MicroRNA expression in infertile men: its alterations and effects.

Infertility is an important reproductive health problem, and male infertility is especially important in more than half of infertility cases. Due to the importance of genetic factors in this condition, analysis of semen alone is not enough to recognize men with idiopathic infertility. A molecular non-invasive investigation is necessary to gain valuable information. Currently, microRNAs (miRNAs) are being used as non-invasive diagnostic biomarkers. miRNAs, single-stranded non-coding RNA molecules, act as post-transcriptional gene silencing regulators either by inhibition or repression of translation. Changes in the regulation of miRNAs have been investigated in several different types of male infertility, therefore the biological role of miRNA and gene targets has been defined. The purpose of this study was to review recent research on the altered expression of miRNA in semen, sperm, and testicular biopsy samples in infertile males with different types of unexplained infertility. Changes in miRNA regulation were investigated using microarray and the miRNA levels were confirmed by real-time qRT-PCR. This review explains why creating a non-invasive diagnostic method for male infertility is necessary and how changes in miRNA expression can be used as new diagnostic biomarkers in patients with differing spermatogenic and histopathologic injury.

Analytical chromatography approaches during the synthesis and conjugation of methoxypolyethylene glycol-succinimidyl butanoate (mPEG-SBA) to epoetin beta.

Conjugation of epoetin beta (EPO) with methoxypolyethylene glycol-succinimidyl butanoate (mPEG-SBA) was studied. The compound mPEG-SBA was synthesized from mPEG, and the obtained intermediates and final product were analyzed by a reversed-phase chromatographic system equipped with an evaporative light scattering detector. Labeling the hydroxyl group in PEGs with benzoyl chloride and succinimide with benzylamine was applied to resolve and characterize different PEGs. The synthesized mPEG-SBA was used for the PEGylation of EPO. A size-exclusion chromatographic method monitored the reaction, simultaneously determining the PEGylated and unreacted EPO and protein aggregates. A borate buffer (0.1 M, pH 7.8) and PEG/protein molar ratio of 3:1 produced a maximum amount of monoPEGylated EPO with the minimum amount of polyPEGylated EPO variants. Although EPO is considered a stable glycoprotein hormone that remains monomeric when refrigerated, PEGylation of EPO with mPEG-SBA resulted in the significant formation of EPO dimer. The formation of EPO dimer and polyPEGylated EPO was pH-dependent, showing higher amounts of aggregates and lower amounts of polyPEGylated forms in lower pH values. Accordingly, aggregated EPO should be considered a major PEGylation-related impurity. In conclusion, the present study highlighted the importance of having suitable analytical approaches in controlling mPEG-SBA synthesis and conjugation to EPO.

Evaluation of Mast Cell Density using CD117 antibody and Microvessel Density Using CD34 Antibody in Different Grades of Oral Squamous Cell Carcinoma.

OBJECTIVE: To compare mast cell and microvessel densities among histologic grades of oral squamous cell carcinoma. SETTING: Armed Forces Institute of Pathology. MATERIALS AND METHODS: A total of 60 specimens of OSCC comprising 20 each of well, moderately and poorly differentiated were evaluated. Immunohistochemical analysis was performed to measure MCD and MVD by applying monoclonal CD117 antibody and monoclonal CD34 antibody, on formalin fixed and paraffin embedded sections. ANOVA and Post Hoc Tukey test was employed to assess the densities and to compare the differences between different grades of OSCC. A p-value.

The Effect of Increased miR-16-1 Levels in Mouse Embryos on Epigenetic Modification, Target Gene Expression, and Developmental Processes.

Changes in microRNA (miRNA) levels are present in numerous diseases. Although these changes are particularly noted in male infertility, little is known about the effects of increased miR-16-1 in sperm from infertile men. In this study, we assessed the effects of increased mir-16-1 expression on the developmental process, epigenetic changes, and target gene expressions. IVF embryos, 6 h after insemination, were divided into three groups: control, control negative (CN), and miR-16-1 harboring plasmid microinjection. The developmental rates of these embryos were recorded after 24, 48, 72, and 96 h of culture. The levels of histone H3 lysine 4 tri-methylation (H3K4me3) and histone H3 lysine 27 tri-methylation (H3K27me3) were assessed in the 2-cell and blastocyst stages by immunofluorescence staining. Expression profiles of the miR16-1, Bax, Bcl-2, Suz12, and Kmt2a genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). There was a significant decrease from the 8-cell stage to the blastocyst stage of embryo development in the miR-16-1 harboring plasmid microinjection group. We observed substantial reductions in the amounts of H3K4me3 and H3K27me3 in the 2-cell and the blastocyst stages in the miR-16-1 harboring plasmid microinjection group (P ≤ 0.05). The miR-16-1 level in the miRNA group was higher than the control group in the 2-cell and the blastocyst stages. There was a significant increase (P ≤ 0.05) in Bax and decreases in Bcl2, Suz12, and Kmt2a following the injection of the miR-16-1 harboring plasmid. These results suggest that a change in miR-16-1 expression can significantly affect embryo development, epigenetic changes, and target gene expressions.

