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Background: Interleukin-1 beta (IL-1β) is a pleiotropic cancer-inflammation-linked cytokine which has been reported upregulated in many cancers. In our previous study, IL-1β was found to be one of the key node genes during oral malignant transformation, and glutaredoxin 1 (Grx1) was identified as one of the downstream genes of IL-1β in tumor microenvironment. Grx1 is ubiquitous oxidoreductase which is necessary for scavenging reactive oxygen species (ROS) and the intracellular redox balance maintenance.Methods: Tissues from different stages of mucosal malignant transformation were obtained from 4NQO-induced rat oral carcinogenesis model and human mucosa for Grx1 expression detection by immunohistochemical staining. The intracellular ROS levels and Grx1 mRNA level of oral squamous carcinoma cell CAL27 were detected after IL-1β treatment with or without pretreatment of IL-1Ra or NAC, respectively. The ROS levels were detected in Leti-si-IL-1β and Leti-si-NC CAL27 cells after IL-1β stimulation. The invasion and migration abilities of CAL27 cells were tested by transwell assay after IL-1β stimulation with or without pretreatment of IL-1Ra.Results: Grx1 expression was associated with the malignant transformation process in vivo. Exogenous IL-1β upregulated the intracellular ROS level and the expression of Grx1 in CAL27 cells, which could be counteracted by IL-1Ra. The intracellular ROS accumulation induced by exogenous IL-1β was responsible for the Grx1 upregulation. Endogenous IL-1β acted as a switch in regulating the ROS level by modulating Grx1 expression, which was involved in the invasion and migration of OSCC cells.Conclusions: IL-1β finely orchestrated the redox balance during carcinogenesis by modulating Grx1 expression. [ABSTRACT FROM AUTHOR]

Reclaimed water is an important source of irrigation and is widely used on agricultural soils throughout the world, particularly in arid and semi-arid regions. However, concerns about the potential risks of this practice are rapidly increasing because reclaimed water may contain various organic pollutants such as pharmaceuticals and personal care products (PPCPs). Trace levels of PPCPs have been found in fields irrigated with reclaimed water, and continual infusion, along with bioaccumulation properties, may result in significant bio-uptake and PPCP contamination in agricultural soils. This review attempts to summarize the literature concerning the fate and behavior of PPCPs in agricultural soils, as well as their adverse effects on soil organisms (including microorganisms and fauna), crops, and even humans via dietary consumption. Strategies and potential technologies for degrading or removing PPCPs from soils are addressed, along with the irrigation strategies and agricultural practices for minimizing PPCP transfer to crops and groundwater. Based on this review, we conclude that the agricultural risks of PPCPs associated with reclaimed water irrigation could be controlled under certain agro-ecological conditions. We suggest developing agro-ecosystem-specific practices and regulations for reclaimed water irrigation on the basis of a systematic assessment and modeling analysis of the fate, transport, accumulation, and transformation of PPCPs in soil–crop systems. [ABSTRACT FROM PUBLISHER]

This study presents a comprehensive approach to estimating annual atrazine residues in China's agricultural soils, integrating machine learning algorithms and mechanism-based models. First, machine learning was used to predict essential parameters influencing atrazine's adsorption, degradation, and dispersivity of solute transport. The results demonstrated that soil organic matter was the most important input variable for predicting adsorption and degradation; clay content was the primary variable for predicting dispersivity. The SHapley Additive exPlanations (SHAP) contribution of various soil properties on target variables were also analyzed to reveal whether each input variable has a positive, negative, or complex effect. Subsequently, these parameters inform the construction of a detailed model across 23,692 subregions of China, with a 20 km × 20 km resolution. The model considered regional variations and soil layer heterogeneity, including rainfall, soil depth-specific properties, and parameters for adsorption, degradation, and dispersivity. Utilizing the convection-dispersion equations and the Phydrus, the model simulated atrazine's transport and degradation patterns across diverse soil environments after applying 250 mL of atrazine (40%) per Chinese mu. The outcomes provided a spatially explicit distribution of atrazine residues, specifying that the arid areas have the highest residual risk, followed by the Northeast, Southwest, and Southeast. Atrazine levels may exceed national drinking water standards at 50 cm depth in Inner Mongolia, the Qinghai-Tibet Plateau, and the Jungar Basin. This study's integrative approach may also offer valuable insights and tools for evaluating residues of various pesticides and herbicides in agricultural soils. [Display omitted] • Machine learning effectively predicted adsorption, degradation, and dispersivity. • The annual fate and transport of atrazine was simulated by Phydrus. • Arid areas have the highest residual risk, followed by the Northeast China. • Atrazine levels may exceed 2 μg L−1 at 50 cm depth in some northwest regions. [ABSTRACT FROM AUTHOR]

