Search Results (12,030)

As plastic and heavy metal pollution continue to escalate, the co-occurrence of microplastics and heavy metals in the environment poses significant threats to ecosystems and human health. This study was designed to explore the combined effects of polyethylene microplastics (PE-MPs) and cadmium (Cd) pollution on wheat seedlings, focusing on antioxidant enzyme activity and Cd bioaccumulation. At low concentrations of PE ($1\mathrm{mg}·{\mathrm{L}}^{-1}$), peroxidase (POD) activity in wheat shoots slightly increased without significance, while at higher concentrations ($50\mathrm{mg}·{\mathrm{L}}^{-1}$ and $100\mathrm{mg}·{\mathrm{L}}^{-1}$) of PE, POD activity was significantly inhibited compared to $0\mathrm{mg}·{\mathrm{L}}^{-1}$ PE treatment. At Cd exposure activity, with POD activity in the shoots increasing by 73.7% at $50\mathsf{\mu }\mathrm{mol}·{\mathrm{L}}^{-1}$${\mathrm{Cd}}^{2+}$ compared to $0\mathsf{\mu }\mathrm{mol}·{\mathrm{L}}^{-1}$ Cd treatment. When wheat seedlings were exposed to a combination of $50\mathrm{mg}·{\mathrm{L}}^{-1}$ PE and Cd at different concentrations Cd, significant differences in POD activity were observed in the shoots compared to the control group, showing an upward trend with increasing Cd concentration. However, the addition of PE suspension generally reduced POD activity in wheat shoots compared to Cd treatment alone. Specifically, the presence of $50\mathrm{mg}·{\mathrm{L}}^{-1}$ PE did not significantly alter POD activity in the wheat shoots ($p>0.05$). Furthermore, exposure to different concentrations of Cd resulted in a general increase in POD activity of roots, with significant differences observed at $5\mathsf{\mu }\mathrm{mol}·{\mathrm{L}}^{-1}$ and $25\mathsf{\mu }\mathrm{mol}·{\mathrm{L}}^{-1}$ Cd ($p<0.05$). Regarding Cd bioaccumulation, at Cd low concentrations ($1\mathsf{\mu }\mathrm{mol}·{\mathrm{L}}^{-1}$ and $5\mathsf{\mu }\mathrm{mol}·{\mathrm{L}}^{-1}$), PE significantly promoted Cd accumulation in the shoots. However, at high Cd concentrations ($50\mathsf{\mu }\mathrm{mol}·{\mathrm{L}}^{-1}$), PE microplastics reduced Cd accumulation in the shoots but promoted its accumulation in the roots.These results suggest that PE microplastics influence the bioavailability of Cd, mitigating the toxic effects of high Cd concentrations. This paper scientifically elucidates the ecotoxicological effects of co-contamination for microplastics and heavy metals, also their potential impacts on agricultural production are discussed. Full article

