Fourth Generation of Next-Generation Sequencing Technologies: Promise and Consequences.

In this review, we discuss the emergence of the fourth-generation sequencing technologies that preserve the spatial coordinates of RNA and DNA sequences with up to subcellular resolution, thus enabling back mapping of sequencing reads to the original histological context. This information is used, for example, in two current large-scale projects that aim to unravel the function of the brain. Also in cancer research, fourth-generation sequencing has the potential to revolutionize the field.

Knockdown of AMPKα2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27(Kip1) Signaling Pathway.

It has been shown that activation of adenosine monophosphate-activated protein kinase (AMPK) suppresses proliferation of a variety of tumor cells as well as nonmalignant cells. In this study, we used post-transcriptional gene silencing with small interfering RNA (siRNA) to specifically examine the effect of AMPK on pulmonary arterial smooth muscle cells (PASMCs) proliferation and to further elucidate its underlying molecular mechanisms. Our results showed that knockdown of AMPKα2 promoted primary cultured PASMCs proliferation; this was accompanied with the elevation of phosphorylation of mammalian target of rapamycin (mTOR) and S-phase kinase-associated protein 2 (Skp2) protein level and reduction of p27(Kip1).

Activation of AMPK Prevents Monocrotaline-Induced Extracellular Matrix Remodeling of Pulmonary Artery.

Background: The current study was performed to investigate the effect of adenosine monophosphate (AMP) - activated protein kinase (AMPK) activation on the extracellular matrix (ECM) remodeling of pulmonary arteries in pulmonary arterial hypertension (PAH) and to address its potential mechanisms.

Material And Methods: PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) into Sprague-Dawley rats. Metformin (MET) was administered to activate AMPK.

Viral dynamic modelling of Hepatitis C and resistance-associated variants in haemophiliacs.

Aim: Chronic hepatitis C virus (HCV) infection is an important source of morbidity and mortality among haemophiliacs. Limited data are available regarding treatment intervention using direct-acting antivirals (DAAs) and theoretical concerns regarding accumulation of drug-associated resistance variants (RAVs) remain. We conducted a pilot study of treatment with telaprevir/pegylated interferon-alfa/ribavirin to evaluate treatment response and the role of lead-in DAA therapy on mutational selection of resistance variants.

Subchorionic hematomas are increased in early pregnancy in women taking low-dose aspirin.

Objective: To determine the frequency of subchorionic hematomas (SCH) in first-trimester ultrasound examinations of patients with infertility and recurrent pregnancy loss (RPL) and in patients from a general obstetric population. To determine if the method of assisted reproduction utilized or the use of anticoagulants, such as heparin and aspirin (ASA), influenced frequency of SCH.

Design: Prospective, cohort study.

LKB1/AMPK inhibits TGF-β1 production and the TGF-β signaling pathway in breast cancer cells.

Adenosine monophosphate-activated protein kinase (AMPK) acts as a fuel gauge that maintains energy homeostasis in both normal and cancerous cells, and has emerged as a tumor suppressor. The present study aims to delineate the functional relationship between AMPK and transforming growth factor beta (TGF-β). Our results showed that expression of liver kinase B1 (LKB1), an upstream kinase of AMPK, impeded TGF-β-induced Smad phosphorylation and their transcriptional activity in breast cancer cells, whereas knockdown of LKB1 or AMPKα1 subunit by short hairpin RNA (shRNA) enhanced the effect of TGF-β.

Fertility Preservation Through Oocyte Cryopreservation in a Patient with Ovarian Dysgerminocarcinoma: A Case Report.

Background: This case evaluates a 20-year-old patient diagnosed with recurrent dysgerminoma who desired fertility preservation.

Case: A 20-year-old woman, GOPO, with a history of fertility-preserving right salpingo-oophorectomy and staging for dysgerminoma presented with interval change of a 5-cm left ovarian solid mass on ultrasound evaluation concerning for recurrent carcinoma. She underwent controlled ovarian hyperstimulation with injectable gonadotropins followed by transvaginal oocyte retrieval immediately followed by laparotomy, at which time ovarian dysgerminoma was confirmed.

Association between IL-17F rs763780 polymorphism and susceptibility of asthma: a meta-analysis.

Published data on the association between interleukin-17F (IL-17F) rs763780 polymorphism and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. A literature search was conducted in PubMed, Web of Science, Elsevier, Wanfang, and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies.

Interleukin-6 gene -174G/C polymorphism and bronchial asthma risk: a meta-analysis.

The Interleukin-6 (IL-6) genetic polymorphism is associated with bronchial asthma, a number of studies have been conducted to investigate the association between IL-6 gene -174G/C polymorphism and bronchial asthma risk. However, the results are inconclusive. This meta-analysis aims to investigate whether -174G/C polymorphism is a potential risk factor for bronchial asthma.

Clinical significance and role of LKB1 in gastric cancer.

Liver kinase B1 (LKB1) functions as a tumor suppressor gene, and loss in the expression of LKB1 contributes to human carcinogenesis and tumor progression. The present study investigated the association between LKB1 and gastric cancer. SGC‑7901 gastric cancer cell lines and 63 patients with gastric cancer were examined in the present study, and lentivirus transfection, reverse transription‑quantitative polymerase chain reaction and flow cytometric analyses were performed.