[Display omitted] • A non-invasive imaging technique was developed for real-time bacterial observation. • Depth for maximum bacterial retention shifted with time under unsaturated flow. • Bacterial retention decreased exponentially with travel distance at lower velocity. • Bacterial retention decreased multi-exponentially with distance at higher velocity. This study investigated the transport and retention of bioluminescent Escherichia coli strain 652T7 under different pore water velocities (8.7 cm h−1 and 13.0 cm h−1) and pore water saturations (85% and 100%) utilizing a non-invasive, real-time bioluminescent imaging technique. Under saturated flow conditions, the concentrations of retained bioluminescent E. coli 652T7 decreased exponentially with distance from the source at the lower velocity but decreased non-exponentially at the higher velocity. Under unsaturated flow conditions, pore water velocity had no significant effect on bacterial breakthrough concentration; however, the concentrations of retained cells were maximal at a significant distance from the source (non-monotonic). The distance from source of the maximum concentration increased from 2.4-cm at 1.05 pore volumes to 4.3-cm at 3.15 pore volumes, indicating slow translation of bacterial down-gradient under unsaturated flow conditions. That conditions were modestly unfavorable to attachment at the solid-water interface (SWI) was indicated by deposition rate coefficients being greater (by a factor of four) for simulations versus experiments, and by significant repulsive barriers to attachment at both the SWI (260 kT) and the air–water interface (AWI, fully repulsive). The inferred slow translation under unsaturated flow conditions therefore reflects either accumulation without arrest in the secondary minimum at the SWI and/or capillary interaction at the AWI. This non-invasive bioluminescence method yielded real-time quantitative observation of bacterial distribution from source and demonstrated contrasting transport behaviors previously obtained solely via more laborious methods with limited spatio-temporal observation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bacterial mobility increased with soil depth. • Soil disturbance increased bacterial dispersion. • Intact soil structure was favorable to bacterial transport. • Soil organic matter, iron oxides, and zeta potential are key to bacterial transport. Pathogenic bacteria, widely present in septic tanks, sewage sludges, and wastewater, can move through the subsurface environment to pollute drinking water. Bacterial transport behaviors vary with soil properties and are subject to soil pore networking. In this study, we investigated the transport of Escherichia coli 652T7 through intact and disturbed soils collected from different soil depths (0−5 cm, 5−10 cm, 10−15 cm, and 15−20 cm). The results obtained under steady-state saturated flow conditions demonstrated significant influences of soil depth and soil structure on the transport of E. coli 652T7. The breakthrough percentages of E. coli 652T7 from the intact soil cores increased with soil depth from 36 % at 0−5 cm to 63 % at 5−10 cm, 83 % at 10−15 cm, and 100 % at 15−20 cm. A similar trend was observed for the breakthrough from the repacked soil cores except with lower percentages (i.e., 16 % at 0−5 cm, 49 % at 5−10 cm, 76 % at 10−15 cm, and 86 % at 15−20 cm). Such an increase with soil depth was attributed to a combined effect of decreases in soil organic matter content (from 3.84 % to 2.47 %), free iron oxides (from 142.25 mg kg−1 to 110.66 mg kg−1), and zeta potential (from −17.6 mV to −29.0 mV) with soil depth. The larger breakthrough percentages of E. coli 652T7 from the intact than the repacked soil cores are speculated due to the existence of larger macropores, lower pore connectivity density, and reduced access to attachment sites in the intact soils than in the disturbed soils. Overall, this study suggests that tillage and organic amendments might be effective measures for reducing bacterial movement in soils. [ABSTRACT FROM AUTHOR]

