Multi-echo turbo spin-echo (ME-TSE) sequences enable rapid T2 mapping but are prone to errors from stimulated echoes and slice cross-talk in multi-slice imaging. Moreover, the impact of different effective echo time (TEeff) selections on T2 measurement accuracy in ME-TSE remains unstudied. Therefore, the purpose of this study was to develop and validate a dictionary-based T2 mapping method for rapid multi-slice ME-TSE that accounts for slice cross-talk and to determine how TEeff selection influences mapping accuracy. Experiments were conducted in five calibrated agarose phantoms and two healthy volunteers at 3 T using an ME-TSE sequence. Nine TEeff combinations were evaluated, and experimental echo modulation curves were fitted to single-slice and multi-slice dictionaries generated via Bloch simulations involving slice interaction. Results showed that TEeff combination affected accuracy (mean relative error range: -1.97% to -6.96%) and homogeneity (SD range: 2.84-17.25 ms). Multi-slice dictionary fitting reduced inter-slice CV from 4.77% to 1.1% (phantoms) and from 1.95% to 1.04% (volunteer 1) and 1.76% to 1.11% (volunteer 2). Relative errors improved in phantoms from -19.22/-1.35% to -8.41/1.29% using multi-slice dictionaries. In conclusion, multi-slice dictionary-based fitting effectively mitigates slice cross-talk, improving T2 accuracy and inter-slice homogeneity in fast ME-TSE acquisitions. TEeff selection impacts precision, with well-separated echoes yielding superior results.
Chitosan-based adsorbents have drawn considerable attention due to their effective removal of hazardous pollutants, such as heavy metal ions, microplastics, and organic pollutants, including phenols, dyes, fertilizers, pesticides, herbicides, and pharmaceuticals. However, the practical application of chitosan is limited by its relatively low adsorption capacity, poor mechanical properties, and susceptibility to dissolution in acidic solutions. Therefore, chitosan is commonly modified using different techniques, including chemical and physical approaches, or combined with other adsorbent materials to enhance its structural stability and adsorption properties. Chitosan has been integrated with various materials, including natural polymers (e.g., cellulose, chitin/chitosan, starch, alginate), clay minerals (e.g., perlite and montmorillonite), inorganic materials (e.g., zeolite, metal oxides, and metal-organic frameworks), and carbonaceous materials (e.g., graphene oxide, activated carbon, biochar, and carbon nanotubes). Among these, carbonaceous materials are promising materials, due to their high surface area, porosity, and stability, which significantly improve the mechanical properties, thermal stability, and electrical properties, as well as adsorption capacity. This review focuses on chitosan-based carbonaceous composite materials as adsorbents and covers several aspects, including their synthesis methods, structural and surface characteristics, mechanical properties, and adsorption performance as well as their applications in wastewater treatment, particularly for the removal heavy metals, dyes, organic pollutants (such as oil, fertilizers, antibiotics, and pharmaceuticals), nuclear wastes, and pathogenic microoganisms.
Nanoplastics are ubiquitous in freshwater ecosystems and pose a threat to environmental and human health. They inhibit the growth of Microcystis aeruginosa and increase its microcystin content, yet the underlying mechanisms remain elusive. Here we investigated the effects of nano-polystyrene on the growth, photosynthesis, microcystin content and transcriptome of M. aeruginosa. The results showed that 10 mg/L nano-polystyrene slightly inhibited the growth during the first two days of exposure (toxicity phase), followed by a rapid recovery and enhanced growth of M. aeruginosa (promotion phase). During the toxicity phase, 10 mg/L nano-polystyrene decreased the content of phycocyanin, ATP and NADPH, and increased transcriptional levels of psbA, cpcA, grxC, trxA, gst, gshB and sod2 key genes in the studied species. During the promotion phase, the growth rate of M. aeruginosa increased with increased phycocyanin, ATP and NADPH production, and a series of photosynthetic parameters increased, which were reflected by the up-regulation of photosynthesis-related genes (e.g., psbH, psb28-1, petJ) to increase the photosynthetic electron transport rate, and the corA gene to absorb more necessary metals to support growth. Additionally, M. aeruginosa increased the microcystin content during both the toxicity and promotion phases, which might suggest it could potentially play a role in promoting photosynthesis and growth. The results indicated that nano-polystyrene could increase the growth and the microcystin content of M. aeruginosa, which could amplify the adverse and harmful effects of nanoplastics on freshwater ecosystems and human health. This study provides novel insights into the restoration and remediation of aquatic ecosystems.
