Case report: Whole exome sequencing and genome-wide methylation profiling of Czech dysplasia in a Chinese pedigree.

Background: Czech dysplasia is a rare skeletal disorder with symptomatology including platyspondyly, brachydactyly of the third and fourth toes, and early-onset progressive pseudorheumatoid arthritis. The disorder segregates in an autosomal dominant fashion. A specific missense mutation (R275C, c.823C > T) in exon 13 of the COL2A1 gene has been identified in German and Japanese families. Case summary: We present the case of a Chinese woman diagnosed with Czech dysplasia (proband) who carried a variant in the COL2A1 gene. Whole-exome sequencing (WES) identified the COL2A1 missense mutation (R275C, c.823C > T) in close relatives of the proband who also exhibited the same disorder. Conclusion: This study is a thorough clinical and physiological description of Czech dysplasia in a Chinese patient.

Overexpression of MxbHLH18 Increased Iron and High Salinity Stress Tolerance in Arabidopsis thaliana.

In the life cycle of apple, it will suffer a variety of abiotic stresses, such as iron stress and salt stress. bHLH transcription factors (TFs) play an indispensable role in the response of plants to stress. In this study, a new bHLH gene named MxbHLH18 was separated from Malus xiaojinensis. According to the results of subcellular localization, MxbHLH18 was localized in the nucleus. Salt stress and iron stress affected the expression of MxbHLH18 in Malus xiaojinensis seedlings to a large extent. Due to the introduction of MxbHLH18, the resistance of Arabidopsis thaliana to salt, high iron and low iron was significantly enhanced. Under the environmental conditions of high iron and low iron, the overexpression of MxbHLH18 increased many physiological indexes of transgenic Arabidopsis compared to wild type (WT), such as root length, fresh weight and iron content. The high level expression of MxbHLH18 in transformed Arabidopsis thaliana can not only increased the content of chlorophyll and proline, as well as increasing the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); it also reduced the content of malondialdehyde (MDA), which was more obvious under high salt conditions. In addition, the relative conductivity, H2O2 content and O2- content in transgenic Arabidopsis decreased under salt stress. Meanwhile, MxbHLH18 can also regulate the expression of downstream genes associated with salt stress (AtCBF1/2/3, AtKIN1 and AtCOR15a/b) and iron stress (AtIRT1, AtFRO2, AtNAS2, ATACT2, AtZIF1 and AtOPT3). Therefore, MxbHLH18 can actively promote the adaptability of plants to the growth environment of salt and low and/or iron.

Co-ablation versus cryoablation for the treatment of stage III-IV non-small cell lung cancer: A prospective, noninferiority, randomized, controlled trial (RCT).

BACKGROUND: This study compared a co-ablation (CA) system, which is a novel ablation device, with an argon-helium cryoablation (AHC) system. We aimed to compare the efficacy and safety of CA and AHC for the treatment of stage III-IV non-small cell lung cancer (NSCLC). METHODS: We conducted a multicenter randomized controlled trial (RCT) to determine whether CA was noninferior to AHC. The primary efficacy endpoints were the iceball coverage rate (ICR) and the disease control rate (DCR) one month after treatment. Noninferiority was declared if the lower limit of two-sided 95% confidence interval (CI) was less than 10%. The ICR and DCR were identified by logistic regression. Treatment safety was assessed. RESULTS: A total of 81 patients underwent randomization (41 assigned to the CA and 40 assigned to the AHC groups)and transthoracic ablation. The ICRs in the CA and AHC groups were 99.24% ± 2.18% and 98.66% ± 3.79%, respectively. Central lesions were associated with an increased risk of an incomplete ICR. The DCRs in the CA and AHC groups were 97.6% and 95%, respectively. A smaller lesion area in the CA group was significantly correlated with a better DCR. The rate of complications was 29.26% in the CA group and 30% in the AHC group. (P = 0.943). There was less probe usage per patient in the CA group. CONCLUSIONS: We determined that CA is noninferior to AHC in terms of efficacy and safety for the treatment of stage III-IV NSCLC. A smaller lesion area in the CA group was significantly correlated with a better DCR. KEY POINTS: CA was noninferior to AHC for stage III-IV NSCLC.

The effect of microwave pretreatment on anaerobic co-digestion of sludge and food waste: Performance, kinetics and energy recovery.

This paper studied the effect of microwave (MW) pretreatment on anaerobic co-digestion of sludge (SS) and food waste (FW). Using SS and FW as digestive substrates, the MW pretreatment method was used to determine the changes in the substrate matrix by means of batch anaerobic digestion at 37 °C. The kinetics of methane production were calculated, and the changes in organic matter during anaerobic co-digestion, the properties of the anaerobic-digested effluent, and the net energy output of the co-digestion system were determinated. The results showed that MW pretreatment was beneficial to the dissolution of organic matter, conversion of protein to NH4+-N, cumulative methane production, unit biomethane yield, and reaction rate of methane production in the SS and FW anaerobic co-digestion system. The highest cumulative methane production in the co-digestion system reached 3446.3 ± 172.3 mL (35 days), which was 19.93% higher than that of the control. Furthermore, MW pretreatment significantly increased the accumulation of VFAs and the content of butyric acid in the anaerobic-digested effluent, which was beneficial to the methanogenesis process. The MW pretreatment of all co-digested substrates produced a greater net energy output than the control, and the MW-SS + MW-FW group yielded the highest net energy output, which was 76.25 kJ/g Fed VS. The results indicated that MW pretreatment prior to SS and FW anaerobic co-digestion is an effective way to improve the anaerobic digestion efficiency and energy recovery rate.