This study examines the effects of soil organic matter (SOM) and water content on the transport of five selected pharmaceutical and personal care products (PPCPs, ibuprofen, carbamazepine, bisphenol A, tetracycline, and ciprofloxacin) in four natural soils with different SOM contents. Batch isotherm experiment results showed that SOM effect was very significant for positively charged tetracycline and ciprofloxacin (>99% adsorption, no desorption), relatively significant for non-dissociated carbamazepine and bisphenol A (17–57% adsorption, 6–71% desorption) and insignificant for negatively charged ibuprofen (4–8% adsorption, 60–87% desorption) in the soils. Transport results showed that neither tetracycline nor ciprofloxacin moved through the saturated and unsaturated soil columns, demonstrating their very limited mobility in soils as a result of significant electrostatic attraction independent of SOM and water conditions. Overall, higher SOM content and lower water content were favorable to the retention of ibuprofen, carbamazepine and bisphenol A in the soils. Breakthrough of ibuprofen, carbamazepine and bisphenol A was 100% (both saturated and unsaturated), 94% (saturated)-97% (unsaturated) and 85% (saturated)-90% (unsaturated) in SOM-removed soils; however only 78% (saturated)-57% (unsaturated), 93% (saturated)-67% (unsaturated), 11% (saturated)-0% (unsaturated) in the SOM-high soils. The effect of water content was not significant in the SOM-removed soils. The SOM could increase the kinetic (type 2) adsorption of PPCPs at the solid-water interface (SWI), and the air phase could increase the instantaneous (type 1) adsorption of PPCPs at the air-water interface (AWI). This result suggests that lowering water content could greatly enhance the adsorption of PPCPs that had high affinities to soils and vice versa. This study provides an important implication that AWI and SWI might have a nonlinear relationship in promoting the adsorption and reducing the mobility of PPCPs under unsaturated flow conditions. • Soil desaturation and organic matter decreased the mobility of PPCPs. • The desaturation effect increased with the affinities of PPCPs to soils. • Air-water interfaces increased instantaneous adsorption of PPCPs. • Solid-water interfaces dominated kinetic adsorption of PPCPs. [ABSTRACT FROM AUTHOR]

Low-cost magnesium- and/or carbon-based materials have a great potential to remove soluble contaminants from surface and ground water. This study examined mechanisms that control the removal of nitrate, phosphate and pesticides (tricyclazole, malathion and isoprothiolane) during their transport through calcined magnesia (MgO) and corn stalk biochar. Various miscible column breakthrough experiments were carried out and morphology and crystallographic structures of reactive materials were examined. Approximately 96% (78,950 mg-NO 3 -/kg) and 48% (27,455 mg-NO 3 -/kg) of nitrate were removed from biochar and MgO columns, respectively. Chemical adsorption dominated nitrate removal during early phase (i.e., <11 PVs for biochar and <100 PVs for MgO, respectively), and microbial denitrification dominated during the following phase. 92% of the applied phosphate (6168 mg-PO 4 3-/kg) was removed in MgO column, while much less in biochar column (4%, 347 mg-PO 4 3-/kg). Mineral surface analyses confirmed that electrostatic attraction, ligand exchange, and chemical precipitation were responsible for phosphate removal. For the three pesticides, biochar exhibited larger removal capacity (1260–2778 mg/kg) than MgO (28–2193 mg/kg) due to the functional groups on biochar. The removal of pesticides based on their physico-chemical properties. Malathion had highest removal rate (98–100%), attributing to chemical sorption and bio-degradation, followed by isoprothiolane (47–79%) and tricyclazole (6–64%). • Biochar showed good performance (∼96%) for the removal of nitrate. • Denitrification dominated nitrate removal after 2.3 days (11 PVs) in biochar and 20.8 days (100 PVs) in MgO. • MgO (∼92%) exhibited higher phosphate removal capacity than that of biochar (∼4%). • Both MgO and biochar showed a good performance for malathion and isoprothiolane removal. [ABSTRACT FROM AUTHOR]

