapy. The strong association between CDCA3 expression and poor therapeutic outcomes suggests that CDCA3 could be targeted in future therapeutic strategies.

Siglec-7 and Siglec-9 expression in primary triple negative and oestrogen receptor positive breast cancer and in vitro signalling.

PD-1/PD-L1 immune checkpoint blockade can be an effective treatment for advanced breast cancer patients. However, patients with oestrogen receptor positive (ER+) tumors often display only low lymphocyte infiltration, while a large part of triple negative (TN) breast tumors does not generate an effective immunotherapy response. Therefore, new treatment strategies have to be developed. Here, we investigate Siglec-7 and Siglec-9 as novel ITIM-bearing inhibitory immune checkpoint receptors similar to PD-1, but expressed on a broader range of immune cells. We assessed Siglec-7 and Siglec-9 (ligand) expression in TN and ER+ breast cancer tumors and their breast cancer cell line-induced signalling. We report that Siglec-7 and Siglec-9 are highly expressed in TN tumors, and to a low extent in ER+ tumors. Siglec-7 was observed on myeloid cells, Tcells, and NKcells and Siglec-9 preferentially on myeloid cells. Expression of sialoglycans, including Siglec-7 and Siglec-9 ligands, was observed in both TN and ER+ breast cancer tissue sections. Expression levels of Siglec-7 and Siglec-9 ligands were higher on in vitro cultured TN cell lines than ER+ cell lines. Importantly, by applying chimeric Siglec-7 reporter cells, we showed the induction of Siglec-7 signalling by multiple TN cell lines, but only by one ER+ cell line. Moreover, Siglec-7 signalling is directly related to Siglec-7 ligand expression levels of breast cancer cell lines. These data imply that immunotherapy targeting Siglec receptors may be particularly interesting for TN breast cancer patients not responding to current treatment strategies with tumors displaying high immune cell infiltration.

502O Pembrolizumab in combination with CAPOX and bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: Preliminary results of FFCD 1703 POCHI trial

502O Pembrolizumab in combination with CAPOX and bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: Preliminary results of FFCD 1703 POCHI trial

JAMES BUTTLE REVIEW: Interflow, subsurface stormflow and throughflow: A synthesis of field work and modelling

AbstractInterflow, throughflow and subsurface stormflow are interchangeable terms that refer to the lateral subsurface flow above a restricting layer of lower hydraulic conductivity that occurs during and following storm events. Interflow (used here) is a more dominant process in steeper catchments with high infiltration capacity soils overlying a more impermeable soil or geologic layer. Interflow as a runoff process was first recognised in the early 1900s, yet hydrologists still struggle to predict its occurrence, persistence, importance, interaction with other streamflow generation processes, and potential to connect to valleys and streams during and following storms. We review the history of interflow research and address some of the challenges in understanding its role in runoff production. We argue that characterising the controls on interflow initiation and occurrence relies on detailed field observations of subsurface properties, which exist only in limited experimental settings. This data shortcoming contributes to our inability to predict interflow or determine its contribution to streamflow more broadly. There remain many opportunities to advance our understanding of interflow that include both modelling and experimental or observational approaches in hydrology.

Assessment of urbanization impacts on soil erosion and groundwater recharge in Enugu, Southeastern Nigeria

