Association between sperm mitochondrial ND2 gene variants and total fertilization failure

The objective of this study was to explore the association of sperm mitochondrial ND2 (MT-ND2) gene variants with total fertilization failure (TFF). A retrospective comparative study of 246 cases of fresh in vitro fertilization (IVF) cycles or half-intracytoplasmic sperm injection cycles in the Han Chinese population was performed from July 2011 to May 2017. A total of 59 cases undergoing TFF, and 187 control cases with normal fertilization (fertilization rates >50%) were included. The sperm mitochondrial genovariation was determined using nested sequencing. A total of 32 homoplasmic variants and 47 heteroplasmic variants of MT-ND2 gene were observed in this study. There were no significant differences in the frequencies of the 32 homoplasmic variants of MT-ND2 gene between the TFF and control groups. A total of 53 pair-wise comparisons were performed, and the general characteristics of the IVF failure and control subjects were adjusted in logistic models. Data suggested that there were no significant differences in the frequencies of point 4914, 5320, and 5426 heteroplasmic variants of MT-ND2 gene between the TFF and control groups. In addition, no significant difference was observed in the frequency of mtDNA haplogroup D or haplogroup G between the IVF failure group and the normal fertilization group. This study suggests that the MT-ND2 gene variants might not be associated with TFF.

Abbreviations: ATP: adenosine triphosphate; dNTP: deoxy-ribonucleoside triphosphate; FADH2: flavin adenine dinucleotide; FDR: false discovery rate; FSH: follicle-stimulating hormone; IVF: in vitro fertilization; LH: luteinizing hormone; MTATP6: mitochondrially encoded ATP synthase 6; MTCYB: mitochondrially encoded cytochrome b; mtDNA: mitochondrial DNA; MT-ND2: mitochondrial ND2; NADH: nicotinamide adenine dinucleotide; ND2: NADH dehydrogenase subunit 2; OXPHOS: oxidative phosphorylation; PCR: single nucleotide polymorphisms; SNPs: single nucleotide polymorphisms; TFF: total fertilization failure     

SimPEL: Simulation‐based power estimation for sequencing studies of low‐prevalence conditions

Power estimations are important for optimizing genotype‐phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill‐suited for the inherent challenges of studies for low‐prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation‐based program providing power estimations for the design of low‐prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low‐frequency condition studies. SimPEL, as a tool, provides researchers studying low‐frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform‐independent “batteries included” executable and default input files are available at https://github.com/precisionomics/SimPEL .     

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.     

mTOR and ERK regulate VKORC1 expression in both hepatoma cells and hepatocytes which influence blood coagulation

Clinical and Experimental Medicine - Deficiency of γ-glutamyl carboxylation of coagulation factors, as evidenced by the elevated level of Des-γ-carboxyl prothrombin (DCP), is a common...     

外周血中hnRNP A2/B1含量及其在肺癌诊断中的意义

目的用FQ-RT-PCR技术检测外周血中hnRNPA2/B1表达水平及在肺癌诊断中的意义.方法用FQ-RT-PCR技术定量分别检测18例健康体检者、12例肺部良性疾病和30例肺癌患者外周血中hnRNPA2/B1 mRNA,并用β-actin对hnRNPA2/B1表达水平进行标化.结果 hnRNPA2/B1与β-actin的比值在正常对照组和良性肺部疾病组间差异无显著性(P>0.05),而肺癌组均高于前两组(P<0.05);hnRNPA2/B1基因在低分化鳞癌中的表达水平很低,与其它类型肺癌差异有显著性(P<0.05).结论 hnRNPA2/B1在血中表达水平的差异在肺癌诊断中具有一定临床应用价值,并与肺癌的病理分级有一定相关性.     

Efficient Production of High‐Quality Polystyrene‐Functionalized Graphene via Graphite Exfoliation in Chloroform with a Heterobifunctional Hyperbranched Polyethylene as Stabilizer

Efficient production of high‐quality, functionalized graphene is highly desirable for large‐scale applications of graphene. Herein, a route for producing high‐quality, polystyrene (PS)‐functionalized graphene is demonstrated via graphite exfoliation in chloroform with a heterobifunctional hyperbranched polyethylene, HBPE@Py@PS, as stabilizer. The HBPE@Py@PS, possessing a pyrene‐functionalized hyperbranched polyethylene backbone and multiple PS side chains, is synthesized by combining chain walking polymerization and atom transfer radical polymerization techniques. It is confirmed that the HBPE@Py@PS can effectively promote graphite exfoliation in chloroform under sonication to render stable dispersions of high‐quality graphene, with an exfoliation efficiency high as 15% and a monolayer proportion, 61%. Meanwhile, it can irreversibly adsorb on the exfoliated graphene surface based on the π–π stacking interactions, concurrently rendering PS‐functionalized graphene that is fluorescent and highly dispersible in chloroform, with a film conductivity reaching 1100 S m^?1. The as‐produced graphene may find its applications as nanofiller for various PS‐based graphene nanocomposites.     

Poly(4‐vinyl imidazole): A pH‐Responsive Trigger for Hierarchical Self‐Assembly of Multicompartment Micelles Based upon Triblock Terpolymers

Poly(vinyl pyridine) has widely been used as a pH‐responsive polymer to trigger changes in self‐assembly of block copolymer micelles. However, the polymer is known to display toxic features, which limits its ultimate applicability for biological applications. Here, poly(4‐vinyl imidazole) (P4VIm), a much more biocompatible polymer, is used as a pH‐responsive block to modulate the self‐assembly of ABC triblock terpolymers. In this article, the synthesis of the poly(1‐acryloyl fructopyranose)‐block‐ poly(n‐butyl acrylate)‐block‐ poly(4‐vinyl imidazole) (PFruA₅₂‐b‐PBuA₃₀₀‐b‐P4VIm₂₅₀) triblock terpolymers is first discussed by sequential reversible addition fragmentation chain transfer (RAFT) polymerization. Subsequently, the structure formation of the triblock terpolymer is elucidated by step‐wise solvent exchange. The polymer readily dissolves in methanol, but self‐assembles into micelles with PBuA cores and mixed shell in methanol–water mixtures. Solvent exchange against buffer solutions of pH 6–6.5 leads to collapse of P4VIm due to deprotonation and induces self‐assembly into caterpillar‐like non‐spherical nanoparticles, most likely via the formation of intermediate Janus particles. The rearrangement into larger hierarchical structure, as seen by small angle X‐ray scattering (SAXS), is found to process within several hours. The article is concluded by demonstrating lower cytotoxicity values for the present polymer in comparison to a structurally analogous triblock terpolymer based on poly(vinyl pyridine).