Search Results (2,382)

Background/Objectives: Segmental duplications (SDs) are major drivers of genome evolution and structural variation in primates, particularly within acrocentric chromosomes, where rDNA arrays and duplicated sequences are densely clustered. However, the evolutionary dynamics of rDNA-linked SDs across great ape lineages have remained poorly characterized due to longstanding technical limitations in genome assembly. Here, we investigate the organization, copy number variation, and evolutionary conservation of acrocentric SDs in great apes by integrating fluorescence in situ hybridization (FISH) with comparative analyses of telomere-to-telomere (T2T) genome assemblies. Methods: Using eight human-derived fosmid probes targeting SD-enriched regions flanking rDNA arrays, we analyzed multiple individuals from chimpanzee, bonobo, gorilla, and both Bornean and Sumatran orangutans. Results: Our FISH analyses revealed extensive lineage-specific variation in SD copy number and chromosomal distribution, with pronounced heteromorphism in African great apes, particularly gorillas, and more conserved patterns in orangutans. Several SDs showed fixed duplications across species, while others exhibited high levels of polymorphism and individual-specific organization. Conclusions: Comparison with T2T assemblies confirmed consistent genomic localization for a subset of probes, whereas others displayed partial discordance, highlighting the persistent challenges in resolving highly repetitive and structurally dynamic regions even with state-of-the-art assemblies. Genome-wide analyses further revealed species-specific enrichment of SDs on rDNA-bearing chromosomes, with chimpanzees and bonobos showing higher proportions than gorillas, and contrasting patterns between the two orangutan species. Overall, our results demonstrate that rDNA-linked SDs represent highly dynamic genomic compartments that have undergone differential expansion and remodeling during great ape evolution. These regions contribute substantially to inter- and intra-species structural variation and provide a mechanistic substrate for lineage-specific genome evolution, underscoring the importance of integrating cytogenetic and T2T-based approaches to fully capture the complexity of duplicated genomic landscapes. Full article

The management of non-small cell lung cancer (NSCLC), including lung adenocarcinomas (LUAD), has been revolutionized with the advent of precision oncology. While advanced cancers often carry poor prognosis, those harboring specific molecular alterations sensitive to targeted therapy (notably tyrosine kinase inhibitor [TKI]) have experienced improved response to treatment and survival outcomes. Consequently, detecting these alterations through molecular screening panel has become standard in several countries, although this necessitates high-quality tissue sampling to inform optimal therapeutic decisions. Oncologic imaging occupies a pivotal role in the routine care of patients, in particular at diagnosis, with a wealth of information gathered but underutilized, as medical imaging reflects the disease in its entirety at a given time point. Moreover, recent advancements in imaging quantitative analysis, including radiomics and artificial intelligence, could aid in better integration and understanding of this information that has been overlooked for years. Several radiological phenotypes (or radiophenotypes) have been linked to tumor genomic alterations, both in standard radiology relying on semantic features and metastatic patterns, and in radiomics. Ultimately, understanding the relationships between imaging and targetable genomic alterations via accurate imaging biomarkers could complement ambiguous tumor or liquid biopsy, detect emerging new alterations, and even substitute biopsy through ‘virtual biopsy’. During the past decade, there has been a surge in research focused on radiogenomic assessment of NSCLC and especially LUAD. However, due to the low prevalence of many oncogenic drivers, the scientific literature may lack clarity or present conflicting findings. This comprehensive review aims to provide a summary of the current state of this research, offering insights into the complex interplay between imaging and genomic alterations in lung adenocarcinoma. Full article

As the “brain” of the information industry and modern manufacturing, chips have emerged as a focal point in global competition over critical technologies. Based on global chip trade data from 2010 to 2023, this study employs social network analysis to investigate the structural evolution of the chip trade network and applies the quadratic assignment procedure (QAP) to examine the driving mechanisms of network reconstruction. The findings are as follows: First, the global chip trade network exhibits a loosely connected core-periphery structure, characterized by clustering and polarization, with a pronounced short-term deglobalization trend. Second, China, the United States, Germany, France, South Korea, and Singapore have long dominated central positions in competitive dynamics, while developing economies such as Mexico, Malaysia, and the Philippines have significantly risen in prominence in recent years. Third, the network takes on a core–subcore–periphery configuration with clearly delineated trade communities, reflecting a community-based, multi-centric, and hierarchical pattern. Fourth, political relations serve as a key driver of network restructuring, with their promotional effect on chip trade being negatively moderated by technological distance yet positively moderated by economic-complexity distance. Full article