The study of Land Use and Land Cover (LULC) in Enugu, southeastern Nigeria, is crucial for understanding its effects on erosion and groundwater recharge. Different LULC types, coupled with varying slope gradients and soil types, create a complex interaction that influences soil stability and water infiltration in the region. This research aims to assess the distribution of LULC types, slope gradients, and soil types in Enugu, and to evaluate their impacts on erosion rates and groundwater recharge potential. Data for LULC, slope gradients, and soil types were collected and analyzed to determine their spatial distribution and characteristics. The study employed GIS techniques to map these variables and assess their interactions. Erosion potential and groundwater recharge capacity were evaluated based on the characteristics of the LULC types, slopes, and soils. The analysis revealed that trees cover the largest area (3709.74 km²), playing a significant role in stabilizing the soil and reducing erosion through their extensive root systems and canopy cover. Rangeland (2631.81 km²) also contributes to soil stability, although less effectively than forested areas. Crops (192.40 km²) have mixed impacts on erosion depending on agricultural practices. Built areas (1162.69 km²) present challenges due to impervious surfaces, which increase surface runoff and reduce groundwater recharge. Slope gradients were found to correlate with erosion processes and groundwater dynamics. Gentle slopes (0 - 1.81 degrees) cover 1870.15 km² and facilitate infiltration, enhancing groundwater recharge. Moderate slopes (1.81 - 4.06 degrees), covering 3275.46 km², are more prone to erosion, while steeper slopes (4.06 - 11.73 degrees) covering 2176.54 km² experience accelerated runoff and increased erosion rates. The steepest slopes (11.73 - 44.06 degrees) are the most erosion-prone areas, requiring significant intervention. The soil analysis showed that Dystric Nitosols (4052.80 km²) with the lowest K-factor (0.0178) are least prone to erosion and have high infiltration capacity, making them beneficial for groundwater recharge. Plinthic Acrisols (2732.53 km²) and Ferric Acrisols (102.36 km²) exhibit moderate erosion susceptibility. Dystric Fluvisols (793.92 km²) with the highest K-factor (0.0223) are highly erosion-prone. Gleysols (20.69 km²) have low to moderate erosion susceptibility. The interplay between LULC types, slope gradients, and soil types significantly influences erosion and groundwater recharge in Enugu. The study highlights the need for targeted land management practices, such as afforestation, contour farming, terracing, and the use of cover crops to mitigate erosion and enhance groundwater recharge. This research provides a comprehensive analysis of the relationships between LULC, slope gradients, and soil types in Enugu, offering valuable insights for developing effective land management strategies to address erosion and groundwater recharge challenges.

High infiltration of immune cells with lower immune activity mediated the heterogeneity of gastric adenocarcinoma and promoted metastasis

BackgroundGastric adenocarcinoma (GA) is a heterogeneous malignancy with high invasion and metastasis. We aimed to explore the metastatic characteristics of GA using single-cell RNA-sequencing (scRNA-seq) analysis. MethodsThe scRNA-seq dataset was downloaded from the GEO database and the “Seurat” package was used to perform the scRNA-seq analysis. The CellMarker2.0 database provided gene markers. Subsequently, differentially expressed genes (DEGs) were identified using the FindMarkers function and subjected to enrichment analysis with the “ClusterProlifer”. “GseaVis” package was used for visualizing the gene levels. Finally, the SCENIC analysis was performed for identifying key regulons. The expression level and functionality of the key genes were verified by quantitative real-time PCR (qRT-PCR), wound healing and transwell assays. ResultsA total of 7697 cells were divided into 8 cell subsets, in which the Cytotoxic NK/T cells, Myeloid cells and Myofibroblasts had higher proportion in the metastatic tissues. Further screening of DEGs and enrichment analysis revealed that in the metastatic tissues, NK cells, monocytes and inflammatory fibroblasts with low immune levels contributed to GA metastasis. In addition, this study identified a series of key immune-related regulons that mediated the lower immune activity of immune cells. Further in vitro experiment verified that CXCL8 was a key factor mediating the proliferation and migration of GA cells. ConclusionThe scRNA-seq analysis showed that high infiltration of immune cells with lower immune activity mediated heterogeneity to contribute to GA metastasis.

Molecular subtypes based on immunologic and epithelial-mesenchymal transition gene sets reveal tumor immune microenvironment characteristics and implications for immunotherapy of patients with glioma

The tumor immune microenvironment (TIME) significantly influences cancer progression and treatment. This study sought to uncover novel TIME-related glioma biomarkers to advance antitumor immunotherapies by integrating data from sequencing of bulk RNA as well as scRNA. Immunologic and epithelial-mesenchymal transition (EMT) characteristics were used to classify glioma patients into two immune subtypes (ISs) and two EMT subtypes (ESs). Patients in IS1 and ES1, characterized by high immune infiltration and low stemness scores, exhibited poor clinical outcomes and limited responsiveness to immunotherapy. A new risk signature was developed using 16 genes and validated in independent glioma cohorts. Among these, HAVCR2, IL18, LAGLS9, and PTPN6 emerged as hub genes, with IL18 identified as a potential independent indicator. The upregulation of IL18 in high-grade gliomas and U-251 MG cells aligned with bioinformatics analysis. These insights deepen the understanding of TIME-related mechanisms in glioma and highlight potential therapeutic targets, offering a theoretical foundation for effective antitumor immunotherapies in glioma.

A comprehensive landscape analysis of autophagy in cancer development and drug resistance.