The exposure history of aquatic organisms can strongly influence the subcellular partitioning of trace elements (TEs) and, consequently, their toxic potential. However, subcellular TE distribution has rarely been compared between chronically exposed native organisms and caged individuals used in active biomonitoring frameworks. Following improvements to subcellular partitioning protocols, the subcellular distribution of four metals (Zn, Cd, Pb, Tl) and four rare earth elements (REEs; Ce, Nd, Pr, Sm) was determined in gills and digestive glands of both caged and native populations of zebra mussels (Dreissena polymorpha), a widely used biomonitoring species. The study was conducted on the historically contaminated Deûle River (France), an ecosystem impacted by TE contamination from various local sources. Results revealed subcellular metal-handling strategies differed not only among elements but also across organs and exposure conditions. Cd detoxification appeared more effective in the gills of caged mussels (31%) than in native mussels (20%), suggesting that granule activation occurs predominantly in newly exposed organisms. All four REEs displayed consistent subcellular distribution across organs and exposure conditions. However, they were preferentially associated with the metal-sensitive compartment (including mitochondria, microsomes/lysosomes, heat-denatured proteins) in digestive glands of native mussels (from 60% to 70%) relative to caged ones (from 48% to 55%), indicating higher susceptibility to REE (Class A) contamination than for other TEs (Class B/Borderline). Detoxification of REEs was mainly associated with granules, while other TEs relied on both heat-stable proteins (including metallothioneins) and granules. These findings enhance our understanding of intracellular metal management strategies and provide key information for toxicokinetic modelling, supporting improved risk assessments of emerging contaminants.
Peripheral Arterial Disease (PAD) is a prevalent but underdiagnosed pathology. Soluble CD146 (sCD146) was described as a marker of endothelial dysfunction and vascular congestion. We hypothesize that sCD146 may represent a novel biomarker of PAD. Our objective was to evaluate the association between plasma sCD146 levels and the occurrence and severity of PAD. In this case-control study, 184 Caucasian men with symptomatic PAD were compared to 163 age-matched healthy control patients. PAD diagnosis was confirmed using ankle-brachial index (ABI) and imaging. Plasma sCD146 was quantified using ELISA. Associations with clinical and biochemical parameters were analyzed through multivariable logistic regression models. sCD146 level was significantly reduced in PAD patients (mean [95% CI]: 288 ng/mL [269-306]) versus control patients (480 ng/mL [460-500], p < 0.0001). A 10 ng/mL decrease in sCD146 was associated with an age-adjusted odds ratio (OR) of 1.17 (95% CI 1.13-1.22) for PAD, increasing to OR 1.25 (95% CI 1.14-1.36, p < 0.0001) after adjustment for risk factors. sCD146 was not associated with PAD severity (by Fontaine stage). Notably, the association between sCD146 and HDL-C was positively correlated in controls (β = 0.220, p = 0.005), but negatively correlated in PAD patients (β = - 0.156, p = 0.041), with significant interaction (p = 0.002). Age-adjusted OR for PAD was highest in individuals with high HDL-C tertiles (OR = 1.41, 95% CI 1.22-1.63). A lower sCD146 concentration is independently associated with PAD. Additionally, an inverse relationship was observed between HDL-C and these patients. These findings suggest that sCD146 may reflect impaired endothelial homeostasis and metabolic dysregulation in PAD, indicating that it could serve as a diagnostic biomarker for the pathology. NCT00377897.
Parasites play a critical yet understudied role in Arctic ecosystems, particularly within key subsistence species such as Arctic char (Salvelinus alpinus). As the Arctic undergoes rapid climate-driven change, establishing baseline parasite biodiversity is essential for monitoring ecological shifts and anticipating emerging health and conservation concerns. This study provides the most comprehensive assessment to date of Arctic char parasites in the North American Arctic by integrating a systematic literature review with new empirical data from 378 Arctic char collected across five Nunavut areas (2020-2024). The literature review (30 studies, 1956-2024) documented 67 parasite taxa-48 identified to species-with helminths (nematodes, cestodes, trematodes, acanthocephalans) dominant. Overall, 82% of taxa occurred in anadromous Arctic char and 54% in freshwater forms, including 22 species unique to anadromous fish. Our empirical assessment identified 35 parasite taxa-23 to species level-including several previously unreported from Arctic char in this region. Common and widespread parasites documented in the empirical assessment included Brachyphallus crenatus, Derogenes varicus, Bothrimonus sturionis, and Alloopistholecithum gibbosum, although notable spatial variation occurred in community composition and infection intensity. The occurrence of rare and previously unreported parasites may suggest emerging shifts in host-parasite dynamics potentially linked to changing prey availability and northward species range expansions. Together, these findings establish an essential baseline for Arctic char parasite biodiversity and highlight the need for continued monitoring to track future changes driven by climate warming, shifting food webs, and their implications for fish health and food security in northern Indigenous communities. The online version contains supplementary material available at 10.1007/s11160-026-10068-x.
