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Background: Based on the bioinformatics prediction, this study investigates the correlation between aberrant transcription factor Frizzled 5 (FZD5) expression and the establishment of non-small cell lung cancer (NSCLC). Methods: A mouse model with regard to primary NSCLC was encouraged by intraperitoneal injection of urethane. Lentivirus-based FZD5 silencing was then administrated to examine its role in tumorigenesis in the mouse lung. Silencing of FZD5 was induced in two NSCLC cell lines to examine its function in the malignant behavior pertaining to cells in vitro. Quantitative methylation-specific PCR was employed to assess the DNA methylation level within the NSCLC cells. DNA methyltransferases (DNMTs) that administer FZD5 were assessed by chromatin immunoprecipitation assay. Consequently, overexpression of DNMT3A was introduced in mice and NSCLC cells to verify its regulation on FZD and its biological roles in NSCLC development. Results: In NSCLC, FZD5 expression is elevated, and its knockdown reduced tumor incidence rate in the urethane-challenged mice. The FZD5 silencing also inhibited proliferation, migration, as well as invasion with regard to Calu-3 and NCI–H1299 cells in vitro. The aberrant upregulation with regard to FZD5 in NSCLC was due to at least partly by reduced promoter methylation level. DNMT3A, which bound to FZD5 promoter to suppress its transcription, was poorly expressed in NSCLC. Artificial upregulation of DNMT3A suppressed urethane-induced lung carcinogenesis in mice and suppressed the malignant phenotype pertaining to NSCLC cells in vitro. Conclusion: This research demonstrates that the lack of DNA methylation level-induced activation of FZD5 is correlated with NSCLC's onset and progression.

Nowadays, global warming and fossil fuel depletion are two unsolved problems. Research is underway on renewable energies, which are new energy sources. This study aims to improve the performance of microbial fuel cells (MFCs), a renewable energy generation method. Urethane was used as the electrode material for MFC. Urethane is an excellent material suitable for use as MFC electrodes because of its durability, porosity, and other properties. However, urethane itself is not conducive. This study used conductive urethane, which is coated with activated carbon powder, as the electrode material. This material is used in deodorizing filters, air conditioning filters, and air cleaner filters. To improve the performance of MFC, carbon nanotubes and activated carbon powder were added to the urethane electrodes. PTFE was also used to improve cathodic function. PTFE is used as a binder in many microbial fuel cells. The performance of the electrodes was compared. The analysis included power density measurements and discharge characteristics. It was confirmed that the use of PTFE improves the power density by a factor of two or more. The MFC generated a maximum power density of 28.27 μW/cm2. SEM image analysis of the electrode after the experiment confirmed that PTFE could reduce the adhesion of microorganisms on the cathode surface. These results imply that the use of conductive urethanes as electrodes in MFCs is effective. The addition of carbon nanotubes, activated carbon powder, and PTFE has enabled the use of urethane as an electrode material for microbial fuel cells.

We compared the effects of two anesthetics, isoflurane and urethane on bladder function in rats. Arterial pressure, cystometry (CMG), and rhythmic bladder contractions (RBCs) under isovolumetric conditions, mechanosensitive single-unit afferent activities (SAAs), bladder compliance and bladder myogenic microcontractions (bladder microcontractions), and bladder blood flow, and blood and urine biochemical tests were investigated in isoflurane- or urethane-anesthetized female rats. In results of the CMG, 3/8 rats in the isoflurane group and 7/7 rats in the urethane group showed constant bladder neurogenic contractions for micturition, whereas 5/8 rats in the isoflurane group showed unstable contractions or overflow incontinence. The RBCs appeared in the urethane group but not in the isoflurane group, and SAAs in both the Aδ- and C-fibers, bladder compliance, and bladder microcontractions in the isoflurane group were higher than those in the urethane group during bladder distension. The blood biochemical test showed that the serum calcium level was higher in the isoflurane group. The mean arterial pressure and bladder blood flow were not different between the groups. The results showed that urethane anesthesia more retains bladder neurogenic contractions for micturition compared to isoflurane. In contrast, isoflurane anesthesia more retains bladder function during the storage phase compared to urethane.

Elastomeric biocomposites based on poly(glycerol adipate urethane) and hydroxyapatite were fabricated for tissue regeneration. The poly(glycerol adipate urethane) (PGAU) elastomeric composite matrices were obtained by chemical crosslinking of the poly(glycerol adipate) prepolymer (pPGA) with diisocyanate derivative of L-lysine. Two series of composites varying in the amount of L-lysine diisocyanate ethyl ester (LDI) used as a crosslinking agent were manufactured. As a ceramic filler both unmodified and L-lysine surface-modified hydroxyapatite (HAP) particles were used. The novelty of our research consists in the manufactured elastomeric materials and characterization of their linear viscoelastic (LVE) properties. The LVE properties of the composites were investigated by means of dynamic thermomechanical analysis. Frequency sweep and amplitude sweep measurements were performed in shear mode. The influence of the crosslinking agent (LDI) amount, HAP content and surface modification of HAP on the LVE properties of the composites was determined based on the analysis of the master curves of storage (G') and loss (G″) moduli and of tanδ of the composites. Depending on the amount of LDI, HAP and surface modification, the materials differ in the values of rubber elasticity plateau modulus (G 0 ) and G' and G″ determined at selected shear frequencies and at the glassy state. G 0 ranges from 278 kPa to 3.98 MPa, G' in the glassy state is within the range of 219 MPa-459 MPa. The G 0 values of the PGAU-based composites are within the stiffness range of soft tissue. In view of the choice of HAP as the ceramic component and the G 0 values, elastomeric composites have the potential to be used as filling materials in small bone defects (due to their mechanical similarity to osteoid) as well as materials for cartilage tissue regeneration., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lignin was functionalised by crosslinking with hexamethylene diisocyanate (HDI) through the heterogenous reaction in the solvent dimethyl sulfoxide for preferential improvement in the mechanical properties of composites. The successful synthesis of lignin modified with HDI was confirmed by the instrumental analyses, e.g., FTIR, XPS, and FESEM. The incorporation of optimum crosslinked lignin in polylactic acid (PLA) matrix was systematically evaluated on the basis of their thermal stability, mechanical property, glass transition temperature (T g ), water contact angle, water absorption, and water permeability. The results displayed that incorporation of fillers had prominent effects on tensile tear strength, which could improve tensile strength up to 231 % and elongation at break up to 53 % due to the good interface compatibility between PLA and modified lignin. Further, with the inclusion of fillers, PLA composites exhibited higher crystallinity in comparison to neat PLA., 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 © 2023. Published by Elsevier B.V.)

