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Hepatic ischemia-reperfusion (I/R) injury, which mainly involves inflammatory responses and apoptosis, is a common cause of organ dysfunction in liver transplantation. As a critical mediator of inflammation and apoptosis in various cell types, the role of tripartite motif-containing 27 (TRIM27) in hepatic I/R injury remains undetermined. This study systemically evaluated the putative role of TRIM27- TGF-β-activated kinase 1 (TAK1)-JNK/p38 signaling in hepatic I/R injury. TRIM27 expression was significantly downregulated in liver tissue from liver transplantation patients, mice subjected to hepatic I/R surgery and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Subsequently, using global Trim27 knockout mice (Trim27-KO mice) and hepatocyte-specific Trim27 transgenic mice (Trim27-HTG mice), TRIM27 functions to ameliorate liver damage, reduce the inflammatory response and prevent cell apoptosis. In parallel in vitro studies, activating TRIM27 also prevented H/R-induced hepatocyte inflammation and apoptosis. Mechanistically, TRIM27 constitutively interacted with the critical components TAK1 and TAK1 binding protein 2/3 (TAB2/3) and promoted the degradation of TAB2/3, leading to inactivation of TAK1 and the subsequent suppression of downstream JNK/p38 signaling. Conclusion TRIM27 is a key regulator of hepatic I/R injury by mediating the degradation of TAB2/3 and the suppression of downstream TAK1-JNK/p38 signaling. TRIM27 may be a promising approach to protect the liver against I/R-mediated hepatocellular damage in transplant recipients. This article is protected by copyright. All rights reserved.The organs of vertebrate species display a wide variety of morphology. A remaining challenge in evolutionary developmental biology is to elucidate how vertebrate lineages acquire distinct morphological features. Developmental programs are driven by spatiotemporal regulation of gene expression controlled by hundreds of thousands of cis-regulatory elements. Changes in the regulatory elements caused by the introduction of genetic variants can confer regulatory innovation that may underlie morphological novelties. Recent advances in sequencing technology have revealed a number of potential regulatory variants that can alter gene expression patterns. However, a limited number of studies demonstrate causal dependence between genetic and morphological changes. Regulation of Shh expression is a good model to understand how multiple regulatory elements organize tissue-specific gene expression patterns. This model also provides insights into how evolution of molecular traits, such as gene regulatory networks, lead to phenotypic novelty. This article is protected by copyright. All rights reserved.BACKGROUND The objective of this study was to evaluate treatment outcomes for patients with desmoid tumors (DTs) receiving local therapy with surgery alone, radiation therapy (RT) alone, or combined modality therapy (RT and surgery). METHODS This was a cross-sectional cohort study of 412 patients with nonmesenteric DTs who received local therapy at the authors' institution between 1965 and 2018. RESULTS The median follow-up time was 95 months (range, 1-509 months). Local recurrence occurred in 127 patients (31%) at a median time of 21 months (interquartile range, 12-38 months). Bozitinib The 5-year local control (LC) rate was 67%. Patient or tumor factors that were significantly associated with poorer 5-year LC in a multivariable analysis included an age ≤ 30 years (57% vs 75% for an age > 30 years; hazard ratio [HR], 1.73; P = .004), an extremity location (57% vs 71% for a nonextremity location; HR, 1.77; P = .004), and large tumors (59% for >10 cm [HR, 2.17; P = .004] and 65% for 5.1-10 cm [HR, 1.71; P = .02] vs 76% for ≤5 cm). Subset analyses of these high-risk patients revealed no local therapy strategy to be superior for young patients ≤ 30 years old (HR for surgery, 1.42; P = .33; HR for RT, 1.36; P = .38) or for large tumors > 10 cm (HR for surgery, 1.55; P = .46; HR for RT, 0.91; P = .91). However, for patients with extremity tumors, surgery alone was significantly associated with inferior LC (HR for surgery, 5.15; P  less then  .001; HR for RT, 1.51; P = .38). CONCLUSIONS Local therapy provides durable tumor control in the majority of patients with DTs. However, young patients, patients with an extremity location, and patients with large tumors are at increased risk of recurrence. When active treatment is indicated, systemic therapy should perhaps be considered as a first-line option in these high-risk subsets. Prospective multi-institutional studies evaluating this strategy are warranted. © 2020 American Cancer Society.BACKGROUND Alcohol use disorder places a heavy burden on global public health systems and thus is in urgent need of improved pharmacotherapies. Previously, our group has demonstrated that 30 mg/kg of the indole alkaloid brucine significantly attenuates alcohol drinking behavior; however, the high toxicity, poor water solubility, short half-life, and limited therapeutic window of brucine restrain its clinical application as an anti-alcoholism medication. We subsequently hypothesized that the oxide of brucine (brucine N-oxide) would produce a similar behavioral effect without the risk profile associated with brucine. METHODS Male Fawn-Hooded rats with high innate alcohol preference underwent two-bottle choice procedures (Experiments 1-3). Experiment 1 examined the effects of 7 daily BNO injections of 0, 30, 50 or 70 mg/kg (s.c.) on voluntary alcohol consumption (n = 9/group). Experiment 2 evaluated the impact of a single dose of 0 or 70 mg/kg BNO on the increased alcohol intake induced by a 4d alcohol deprivatiid not affect spontaneous locomotor activity or induce a place preference. CONCLUSIONS BNO may help to control excessive alcohol use and should be considered a treatment