Nucleotide analogues (NAs) have been successfully used for the treatment of various RNA virus infections by selectively targeting the viral RNA-dependent RNA polymerase (RdRp) for incorporation into the viral genome. However two major families of human-infecting RNA viruses, Coronaviridae (CoV) and Arenaviridae, encode exonuclease domains that may recognize and remove incorporated NAs, thus providing natural resistance against some of these drugs. Both polymerization and excision reactions are mechanistically centered on the nucleotide α-phosphate, enabling the potential for sequential inhibition of both RNA synthesis and repair. Here, we provide structural evidence of inversion of configuration at the phosphorus center during polymerization, demonstrating that the SARS-CoV-2 RdRp proceeds through an SN2 mechanism. A 2.39 Å resolution cryo-EM structure of a ternary replication complex bound to RNA and an α-thio-modified NTP shows that incorporation of the preferred SP isomer at the 3' end of the RNA yields a phosphorothioate linkage in the RP configuration. This RP-phosphorothioate RNA product shows reduced cleavage by both the SARS-CoV-2 and three arenavirus RNA exonucleases, revealing a stereochemical preference opposite to that of structurally related DNA exonucleases. This observation contradicts the prevailing assumption that sulfur substitution at the metal-coordinating oxygen universally blocks catalysis. Instead, RNA exonuclease stereoselectivity appears to be shaped not only by metal-sulfur interactions but also by the geometry of nucleophile activation. These findings provide mechanistic insights into phosphoryl transfer in viral polymerases and exonucleases and highlight opportunities to counteract intrinsic nuclease-mediated resistance against antiviral nucleotide analogues.
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N-ethylpentedrone (NEP) is a New Psychoactive Substance (NPS) of the cathinone class that has raised public health concerns, scheduled by both the United Nations Office on Drugs and Crime and the European Union Drugs Agency, since 2024. We report here a fatal case involving a 29-years-old man who used NEP in a chemsex context. Three plastic bags containing off-white to beige powders and crystals were found near the body. Proton and carbon nuclear magnetic resonance spectrometry (1H and 13C NMR) and ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analyses confirmed all three bags contained NEP with purity above 98%. UHPLC-HRMS data analyses using molecular networking and in silico prediction allowed to propose NEP metabolic profile in peripheral and cardiac blood, bile, gastric fluid, urine and hair. We described here six Phase I metabolites, and we proposed NEP (C13H19NO) as the principal biomarker in NEP intake, metabolites M4 (C11H17NO) and M1 (C11H15NO) serving as biomarkers of consumption, as all of which were detected in all postmortem body fluid samples as well as in hair. Predominant metabolic pathways involved keto-reduction, N-dealkylation, hydroxylation, and oxidation, while no Phase II metabolites were detected under the applied analytical conditions. NEP was quantified at 18 mg/L and 20 mg/L in peripheral and cardiac blood, respectively, and 654-755 pg/mg in hair. These exceptionally high concentrations in biological fluids indicate an acute NEP intoxication, while hair analyses confirm repeated exposure over several months, consistent with chronic use. In summary, the identification of these metabolites in various postmortem body fluid matrices and in hair will improve our understanding of potential drug consumption markers and contribute to better monitoring and detection of N-ethylpentedrone use and abuse.