Seizures can be evident within minutes of exposure to an organophosphorus (OP) agent and often progress to status epilepticus (SE) resulting in a high mortality if left untreated. Effective medical countermeasures are necessary to sustain patients suffering from OP poisoning and to mitigate the ensuing brain injury. Here, the hypothesis was tested that a single subanesthetic dose of urethane prevents neuropathology measured 24 h following diisopropylfluorophosphate (DFP)-induced SE. Adult Sprague-Dawley rats were injected with DFP to induce SE. During SE rats displayed increased neuronal activity in the hippocampus and an upregulation of immediate early genes as well as pro-inflammatory mediators. In additional experiments rats were administered diazepam (10 mg/kg, ip) or urethane (0.8 g/kg, sc) 1 h after DFP-induced SE and compared to rats that experienced uninterrupted SE. Cortical electroencephalography (EEG) and power analysis strengthen the conclusion that urethane effectively terminates SE and prevents the overnight return of seizure activity. Neurodegeneration in limbic brain regions and the seizure-induced upregulation of key inflammatory mediators present 24 h after DFP-induced SE were strongly attenuated by administration of urethane. A trivial explanation for these beneficial effects, that urethane simply reactivates acetylcholinesterase, has been ruled out. These findings indicate that, by contrast to rats administered diazepam or rats that experience uninterrupted SE, the early neuropathology after SE is prevented by subanesthetic urethane, which terminates rather than interrupts, SE.

The reaction mechanism of the urethane formation for both aliphatic and aromatic isocyanates in the presence of organotin dicarboxylate as a catalyst is investigated theoretically and experimentally. Modelling on a dispersion corrected DFT level of theory (B3LYP-D3) shows that an alkoxide complex is formed between organotin dicarboxylate and alcohol. This complex is the dominant catalyst for the urethane formation reaction. In this study, the interaction between the alkoxide complex and isocyanate through N-coordination is considered. By using thermochemical data, it is possible to show that aliphatic isocyanates can be more sensitive to the carboxylic ligand content of the organotin compound as a catalyst in urethane formation in non-polar solvents compared to aromatic isocyanates. The interactions of carboxylic acid, which is formed as an intermediate in the catalysis process, with isocyanate and the effects on the catalytic process are also discussed.

The homeostasis of the gut microbiota and circadian rhythm is critical to host health, and both are inextricably intertwined with lung cancer. Although time-restricted feeding (TRF) can maintain circadian synchronization and improve metabolic disorders, the effects of TRF on the fecal microbiome, metabolome and their diurnal oscillations in lung cancer have not been discussed. We performed 16S rRNA sequencing and untargeted metabonomic sequencing of the feces prepared from models of tumor-bearing BALB/c nude mice and urethane-induced lung cancer. We demonstrated for the first time that TRF significantly delayed the growth of lung tumors. Moreover, TRF altered the abundances of the fecal microbiome, metabolome and circadian clocks, as well as their rhythmicity, in lung cancer models of tumor-bearing BALB/c nude mice and/or urethane-induced lung cancer C57BL/6J mice. The results of fecal microbiota transplantation proved that the antitumor effects of TRF occur by regulating the fecal microbiota. Notably, Lactobacillus and Bacillus were increased upon TRF and were correlated with most differential metabolites. Pathway enrichment analysis of metabolites revealed that TRF mainly affected immune and inflammatory processes, which might further explain how TRF exerted its anticancer benefits. These findings underscore the possibility that the fecal microbiome/metabolome regulates lung cancer following a TRF paradigm., 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 © 2023. Published by Elsevier Inc.)

Bisphthalamic acids were prepared by reaction of maleic anhydride and aromatic diamines. Novel poly(ester-amide)s (PEAs) were prepared by reaction of DGEBF with bisphthalamic acids. Acrylation of PEAs was carried out using acryloyl chloride; products are called acrylated poly(ester-amide)s (APEAs). Epoxy resin based unsaturated poly(ester-amide) resins (UPEAs) can be prepared by many methods but here these were prepared by reported method. These UPEAs were then treated with acryloyl chloride to afford acrylated UPEAs resin (i.e. AUPEAs). Interpenetrating networks of equal proportional urethane modified poly(ester-amide) and acrylated poly(ester-amide) and vinyl ester of biaphenol c (VE) resin were prepared. Urethane modified APEAs and AUPEAs were characterized by elemental analysis, molecular weight was determined by vapor pressure osmometer and by IR spectral study and by thermogravimetry. Based on DSC data in situ glass reinforced composites of the resultant blends have been prepared and characterized for mechanical, electrical and chemical properties. Unreinforced blends were characterized by thermogravimetry (TGA).

