A sensitive intelligent point-of-care test method for tert-butylhydroquinone in edible oil via a test strip with a smartphone.

Tert-butylhydroquinone (TBHQ) is easily overused or illegally added to edible oil and attracts a growing concern because of its cytotoxic, liver-damaging, and carcinogenic effects. Thus, a sensitive and intelligent point-of-care testing (iPOCT) method is developed to fulfill the on-site monitoring. This iPOCT method depended on a fluorescent immunochromatographic assay within 15 min. Under optimization, the limit of quantification (LOQ) was calculated as 0.03 µg mL-1. The iPOCT method provided a low limit of detection (LOD) of 0.02 µg mL-1, a wide linear range of 0.03-100 µg mL-1, and great selectivity. Recoveries by the spiking experiments ranged from 97.4% to 103.5% with relative standard deviations (RSDs) of 2.4%-4.9% in soybean, peanut, rapeseed, and corn oil samples. The results showed that the iPOCT method is highly consistent with the high-performance liquid chromatography (HPLC) method.

Synthesis and Analysis of (g,g', g'', - Trifluoro)neopentyl (TFNP) Aryl ethers as a Polar Aliphatic Motif.

A route is developed to (g,g',g''''-trifluoro)neopentyl (TFNP) aryl ethers to extend the methods for the introduction of the tert-butyl group, carrying a fluorine on each of the methyl  substituents. The route combines neopentyltosylate 3 with phenols and thiophenols to give efficient substitution reactions to the corresponding TFNP aryl ethers. The three C-F bonds adopt a helical propeller conformation as revealed by computation and single crystal X-ray structure analysis. The LogPs of TFNP ethers are lower (more hydrophilic) than their tert-butyl analogues. The metabolism of selected TFNP ethers was explored in the fungus Cunninghamella elegans.

Immortalization of Mesenchymal Stem Cell Lines from Sheep Umbilical Cord Tissue.

Mesenchymal stem cells (MSCs) possess significant differentiation potential, making them highly promising in medicine and immunotherapy due to their regenerative capabilities and exosome secretion. However, challenges such as limited cell divisions and complex testing hinder large-scale MSC production. In this study, we successfully established an immortalized MSC line by transfecting the human telomerase reverse transcriptase (TERT) gene into MSCs isolated from pregnant sheep umbilical cords. This approach effectively inhibits cell senescence and promotes cell proliferation, enabling the generation of umbilical cord mesenchymal stem cells (UCMSCs) on a larger scale. Our findings demonstrate that these transfected TERT-UCMSCs exhibit enhanced proliferative capacity and a reduced aging rate compared to regular UCMSCs while maintaining their stemness without tumorigenicity concerns. Consequently, they hold great potential for medical applications requiring large quantities of functional MSCs.

Excellent Electroluminescent Property of Eu3+-Induced Polystyrene-co-poly(acrylic acid) Aggregates (EIPAs) in Polymeric Light-Emitting Diodes.

Eu3+-induced polystyrene-co-poly(acrylic acid) aggregates (EIPAs) were synthesized using a self-assembly approach, and their structures and photophysical characteristics were examined to achieve effective monochromatic red emission in polymer light-emitting diodes (PLEDs). By adjusting the monomer ratio in RAFT polymerization, the size of Eu3+-induced block copolymer nanoaggregates can be regulated, thereby modulating the luminescence intensity. High-performance bilayer polymer light-emitting devices were fabricated using poly(9,9-dioctylfluorene) (PFO) and 2-(tert-butylphenyl)-5-biphenylyl-1,3,4-oxadiazole (PBD) as the host matrix, with EIPAs as the guest dopant. The devices exhibited narrow red emission at 615 nm with a full width at half-maximum (fwhm) of 15 nm across doping concentrations of 1, 3, 5, and 10 wt %. At a doping concentration of 3 wt %, the device achieved a maximum brightness of 1864.48 cd/m2 at 193.82 mA/cm2 and an external quantum efficiency of 3.20% at a current density of 3.5 mA/cm2. These results indicate that incorporating polystyrene-co-poly(acrylic acid) with Eu3+ complexes enhances the excitation and emission intensity, as well as the structural stability of the emitting layer in PLEDs, thereby improving the device performance.