strategy for future study and development. This article is protected by copyright. All rights reserved.AIM Cherubism is an uncommon hereditary disease that leads to the development of giant cell lesions in the jaws, alterations in the dentition, and malocclusion. The biological behavior of bones to orthodontic forces in these patients is not described in the literature, leading dentists to avoid this management. The aim of this article was to describe a case report of management with orthodontics. We present details regarding clinicoradiographic features, diagnosis, treatment, and follow-up. CASE REPORT A 12-year-old male patient diagnosed with cherubism presented to our service with complaints about his esthetic facial and dental appearance. Management was interdisciplinary, including careful and controlled orthodontic treatment. The results were satisfactory; alignment, dental leveling, and correction of the malocclusion were achieved. CONCLUSION Patients with cherubism may benefit from orthodontics, improving oral function, and esthetic and psychosocial well-being. The orthodontic treatment might be performed according to the severity of clinical manifestation, expectations of the patients, and limitations of each case. © 2020 Special Care Dentistry Association and Wiley Periodicals, Inc.The mTERF gene family encodes for nucleic acid binding proteins that are predicted to regulate organellar gene expression in eukaryotes. Despite the implication of this gene family in plant development and response to abiotic stresses, a precise molecular function was assigned to only a handful number of its ~30 members in plants. Using a reverse genetics approach in Arabidopsis thaliana and combining molecular and biochemical techniques, we revealed new functions for the chloroplast mTERF protein, MDA1. We demonstrated that MDA1 associates in vivo with components of the plastid-encoded RNA polymerase and transcriptional active chromosome complexes. MDA1 protein binds in vivo and in vitro with specificity to 27-bp DNA sequences near the 5'-end of psbE and ndhA chloroplast genes to stimulate their transcription and additionally promote the stabilization of the 5'-ends of processed psbE and ndhA mRNAs. Finally, we provided evidence that MDA1 function in gene transcription likely coordinates RNA folding and the action of chloroplast RNA binding proteins on mRNA stabilization. Our results provide examples for the unexpected implication of DNA binding proteins and gene transcription in the regulation of mRNA stability in chloroplasts blurring the boundaries between DNA and RNA metabolism in this organelle. This article is protected by copyright. All rights reserved.The need to find new pharmacological targets for treating alcohol use disorder (AUD) has been an extensive effort in alcohol research. Changes in immune function due to AUD may represent an exploitable target for developing new medications to treat AUD, since the cytotoxic effect of alcohol has shown to alter the expression of inflammatory mediators in the periphery and in the central nervous system (CNS). This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE Anxiety disorder is a common mental health disorder. However, there are few safe and fast-acting anxiolytic drugs available that can treat anxiety disorder. We previously demonstrated that the interaction of neuronal nitric oxide synthase (nNOS) with its carboxy-terminal PDZ ligand (CAPON) is involved in regulating anxiety-related behaviours. Here, we further investigated the anxiolytic effects of nNOS-CAPON disruptors in chronic stress-induced anxiety in animals. EXPERIMENTAL APPROACH Mice were intravenously treated with nNOS-CAPON disruptors, ZLc-002 or Tat-CAPON12C, at the last week of chronic mild stress (CMS) exposure. Moreover, we also infused corticosterone (CORT) into the hippocampus of mice to model anxiety behaviours, and delivered ZLc-002 or Tat-CAPON12C into the hippocampus on the last week of chronic CORT treatment via pre-implanted cannula. Anxiety-related behaviours were examined using elevated plus maze (EPM), open-field (OF), novelty-suppressed feeding (NSF) and light-dd.The "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease-19 (COVID-19) and satisfying the epidemiological criteria for a pandemic [1]. As of April 1, 2020, more than one million COVID-19 positive cases have been identified and more than 54,000 deaths have occurred worldwide [2]. In Italy, 110,574 positive cases, 49,285 hospitalized patients and 13,155 deaths out of a population of 60,359,546 inhabitants, have been reported, respectively [3]. The highest number of deaths occurred in the northern Italian regions, i.e. Lombardy, Emilia-Romagna, Veneto and Piedmont [3]. This article is protected by copyright. All rights reserved.PURPOSE Magnetoacoustic tomography with magnetic induction (MAT-MI) is a technique that utilizes the acoustic signals induced by magnetic stimulation to reconstruct the electrical impedance distribution in biological tissues. Most algorithms ignored the fact that acoustic properties in human tissues are heterogeneous, which lead to distortion and blurring of small reconstructed objects. In this study, a novel algorithm is proposed for exactly reconstructing of the sound source distribution in acoustic heterogeneous tissues. METHODS Based on the ring transducer array, we develop an algorithm which combines algebraic reconstruction technique (ART) and time reversal method. Different to existing reconstruction methods, the ultrasonic transmission tomography (UTT) and the MAT-MI can be completed in same system, which decreases the system complexity. The sound velocity distribution is reconstructed with the ART so that the propagation time of the magnetoacoustic signals in the heterogeneous tissue is corrected. And then, the sound source image is reconstructed based on the time reversal method from new sound pressure data.