Transgenerational Effects of Di(2-Ethylhexyl) Phthalate on Anogenital Distance,Sperm Functions and DNA Methylation in Rat Offspring

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system.     

Re-evaluation of Radiation-Energy Transfer to an Extraction Solvent in a Minor-Actinide-Separation Process Based on Consideration of Radiation Permeability

ABSTRACT

Absorbed-dose estimation is essential for evaluation of the radiation tolerance of minor-actinide-separation processes. We propose a dose-evaluation method based on radiation permeability, with comparisons of heterogeneous structures seen in the solvent-extraction process, such as emulsions forming in the mixture of the organic and aqueous phases. A demonstration of radiation-energy-transfer simulation is performed with a focus on the minor-actinide-recovery process from high-level liquid waste with the aid of the Monte Carlo radiation-transport code PHITS. The simulation results indicate that the dose absorbed by the extraction solvent from alpha radiation depends upon the emulsion structure, and that from beta and gamma radiation depends upon the mixer-settler-apparatus size. Non-negligible contributions of well-permeable gamma rays were indicated in terms of the plant operation of the minor-actinide-separation process.     

DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

应变纤锌矿ZnO/MgxZn1-xO量子点中离子施主束缚激子的光学性质

Within the framework of the effective-mass approximation and the dipole approximation, considering the three-dimensional confinement of the electron and hole and the strong built-in electric field(BEF) in strained wurtzite Zn O/Mg0:25Zn0:75O quantum dots(QDs), the optical properties of ionized donor-bound excitons(D+, X)are investigated theoretically using a variational method. The computations are performed in the case of finite band offset. Numerical results indicate that the optical properties of(D+, X) complexes sensitively depend on the donor position, the QD size and the BEF. The binding energy of(D+, X) complexes is larger when the donor is located in the vicinity of the left interface of the QDs, and it decreases with increasing QD size. The oscillator strength reduces with an increase in the dot height and increases with an increase in the dot radius. Furthermore, when the QD size decreases, the absorption peak intensity shows a marked increment, and the absorption coefficient peak has a blueshift. The strong BEF causes a redshift of the absorption coefficient peak and causes the absorption peak intensity to decrease remarkably. The physical reasons for these relationships have been analyzed in depth.     

Knowledge-Based Virtual Modeling and Simulation of Manufacturing Processes for Industry 4.0

Abstract

Industry 4.0 aims at providing a digital representation of a production landscape, but the challenges in building, maintaining, optimizing, and evolving digital models in inter-organizational production chains have not been identified yet in a systematic manner. In this paper, various Industry 4.0 research and technical challenges are addressed, and their present scenario is discussed. Moreover, in this article, the novel concept of developing experience-based virtual models of engineering entities, process, and the factory is presented. These models of production units, processes, and procedures are accomplished by virtual engineering object (VEO), virtual engineering process (VEP), and virtual engineering factory (VEF), using the knowledge representation technique of Decisional DNA. This blend of the virtual and physical domains permits monitoring of systems and analysis of data to foresee problems before they occur, develop new opportunities, prevent downtime, and even plan for the future by using simulations. Furthermore, the proposed virtual model concept not only has the capability of Query Processing and Data Integration for Industrial Data but also real-time visualization of data stream processing.     

Angiotensin I‐converting enzyme inhibitory and Ca‐binding activities of peptides prepared from tuna cooking juice and spleen proteases

Tuna cooking juice is a by‐product from the tuna canning industry. In this study, tuna cooking juice was hydrolysed by proteases extracted from the spleen. Tuna cooking juice showed the highest ACE inhibitory and Ca‐binding activities after hydrolysis for 270 and 180 min, respectively. The hydrolysate was further fractionated by ultrafiltration. The permeate exhibited highest ACE inhibitory and Ca‐binding activities when passed through 1 and 5 kDa cut‐off membranes, respectively. Gel filtration chromatography was used to determine the MW of bioactive peptides that exhibited highest ACE inhibitory and Ca‐binding activities. Those peptides that exhibited highest ACE inhibitory and Ca‐binding activities were the MW range of 238–829 Da and 1355–1880 Da, respectively. These results suggest that the tuna cooking juice and the spleen protease extract are a potential source of bioactive peptides that can be utilised as bioactive ingredients in functional food and nutraceuticals.     

Study on the non-uniform contact during ELID groove grinding

This paper introduces the potential feasibility that ELID (electrolytic in-process dressing) grinding replaces superfinishing in bearing manufacturing, but ELID grinding will bring new challenges. Different regions present distinguish surface profile due to the non-uniform contact in ELID groove grinding. However, few reports explaining the non-uniform contact are available. This article explores the mechanisms of the non-uniform contact during ELID groove grinding. Experiments on the non-uniform contact between bearing raceway and grinding wheel have been carried out under different conditions. The results show that non-uniform contact exists in ELID groove grinding process and it exerts influence on the profile of the raceway surface. Non-uniform contact influences the Rsk and Rku value all the time, but it influences the Ra value occasionally. Improvement strategies of eliminating the non-uniform contact are also discussed based on the experimental study.     

Epigenetic Targets for Oligonucleotide Therapies of Pulmonary Arterial Hypertension

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverse established arterial wall thickening, stiffening, and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from a better understanding of pulmonary vascular gene expression programs. In this review, potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying the growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery, and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. The progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.