Effects of Nitrosyl Iron Complexes with Thiol, Phosphate, and Thiosulfate Ligands on Hemoglobin.

Nitrosyl iron complexes are remarkably multifactorial pharmacological agents. These compounds have been proven to be particularly effective in treating cardiovascular and oncological diseases. We evaluated and compared the antioxidant activity of tetranitrosyl iron complexes (TNICs) with thiosulfate ligands and dinitrosyl iron complexes (DNICs) with glutathione (DNIC-GS) or phosphate (DNIC-PO4-) ligands in hemoglobin-containing systems. The studied effects included the production of free radical intermediates during hemoglobin (Hb) oxidation by tert-butyl hydroperoxide, oxidative modification of Hb, and antioxidant properties of nitrosyl iron complexes. Measuring luminol chemiluminescence revealed that the antioxidant effect of TNICs was higher compared to DNIC-PO4-. DNIC-GS either did not exhibit antioxidant activity or exerted prooxidant effects at certain concentrations, which might have resulted from thiyl radical formation. TNICs and DNIC-PO4- efficiently protected the Hb heme group from decomposition by organic hydroperoxides. DNIC-GS did not exert any protective effects on the heme group; however, it abolished oxoferrylHb generation. TNICs inhibited the formation of Hb multimeric forms more efficiently than DNICs. Thus, TNICs had more pronounced antioxidant activity than DNICs in Hb-containing systems.

Detection of human papillomavirus (HPV) in malignant melanoma.

The most common type of melanoma is cutaneous melanoma (CM). The predominant mutational signature is that of ultraviolet radiation (UVR) exposure. The Cancer Genome Atlas (TCGA) molecular classification includes four major subtypes of CM based on common genetic alterations involving the following genes: BRAF, NRAS, and NF1, with a small fraction being "triple" wild-type. The two main signaling pathway abnormalities in CM are the mitogen-activated protein kinase (MAPK) pathway and the phosphoinositol-3-kinase (PI3K) pathway. Other less common types include mucosal melanomas (MM) and uveal melanoma (UM), which have a significantly different genomic landscape. Although few studies reported rare cases with HPV-positive (HPV+) melanoma, the clinicopathological and molecular characteristic of this entity has not been well-described. Among the 2084 melanoma cases queried at our institution, we identified seven patients diagnosed with HPV+ melanoma (prevalence 0.03 %), including five instances of CM and two of MM. The majority of cases were positive for HPV16 (n = 6). Most of the patients were elderly and with advanced disease (n = 6), although this finding may be attributed to the relative frequency of our institution testing advanced-stage tumors. Histologically, most cases showed high degree of pleomorphism and high mitotic count (5 or more mitoses/mm2) (n = 6). UVR signature was present in the CM, but not in the MM cases. Alterations in either MAPK and/or PI3K pathways were detected in the majority of cases (n = 6). The most common genetic abnormalities detected in this study occurred in the TERT promoter (TERTp) (n = 5), a finding that has been reported to be associated with aggressive disease. Our data shows that while HPV+ melanoma is rare, identifying this disease entity could help guide therapy given the demonstrated genomic alterations.

Protective effect of tert-butylhydroquinone against cisplatin-induced hepatorenal injury via modulating oxidative stress, inflammation, and apoptosis.

CONTEXT: Cisplastin (CDDP) is a chemotherapeutic drug frequently used to manage a variety of cancers. However, its use is associated with hepatorenal toxicity resulting from elevated reactive oxygen species production. OBJECTIVE: Herein, the hepatorenal protective effect of tert-butylhydroquinone (tBHQ) in cisplatin (CDDP)-treated rats was examined. METHODS: Wistar male rats randomly divided into four groups: normal control, tBHQ, CDDP and tBHQ + CDDP received 50 mg/kg b.w./day of tBHQ orally for 14 days while 7 mg/kg b.w of CDDP was administered intraperitoneally on Day 8. RESULTS: CDDP increased serum biomarkers of hepatic (AST, ALP, ALT, GGT) and renal (creatinine, urea, uric acid, kidney injury molecule 1) function. The levels of nuclear factor erythroid-2-related factor 2 protein and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities were decreased in liver and kidney. Also, CDDP increased hepatic and renal levels of NF-κB, TNFα, Bax and caspase-3 proteins and decreased hepatorenal levels of Bcl-2 protein in the liver and kidney. Pre-treatment with tBHQ prevented these negative effects. SIGNIFICANCE: Pre-intervention with tBHQ attenuates hepatorenal toxicity of CDDP by dampening oxidative stress, inflammation and apoptosis.

