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The IL6-GP130-STAT3 pathway facilitates lung cancer progression and resistance to tyrosine kinase inhibitors. Although glycosylation alters the stability of GP130, its effect on the ligand IL6 remains unclear. We herein find that N-glycosylated IL6, especially at Asn73, primarily stimulates JAK-STAT3 signaling and prolongs STAT3 phosphorylation, whereas N-glycosylation-defective IL6 (deNG-IL6) induces shortened STAT3 activation and alters the downstream signaling preference for the SRC-YAP-SOX2 axis. This signaling shift induces epithelial-mesenchymal transition (EMT) and migration in vitro and metastasis in vivo, which are suppressed by targeted inhibitors and shRNAs against SRC, YAP, and SOX2. Osimertinib-resistant lung cancer cells secrete a large amount of deNG-IL6 through reduced N-glycosyltransferase gene expression, leading to clear SRC-YAP activation. deNG-IL6 contributes to drug resistance, as confirmed by in silico analysis of cellular and clinical transcriptomes and signal expression in patient specimens. Therefore, the N-glycosylation status of IL6 not only affects cell behaviors but also shows promise in monitoring the dynamics of lung cancer evolution., (© 2024. The Author(s).)

In order to examine the mechanical properties and rotational bending fatigue performance of 40CrNi2MoE steel subsequent to tempering at varying temperatures, the steel specimen was subjected to tempering within the range of 400~460 °C. SEM, EBSD, and TEM were used to analyze the microstructure as well as precipitates. The strain hardening law was studied using the modified Crussard-Jaoult method. Investigations were undertaken to reveal the rotational bending fatigue life with respect to the tempering temperature. The findings indicate that the strength and fatigue life of the examined steels exhibit a decline as the tempering temperature increases, with the primary factor affecting this trend being the alteration in dislocation density. No notable impact on the fatigue fracture morphology exerted by tempering temperature was found within the range of the experiment. The C-J model analysis reveals that the work-hardening behavior of the trial steels is influenced by dislocations and the second phase.

Background: Photodocumentation during endoscopy procedures is one of the indicators for endoscopy performance quality; however, this indicator is difficult to measure and audit in the endoscopy unit. Emerging artificial intelligence technology may solve this problem, which requires a large amount of material for model development. We developed a deep learning-based endoscopic anatomy classification system through convolutional neural networks with an accelerated data preparation approach., Patients and Methods: We retrospectively collected 8,041 images from esophagogastroduodenoscopy (EGD) procedures and labeled them using two experts for nine anatomical locations of the upper gastrointestinal tract. A base model for EGD image multiclass classification was first developed, and an additional 6,091 images were enrolled and classified by the base model. A total of 5,963 images were manually confirmed and added to develop the subsequent enhanced model. Additional internal and external endoscopy image datasets were used to test the model performance., Results: The base model achieved total accuracy of 96.29%. For the enhanced model, the total accuracy was 96.64%. The overall accuracy improved with the enhanced model compared with the base model for the internal test dataset without narrowband images (93.05% vs. 91.25%, p < 0.01) or with narrowband images (92.74% vs. 90.46%, p < 0.01). The total accuracy was 92.56% of the enhanced model on the external test dataset., Conclusions: We constructed a deep learning-based model with an accelerated approach that can be used for quality control in endoscopy units. The model was also validated with both internal and external datasets with high accuracy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale & Objective: Hemodialysis facilities are high-risk environments for the spread of hepatitis C virus (HCV). Eliminating HCV from all dialysis facilities in a community may be achieved more effectively under a collaborative care model., Study Design: Quality improvement study of multidisciplinary collaborative care teams including nephrologists, gastroenterologists, and public health practitioners., Setting & Participants: All dialysis patients in Changhua County, Taiwan were treated using an interdisciplinary collaborative care model implemented within a broader Changhua-Integrated Program to Stop HCV Infection (CHIPS-C)., Quality Improvement Activities: Provision of an HCV care cascade to fill 3 gaps, including screening and testing, diagnosis, and universal direct-acting antiviral (DAA) treatment implemented by collaborating teams of dialysis practitioners and gastroenterologists working under auspices of Changhua Public Health Bureau., Outcome: Outcome measures included quality indicators pertaining to 6 steps in HCV care ranging from HCV screening to treatment completion to cure., Analytical Approach: A descriptive analysis., Results: A total of 3,657 patients from 31 dialysis facilities were enrolled. All patients completed HCV screening. The DAA treatment initiation rate and completion rate were 88.9% and 94.0%, respectively. The collaborative care model achieved a cure rate of 166 (96.0%) of 173 patients. No virologic failure occurred. The cumulative treatment ratios for patients with chronic HCV infection increased from 5.3% before interferon-based therapy (2017) to 25.6% after restricted provision of DAA (2017-2018), and then to 89.1% after universal access to DAA (2019)., Limitations: Unclear impact of this collaborative care program on incident dialysis patients entering dialysis facilities each year and on patients with earlier stages of chronic kidney disease., Conclusions: A collaborative care model in Taiwan increased the rates of diagnosis and treatment for HCV in dialysis facilities to levels near those established by the World Health Organization., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Tumor heterogeneity and lack of knowledge about resistant cell states remain a barrier to targeted cancer therapies. Basal cell carcinomas (BCCs) depend on Hedgehog (Hh)/Gli signaling, but can develop mechanisms of Smoothened (SMO) inhibitor resistance. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies noncanonical Gli1 activity, but characteristics and drivers of the nMRTF cell state remain unknown. Here, we use single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlate with nMRTF and resistance to SMO inhibitors. The nMRTF cell state resembles transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFß cooperativity driving nMRTF activation. JNK/AP-1 signaling commissions chromatin accessibility and Smad3 DNA binding leading to a transcriptional program of RhoGEFs that facilitate nMRTF activity. Importantly, small molecule AP-1 inhibitors selectively target LYPD3+/TACSTD2+/LY6D+ nMRTF human BCCs ex vivo, opening an avenue for improving combinatorial therapies.