High Mobility Group ^{Box 1} (HMGB1) and S100 proteins are major ligands of Receptor for Advanced Glycation End-products (RAGE) and have causal roles in endometriosis lesions. Yet the AGE–RAGE pathway that unifies Advanced Glycation End-products (AGEs) with these ligands has not been assessed in endometriosis. In diabetes, atherosclerosis, and chronic kidney disease, AGE–RAGE links insulin resistance and oxidative stress to inflammation, fibrosis, and organ harm. Endometriosis shares key drivers of AGE accumulation, including insulin resistance, oxidative stress, and chronic inflammation. Endometriosis is also linked to higher vascular risk and arterial stiffness. We asked whether AGE–RAGE could bridge metabolic stress to pelvic lesions and systemic risk. We did a focused review of mechanisms and an evidence map of studies on AGEs, RAGE, or known RAGE ligands in endometriosis. We grouped findings as most consistent with a driver, amplifier, consequence, or parallel role. We included 29 studies across human samples, cell systems, and animal models. Few studies measured AGE adducts directly. Most work tracked RAGE ligands (mainly HMGB1 and S100 proteins) and downstream immune and angiogenic programs. Across models, this pattern fits best with a self-reinforcing loop after lesions form. RAGE expression often aligned with lesion remodeling, especially fibrosis. Blood and skin readouts of AGE burden were mixed and varied by cohort and sample type. A central gap is receptor proof. Many models point to shared Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signaling, but few test RAGE dependence. Overall, current evidence supports AGE–RAGE as a disease-amplifying loop involved in chronic inflammation and fibrosis rather than an initiating trigger. Its effects likely vary by stage and site. Priorities now include direct lesion AGE measurement, paired systemic–pelvic sampling over time, receptor-level studies, and trials testing diet or drug interventions against clear endpoints. Outcomes could include fibrosis, angiogenesis, immune state, pain, and oocyte and follicle function. Full article

Grassland productivity faces heightened uncertainty under nonlinear climatic forcing. This study characterizes the spatial heterogeneity of nonlinear variations and nonstationary climate sensitivities across the Eurasian Steppe Region (EASR) to provide a scientific basis for its adaptive management. Using the aboveground net primary productivity (ANPP) and climate datasets (1982–2015), we employed piecewise linear regression, LOWESS, and sliding window partial correlation analysis to identify temporal turning points and dynamic climate–productivity relationships. We identified distinct turning points in 1994 and 2008, revealing a phased “Increasing–Decreasing–Increasing” trajectory. A key novelty is the mapping of eight phased trajectory patterns, illustrating significant spatial heterogeneity in productivity trends. Furthermore, we demonstrate temporally reversed climate sensitivities. Notably, the sensitivity of ANPP to temperature shifted from positive to negative as warming-induced water stress intensified. While precipitation remains the dominant driver (68% of the region), its influence is nonstationary and state-dependent. In the Qinghai–Tibet Plateau, the limiting factor transitioned from thermal to water availability. Overall, productivity in the EASR appears to undergo phased reorganization under shifting climatic baselines. Our findings suggest that future ecosystem models should incorporate time-varying sensitivity parameters to account for nonlinear dynamics and potential trend reversals in grassland ecosystems. Full article

Forests face significant pressures from human activities, mainly through deforestation and land-use changes driven by agricultural expansion. This study aims to conduct a literature review to identify and analyze the primary factors that have driven farmers to engage in deforestation and agricultural expansion over the past 25 years. The review followed the methodology proposed by Arksey and O’Malley, with an initial broad search followed by article selection and exclusion. The analysis of the results revealed interacting factors with varying intensities by region, extending to different levels. At the demographic level, factors such as gender, age, household composition, and education play a significant role. At the social level, factors are mainly related to migration, population growth, and the phenomenon of “imitation”. At the economic level, poverty, unemployment, the need for supplementary income, and the growing demand for cash crops are key drivers of agricultural expansion in forests. At the political level, state licensing of deforestation, either as part of poverty reduction strategies or to meet market demand, and the inability to impose sanctions, reinforce deforestation for agricultural cultivation. Finally, at the environmental level, factors such as climate change and soil fertility decline constitute another critical area of pressure on forest ecosystems. Full article