Background: Advances in molecular pathology have transformed NSCLC (Non-Small Cell Lung Cancer) diagnosis, prognosis, and treatment by enabling precise tumor characterization and targeted therapeutic strategies. We review key genomic alterations in NSCLC, including EGFR (epidermal growth factor receptor) mutations, ALK (anaplastic lymphoma kinase) and ROS1 (ROS proto-oncogene 1) rearrangements, BRAF (B-Raf proto-oncogene serine/threonine kinase) mutations, MET (mesenchymal–epithelial transition factor) alterations, KRAS (Kirsten rat sarcoma) mutations, HER2 (human epidermal growth factor receptor 2) alterations and emerging NTRK (neurotrophic receptor tyrosine kinase) fusions and AXL-related pathways. Methods: A total of 48 patients with NSCLC was analyzed, including 22 women and 26 men (mean age 70 years, range 44–86). Tumor specimens were classified histologically as adenocarcinomas (n = 81%) or squamous cell carcinomas (n = 19%). Smoking history, PD-L1 (programmed death-ligand 1) expression, and genetic alterations were assessed. NGS (Next-generation sequencing) identified genomic variants, which were classified according to ACMG (American College of Medical Genetics and Genomics) guidelines. Results: The cohort consisted of 29 former smokers, 13 current smokers, and 5 non-smokers (12%), with a mean smoking burden of 33 pack years. PD-L1 TPS (tumor proportion score) was ≥50% in 10 patients, ≥1–<50% in 22, and <1% in 15 patients. In total, 120 genomic variants were detected (allele frequency ≥ 5%). Of these, 52 (43%) were classified as likely pathogenic or pathogenic, 48 (40%) as variants of unknown significance, and 20 (17%) as benign or likely benign. The most frequently altered genes were TP53 (tumor protein p53) (31%), KRAS and EGFR (15% each), and STK11 (serine/threonine kinase 11) (12%). Adenocarcinomas accounted for 89% of all alterations, with TP53 (21%) and KRAS (15%) being most common, while squamous cell carcinomas predominantly harbored TP53 (38%) and MET (15%) mutations. In patients with PD-L1 TPS ≥ 50%, KRAS mutations were enriched (50%), particularly KRAS G12C and G12D, with frequent co-occurrence of TP53 mutations (20%). No pathogenic EGFR mutations were detected in this subgroup. Conclusions: Comprehensive genomic profiling in NSCLC revealed a high prevalence of clinically relevant mutations, with TP53, KRAS and EGFR as the dominant drivers. The strong association of KRAS mutations with high PD-L1 expression, irrespective of smoking history, highlights the interplay between genetic and immunological pathways in NSCLC. These findings support the routine implementation of broad molecular testing to guide precision oncology approaches in both adenocarcinoma and squamous cell carcinoma patients. Full article

Background: While intravenous administration of nanoparticles (NPs) is effective for targeting the lungs and liver, directing them to other organs and tissues remains challenging. Methods: Here, we report alternative administration routes that improve organ-specific accumulation of poly (lactic-co-glycolic acid) (PLGA) NPs (100 nm, negatively charged) loaded with the near-infrared dye Cyanine 7 (Cy7). NP cytotoxicity was evaluated in HEK293, mMSCs, C2C12, L929, and RAW264.7 cells. Hemocompatibility was assessed using WBCs and RBCs. NPs were administered via the tail vein, carotid, renal, and femoral arteries in BALB/c mice. Administration safety was evaluated by laser speckle contrast imaging and histological analysis. NP biodistribution and accumulation were assessed using in vivo and ex vivo fluorescence tomography and confocal microscopy of cryosections. Results: PLGA-Cy7 NPs demonstrate low cytotoxicity even at high doses and exhibit good hemocompatibility. Administration of NPs through the mouse carotid, renal, and femoral arteries significantly increases accumulation in the target ipsilateral brain hemisphere (31.7-fold) and salivary glands (28.3-fold), kidney (13.7-fold), and hind paw (3.6-fold), respectively, compared to intravenous administration. Injection of NPs through arteries supplying the target organs and tissues does not result in significant changes in blood flow, morphological alterations, or irreversible embolization of vessels, provided the procedure is performed correctly and the optimal dosage is used. Conclusions: These results highlight the potential of intra-arterial delivery of NPs for organ-specific drug targeting, underscoring the synergistic impact of advances in materials science, minimally invasive endovascular surgery, and nanomedicine. Full article

