Population Trends Research Articles

Detecting and attributing the impact of human activities on grassland aboveground biomass in China's Loess Plateau

Human activities significantly influence grassland ecosystem functions, particularly plant biomass. However, the direction and magnitude of these effects remain insufficiently explored. Herein, we quantitively assessed both the positive and negative effects of various human activities on grassland aboveground biomass (AGB) in China's Loess Plateau from 2000 to 2022. The results indicated that the magnitudes of positive effects increased by 0.29 g m−2 per year, whereas the negative effects decreased by 0.31 g m−2 per year. Spatially, 32 % of the grasslands experienced significant positive effects, whereas the rest grasslands faced negative effects. Notably, only 20 % of the areas with negative effects showed worsening trends mainly due to ecological restoration, sustainable agriculture, and population migration. Agricultural production activities and population changes emerged as dominant factors, with some activities, like livestock farming, exhibiting dual effects (i.e., positive and negative effects) on AGB. These findings underscore the complexity of human activities in affecting the grassland production function and highlight the necessity for balanced management strategies to sustain grassland productivity and resilience.

An interlinked dynamic model of timber and carbon stocks in Japan's wooden houses and plantation forests

Carbon absorption in growing trees is an important element of a carbon-neutral society, and the long-term storage of carbon stocks is a crucial sustainability challenge. Previous studies have focused on either live-biomass carbon stocks in plantation forests or anthropogenic carbon stocks in man-made objects. For a comprehensive nature-based climate solution, an analytical framework, dataset, and scenario setup for modeling the interrelationship between timber supply and demand are required. This study developed an interlinked material flow analysis model in which the timber demand for wooden houses is connected with timber supply from managed plantation forestry. We demonstrate the model by quantifying both live-biomass and anthropogenic carbon stocks and their potentials in Japan. We compared multiple scenario-runs of the model for wooden house demands estimated by population change with varying combinations of house types, structures, and lifespans. Our results show that carbon stocks will reach a maximum amount of 1.1 billion t-C by 2050 in a scenario of high demand for wooden detached houses with lifespan extensions. On the other hand, we also found that the aging of plantation forests and their reduced carbon-stocking capacities appear inevitable in any scenario owing to the limited demand for timber. Notably, despite the widely different settings of the various scenarios, our results exhibited narrow variances in future potential carbon storage in Japan. This can be explained by the unique population characteristics and building demographics of Japan. These counterintuitive findings highlight the need for interrelated modeling of the forestry and construction sectors. Our model and its scope are versatile and applicable to other case study areas, estimation periods, and target materials.

Study on volatile metabolites and microbial community in the fermentation process of black tea (Jiuqu hongmei tea)

Jiuqu hongmei tea (JQHM tea), unique to Zhejiang Province, China, is celebrated for its vibrant, delightful taste and distinctive flavor profile. This research explored the relationship between the tea's characteristic flavor during fermentation and the dynamics of microbial communities. Volatile organic compounds (VOCs) were analyzed using Headspace Solid-Phase Microextraction coupled with Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) at three key stages: machine kneading (MK, 0.5 hours), primary fermentation (F1, 1.5 hours), and secondary fermentation (F2, 3 hours). Concurrently, microbial communities were characterized through high-throughput sequencing. The study identified 12 significant VOCs and pinpointed 10 core bacterial and 9 core fungal genera. These findings revealed the intricate changes in aroma compounds and microbial populations throughout JQHM tea's fermentation process, highlighting the interplay between key aroma compounds and principal microbial genera. This knowledge provided a crucial theoretical foundation for refining the tea's processing stages and enhancing its flavor quality.

The impact of COVID-19 on dengue cases in low- and middle-income countries: a systematic review