Vascular Fusarium wilt and floral virescence are two significant diseases affecting cotton production in Côte d'Ivoire, leading to substantial crop losses. Current knowledge regarding the distribution of these diseases is limited as most existing studies are outdated. Consequently, there is a need for updated data to assess the evolution of these diseases in cotton-growing regions. This study aimed to investigate the spatial and temporal occurrence of these diseases by examining 600 small farms between 2022 and 2024. The incidence of Fusarium wilt varied among cropping seasons, with no statistically significant differences observed (p = 0.351). The highest incidence was recorded in 2022, with peaks of 0.023% in late July, 0.020% in mid-August, and 0.066% in mid-September, followed by a complete decline at the end of the cropping cycle. During the 2023 and 2024 seasons, Fusarium wilt incidence remained very low, ranging from 0 to 0.01%. Regarding floral virescence, a similar seasonal pattern was observed across the three years, with disease onset occurring in late July. The highest incidence was observed in 2022, peaking at 0.25% in early September. Interannual variation in virescence incidence was statistically significant (p = 0.007). Spatially, Fusarium wilt was mainly concentrated in the southern part of the cotton-growing basin, with a progressive extension toward central areas. In contrast, floral virescence was predominantly observed in the northern basin, with a gradual spread toward central and southern localities. A highly significant geographical effect was recorded (p < 0.001). These results highlight the need to implement targeted phytosanitary strategies, including vector control and introduction of resistant cotton varieties. They may also guide the selection of plots for seed production.
Bats and their ectoparasites are significant reservoirs and potential vectors of emerging zoonotic pathogens, yet the viral diversity within bat-associated arthropods remains poorly characterized. This study reports the identification of a novel coltivirus (order Reovirales), provisionally designated Stricticimex coltivirus (SCCV), in a newly described bat bug species, Stricticimex phnomsampovensis, collected from cave-dwelling wrinkle-lipped free-tailed bats (Mops plicatus) in Cambodia. Metagenomic sequencing and phylogenetic analysis revealed that SCCV clusters within the Coltivirus genus, showing closest similarity to Tai Forest Reovirus (TFRV) previously isolated from African bats. SCCV was detected in 18.4% of examined bat bugs and successfully isolated in VeroE6 cells, with replication confirmed in multiple mammalian cell lines. The discovery of SCCV extends the known diversity and geographic range of coltiviruses and highlights bat ectoparasites as overlooked hosts of potentially zoonotic viruses. These findings underscore the importance of integrated One Health surveillance targeting both bats and their ectoparasites to better assess the risk of pathogen spillover in biodiverse regions with high human-animal contact.
Spanning over 500 million years, the fossil record of Retaria is a cornerstone of paleobiology, paleoclimate reconstruction, and stratigraphy. Yet, the constitutive branches of Retaria, Foraminifera, and Radiolaria, not only have been studied independently, but just a fraction of this research has focused on living representatives of these lineages. Here we tentatively identify the "Big Five" areas of biological research into Retaria, articulated around novel and transformative understanding of their evolution and diversity, role in ocean biogeochemistry, life cycles, and ecology. Through this perspective, we argue that a unified Retaria framework that seamlessly integrates biological and paleontological data will benefit the scientific community at large, train the next generation of researchers broadly and open novel perspectives to understand the global ocean's evolution.
The delta opioid receptor (DOR) has been a focus of research for the treatment of depression and certain pain disorders. Unfortunately, clinical translation of delta opioid agonists to humans has proved challenging partly because of their propensity to cause convulsions at higher doses. The discovery that the DOR can be allosterically modulated has opened the possibility of developing compounds that may be able to produce some of the positive therapeutic effects, either as standalone treatments to enhance the action of endogenous opioid peptides or as sparing agents allowing the use of lower doses of DOR agonists, which could reduce the chance of inducing convulsions. BMS-986187 is a positive allosteric modulator of DOR. The behavioral effects of BMS-986187 related to depression and pain have not been investigated. In this study, we examined the impact of BMS-986187 on DOR-mediated antidepressant-like effects in the forced swim test, antinociceptive and antiallodynic actions and propensity to cause convulsions. BMS-986187 (1 mg/kg) showed antidepressant-like effects when administered alone, but did not produce convulsions. BMS-986187 (10 mg/kg) also enhanced the antinociceptive and antiallodynic effects of the standard DOR agonist SNC80, with only a very minor effect on SNC80-mediated convulsions. The results suggest the development of positive modulators of DOR for the management of pain and/or depression. SIGNIFICANCE STATEMENT: The delta opioid receptor (DOR) has been suggested as a target to treat depression and pain. However, agonists at this receptor can cause convulsions. This study demonstrates that a positive allosteric modulator of DOR administered alone reduces depression-like behaviors and, in combination with a DOR agonist, shows robust pain-relieving actions, without convulsive effects. This suggests a novel and safe treatment for depression and/or pain.