The Rhodomyrtus tomentosa (Aiton.) Hassk. berry is rich in structurally diverse polysaccharides with potential biological activity. However, its immunomodulatory properties remain understudied, limiting our current understanding of its functional significance. Two structurally distinct polysaccharides from Rhodomyrtus tomentosa (RTP-1 and RTP-2) were evaluated for immunostimulatory activity in RAW264.7 macrophages. Phagocytic function was assessed by neutral red assay, nitric oxide (NO) and reactive oxygen species were measured using the Griess assay and fluorescent probes, and cytokines (TNF-α, IL-6 and IL-1β) were quantified by enzyme-linked immunosorbent assay. Analysis of RNA-seq data using weighted gene co-expression network analysis revealed co-expression modules. The selected transcripts were independently validated by quantitative real-time PCR (RT-qPCR). The results showed that both polysaccharides enhanced phagocytosis, increased NO/ROS levels, and promoted cytokine secretion. Transcriptome results indicated that RTP-2 activated the MEturquoise co-expression module containing 222 hub genes, whereas RTP-1 was mainly associated with the MECyan module containing 49 hub genes. Module enrichment for RTP-2 revealed links with mitophagy–immune regulation, proteostasis/stress, and innate immune signaling. RT-qPCR further confirmed that in the RTP-2 group, Dram1 expression was upregulated approximately 121 times, Bmf1 expression was upregulated approximately 18 times, and Bnip3 was significantly downregulated, whereas Bnip3l expression remained unchanged. Overall, RTP-2 exhibited a more pronounced and coherent macrophage-stimulating profile in vitro, supporting its potential as a macrophage-targeted immunostimulatory ingredient. Full article

With the growing demand for eco-friendly food packaging, poly(butylene adipate-co-terephthalate) (PBAT)/polylactic acid (PLA) composite films have emerged as promising biodegradable alternatives, but their inherent limitations (e.g., poor antioxidant capacity, weak UV stability, and insufficient antimicrobial activity) hinder practical applications. This study aimed to address these drawbacks by incorporating Rosmarinus officinalis L. extract (RM) as a natural multifunctional additive. PBAT/PLA/RM blend films with RM concentrations of 0.1%, 0.3%, 0.5%, and 1% were fabricated via melt extrusion and blown film processing. Key characterizations were conducted to evaluate thermal stability, mechanical properties, morphology, antioxidant activity, UV-shielding performance, antimicrobial efficacy, and biodegradability. The results showed that RM significantly enhanced the antioxidant capacity of the films, with the highest DPPH radical scavenging activity achieved at 0.3% RM. UV-blocking performance improved incrementally with increasing RM concentration, and films containing ≥0.5% RM filtered over 90% of UVA and UVB radiation. All composite films met biodegradability standards, with over 90% degradation observed after 240 days of composting, though RM prolonged the initial degradation stage by inhibiting early microbial activity. However, the antimicrobial effect of RM was limited, and concentrations exceeding 1% caused film stickiness, impeding processing. This work demonstrates that RM is a viable natural additive for functionalizing PBAT/PLA films, offering enhanced antioxidant and UV-shielding properties while maintaining biodegradability, thus providing a promising solution for sustainable food packaging. Full article

Milk beer, a modern Chinese dairy beverage, is usually fermented by the co-culture of lactic acid bacteria (LAB) and Kluyveromyces marxianus (K. marxianus), with the latter known for its ability to produce aroma compounds. However, the accumulation of lactic acid produced by LAB can inhibit the growth of K. marxianus, which inevitably hinders the diversity and intensity of flavor compounds in milk beer. In this study, adaptive laboratory evolution (ALE) was applied to the parental strain Kluyveromyces marxianus CICC1953 (Km-P) under different concentrations of lactic acid to obtain an evolved strain Km-ALE-X20 with enhanced acid tolerance and increased titer of phenylethyl alcohol, which has a floral, rose-like aroma. Km-ALE-X20 demonstrated a 16-fold increase in OD₆₀₀ and a 28-fold increase in phenylethyl alcohol production compared with Km-P in chemically defined medium (CDM) containing 20 g/L lactic acid. Comparative genomics analysis suggested that mutated genes CTA1, TSL1, ERG2 were related to enhanced acid tolerance, while ARO8, ARO9, FKS2 were related to increased production of aroma compounds. Furthermore, Km-ALE-X20-fermented milk beer showed 33.87% and 32.43% higher production in alcohol and ester compounds than that of Km-P-fermented milk beer. Interestingly, sensory analysis showed that while Km-ALE-X20-fermented milk beer had higher sensory scores for rose and fruity aroma attributes, Km-P-fermented milk beer possessed a more balanced aroma profile. This paper highlights the first application of ALE to enhance the signature rose aroma of K. marxianus-fermented milk beer and provides an efficient framework for ALE-based breeding of aroma-producing food microorganisms. Full article