The WHO declared the COVID-19 pandemic on March 11, 2020, impacting infectious disease surveillance in low-resource, low-income countries, low- and middle-income countries (LMICs). Governments are focusing on COVID-19 reduction, including healthcare workers and epidemiological teams. A comprehensive literature review was conducted to assess this impact. After examining over 19,000 studies, only six were found to provide relevant data. Our analysis revealed that the pandemic substantially affected dengue incidence. The total number of articles obtained was 19,382. Out of the 136 articles screened based on their abstracts, only six were selected for data extraction. The databases utilized in this article were Pubmed and NCBI. Based on the chosen papers, we discovered that the COVID-19 pandemic has had a notable impact on the occurrence of dengue compared to the period before the pandemic emerged. The occurrence of dengue varied in several nations, such as Peru, Brazil, Sri Lanka, India, and Malaysia. This variation can be attributed to factors such as reliance on traditional approaches, for example community health volunteers in epidemiological investigations. Additionally, misdiagnoses by healthcare professionals due to the similarity of symptoms with COVID-19 have been reported during the pandemic. While the prevalence of dengue fever cases has generally declined in low- and middle-income countries (LMICs), one country has experienced an increased case. This trend is possibly linked to heightened pandemic surveillance and changes in mosquito populations. To improve monitoring and surveillance, a digital approach is proposed.

Collaborative water-electricity operation optimization of a photovoltaic/pumped storage-based aquaculture energy system considering water evaporation effects

The increasing global population, economic development, and urbanization trends have led to a heightened demand for seafood, presenting a significant challenge to the growth trajectory of the food industry. As the most rapidly expanding segment within the food industry, aquaculture presents a sustainable solution to mitigate the overexploitation of marine resources and address the growing demand for food. Aquaculture's sufficient aquatic expanses offer considerable potential for PV deployment, thereby relieving the demand for limited land resources. However, existing research rarely addresses the collaborative operation of water and electricity in aquaculture systems. The effects of water evaporation from PV panel-covered water surfaces on the collaborative water-electricity operation are generally neglected. Hence, this work proposes a collaborative water-electricity operation of a photovoltaic (PV)-pumped storage-based aquaculture energy system considering the water evaporation effects. This optimization method accounts for the reduced water evaporation due to PV panel shading. Water surface PV and pumped storage are integrated into the system to fulfill electricity needs, with pumped storage serving as a dual-purpose device for water and electricity supply. Environmentally sustainable water-electricity generation and aquaculture energy system requirements are established. Water surface PV electricity generation is modeled based on climate and engineering conditions, while aquaculture pond electricity requirement includes oxygenation, feeding, and water replenishment. Finally, a collaborative water-electricity operation model is introduced to optimize operation strategies for various devices. A case study on a fish-light complementation project demonstrates that this optimization method can reduce reliance on the utility grid and overall system operational costs.

Optimizing IoT-driven smart grid stability prediction with dipper throated optimization algorithm for gradient boosting hyperparameters

With the surge in global population and economic expansion, there's been a marked increase in electricity demand. This necessitates the efficient distribution of electricity to both residential and industrial sectors to minimize energy loss. Smart Grids (SG) emerge as a promising solution to reduce power dissipation in distribution networks. The application of machine learning and artificial intelligence in SGs has significantly improved the precision of predicting consumer electricity needs. This paper presents a novel approach to improving the stability prediction of Internet of Things (IOT)-driven SGs using different advanced machine learning models. This study explores multiple advanced machine-learning techniques, including Gradient Boosting (GB), K-Nearest Neighbor (KNN), Support Vector Machine (SVM), Neural Networks, and the Decision Tree classifier, focusing on the stability prediction of SGs. This study explores the efficiency of hyperparameter-optimized GB models in predicting SG dynamic stability that encompasses the ability of the system to return to a stable operating point following a disturbance. Focusing on various models, it identifies the Dipper Throated Optimization Algorithm DTO+GB model as the standout, exhibiting unparalleled accuracy and reliability across critical performance metrics such as accuracy (99.32 %), sensitivity (99.16 %), and specificity (99.54 %). Diagnostic and regression analyses further emphasize its better predictive power and the need for hyperparameter optimization to improve the model. This paper highlights the capabilities of advanced machine learning algorithms in conjunction with tactical hyperparameter optimization in enhancing SG stability prediction, introducing a new baseline for future technological and methodological developments in this application.

