Search Results (783)

While chimeric antigen receptor (CAR)-T-cell therapies have shown significant effectiveness in hematological malignancies, their efficacy in solid tumors remains limited by the hostile tumor microenvironment (TME) and antigen heterogeneity. Recently, CAR-Macrophage (CAR-M) therapy has emerged as a paradigm-shifting approach, leveraging the innate capability of macrophages to deeply infiltrate tumors and their plasticity to reverse immunosuppression. Unlike T cells, CAR-Ms not only mediate direct phagocytosis but also initiate epitope spreading, effectively bridging innate and adaptive immunity. This review critically examines the trajectory of CAR-M therapy from biological rationale to clinical reality. We dissect the engineering evolution of CAR constructs, arguing for macrophage-specific signaling domains (e.g., FcRγ, Megf10) over traditional T-cell designs. Crucially, we address the major bottlenecks in clinical translation, including the manufacturing challenges of non-expanding primary macrophages and the emerging shift toward induced pluripotent stem cell (iPSC)-derived platforms. Furthermore, we evaluate current clinical trial landscapes and discuss next-generation strategies such as in vivo programming via lipid nanoparticles (LNPs) and synthetic logic-gating to enhance safety. Ultimately, overcoming manufacturing constraints and optimizing delivery systems will be pivotal for CAR-M to evolve from a niche therapy into a standard-of-care modality for solid tumors. Full article

Background: The upper gastrointestinal (GI) tract is a complex environment characterized by sharp physicochemical gradients. While the oral microbiome is a major source of microbial seeding for downstream organs, it remains unclear how these communities correlate and diverge across different anatomical sites. This study provides a high-resolution re-analysis of a comprehensive multi-site dataset to delineate the microbial architecture and ecological signatures along the oral–upper GI axis. Method: Human oral, esophageal, gastric mucosal, and gastric juice microbiome sequencing data were retrieved from the publicly available National Center for Biotechnology Information (NCBI) BioProject PRJNA1049979 database. Using these publicly available 16S rRNA sequencing data, we performed an integrated ecological analysis. Microbial diversity, taxonomic composition, and niche-specific community structures were evaluated using Quantitative Insights Into Microbial Ecology 2 (QIIME2) and R-based tools, including linear discriminant analysis effect size (LEfSe) and phylogenetic mapping. Results: The esophageal microbiome showed significantly greater richness and evenness than the oral cavity and stomach. Beta diversity analysis demonstrated clear compositional separation between oral and downstream upper GI communities, whereas gastric samples, particularly gastric juice, showed greater heterogeneity. Although major phyla were shared across sites, their relative abundances differed markedly. Oral samples were enriched with periodontal-associated taxa, including Porphyromonas, Prevotella, Alloprevotella, and Fusobacterium. In contrast, gastric mucosal samples were enriched with Akkermansia muciniphila and Helicobacter pylori, whereas gastric juice was characterized by Sarcina ventriculi, Fusobacterium periodonticum, and Clostridium perfringens. These findings indicate both taxonomic continuity and pronounced site-specific ecological divergence along the oral–upper GI axis. Conclusion: The oral cavity, esophagus, stomach, and gastric juice share a common microbial framework but exhibit distinct community restructuring driven by local environmental selection. This study provides a detailed ecological view of the oral–upper GI microbiome and highlights the importance of site-specific microbial organization in upper GI health and disease. Full article

Neonatal hyperoxia induces oxidative stress that disrupts neurodevelopmental processes. While dexmedetomidine (DEX) exhibits acute neuroprotective properties, its long-term impact on developmental trajectories during recovery remains incompletely understood. This study examined whether a single neonatal dose of DEX modulates hippocampal neurogenesis following hyperoxia across defined postnatal stages. Six-day-old Wistar rats were exposed to 80% oxygen for 24 h and evaluated at postnatal days (P) 9, 11, and 14 after recovery in room air. Mechanistically, hyperoxia permanently triggered apoptotic cascades, evidenced by sustained transcript upregulation and increased histological apoptosis and cell loss across the cortex and hippocampus, while disrupting the hippocampal progenitor niche, suppressing key differentiation factors (Sox2, Tbr2, Prox1, Calb1) and altering mature NeuN expression. Likewise, markers for autophagy (Atg5/12, Beclin1), neurotrophins (BDNF, NGF, NT3), and plasticity markers (Nrp1, Sem3a) showed reduced expression. Proactive treatment with DEX (5 µg/kg) significantly reversed these detrimental patterns. First, DEX elicited a robust antioxidant response (Nrf2, SOD1, SOD3 induction). Second, DEX effectively suppressed hyperoxia-induced programmed cell death and tissue degeneration up to P14. Crucially, this dual protection sustained the neurogenic niche, safeguarding autophagy processes as well as neurotrophic and neuronal plasticity mediators, while showing excellent safety under normoxia. In conclusion, a single dose of DEX mitigates acute oxygen injury and exhibits beneficial, stage-specific effects within hippocampal neurogenic niches during the postnatal phase, highlighting its potential to preserve neurodevelopmental trajectories. Full article