The primary visual cortex (V1) is tuned to several visual features, including orientation and spatial frequency, that are organized into overlapping functional maps. Local neurons sharing tuning properties tend to connect more strongly, but how these features lead to distal functional connectivity in V1 remains unclear. We recorded multiunit activity from layers II/III of cat V1 using electrode pairs separated by 410 µm and assessed functional connectivity using shift-corrected cross-correlograms. Visual stimuli were positioned to largely overlap the receptive fields of neurons at both recording sites. Functional connectivity was compared during orientation-constant and spatial frequency-constant stimulus conditions. Neurons in the same ensemble exhibited significantly more and stronger distal functional connections during the spatial frequency-constant condition than during the orientation-constant condition. This effect persisted at the population level, indicating that distal connectivity is selectively recruited depending on the stimulus feature rather than anatomical proximity or differential stimulus drive. These findings demonstrate that functional connectivity in V1 is stimulus-dependent, with spatial frequency processing preferentially engaging distributed cortical interactions. Such feature-dependent distal connectivity may support integration across spatial scales and reflect the flexible organization of early visual cortical networks.
In Myxococcus xanthus, a predatory soil bacterium, cell polarity and motility are regulated by MglA (a small GTPase) and its regulators, MglB (a potential GAP) and RomRX (a previously proposed GEF), but their precise roles remain unclear. Using fluorescent nucleotides suitable for fluorescence anisotropy measurements, we show that RomRX does not function as a GEF but instead acts as an effector binding MglAGTP. We further find, using an enzymatic model, that MglB exhibits both GAP and GEF properties depending on the local MglAGDP concentration. Additionally, RomRX, specifically RomR, effectively dissociates the MglA-MglB complex by sequestering MglB. This low-affinity interaction permits GAP activity while still partitioning the proteins in vivo, as shown by a biomimetic oil-emulsion droplet assay in a cell-sized system. A minimal mathematical model incorporating these interactions and previous findings recapitulates how dynamic interactions between these three players form an invertible polarity axis in the M. xanthus cell.
Physiological and metabolic responses of the Pb-tolerant Brassicaceae Hirschfeldia incana to short-term (3 days) and medium-term (15 days) Pb exposure were evaluated. Physiological traits revealed an early and sustained control of oxidative stress. By day 3, non-enzymatic antioxidants and soluble sugars increased to support ROS quenching and promote osmotic adjustment. By day 15, POD activity further increased, while phenolic and soluble sugar contents remained elevated and chl b decreased selectively. Non-targeted metabolomics revealed a stronger response in roots than in shoots, highlighting the organ-specific nature of Pb tolerance in H. incana. Constitutive metabolic features were distinguished from time-dependent induced ones. Roots displayed a constitutive antioxidant defense driven by metabolic diversion from tryptophan and glucosinolates. Over time, this constitutive strategy was strengthened by an expansion of phenolics, particularly ferulic acid and sinapic acid to enhanced cell wall lignification. By day 15, the marked depletion of soluble non-enzymatic antioxidants (ascorbate and glutathione) likely reflected the sustained ROS turnover under elevated H2O2 levels. Although shoots accumulated less Pb, they still mounted an antioxidant response centered on anthocyanins and phenolics, along with an increase in small dipeptides, consistent with peptide-mediated nitrogen shuttling and repair. These data provide a comprehensive insight into the overall Pb stress response mechanisms in H. incana. These findings also support the potential use of this species as a model for understanding Pb tolerance and for developing phytoremediation-oriented strategies in contaminated environments.