Wastewater treatment plants circular performance models evaluation: Portugal case-study

Population growth, economic growth, and changes in societal habits have led to significant changes in resource consumption. Therefore, it's crucial to accelerate the “reduce, reuse, recycle, and recover” of resources to ensure the balance of ecosystems, and water is surely one of the most fundamental resources. The acceleration of this approach in the water cycle makes sense only if we combine a circular economy (CE) transition with a sustainable perspective. In this context, more rational usage of water resources (which are under pressure) and more sustainable wastewater practices are expected to be a way towards the CE in the water and wastewater sector. This study provides a description and evaluation of existing frameworks that can be used to measure and assess the level of circularity of the wastewater treatment plant (WWTP). The treatment of urban wastewater requires new concepts of management and operation for the adaptation of existing plants, which lack robustness and flexibility, to face these new challenges and requirements because we can no longer continue to look at the WWTP only as treatment units, but as wastewater resource recovery facilities. This transformation must be transposed according to a matrix that allows the assessment to describe the current situation, analyse the problem, identify vulnerabilities and opportunities, identify, and evaluate measures, and identify and evaluate strategies. Considering that decision-makers face profound uncertainties such as climate change, population growth, population needs, innovative technologies, economic developments, ecosystem preservation and the impacts of human and natural activities.

Surviving the Tide: Assessing Guiana dolphin persistence amidst growing threats in a protected estuary in South-eastern Brazil

This study investigated the population viability of Sotalia guianensis in the Cananéia Estuarine-Lagoon Complex, considering current and potential future scenarios. Simulations, using VORTEX software v. 10.5.5.0, spanned 100 years and were iterated 1000 times. Scenarios encompassed adjustments to demographic and environmental factors, evaluating population trajectories (baseline; increase fisheries; increase tourism; and increase harbour activity scenarios). Findings revealed a potential stochastic growth rate and population stabilization in baseline and increase tourism scenarios when major threats were absent. Conversely, increase fishing and harbour activity scenarios exhibited population decline, leading to eventual extinction within 100 years. Projected growth rates for all Scenarios were 0.0298 (SD=0.0424), −0.2650 (SD=0.2825), 0.0294 (SD=0.0654), and −0.0334 (SD=0.1145) respectively, with extinction probabilities of 0.0 for baseline and increase tourism scenarios, 1.0 for increase fishing scenario with mean estimated extinction time at 14 years, and 0.4430 for increase harbour activity scenario with mean estimated extinction time at 80.1 years. Sensitivity testing identified the percentage of adult females breeding and female mortality as the parameters most significantly impacting population trends. The simulations provided important insights into the primary factors impacting the viability of Sotalia guianensis and lay the groundwork for future population assessments and conservation plans.

Sustainability of collective irrigation under water competition between agriculture and civil uses: the case study of Alanya Water Users Association (Türkiye)

This study explores the patterns of sustainable use and management of competing water sectors in the Alanya Water Users Association (WUA) in Southern Türkiye, over eight years (2013-2020) before the SARS-CoV-19 pandemic, focusing on the impacts of the recorded huge growth of tourism. Performance indicators of collective irrigation services are used to identify performance patterns and trends over time. The analysis has revealed a notable increase in water consumption for agricultural activities (+30%), driven by the cultivation of tropical fruits, without a proportional rise in crop production. Concurrently, effective financial management is observed in the WUA, with a consistent reduction in unit Management, Operation and Maintenance costs (-40% to 70%). Additionally, the total water demand has surged (+100%) due to population growth and tourist flux. However, this increase has tensioned water delivery to crops, indicating higher pressures over water availability for all uses. The study has identified three distinct patterns in the technical, financial, and socio-economic performance of the WUA, particularly highlighting the last four years of increased water usage and the disruption caused by the SARS-CoV-19 pandemic in 2020. Despite the current adequacy of water resources, optimized strategies for water management are advocated to address anticipated demographic growth, the introduction of tropical crops and the environmental impacts of climate change.

Lower prognostic nutritional index is associated with a greater decline in long-term kidney function in general population.

The prognostic nutritional index (PNI) is an integrated index of serum albumin and peripheral lymphocyte count, where low values may reflect poor nutritional status or inflammation. The long-term effect of PNI on renal function is not well known in the general population. Therefore, we investigated whether the PNI is related to renal function changes in the general population. Data from participants who underwent a health check-up between 2002 and 2018 were retrospectively examined. PNI was computed by 10×serum albumin (g/dL) + 0.005×total lymphocyte count (per mm3). The primary exposure was PNI, divided into quintiles. The primary outcome was a 25% decline in eGFR from baseline over a 5-year follow-up period. This study included 15,437 participants (mean [standard deviation, SD] age, 43.7 [7.9] years; 46% male). The median (interquartile ranges) 5-year change of eGFR was - 5.2 (- 18.8, - 3.3) mL/min/1.73m2. A total of 2,272 participants (14.7%) experienced a 25% decline in eGFR at 5 years. Compared to the highest PNI group, lower PNI groups were at greater risk for a 25% decline in eGFR; odds ratios and 95% confidence intervals were 1.42 (1.20, 1.68), 1.23 (1.04, 1.45), 1.21 (1.03, 1.43), and 1.19 (1.01, 1.40) for the first to fourth quintiles of PNI, respectively. In linear regression analyses, lower PNI groups also showed a larger decline in eGFR over 5 years compared to the highest PNI group. Lower PNI was associated with a larger decline in renal function in the general population.

