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.     

Systematic Review: Adipose-Derived Mesenchymal Stem Cells,Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.     

Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.     

New Insights into the Pathogenesis of Systemic Mastocytosis

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management of SM is highly individualized and was largely palliative for patients without a targeted form of therapy in past decades. Targeted therapy with midostaurin, a multiple kinase inhibitor that inhibits KIT, has demonstrated efficacy in patients with advanced SM. This led to the recent approval of midostaurin by the United States Food and Drug Administration and European Medicines Agency. However, the overall survival of patients treated with midostaurin remains unsatisfactory. The identification of genetic and epigenetic alterations and understanding their interactions and the molecular mechanisms involved in mastocytosis is necessary to develop rationally targeted therapeutic strategies. This review briefly summarizes recent developments in the understanding of SM pathogenesis and potential treatment strategies for patients with SM.     

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

计算机网络办公自动化及安全策略探究

互联网通讯采取标准化模式主要以TCP/IP协议为载体,通讯的优越特性体现在同时具备便捷性与开放性,为办公提供很大的便利,但基于网络系统也会入侵病毒、也会给信息数据与办公体系安全性造成威胁,直接影响企业综合稳定发展。据此,为保障办公工作的顺利开展,本文对计算机网络办公自动化及安全策略进行详细分析。     

Effect of wind condition on unintended hydrogen release in a hydrogen refueling station

Ambient condition, especially the wind condition, is an important factor to determine the behavior of hydrogen diffusion during hydrogen release. However, only few studies aim at the quantitative study of the hydrogen diffusion in a wind-exist condition. And very little researches aiming at the variable wind condition have been done. In this paper, the hydrogen diffusion in different wind condition which including the constant wind velocity and the variable wind velocity is investigated numerically. When considering the variable wind velocity, the UDF (user defined function) is compiled. Characteristics of the FGC (flammable gas cloud) and the HMF (hydrogen mass fraction) are analyzed in different wind condition and comparisons are made with the no-wind condition. Results indicate that the constant wind velocity and the variable wind velocity have totally different effect for the determination of hydrogen diffusion. Comparisons between the constant wind velocity and the variable wind velocity indicate that the variable wind velocity may cause a more dangerous situation since there has a larger FGC volume. More importantly, the wind condition has a non-negligible effect when considering the HMF along the radial direction. As the wind velocity increases, the distribution of the HMF along the radial direction is not Gaussian anymore when the distance between the release hole and the observation line exceeds to a critical value. This work can be a supplement of the research on the hydrogen release and diffusion and a valuable reference for the researchers.     

Influence of α′‐/α‐crystal polymorphism on properties of poly(l‐lactic acid)

Poly(l ‐lactic acid) (PLLA) is a biodegradable and biocompatible thermoplastic polyester produced from renewable sources, widely used for biomedical devices, in food packaging and in agriculture. It is a semicrystalline polymer, and as such its properties are strongly affected by the developed semicrystalline morphology. As a function of the crystallization temperature, PLLA can form different crystal modifications, namely α′‐crystals below about 120 °C and α‐crystals at higher temperatures. The α′ modification is therefore of special importance as it may be the preferred polymorph developing at processing‐relevant conditions. It is a metastable modification which typically transforms into the more stable α‐crystals on annealing at elevated temperature. The structure, kinetics of formation and thermodynamics of α′‐ and α‐crystals of PLLA are reviewed in this contribution, together with the effect of α′‐/α‐crystal polymorphism on the properties of PLLA. © 2018 Society of Chemical Industry     

Current trends in structural development and modification strategies for metal-organic frameworks (MOFs) towards photocatalytic H2 production: A review

Photocatalytic H₂ generation using semiconductor photocatalysts is considered as a cost-effective and eco-friendly technology for solar to energy conversion; however, the present photocatalysts have been recognized to depict low efficiency. Currently, porous coordination polymers known as metal-organic frameworks (MOFs) constituting flexible and modifiable porous structure and having excess active sites are considered to be appropriate for photocatalytic H₂ production. This review highlights current progress in structural development of MOF materials along with modification strategies for enhanced photoactivity. Initially, the review discusses the photocatalytic H₂ production mechanism with the concepts of thermodynamics and mass transfer with particular focus on MOFs. Elaboration of the structural categories of MOFs into Type I, Type II, Type III and classification of MOFs for H₂ generation into transition metal based, post-transition metal based, noble-metal based and hetero-metal based has been systematically discussed. The review also critically deliberate various modification approaches of band engineering, improvement of charge separation, efficient irradiation utilization and overall efficiency of MOFs including metal modification, heterojunction formation, Z-scheme formation, by introducing electron mediator, and dye based composites. Also, the MOF synthesized derivatives for photocatalytic H₂ generation are elaborated. Finally, future perspectives of MOFs for H₂ generation and approaches for efficiency improvement have been suggested.