Influence of humic acid on the p-tert-Butylphenol removal efficiency by Spirodela polyrhiza-Tas13 association.

Plant-microbe remediation technique is considered as a promising technology in removal of organic pollutants and its remediation efficiency is largely affected by a variety of surrounding environmental factors. Humic acid (HA) is the complex organic substance ubiquitous in environment, which characterized by its surfactant-like micelle microstructure and various reaction activity. In our study, a plant-microbe association with high p-tert-Butylphenol (PTBP) degradation potential constructed by Spirodela polyrhiza and Sphingobium phenoxybenzoativorans Tas13 has been used, and the influence of HA on the PTBP degradation efficiency of S. polyrhiza-Tas13 association was investigated. The result showed that the presence of HA greatly improved PTBP removal efficiency of S. polyrhiza-Tas13. The reason accounted for this may be due to the presence of HA promoted bacterial cell propagation, altered bacterial cell wall permeability, increased catechol 2,3-dioxygenase (C23O) enzyme activity of strain Tas13, rather than increasing the colonization ability of strain Tas13 on to the root surface. This study will greatly facilitate the application of aquatic plant-microbe association in environmental remediation.

Freeze-drying cycle optimization of an amorphous solid dispersion of resveratrol.

Resveratrol (RES) has demonstrated advantages as anti-cancer, anti-inflammatory, blood sugar-lowering agent and as cardioprotective agent, among others. Despite RES therapeutic advantages its use in pharmaceutical applications is limited by its low oral bioavailability, mainly due to its poor water solubility. Formulation of poorly water-soluble compound as solid dispersion (SD) converts a crystalline into a more soluble in water amorphous drug. Lyophilization or freeze-drying is a process in which water, an organic solvent, or a co-solvent system is frozen, followed by its removal from the sample, initially by sublimation (primary drying) and then by desorption (secondary drying). This study aimed the development and optimization of a bulk freeze-drying cycle by critical process parameters assessment in each phase to prepare a RES third-generation SD, containing Eudragit E PO as hydrophilic polymer at 1:2 ratio, and Gelucire 44/14 as surfactant at 16 % (w/w) to RES, using a tert-butanol (TBA)/Acetate buffer pH 4.5 (75:25) co-solvent system. A RES third-generation SD with good appearance, not cracked, collapsed, or melted was prepared by an optimized and robust bulk lyophilization process. A physicochemical characterization confirmed the conversion of RES to the amorphous state in the SD and formulation stability after 1 month at 40 °C/75 % RH. Increased solubility and higher dissolution rate compared with pure RES were also obtained.

Development of a Global Metabo-Lipid-Prote-omics Workflow to Compare Healthy Proximal and Distal Colonic Epithelium in Mice.

A multimetabo-lipid-prote-omics workflow was developed to characterize the molecular interplay within proximal (PC) and distal (DC) colonic epithelium of healthy mice. This multiomics data set lays the foundation to better understand the two tissue types and can be used to study, for example, colon-related diseases like colorectal cancer or inflammatory bowel disease. First, the methyl tert-butyl ether extraction method was optimized, so that from a single tissue biopsy >350 reference-matched metabolites, >1850 reference-matched lipids, and >4500 proteins were detected by using targeted and untargeted metabolomics, untargeted lipidomics, and proteomics. Next, each omics-data set was analyzed individually and then merged with the additional omics disciplines to generate a deep understanding of the underlying complex regulatory network within the colon. Our data demonstrates, for example, differences in mucin formation, detected on substrate level as well as on enzyme level, and altered lipid metabolism by the detection of phospholipases hydrolyzing sphingomyelins to ceramides. In conclusion, the combination of the three mass spectrometry-based omics techniques can better entangle the functional and regional differences between PC and DC tissue compared to each single omics technique.

Distinct transcriptional and prognostic impacts of TERT promoter mutations C228T and C250T in papillary thyroid carcinoma.