Population genetics analysis based on mitochondrial cytochrome c oxidase subunit I (CO1) gene sequences of Cottus koreanus in South Korea.

The freshwater sculpin Cottus koreanus is endemic to the Korean Peninsula and has a fluvial life history. However, its population has been greatly reduced and it is now listed as an endangered class II species. To obtain important information for its conservation, we examine the genetic diversity, population structure, and demographic history of C. koreanus through mitochondrial cytochrome c oxidase subunit I (CO1) gene sequence analysis. We analyzed the CO1 gene sequences of 430 individuals of C. koreanus from 23 populations in South Korea. In all, 32 haplotypes were defined by 124 variable nucleotide sites, of which 28 were unique haplotypes not shared with other regional populations. All sampled populations had high haplotype diversity (Hd = 0.941) and low nucleotide diversity (π = 0.0146). Median-joining network analysis identified two divergent clusters: cluster I that had unique haplotype patterns assigned to each population and cluster II that had a star-like pattern. Each was supported by pairwise FST values and hierarchical analysis of molecular variance. The results of the mismatch distribution, goodness-of-fit test, and extended Bayesian skyline plot analysis showed that cluster I has experienced a gradual population expansion since the last glacial maximum, while cluster II experienced a sudden one. The results of neutrality testing supported the results for cluster II but the signal was weak. C. koreanus inhabits the upper reaches of rivers and has extremely low dispersal ability, resulting in unique genetic structure patterns among populations. Therefore, all populations should be managed and conserved separately.

Genome editing in future crop protection: utilizing CRISPR/Cas9 to improve crop resistance against diseases, pests, and weeds

AbstractIncreasing population and climate change pose significant threats to global food security by imposing stresses on plants, making them more susceptible to diseases and productivity losses caused by pathogens, pests, and weeds. Traditional breeding strategies are insufficient for rapid development of new plant traits that can outpace this productivity downtrend. Modern advances in genome editing technologies, particularly CRISPR/Cas9, have revolutionised crop protection through precise and targeted genome modifications. This allows for the development of resilient crops with enhanced resistance against pathogens, pests, and weeds. This review explores various approaches with which CRISPR/Cas9 is applied for crop protection: knocking out of susceptibility genes, introduction of resistance genes, and modulation of defence genes. Potential applications of CRISPR/Cas9 in crop protection include the introduction of genes conferring resistance to pathogens, disruption of insect genes responsible for survival and reproduction and engineering of herbicide-resistant crops. In conclusion, CRISPR/Cas9 holds great promises in advancing crop protection and thus ensuring food security amidst environmental and population pressures. This review highlights the transformative potential of genome editing in crop protection and calls for continued research and development in this field.

Do penguins care about their neighborhood? Population implications of bioerosion in Magellanic penguin, Spheniscus magellanicus, at Martillo Island, Beagle Channel, Argentina.

Intrinsic and extrinsic factors, such as bioerosion at nesting sites, regulate population dynamics and are relevant for the long-term conservation of penguins. Colony trends (between 2004-2022) were studied in a Magellanic penguin colony on Martillo Island, Beagle Channel, Argentina and compared between zones with contrasting degrees of erosion (high, medium, low). Individuals from each zone were characterized for foraging ecology, stress, and reproductive performance during the 2017-2018 breeding season to better understand the colony dynamics. Changes in nest abundance varied in magnitude between nesting zones with different characteristics of occupation time, density and erosion. Declines in nest abundance in the densest, most eroded and longest occupied zone suggests that environmental degradation may be limiting the colony's carrying capacity. A higher percentage of late breeders (probably younger breeders) occupied the less eroded and more recently occupied zone. Foraging, breeding and stress barely differed between zones. New individuals recruiting into the breeding colony select less-eroded zones, either to reduce competition for nests or to avoid other effects of erosion and high-density areas. If this is the mechanism behind the shift in numbers throughout the island, we expect the island to be progressively occupied to the west. If competition or other density dependent factors are at play, a time will come when the vacant east side will begin to be recolonized by younger individuals. However, if erosion or other long-term effects spread throughout the island, recolonization may not occur and the colony may ultimately be abandoned as individuals search for new breeding grounds. Erosion at the breeding site may be a key factor in regional population trends of this burrow nesting species, by following an extinction / colonization of new sites process.