We assessed the current and possible future predicted distributions of the Mexican narrow-mouthed toad, Amphibia, Microhylidae Hypopachus variolosus (Cope, 1866) across its range to evaluate vulnerability under global change. (2) Methods: We integrated 481 validated occurrence records across the species’ distribution range, including 120 records from Mexico, with bioclimatic and land-cover predictors to build ensemble ecological niche models. We additionally incorporated human footprint metrics to evaluate anthropogenic pressure and projected future habitat suitability under climate and land-use change scenarios. (3) Results: Models showed high performance (TSS > 0.80; AUC > 0.90), identifying temperature and precipitation extremes as main drivers. Suitable habitats extended across both coasts and revealed novel areas in central Mexico. The most suitable habitat occurred under low human pressure, although localized impacts were detected. Deforestation in the Yucatán Peninsula reduced tree cover despite high climatic suitability. Future projections for 2050 under RCP 8.5 indicated marked reductions in modeled high-suitability areas, particularly in central Mexico. (4) Conclusions: These findings indicate high vulnerability to climate and land-use change and support updating distribution limits, incorporating new regions into conservation planning, and reassessing threat status to promote long-term persistence. Full article

Direct-seeded industrial tomato (Solanum lycopersicum L.) systems are highly vulnerable to early-season interference, yet the role of seed vigor as a competitive determinant remains under-quantified. This study evaluated the performance of high-vigor (HV; 91% germination) and accelerated-aged low-vigor (LV; 60% germination) tomato seeds against two weeds: green foxtail (Setaria viridis) and jimsonweed (Datura stramonium). While mean emergence timing was statistically comparable between HV and LV cohorts (6.0 vs. 7.2 days), LV seedlings entered the post-emergence phase with a numerical deficit in initial seedling dry weight (7.1 mg vs. 8.5 mg for HV; difference not statistically significant), suggesting a potential early competitive disadvantage. In replacement series experiments, HV tomatoes maintained stable leaf and root biomass within the 0.76–1.24 relative yield (RY) confidence interval when competing with jimsonweed. In contrast, LV plants were significantly suppressed at low weed proportions (25%), where root RY dipped below the 0.76 threshold. Against the aggressive below-ground strategy of S. viridis (which produced ~1200 mg of root mass by 40 DAE), LV tomato root RY collapsed to 0.10–0.15, whereas HV plants maintained significantly higher niche occupancy. Physical separation of above- and below-ground competition confirmed that HV seeds provide a “physiological buffer”; specifically, in below-ground treatments, HV plants achieved a root mass of 0.25 g/plant compared to only 0.15 g/plant for LV plants. These results identify seed vigor as a primary driver of the “priority effect” and suggest that high-vigor lots are essential for Integrated Weed Management (IWM) strategies to mitigate early-season resource pre-emption. These findings suggest that seed vigor assessment should be integrated into seed quality standards for direct-seeded tomato systems as a component of Integrated Weed Management. Future field-based studies are needed to validate these greenhouse findings under variable agronomic conditions. Full article

Umbrella species can facilitate efficient biodiversity conservation, as their targeted protection effectively safeguards co-occurring species and entire ecosystems in conservation management. To verify Hainan gibbon (Nomascus hainanus) as an umbrella species for sympatric endangered species, this study evaluated the conservation efficacy of the Hainan four-eyed turtle (Sacalia insulensis) through multidimensional spatiotemporal analysis. By comparing the population data collected using cage-trapping methods from 2005 to 2025, the S. insulensis population in the Bawangling region of the Hainan Tropical Rainforest National Park has exhibited obvious recovery, from no initial records to 25 individuals (mean relative population density: 0.0404 individuals/cage-day). Its growth trajectory is closely linked to the continuous enhancement of conservation efforts for Hainan gibbons, confirming umbrella effects stemming from poaching suppression and habitat restoration. However, when compared with recent surveys in other park regions, significant spatial limitations were revealed that the mean relative population densities at Yinggeling (0.01 individuals/cage-day) and Diaoluoshan (0.0064 individuals/cage-day) were only 25.74% and 15.84%, respectively. Additionally, juveniles constituted only 12% of Bawangling’s population, indicating that while the umbrella strategy delivers meaningful conservation outcomes, supplementary targeted initiatives are still needed to improve efficiency in resolving the species reproductive bottlenecks (e.g., nesting habitat quality). Those findings demonstrate that umbrella species conservation can establish an ecological conservation force field; however, its effectiveness is constrained by unequal resource allocation and species niche differences. Future efforts should overcome the spatial and ecological limitations of single-species umbrella effects by using smart patrol networks, secondary umbrella species mechanisms, and dedicated management plans. Full article

