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Ce oxide-based catalysts with different molar ratio of Co/Ce (denoted as CoCe-x, x represents the Co to Ce ratio) were examined as the catalyst of 5-hydroxymethylfurfural (5-HMF) oxidation to 2,5-furandicarboxylic acid (FDCA). The Co to Ce ratio, catalyst amount and reaction temperature all have remarkable effects on yield and selectivity. Complete conversion of 5-HMF with 86.3% selectivity of FDCA has been achieved over the CoCe-0.15 catalyst at 130 °C with 0.6 MPa O2 pressure (gauge) for 4 h. The good performance is attributed to the high specific surface area and the high oxygen vacancy concentration to promote the mobility and adsorption of oxygen species. In addition, the CoCe-0.15 catalyst is reused for five times without significant activity loss. Finally, the reaction mechanism over the CoCe-0.15 catalyst under base-free condition is discussed. 5-HMF is oxidized by the lattice oxygen via Mars-van Krevelen mechanism with the redox of Ce4+/Ce3+ and Co3+/Co2+, and the lattice oxygen is replenished by adsorbing and activating O2 molecules.

Evidence has shown that neuromedin S (NMS) and its receptor (NMU2R) are expressed in the hypothalamus, pituitary, and testis of pigs. To determine the potential mechanisms of NMS, we systematically investigated the direct effects of NMS on the hypothalamic-pituitary-testicular (HPT) axis of male pigs in vitro. We initially confirmed that NMU2R distributed in isolated hypothalamic cells, anterior pituitary cells and Leydig cells using immunocytochemistry. Subsequently we investigated the direct effects of NMS on hormone secretion from cells (anterior pituitary cells and Leydig cells) treated with different doses of NMS. The results showed that NMS increase the release of LH and FSH from anterior pituitary cells and testosterone from Leydig cells. NMS up-regulated the expression of NMU2R and GnRH mRNAs in hypothalamic cells, NMU2R, LH and FSH mRNAs in anterior pituitary cells, and NMU2R, STAR, P450 and 3β-HSD mRNAs and the expression of PCNA and Cyclin B1 protein in Leydig cells; moreover, it down-regulated the expression of GnIH mRNA in hypothalamic cells. Using immunofluorescence staining and confocal microscopy, we also demonstrated the colocalization of NMU2R and AR or GnIH in Leydig cells. These data in vitro indicated that NMS may regulate the release and/or synthesis of LH, FSH and testosterone at different levels of the reproductive axis through NMU2R, which provided novel evidence of the potential roles of NMS in regulation of pig reproduction.

Microglia are critical in brain development and Alzheimer's disease (AD) etiology. Down syndrome (DS) is the most common genetic developmental disorder and risk factor for AD. Surprisingly, little information is available on the impact of trisomy of human chromosome 21 (Hsa21) on microglial functions during DS brain development and in AD in DS. Using induced pluripotent stem cell (iPSC)-based organoid and chimeric mouse models, we report that DS microglia exhibit an enhanced synaptic pruning function, which alters neuronal synaptic functions. In response to human brain tissue-derived pathological tau, DS microglia undergo cellular senescence and exhibit elevated type-I-interferon signaling. Mechanistically, knockdown of Hsa21-encoded type I interferon receptors, IFNARs, rescues the DS microglial phenotypes both during brain development and in response to pathological tau. Our findings provide in vivo evidence that human microglia respond to pathological tau by exhibiting dystrophic phenotypes. Targeting IFNARs may improve DS microglial functions and prevent senescence.

MicroRNA-29a (miR-29a) plays an important role in the differentiation and proliferation of various uterine cells. However, whether miR-29a can regulate the proliferation and decidualisation of endometrial stromal cells (ESCs) remain to be elucidated. Inhibition of miR-29a led to decreased decidualisation and viability of ESCs in vitro. The expression of biomarkers PRL and IGFBP1, induced by decidualisation, reduced in the absence of miR-29a, while Tetmethylcytosine dioxygenase 3 (TET3) and its potential demethylation target, the collagen type I alpha 1 chain (COL1A1), were restored. The ChIP assay demonstrated that the binding capacity of TET3 to the Col1A1 promoter could be enhanced by the inhibition of miR-29a. Our study revealed that inhibition of miR-29a suppressed the decidualisation of ESCs by enhancing the recruitment of TET3 to the promoter region of Col1A1, thus revealing the critical role of the miR-29a/TET3/Col1A1 axis involved in the regulation of endometrial decidualisation and embryo implantation during early pregnancy.