The use of methanol in combination with diesel fuel is an effective measure to reduce particulate matter (PM) and nitrogen oxides (NOx) emissions from in-use diesel vehicles. In this study, a diesel/methanol compound combustion (DMCC) scheme was proposed and a 4-cylinder naturally-aspirated direct-injection diesel engine modified to operate on the proposed combustion scheme. The effect of DMCC and diesel oxidation catalyst (DOC) on the regulated emissions of total hydrocarbons (THC), carbon monoxide (CO), NOx and PM was investigated based on the Japanese 13 Mode test cycle. Certain unregulated emissions, including methane, ethyne, ethene, 1,3-butadiene, BTX (benzene, toluene, xylene), unburned methanol and formaldehyde were also evaluated based on the same test cycle. In addition, the soluble organic fraction (SOF) in the particulate and the particulate number concentration and size distribution were investigated at certain selected modes of operation. The results show that the DMCC scheme can effectively reduce NOx, particulate mass and number concentrations, ethyne, ethene and 1,3-butadiene emissions but significantly increase the emissions of THC, CO, NO(2), BTX, unburned methanol, formaldehyde, and the proportion of SOF in the particles. After the DOC, the emission of THC, CO, NO(2), as well as the unregulated gaseous emissions, can be significantly reduced when the exhaust gas temperature is sufficiently high while the particulate mass concentration is further reduced due to oxidation of the SOF., (Copyright 2009 Elsevier B.V. All rights reserved.)

This study is aimed to investigate the combined application of fumigation methanol and a diesel oxidation catalyst for reducing emissions of an in-use diesel engine. Experiments were performed on a 4-cylinder naturally-aspirated direct-injection diesel engine operating at a constant speed of 1800 rev/min for five engine loads. The experimental results show that at low engine loads, the brake thermal efficiency decreases with increase in fumigation methanol; but at high loads, it slightly increases with increase in fumigation methanol. The fumigation method results in a significant increase in hydrocarbon (HC), carbon monoxide (CO), and nitrogen dioxide (NO(2)) emissions, but decrease in nitrogen oxides (NO(x)), smoke opacity and the particulate mass concentration. For the submicron particles, the total number of particles decreases. In all cases, there is little change in geometrical mean diameter of the particles. After catalytic conversion, the HC, CO, NO(2), particulate mass and particulate number concentrations were significantly reduced at medium to high engine loads; while the geometrical mean diameter of the particles becomes larger. Thus, the combined use of fumigation methanol and diesel oxidation catalyst leads to a reduction of HC, CO, NO(x), particulate mass and particulate number concentrations at medium to high engine loads.

Experiments were conducted on a 4-cylinder direct-injection diesel engine with fumigation methanol injected into the air intake of each cylinder. The fumigation methanol was injected to top up 10%, 20% and 30% of the power output under different engine operating conditions. The effects of fumigation methanol on engine performance, gaseous emissions and particulate emission were investigated. The experimental results show that there is a decrease in the brake thermal efficiency when fumigation methanol is applied, except at the highest load of 0.67 MPa. At low loads, the brake thermal efficiency decreases with increase in fumigation methanol; but at high loads, it increases with increase in fumigation methanol. The fumigation method results in a significant increase in hydrocarbon (HC), carbon monoxide (CO), and nitrogen dioxide (NO(2)) emissions. The concentration of nitrogen oxides (NOx) is significantly reduced except at close to full load condition. There is also a reduction in the smoke opacity and the particulate matter (PM) mass concentration. For the submicron particles, the total number of particles decreases at low and medium loads but increases at high loads. In all cases, there is a shift of the particles towards smaller geometrical mean diameter, especially at high loads. The increase in nano-sized particles and the increase in NO(2) emission could have serious impact on human health.

The gene libraries of laryngeal squamous cell carcinoma (LSCC) and laryngeal papilloma (LP) were screened by hybridization analysis with alpha-32P-labelled HPV-16 DNA under low stringency (Tm = 40 degrees C). It showed that the relative sequences were detected in LSCCs (11/16, 68.8%), but not in LP. The HPV-16-related DNA harbored in negative hybridization lesions were further analysed by polymerase chain reaction to amplify E6/E7 gene of HPV-16-related DNA. The results showed that 1/5 LSCCs and 2/2 LPs, were positive. The data suggest that development of LSCC should be related to the HPV infection, and HPV may be one of the inducers of LSCC.