Swine manure, a heterogeneous livestock waste composed of solid and liquid excreta, can be sustainably converted through Chemical Looping Gasification (CLG) to produce syngas and bioenergy. Integrated with CO₂ capture, the process enables high-purity hydrogen generation and offers a potential route toward net-negative carbon emissions. The experimental campaign was conducted at 900 °C in a continuously operated 0.5 kW_th CLG unit consisting of two interconnected fluidized bed reactors (fuel and air). Ilmenite was employed as the oxygen carrier to provide the oxygen required for gasification. This study focuses on the gasification of raw swine manure, comprising both solid and liquid fractions. The solid fraction was introduced via a screw feeder, while the liquid fraction was simulated by injecting an ammonia–water solution as gasifying agents (water or ammonia + water). The effect of the liquid fraction on syngas composition, carbon conversion, and nitrogen species (N₂, NH₃, N₂O, NO₂, and NO) was evaluated at ammonia concentrations typical of swine manure (800–5600 mg/L). Results showed an average syngas composition for solid and liquid fraction feeding of ~31% CO₂, 20% CO, 41% H₂, 7% CH₄, and 0.5% C₂ hydrocarbons, with 91–96% carbon conversion. Benzene and naphthalene dominated the tar compounds. CO₂ capture potential reached 60%, with nitrogen mainly converted to N₂. Full article

Influenza A virus (IAV) continues to present a threat to public health, highlighting the need for safe and multi-target antivirals. In this study, anti-influenza activity, airborne transmission blocking capacity, and immunomodulatory effects of Cnidium monnieri polysaccharides (CMP) were evaluated. Cytotoxicity in A549 cells was assessed by CCK-8 (CC₅₀ = 8.49 mg/mL), antiviral efficacy against A/California/04/2009 (CA04) by dose–response (EC₅₀ = 1.63 mg/mL), and the stage of action by time-of-addition assays (pre-, co-, post-treatment). A guinea pig model infected with CA04 was used for testing the effect of pre-exposure CMP on transmission, with readouts including nasal-wash titers, seroconversion, lung index, and tissue titers (EID₅₀). RT-qPCR was employed to quantify the mRNA expression levels of proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, in lung tissue, while Western blot analysis was performed to assess the expression and phosphorylation status of key proteins involved in the NF-κB signaling pathway. CMP suppressed viral replication in vitro within non-cytotoxic ranges, and pre-treatment—rather than co- or post-treatment—significantly reduced titers and cytopathic effect, consistent with effects at pre-entry steps and/or host priming. In vivo, pre-exposure CMP lowered nasal shedding, reduced aerosol transmission (3/6 seroconverted vs. 6/6 controls), decreased lung indices, and diminished tissue viral loads; IAV was undetectable in trachea at 7 days post-infection in pre-exposed animals, and nasal-turbinate titers declined relative to infection controls. Moreover, during in vivo treatment in mice, CMP significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in lung tissue. This effect was mechanistically associated with CMP-mediated regulation of the NF-κB signaling pathway, leading to attenuation of inflammatory responses. These data indicate that CMP combines a favorable in vitro safety and efficacy profile with inhibition of airborne spread in vivo, supporting further mechanistic, pharmacokinetic, and fractionation studies toward translational development. Full article