Glucagon-like peptide-1 (GLP-1) is a potent therapeutic agent for the treatment of diabetes and has been proven to protect pancreatic β-cells from glucotoxicity; however, its mechanisms of action are not entirely understood. Autophagy is a dynamic lysosomal degradation process that can protect organisms against metabolic stress. Studies have shown that autophagy plays a protective role in the survival of pancreatic β-cells under high glucose conditions. In the present study, we explored the role of autophagy in GLP-1-induced protection of pancreatic β-cells exposed to high glucose. We demonstrated that the GLP-1 analogue liraglutide increased autophagy in rat INS-1 β-cells, and inhibition of autophagy abated the anti-apoptosis effect of liraglutide under high glucose conditions. Our results also showed that activation of 5'-AMP-activated protein kinase (AMPK) reduced liraglutide-induced autophagy enhancement and inhibited liraglutide-induced protection of INS-1 β-cells from high glucose. These data suggest that GLP-1 may protect β-cells from glucotoxicity through promoting autophagy by the modulation of AMPK. Deeper insight into the molecular mechanisms linking autophagy and GLP-1-induced β-cell protection may reveal novel therapeutic targets to preserve β-cell mass.

Summary A conceptual framework for understanding abnormal endometrial decidualization, with considerable significance for the diagnosis and treatment of abnormal decidualization-related changes in non-receptive endometrium in implantation failure during early pregnancy is very important. Here, we found the expression levels of miR-29a in endometrial tissues were associated with the menstrual phases and pregnancy outcome. Inhibition of miR-29a led to decreased decidualization of endometrial stromal cells (ESCs) in vitro, whereas Tet methylcytosine dioxygenase 3 (TET3) and its potential demethylation target, the collagen type I alpha 1 chain (Col1A1), were restored. The binding capacity of TET3 to the Col1A1 promoter could be enhanced by the inhibition of miR-29a. Finally, deletion of TET3 rescued the inhibitory effect of the miR-29a antagomir on the proliferation of decidualized ESCs in vitro and embryo implantation in vivo. Thus, loss of miR-29a causes implantation failure because of the limitation of ESCs decidualization-related changes in non-receptive endometrium during early pregnancy.

Structure modulation of transition metal phosphides at the atomic scale can significantly modify their catalytic properties. Herein, stacking faults abundant Ni2P/Co2P electrocatalysts with outstanding bifunctional oxygen evolution and hydrogen evolution property have been prepared. The stacking faults are formed by slow dissolution of Ni substrate by Mo6+ and further redeposition of Ni2+ during the growth of Co(OH)F crystals. Unprecedentedly, the distinct mechanistic etching-redeposition pathway dictated by the stacking faults, heterostructures and crystal lattice deformation leads to lattice expansion of Co2P and enables preferred reactants adsorption. Electrolysis cell employing Ni2P/Co2P electrocatalysts as a bifunctional catalyst for both the cathode and the anode delivers a current density of 10 mA cm−2 at a cell voltage of 1.57 V, which is comparable to the integrated Pt/C and IrO2 counterparts. The exceptional electrocatalytic performance of Co2P/Ni2P-x%Mo indicates the redeposition mechanism a new methodology to modulate the structure and surface reactivity of electrocatalysts.

Catalytic conversion of carbohydrates into the platform chemical 5-hydroxymethylfurfural (HMF) is an important reaction in biomass conversion. In this work, the catalytic conversion of carbohydrates into HMF was studied over a heterogeneous chromium-exchanged zirconium phosphate catalyst (ZrP-Cr). Some important reaction parameters were studied with the aim to obtain high HMF yield from the dehydration of carbohydrates. Under optimal conditions, the dehydration of fructose afforded HMF in a high yield of 94.5%, and that was 43.2% when glucose was used as the feedstock. The recycling experiment indicated that the catalyst was stable, which indicated that catalyst can be reused by six times without significant loss of its catalytic activity.

Neuropeptide W (NPW), a novel hypothalamic peptide, is an endogenous ligand for the orphan G protein-coupled receptors GPR7 (NPBWR1) and GPR8 (NPBWR2). Although several studies have implicated NPW in the regulation of feeding and energy metabolism in many species, the precise physiological function of NPW in pigs remains unclear. In this study, we cloned and sequenced NPW, GPR7, and GPR8 cDNA from pigs. NPW, GPR7, and GPR8 mRNA expression was quantified in the pig brain and peripheral tissues by semiquantitative reverse transcriptase polymerase chain reaction. Immunohistochemistry showed that NPW protein expression was limited in the brain and abundant in peripheral tissues. These results suggest that NPW is involved in the regulation of various physiological functions in pigs. The molecular and morphological data from this study provide a basis for further research on the functions of NPW in pigs.

Neuromedin B (NMB) is a highly conserved bombesin-related neuropeptide found in mammals. Neuromedin B (NMB) executes its effect by binding to the cell surface receptor, neuromedin B receptor (NMBR). In this study, we cloned the rabbit NMB and NMBR genes. The similarity and phylogenetic analyses of NMB and NMBR gene sequences were performed. The expression of NMB and NMBR mRNA in the rabbit was investigated using real-time RT-PCR. Our bioinformatic analysis demonstrated that the cloned rabbit NMB precursor cDNA encoded Gly-His-Phe-Met-NH2 amino acids at the C-terminus, and that its receptor possessed typical transmembrane features. The NMB mRNA was highly expressed in the CNS, while the NMBR mRNA was widely expressed in many tissues, with the highest expression in the gastrointestinal tract. The studies on the NMB distribution and function are limited by the lack of a specific antibody to this neuropeptide. In this paper, polyclonal NMB antibody was generated in mice. Western blotting analysis revealed that the prepared antibody could specifically recognize the recombinant and the endogenous NMB proteins. Immunohistochemistry analysis indicated that the NMB protein was localized in the cytoplasm of the pituitary cells. The existence of NMB protein in the hypothalamic-pituitary-gonadal axis suggests that NMB might function in rabbit reproduction.