Lung carcinoma is one of the most prevalent and deadly neoplasia worldwide. Numerous synthetic medications have been used in the treatment of cancer. However, there are several drawbacks, such as side effects and inefficiency. The current study focused on the potential anti-cancer effectiveness of tangeretin, an antioxidant flavonoid, on lung cancer induced experimentally in BALB/c mice and explored the involvement of NF-κB/ICAM-1, JAK/STAT-3, and caspase-3 signaling in its anti-cancer effect. BALB/c mice were injected with urethane (1.5 mg/kg) twice; on the first day and on the 60 th day of the experiment, then treated with 200 mg/kg tangeretin orally once daily for the last 4 weeks of the experiment. Compared with urethane group, tangeretin normalized oxidative stress markers; MDA, GSH, and SOD activity. Moreover, it had an anti-inflammatory effect by decreasing lung MPO activity, ICAM-1, IL-6, NF-қB, and TNF-α expressions. Interestingly, tangeretin decreased cancer metastasis by reducing p-JAK, JAK, p-STAT-3, and STAT-3 protein expression levels. Furthermore, it increased the apoptotic marker, caspase-3, indicating enhanced apoptosis of cancer cells. Finally, histopathology confirmed the anti-cancer effect of tangeretin. In conclusion, tangeretin could have a promising effect in counteracting lung cancer via modulation of NF-κB/ICAM-1, JAK/STAT-3, and caspase-3 signaling., 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 © 2023 Elsevier Inc. All rights reserved.)

This study investigated the effect of preheating an elastomeric urethane monomer (Exothane-24) experimental resin composite on its physicochemical properties. Two resin matrices were formulated: (a) 50 wt% Bisphenol-glycidyl methacrylate (Bis-GMA) and 50 wt% triethylene glycol dimethacrylate (TEGDMA); and (b) 20 wt% Exothane-24, 40 wt% Bis-GMA and 40 wt% TEGDMA. A photoinitiator system (0.25 wt% camphorquinone and 0.50 wt% ethyl-4-dimethylamino benzoate) and 65 wt% of the inorganic filler (20 wt% 0.05 μm silica and 80 wt% 0.7 μm BaBSiO 2 glass) were added to both matrices. These formulations were then assigned to four groups: Exothane-24 (E); Exothane-24 plus preheating (EH); no Exothane-24 (NE); and no Exothane-24 plus preheating (NEH). NEH and EH were preheated at 69 °C. The dependent variables were as follows: film thickness (FT); polymerization shrinkage stress (PSS); gap width (GW); maximum rate of polymerization (Rp max ); and degree of conversion (DC). Data were statistically analyzed by two-way ANOVA and Tukey's test (α = 0.05). Preheating reduced FT for both composites. PSS and GW were significantly lower for EH, when compared with E. The DC for EH and NEH and the Rp max for EH increased significantly. Preheating improved most of the physicochemical properties (FT, PSS, GW, and DC) of the experimental resin composite containing Exothane-24., 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 © 2023 Elsevier Ltd. All rights reserved.)

Lung cancer progresses without obvious symptoms and is detected in most patients at late stages, causing a high rate of mortality. Avocado peels (AVP) were thought to be biowaste, but they have antioxidant and anticancer properties in vitro. Chitosan nanoparticles (Cs-NPs) were loaded with various plant extracts, increasing their in vitro and in vivo anticancer activities. Our goal was to load AVP onto Cs-NPs and determine the role of AVP-extract or AVP-loaded Cs-NPs in controlling the progression of lung cancer caused by urethane toxicity. The AVP-loaded chitosan nano-combination (Cs@AVP NC) was synthesized and characterized. Our in vitro results show that Cs@AVP NC has higher anticancer activity than AVP against three human cancer cell lines. The in vivo study proved the activation of apoptosis in lung cancer cells with the Cs@AVP NC oral treatment more than the AVP treatment. Additionally, Cs@AVP NC-treated animals showed significantly higher p53 and Bax-expression levels and lower NF-κB p65 levels in their lung tissues than in positive control animals. In conclusion, our study demonstrated the superior anticancer potency of Cs@AVP NC over AVP extract and its ability to inhibit lung cancer proliferation. Therefore, oral consumption of Cs@AVP NC might be a promising treatment for lung cancer., Competing Interests: Declaration of competing interest There are no conflicts of interest associated with this research publication, according to the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In the present study, the feasibility of applying highresolution microtomography (micro-CT) for the detection of lung tumors was investigated in live mice at an early and more advanced stage of tumor development. The chest area of anesthesized mice was scanned by X-ray micro-CT. In mice with a minor and heavy tumor load, micro-CT proved to be a fast and noninvasive imaging device for the detection of lung tumors. After validation of the CT data by histologic sectioning, it was shown that the majority of tumors could be distinguished in the reconstructed virtual slices obtained by micro-CT. The data from micro-CT were also confirmed by visual inspection of the inflated and excised lungs postmortem. In vivo micro-CT opens broad perspectives for imaging tumor development and its progression in a noninvasive way. Micro-CT also allows for longitudinal evaluation of the treatment of lung cancer by drugs.

For environmental preservation, it is crucial to effectively remove organic waste from water. Several approaches have been put forth, but photocatalysis stands out as a quick and effective solution. In this study, some hybrid polymeric structures that were created by photopolymerizing cellulose acetate/castor oil urethane methacrylates with embedded CeO 2 nanoparticles (NPs) and in situ photogenerated noble metal nanoparticles (Ag, Au, Pd) are characterized, and photochemically thoroughly evaluated. The effective modification of cellulose acetate with urethane methacrylate sequences and the degree of functionalization were first observed using 1 H NMR and FTIR spectra. Additionally, scanning and transmission electron microscopy, X-ray diffraction, FT-IR and UV-visible spectroscopy were utilized to analyse the resultant nanocomposites. The homogeneous dispersion of CeO 2 NPs (10-40 nm) into an organic matrix with the suitable functionalities, namely urethane and hydroxyl groups, favour the interfacial charge transfer reducing the E g up to 2.85 eV. Moreover, noble metal nanoparticles (5-15 nm), such as Ag, Au and Pd introduction in nanocomposites, significantly lowered the E g : 2.1 eV for CeAg samples, 1.7 eV for CeAu films and 1.5 eV for CePd films, respectively. This opens up new avenues for the creation of flexible cellulose-based photocatalysts that are active in visible light., 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 © 2022 Elsevier B.V. All rights reserved.)