The balance of protein farnesylation and geranylgeranylation during the progression of nonalcoholic fatty liver disease.

Protein prenylation is an essential posttranslational modification and includes protein farnesylation and geranylgeranylation using farnesyl diphosphate or geranylgeranyl diphosphate as substrates, respectively. Geranylgeranyl diphosphate synthase is a branch point enzyme in the mevalonate pathway that affects the ratio of farnesyl diphosphate to geranylgeranyl diphosphate. Abnormal geranylgeranyl diphosphate synthase expression and activity can therefore disrupt the balance of farnesylation and geranylgeranylation and alter the ratio between farnesylated and geranylgeranylated proteins. This change is associated with the progression of nonalcoholic fatty liver disease (NAFLD), a condition characterized by hepatic fat overload. Of note, differential accumulation of farnesylated and geranylgeranylated proteins has been associated with differential stages of NAFLD and NAFLD-associated liver fibrosis. In this review, we summarize key aspects of protein prenylation as well as advances that have uncovered the regulation of associated metabolic patterns and signaling pathways, such as Ras GTPase signaling, involved in NAFLD progression. Additionally, we discuss unique opportunities for targeting prenylation in NAFLD/hepatocellular carcinoma with agents such as statins and bisphosphonates to improve clinical outcomes.

G Protein-Coupled Receptor 30 Mediates the Anticancer Effects Induced by Eicosapentaenoic Acid in Ovarian Cancer Cells.

PURPOSE: While numerous epidemiological studies have indicated that omega-3 polyunsaturated fatty acids have anticancer properties in various cancers, the effects and mechanisms of eicosapentaenoic acid (EPA) in ovarian cancer cell growth are poorly understood. MATERIALS AND METHODS: ES2 ovarian clear cell carcinoma cells and SKOV3 adenocarcinoma cells were treated with palmitic acid or EPA, followed by flow cytometry and cell counting to measure apoptosis and proliferation, respectively. A modified protein lipid overlay assay was used to further verify whether EPA was a ligand of G protein-coupled receptor 30 (GPR30) in ES2 cells. The levels of apoptosis-related genes, phosphorylated AKT, and phosphorylated ERK1/2 were detected to explore the underlying mechanism. Finally, inhibitory effect of EPA on tumor growth via GPR30 was determined in vitro and in vivo. RESULTS: EPA suppressed ES2 ovarian clear cell carcinoma cells growth via GPR30, a novel EPA receptor, by inducing apoptosis. As a ligand of GPR30, EPA activated the GPR30-cAMP- protein kinase A signaling pathway. When GPR30 was suppressed by siRNA or its inhibitor G15, the antiproliferative action of EPA was impaired. Furthermore, EPA inhibited tumor growth by blocking the activation of AKT and ERK. In the mouse xenograft model, EPA decreased tumor volume and weight through GPR30 by blocking tumor cell proliferation. CONCLUSION: These results confirm that EPA is a tumor suppressor in human ovarian clear cell carcinoma cells and functions through a novel fatty acid receptor, GPR30, indicating a mechanistic linkage between omega-3 fatty acids and cancers.

Cardioprotective Effects of Exosomes and Their Potential Therapeutic Use.

Exosomes are membrane-contained vesicles released by various types of cells both in animals and human. They contain microRNAs and proteins and can travel to target cells, affecting their functions. There are specific factors on the surface of every exosomes, making sure that they will be taken up by certain type of cells. With these features, exosomes have been recognized to be one of the fundamental "messengers" for cell-cell communication. Recently, increased interest has been raised in exosomes since they were discovered to play an unneglectable role in preserving cardiac function and cardiomyocyte repair during stress. The widely explored stem cell therapy for cardiomyopathy uncovered the contribution of exosomes. Here we summarized cardioprotective effects of exosomes and their potential therapeutic use.

Individual exposure of graduate students to PM2.5 and black carbon in Shanghai, China.

The personal exposure of 51 graduate students to PM2.5 and BC in Shanghai was evaluated using portable PM2.5 and BC samplers. Global positioning systems and activity diaries were used to evaluate the microenvironments/activities that contributed to the total daily exposure of the participants, as well as to accurately estimate the PM2.5 and BC doses received by each participant. The mean PM2.5 and BC exposure concentrations were 110.0 and 5.3 µg m(-3), respectively. These exposure levels were considered extremely high and comparable to those measured in a busy urban street canyon for 24 h. High daily inhaled doses in terms of both PM2.5 and BC concentrations were measured, obtaining 1062.2 and 45.9 µg day(-1), respectively. Indoor activities significantly contributed to the students' daily dose. Eating contributed the least to PM2.5 and BC exposure, whereas outdoor activities contributed the most. PM2.5 dose intensity from indoor eating slightly exceeded BC dose intensity; conversely, transportation showed higher exposure for BC than PM2.5.