New technologies for DNA analysis--a review of the READNA Project.

The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 41/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.

Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.

Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment.

Self-catalytic polymerization of a water-soluble selenium/polypyrrole nanocomposite and its nonlinear optical properties.

A facile one-step method for the synthesis of a water-soluble selenium/polypyrrole (Se/PPy) nanocomposite was developed. In the aqueous synthesis process, the pyrrole acted as a reductant for the reduction of H2SeO3, and then the elemental Se formed in situ acted as a catalyst for the polymerization of pyrrole. The characterization results show that the as-obtained composite (Se/PPy) is a spherical (Φ80 nm) product that is made up of amorphous Se particles coated by PPy layers.

Identification and proteomic analysis of osteoblast-derived exosomes.

Exosomes are nanometer-sized vesicles with the function of intercellular communication, and they are released by various cell types. To reveal the knowledge about the exosomes from osteoblast, and explore the potential functions of osteogenesis, we isolated microvesicles from supernatants of mouse Mc3t3 by ultracentrifugation, characterized exosomes by electron microscopy and immunoblotting and presented the protein profile by proteomic analysis. The result demonstrated that microvesicles were between 30 and 100 nm in diameter, round shape with cup-like concavity and expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1.

Interleukin-6 gene -174G>C polymorphism and chronic obstructive pulmonary disease risk: a meta-analysis.

Association studies of interleukin-6 (IL-6) -174G>C polymorphism and chronic obstructive pulmonary disease (COPD) have yielded inconsistent results, possibly because single studies often lack sufficient statistical power. A comprehensive search was performed in the PubMed, Embase, Elsevier, Web of Science databases, Wanfang, and the Chinese National Knowledge Infrastructure (CNKI) databases for published studies investigating the associations between IL-6 -174G>C polymorphism and COPD. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess the possible associations.

Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension.

It has been shown that activation of Notch3 signaling is involved in the development of pulmonary arterial hypertension (PAH) by stimulating pulmonary arteries remodeling, while the molecular mechanisms underlying this are still largely unknown. The aims of this study are to address these issues. Monocrotaline dramatically increased right ventricle systolic pressure to 39.

Compact, battery powered, wireless digitizers for in situ data acquisitions in the sino-united spherical tokamak.

Potential isolation and long cable drive are very important in acquiring certain signals from tokamak diagnostics. Compact, battery powered, wireless digitizers for in situ data acquisition have been developed and routinely used in the sino-united spherical tokamak to solve the problems of isolation and long cables. The wireless digitizers utilize the integrated analog to digital converters and the static random access memory of microcontrollers but transfer data wirelessly.

Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection.

Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes.

Metformin, an old drug, brings a new era to cancer therapy.

Metformin is the most commonly prescribed drug for type 2 diabetes mellitus as it is inexpensive, safe, and efficient in ameliorating hyperglycemia and hyperinsulinemia. Epidemiological and clinical observation studies have shown that metformin use reduces risk of cancer in patients with type 2 diabetes mellitus and improves prognosis and survival rate of the cancer patients. Furthermore, ongoing clinical trials of metformin in cancer therapy are extending to nondiabetic population.

Engraftment of embryonic stem cells and differentiated progeny by host conditioning with total lymphoid irradiation and regulatory T cells.

Embryonic stem cells (ESCs) hold promise for the treatment of many medical conditions; however, their utility is limited by immune rejection. The objective of our study is to establish tolerance or promote engraftment of transplanted ESCs as well as mature cell populations derived from ESCs. Luciferase (luc(+))-expressing ESCs were utilized to monitor the survival of the ESCs and differentiated progeny in living recipients.

Vitamin D-binding protein gene polymorphisms and chronic obstructive pulmonary disease susceptibility: A meta-analysis.

The vitamin D-binding protein () genetic polymorphisms have been associated with chronic obstructive pulmonary disease (COPD). A number of studies have been conducted to investigate the combined effects of the gene (GC) rs7041 and rs4588 polymorphisms on the COPD risk. However, the results obtained are inconclusive.

S267P mutation in FGFR2: first report in a patient with Crouzon syndrome.

It has been known for several years that mutations in the fibroblast growth factor receptor (FGFR2) result in syndromic craniosynostosis including Apert, Crouzon, or Pfeiffer syndromes. Here, we report on a child with a clinically diagnosed Crouzon syndrome that shows the missense point mutation S267P in FGFR2 gene. The mutation is firstly identified in Crouzon syndrome.

The C342R mutation in FGFR2 causes Crouzon syndrome with elbow deformity.

Crouzon syndrome is an autosomal dominant craniosynostosis syndrome caused by mutation in the fibroblast growth factor receptor 2 (FGFR-2). Numerous findings from animal studies imply a critical role for FGFRs in the regulation of skeletal development. Here, we report 2 unrelated patients with Crouzon syndrome accompanied by elbow deformity.

Skeleton first in surgical treatment of facial disharmony.

Purpose: The aim of this study was to correct facial disharmony with or without occlusal dysfunction.

Methods: Based on computed tomography and presurgical design, restoration of normal skeleton relationship is a priority for selected facial deformities. Combination of different osteotomies for facial skeleton was chosen in 1-stage operation such as orthognathic surgery, zygomatic reduction, and mandibular angle reduction.