The medial preoptic area (mPOA) undergoes through neuroanatomical changes across the postpartum period, during which its neurons play a critical role in the regulation of maternal behavior. In addition, this area is also crucial for sleep-wake regulation. We have previously shown that hypocretins (HCRT) within the mPOA facilitate active maternal behaviors in postpartum rats, while the blockade of endogenous HCRT in this area promotes nursing and sleep. To explore the mechanisms behind these HCRT actions, we aimed to evaluate the effects of juxta-cellular HCRT-1 administration on mPOA neurons in urethane-anesthetized postpartum and virgin female rats. We recorded mPOA single units and the electroencephalogram (EEG) and applied HCRT-1 juxta-cellular by pressure pulses. Our main results show that the electrophysiological characteristics of the mPOA neurons and their relationship with the EEG of postpartum rats did not differ from virgin rats. Additionally, neurons that respond to HCRT-1 had a slower firing rate than those that did not. In addition, administration of HCRT increased the activity in one group of neurons while decreasing it in another, both in postpartum and virgin rats. This study suggests that the mechanisms by which HCRT modulate functions controlled by the mPOA involve different cell populations., (Copyright © 2022 Japan Neuroscience Society and Elsevier Ltd. All rights reserved.)

Solid dispersions are one of methods for solubilizing water-insoluble drugs. To enhance the bioavailability, maintenance of the supersaturated state and absorption of the dissolved drug in the gastrointestinal tract are important. We designed and synthesized amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers as carriers for solid dispersions and evaluated the dissolution behavior in test solutions with different pH and additives. Solid dispersion of troglitazone with amphiphilic MPC copolymers having both aromatic rings and urethane bonds in the side chains showed rapid dissolution and excellent supersaturation maintenance. It was indicated that the balance between the interactions with drug molecules and the water affinity of the polymer should be considered when carriers for solid dispersions are designed. In addition, cell membrane permeability of the solid dispersion with the amphiphilic MPC copolymer was evaluated by the Dissolution / Permeation system, which consists of two liquid chambers and a monolayer of epithelial cells that mimics the intestinal dissolution and permeation process. Further, blood concentration of the drug when solid dispersions were orally administered in mice was also evaluated. The cell membrane permeability and oral absorbability were significantly improved, compared to the solid dispersions with poly(N-vinylpyrrolidone) and suspension or solution of crystalline troglitazone., 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 © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

There is still a great challenge of on-site and rapid detection for ethyl carbamate (EC) in liquor. Herein, the aptamer (EC1) against EC was firstly screened by Capture-SELEX strategy, and its affinity and binding sites for EC were further investigated by fluorescence assay and molecular docking. Under the premise of retaining the structural features, the obtained aptamer was further truncated into a short sequence (named EC1-34), which has the dissociation constant of 17.97 ± 0.98 nM for EC. Subsequently, a visible, rapid, and cost-effective test strip was firstly designed for EC detection in liquor, in which the cationic polymer was used to efficiently capture the recognition probe conjugated with EC1-34 aptamer and gold nanoparticles (AuNPs). The minimum detection limit of the test strip is calculated as 2.14 μg⋅L -1 . The rapid test strip can be widely used for EC detection in liquor due to the advantages of high stability, convenience and selectivity., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Temporal patterns of stimulation represent a novel dimension for improving the efficacy of spinal cord stimulation to treat chronic neuropathic pain., Objective: We hypothesized that nonregular temporal patterns of stimulation designed using a computational model would be superior to conventional stimulation at constant frequencies or completely random patterns of stimulation., Methods: Using a computational model of the dorsal horn network and an optimization algorithm based on biological evolution, we designed an optimized pattern of spinal cord stimulation with comparable efficacy and increased efficiency relative to constant frequency (CF) stimulation. We evaluated the effect of different temporal patterns on individual neurons recorded in the dorsal horn of urethane-anesthetized rats., Results: The optimized pattern and 50 Hz CF stimulation produced greater inhibition of spontaneously firing neurons recorded in vivo than random 50 Hz stimulation or a pattern designed intentionally with poor fitness. Spinal Cord Stimulation (SCS) led to significant changes in the firing patterns of recorded units, and stimulation patterns that generated significant inhibition also tended to reduce entropy and regularize the firing patterns of units, suggesting that patterns of dorsal horn neuron activity may be important for pain perception in addition to the firing rate., Conclusions: These results demonstrate that the computational model can be used as a tool for optimizing stimulation parameters and suggest that optimized temporal patterns may increase the efficacy of spinal cord stimulation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John E Gilbert is an inventor on intellectual property on temporal patterns of spinal cord stimulation, owned by Duke University, for which he receives royalty payments. Tianhe C. Zhang is an inventor on intellectual property on temporal patterns of spinal cord stimulation, owned by Duke University, for which he receives royalty payments. Tianhe Zhang is a full-time employee of Boston Scientific Neuromodulation, and Tianhe Zhang owns shares of Boston Scientific stock. Rosana Esteller is an employee of Boston Scientific and holds stocks with this company and also has stocks with NeuroPace, Inc. Warren M Grill is an inventor on intellectual property on temporal patterns of spinal cord stimulation, owned by Duke University, for which he receives royalty payments. Warren M Grill is Principal Investigator on Research Grants to Duke University sponsored by Boston Scientific. Warren M Grill serves as a Paid Consultant for Boston Scientific., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Talus implants can be utilized in cases of talus avascular necrosis and has been regarded as a promising treatment method. However, existing implants are made of stiff materials that directly oppose natural cartilage. The risk of long-term cartilage wear and bone fracture from the interaction between the cartilage and stiff implant surfaces has been documented in post-hemiarthroplasty of the hip, knee and ankle joints. The aim is to explore the effects of adding a layer of compliant material (polycarbonate-urethane; PCU) over a stiff material (cobalt chromium) in talus implants. To do so, we obtained initial ankle geometry from four cadaveric subjects in neutral standing to create the finite element models. We simulated seven models for each subject: three different types of talus implants, each coated with and without PCU, and a biological model. In total, we constructed 28 finite element models. By comparing the contact characteristics of the implant models with their respective biological model counterparts, our results showed that PCU coated implants have comparable contact area and contact pressure to the biological models, whereas stiff material implants without the PCU coating all have relatively higher contact pressure and smaller contact areas. These results confirmed that adding a layer of compliant material coating reduces the contact pressure and increases the contact area which in turn reduces the risk of cartilage wear and bone fracture. The results also suggest that there can be clinical benefits of adding a layer of compliant material coating on existing stiff material implants, and can provide valuable information towards the design of more biofidelic implants in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abstract: Ethyl carbamate (EC) is a process contaminant that can be formed as a by-product during fermentation and processing of foods and beverages. Elevated EC concentrations are primarily associated with distilled spirits, but this compound has also been found at lower concentrations in foods and beverages, including breads, soy sauce, and wine. Evidence from animal studies suggests that EC is a probable human carcinogen. Consequently, several governmental institutions have established allowable limits for EC in the food supply. This review includes EC formation mechanisms, occurrence of EC in the food supply, and EC dietary exposure assessments. Current analytical methods used to detect EC will be covered, in addition to emerging technologies, such as nanosensors and surface-enhanced Raman spectroscopy. Various mitigation methods have been used to maintain EC concentrations below allowable limits, including distillation, enzymatic treatments, and genetic engineering of yeast. More research in this field is needed to refine mitigation strategies and develop methods to rapidly detect EC in the food supply., (Published 2021 by the International Association for Food Protection. Not subject to U.S. Copyright.)