Combined transjugular intrahepatic portosystemic shunt and other interventions for hepatocellular carcinoma with portal hypertension.

AIM: To evaluate combination transjugular intrahepatic portosystemic shunt (TIPS) and other interventions for hepatocellular carcinoma (HCC) and portal hypertension. METHODS: Two hundred and sixty-one patients with HCC and portal hypertension underwent TIPS combined with other interventional treatments (transarterial chemoembolization/transarterial embolization, radiofrequency ablation, hepatic arterio-portal fistulas embolization, and splenic artery embolization) from January 1997 to January 2010 at Beijing Shijitan Hospital. Two hundred and nine patients (121 male and 88 female, aged 25-69 years, mean 48.3 ± 12.5 years) with complete clinical data were recruited. We evaluated the safety of the procedure (procedure-related death and serious complications), change of portal vein pressure before and after TIPS, symptom relief [e.g., ascites, hydrothorax, esophageal gastric-fundus variceal bleeding (EGVB)], cumulative rates of survival, and distributary channel restenosis. The characteristics of the patients surviving ≥ 5 and < 5 years were also analyzed. RESULTS: The portosystemic pressure was decreased from 29.0 ± 4.1 mmHg before TIPS to 18.1 ± 2.9 mmHg after TIPS (t = 69.32, P < 0.05). Portosystemic pressure was decreased and portal hypertension symptoms were ameliorated. During the 5 year follow-up, the total recurrence rate of resistant ascites or hydrothorax was 7.2% (15/209); 36.8% (77/209) for EGVB; and 39.2% (82/209) for hepatic encephalopathy. The cumulative rates of distributary channel restenosis at 1, 2, 3, 4, and 5 years were 17.2% (36/209), 29.7% (62/209), 36.8% (77/209), 45.5% (95/209) and 58.4% (122/209), respectively. No procedure-related deaths and serious complications (e.g., abdominal bleeding, hepatic failure, and distant metastasis) occurred. Moreover, Child-Pugh score, portal vein tumor thrombosis, lesion diameter, hepatic arterio-portal fistulas, HCC diagnosed before or after TIPS, stent type, hepatic encephalopathy, and type of other interventional treatments were related to 5 year survival after comparing patient characteristics. CONCLUSION: TIPS combined with other interventional treatments seems to be safe and efficacious in patients with HCC and portal hypertension.

Transjugular intrahepatic portosystemic shunt for severe jaundice in patients with acute Budd-Chiari syndrome.

AIM: To evaluate the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) for severe jaundice secondary to acute Budd-Chiari syndrome (BCS). METHODS: From February 2009 to March 2013, 37 patients with severe jaundice secondary to acute BCS were treated. Sixteen patients without hepatic venule, hepatic veins (HV) obstruction underwent percutaneous angioplasty of the inferior vena cava (IVC) and/or HVs. Twenty-one patients with HV occlusion underwent TIPS. Serum bilirubin, liver function, demographic data and operative data of the two groups of patients were analyzed. RESULTS: Twenty-one patients underwent TIPS and the technical success rate was 100%, with no technical complications. Sixteen patients underwent recanalization of the IVC and/or HVs and the technical success rate was 100%. The mean procedure time for TIPS was 84.0±12.11 min and angioplasty was 44.11±5.12 min (P<0.01). The mean portosystemic pressure in the TIPS group decreased significantly from 40.50±4.32 to 16.05±3.50 mmHg (P<0.01). The mean portosystemic pressure gradient decreased significantly from 33.60±2.62 to 7.30±2.21 mmHg (P<0.01). At 8 wk after the procedures, in the TIPS group, total bilirubin (TBIL) decreased significantly from 266.24±122.03 before surgery to 40.11±3.52 µmol/L (P<0.01) and direct bilirubin (DBIL) decreased significantly from 194.22±69.82 µmol/L to 29.82±3.10 µmol/L (P<0.01). In the angioplasty group, bilirubin returned to the normal range, with TBIL decreased significantly from 258.22±72.71 µmol/L to 13.33±3.54 µmol/L (P<0.01) and DBIL from 175.08±39.27 to 4.03±1.74 µmol/L (P<0.01). Liver function improved faster than TBIL. After 2 wk, in the TIPS group, alanine aminotransferase (ALT) decreased significantly from 50.33±40.61 U/L to 28.67±7.02 U/L (P<0.01) and aspartate aminotransferase (AST) from 49.46±34.33 U/L to 26.89±8.68 U/L (P<0.01). In the angioplasty group, ALT decreased significantly from 51.56±27.90 to 14.22±2.59 µmol/L (P<0.01) and AST from 60.66±39.89 µmol/L to 8.18±1.89 µmol/L (P<0.01). After mean follow-up of 12.6 mo, there was no recurrence of jaundice in either group. CONCLUSION: Severe jaundice is not a contraindication for TIPS in patients with acute BCS and TIPS is appropriate for severe jaundice due to BCS.