Melanoma is the most aggressive type of skin cancer, driven by early invasion, phenotypic plasticity, and frequent resistance to targeted therapies. Although genomic profiling informs treatment selection, genotype alone often fails to predict therapeutic response, underscoring the need for rapid and physiologically relevant functional testing platforms. Here, we present a three-dimensional melanoma–skin organoid (mSO) model that integrates primary skin cells with melanoma cell lines in a self-assembling, high-throughput format. The spherical mSOs recapitulate native human skin architecture, including a stratified epidermis and a dermal–hypodermal core, while supporting melanoma growth within an appropriate tissue microenvironment. In this niche, melanoma cells display epidermal spreading in radial growth-like patterns, outward invasion, and transcriptional shifts toward a pro-invasive phenotype. Using live confocal imaging coupled with a custom automated image analysis pipeline, we quantitatively measured tumor growth, migration beyond the organoid boundary, and interactions between melanoma cells and normal melanocytes. The mSOs also captured genotype-specific drug responses: BRAF-mutant melanoma cells were sensitive to BRAF and MEK inhibition, whereas NRAS-mutant, BRAF–wild-type cells were resistant to BRAF inhibition but remained responsive to MEK inhibition. Altogether, our mSO platform combines architectural and functional complexity with experimental scalability, providing a robust framework for modeling melanoma progression and evaluating targeted therapeutic responses within a relevant skin microenvironment. In the future, adaptation of this system to include patient-derived tumor cells could support personalized therapeutic decision-making in melanoma. Full article

Hyporheic zone exchange processes are strongly influenced by channel morphology, producing heat transfer patterns with distinct vertical stratification. To evaluate the effects of different channel geomorphic units on hyporheic temperature dynamics, monitoring sites were established along a segment of the Xiajiasi River (Hubei Province, China) encompassing four representative channel types: a meandering reach, a pool–riffle reach, a weir reach, and a straight reach. Hyporheic temperatures were recorded at multiple depths (0, 0.1, 0.2, and 0.3 m) during both summer and winter. The results indicate that channel morphology strongly controls the spatiotemporal distribution of hyporheic temperatures. Across all channel types, sediment temperatures exhibited depth-dependent amplitude attenuation and phase lag, with mean temperatures decreasing with depth in summer and increasing with depth in winter. The meandering reach exhibited the highest summer temperatures (28.3–30.6 °C), whereas the pool–riffle reach displayed the steepest thermal gradients (deep sediment temperatures as low as 25.6 °C). In contrast, the straight reach exhibited the weakest thermal buffering capacity. The presence of the weir markedly modified downstream thermal conditions, reducing sediment temperatures by approximately 1.6–3.2 °C during summer, whereas overall winter observations demonstrated a pronounced thermal inversion with deep sediment temperatures increasing by 1.2–2.9 °C. These findings demonstrate that distinct geomorphic units create diverse thermal niches; river managers can incorporate diverse geomorphic features into river restoration designs to create localized thermal refugia, thereby protecting temperature-sensitive aquatic species. Full article