Improving wound healing by developing innovative dressing materials has been an important focus over the past few years in the biomedical field. In this regard, the current study focuses on developing new dressings based on acrylate-endcapped urethane-based polymers (AUPs). The materials have been processed into films and electrospun mats. Exudate uptake capacity, mechanical properties and fiber morphology were evaluated herein. The results showed superior uptake capacity of both films and mats when compared to Aquacel®Ag, Exufiber® and Help®. Addition of a high molar mass poly(ethylene glycol) to the AUP polymers benefits both the film and electrospun dressings in terms of flexibility and elongation. An in vivo study was conducted to assess the wound healing properties of these dressings on an acute wound model induced to rats. A macroscopic evaluation indicated that wound contraction and wound fraction percentages were improved significantly in case of the AUP-materials when compared to both the positive (Aquacel®Ag) and negative (Exufiber® and Help®) controls. A histopathological assay, to underline the changes noticed on a macroscopical level, was also performed. The data obtained proved that the developed dressings are beneficial towards tissue regeneration and accelerated wound healing. These findings offer a practical yet adequate strategy for the fabrication of acrylate-endcapped urethane-based materials for wound healing applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A strategy to enhance drug effectiveness while minimizing controversial effects consists in exploiting host-guest interactions. Moreover, these phenomena can induce the self-assembly of physical hydrogels as effective tools to treat various pathologies (e.g., chronic wounds or cancer). Here, two Poloxamers®/Pluronics® (P407/F127 and P188/F68) were utilized to synthesize various LEGO-like poly(ether urethane)s (PEUs) to develop a library of tunable and injectable supramolecular hydrogels for drug delivery. Three PEUs were synthesized by chain extending Poloxamer/Pluronic with 1,6-cyclohexanedimethanol or N-Boc serinol. Other two amino-functionalized and highly responsive polymers were obtained thorough Boc-group cleavage. For hydrogel design, the spontaneous self-assembly of the poly(ethylene oxide) domains of PEUs with α-cyclodextrins was exploited to form poly(pseudo)rotaxanes (PPRs). PPR-derived channel-like crystals were characterized by X-Ray powder diffraction, Infra-Red and Proton Nuclear Magnetic Resonance spectroscopies. Cytocompatible hydrogel formulations were designed at PEU concentrations between 1% and 5% w/v and α-cyclodextrin at 10% w/v. Supramolecular gels showed good mechanical performances (storage modulus up to 20 kPa) coupled with marked thixotropic and self-healing properties (mechanical recovery over 80% within 30 s after cyclic rupture) as assessed through rheology. Hydrogels exhibited stability and high responsiveness in watery environment up to 5 days: the release of less stable components as suitable drug carriers was coupled with high swelling (doubling the content of fluids with respect to their dry mass) and shape retention. Curcumin was encapsulated into the hydrogels at high concentration (80 μg ml -1 ) through its complexation with α-cyclodextrins and delivery tests showed controllable and progressive release profiles up to four days., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Traditional enzyme-linked immunosorbent assay (t-ELISA) method suffers from its relatively low sensitivity or accuracy in the detection of trace level of analyte in complicated samples. In this work, to extend the application of ELISA in practical samples, a newly electrochemical immunoassay (ECIA) was developed based on an enzyme-induced Cu 2+ /Cu + conversion for the determination of ethyl carbamate (EC). Wherein, three rounds of signal transformation-the catalysis of ALP enzyme, the conversion of Cu 2+ /Cu + and signal output of square wave voltammetry (SWV), can be realized to obtain higher sensitivity as compared to t-ELISA. The ECIA method combines the advantages of electrochemistry and ELISA, behaving superior detection performance, such as good selectivity, high sensitivity, and low background signal. For the wine samples, the method showed a linear detection range from 2.5 nM to 2.5 × 10 4  nM with a limit of detection of 2.28 nM (S/N = 3), which reveals that the ECIA sensor is a promising platform for the detection of trace level of EC in practical samples., 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 © 2021 Elsevier B.V. All rights reserved.)