TERT promoter mutations C228T and C250T are associated with disease aggressiveness and poor clinical outcomes in patients with papillary thyroid carcinomas. However, very little is known about the transcriptional consequences of these mutations and whether they both carry similar oncogenic potential. Here we characterized the transcriptional disturbances and clinical outcomes associated with the presence of each of these two mutations using data derived from The Cancer Genome Atlas. We observed that tumors harboring the C228T mutation (n = 27) exhibited a 16-fold increase in TERT mRNA levels (P = 5.3 × 10-42), whereas C250T tumors (n = 8) showed only a two-fold increase in expression (P = 0.034). The C228T mutation was associated with the activation of signaling pathways controlling the cell cycle, cellular division, and extracellular matrix degradation. Univariate analysis demonstrated that the C228T mutation was associated with older age at diagnosis, large tumor size, lymph node invasion, and distant metastases at diagnosis. The C228T mutation was also associated with worse progression-free interval (PFI) in comparison to WT tumors (HR = 5,04; P < 0.001). This association remained significant in a multivariate analysis (HR = 3.74, P = 0.003) adjusting for BRAF-V600E status and ATA risk group. Our data indicate that TERT promoter mutations C228T and C250T have distinct transcriptional consequences in papillary thyroid carcinoma (PTC), suggesting a greater oncogenic potential for the C228T mutation. TERT promoter mutation C228T may be a useful prognostic marker to identify patients at high risk of distant recurrence. Clinical data for the C250T mutation is still limited, with no evidence up to date to confirm its prognostic significance.

Loss of Chromosome Y in Neuroblastoma Is Associated With High-Risk Disease, 11q-Deletion, and Telomere Maintenance.

Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased age at diagnosis and enriched in tumors with 11q-deletion and activated telomere maintenance mechanisms. In contrast, tumors with an MYCN-amplified genomic profile retained their Y chromosome. The understanding of LoY in cancer is limited, making it difficult to conclude whether LoY is a driving event in NB or function of increased genomic instability. Gene expression analysis of Y chromosome genes in male NB tumors showed low expression of certain genes correlating with worse overall survival. KDM5D, encoding a histone demethylase stands out as an interesting candidate for further studies. LoY has been shown to impact the epigenomic layer of autosomal loci in nonreproductive tissues, and KDM5D has been reported as downregulated and/or associated with poor survival in different malignancies. Further studies are needed to explore the mechanisms and functional consequences of LoY in NB.

Regulation of Tert methylation alleviates food allergy via regulating the Tert-IL10 signal pathway.

BACKGROUND: The cause of food allergy (FA) is still a mystery. Telomerases are involved in the regulation of immune responses. This study aims to gain an understanding of the contribution of telomerase reverse transcriptase (TERT) to the pathogenesis of FA. METHODS: A murine FA model was established with ovalbumin as the specific antigen. The role of TERT in regulating dendritic cell (DC) immune tolerogenic functions was evaluated in this murine model. RESULTS: We observed that the Tert promoter was at demethylation status and the Tert expression was elevated in DCs of FA mice. The Tert expression in DCs had a positive correlation with the FA response. TERT prevented the induction of Il10 expression in DCs. The immune tolerogenic functions of DCs were diminished by TERT. The immune tolerogenic functions of DC were restored by CpG by boosting the Tert promoter methylation. Administration of CpG promoted the therapeutic effects of allergen specific immunotherapy in FA mice. CONCLUSIONS: Low levels of Il10 expression and high levels of Tert expression were observed in intestinal DCs of FA mice. CpG exposure restored the expression of Il10 and increased the therapeutic benefits of allergen-specific immunotherapy.

Extended longevity of termite kings and queens is accompanied by extranuclear localization of telomerase in somatic organs and caste-specific expression of its isoforms.