"You should smile more": Population-level sex differences insmiling also exist in autistic people.

Societal expectations for social-emotional behavior differ across sexes; however, diagnostic definitions of autism do not account for this when delineating "typical" versus "atypical." This study examines sex differences in autism in one behavior associated with strong gender biases: smiling. Computer vision was used to quantify smiling in 60 autistic (20 female) and 67 neurotypical (25 female) youth during conversations. Effects of sex and diagnosis were examined on degree of smiling, smile prototypicality, changes in smiling, and impact of smiling on interaction quality. Sex differences in smiling persisted across diagnosis groups: females smiled more than males, and their smiles were more prototypical. Autistic youth smiled less, and less prototypically, than neurotypical youth, with no sex by diagnosis interactions. In autism, the association between smile activity and interaction quality approached statistical significance, seemingly driven by autistic males but not females. Findings are consistent with population trends for females to smile more during social exchanges and "display rules" requiring more positive expressivity from females. Autism has historically been defined based on differences between autistic and neurotypical males. Failure to acknowledge sex-based differences in social-emotional behavior may leave some females appearing to have fewer autistic traits, increasing their risk of being under-identified and misunderstood.

Seasonal macro‐demography of North American bird populations revealed through participatory science

Avian population sizes fluctuate and change over vast spatial scales, but the mechanistic underpinnings remain poorly understood. A key question is whether spatial and annual variation in avian population dynamics is driven primarily by variation in breeding season recruitment or by variation in overwinter survival. We present a method using large‐scale volunteer‐collected data from project eBird to develop species‐specific indices of net population change as proxies for survival and recruitment, based on twice‐annual, rangewide snapshots of relative abundance in spring and fall. We demonstrate the use of these indices by examining spatially explicit annual variation in survival and recruitment in two well‐surveyed nonmigratory North American species, Carolina wren Thryothorus ludovicianus and northern cardinal Cardinalis cardinalis. We show that, while interannual variation in both survival and recruitment is slight for northern cardinal, eBird abundance data reveal strong and geographically coherent signals of interannual variation in the overwinter survival of Carolina wren. As predicted, variation in wintertime survival dominates overall interannual population fluctuations of wrens and is correlated with winter temperature and snowfall in the northeastern United States, but not the southern United States. This study demonstrates the potential of participatory science (also known as citizen science) datasets like eBird for inferring variation in demographic rates and introduces a new complementary approach towards illuminating the macrodemography of North American birds at comprehensive continental extents.

Formation of the spatial structure of the bird population in High-mountainous Dagestan and the concept of preserving its avifauna

The presented work is the concluding part of a previously published article (Vilkov 2023) and based on a mathematical analysis of the empirical material collected during route bird surveys in 1998–2021 in the High­mountainous Province of Dagestan. Based on the long­term average population density data for 96 birds nesting and likely nesting, a cluster analysis was carried out, during which the identified avifaunal communities were grouped according to the similarity of their abundance. Using correlation analysis, environmental factors were identified that determine the territorial variability of bird population abundance. Based on the estimates of the strengths of connections determined from the Jaccard­Naumov coefficients similarity data matrix, a graph was constructed that reflects the spatial structure of the bird population at the level of selected key areas. When interpreting the spatial structure of the bird population using cluster and correlation analysis data, as well as faunal and ecological ranking data, similarities between the compared avifaunal communities were revealed, and 4 main trends in bird population changes in factor space were identified. Based on the results of assessing the strength and generality of the relationships between structure­forming factors and the territorial variability of the bird population (taking into account the areas of landscapes), the most significant was the impact of afforestation, the area of open spaces and the area of residential landscapes. When interpreting spatial differences taking into account natural and anthropogenic changes, it is possible to create a predictive model of the transformation of avifaunal communities within the study area. Analysis of existing threats that have a negative impact on the number and species diversity of birds allowed developing a population management concept based on 4 strategic directions. 1. Gasification of High­Mountain Dagestan to prevent deforestation and restore the species diversity of forest birds. 2. To preserve the species diversity of meadow birds, redirect cattle grazing to areas of meadows with increased overgrowth of grassy vegetation. 3. Increase the area of fields for sowing grain crops to preserve the species diversity of granivorous birds. 4. To preserve the species diversity of birds of prey, install perches in a mosaic pattern in the fields of grain crops.