Autophagy plays important roles in cancer progression and therapeutic resistance, and the autophagy underlying the tumor pathogenesis and further mechanisms of chemoresistance emergence remains unknown. In this study, via the single-sample gene set enrichment analysis (ssGSEA) method, an autophagy 45-gene list was identified to evaluate samples' autophagy activity, verified through six GEO datasets with a confirmed autophagy phenotype. It was further utilized to distinguish tumors into autophagy score-high and score-low subtypes, and analyze their transcriptome landscapes, including survival analysis, correlation analysis of autophagy- and resistance-related genes, biological functional enrichment, and immune- and hypoxia-related and genomic heterogeneity comparison, in TCGA pan-cancer datasets. Furthermore, we performed an analysis of autophagy status in breast cancer chemoresistance combined with multiple GEO datasets and in vitro experiments to validate the mechanisms of potential anticancer drugs for reversing chemoresistance, including CCK-8 cell viability assays, RT-qPCR, and immunofluorescence. The 45-gene list was used to identify autophagy score-high and score-low subtypes and further analyze their multi-dimensional features. We demonstrated that cancer autophagy status correlated with significantly different prognoses, molecular alterations, biological process activations, immunocyte infiltrations, hypoxia statuses, and specific mutational processes. The autophagy score-low subtype displayed a more favorable prognosis compared with the score-high subtype, associated with their immune-activated features, manifested as high immunocyte infiltration, including high CD8+T, Tfh, Treg, NK cells, and tumor-associated macrophages M1/M2. The autophagy score-low subtype also showed a high hypoxia score, and hypoxic tumors showed a significantly differential prognosis in different autophagy statuses. Therefore, "double-edged" cell fates triggered by autophagy might be closely correlated with the immune microenvironment and hypoxia induction. Results demonstrated that dysregulated autophagy was involved in many cancers and their therapeutic resistance and that the autophagy was induced by the resistance-reversing drug response, in five breast cancer GEO datasets and validated by in vitro experiments. In vitro, dihydroartemisinin and artesunate could reverse breast cancer doxorubicin resistance, through inducing autophagy via upregulating LC3B and ATG7. Our study provided a comprehensive landscape of the autophagy-related molecular and tumor microenvironment patterns for cancer progression and resistance, and highlighted the promising potential of drug-induced autophagy in the activation of drug sensitivity and reversal of resistance.

Using Indoor and Outdoor Measurements to Understand Building Protectiveness against Wildfire, Atmospheric Inversion, and Firework PM2.5 Pollution Events

The world has seen an increase in the frequency and severity of elevated outdoor pollution events exacerbated by the rise in distant polluting events (i.e., wildfires). We examined the intersection between indoor and outdoor air quality in an urban area using research-grade sensors to explore PM2.5 infiltration across a variety of pollution events by testing two separate indoor environments within the same building. We confirmed prior work suggesting that indoor environments in buildings are most protective during wintertime inversion events and less so during fireworks and wildfire events. The building indoor environment protectiveness varies notably during different pollution episodes, especially those that have traveled longer distances (e.g., wildfires), and we found evidence of varied infiltration rates across PM2.5 types. Inversion events have the lowest infiltration rates (13–22%), followed by fireworks (53–58%), and wildfires have the highest infiltration rates (62–70%), with distant wildfire events persisting longer and, therefore, infiltrating for greater durations than local-wildfire-related particle matter. The differences in PM infiltration rates were likely due to the combined effects of several factors, including varying particle size, concentration, and chemistry. Subsequently, the local wildfires had different temporal air quality impacts than distant wildfire pollution in this case. Based on these findings, indoor air quality appears more conducive to protective action and policies than outdoor air quality because the built environment may serve to shield individuals from outdoor air.

Effects of an extreme heat event on indoor conditions of social heritage housing in Mediterranean climate

Social heritage housing in Mediterranean historic cities is particularly vulnerable to climate change hazards as protection policies lead to its exclusion from energy retrofitting programmes, leaving their residents - at higher risk of fuel poverty and the heat-island effect – defenceless. Increasingly frequent heatwaves can potentially produce “overheating” in these buildings, a thermal state that impedes people's comfort with harmful consequences to their health. Other indoor air quality factors, like humidity and CO₂ levels, also affect residents' health. The objective of this research is to evaluate the actual indoor environmental quality of three occupied dwellings in social buildings of high heritage value located in two historic cities in Andalusia (Spain) during the extreme heat events that occurred in 2022. A monitoring campaign was conducted and the data collected over the summer was analysed and evaluated using existing metrics. Our results show that the CO2 concentration rates generally remained below the upper limit of 1000 ppm in all cases, probably due to the high air infiltration rates measured (5.83 h−1, 4.39 h−1 and 14.65 h−1). On the contrary, the relative humidity rates were outside the acceptable range (45–60 %) for 90 % of the occupied hours in all cases. In the warmest city, overheating was continuous and severe in all rooms, according to the metric adopted (CIBSE standards TM52 and TM59 under the adaptive thermal comfort model). The situation was particularly critical in the free-running bedroom, but the overheating index values in the living rooms, where air conditioning was installed and used about 50 % of the occupied time, also deviated significantly from the acceptable limits.