Kings and queens of termites are endowed with an extraordinary longevity coupled with lifelong fecundity. We recently reported that termite kings and queens display a dramatically increased enzymatic activity and abundance of telomerase in their somatic organs when compared to short-lived workers and soldiers. We hypothesized that this telomerase activation may represent a noncanonical pro-longevity function, independent of its canonical role in telomere maintenance. Here, we explore this avenue and investigate whether the presumed noncanonical role of telomerase may be due to alternative splicing of the catalytic telomerase subunit TERT and whether the subcellular localization of TERT isoforms differs among organs and castes in the termite Prorhinotermes simplex. We empirically confirm the expression of four in silico predicted splice variants (psTERT1-A, psTERT1-B, psTERT2-A, psTERT2-B), defined by N-terminal splicing implicating differential localizations, and C-terminal splicing giving rise to full-length and truncated isoforms. We show that the transcript proportions of the psTERT are caste- and tissue-specific and that the extranuclear full-length isoform TERT1-A is relatively enriched in the soma of neotenic kings and queens compared to their gonads and to the soma of workers. We also show that extranuclear TERT protein quantities are significantly higher in the soma of kings and queens compared to workers, namely due to the cytosolic TERT. Independently, we confirm by microscopy the extranuclear TERT localization in somatic organs. We conclude that the presumed pleiotropic action of telomerase combining the canonical nuclear role in telomere maintenance with extranuclear functions is driven by complex TERT splicing.

Measurement of cellular MDA content through MTBE-extraction based TBA assay by eliminating cellular interferences.

Malondialdehyde (MDA) has long been served as a crucial indicator for assessing cellular oxidative stress levels. In this study, we introduce a new approach to determine cellular MDA levels based on a methyl tert-butyl ether (MTBE) extraction, aimed at eliminating interferences from cellular components during thiobarbituric acid (TBA) derivatization of MDA. By leveraging the effective MTBE extraction, we identified that the determination of the MDA-TBA adduct formed from the MTBE extraction layer can effectively eliminate the interferences from cellular proteins and metabolites. This method demonstrated acceptable linearity and precision in cellular samples and showed significant differences in H2O2 treated cellular oxidative stress models. The MTBE extraction-based MDA-TBA approach provides a reliable, cost-effective, and feasible method to determine cellular MDA levels using batch microplate reader approach for the assessment of cellular oxidative stress.

Development of ZrO(OH)2@HCS co-modified molecularly imprinted gel-based electrochemical sensing platform for sensitive and selective detection of tert-butylhydroquinone in foods.

Herein, a novel molecularly imprinted gel (MIG)-based electrochemical sensor equipped with hydrated zirconium oxide@hollow carbon spheres (ZrO(OH)2@HCS) was developed for highly sensitive and selective detection of tert-butylhydroquinone (TBHQ) in foods. The MIG was synthesized by using L-histidine to rapidly cross-link cationic guar gum, acrylamide and TBHQ through intermolecular hydrogen bonds and electrostatic interactions at room temperature, which offered outstanding specific recognition performance for TBHQ. ZrO(OH)2@HCS possessing excellent conductivity and water dispersibility was employed for signal amplification. Under optimal conditions, the MIG-ZrO(OH)2@HCS/GCE sensor showed a wide dynamic detection range (0.025-100 µM) with a low limit of detection (6.7 nM). TBHQ recovery experiments were conducted in spiked peanut oil and milk powder, yielding excellent recoveries. Moreover, the sensor was successfully utilized to detect TBHQ levels in snowflake chicken cutlets, crispy fried pork and boneless chicken fillets, and the results were in agreement with those obtained by the high performance liquid chromatography method.

Human risk assessment through development and application of a physiologically based toxicokinetic model for 4-tert-octylphenol.