Ethyl carbamate is a group of 2A carcinogen ubiquitously existed in fermented foods. The monitoring of its residues was important for evaluating the potential risk to human beings. Immunoassays with good accuracy and simplicity are great analytical tools for small molecule contaminants. However, it is typically confined in a competitive mode for small molecules with drawback of the sensitivity curbing. In this work, three different phages displayed peptides with capability of identifying the xanthyl ethyl carbamate immunocomplex were isolated from phage library. The binding mechanism of peptides and immunocomplex was studied by computer-assisted simulation. Results indicated that the xanthydrol group of xanthyl ethyl carbamate and the Asn-32 and Asn-92 residues of the antibody light chain were mainly responsible for binding. Simultaneously, a sensitive non-competitive immunoassay for detecting ethyl carbamate in wine samples was developed. The established method exhibited a limit of detection of 5.4 ng/mL and a linear range from 8.7 ng/mL to 32 ng/mL for wine samples. In comparison with the conventional competitive immunoassay, the sensitivity of the proposed non-competitive immunoassay was improved by 17-fold. The results of the immunoassay were validated by a standard ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry, which illustrated good reliability of the proposed assay., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Biodegradable strain sensors able to undergo controlled degradation following implantation have recently received significant interest as novel approaches to detect pathological tissue swelling or non-physiological stresses. In this study, the physicomechanical, electrochemical and active pressure sensing behavior of an electrically conductive and biodegradable poly(glycerol sebacate urethane) (PGSU) composite, reinforced with poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) functionalized carbon nanotubes (CNTs), was evaluated in vitro. Analysis of these PGSU-CNTs composites demonstrated that the incorporation of functionalized CNTs into a biodegradable elastomer resulted in enhanced mechanical strength, conductivity and tailored matrix biodegradation. PGSU-CNT composites were subsequently formulated into flexible and active pressure sensors which demonstrated optimal sensitivity to applied 1% uniaxial tensile strains. Finally, cytocompatibility analysis a with primary neural culture confirmed that PGSU-CNT composites exhibited low cytotoxicity, and supported neuron adhesion, viability, and proliferation in vitro., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Acyclovir is a poorly permeable, short half-life drug with poor colonic absorption, and current conventional controlled release formulations are unable to decrease the frequency of administration. We designed acyclovir dosage forms to be administered less frequently by being retained in the stomach and releasing drug over an extended duration. We developed a conventional modified-release matrix tablet to sustain the release of acyclovir and surrounded it with a hydrophilic poly(urethane) layer. When hydrated, the porous poly(urethane) swells to a size near or beyond that of the relaxed pylorus diameter and does not affect drug release rate. We demonstrated that the formulation is retained in the stomach for extended durations as it slowly releases drug, allowing for similar area under the curve but delayed t max relative to a nongastroretentive control tablet. Unlike many other gastroretentive formulations, this dosage form design decouples drug release rate from gastric retention time, allowing them to be modulated independently. It also effectively retains in the stomach regardless of the prandial state, differentiating from other approaches. Our direct observation of excised rat stomachs allowed for a rigorous assessment of the impact of polymer swelling extent and the prandial state on both the dosage form integrity and retention time., (Copyright © 2020. Published by Elsevier Inc.)

The behavioral state of animals is essential information for functional recordings of neuronal activity; practically, the exact timing when animals recover from anesthesia is important information. Recordings of cortical local field potentials and dorsal neck electromyograms (EMGs), a widely used method to identify behavioral states, requires at least two recording electrodes, one of which also requires a craniotomy procedure. In the present study, recordings of whisker EMGs alone are sufficient to detect the state switch from anesthesia to awakening in head-fixed mice. This method uses a single electrode and thus is technically simple and demands a less physical burden to animals. Moreover, whisker EMGs recorded under anesthesia reflect respiratory rhythms., (Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

The aim of this study was to synthesize and characterize new multifunctional-urethane-methacrylate monomers to be used as the organic matrix in restorative dental composites, and evaluate the main physical-chemical properties of the resulting material. Bis-GMA (bisphenol-A-diglycidylmethacrylate) and GDMA (glycerol dimethacrylate) were modified by reacting the hydroxyl groups with isocyanate groups of urethane-methacrylate precursors to result in the new monomeric systems U-(bis-GMA)-Mod and U-(GDMA)-Mod, U=Urethane and Mod=Modified. The modifications were characterized by FTIR and 1 H NMR. The final monomeric synthesized system was used to prepare dental resins and composites. The physical-chemical properties were evaluated and compared with those of bis-GMA composites with varying filler contents or unfilled resins. U-(bis-GMA)-Mod and U-(GDMA)-Mod can be used to prepare dental restorative composites, with some foreseeable advantages compared with bis-GMA composites. One significant advantage is that these composites have the potential to be less toxic, once they presented a reduction of 50% in leaching of unreacted monomers extracted by solvent., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The rat red blood cell (RBC) Pig-a assay has been recommended by an expert working group of the International Workshop on Genotoxicity Testing as a potential new method to evaluate in vivo gene mutations in regulatory genotoxicity risk assessments. In a collaborative study in Japan, an improved Pig-a assay using reticulocytes (PIGRET assay) with magnetic enrichment of CD71-positive cells was evaluated, and it was revealed that this assay could detect the mutagenicity of chemicals earlier than the RBC Pig-a assay could. To verify further the suitability of the PIGRET assay for an in vivo short-term genotoxicity screening test, a joint research study was conducted by the Japanese Environmental Mutagen Society, and 24 compounds were evaluated. One of the compounds evaluated in this study was urethane, a multi-organ rodent carcinogen. Urethane (250, 500, and 1000mg/kg body weight) was orally administered once to 8-week-old male Crl:CD (SD) rats. Blood samples were collected at 1, 2, and 4 weeks after the administration and processed for the RBC Pig-a and PIGRET assays. In the PIGRET assay, the Pig-a mutant frequency (MF) significantly increased at both 2 and 4 weeks after the treatment of 1000mg/kg of urethane. However, in the RBC Pig-a assay, a significant increase in the Pig-a MF was observed only at 1 week after the treatment with 500mg/kg, but the MF value was within our historical control range; therefore, it was judged to be negative. These results suggest that the PIGRET assay might be useful for evaluating the in vivo mutagenicity more clearly than the RBC Pig-a assay after a single treatment of test compounds., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Urethane is a recognized genotoxic carcinogen in fermented foods and beverages. This study is to compare susceptibility of ICR mice, BALB/c mice and C57BL/6 mice to urethane-induced lung carcinogenesis. The mice were injected intraperitoneally with 600 mg/kg of urethane for three times or ten times at 7-day intervals. At week 26, lung carcinogenic incidence was found in 40% ICR mice, 20% BALB/c mice and 10% C57BL/6 mice of the 3× injection group, respectively, whereas 100% lung tumor incidence took place in three mouse strains of the 10× injection group. In the 10× injection group, urethane induced lasting glycolytic stress of lung with an increase in lactate, monocarboxylate transporter 1 (MCT-1), reactive oxygen species(ROS) and 7,8-dihydro-8-oxo-29-deoxyguanosine (8-OHdG) and a decrease in pyruvate dehydrogenase (PDH) and cytochrome C oxidase (COX). In the 3× injection group, urethane also promoted lung glycolytic stress at the end of urethane injection but it lasted no more than 7 days besides in lung tumor-bearing mice. Metformin as a glycolytic enhancer promoted urethane carcinogenic efficacy in the 3× injection group, whereas 2-deoxy-glucose (2-DG) as a glycolytic inhibitor decreased urethane carcinogenic efficacy in the 10× injection group. Further, urethane promoted tumor survival in A549 cells by inducing cancer stem-like cellular state. These data suggest that lasting glycolytic stress is sufficient for urethane-induced lung tumorigenesis, and that urethane 10× injection-induced lung cancer can serve as a valuable model for lung tumor biology and tumor prevention., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The aim of this paper was to analyze the impact of anesthesia induced by urethane on pharmacokinetics (PK) parameters of fluconazole (FCZ), mostly eliminated via renal excretion and voriconazole (VRC), eliminated mainly by hepatic metabolism. FCZ and VRC PK were investigated after administration of 10 mg/kg i.v. and 5 mg/kg i.v. doses to awake and urethane anesthetized Wistar rats (n = 6 per group), respectively. After dosing, blood samples were collected up to 18 h (FCZ) or 12 h (VRC) and the plasma data analysis was performed using the software MONOLIX v. 4.2.2. The population PK parameters and microconstants were determined by fitting plasma concentration-time profiles to two-compartment model for FCZ and three-compartment model for VRC. Fitting of FCZ plasma profiles after dosing to awake and anaesthetized animals resulted in a volume of distribution (V) of 9.3 and 8.1 L/kg, and k10 values of 0.12 and 0.14 h(-1) , respectively. VRC plasma profiles in awake and anaesthetized showed V 8.7 of and 7.6 L/kg, and k10 of 0.15 and 0.16 h(-1) , respectively. No statistical differences between plasma PK parameters and microconstants for the same drug in both animal conditions studied were observed (α = 0.05)., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

