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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.

Background: To investigate prenatal ultrasound findings and the chromosomal outcomes of mosaic embryo transfer. Methods: This retrospective study was conducted on pregnant women who underwent mosaic embryo transfer following blastocyst-stage preimplantation genetic testing for aneuploidy (PGT-A) at CHA Gangnam Medical Center from January 2021 to July 2024. Trophectoderm biopsy specimens were collected using standard protocols, and next-generation sequencing profiles were defined as mosaics when displaying copy number counts in the 20–80% range. The results of the PGT-A, the amniocentesis results, the findings of prenatal ultrasounds, and the pregnancy outcomes were analyzed. Results: A total of 88 mosaic embryos were transferred, of which 77 embryos were successfully implanted. Sixty-seven embryo-maintained pregnancies went beyond 11 weeks (87.0%), all among 58 patients with singleton pregnancies. The chaotic subtype showed the lowest ongoing pregnancy rate, and high-level mosaicism was less frequent in the ongoing group, compared to the total study group and the successful implantation group. Amniocentesis was performed on 33 mothers (56.9%), revealing two cases with abnormal findings that did not correlate with the PGT-A results. Two cases showed abnormalities in the second trimester detailed ultrasound, and both subsequently demonstrated normal findings in the third trimester and after birth. The average gestational age at birth was 38.4 weeks, and the average birth weight was 3313 g. No congenital anomalies were detected in 16 postnatal cases. Conclusions: Our study indicated that mosaic embryos can develop into euploid healthy infants with various levels or types of mosaicism, although the postnatal follow-up data are limited. This study is invaluable for counseling clinical results after mosaic embryo transfer, reassuring that, if patients do not have euploid embryos available, mosaic embryos can also be a viable option for transfer. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of cerclage on twin pregnancies. Methods: A multicenter, retrospective, cohort study was conducted at 10 tertiary centers using a web-based data collection platform. The study population included twin pregnancies delivered after 20 weeks of gestation. Patients with one or two fetal deaths before 20 weeks of gestation were excluded. Maternal characteristics, including prenatal cervical length (CL) and obstetric outcomes, were retrieved from the electronic medical records. Results: A total of 1,473 patients had available data regarding the CL measured before 24 weeks of gestation. Seven patients without CL data obtained prior to cerclage were excluded from the analysis. The study population was divided into two groups according to the CL measured during the mid-trimester: the CL ≤2.5 cm group (n = 127) and the CL >2.5 cm group (n = 1,339). A total of 127 patients (8.7%) were included in the CL ≤2.5 cm group, including 41.7% (53/127) who received cerclage. Patients in the CL >2.5 cm group who received cerclage had significantly lower gestational age at delivery than the control group (hazard ratio (HR): 1.8; 95% confidence interval (CI): 1.11–2.87; p =.016). Patients in the CL ≤2.5 cm group who received cerclage had a significantly higher gestational age at delivery than the control group (HR: 0.5; 95% CI: 0.30–0.82; p value =.006). Conclusions: In twin pregnancies with a CL ≤2.5 cm, cerclage significantly prolongs gestation. However, unnecessary cerclage in women with a CL >2.5 cm may result in a higher risk of preterm labor and histologic chorioamnionitis although this study has a limitation originated from retrospective design. [ABSTRACT FROM AUTHOR]

Exploring the microscopic reaction mechanism of dicyandiamide (DCD) synthesis using calcium cyanamide (CaCN2) is highly desirable because of the low conversion of reactants and selectivity of DCD products. DCD synthesis consists of a two-step sequential hydrolysis of CaCN2, followed by dimerization of cyanamide to DCD in an alkaline environment. Density functional theory (DFT) results revealed that the rate-limiting step (RLS) was the formation of a C-N bond between the cyanamide and cyanamide anion in the dimerization of the DCD reaction. Secondary reactions of cyanamide with water, hydrogen sulfide, and DCD were also analyzed. The effects of solvation on the principal and secondary reactions were systematically explored. A single explicit water molecule can significantly lower the free energy barrier of the RLS. Water molecules facilitate the C-N bonding of the reactants in DCD reactions, resulting in a reduction in the free energy barrier of the RLS. The facilitation of double explicit water for the reaction is weaker than that of single explicit water and even yields negative catalysis. The effect of the [OH(H2O)3]− cluster lowering the reaction barrier with the hydrogen-bonding network is the most remarkable, which can alter the reaction path by the direct and indirect involvement of OH− ions. Furthermore, the reaction rate constants were computed by canonical variational theory with the Eckart tunneling correction (CVT/Eckart) and fitted to the Arrhenius expression. The reaction mechanism and kinetics revealed at the microscopic level provide efficient and clean production of DCD with certain theoretical guidance. [ABSTRACT FROM AUTHOR]

Rotors of steam turbines in power plants can be locally deformed by undesired situations, such as rubbing between the rotors and stationary parts. A straightening process is required to correct bending without causing additional damage because a rotor bending displacement of ∼0.15 mm can stop turbine unit operation. In this study, a numerical framework was established to simulate the straightening process using electromagnetic induction heating, which is straightforward and economical among the methods for straightening bent rotors. The straightening process involves complex coupling of electromagnetic, thermal, and mechanical phenomena. For efficiency, sequential coupling was used in the simulations, dividing the multiphysics phenomena into electromagnetic–thermal and thermal–mechanical fields. The temperature distributions resulting from electromagnetic induction heating were calculated through two-way coupling of the electromagnetic–thermal analysis. The thermal deformations of the rotors were obtained by solving the coupled equations for the thermal field obtained from the electromagnetic–thermal analysis and the mechanical field. Using the established numerical framework, the thermal–mechanical behaviors and straightening mechanisms of bent rotors were investigated. Furthermore, the effects of process parameters, including the direction of gravity and heating and cooling conditions, on the straightening performance were determined. Appropriate parameters were identified to achieve the desired straightening performance with final bending displacements of <0.1 mm for bent rotors with initial bending displacements of 0.15–0.3 mm. For a rotor made of A182 F11 Class 2, the best straightening performance was obtained by heating the rotor to a maximum temperature of 650 °C for 20 h under insulation, followed by natural cooling. The simulation results revealed that the straightening performance can be improved when the rotor is rapidly heated to a high maximum temperature and cooled immediately, as long as the temperature conditions do not cause phase transformation or unintended plastic deformation of the bent rotors. [ABSTRACT FROM AUTHOR]