Species traits explaining long-term abundance changes of breeding birds in farmland areas in Álava (N Spain)

In recent decades, the populations of many common bird species have greatly declined in Europe, particularly in farmland habitats. However, this decline has not affected every species, and to understand the mechanisms behind this interspecific variability, its relationship with several species-specific traits has been studied repeatedly. We used this approach to analyse long-term changes in the abundance of breeding passerines in farmland areas in northern Spain. Abundance changes were quantified in 2015 and 2016 by repeating the same line transects conducted in 1988/89 in three agricultural habitats located along a steep Atlantic-Mediterranean gradient in the province of Álava. We found that total bird abundance did not decline, as most species not closely linked to farmland habitats showed positive population changes, while the number of increasing and decreasing farmland specialists was similar. Specific traits explained a substantial proportion of the variability in abundance change, as warm-dwelling species and those occupying habitats with a complex vegetation structure showed more positive changes than those preferring colder conditions and more open habitats. These patterns can be explained by climate warming and by the increase in hedge and forest cover in the study area. Although we did not find a long-term decline in the overall abundance of the studied bird community nor in that of farmland specialists, open habitat species associated with a cool climate should be the focus of particular concern.

Estimation of PfRh5-based vaccine efficacy in asymptomatic Plasmodium falciparum patients from high-endemic areas of Tanzania using genetic and antigenicity variation screening

BackgroundPlasmodium falciparum is the most lethal malaria parasite. Recent phase 1b vaccine trials using P. falciparum reticulocyte binding protein homolog 5 (PfRh5) demonstrated safety and promising efficacy in preventing merozoite invasion. PfRh5 has emerged as a strong vaccine candidate due to its essential role in merozoite invasion and limited sequence variation. For effective malaria vaccine development, especially in high-transmission settings, strain-transcending activity must be considered. Ongoing monitoring of antigenic variation and natural immune responses is important to estimate vaccine efficacy across geographically diverse populations.MethodsSamples for this study were collected from four villages in each of the Kigoma and Geita regions, known malaria transmission hotspots in Tanzania. This community-based cross-sectional study was conducted from December 2022 to July 2023. Genetic variation and natural selection pressure on pfrh5 were analyzed in 164 asymptomatic P. falciparum isolates. The humoral immune response to PfRh5 was also assessed using a protein microarray with 242 sera samples from asymptomatic patients in the same population. Finally, a correlation analysis was conducted to compare pfrh5 genetic variation with the humoral immune response.ResultsThe results revealed that pfrh5 was well conserved, but novel non-synonymous mutations were found at D65H, H170N, and I227M. Additionally, natural selection metrics indicated the potential for positive selection and a recent population expansion of PfRh5 in the study area, both of which could influence vaccine effectiveness. Antigenicity screening revealed variable sensitivity, ranging from 3.3% in Bunyambo to 82.8% in Rwantaba, with no significant relationship between antigenicity and parasitemia, haplotypes, or gender. However, age was significantly associated with humoral immune response (ρ = 0.170, p = 0.008).ConclusionsThese findings underscore the need for future PfRh5-based vaccines to consider for increasing genetic variation and geographical differences in humoral immune responses.

Abstract C024: MPLA+IFNg-activated tumor-associated macrophages alter fibroblast composition