Interactions between alkaline solutions and the surface of pyrolytically coated graphite tubes (PCGTs) with/without a platform for determination of vanadium using high-resolution continuum source graphite furnace atomic absorption spectrometry (HR CS GFAAS) are discussed. Changes on the surface of tubes, lifetime of tubes, and formation of memory effect in the determination of vanadium in alkaline solutions (NaOH, Na₂CO₃, and real alkaline slag leachates) were investigated. Based on the results obtained, it is possible to state that HR CS GFAAS determination of vanadium content in alkaline solutions reveals that PCGTs with a platform are more susceptible than those without a platform to the formation of deposits and degradation of the platform surface, especially after the application of hydroxide environments. More marked and faster formation of deposits leads to shortening of the analytical lifetime of PCGTs with a platform (approx. 70 atomization/analytical cycles (ACs)) compared to PCGTs without a platform (approx. 290 ACs). The mechanical life of both types of tubes is comparable (approx. 500 ACs). Deposits formed on the internal surface of PCGTs can be removed in the presence of a carbonate environment and higher temperatures. Damage to the PCGT surface leads to the formation of scaled shapes and cavities, which can result in decreased absorbance due to losses of vanadium in the cavities (negative measurement error), or in increased absorbance by washing out of vanadium from the cavities (positive measurement error, and formation of memory effect). It was found that more frequent cleaning of PCGTs by performing ACs in an environment of 4 mol L⁻¹ HNO₃ can eliminate these unfavourable phenomena. Our results have shown that in the case of samples analysed with different sample environments (acidic vs. alkaline), the surface material of the tube/platform wears out more quickly, and therefore it is necessary to include a cleaning stage after changing the nature of the environment. Full article

In this study, cationic surfactant cetyltrimethylammonium bromide (CTAB) and anionic surfactant sodium bis(2-ethylhexyl) sulfosuccinate (AOT) are employed to systematically investigate surface and wetting properties on hydrophobic surfaces, specifically in mixed solvents composed of ethylene glycol (EG) and water at 298.15 K. By varying the concentration of each surfactant within the EG–water mixture, both surface tension and contact angle measurements are performed to elucidate how surfactant type and solvent composition influence interfacial behavior and wettability. PTFE and wax surfaces were chosen as model hydrophobic surfaces. Surface tension measurements obtained in pure water and in water–EG mixtures containing 5, 10, and 20 volume percentage EG reveal a consistent decrease in the premicellar slope (${\displaystyle \frac{d\gamma }{d\mathit{log}C}}$) with increasing EG content. This reduction reflects weakened hydrophobic interactions and less effective surfactant adsorption at the air–solution interface. The corresponding decline in maximum surface excess (${\Gamma }_{max}$) and increase in minimum area per molecule ($A_{min}$) confirm looser interfacial packing due to EG participation in the solvation layer. Plots of adhesion tension (A_T) versus surface tension (γ) exhibit negative slopes, consistent with reduced solid–liquid interfacial tension (${\Gamma }_{LG}$) and greater redistribution of surfactant molecules toward the solid–liquid interface. AOT shows stronger sensitivity to EG compared to CTAB, reflecting structural headgroup-specific adsorption behavior. Work of adhesion (W_A) measurements demonstrate enhanced wettability at higher EG concentrations, highlighting the cooperative impact of co-solvent environment and surfactant type on wetting phenomena. Full article

