Characterization of the Group II Intron Gs. Int1 from the Thermophilic Bacterium \u3cem\u3eGeobacillus stearothermophilus\u3c/em\u3e.

Group II Introns are small segments of DNA that reside in the chromosome of bacteria or the organelles of primitive eukaryotes. These elements have some very interesting properties. First, they are retrotransposons that can move from one location to a new location in DNA via a reverse transcription mechanism. Second, they form a large ribozyme that mediates self-splicing of the intron from pre-mRNA. A Group II Intron type protein with similarity to reverse transcriptase was discovered in the thermophilic bacterium Geobacillus stearothermophilus strain 10 (Vellore et al., 2004, Appl. Environ. Microbiol. 70: 7140-7147). Numerous copies of the intron, designated Gs. Int1, are present in the chromosome of strain 10 but absent from a related strain ATCC 12980. Experiments to detect the in vivo splicing of intron Gs.Int1 from G. stearothermophilus cells did not work. Plasmids to that will over-express the Gs. Int1 intron to detest splicing in vivo in Escherichia coli have been constructed

Impulsivity and craving in subjects with opioid use disorder on methadone maintenance treatment.

BACKGROUND: Methadone maintenance treatment (MMT) is effective in decreasing opioid use or facilitating abstinence. Previous studies using small opioid use disorder samples suggest that cognitive impairments including impulsivity and executive functions may partially improve on MMT, but a range of deficits may persist. However, systematic assessments with larger samples are needed to confirm the profile of cognitive functions on MMT. METHODS: We assessed four types of impulsivity (delay discounting, reflection impulsivity, risk taking and motoric impulsivity), executive functioning (spatial working memory, paired associative learning and strategic planning) and drug cue-induced craving in a relatively large population (115 MMT patients, 115 healthy controls). The relationships between impulsivity, drug cue-induced craving and addiction-related variables were also assessed. RESULTS: Delay discounting, as well as drug cue-induced craving was increased in patients, while motoric impulsivity was lower than in controls. Paired associative learning was additionally impaired, which was explained by increased depression and anxiety levels in patients. Within the MMT group, the delay discounting and drug-cue induced craving scores were positively correlated with self-reported urgency, but unrelated to methadone dosage, duration on methadone, withdrawal symptoms, or presence of nicotine dependence. CONCLUSIONS: Our findings highlight increased delay discounting and cue-induced craving in MMT patients suggesting a potential role for trait effects in delay discounting. Although previous smaller studies have shown impaired executive function, in our large sample size on chronic MMT we only observed impaired associative learning related to depressive and anxiety symptoms highlighting a role for managing comorbid symptoms to further optimize cognitive function

The Chinese version of obsessive compulsive drug use scale: validation in outpatient methadone maintenance treatment program

Funder: Guangci Professorship Program of Ruijin Hospital and Shanghai Jiao Tong University School of Medicine 2018 International and Hong Kong, Macao and Taiwan Regional Research Cooperation ProjectAbstract: Background: The Obsessive Compulsive Drug Use Scale (OCDUS) measures the overall craving level within a period from a multidimensional perspective. However, no studies have addressed the validity of the new OCDUS factor structure, presented in 2016, in China. Additionally, there is lack of evidence on the interaction among risk factors for relapse. We aimed to assess the psychometric properties of the scores of the Chinese version of the OCDUS in patients with heroin dependence receiving methadone maintenance treatment (MMT). Further, we aimed to assess the correlations of the OCDUS scores with withdrawal symptoms, depression, anxiety, and nicotine dependence. Methods: We enrolled 113 adults (age 32–64 years) and administered them with the OCDUS, Subjective Opioid Withdrawal Scale (SOWS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI), and Fagerstrom Test for Nicotine Dependence (FTND). Results: Exploratory factor analysis identified a 3-dimensional component that included “Frequency of craving,” “Inference of heroin,” and “Control of heroin.” These factors showed acceptable internal consistency, adequate item-total correlations, and significant item-subscale correlations. There was no correlation between the OCUDS scores and age, education, duration of receiving MMT, and MMT dosages. However, there was a significant correlation between the OCDUS total scores and the SOWS, STAI, BDI-II, and FTND scores. The scores of all the subscales were associated with the SOWS scores; further, the scores of the first two subscales were associated with BDI-II scores while only the scores of the first subscale were associated with the FTND scores. Conclusions: Our findings support the reliability and structure validity of the OCDUS scores. Heroin craving, withdrawal symptoms, negative emotions, and nicotine dependence, which are considered as risk factors for heroin relapse, might interact with each other. There is a need for further studies on the underlying mechanism of these clinical phenomena