Abstract In a previous study, we developed a strategy to reprogram tumor-associated macrophages (TAMs) and induce a collaborative innate-adaptive immune response by combining monophosphoryl lipid A (MPLA) with IFNγ. However, we also observed downregulation of extracellular matrix (ECM)-associated genes in MPLA+IFNγ-treated mammary tumors, indicating that the combination treatment impacts the tumor microenvironment beyond just the immune cells. In this study, we investigated how MPLA+IFNg treatment modulates the tumor ECM, with a particular focus on fibroblasts-the major ECM-producing cells. Using scRNA-seq to profile mammary carcinomas, we identified six macrophage populations (C1q+, Ccr2+, Spp1+, Lyz+, mt+ and ki67+ TAMs) and two fibroblast populations (Cd34+ and a-SMA+ fibroblasts) in MMTV-PyMT tumor. MPLA+IFNγ treatment increased the numbers and percentages of Lyz+ TAMs and Cd34+ fibroblasts, while the numbers and percentages of Spp1+ TAMs and α-SMA+ fibroblasts were decreased by the treatment. Thus, MPLA+IFNγ treatment induced significant changes in both macrophage and fibroblast populations. Further analysis revealed an unusual gene expression pattern in Lyz+ TAMs. Mgst1 and Gng12 expression was detected in Lyz+ TAMs at levels comparable to those in fibroblasts, despite these genes typically being expressed in fibroblasts but not in macrophages of normal human tissues. However, to our surprise, MPLA+IFNγ treatment did not significantly increase Mgst1 and Gng12 expression of mono-cultured TAMs or bone marrow-derived macrophages, suggesting that these genes were not directly upregulated by MPLA+IFNγ treatment. Instead, the Mgst1 and Gng12 transcripts may have originated from engulfed fibroblasts. In addition, following MPLA+IFNγ treatment, more iNOS+ macrophages (which we previously identified as tumoricidal macrophages) were found in very close proximity to α-SMA+ fibroblasts. To directly test whether MPLA+IFNg-treated TAMs kill and engulf fibroblasts, we performed ex vivo co-cultures of TAMs and fibroblasts. Following MPLA+IFNγ treatment, TAMs effectively killed and engulfed the fibroblasts, whereas minimal fibroblast engulfment was observed in the control co-cultures. Our data suggest that tumoricidal MPLA+IFNγ-treated TAMs can regulate the ECM of tumors by targeting and eliminating the major ECM-producing cells, the fibroblasts. Ongoing studies are determining the functional consequences of the TAM-mediated regulation of fibroblasts and ECM composition. Citation Format: Lijuan Sun, Bodu Liu, Yixin Zhao, Mikala Egeblad. MPLA+IFNg-activated tumor-associated macrophages alter fibroblast composition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C024.

Abstract C008: New insights from a novel mouse model of synovial sarcoma

Abstract Mouse models are the basis of preclinical and translational research in solid tumors. Multiple methods exist to induce tumor formation in mice, including genetically engineered mouse models, chemotoxic agents, injection of tumor cells, and xenograft approaches. Synovial sarcoma, a rare highly malignant soft-tissue tumor, poses a serious threat to patients due to its aggressive nature and associated high rates of mortality and morbidity. This disease's underlying cause and development remain poorly comprehended, and existing treatment approaches have yielded unsatisfactory outcomes. In the last two decades, numerous effective animal models of soft tissue sarcoma (STS) have been created, primarily utilizing genetically engineered mice and zebrafish, however long latency of tumor development for several months in these models creates a barrier for practical in-vivo experiments for drug testing or manipulating the cellular composition of the tumor microenvironment. In studying cancer immunotherapy, it is important to consider aspects of antitumor immune responses and to produce a model that mimics the complexity of the immune system We have generated a new mouse model of synovial sarcoma of exceptionally fast tumor development. Intramuscular delivery of Cre recombinase protein in mice which drives conditional knockdown in PTEN, stabilization of β-catenin, and formation of fusion oncogenes of SS18-SSX2 was sufficient to initiate high-grade synovial sarcomas with myofibroblastic differentiation in 3 weeks. As immunotherapy is increasingly applied to sarcomas, our mouse model will serve as a great tool for preclinical data. Flow cytometry-based analysis of peripheral blood shows significant changes in immune cell populations as early as five days after Tat-Cre injection and continues throughout the development of synovial sarcoma. These results suggest a significant systemic phenotypic alteration of circulating immune cells, which may impact other major organs in this genetic mouse model of synovial sarcoma. Single- cell RNA sequencing of the CD45+ leukocytes in the tumor microenvironment reveals subsets that may promote tumor progression. Our work promises to significantly enhance our understanding of the pathogenesis of this disease and establish a reliable preclinical platform for devising and assessing therapeutic interventions. Citation Format: Hesham Mohei, Donn Van Deren, Irene S. Molina, Malay Haldar. New insights from a novel mouse model of synovial sarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C008.