The oxidation of chlorophenolic compounds is essential for converting these persistent and toxic pollutants into less harmful products, thereby reducing their environmental and health impacts. In this study, a p-coumaric acid ester derivative was employed as the starting material to synthesize the corresponding phthalonitrile precursor (EnCA-CN), followed by the preparation of non-peripherally substituted Co(II) and Cu(II) phthalocyanine complexes (EnCA-Copc and EnCA-CuPc). These complexes were subsequently characterized using a range of spectroscopic techniques and designed to engage in π–π interactions with graphitic carbon nitride to form efficient photocatalytic materials. The structures of the two effective catalysts were characterized by FT-IR, SEM, and XRD analyses, after which their photocatalytic performance and recyclability in the degradation of 2-chlorophenol, 2,3-dichlorophenol, and 2,3,6-trimethylphenol were evaluated. The optimum catalyst loading for the MPc/g-C₃N₄ composites was determined to be 0.5 g/L, yielding the highest photocatalytic efficiency. The EnCA-CoPc/g-C₃N₄ catalyst achieved 90.8% product selectivity and 82.6% conversion in the oxidation of 2-chlorophenol, whereas the EnCA-CuPc/g-C₃N₄ catalyst exhibited approximately 80.0% pollutant removal. The degradation efficiencies followed the order 2-CP > 2,3-DCP > 2,3,6-TCP, with benzoquinone derivatives identified as the major oxidation products. In recyclability tests, both catalysts retained more than 50% of their activity after five cycles; EnCA-CoPc/g-C₃N₄ maintained 68% conversion in the 5th cycle, while EnCA-CuPc/g-C₃N₄ retained 60% conversion in the 4th cycle. Full article

Following the normalization of the COVID-19 pandemic, the focus of wastewater-based epidemiology (WBE) must be broadened from SARS-CoV-2 to encompass surveillance of other major infectious diseases, particularly for pathogens where conventional clinical monitoring systems exhibit inherent surveillance gaps. In this study, we conducted a continuous two-year WBE study (January 2023 to December 2024) across three high-population-density cities in Guangdong, China to establish epidemiological baselines for enteric diarrheal viruses. We analyzed monthly raw wastewater samples from major treatment plants using advanced molecular methods, including digital PCR (ddPCR) for viral load quantification and targeted high-throughput sequencing (tNGS) for genotypic analysis. Our findings revealed diverse circulation patterns among the monitored enteric viruses. Astrovirus (AstV) had the highest detection rate (100%), reflecting its broad endemic distribution, while Norovirus genogroup II (NoV GII) exhibited relatively high viral loads (median 4 × 10⁴ copies/mL) and presented explosive seasonal peaks (significant upward trend in spring.), highlighting its epidemic potential. Furthermore, distinct spatiotemporal patterns were observed, with Sapovirus showing a significant summer peak in Foshan city, contrasting with the winter/spring peaks in the other cities. The tNGS results demonstrated similar sensitivity to RT-PCR in virus detection, and sequencing analyses uncovered the co-circulation and periodic shifts in dominant viral genotypes, such as the emergence of multiple NoV and AstV lineages. This longitudinal WBE surveillance successfully established critical baseline data and demonstrated significant regional heterogeneity in viral circulation, providing essential, complementary data to inform public health strategies for preventing diarrheal outbreaks in urban settings. Full article

The essential oil (EO) of Mentha spicata L. (spearmint) exhibits pronounced biological activity, making it valuable for applications in agrochemistry as an insecticidal agent, in perfumery and cosmetics, and as a natural preservative in the food industry. However, maintaining the integrity and yield of EO during post-harvest processing and extraction remains a key technological challenge. This study aimed to enhance the vacuum-drying (VD) process of spearmint using calcium chloride as a desiccant and to optimize the conditions of supercritical CO₂ extraction (SC-CO₂), including EO separation and the evaluation of its solubility under dynamic extraction conditions. The incorporation of calcium chloride into the VD process reduced drying duration by 21.1% and processing costs by 31.0%, while increasing EO yield by 11%. A decrease in separator pressure from 70 to 10 bar during SC-CO₂ extraction resulted in nearly a threefold increase in EO yield by minimizing the loss of volatile constituents. The solubility of spearmint EO in supercritical CO₂ was successfully described by the Chrastil model and correlated with carvone solubility. The maximum total phenolic content (72.3 ± 2.2 mg gallic acid equivalent per gram) was observed at a CO₂ density of 353.91 kg/m³. The solubility of EO was studied directly using the plant matrix under dynamic conditions. Full article

