Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice

Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (−/−) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2 −/− mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2 −/− mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K 572 cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis

Ultra-high pressure balloon angioplasty for pulmonary artery stenosis in children with congenital heart defects: Short- to mid-term follow-up results from a retrospective cohort in a single tertiary center

ObjectiveBalloon angioplasty (BA) has been the treatment of choice for pulmonary artery stenosis (PAS) in children. There remains, however, a significant proportion of resistant lesions. The ultra-high pressure (UHP) balloons might be effective in a subset of these lesions. In this study, we analyzed the safety and efficacy with short- to mid-term follow-up results of UHP BA for PAS in children with congenital heart defects (CHD) in our center.MethodsThis is a retrospective cohort study in a single tertiary heart center. Children diagnosed with PAS associated with CHD were referred for UHP BA. All data with these children were collected for analysis with updated follow-up.ResultsA total of 37 UHP BAs were performed consecutively in 28 children. The success rate was 78.4%. A significantly (P = 0.005) larger ratio of the balloon to the minimal luminal diameter at the stenotic waist (balloon/waist ratio) was present in the success group (median 3.00, 1.64–8.33) compared to that in the failure group (median 1.94, 1.41 ± 4.00). Stepwise logistic regression analysis further identified that the balloon/waist ratio and the presence of therapeutic tears were two independent predictors of procedural success. The receiver operating characteristic curve revealed a cut-off value of 2.57 for the balloon/waist ratio to best differentiate success from failure cases. Signs of therapeutic tears were present in eight cases, all of whom were in the success group. Perioperative acute adverse events were recorded in 16 patients, including 11 pulmonary artery injuries, three pulmonary hemorrhages, and two pulmonary artery aneurysms. During a median follow-up period of 10.4 (0.1–21.0) months, nine cases experienced restenosis at a median time of 40 (4–325) days after angioplasty.ConclusionsThe UHP BA is safe and effective for the primary treatment of PAS in infants and children with CHD. The success rate is high with a low incidence of severe complications. The predictors of success are a larger balloon/waist ratio and the presence of therapeutic tears. The occurrence of restenosis during follow-up, however, remains a problem. A larger number of cases and longer periods of follow-up are needed for further study

Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher grade of cervical intraepithelial neoplasia

<p>Abstract</p> <p>Background</p> <p>D2-40 has been shown a selective marker for lymphatic endothelium, but also shown in the benign cervical basal cells. However, the application of D2-40 immunoreactivity in the cervical basal cells for identifying the grade of cervical intraepithelial neoplasia (CIN) has not been evaluated.</p> <p>Methods</p> <p>In this study, the immunoreactive patterns of D2-40, compared with p16^INK4A, which is currently considered as the useful marker for cervical cancers and their precancerous diseases, were examined in total 125 cervical specimens including 32 of CIN1, 37 of CIN2, 35 of CIN3, and 21 of normal cervical tissue. D2-40 and p16^INK4Aimmunoreactivities were scored semiquantitatively according to the intensity and/or extent of the staining.</p> <p>Results</p> <p>Diffuse D2-40 expression with moderate-to-strong intensity was seen in all the normal cervical epithelia (21/21, 100%) and similar pattern of D2-40 immunoreactivity with weak-to-strong intensity was observed in CIN1 (31/32, 97.2%). However, negative and/or focal D2-40 expression was found in CIN2 (negative: 20/37, 54.1%; focal: 16/37, 43.2%) and CIN3 (negative: 22/35, 62.8%; focal: 12/35, 34.3%). On the other hand, diffuse immunostaining for p16^INK4Awas shown in 37.5% of CIN1, 64.9% of CIN2, and 80.0% of CIN3. However, the immunoreactive pattern of D2-40 was not associated with the p16^INK4Aimmunoreactivity.</p> <p>Conclusions</p> <p>Immunohistochemical analysis of D2-40 combined with p16^INK4Amay have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia, especially for distinguishing CIN1 from CIN2/3.</p

Study Group for Roman Pottery Bibliography

The Study Group for Romano-British Pottery (Study Group for Roman Pottery from 1980) was founded in 1971 to provide a forum for the discussion of all matters relating to Roman pottery found in Britain, including the presentation and discussion of the latest research, and issues affecting the subject and its practitioners. The Group aims to provide a lead in Roman pottery studies as well as guidance towards best practice, and also collaborates with other specialist groups on matters of mutual interest and concern. It has published the Journal of Roman Pottery Studies since 1986, Research Frameworks for the Study of Roman Pottery and Guidelines for the Archiving of Roman Pottery (both in JRPS vol 11, 2004) and A Research Strategy and Updated Agenda for the Study of Roman Pottery in Britain (2011)

Utilization of Surplus Air Thermal Energy by a Water Cycle System in a Chinese-Type Solar Greenhouse

Solar greenhouses are commonly overheated during the day, and the remaining air heat can only be dissipated through ventilation, which is a severe energy waste problem. In order to improve the energy utilization of the greenhouse, this study proposes a water cycle system using surplus air thermal energy, which consists of an air-water heat exchanger, supply and return pipes, a submersible pump, a water tank, and an automatic control system. The proposed system stores the surplus air thermal energy in the greenhouse in the water tank. It releases it into the greenhouse using water circulation, and experimental analyses were carried out using a solar greenhouse in the Shenyang area. The effects of different air and water flow rates on the performance of the surplus air thermal energy water recycling system and the environment inside the greenhouse were analyzed by establishing a CFD model and model validation, and the average difference between the experimental data and the simulated data was 6.98%. The results show that the circulating air flow rate significantly affects the system performance and the environment inside the greenhouse. In the heat collection stage, the water circulation system with an airflow rate of 9 m/s has a minor average temperature difference in the vertical plane of the greenhouse. The water circulation system with an airflow rate of 6.0 m/s collects and releases the most significant heat. The temperature cloud between the vertical and horizontal planes is more uniform. This research provides new ideas for efficient energy use in solar greenhouses

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage

ABSTRACTDecidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. GPR133 was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that GPR133 expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased GPR133 expression. Increased GPR133 expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of GPR133 resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of GPR133 on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM

Association between P2RY12 Gene Polymorphisms and IVIG Resistance in Kawasaki Patients

Children with Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) have a higher incidence of coronary artery lesions (CAL). Despite the association between Purinergic receptor P2Y12 (P2RY12) polymorphism, KD genetic susceptibility, and CAL complications being proved, few studies have assessed the relationship between P2RY12 polymorphisms and IVIG resistance in patients with KD. We recruited 148 KD patients with IVIG resistance and 611 with IVIG sensitivity and selected five P2RY12 polymorphisms: rs9859538, rs1491974, rs7637803, rs6809699, and rs2046934. A significant difference in the genotype distributions between patients was only observed for the rs6809699 A > C polymorphism (AC vs. AA: adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.27–0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27–0.83, P=0.0084). After adjusting for age and gender, the carriers of the rs6809699 C allele had OR of 0.44 to 0.49 for IVIG sensitivity (AC vs. AA: adjusted OR = 0.48, 95% confidence interval (CI) = 0.27–0.84, P=0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27–0.83, P=0.0084) compared to the carriers of a rs6809699 AA genotype, suggesting the protective effect of this SNP against IVIG resistance. Moreover, individuals with all five protective polymorphisms experienced a significantly decreased IVIG resistance compared to that of individuals with up to three protective polymorphisms (adjusted OR = 0.27, 95% CI = 0.13–0.57, P=0.0006). Our results suggest that the P2RY12 rs6809699 polymorphism could be used as a biomarker to predict IVIG resistance in KD patients