Investigating how climatic and hydrological conditions in ecological resource-enriched zones of marginal seas respond to external forcing, particularly during past greenhouse climates, holds considerable significance for understanding current environmental and resource challenges driven by global warming. In marginal seas, climatic hydrological states, including salinity, redox conditions, and productivity, are key environmental parameters controlling organic matter production, preservation, and ultimately the formation of high-quality shale. Herein, high-resolution cyclostratigraphic and multi-proxy geochemical analyses were conducted on a continuous core from the upper part of Member 4 of the Eocene Shahejie Formation (Es4cu) in Well NY1, Dongying Sag, Bohai Bay Basin. Based on these data, a refined astronomical timescale was accordingly established for the studied interval. By integrating sedimentological observations with multiple proxy indicators, including elemental geochemistry (e.g., Sr/Ba and Ca/Al ratios), organic geochemistry, and mineralogical data, the evolution of climate and paleo-water mass conditions during the study period was reconstructed. Spectral analyses revealed prominent astronomical periodicities in paleosalinity, productivity, and redox proxies, indicating that sedimentation was modulated by cyclic changes in eccentricity, obliquity, and precession. It was hereby proposed that orbital forcing governed periodic shifts in basin hydrology by regulating the intensity and seasonality of the East Asian monsoon. Intervals of enhanced summer monsoon associated with high eccentricity and obliquity were typically accompanied by increased sediment supply and intensified chemical weathering. Increased precipitation and runoff raised the lake level while promoting stronger connectivity with the ocean. In contrast, during weak seasonal monsoon intervals linked to eccentricity minima, basin conditions shifted from humid to arid, characterized by reduced precipitation, lower lake level, decreased sediment supply, and a concomitant decline in proxies for water salinity. The present results demonstrated orbital forcing as a primary external driver of cyclical changes in conditions favorable for resource formation in the Eocene lacustrine strata of the Bohai Bay Basin. Overall, this study yields critical paleoclimate evidence and a mechanistic framework for predicting the spatial-temporal distribution of high-quality shale under comparable astronomical-climate boundary conditions. Full article

Ecosystem vulnerability assessment is paramount for local environmental stability and lasting economic progress. This study selects Hubei Province as the research area, applying multi-source spatiotemporal datasets spanning the period 2000–2023. A pressure–state–response (PSR) framework, incorporating 14 distinct indicators, was developed. The selection criteria for these indicators adhered to principles of scientific rigor, all-encompassing scope, statistical representativeness, and practical applicability. The chosen indicators effectively encompass natural, anthropogenic, and socio-economic drivers, aligning with the specific ecological attributes and key vulnerability factors pertinent to Hubei Province. The analytic network process (ANP) method and entropy weighting (EW) method were integrated to ascertain comprehensive weights, thereby computing the ecological vulnerability index (EVI). In the meantime, we analyzed temporal and spatial EVI shifts. Spatial autocorrelation analysis, the geodetic detector, the Theil–Sen median, the Mann–Kendall trend test, and the Grey–Markov model were employed to elucidate spatial distribution, driving factors, and future trends. Results indicate that Hubei Province exhibited mild ecological vulnerability from 2000 to 2023, but with a notable deteriorating trend: extreme vulnerability areas expanded from 0.34% to 0.94%, while moderate and severe vulnerability zones also increased. Eastern regions demonstrate elevated vulnerability, but they were lower in the west, correlating with human activity intensity. The global Moran’s I index ranged from 0.8579 to 0.8725, signifying a significant positive spatial correlation of ecological vulnerability, with the highly vulnerable areas concentrated in regions with intense human activities, while the less vulnerable areas are located in ecologically intact areas. Habitat quality index and carbon sinks emerged as key drivers, possibly stemming from the forest–wetland composite ecosystem’s high dependence on water conservation, biodiversity maintenance, and carbon storage functions. Future projections based on Grey–Markov models indicate that ecological fragility in Hubei Province will exhibit an upward trend, with ecological conservation pressures continuing to intensify. This research offers a preliminary reference basis of grounds for ecological zoning, as well as sustainable regional development in Hubei Province, while also providing a theoretical and practical framework for constructing an ecological security pattern within the Yangtze River Economic Belt (YREB) and facilitating ecological governance in analogous river basins globally, thereby contributing to regional sustainable development goals. Full article