In this study, the advanced oxidation system of peroxymonosulfate (PMS) was activated by molybdenite supported on biochar (Molybdenite@BC), and the degradation efficiency, influencing factors and degradation mechanism of sulfamethoxazole (SMX) were explored through experiments. Molybdenite@BC, a composite material used in the study, was prepared by pyrolysis at high temperature. The optimum pyrolysis temperature was 700 °C, and the mass ratio of molybdenite to biochar (BC) was 1:3. By changing dosage of Molybdenite@BC, pH value, initial concentration of PMS, and the types and concentration of inorganic anions, the effects of various factors on SMX degradation were systematically studied. The optimum reaction conditions of the Molybdenite@BC/PMS process were as follows: Molybdenite@BC dosage was 100 mg/L, PMS concentration was 0.2 mM, pH value was 6.9 ± 0.2, and initial SMX concentration was 6 mg/L. Under these conditions, the degradation rate of SMX was 97.87% after 60 min and 99.06% after 120 min. The material characterization analysis showed that Molybdenite@BC had a porous structure and rich active sites, which was beneficial to the degradation of pollutants. After the composite material was used, the peaks of MoO₂ and MoS₂ became weaker, which indicated that there was some loss of molybdenum from the material structure. Electron paramagnetic resonance (EPR) and radical quenching experiments revealed that Molybdenite@BC effectively catalyzed PMS to generate various reactive oxygen radicals and non-free radicals, including singlet oxygen (¹O₂), hydroxyl radical (^•OH), sulfate radical (SO₄^•−) and superoxide radical (^•O₂⁻). ¹O₂ played a leading role in the degradation of SMX, while ^•OH and SO₄^•− had little influence. The intermediate products of the degradation of SMX in Molybdenite@BC/PMS system were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS). The results showed that there were nine main intermediate products in the process of degradation, and the overall toxicity tended to decrease during the degradation of SMX. The degradation path analysis showed that with the gradual ring opening and bond breaking of SMX, small molecular compounds were generated, which were finally mineralized into H₂O, CO₂, CO₃²⁻, H₂SO₄ and other substances. The research results confirmed that the Molybdenite@BC/PMS process provided a feasible new method for the degradation of SMX in water. Full article

Background. Contributions of tumor-derived extracellular vesicles, TEX, to tumor progression and metastasis involve their crosstalk with immune cells in the tumor microenvironment. This crosstalk results in metabolic reprogramming of immune cells from anti-tumor to pro-tumor activity. Mechanistic underpinnings of the TEX entry and delivery of molecular signals responsible for metabolic reprogramming may be unique for different types of immune cells. Methods. An in vitro model of THP-1 myeloid cells co-incubated with TEX illustrates the role TEX play in polarization of macrophages to TAMs. Results. In THP-1 cells, the dominant signaling pathway of melanoma cell-derived TEX involves HSP-90/TLR2. This leads to activation of the NF-κB and MAP kinase pathways and initiates THP-1 cell polarization from M0 to M2 with strong expression of immunosuppressive PD-L1. TEX may be seen as “danger” by the myeloid cells, which utilize the pattern recognition receptors (PRR), such as PAMPs or DAMPs, for engaging the complementary ligands carried by TEX. The same melanoma TEX signaling to T cells via DAMPs induced mitochondrial stress, resulting in T-cell apoptosis. Conclusions. As the signaling receptors/ligands in TEX are determined by the tumor, it appears that the tumor equips TEX with an address recognizing specific PRRs expressed on different recipient immune cells. Thus, TEX, acting like pathogens, are equipped by the tumor to alter the context of intercellular crosstalk and impose a distinct autophagy-not-apoptosis signature in recipient THP-1 cells. The tumor might endorse TEX to promote tumor progression and metastasis by enabling them to engage the signaling system normally used by immune cells for defense against pathogens. Full article