A synthetic meniscus implant was recently developed for the treatment of patients with mild to moderate osteoarthritis with knee pain associated with medial joint overload. The implant is distinctively different from most orthopedic implants in its pliable construction, and non-anchored design, which enables implantation through a mini-arthrotomy without disruption to the bone, cartilage, and ligaments. Due to these features, it is important to show that the material and design can withstand knee joint conditions. This study evaluated the long-term performance of this device by simulating loading for a total of 5 million gait cycles (Mc), corresponding to approximately five years of service in-vivo. All five implants remained in good condition and did not dislodge from the joint space during the simulation. Mild abrasion was detected by electron microscopy, but µ-CT scans of the implants confirmed that the damage was confined to the superficial surfaces. The average gravimetric wear rate was 14.5 mg/Mc, whereas volumetric changes in reconstructed µ-CT scans point to an average wear rate of 15.76 mm(3)/Mc (18.8 mg/Mc). Particles isolated from the lubricant had average diameter of 15 µm. The wear performance of this polycarbonate-urethane meniscus implant concept under ISO-14243 loading conditions is encouraging., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A hollow brain model was created using soft urethane. A tube passing through the hollow was attached for use as a water inlet and manometer. Water sufficient in quantity to realize the intended initial pressure was infused through the tube. The brain model was retracted with a brain spatula and the surgical corridor was opened. By measuring local force with a sensor set on the brain spatula, the model could be used for training in brain retraction. At the same time, the water column of the manometer was measured and the relationship with the force of the brain spatula was investigated. A positive correlation between the water column and local force was confirmed. This indicated that it was possible to use this model without a force sensor for the same training using water column measurements., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The hypothalamic paraventricular nucleus (PVN) is one of the most important autonomic control centers in the brain. Several kinds of prostanoids, such as prostaglandin (PG) E2, are considered to act in the PVN as mediators of autonomic responses. In the present study, we used liquid chromatography ion trap tandem mass spectrometry (LC-ITMS(n)) to simultaneously quantify four prostanoids, thromboxane (Tx) B2, PGE2, PGD2 and 15-deoxy-∆(12,14) (15d)-PGJ2 in PVN microdialysates from urethane-anesthetized rats. The quantification limits were estimated to be 0.05ng/mL for TxB2, 0.025ng/mL for PGE2, 0.1ng/mL for PGD2, and 0.5ng/mL for 15d-PGJ2. The RSD% obtained from all prostanoids was <15%, indicating an acceptable level of reproducibility. LC-ITMS(n) analysis of rat PVN microdialysates revealed that TxA2 may play an important role in adrenomedullary outflow evoked by centrally administered N-methyl-d-aspartate, corticotrophin-releasing factor and glucagon-like peptide-1. This is the first study to use LC-ITMS(n) to analyze prostanoid levels in rat PVN microdialysates. This LC-ITMS(n) method will be useful for investigating the potential involvement of prostanoids in brain function., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: The endovascular treatment of abdominal aortic aneurysms was introduced in the early 1990s, with different generations of devices using various options for either the stent skeleton or the membrane., Report: Corvita generated one of these devices using braided stainless steel and a porous spun polycarbonate urethane membrane., Discussion: In this report, we describe a case involving Corvita stentgraft explantation for complete aneurysm reperfusion after 13 years, demonstrating major degradation of the polyurethane membrane., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Acute intermittent hypoxia (AIH) triggers a form of respiratory plasticity known as long-term facilitation (LTF), which is manifested as a progressive increase in respiratory motor activity that lasts for minutes to hours after the hypoxic stimulus is removed. Respiratory LTF has been reported in numerous animal models, but it appears to be influenced by a variety of factors (e.g., species, age, and gender). While most studies focusing on respiratory LTF have been conducted in adult (including young adult) rat preparations, little is known about the influence of postnatal maturation on AIH-induced respiratory LTF. To begin to address this issue, we examined diaphragm EMG activity in response to and at 5-min intervals for 60 min following three 5-min episodes of hypoxia (8% O2) in urethane-anesthetized spontaneously breathing P14-P15 neonatal rats (n=15). For these experiments, the hypoxic episodes were separated by hyperoxia (40% O2), and all rats were continuously supplied with ~4% CO2. During the AIH trials, burst frequency was increased by ~20-90% above baseline in each of the rats examined while changes in burst amplitude were highly variable. Following the AIH episodes, respiratory LTF was characterized by predominantly an increase in burst frequency (fLTF) ranging from ~10% to 55%, with most rats exhibiting a 20-40% increase. In seven rats, however, an increase in amplitude (ampLTF) (~10%, n=3; ~20%, n=3; ~30%, n=1) was also noted. These data suggest that in contrast to observations in anesthetized ventilated adult rats, in anesthetized spontaneously breathing P14-P15 neonatal rats, respiratory LTF is dominated by fLTF, not ampLTF., (© 2014 Elsevier B.V. All rights reserved.)

