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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer.

ObjectiveTo explore any correlation between serum urate (SU) level or insulin resistance (IR) and metabolic dysfunction associated steatotic liver disease (MASLD) in patients with metabolic syndrome (MS).MethodsData from all MASLD patients, diagnosed by liver biopsy, were enrolled and divided into MASLD alone group and MASLD with MS group. They were subdivided into hyperuricemia group and normal SU group to find correlation between SU/IR and MASLD in patients with MS and independent risk factors for MASLD.ResultsData from 539 MASLD patients were analyzed. Body mass index (BMI) (p = 0.000), waist circumference (WC) (p = 0.004), and low-density lipoprotein (LDL) (p = 0.000) were dramatically higher in MASLD with MS group than those with MASLD alone; MASLD with MS patients had significantly more family history of diabetes (p = 0.000) and hypertension (p = 0.000) than patients with MASLD alone. Height (p = 0.000), weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.001), and LDL (p = 0.007) were dramatically higher in hyperuricemia patients than those with normal SU. SU was inversely associated with age (p = 0.000) and high-density lipoprotein (HDL) (p = 0.003), and positively correlated with weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.000), TG (p = 0.000), and LDL (p = 0.000). Logistic Regression analysis showed that age (p = 0.031), TG (p = 0.002), LDL (p = 0.010), HbA1c (p = 0.026), and family history of hypertension (p = 0.000) may be independent risk factors for MASLD in patient with MS.ConclusionInsulin resistance (IR) in MASLD patients with MS, but not higher SU levels, has closer correlation with the occurrence of MASLD in patients with family history of hypertension and diabetes having higher BMI, LDL, HbA1c.

Background Fluent sentence reading is widely acknowledged to depend on top-down contextual prediction, wherein sentential and contextual cues guide the pre-activation of linguistic representations before encountering stimuli, facilitating subsequent comprehension. The Prediction-by-Production hypothesis posits an explanation for predictive processes in language comprehension, suggesting that prediction during comprehension involves processes associated with language production. However, there is a lack of eye movement evidence supporting this hypothesis within sentence reading contexts. Thus, we manipulated reading mode and word predictability to examine the influence of language production on predictive processing. Methods Participants engaged in silent or oral reading of sentences containing either high or low-predictable target words. Eye movements were recorded using the Eyelink1000 eye tracker. Results The findings revealed a higher skipping rate and shorter fixation times for high-predictable words compared to low-predictable ones, and for silent compared to oral reading. Notably, interactive effects were observed in the time measures (FFD, SFD, GD) during first-pass reading, indicating that word predictability effects were more pronounced during oral reading than silent reading. Discussion The observed pattern of results suggests that the activation of the production system enhances predictive processing during the early lexical access, providing empirical support for the Prediction-by-Production hypothesis in eye movement sentence reading situations, extending the current understanding of the timing and nature of predictions in reading comprehension.

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

RNA-binding proteins (RBPs) bind to RNAs and are crucial for regulating RNA splicing, stability, translation, and transport. Among these proteins, the CUGBP Elav-like family (CELF) is a highly conserved group crucial for posttranscriptional regulation by binding to CUG repeats. Comprising CELF1–6, this family exhibits diverse expression patterns and functions. Dysregulation of CELF has been implicated in various neural disorders, encompassing both neurodegenerative and neurodevelopmental conditions, such as Alzheimer's disease and autism. This article aims to provide a comprehensive summary of the CELF family's role in neurodevelopment and neurodevelopmental disorders. Understanding CELF's mechanisms may offer clues for potential therapeutic strategies by regulating their targets in neurodevelopmental disorders.

Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.

The preparation of activated carbon (AC) from agricultural and forestry wastes is one of the effective methods for resource utilization. In this study, AC was prepared from corn stalk (CS) by pyrolysis, one-step activation, and two-step activation to determine the optimum preparation method. Based on this, a single-factor design was used to investigate the influence of activating agents (KOH, NaOH, KOH/NaOH), activation temperatures (600, 700, 800 °C), and activation times (60, 90, 120 min) on the physicochemical properties of AC. The physicochemical properties of AC were characterized by Thermal gravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Scanning electron microscopy (SEM), and Cyclic voltammetry (CV). The results showed that the AC obtained by the one-step activation method (KOH, 800 °C, 120 min) exhibited a rich pore structure and excellent electrochemical properties (Ipa = 159.8 μA, Ipc = −169.5 μA). However, for the two-step activation method, the AC exhibited a poor pore structure and electrochemical properties (Ipa = 130.8 μA, Ipc = −129.9 μA). In addition, one-step activation provides high-quality AC in a shorter activation time than two-step activation.

Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, aggressive subtype of primary gastrointestinal T-cell lymphoma. Owing to the absence of symptoms characteristic of MEITL, diagnosis can be challenging, and the low response rate to conventional chemotherapy leads to an abysmal prognosis. This study aimed to define the clinicopathologic characteristics of MEITL in Korea, evaluate the clinical outcomes of intensive chemotherapy with and without hematopoietic stem cell transplantation (HSCT), and explore prognostic factors. Methods: This single-center retrospective study examined the clinical data of 35 patients diagnosed with MEITL at Seoul St. Mary's Hospital from May 2012 to May 2023. Results: We included 22 men and 13 women (median age: 59 years; range: 37–79 years). Many patients exhibited acute abdominal pain (n=23, 65.7%) related to bowel perforation (n=21, 60.0%). Most patients (30/35, 85.7%) underwent surgical intervention to diagnose MEITL, whereas only five were diagnosed via endoscopic evaluation. Of the 32 patients receiving first-line therapy, 4 died before assessment, 10 achieved a complete response (CR), 6 had a relapse, and 18 exhibited progressive disease (PD). Seven of 10 patients received upfront HSCT, either autologous (auto-HSCT, n=4) or allogeneic (allo-HSCT, n=3). All four patients on auto-HSCT died after relapse. All three patients who received allo-HSCT maintained a CR by the final follow-up. Three of 6 patients who relapsed and 13 of 18 exhibiting PD received salvage therapy; one patient on salvage auto-HSCT with cytokine-induced killer cell infusion has survived progression free. Salvage allo-HSCT was performed on 6 of 16 patients; among them, 2 achieved a CR, 2 died after relapse, and 2 died owing to septic shock while maintaining a CR. The remaining patients, who received salvage therapy without HSCT, mostly died owing to PD. The median overall survival was 12.1 months, and the median follow-up was 33.2 months. The 1- and 5-year overall survival was 50.9% and 13.3%, respectively. Discussion: MEITL is an aggressive disease resistant to conventional therapy. Therefore, intensive chemotherapy followed by upfront allo-HSCT should be considered upon diagnosis. These findings underscore the need for novel therapeutic strategies and further investigation into optimizing treatment protocols for MEITL. [ABSTRACT FROM AUTHOR]

This study explores the influence of first language (L1) on the acquisition of second language (L2) English, specifically examining the use of copula be as a topic marker. Although prior research suggests that L1 transfer may impact L2 acquisition of copula be, the evidence remains inconclusive. To address this issue, the study analyzes the use of be in L2 English spoken by learners with topic-prominent L1s (viz., Mandarin Chinese, Japanese, Korean) and those with non-topic-prominent L1s (viz., Filipino). Using the ICNALE corpus, the study investigates whether L1 topic-prominence affects the use of be in L2 English. The findings reveal that L2-English learners with topic-prominent L1s use copula be more often with definite NPs than those with non-topic-prominent L1s, indicating the influence of L1 topic-prominence properties on the use of copula be. Additionally, learners from topic-prominent L1s more frequently produce nontargetlike topic-comment structures using be verb (e.g., restaurant is many people eat their foods). Based on these findings, the study discusses the implication of L1 transfer effects in L2 acquisition and emphasizes the importance of a more global and refined understanding of language variation in L2 teaching and learning. [ABSTRACT FROM AUTHOR]

This study explores the formation of δ-ferrite and its self-tempering behavior in the microstructure of Type 410 martensitic stainless steel produced via laser powder bed fusion (L-PBF). The study investigates the correlation between varying energy densities applied during the L-PBF process and the resultant mechanical properties of the as-built specimens. A microstructural analysis shows that with an increase in energy density, the δ-ferrite fraction decreases, while the martensite content increases, leading to changes in tensile strength and elongation. Higher energy densities reduce tensile strength but significantly enhance ductility. The self-tempering effect of martensite in reheated zones, caused by the complex thermal cycling during the L-PBF process, plays a critical role in determining mechanical behavior. These findings provide valuable insights for optimizing the additive manufacturing of martensitic stainless steels to achieve the desired mechanical properties. [ABSTRACT FROM AUTHOR]