Stereotactic body radiotherapy (SBRT), most commonly delivered in 5 fractions, is an established treatment option for patients with localized prostate cancer. While efforts to further reduce treatment to fewer than 5 fractions are ongoing, the efficacy and tolerability of single high-dose SBRT remain to be established. To determine in men with localized prostate cancer whether a single-fraction SBRT can be a valid treatment option in terms of biochemical disease control and safety. This multicenter, single-arm, prospective, phase 1/2 nonrandomized clinical trial included men with localized prostate cancer at low or intermediate risk, with International Society of Urological Pathology grade group 1 or 2, and without significant tumor in the transitional zone. Participants were recruited between 2017 and 2022 in 5 academic centers in Europe and the US. Data were analyzed between February and May 2026. Participants were treated with a 19-Gy single-fraction prostate SBRT with urethra-sparing and intrafraction motion control. The primary end point was biochemical relapse-free survival (bRFS) at 3 years (expected value of 96% included in the 95% CI). Secondary end points included occurrence of genitourinary (GU), gastrointestinal (GI), and sexual adverse events (AEs) and quality of life (QOL) assessment. Among the 45 patients recruited (median age, 72 [range, 60-82] years), 43 were treated per protocol. After a median follow-up of 55.3 (IQR, 49.9-60.7) months, the estimated 3-year bRFS was 92.9% (95% CI, 85.4%-100%), meeting the primary end point. At 3 years, grade 2 GU and GI AEs were observed in 4 (9.8%) and 2 (4.9%) participants, respectively, with only a grade-3 proctitis observed in 1 patient at month 12. Grade 2 or higher erectile dysfunction increased from 9 of 42 patients (21.4%) at baseline to 15 of 39 (38.4%) at 3 years. A significant minimally clinically important change in Expanded Prostate Cancer Index Composite scores was observed in 6 (14%) and 12 (28%) participants for GU and sexual scores, respectively. The impact in GI bother scores was minimal. In this multicenter phase 1/2 trial, a single-fraction 19-Gy urethra-sparing SBRT met the primary end point, achieving a 3-year bRFS of 92.9%, with grade 2 GU and GI AEs remaining below 10% and 5%, respectively, at 3 years. Longer follow-up is warranted to assess long-term disease control. ClinicalTrials.gov Identifier: NCT03294889.
Charcot-Marie-Tooth disease type 2A (CMT2A) is the most common axonal CMT and is associated with an early onset and severe motor neuropathy. CMT2A is mainly caused by dominant mutations in the MFN2 gene, encoding mitofusin-2, a GTPase located in the outer membrane of the mitochondria and endoplasmic reticulum (ER). Mutations in MFN2 affect mitochondrial dynamics. We previously demonstrated that mutated MFN2 further disrupts contacts between the ER and the mitochondria, leading to axonal degeneration. There are no treatments for CMT2A, and those currently under development primarily focus on restoring mitochondrial function. Here, we provide proof of concept that neuronal overexpression of wild-type MFN2 (MFN2WT) provides therapeutic benefit in transgenic CMT2A mice as well as in CMT2A-motor neurons derived from induced pluripotent stem cells. Intrathecal delivery of an AAV9 vector expressing MFN2WT effectively targets motor and sensory neurons, restoring ER-mitochondria contacts and mitochondrial morphology, thereby preserving both neuromuscular junction integrity and motor function. Strikingly, therapeutic efficacy is also achieved by administering the vector after the onset of symptoms. Importantly, AAV administration was well tolerated, with no evidence of hepatotoxicity or dorsal root ganglion inflammation. We further show that CMT2A pathology can be corrected in vitro and in vivo using an ER-targeting MFN1 isoform that selectively enhances ER-mitochondria contacts. These results establish that restoring contacts between the ER and mitochondria using gene therapy is a promising therapeutic avenue for CMT2A.
Although immune checkpoint inhibitors have revolutionized lung cancer treatment, their limited efficacy and significant toxicity highlight the need for improved therapeutic strategies. Immunomodulatory agents are known to enhance anti-tumor immune responses. In this study, we investigated how the route of administration affects the tolerability and immunological impact of these immunostimulants. We demonstrate that airway administration of poly I: C, CpG, and an anti-CD137 antibody in healthy mice results in significantly reduced liver toxicity and systemic inflammation compared with intravenous delivery. This was evidenced by lower AST levels, preserved body weight, and a reduced neutrophil-to-lymphocyte ratio. In addition, airway delivery of immunostimulant promoted dose-dependent recruitment of both myeloid and lymphoid cells as compared to intravenous administration. Using a syngeneic orthotopic mouse model of lung carcinoma, we further showed that local airway administration of anti-CD137 antibody resulted in increased pulmonary infiltration of CD4⁺, CD8⁺, and CD4⁺ TRM cells compared with intravenous injection. This enhanced immune infiltration correlated with improved tumor control. Overall, our findings indicate that local administration of immunostimulants enhances pulmonary adaptive immune responses and tumor suppression while limiting systemic toxicity.