Silencing METTL14 alleviates liver injury in non-alcoholic fatty liver disease by regulating mitochondrial homeostasis

Mitochondrial dysfunction is an important pathogenic factor in non-alcoholic fatty liver disease (NAFLD). Methyltransferase-like 14 (METTL14) has been implicated in mitochondrial fission processes. This research aimed to investigate the mechanism of METTL14 in the mitochondrial function of NAFLD. We first established NAFLD mouse models and cell models, recording body and liver weights and examining pathological changes in liver tissues. Subsequently, serum levels of liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total cholesterol [TC], and triglycerides [TG]), inflammatory markers (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, and IL-1β), and mitochondrial dysfunction indicators (fission 1 protein [Fis1], dynamin-related protein 1 [Drp1], mitofusin 2 [Mfn2], SID1 transmembrane family member 2 [SIDT2], and mitochondrial membrane potential [MMP]) in the liver and cells were evaluated. The N6-methyladenosine (m6A) modification level of primary microRNA (pri-miRNA) and m6A enrichment on pri-miR-34a were quantified. Co-immunoprecipitation and dual-luciferase reporter gene assays were utilized to validate gene interactions. Our findings revealed highly elevated METTL14 expression in NAFLD mouse and cell models. Silencing METTL14 reduced weight gain and mitigated adverse liver function indices, inflammation, hepatic steatosis, and structural damage in NAFLD mice. It also led to a decrease in Fis1/Drp1 levels and an increase in MMP/Mfn2 in the liver and cells. Moreover, METTL14 increased the m6A level, promoting the binding of DiGeorge syndrome critical region 8 (DGCR8) to pri-miR-34a, which enhanced miR-34a-5p expression. Databases and dual-luciferase reporter gene assays indicated that miR-34a-5p could suppress SIDT2 expression. The overexpression of miR-34a-5p or inhibition of SIDT2 expression negated the alleviative effects of METTL14 silencing on mitochondrial homeostasis imbalance. In conclusion, METTL14, through m6A modification, modulates the miR-34a-5p/SIDT2 axis, impairing mitochondrial homeostasis in NAFLD

Efficacy of Chinese Herbal Medicine for Diarrhea-Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Objective. To explore the efficacy of Chinese herbal medicine in treating diarrhea-predominant irritable bowel syndrome (D-IBS). Methods. Four English and four Chinese databases were searched through November, 2015. Randomized, double-blind and placebo-controlled trials were selected. Data extraction and quality evaluation were performed by two authors independently. RevMan 5.2.0 software was applied to analyze the data of included trials. Results. A total of 14 trials involving 1551 patients were included. Meta-analysis demonstrated superior global symptom improvement (RR = 1.62; 95% CI 1.31, 2.00; P<0.00001; number needed to treat = 3.6), abdominal pain improvement (RR = 1.95; 95% CI 1.61, 2.35; P<0.00001), diarrhea improvement (RR = 1.87; 95% CI 1.60, 2.20; P<0.00001), pain threshold assessment (MD = 54.53; 95% CI 38.76, 70.30; P<0.00001), and lower IBS Symptom Severity Score (SMD = −1.01; 95% CI −1.72, −0.30; P=0.005), when compared with placebo, while for defecation threshold assessment, quality of life, and adverse events, no differences were found between treatment groups and controlled groups. Conclusion. This meta-analysis shows that Chinese herbal medicine is an effective and safe treatment for D-IBS. However, due to the small sample size and high heterogeneity, further studies are required

Probability or time: Effect of presentation format on continuous risky decisions

Continuous risky decisions refer to decisions that involve trade-offs among options with persistent risks. People can use the probability of occurrence per unit time (e.g., ‘the probability of occurrence is 1% per month’) or the average time of risk occurrence (e.g., ‘the average occurrence time is 100 months’) to represent continuous risky options. In this study, we examined the effect of the presentation format (i.e., the probability of occurrence per unit time vs. the average time of risk occurrence) on continuous risky decisions in the gain domain and further explored the underlying mechanism. In Study 1 (N = 122), we demonstrated the effect of presentation format on continuous risky decisions and the moderating effect of the magnitude of probabilities. Specifically, when the probabilities were relatively low, compared with the probability of occurrence per unit time, using the average time of risk occurrence to present the continuous risky options led to more risk-averse decisions. However, when the probabilities were relatively high, compared with the probability of occurrence per unit time, the presentation format of the average time occurrence led to more risk-seeking decisions. In Study 2 (N = 136), we found that the moderating effect of the option probabilities on continuous risky decisions was mediated by the subjective attribute-wise difference judgment. In Study 3 (N = 221), we replicated the effect of presentation format on continuous risky decisions in more natural scenarios. The study offered a deep understanding of the mechanism of continuous risky decision-making, and the results were conducive to further developing theories in relevant fields

Kosterlitz-Thouless melting of magnetic order in the triangular quantum Ising material TmMgGaO4

Frustrated magnets hold the promise of material realizations of exotic phases of quantum matter, but direct comparisons of unbiased model calculations with experimental measurements remain very challenging. Here we design and implement a protocol of employing many-body computation methodologies for accurate model calculations-of both equilibrium and dynamical properties-for a frustrated rare-earth magnet TmMgGaO4 (TMGO), which explains the corresponding experimental findings. Our results confirm TMGO is an ideal realization of triangular-lattice Ising model with an intrinsic transverse field. The magnetic order of TMGO is predicted to melt through two successive Kosterlitz-Thouless (KT) phase transitions, with a floating KT phase in between. The dynamical spectra calculated suggest remnant images of a vanishing magnetic stripe order that represent vortex-antivortex pairs, resembling rotons in a superfluid helium film. TMGO therefore constitutes a rare quantum magnet for realizing KT physics, and we further propose experimental detection of its intriguing properties. TmMgGaO4 is one of a number of recently-synthesized quantum magnets that are proposed to realize important theoretical models. Here the authors demonstrate the agreement between detailed experimental measurements and state-of-the-art predictions based on the 2D transverse-field triangular lattice Ising model

Ab initio calculated dynamic structure factor and optical properties of beryllium along the Hugoniot

Beryllium is an ablator material in the inertial-confinement fusion and hypervelocity impact studies. The thermoelastic properties, structure factors, and optical properties of beryllium are important in the study. In this paper, the static structure factors, ion-ion dynamic structure factors, adiabatic velocity, and optical properties of beryllium along the Hugoniot are calculated by ab initio simulations concurrently. The dynamic structure factor via the intermediate scattering function extracts the dispersion relation for the collective excitations. The static structure factors show that beryllium atoms are randomly distributed. By collecting the peak position of dynamic structure factors, the dispersion relation and adiabatic sound velocity are derived. By the calculated equation of state, the thermoelastic properties and adiabatic sound velocity are derived. The two calculated methods about adiabatic sound velocity are verified to be equivalent