Introduction: Retrodialysis, as used in neuropharmacological research, is a technique for in vivo delivery of neuroactive agents with concurrent monitoring of their effects on cellular activity with a separation between certain degree of spatial and temporal resolution. Typically, this is accomplished either by the use of a liquid-switch requiring multiple pumps, or by exchange of flow tubing requiring stopping and restarting dialysis. In the present study, we describe the use of a medium pressure injection valve for retrodialysis that overcomes these problems., Methods: The valve was configured with a loop to deliver 20μL of solution, and artificial CSF flow from the pump to the probe was established via this device. The application of this setup was evaluated in urethane anesthetized adult male C57BL/6J mice prepared with a CMA 11 probe implanted in the ventral hippocampus. By switching between the load and inject positions, the loop was filled with escitalopram solution (0.3μM) and delivered at a rate of 1μL/min at the probe for retrodialysis. Escitalopram (2mg/kg BW) was administered subcutaneously for microdialysis studies. During these treatments, dialysate fractions were collected for the determination of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)., Results: Irrespective of route of escitalopram administration, the pattern of dialysate 5-HT, and 5-HIAA response was comparable to that reported by other investigators. Accordingly, the in-line valve assembly did not compromise retrodialysis or microdialysis sampling. The manipulations to carry out retrodialysis using the valve setup are easy and simple., Discussion: An in-line injection valve is a promising adaptation for retrodialysis studies and can be incorporated as a standard part of in vivo dialysis instrumentation., (© 2013.)

Objectives: Myeloid-derived suppressor cells contribute to the immunosuppressive microenvironment during tumor development and limit the efficacy of cancer immunotherapy. Identifying myeloid-derived suppressor cells and associated factors is the first step in creating strategies to reverse the suppressive effects of these cells on the immune system., Methods: To induce lung cancer, we administered 2 doses of urethane to BALB/c mice and observed these animals for 120 days. After this period, we evaluated the percentage of myeloid-derived suppressor cells in the blood, lung and bone marrow. The expression of alpha-smooth muscle actin, transforming growth factor-β, Toll-like receptor 2, Toll-like receptor 4, and interleukin-6 was also determined in the lung tissue., Results: Myeloid-derived suppressor cells were increased in all evaluated tissues after lung cancer development in association with increased Toll-like receptor 4 expression and decreased interleukin-6 expression in the lung. We observed alpha-smooth muscle actin and transforming growth factor-β expression in lung nodules., Conclusions: We believe that the early diagnosis of cancer through determining the blood levels of myeloid-derived suppressor cells followed by the depletion of these cells should be further investigated as a possible approach for cancer treatment.

Flexane® 80 is a trowelable urethane product used in combination with cleaners and primers to effect rubber conveyor belt repairs. These products are of concern due to the potential for worker exposure to isocyanates and volatile organic compounds (VOCs). Small chamber experiments were used to identify chemicals liberated to the ambient air from each of the Flexane®-related products. A new sample collection method using treated cotton sleeves as a surrogate skin surface to assess potential dermal exposure to isocyanates during mixing and application of the Flexane® product was validated. Six simulations of a worst case scenario were performed by an experienced belt repair technician in a walk-in laboratory exposure chamber. Analysis of air samples from the large chamber simulations did not detect airborne isocyanates. The average airborne VOC concentrations were below established occupational exposure levels. Dermal sleeve samples detected intermittent and low levels of isocyanates from self-application while wearing gloves having surface residues of uncured Flexane®. The data strongly suggest that the normal and intended use of Flexane® putty, and its associated products under worst case or typical working conditions is not likely to result in worker VOC or isocyanate exposure levels sufficient to produce adverse health effects., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The present study was designed to evaluate the effects of urban, traffic-related, fine particulate matter (PM2.5) on mice lung tumorigenesis under controlled exposure conditions., Methods: Four groups of female Swiss mice were treated with intraperitonial injections of urethane and saline solution. Urethane was used to start the carcinogenesis process. The animals were housed in two chambers receiving filtered and polluted air. In the polluted air chamber, pollutant levels were low. After two months of exposure, the animals were euthanized and lung tumoral nodules were counted., Results: Saline-treated animals showed no nodules. Urethane-treated animals showed 2.0+2.0 and 4.0+3.0 nodules respectively, in the filtered and non-filtered chambers (p = 0.02), thus showing experimental evidence of increased carcinogenic-induced lung cancer with increasing PM2.5 exposure., Conclusion: Our data support the concept that low levels of PM2.5 may increase the risk of developing lung tumors.