Release of antibiotics into the environment has caused ecological and human health concerns in recent years. However, little is known about their transport behaviors in chemically heterogeneous porous media. In this study, we investigated the coupled effects of surface chemistry and soil colloids on the transport of ciprofloxacin and tetracycline through sand under steady state saturated flow conditions. Both antibiotics had a much higher capacity of adsorption on soil colloids (17,500 mg/kg for ciprofloxacin and 8600 mg/kg for tetracycline) than on sand (5.11 mg/kg for ciprofloxacin and 2.80 mg/kg for tetracycline). However, ciprofloxacin adsorption increased to 8.91 mg/kg after the sand was coated with iron oxide and to 8.73 mg/kg after the sand was coated with humic acid. Tetracycline, adsorption increased to 7.99 mg/kg after sand was coated with iron oxide coated sand and to 8.35 mg/kg after the sand was coated with humic acid coated The high adsorption capacity of ciprofloxacin led to a recovery rate of <4% in the effluents of the columns containing 0%, 20% and 50% of iron oxide/humic acid coated sand. The surface coating decreased the recovery rates of tetracycline from 35.4% (in uncoated sand) to 12.0% (in column containing 50% iron oxide coated sand) and 0.010% (in column containing 50% humic acid coated sand), respectively. Once adsorbed to soil colloids, the recovery rate of ciprofloxacin increased by 26.7% in uncoated sand column, 21.1% in iron oxide coated sand column, and 32.7% in humic acid coated sand column. Similarly, the presence of the colloids increased the recovery rate of tetracycline from 13.8% to 33.2% after the sand was coated with humic acid. Colloids did not significantly influence the transport and recovery of tetracycline in the uncoated sand and iron oxide coated sand due likely to its lower adsorption affinity. Unlabelled Image • Surface chemical heterogeneity increases adsorption of antibiotics. • Colloids are significant carriers of antibiotics during transport. • Effect of colloids depends on soil surface chemistry and properties of antibiotics. [ABSTRACT FROM AUTHOR]

As emerging contaminants of global concern, nanoplastics are significantly potential carriers of hydrophobic organic compounds in aquatic and soil environment. However, little is known about the interactions between the transports of nanoplastics and organic contaminants in porous media. In this study, the cotransport of naphthalene with polystyrene nanoplastics (PSNP) in saturated sand columns as influenced by the PSNP/naphthalene ratio and ionic strength (IS) was investigated. The presence of PSNP dramatically enhanced the mobility of naphthalene at low IS (0.5 mM), but such effect was prohibited at high IS (5 mM and 50 mM). The mobility of PSNP in the sand column was higher when it was solely exist in the pore-water than that when in the presence of naphthalene, because of the charge-shielding effect. This work showed that the coexistence of PSNP and naphthalene would influence the mobility of each other in the saturated porous media, which highly related to their concentration ratio and IS levels. Image 1 • Nanoplastics enhanced the naphthalene mobility at low IS, but not at high IS. • Naphthalene decreased nanoplastics mobility because of the charge-shielding effect. • Nanoplastics breakthrough curves were well described by the two kinetic sites model. • DLVO/xDLVO forces are contributors affecting the mobility of nanoplastics. [ABSTRACT FROM AUTHOR]