Global climate change is intensifying extreme weather events such as floods and heatwaves, posing serious threats to lake ecosystems. The Huayanghe Lakes experienced a catastrophic flood in 2020 and a prolonged heatwave in 2022, providing an opportunity to compare zooplankton responses to contrasting extreme climate events. Based on summer water quality and zooplankton data collected from the Huayanghe Lakes during 2020–2023, this study used 2021 and 2023 as reference years to examine the summer zooplankton community state during the post-event period following extreme climate events. In 2020, 43 species belonging to 14 families and 25 genera were recorded, dominated by rotifers such as Polyarthra euryptera and Trichocerca spp., with a mean density of 239.26 ind./L. In contrast, 34 species from 12 families and 21 genera were identified in 2022, with dominant taxa including Diurella rousseoeti, Trichocerca cylindrica and Thermocyclops hyalinus, resulting in a lower mean density of 149.17 ind./L. Zooplankton density and species richness were higher during flood conditions but declined under prolonged heatwave conditions. Mantel correlation analysis identified water transparency as the primary environmental factor shaping zooplankton communities. Overall, zooplankton responded more strongly to flooding than to sustained heatwaves, indicating that different extreme climate events amplify the regulatory roles of distinct environmental drivers. Full article

Artificial Intelligence (AI) is increasingly shaping materials research, particularly in the development and optimization of Glass Fibre Reinforced Polymer (GFRP) bars used as innovative alternatives to steel reinforcement. Despite this growing intersection, no prior bibliometric study has systematically mapped how AI contributes to the advancement of GFRP technologies. This paper fills this gap through a comprehensive bibliometric analysis based on 102 Scopus-indexed publications from 2015 to 2025. Following PRISMA guidelines, the study combines performance analysis and science mapping using VOSviewer to identify publication dynamics, leading journals, key contributors, and thematic clusters. The results reveal a tenfold growth in annual output (compound annual growth rate, CAGR = 10.1%) and five dominant research directions: (1) machine learning in structural analysis, (2) AI-driven composite materials modeling, (3) smart damage detection, (4) mechanical characterization, and (5) advanced deep learning frameworks. China, India, and the United States collectively account for more than half of global publications, highlighting strong international collaboration. The findings demonstrate that AI has evolved from an exploratory tool to a transformative driver of innovation in GFRP research. This study provides the first quantitative overview of this emerging field, identifies critical gaps such as sustainability integration and standardization, and proposes future directions to foster cross-disciplinary collaboration toward intelligent and sustainable composite structures. Full article

Background: Hepatocellular carcinoma (HCC) is characterized by marked intratumoral heterogeneity and poor clinical outcomes. Dysregulated ribosome biogenesis has emerged as a fundamental hallmark of tumor initiation and progression; however, the specific molecular drivers linking this machinery to HCC pathogenesis remain largely undefined. Methods: By integrating multi-omics data from the TCGA and ICGC cohorts, FBLL1 was identified as a key prognostic candidate gene. Its cellular and spatial distribution was analyzed using single-cell RNA sequencing and spatial transcriptomics. Its biological functions in vitro and in vivo were validated through functional experiments, including lentivirus-mediated ectopic expression and siRNA-mediated gene knockdown. Finally, its molecular mechanism was elucidated through transcriptomic analysis and Western blotting. Results: FBLL1 was significantly upregulated in HCC and correlated with poor patient survival. Spatial and single-cell analyses showed that FBLL1 expression was preferentially enriched in malignant hepatocytes within the tumor region. Functionally, knockdown FBLL1 could inhibit the proliferation and clonogenic capacity of HCC cells, while overexpression FBLL1 in non-tumorigenic hepatocytes could promote the tumorigenic phenotype in xenograft models. Transcriptomic analysis indicated that FBLL1 overexpression was associated with the synergistic upregulation of c-Myc and multiple EGFR ligands, as well as decreased expression of hepatocyte functional markers. Consistently, modulation of FBLL1 expression affected the activity of the EGFR–MAPK signaling pathway. Conclusions: Our study identifies FBLL1 as a previously unrecognized regulator associated with malignant state transition in HCC. Rather than acting as a direct regulator of core signaling components, FBLL1 is associated with ligand-dependent activation of the EGFR–MAPK pathway in conjunction with c-Myc upregulation. These findings indicate that FBLL1 represents a promising therapeutic target for disrupting oncogenic signaling programs in liver cancer. Full article

