One-Pot Facile Fabrication of Bioavailable Iron Nanoparticles with Good Biocompatibility for Anemia Therapy.

BACKGROUND Iron deficiency anemia (IDA) has been a major public health problem all over the world. Developing new iron (Fe) fortificants with both high bioavailability and negligible food sensory changes for IDA is in urgent demand. MATERIAL AND METHODS The Fe nanoparticles were fabricated through a one-pot reduction process under the protection of bovine serum albumin (BSA). The BSA-Fe nanoparticles were characterized systematically. The comparisons between BSA-Fe nanoparticles and FeSO4 in bioavailability were carried out through hemoglobin (Hb) repletion method. The biocompatibility of BSA-Fe nanoparticles was also investigated through in vitro and in vivo assays. RESULTS BSA-Fe nanoparticles have super-small size and good water solubility as well as water stability. The Hb repletion assay demonstrated that BSA-Fe nanoparticles have comparative bioavailability with FeSO4. The in vitro cell viability assay, in vivo histological analysis, and biochemical measurements proved the remarkable biocompatibility of BSA-Fe nanoparticles. CONCLUSIONS The BSA-Fe nanoparticles fabricated through a one-pot facile method have good water solubility, comparative bioavailability with FeSO4, and acceptable biocompatibility, exhibiting good potential for further clinical translations.

Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells.

Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme catalyzing de novo biosynthesis of guanine nucleotides, aggregates under certain circumstances into a type of non-membranous filamentous macrostructure termed "cytoophidium" or "rod and ring" in several types of cells. However, the biological significance and underlying mechanism of IMPDH assembling into cytoophidium remain elusive. In mouse ovaries, IMPDH is reported to be crucial for the maintenance of oocyte-follicle developmental synchrony by providing GTP substrate for granulosa cell natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system to produce cGMP for sustaining oocyte meiotic arrest. Oocytes and the associated somatic cells in the ovary hence render an exciting model system for exploring the functional significance of formation of IMPDH cytoophidium within the cell. We report here that IMPDH2 cytoophidium forms in vivo in the growing oocytes naturally and in vitro in the cumulus-enclosed oocytes treated with IMPDH inhibitor mycophenolic acid (MPA). Inhibition of IMPDH activity in oocytes and preimplantation embryos compromises oocyte meiotic and developmental competences and the development of embryos beyond the 4-cell stage, respectively. IMPDH cytoopidium also forms in vivo in the granulosa cells of the preovulatory follicles after the surge of luteinizing hormone (LH), which coincides with the resumption of oocyte meiosis and the reduction of IMPDH2 protein expression. In cultured COCs, MPA-treatment causes the simultaneous formation of IMPDH cytoopidium in cumulus cells and the resumption of meiosis in oocytes, which is mediated by the MTOR pathway and is prevented by guanosine supplementation. Therefore, our results indicate that cytoophidia do form in the oocytes and granulosa cells at particular stages of development, which may contribute to the oocyte acquisition of meiotic and developmental competences and the induction of meiosis re-initiation by the LH surge, respectively.

DPAGT1-Mediated Protein N-Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice.

Post-translational modification of proteins by N-linked glycosylation is crucial for many life processes. However, the exact contribution of N-glycosylation to mammalian female reproduction remains largely undefined. Here, DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation, is identified to be indispensable for oocyte development in mice. Dpagt1 missense mutation (c. 497A>G; p. Asp166Gly) causes female subfertility without grossly affecting other functions. Mutant females ovulate fewer eggs owing to defective development of growing follicles. Mutant oocytes have a thin and fragile zona pellucida (ZP) due to the reduction in glycosylation of ZP proteins, and display poor developmental competence after fertilization in vitro. Moreover, completion of the first meiosis is accelerated in mutant oocytes, which is coincident with the elevation of aneuploidy. Mechanistically, transcriptomic analysis reveals the downregulation of a number of transcripts essential for oocyte meiotic progression and preimplantation development (e.g., Pttgt1, Esco2, Orc6, and Npm2) in mutant oocytes, which could account for the defects observed. Furthermore, conditional knockout of Dpagt1 in oocytes recapitulates the phenotypes observed in Dpagt1 mutant females, and causes complete infertility. Taken together, these data indicate that protein N-glycosylation in oocytes is essential for female fertility in mammals by specific control of oocyte development.

In situ synthesis of molybdenum carbide/N-doped carbon hybrids as an efficient hydrogen-evolution electrocatalyst.

The development of non-precious metal based electrocatalysts for the hydrogen evolution reaction (HER) has received more and more attention over recent years owing to energy and environmental issues, and Mo based materials have been explored as a promising candidate. In this work, molybdenum carbide/N-doped carbon hybrids (Mo2C@NC) were synthesized facilely via one-step high-temperature pyrolysis by adjusting the mass ratio of urea and ammonium molybdate. The Mo2C@NC consisted of ultrasmall nanoparticles encapsulated by N-doped carbon, which had high specific surface area. They all exhibited efficient HER activity, and the Mo2C@NC with a mass ratio of 160 (Mo2C@NC-160) showed the best HER activity, with a low overpotential of 90 mV to reach 10 mA cm-2 and a small Tafel slope of 50 mV dec-1, which was one of the most active reported Mo2C-based electrocatalysts. The excellent HER activity of Mo2C@NC-160 was attributed to the following features: (1) the highly dispersed ultrasmall Mo2C nanoparticles, which exhibited high electrochemically active surface areas; (2) the synergistic effect of the N-doped carbon shell/matrix, which facilitated the electron transport.