Grasslands and flood mitigation – Contrasting forages improve surface water infiltration rates

Grasslands globally deliver many ecosystem services, including water management to alleviate flood risk reduction. Two replicated field experiments were conducted to study how agricultural forage species with diverse rooting systems, sown as single species, affected rooting, soil structure and earthworm populations, and consequently water infiltration to understand how they each might influence flood risk from grasslands. Experiment One showed soils under red clover (Trifolium pratense), white clover (Trifolium repens) and chicory (Cichorium intybus) had higher infiltration rates three years after establishment, compared to perennial ryegrass (Lolium perenne). Higher red clover and chicory root biomass or increased earthworm abundance under white clover may have caused these effects. Experiment Two monitored infiltration at intervals over several years post establishment to understand the timeframe for changes in rates; plantain (Plantago lanceolata) was sown as an additional forage. Infiltration declined post establishment, the timing and extent of decline varying with forages; forage effects were significant after 27 months (P < 0.05). Infiltration rates were higher under red and white clover compared to ryegrass, with chicory and plantain intermediate (P < 0.05). Forages again differed in likely mechanisms delivering higher water infiltration, notably between the two clover species. White clover had higher earthworm biomass (P < 0.05), whereas red clover had a higher average root diameter compared to the other forages (P < 0.05). Drivers of intermediate benefits of chicory and plantain also differed: chicory had higher earthworm abundance (month 38) compared to plantain, which had higher average root diameter compared to ryegrass (month 41); 30 months post-establishment soil bulk density was lower under both forages compared to ryegrass and red clover, with white clover intermediate (P < 0.05); bulk density and penetration resistance did not relate to infiltration. Findings demonstrate that a shift from perennial ryegrass-dominated pastures to swards with more contrasting forages provides an ecohydrological approach to mitigating flood risk and climate adaptation.

Modelling analysis of nitrogen removal from paddy water with high infiltration rate

AbstractAn understanding of nitrogen processes in a paddy field, characterised by large water flux for irrigation and outflows under continuous irrigation, is required to manage adequate nitrogen inputs and outputs. This study identifies the effect of large water flux, especially high infiltration rate, on nitrogen processes in a paddy field under continuous irrigation. The developed nitrogen process model in this study was applied to two paddy fields having different infiltration rates (216 and 106 mm day− 1 on average), and simulated physicochemical and biological nitrogen processes in ponded water, soil water and soil, including whole water flows as well as organic, and inorganic nitrogen forms. In each field, irrigation was found to be the major nitrogen input (153.2–461.5 kg N ha− 1 year− 1), and nitrogen outflow (65.2–284.3 kg N ha− 1 year− 1) found to be smaller than the input from irrigation. The irrigation water was primarily contaminated by dissolved organic nitrogen (DON) and nitrate. Nitrogen transportation from ponded water to soil water was four times greater under high infiltration condition than under low infiltration condition. High nitrogen transport to the soil layer increased air emission via denitrification and decreased outflows. In particular, DON and ammonium transported to soil water are sources of nitrite and nitrate, and denitrification was five times higher under high infiltration than low infiltration. The results of this study imply that paddy fields with high infiltration rates have a greater possibility of nitrogen removal from paddy water, rather than being a pollutant source for the water environment.

Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy

The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi) with radiotherapy (RT) increases the frequency of activated NKG2A+PD-1+ T cells in animal models of HNSCC. Compared with the ATRi/RT treatment regimen alone, the addition of simultaneous NKG2A and PD-L1 blockade to ATRi/RT, in the adjuvant, post-radiotherapy setting induces a robust antitumour response driven by higher infiltration and activation of cytotoxic T cells in the tumour microenvironment. The efficacy of this combination relies on CD40/CD40L costimulation and infiltration of activated, proliferating memory CD8+ and CD4+ T cells with persistent or new T cell receptor (TCR) signalling, respectively. We also observe increased richness in the TCR repertoire and emergence of numerous and large TCR clonotypes that cluster based on antigen specificity in response to NKG2A/PD-L1/ATRi/RT. Collectively, our data point towards potential combination approaches for the treatment of HNSCC.