4-tert-octylphenol (4-tert-OP) is an ecologically hazardous substance, and exposure to it in the environment has been consistently reported in the past. Despite the hazards and widespread exposure to 4-tert-OP, tools for scientific assessment of 4-tert-OP exposure risk level in humans are lacking. The main purpose of this study was to develop a physiologically-based-toxicokinetic (PBTK) model for 4-tert-OP and to perform quantitative risk assessment of 4-tert-OP in various population groups using the established model. Based on the results of toxicokinetic experiments on male rats, the PBTK model for 4-tert-OP was established and verified, and this was converted to a model for humans through interspecies extrapolation. Based on the previously reported no-observed-adverse-effect-levels for rats, it was possible to estimate the 4-tert-OP reference dose in humans through reverse dosimetry using the model. Biomonitoring data derived from various population groups were applied to the human PBTK model to calculate external exposures and margin of safety for 4-tert-OP for each population group. The PBTK model established in this study adequately explained the toxicokinetic experimental values at acceptable levels and was able to quantitatively predict the 4-tert-OP exposure level in the testes related to male reproductive toxicity. In addition, the degree of external exposure to 4-tert-OP could be scientifically estimated based on biomonitoring values derived from various biological matrices. The reference doses for systemic and reproductive toxicity caused by 4-tert-OP in male humans were calculated to be 0.16 and 1.12 mg/kg/day, respectively. The mean external exposure to 4-tert-OP in each population group estimated based on plasma and urine biomonitoring data was 0.04-66.24 mg/kg/day, showing very large exposure diversity between groups. Exposure risks to 4-tert-OP in populations ranged from safe to risky, suggesting the need for continued monitoring and risk management of 4-tert-OP worldwide. This study provides valuable scientific insight regarding the 4-tert-OP human risk assessment.

Prognostic Impact of TERT Promoter Mutations in Adult-Type Diffuse Gliomas Based on WHO2021 Criteria.

Mutation in the telomerase reverse transcriptase promoter (TERTp )is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan-Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas.

4-tert-Butylphenol impairs the liver by inducing excess liver lipid accumulation via disrupting the lipid metabolism pathway in zebrafish.

Endocrine disrupting chemicals (EDCs) can disrupt normal endocrine function by interfering with the synthesis and release of hormones, causing adverse reactions to development, immunity, nerves, and reproduction. 4-tert-Butylphenol (4-t-BP) is disruptive to early zebrafish development, but its effects on zebrafish liver are unknown. In this study, the adverse effects of 4-t-BP on the liver were investigated using zebrafish as a model organism. 4-t-BP inhibited liver development in zebrafish embryos and induced liver damage in adult zebrafish. Even if F1 was not directly exposed to 4-t-BP, its growth and development were inhibited. 4-t-BP can lead to an increase in lipid accumulation, total cholesterol and triglycerides contents, and the activities of alanine transaminase and aspartate aminotransferase in zebrafish embryos and adult zebrafish livers, and also cause an acceleration of glucose metabolism in zebrafish embryos. In addition, qRT-PCR showed that 4-t-BP induced the changes in the expressions of liver development-, steroid and unsaturated fatty acid biosynthesis-, and glycerolipid and arachidonic acid metabolism-related genes in zebrafish embryos and inflammatory factors-, antioxidant enzymes- and lipid metabolism-related genes in adult zebrafish livers. Transcriptome sequencing of embryos showed that 4-t-BP altered the expressions of lipid metabolism pathways such as steroid and unsaturated fatty acid biosynthesis, glycerolipid, and arachidonic acid metabolism pathways. Therefore, 4-t-BP may be external stimuli that cause oxidative stress, inflammation, and lipid accumulation in zebrafish liver, resulting in tissue damage and dysfunction in zebrafish liver.

Different Role of TRF1 and TRF2 Expression in Non-Small Cell Lung Cancers.

Background: TRF1, TRF2, and TERT (Telomerase reverse transcriptase) are telomere-associated factors that regulate telomere length. Genetic changes in these genes may be associated with cancer pathogenesis; however, this relationship has not yet been comprehensively elucidated in lung cancer. Aim: : Exploring the clinicopathologic and prognostic values of TRF1, TRF2, and TERT mRNA expression in non-small cell lung cancers (NSCLC). Methods: : The clinical significance of TRF1, TRF2, and TERT expression in 141 patients with NSCLC was investigated. Additionally, these findings were supported by the open big data from The Cancer Genome Atlas (TCGA). Results: : TRF1 and TRF2 expression levels tended to be associated with smoking, and TERT expression was positively correlated with age. The survival analysis showed that TRF1 expression predicted a better prognosis for squamous cell carcinoma (SCC), whereas TRF2 expression was associated with a shorter survival in adenocarcinoma. TCGA data also showed a better prognosis for SCC with TRF1 expression. However, the TRF2 results were not in agreement with our data. Conclusions: : We present the clinical and prognostic values of TRF1, TRF2, and TERT expression in NSCLC tissues and TCGA. Our findings suggest that TRF1 expression is a possible prognostic marker for NSCLC, particularly SCC.