Hexagonal layered group IV-VI semiconductors and derivatives: fresh blood of the 2D family.

New phases of group IV-VI semiconductors in 2D hexagonal structures are predicted and their unusual physical properties are revealed. The structures of monolayer group IV-VI semiconductors are similar to those of blue phosphorene and each unit has the same ten valence electrons. The band gap of 2D hexagonal group IV-VI semiconductors depends on both the thickness and stacking order. Atomic functionalization can induce ferromagnetism, and the Curie temperature can be tuned. Gapped Dirac fermions with zero mass are developed and this makes it exceed that of graphene. The Fermi velocity can be compared to or even above that of graphene.

Comparing the Efficacy of Two Drugs Senalin and Bisacodyl in Treatment of Constipation in Intensive Care Units' Patients.

BACKGROUND: Constipation is an intestinal syndrome that can be created alone or in the context of another disease in patients admitted to intensive care units (ICUs). Given the role of sennosides in increasing the transfer rate of materials from the large intestine, we aimed to compare the effect of senalin with bisacodyl on the treatment of constipation in patients admitted to ICUs. MATERIALS AND METHODS: In this randomized, double-blind study, 70 patients admitted to the ICU were divided into two groups. The senalin recipient group received senalin with a dose of 500 mg daily for 3 days. The bisacodyl recipient group received bisacodyl with a dose of 10 mg daily for 3 days. RESULTS: The mean of defecation frequency during the 2nd day of treatment of constipation was significantly higher in the group receiving bisacodyl than in the senalin group (P < 0.01). There was no significant difference between the two groups in terms of fecal consistency in any of the study days (P < 0.05). The prevalence of complications in the 3rd day of treatment was significantly higher in bisacodyl group than in the senalin group (P = 0.04). CONCLUSION: Given the lack of difference in the efficacy of two drugs, fecal consistency, daily defecation frequency and fewer complications of senalin compared to bisacodyl, it s eems that this drug can be used as an appropriate treatment for constipation in patients admitted to ICUs.

Fe-doped mayenite electride composite with 2D reduced Graphene Oxide: As a non-platinum based, highly durable electrocatalyst for Oxygen Reduction Reaction.

Since the last decades, non-precious metal catalysts (NPMC), especially iron based electrocatalysts show sufficient activity, potentially applicant in oxygen reduction reaction (ORR), however they only withstand considerable current densities at low operating potentials. On the other hand iron based electrocatalysts are not stable at elevated cathode potentials, which is essential for high energy competence, and its remains difficult to deal. Therefore, via this research a simple approach is demonstrated that allows synthesis of nanosize Fe-doped mayenite electride, [Ca24Al28O64]4+·(e-)4 (can also write as, C12A7-xFex:e-, where doping level, x = 1) (thereafter, Fe-doped C12A7:e-), consist of abundantly available elements with gram level powder material production, based on simple citrate sol-gel method. The maximum achieved conductivity of this first time synthesized Fe-doped C12A7:e- composite materials was 249 S/cm. Consequently, Fe-doped C12A7:e- composite is cost-effective, more active and highly durable precious-metal free electrocatalyst, with 1.03 V onset potential, 0.89 V (RHE) half-wave potential, and ~5.9 mA/cm2 current density, which is higher than benchmark 20% Pt/C (5.65 mA/cm2, and 0.84 V). The Fe-doped C12A7:e- has also higher selectivity for desired 4e- pathway, and more stable than 20 wt% Pt/C electrode with higher immunity towards methanol poisoning. Fe-doped C12A7:e- loses was almost zero of its original activity after passing 11 h compared to the absence of methanol case, indicates that to introduce methanol has almost negligible consequence for ORR performance, which makes it highly desirable, precious-metal free electrocatalyst in ORR. This is primarily described due to coexistence of Fe-doped C12A7:e- related active sites with reduced graphene oxide (rGO) with pyridinic-nitrogen, and their strong coupling consequence along their porous morphology textures. These textures assist rapid diffusion of molecules to catalyst active sites quickly. In real system maximum power densities reached to 243 and 275 mW/cm2 for Pt/C and Fe-doped C12A7:e- composite, respectively.