This study aims to present a comprehensive study on the risks associated with the residual presence and transport of Escherichia coli (E. coli) in soil following the application of livestock manure in Chinese farmlands by integrating machine learning algorithms with mechanism-based models (Phydrus). We initially review 28 published papers to gather data on E. coli's die-off and attachment characteristics in soil. Machine learning models, including deep learning and gradient boosting machine, are employed to predict key parameters such as the die-off rate of E. coli and first-order attachment coefficient in soil. Then, Phydrus was used to simulate E. coli transport and survival in 23692 subregions in China. The model considered regional differences in E. coli residual risk and transport, influenced by soil properties, soil depths, precipitation, seasonal variations, and regional disparities. The findings indicate higher residual risks in regions such as the Northeast China, Eastern Qinghai-Tibet Plateau, and pronounced transport risks in the fringe of the Sichuan Basin fringe, the Loess Plateau, the North China Plain, the Northeast Plain, the Shigatse Basin, and the Shangri-La region. The study also demonstrates a significant reduction in both residual and transport risks one month after manure application, highlighting the importance of timing manure application and implementing region-specific standards. This research contributes to the broader understanding of pathogen behavior in agricultural soils and offers practical guidelines for managing the risks associated with manure use. This study's comprehensive method offers a potentially valuable tool for evaluating microbial contaminants in agricultural soils across the globe., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Radiotherapy (RT) can drive cancer cells to enter a state of cellular senescence in which cells can secrete senescence-associated secretory phenotype (SASP) and produce small extracellular vesicles (sEVs) to interact with cells in the tumor microenvironment (TME). Tumor-derived sEVs that are taken up by recipient cells contribute to cancer cell metabolic plasticity, resistance to anticancer therapy, and adaptation to the TME. However, how radiation-induced sEVs support oral squamous cell carcinoma (OSCC) progression remains unclear., Methods: Beta-galactosidase staining and SASP mRNA expression analysis were used to evaluate the senescence-associated activity of OSCC cells after irradiation. Nanoparticle tracking analysis was performed to identify radiation-induced sEVs. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to explore changes in the levels of proteins in radiation-induced sEVs. Cell Counting Kit-8 and colony formation assays were performed to investigate the function of radiation-induced SASP and sEVs in vitro. A xenograft tumor model was established to investigate the functions of radiation-induced sEVs and V-9302 in vivo as well as the underlying mechanisms. Bioinformatics analysis was performed to determine the relationship between glutamine metabolism and OSCC recurrence., Results: We determined that the radiation-induced SASP triggered OSCC cell proliferation. Additionally, radiation-induced sEVs exacerbated OSCC cell malignancy. LC-MS/MS and bioinformatics analyses revealed that SLC1A5, which is a cellular receptor that participates in glutamine uptake, was significantly enriched in radiation-induced sEVs. In vitro and in vivo, inhibiting SLC1A5 could block the oncogenic effects of radiation-induced sEVs in OSCC., Conclusion: Radiation-induced sEVs might promote the proliferation of unirradiated cancer cells by enhancing glutamine metabolism; this might be a novel molecular mechanism underlying radiation resistance in OSCC patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine-glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8 + T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment., (© 2024. The Author(s).)

Background: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC., Methods: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints., Discussion: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC., Trial Registration: ChiCTR1800017646., (© 2024. The Author(s).)

Mitochondria are essential organelles in balancing oxidative stress and cell death during cancer cell proliferation. Rapid tumor growth induces tremendous stress on mitochondria. The mammalian tumor necrosis factor-α-induced protein 8-likes (TIPEs) family plays critical roles in balancing cancer cell death and survival. Yet, the roles of TIPEs in HNSCC tumorigenesis and mitochondria stress maintenance is unclear. Based on an integrative analysis of public HNSCC datasets, we identified that the downregulation of TIPE3 via its promoter hypermethylation modification is the major event of TIPEs alterations during HNSCC tumorigenesis. Low expression levels of TIPE3 were correlated with high malignancy and poor clinical outcomes of HNSCC patients. Restoring TIPE3 represses HNSCC proliferation, migration, and invasion in vitro and in vivo, while silencing TIPE3 acted on an opposite way. Mechanistically, TIPE3 band to the PGAM5 and electron transport chain (ETC) complex. Restoring TIPE3 promoted PGAM5 recruiting BAX and dephosphorylating p-DRP1(Ser637), which triggered mitochondrial outer membrane permeabilization and fragmentation. Ultimately, TIPE3 induced ETC damage and oxygen consumption rate decrease, ROS accumulation, mitochondrial membrane potential depolarization, and cell apoptosis. Collectively, our work reveals that TIPE3 plays critical role in maintaining mitochondrial stress and cancer cell progression in HNSCC, which might be a potential therapeutic target for HNSCC patients., (© 2023. The Author(s).)

