Search

METTL3 catalyzes mRNA m6A deposition. The authors identify an acetylation-mediated regulation of METTL3 subcellular localization and compartment-specific functions, a process that is fine-tuned by anti-inflammatory and pro-inflammatory signals, which ultimately determine breast cancer metastasis.

Abstract Lacking a clear understanding of the molecular mechanism determining cancer cell sensitivity to oxidative phosphorylation (OXPHOS) inhibition limits the development of OXPHOS‐targeting cancer treatment. Here, cancer cell lines sensitive or resistant to OXPHOS inhibition are identified by screening. OXPHOS inhibition‐sensitive cancer cells possess increased OXPHOS activity and silenced nicotinamide N‐methyltransferase (NNMT) expression. NNMT expression negatively correlates with OXPHOS inhibition sensitivity and functionally downregulates the intracellular levels of S‐adenosyl methionine (SAM). Expression of DNA methyltransferase 1 (DNMT1), a SAM consumer, positively correlates with OXPHOS inhibition sensitivity. NNMT overexpression and DNMT1 inhibition render OXPHOS inhibition‐sensitive cancer cells resistant. Importantly, treatments of OXPHOS inhibitors (Gboxin and Berberine) hamper the growth of mouse tumor xenografts by OXPHOS inhibition sensitive but not resistant cancer cells. What's more, the retrospective study of 62 tumor samples from a clinical trial demonstrates that administration of Berberine reduces the tumor recurrence rate of NNMTlow/DNMT1high but not NNMThigh/DNMT1low colorectal adenomas (CRAs). These results thus reveal a critical role of the NNMT‐DNMT1 axis in determining cancer cell reliance on mitochondrial OXPHOS and suggest that NNMT and DNMT1 are faithful biomarkers for OXPHOS‐targeting cancer therapies.

Abstract Background This study analyzed the characteristics of hydrogen fluoride-exposed patients (HFEPs) treated in the emergency department (ED) of a local university hospital, and reviewed the hospital’s disaster response according to space, staff, supplies, and systems (4Ss). Methods This retrospective observational chart review and descriptive study included 199 HFEPs among 2588 total ED patients who visited a local university emergency medical center for treatment between September 27, 2012 and October 20, 2012, following a hydrofluoric acid leak at the Hube Globe factory in Gumi City, Republic of Korea. Descriptive results concerning the 4Ss were obtained by interviewing ED specialist staff physicians on duty during the study period. In accordance with American Burn Association criteria, patients requiring burn center referral were assigned to the major burn group (MBG) as severe condition. Results During the acute phase (within 8 h after leak initiation), there were 43 patients in the ED, which was staffed with 3 doctors and 3 nurses, without 4S resources. Of these 43 patients, there were 8 HFEPs (100%) in the MBG and 0 in the non-MBG (NMBG). During the subacute phase (24 h after the acute phase), there were 262 patients in the ED including 167 HFEPs, of whom 45 (26.95%) were in the MBG and 122 (73.05%) were in the NMBG. The ED was then staffed with 6 doctors (3 on day shift and 3 on night shift) and 10 nurses (3 on day shift, 4 on evening shift, and 3 on night shift), and no 4S resources were available. Throughout the study period, no 4Ss were available. First, there was no expansion of ED space or secured disaster reserve beds. Second, there was no increase in manpower with duty time adjustments or duty relocation for ED working personnel. Third, there was no logistics reinforcement (e.g., antidote or personal protective equipment). Fourth, there were no disaster-related measures for the administration department, decontamination zone setup, safety diagnostic testing, or designated disaster triage implementation. Conclusions The hospital’s disaster response was insufficient for all aspects of the 4Ss. Detailed guidance concerning a hospital disaster management plan is required.

Abstract Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis is poorly understood. Lysine‐specific demethylase 1 (LSD1) is known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms by which cells maintain LSD1/CoREST complex integrity are unknown. Here, it is reported that LSD1 protein undergoes K63‐linked polyubiquitination. OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63‐linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62‐mediated proteolysis. Consequently, OTUD7B deficiency impairs genome‐wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis. Moreover, physiological fluctuation of OTUD7B modulates cell cycle‐dependent LSD1 oscillation, ensuring the G1/S transition. Both OTUD7B and LSD1 proteins are overpresented in high‐grade or metastatic human breast cancer, while dysregulation of either protein is associated with poor survival and metastasis. Thus, OTUD7B plays a unique partner‐switching role in maintaining the integrity of LSD1/CoREST corepressor complex, LSD1 turnover, and breast cancer metastasis.

Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.

Focusing on local non-"Double First-Class" higher colleges in China, this study aims to explore the effects of classroom teaching, integration of industry and education, classroom involvement, interdisciplinary awareness and abilities, as well as teacher-student investment, on the increment of professional abilities of industrial design students, and explore effective teaching modes. Organizing questionnaire survey data, constructing a multiple linear regression model, and using the analytical method of sheaf coefficient found that student investment has the most decisive influence on low-order and high-order professional abilities, while other variables have their focuses. Teacher investment only has a direct impact on partial high-order professional capacities. The analysis of interactive effect regression models found that the interactive effects of significant influencing variables only mutually reinforce partial high-order professional abilities. The second-order factor structural equation modeling found that the professional capacities of industrial design have a strong endogeneity. The core mission of teachers is to promote "student-centered" teaching and integration of production and education and encourage students' investment to improve their professional ability. This study provides an empirical basis for optimizing and reconstructing the conceptual framework of low-order and high-order professional capacities in higher education.

Abstract Introduction Subacute lymphocytic thyroiditis is anautoimmune thyroid disease presenting with transient thyrotoxicosis as well as transient hypothyroidism. Several factors have been thought to be the initiating event in subacute lymphocytic thyroiditis. However, subacute lymphocytic thyroiditis that develops after thyroid lobectomy has not yet been reported in the literature. We report a case of subacute lymphocytic thyroiditis after lobectomy in a patient with papillary thyroid carcinoma. Case presentation A 30-year-old Korean woman was referred to our center for thyroid tumor operation. She was diagnosed with suspicious papillary thyroid carcinoma by fine needle aspiration at a local medical clinic. The thyroid ultrasonography demonstrated a diffusely enlarged thyroid gland with a 0.4×0.3cm sized hypoechoic nodule in the left lobe. Left thyroid lobectomy by endoscopic thyroidectomy was performed via a transaxillary approach, and the nodule was confirmed to be a papillary thyroid carcinoma. On postoperative day 1, a thyroid function test revealed hyperthyroidism, and on postoperative day 8, a thyroid function test again revealed hyperthyroidism with decreased radioactive iodine uptake. Thyroid function tests showed euthyroid on postoperative day 48 and hypothyroidism on postoperative day 86. She was treated with levothyroxine. Conclusion Subacute lymphocytic thyroiditis can develop after thyroid lobectomy. Thyroid autoantigen released during thyroid lobectomy may cause the onset or exacerbation of the destructive process.

Objectives To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women. Methods We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status. Results Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was < 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise. Conclusion We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income., Author(s): Seung-Ah Choe [sup.1] , Seung Mi Lee [sup.2] , You Jung Han [sup.3] , Min Hyoung Kim [sup.4] , Jae-Yoon Shim [sup.5] , Mi-Young Lee [sup.6] , Soo-young Oh [...]