A predictive gate-to-gate life cycle assessment (LCA) of plasma-assisted ammonia synthesis at TRL 4 is presented according to ISO 14040/44 standards. General plasma-assisted synthesis was evaluated through a mini-review‚ sensitivity analysis‚ and predictive LCA. The specific DBD needle-to-plate configuration LCA is performed using previously published experimental data. Two distinct scenarios were investigated. In the literature-based baseline scenario derived from sensitivity analysis, electricity consumption was 533 kWh/kg NH₃, giving a carbon footprint of 26.65–639.60 kg CO₂-eq/kg NH₃; electricity contributed 98.5% of total emissions, and impacts remained about 2.05 times higher than conventional Haber–Bosch. In contrast, the experimental DBD case study required 63,450 kWh/kg NH₃, showing reactor efficiency as the dominant driver of environmental performance. The BCS (≈1.39 kWh/kg NH₃) suggests that optimized plasma systems could potentially surpass conventional ammonia synthesis in energy efficiency. The environmental performance of plasma-assisted ammonia synthesis is affected by NH₃, NO_x, N₂O, and hydrogen emissions due to impacts on climate, air quality, water systems, and biodiversity. Future improvements may come from reactor and electrode optimization, catalyst integration, alternative plasma sources, and better process and heat integration, although deployment will likely depend on major efficiency gains and may be limited to niche decentralized applications. Full article

Pancreatic ductal adenocarcinoma frequently metastasises to the liver, although the mechanisms underlying hepatic pre-metastatic niche formation remain unclear. Small extracellular vesicles mediate tumour–host communication and may drive hepatic microenvironment reprogramming. This study investigated the effects of pancreatic ductal adenocarcinoma-derived small extracellular vesicles on extracellular matrix remodelling and epithelial–mesenchymal transition-related plasticity in hepatic cells. Small extracellular vesicles were isolated from pancreatic ductal adenocarcinoma cell lines (MIAPaCa-2, PANC-1) and from the serum of 25 patients, characterized, and administered to hepatic stellate (LX-2) and hepatocyte-like (HEPA-RG) cells. Cell viability and migration were evaluated by functional assays, morphology by scanning electron microscopy, and molecular changes by RT-PCR, Western blotting, and immunofluorescence. In LX-2 cells, small extracellular vesicles exposure increased metabolic activity, adhesion, and migration, while inducing morphological and molecular changes associated with extracellular matrix remodelling, including reduced collagen type I alpha 2 chain, vimentin, and E-cadherin expression. In HEPA-RG cells, viability was minimally affected, whereas migration and EMT-related plasticity were enhanced. Patient-derived small extracellular vesicles induced similar but less pronounced effects. Overall, pancreatic ductal adenocarcinoma-derived small extracellular vesicles induced early hepatic microenvironmental remodelling, supporting a potential role for tumour–liver crosstalk in pre-metastatic niche-associated processes, highlighting tumour–liver crosstalk as a potential therapeutic target. Full article

Dairy goat farming is a niche but relevant livestock system in alpine regions, yet its economic viability and environmental performance remain poorly quantified. This study assessed the relationship between profitability and environmental impacts in dairy goat farms in South Tyrol (Northern Italy). Data were collected from ten alpine dairy goat farms through on-farm interviews and accounting records and exploratorily analyzed using full-cost accounting and life cycle assessment (LCA). Given the small and purposive sample, all findings should be interpreted as preliminary and hypothesis-generating rather than statistically representative. Environmental impacts were evaluated from cradle to farm gate using two functional units: 1 kg of fat- and protein-corrected milk (FPCM) and 1 ha of agricultural land. Farm income per kg FPCM was highly variable, ranging from −€1.10 to €2.50, and depended strongly on herd size and subsidies. Average global warming potential was 2.96 ± 1.18 kg CO₂ eq per kg FPCM, but farm rankings changed when impacts were expressed per hectare. Pearson correlation and linear regression analyses showed a significant positive relationship between income and greenhouse gas emissions (r = 0.80, p < 0.05), indicating a trade-off between economic and environmental performance. Enteric methane and energy use were the main contributors to climate impacts. Improving productivity per animal rather than expanding herd size appears to be the most promising strategy to enhance profitability while limiting environmental burdens. Full article

Global climate change profoundly impacts the geographical distribution patterns and evolutionary dynamics of plants. As a vital ornamental and ecological shrub native to the temperate regions of the Northern Hemisphere, the wild germplasm resources of Weigela florida are facing dual threats from habitat fragmentation and climate warming. To elucidate the biogeographical mechanisms underlying the species’ responses to climate change and to formulate scientific conservation strategies, this study simulated the spatiotemporal dynamics of suitable habitats for W. florida across key historical periods spanning the Late Pliocene (~3.3 million years ago), Quaternary (~2.58 million years ago), the current period, and future climate scenarios using an optimized Maximum Entropy ecological niche model, and further tracked the migration trajectories of its spatial centroids. The results indicate that precipitation conditions, dry-season temperatures, and temperature seasonality are the dominant environmental factors limiting the distribution of wild W. florida. During the glacial–interglacial cycles, the area of its suitable habitat fluctuated significantly. Notably, the Korean Peninsula and the southern part of Northeast China maintained high habitat suitability across all geological historical periods, serving as long-term stable Quaternary glacial refugia for the species. Under various future climate scenarios, the total suitable habitat area of W. florida generally exhibits a shrinking trend, with habitat loss primarily concentrated at the western and southern edges of its distribution range. In the future, its spatial centroid shows a significant tendency to migrate towards higher latitudes (northeastward) to track suitable climatic niches. This study clarifies the macroscopic driving mechanisms behind the habitat dynamics of wild W. florida, providing critical spatial planning guidance for the refined evaluation and long-term sustainable utilization of its germplasm resources. Full article