Objective: Oral squamous cell carcinoma (OSCC) is characterized by high recurrence and metastasis and places a heavy burden on societies worldwide. Cancer cells thrive in a changing microenvironment by reprogramming lipidomic metabolic processes to provide nutrients and energy, activate oncogenic signaling pathways, and manage redox homeostasis to avoid lipotoxicity. The mechanism by which OSCC cells maintain lipid homeostasis during malignant progression is unclear., Methods: The altered expression of fatty acid (FA) metabolism genes in OSCC, compared with that in normal tissues, and in OSCC patients with or without recurrence or metastasis were determined using public data from the TCGA and GEO databases. Immunohistochemistry was performed to examine the carboxylesterase 2 (CES2) protein level in our own cohort. CCK-8 and Transwell assays and an in vivo xenograft model were used to evaluate the biological functions of CES2. Mass spectrometry and RNA sequencing were performed to determine the lipidome and transcriptome alterations induced by CES2. Mitochondrial mass, mtDNA content, mitochondrial membrane potential, ROS levels, and oxygen consumption and apoptosis rates were evaluated to determine the effects of CES2 on mitochondrial function in OSCC., Results: CES2 was downregulated in OSCC patients, especially those with recurrence or metastasis. CES2 high OSCC patients showed better overall survival than CES2 low OSCC patients. Restoring CES2 expression reduced OSCC cell viability and suppressed their migration and invasion in vitro, and it inhibited OSCC tumor growth in vivo. CES2 reprogrammed lipid metabolism in OSCC cells by hydrolyzing neutral lipid diacylglycerols (DGs) to release free fatty acids and reduce the membrane structure lipid phospholipids (PLs) synthesis. Free FAs were converted to acyl-carnitines (CARs) and transferred to mitochondria for oxidation, which induced reactive oxygen species (ROS) accumulation, mitochondrial damage, and apoptosis activation. Furthermore, the reduction in signaling lipids, e.g., DGs, PLs and substrates, suppressed PI3K/AKT/MYC signaling pathways. Restoring MYC rescued the diminished cell viability, suppressed migratory and invasive abilities, damaged mitochondria and reduced apoptosis rate induced by CES2., Conclusions: We demonstrated that CES2 downregulation plays an important role in OSCC by maintaining lipid homeostasis and reducing lipotoxicity during tumor progression and may provide a potential therapeutic target for OSCC., Competing Interests: Conflict of Interest None declared., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Although obesity has been associated with an increased risk and aggressiveness of many types of carcinoma, whether it promotes squamous cell carcinoma remains unclear. To reveal the role of obesity in oral squamous cell carcinoma (OSCC) initiation and development, we used 4NQO-induced OSCC model mice to examine the impact of dietary obesity on carcinogenesis. The results showed that high-fat diet (HFD)-induced obesity significantly promoted the incidence of OSCC and altered the local immune microenvironment with the expansion of CD11b + Gr1 + myeloid-derived suppressor cells (MDSCs). The underlying mechanism that induced an immunosuppressive local microenvironment in obesity was the recruitment of MDSCs through the CCL9/CCR1 axis and enhancement of MDSC immunosuppressive function via intracellular fatty acid uptake. Furthermore, clinical samples verified the increase in infiltrated CD33 + (a marker of human MDSCs) cells in obese OSCC patients, and data from the TCGA dataset confirmed that CD33 expression was positively correlated with local adipocytes in OSCC. Survival analysis showed that enrichment of adipocytes and high expression of CD33 were associated with poor prognosis in OSCC patients. Strikingly, depletion of MDSCs significantly ameliorated HFD-promoted carcinogenesis in 4NQO-induced model mice. These findings indicate that obesity is also an important risk factor for OSCC, and cancer immunotherapy, especially targeting MDSCs, may exhibit greater antitumor efficacy in obese patients., (© 2021. The Author(s).)

Radiotherapeutic resistance is a major obstacle for the effective treatment of colorectal cancer (CRC). MicroRNAs (miRNAs) play a critical role in chemoresistance and radioresistance. Here, we aimed to investigate whether miR-590-3p participates in the radioresistance of CRC. High expression of miR-590-3p and low expression of CLCA4 were found in both CRC tissues and cell lines. CLCA4 was indicated to be a target gene of miR-590-3p. CAF-derived exosomes were extracted and co-cultured with CRC cells, which were then exposed to radiation. CRC cells were transfected with plasmids and injected into nude mice to detect the in vivo effect of CAF-derived exosomes. Treatment with CAF-derived exosomes decreased the sensitivity of CRC cells to radiation. CAF-derived exosomes overexpressing miR-590-3p increased cell survival and the ratio of p-PI3K/PI3K and p-AKT/AKT while lowering the expressions of cleaved-PARP, cleaved-caspase 3, and γH2AX in cells. Furthermore, in vivo experimental results confirmed that CAF-derived exosomal miR-590-3p stimulated tumor growth in mice following radiotherapy. Our results demonstrate that miR-590-3p delivery via exosomes derived from CAFs enhances radioresistance in CRC through the positive regulation of the CLCA4-dependent PI3K/Akt signaling pathway., (© 2021 The Authors.)