An investigation into the prevalence of cognitive impairment and the performance of older adults in Guilan province.

Introduction: The escalating rate of old people with a functional impairment in Iran and the weakness of the family support due to the diminishing of family size have increased the demand for long-term care for the elderly with cognitive impairment (CI). Objective: The purpose of this research is to explore the frequency of cognitive impairment in the elderly and its association with their daily functional impairment and disability. Method: This is a cross-sectional and descriptive-analytic study conducted in 2016-2017. The study sample consisted of 393 elderly people who were 60 years old or older who live in of Guilan different counties. Samples were selected by using multi-stage cluster sampling. Subsequently, data were analyzed by using the Chi-square test and correlation and regression analysis conducted in SPSS 22. Results: It was observed that 4.3, 28.6, and 37% of the subjects suffered from severe, moderate, and mild cognitive impairment, respectively. Cognitive impairment had a significant relationship with daily functioning and activities requiring special tools. Moreover, cognitive impairment in women, people with low education, and those over 70 years old was more common, and the difference between them was significant (p <0.001). Also, disability was significantly greater in the elderly with cognitive impairment. Conclusion: Many old people need to be cared for after the appearance of cognitive impairment. Therefore, appropriate screening of cognitive impairments is conducive to early diagnosis and prevention of executive functioning problems.

Correction to: An investigation into the prevalence of cognitive impairment and the performance of older adults in Guilan province.

[This corrects the article on p. 247 in vol. 11, PMID: 30364719.].

Protection of the Queuosine Biosynthesis Enzyme QueF from Irreversible Oxidation by a Conserved Intramolecular Disulfide.

QueF enzymes catalyze the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ0) to 7-aminomethyl-7-deazaguanine (preQ1) in the biosynthetic pathway to the tRNA modified nucleoside queuosine. The QueF-catalyzed reaction includes formation of a covalent thioimide intermediate with a conserved active site cysteine that is prone to oxidation in vivo. Here, we report the crystal structure of a mutant of Bacillus subtilis QueF, which reveals an unanticipated intramolecular disulfide formed between the catalytic Cys55 and a conserved Cys99 located near the active site. This structure is more symmetric than the substrate-bound structure and exhibits major rearrangement of the loops responsible for substrate binding. Mutation of Cys99 to Ala/Ser does not compromise enzyme activity, indicating that the disulfide does not play a catalytic role. Peroxide-induced inactivation of the wild-type enzyme is reversible with thioredoxin, while such inactivation of the Cys99Ala/Ser mutants is irreversible, consistent with protection of Cys55 from irreversible oxidation by disulfide formation with Cys99. Conservation of the cysteine pair, and the reported in vivo interaction of QueF with the thioredoxin-like hydroperoxide reductase AhpC in Escherichia coli suggest that regulation by the thioredoxin disulfide-thiol exchange system may constitute a general mechanism for protection of QueF from oxidative stress in vivo.

Facile synthesis of flower-like platinum nanostructures as an efficient electrocatalyst for methanol electro-oxidation.

This paper presents a facile approach for the synthesis of a novel Pt/graphene-nickel foam (Pt/GNF) electrode composed of flower-like Pt nanoparticles (NPs) and 3D graphene. The fabrication process involved the chemical vapor deposition of graphene onto Ni foam as a substrate and the subsequent growth of Pt NPs via a galvanic replacement reaction without using any seed and organic solvent. The surface morphology and composition of the prepared materials were characterized. Meanwhile, cyclic voltammetry and electrochemical impedance spectroscopy were employed to confirm their typical electrochemical characteristics. The as-prepared nanocomposites displayed enhanced catalytic activity and kinetics toward methanol electro-oxidation. Such an excellent performance can be ascribed to the high dispersion of flower-like Pt NPs and to the exposure of more sites provided by the flower-like structure. The improved stability, decreased charge transfer resistance, and enhanced reaction rate of the nanocomposites promise new opportunities for the development of direct methanol fuel cells.