Zinc homeostasis is fundamental to metabolic health, orchestrated by the coordinated actions of two major zinc transporter families: ZIP (Zrt- and Irt-like proteins) and ZnT (zinc transporters). ZIP transporters facilitate zinc influx into the cytosol from the extracellular space or from the lumen of intracellular organelles, whereas ZnT transporters control zinc efflux from the cytosol to the extracellular space or facilitate its sequestration into intracellular vesicles and organelles, concurrently harboring the meticulous intracellular zinc homeostasis. This equilibrium is essential for all critical functions like cellular response, metabolic control, and immune pathway alteration. Disruption of this homeostasis is a driver of different pathological alterations like metabolic inflammation, a chronic low-grade inflammatory state underlying obesity; type 2 diabetes; and nonalcoholic fatty liver disease. Recent studies revealed that ZIP and ZnT transporters dynamically regulate metabolic and inflammatory cues, with their tissue-specific expression varying by tissue and acclimating to different physiological and pathological conditions. Recent advanced research in molecular and genetic understanding has helped to deepen our knowledge of the interplay of activity between ZIP and ZnT transporters and their crosstalk in metabolic tissues, underscoring the potential therapeutic prospect for restoring zinc balance and ameliorating metabolic inflammation. This review provides a comprehensive overview that covers the function, regulation, and interactive crosstalk of ZIP and ZnT zinc transporters in metabolic tissues and their pathological conditions. Full article

Bone conduction hearing implant systems (BCHIs) are established treatments for patients with conductive or mixed hearing loss or single-sided deafness when conventional hearing aids are unsuitable. This study evaluated the cost-effectiveness of the active transcutaneous system Sentio versus a similar system, i.e., Osia in an Australian setting. Scenario analyses also compared Sentio to other systems, i.e., Ponto and Baha Attract. A Markov cohort model was adapted from a previously published source to reflect Australian practice, incorporating device acquisition, surgery, maintenance, battery replacement and adverse event management over a 15-year horizon from a healthcare perspective. Effectiveness inputs were derived from published evidence using a naïve indirect comparison. Extensive sensitivity analyses and external validation tested robustness. In the base case, Sentio was associated with lower costs and a small modelled incremental quality-adjusted life years (QALYs) gain versus Osia. Scenario analyses confirmed cost-effectiveness relative to Ponto and Baha Attract, with outcomes below the Australian willingness-to-pay threshold. Health state utility, device price and reimplantation assumptions were the most influential drivers, yet Sentio remained cost-effective in over 95% of simulations. These findings support Sentio as a clinically and economically efficient BCHI in Australia and highlight the need for direct utility and long-term durability data. Full article

Food insecurity is not merely an outcome of individual deprivation but a place-based expression of how urban food systems operate within unequal socio-spatial contexts. Using the Drivers–Pressures–State–Impacts–Responses (DPSIR) framework as a policy-relevant analytical lens, this study examines the Metropolitan Region of Rome to show how structural inequalities and uneven food infrastructures shape exposure to food-related risks. The results show that vulnerability is amplified by food price inflation, the rising cost of a healthy diet, and spatial gaps in retail provision—captured through the combined presence of food deserts and food blackouts—disproportionately affecting peripheral municipalities. State indicators, including the Food Insecurity Experience Scale (FIES), the Food Affordability Index (FAI), and the spatial distribution of FEAD beneficiaries, reveal a markedly uneven geography of food poverty, mirroring a higher prevalence of overweight, obesity, and diabetes. These spatial configurations point to obesogenic environments in which constrained affordability and limited accessibility restrict the capacity to maintain healthy diets, generating hidden social and health costs that disproportionately burden peripheral areas. Overall, food insecurity in Rome follows a pronounced centre–periphery gradient rooted in structural and institutional arrangements rather than incidental variation. Addressing this condition requires place-based, justice-oriented interventions that strengthen food infrastructures, improve coordination across governance scales, and place food security at the core of an integrated metropolitan Food Policy. Full article

This article examines the persistence of structural racism and the process of ethno-stratification affecting immigrants from the Global South in Spain. Drawing on national survey data and recent research, it analyses the socio-economic incorporation of immigrants in the aftermath of the Great Recession and subsequent economic recovery, emphasising both their rootedness in Spanish society and their continued segregation. The findings indicate that immigrants remain disproportionately concentrated in low-wage and temporary employment, positioned beneath the native-born precariat and distant from average living standards. This persistent segmentation cannot be explained solely by immigrants’ qualifications or cultural adaptation, but rather by an interplay of structural, institutional, social, and ethnic factors. At the core lies the Spanish “Mediterranean” development model, characterised by a low-productivity economy dependent on cheap labour, a limited welfare state, and strong family-based social protection, which together generate continuous demand for flexible immigrant workers. Additional drivers include migration and labour policies, gendered labour segmentation, and ethnic discrimination, all reinforcing immigrants’ vulnerability. The article concludes that immigrant labour has become essential to Spain’s economic and demographic model, yet its enduring segregation underscores the need for renewed public policies that promote social cohesion and intercultural integration. Full article