Oral squamous cell carcinoma (OSCC) shows substantial immune and clinical heterogeneity that is not fully captured by conventional clinicopathologic risk factors. This systematic review synthesized primary studies evaluating immune biomarker signatures in OSCC identified through spatial transcriptomics, single-cell transcriptomics, and artificial intelligence (AI)-enabled pathology. PubMed/MEDLINE, Scopus, and Embase were searched without language or date restrictions. Eligible studies included original human OSCC investigations reporting immune-relevant biomarker outputs derived from spatial/single-cell transcriptomics or AI-enabled pathology. Nine studies met the inclusion criteria. Six used spatial and/or single-cell transcriptomic approaches, and three used AI-enabled pathology applied to histopathological whole-slide images. Functional meta-synthesis identified four interconnected domains: AI-derived tissue immune infiltration for prognostic stratification; T-cell states and tertiary lymphoid structure-associated antitumor immunity; spatial and metabolic immunosuppressive niches; and stromal–myeloid programs linked to T-cell exhaustion and resistance. Quantitative synthesis was considered but not performed because no group of studies was sufficiently comparable in biomarker construct, comparator, outcome, and effect measure. Clinical confidence remains limited by heterogeneity and prospective validation gaps. These findings suggest that emerging OSCC immune biomarkers may integrate tissue architecture, cellular states, and stromal–immune interactions; however, the current evidence remains exploratory and requires standardized, prospective validation before clinical translation can be considered. Full article

Three-dimensional species, such as some cnidarians, act as habitat formers, providing physical structures and biological activities that favor epibiosis and result in increased local diversity. In general, basibiont (=substrate organism) complexity influences the diversity of epibionts, but little is known about the role of its morphological attributes in shaping the associated community. Thus, we evaluated the role of 10 morphological attributes of cnidarian basibionts in the taxonomic and trophic structure of the associated Amphipoda community on tropical reefs. The results show that the morphological attributes of basibionts played an important role in structuring the associated amphipod community, but their effects varied among the taxonomic and functional components of the assemblage. Abundance and species composition were influenced by the type of basibiont, but without significant differences in other diversity descriptors, indicating a pattern of species turnover. On the other hand, trophic structure showed more consistent differences among basibionts and was better explained by morphological attributes, especially those related to size and complexity, suggesting that habitat architecture acts more strongly as a functional filter than a taxonomic one. Thus, the coexistence of multiple basibionts may increase regional amphipod diversity by expanding the availability of niches. Full article

Litter accumulation and small mammal disturbances create specific fine-scale microhabitats in grasslands. These microhabitats serve as safe sites and regeneration niches for subordinate plant species and are important in diversity maintenance. Previous experiments manipulating litter and disturbance and studying their effects on diversity revealed complex relationships. However, little is known about the realized net effects of these mechanisms in different types of grasslands. We conducted a long-term observational study exploring these patterns and their effects in successional and mature grasslands. We applied a specific mapping technique: the presences of litter, disturbance, and living plant species were recorded in 5 cm × 5 cm contiguous microquadrats along 52 m permanent transects. Sampling was repeated annually over 10 years. Spatial dynamics and associations with subordinate grassland specialists were evaluated using information theory models. Analyses were performed at increasing spatial and temporal scales. Varying associations were found across years. Negative associations dominated the relationships between litter and local diversity hotspots, while the relationships with disturbances were mainly neutral. When analyses were repeated at longer time scales, consistent negative associations were detected between litter and diversity hotspots. Long-term relationships between disturbance and diversity were negative in old-fields and positive in the natural grassland. To collect more representative and reliable data on the role of plant litter accumulation and small mammal disturbances, we recommend long-term annual monitoring and the application of temporal scaling based on cumulative diversity. Full article