G9a Is Essential for EMT-Mediated Metastasis and Maintenance of Cancer Stem Cell-Like Characters in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 (H3K9). Moreover, G9a is required for both lymph node-related metastasis and TGF-β-induced EMT in HNSCC cells since knockdown of G9a reversed EMT, inhibited cell migration and tumorsphere formation, and suppressed the expression of CSC markers. Our study demonstrates that the G9a protein is essential for the induction of EMT and CSC-like properties in HNSCC. Thus, targeting the G9a-Snail axis may represent a novel strategy for treatment of metastatic HNSCC

Autocrine Epiregulin Activates EGFR Pathway for Lung Metastasis Via EMT in Salivary Adenoid Cystic Carcinoma

Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, EREG-neutralizing antibody, but not normal IgG, blocked the autocrine EREG-induced EGFR phosphorylation and the migration of SACC cells, suggesting that EREG-induced EGFR activation is essential for induction of cell migration and invasion by SACC cells. Moreover, EREG-activated EGFR stabilized Snail and Slug, which promoted EMT and metastatic features in SACC cells. Of note, targeting EGFR with inhibitors significantly suppressed both the motility of SACC cells in vitro and lung metastasis in vivo. Finally, elevated EREG expression showed a strong correlation with poor prognosis in head and neck cancer. Thus, targeting the EREG-EGFR-Snail/Slug axis represents a novel strategy for the treatment of metastatic SACC even no genetic EGFR mutation

Fatigue resistant lead-free multilayer ceramic capacitors with ultrahigh energy density

The critical role of electrical homogeneity in optimising electric-field breakdown strength (BDS) and energy storage in high energy density (0.7 − x)BiFeO3–0.3BaTiO3–xBi(Li0.5Nb0.5)O3 (BF–BT–xBLN) lead-free capacitors is demonstrated. The high BDS for bulk ceramics and multilayers (dielectric layer thickness ∼ 8 μm) of ∼260 and ∼950 kV cm−1, respectively, gives rise to record-performance of recoverable energy density, Wrec = 13.8 J cm−3 and efficiency, η = 81%. Under an electric field of 400 kV cm−1, multilayers are temperature stable up to 100 °C, frequency independent in the range 10−2 to 102 Hz, have low strain (<0.03%) and are fatigue-resistant up to 104 cycles (Wrec variation < 10%). These properties show promise for practical use in pulsed power systems

Effects of high-intensity interval training, moderate-intensity continuous training, and guideline-based physical activity on cardiovascular metabolic markers, cognitive and motor function in elderly sedentary patients with type 2 diabetes (HIIT-DM): a protocol for a randomized controlled trial

Background and objectiveSedentary behavior is of increasing concern in older patients with type 2 diabetes mellitus (T2DM) due to its potential adverse effects on cardiovascular health, cognitive function, and motor function. While regular exercise has been shown to improve the health of individuals with T2DM, the most effective exercise program for elderly sedentary patients with T2DM remains unclear. Therefore, the objective of this study was to assess the impact of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and guideline-based physical activity programs on the cardiovascular health, cognitive function, and motor function of this specific population.MethodsThis study will be a randomized, assessor-blind, three-arm controlled trial. A total of 330 (1:1:1) elderly sedentary patients diagnosed with T2DM will be randomly assigned the HIIT group (10 × 1-min at 85–95% peak HR, intersperse with 1-min active recovery at 60–70% peak HR), MICT (35 min at 65–75% peak HR), and guideline-based group (guideline group) for 12 weeks training. Participants in the guideline group will receive 1-time advice and weekly remote supervision through smartphones. The primary outcomes will be the change in glycosylated hemoglobin (HbA1c) and brain-derived neurotrophic factor (BDNF) after 12-weeks. Secondary outcomes will includes physical activity levels, anthropometric parameters (weight, waist circumference, hip circumference, and body mass index), physical measurements (fat percentage, muscle percentage, and fitness rate), cardiorespiratory fitness indicators (blood pressure, heart rate, vital capacity, and maximum oxygen), biochemical markers (high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and HbA1c), inflammation level (C-reactive protein), cognitive function (reaction time and dual-task gait test performance), and motor function (static balance, dynamic balance, single-task gait test performance, and grip strength) after 12 weeks.DiscussionThe objective of this study is to evaluate the effect of 12 weeks of HIIT, MICT, and a guideline-based physical activity program on elderly sedentary patients diagnosed with T2DM. Our hypothesis is that both HIIT and MICT will yield improvements in glucose control, cognitive function, cardiopulmonary function, metabolite levels, motor function, and physical fitness compared to the guideline group. Additionally, we anticipate that HIIT will lead to greater benefits in these areas. The findings from this study will provide valuable insights into the selection of appropriate exercise regimens for elderly sedentary individuals with T2DM.Ethics and disseminationThis study has been approved by the Ethics Review Committee of the Reproductive Hospital Affiliated with China Medical University (approval number: 202203). Informed consent will be obtained from all participants or their guardians. Upon completion, the authors will submit their findings to a peer-reviewed journal or academic conference for publication.Clinical trial registrationChinese Clinical Trial Registry, identifier ChiCTR2200061573