Gonadotropin-inhibitory hormone (GnIH), a key regulator of vertebrate reproduction, was identified in the Japanese quail in 2000, and RFamide-related peptide-3 (RFRP-3) was found to be a mammalian GnIH ortholog. To further determine its role in the reproductive system of male Xiaomeishan pigs, we systematically investigated changes in GnIH and its receptors (GPR147 and GPR74) during the development of the reproductive axis of male pigs. We also investigated the direct effect of RFRP-3 on the synthesis and secretion of testosterone in Leydig cells in vitro. The expression patterns of GnIH in the reproductive axis of male pigs at different stages of development (postnatal 3, 30, 60, 90, and 120D) were studied using semiquantitative RT-PCR and immunohistochemistry. Our results show that hypothalamic, pituitary and testicular levels of GnIH and its receptors mRNA significantly changed on postnatal day 30 and postnatal day 90. The immunoreactivities of the GnIH proteins were mainly localized to the spermatogenic cells, sustentacular cells and interstitial cells of the testis throughout sexual development. It was confirmed that different doses of GnIH/RFRP-3 inhibited the release and synthesis of testosterone, and impacted on the gene expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and P450, enzymes that play a key role in the synthesis of testosterone. Together, this research provides molecular and morphological data on the regulation of GnIH in the reproductive development of male pigs.

Laser welded DP steel joints are used widely in the automotive industry for weight reduction. Understanding the deformation and fracture behavior of the base metal (BM) and its welded joint (WJ), especially at high strain rates, is critical for the design of vehicle structures. This paper is concerned with the effects of strain rate on the tensile properties, deformation and fracture behavior of the laser welded DP780 steel joint. Quasi-static and dynamic tensile tests were performed on the WJ and BM of the DP780 steel using an electromechanical universal testing machine and a high-speed tensile testing machine over a wide range of strain rate (0.0001–1142 s −1 ). The microstructure change and microhardness distribution of the DP780 steel after laser welding were examined. Digital image correlation (DIC) and high-speed photography were employed for the strain measurement of the DP780 WJ during dynamic tensile tests. The DP780 WJ is a heterogeneous structure with hardening in fusion zone (FZ) and inner heat-affected zone (HAZ), and softening in outer HAZ. The DP780 BM and WJ exhibit positive strain rate dependence on the YS and UTS, which is smaller at lower strain rates and becomes larger with increasing strain rate, while ductility in terms of total elongation (TE) tends to increase under dynamic loading. Laser welding leads to an overall reduction in the ductility of the DP780 steel. However, the WJ exhibits a similar changing trend of the ductility to that of the BM with respect to the strain rate over the whole strain rate range. As for the DP780 WJ, the distance of tensile failure location from the weld centerline decreases with increasing strain rate. The typical ductile failure characteristics of the DP780 BM and WJ do not change with increasing strain rate. DIC measurements reveal that the strain localization starts even before the maximum load is attained in the DP780 WJ and gradual transition from uniform strains to severely localized strains occurs at high strain rates. The diffuse necking of the DP780 WJ occurs earlier during the tensile deformation process at higher strain rates under dynamic loadings.

Zebrafish retinas, undergoing life-long neurogenesis, provide an integrating model to resolve molecular landscapes of embryonic and post-embryonic neurogenesis. By single-cell RNAseq of zebrafish embryonic retinal progenitors and post-embryonic ciliary marginal zone (CMZ) progenitors, we define 7 distinguished states, 4 independent states (S1/S3/S5/S7) separated by 3 transitional states (S2/S4/S6), that develop over time and reveal aspects of lineage evolution. Genes that define earlier states are more critical for making retinas and post-embryonic CMZ, while genes that define later states are more critical for specifying individual cell fates. Remarkably, transitional and independent states expressed different cell-cycle phase genes, suggesting state transition relies on cell cycle. Intriguingly, similar analysis CMZ cells revealed similar set of states, suggesting embryonic and post-embryonic retinogensis conform to the same molecular program, although some interesting differences in rod genesis. Thus, our findings exemplify molecular landscapes of embryonic and post-embryonic neurogenesis in a vertebrate CNS tissue.

Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs.

Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-α, iNOS and COX-2/PGE2 but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-β-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500μmol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype.

Since its discovery, gonadotropin-inhibitory hormone (GnIH) has appeared to act as a key neuropeptide in the control of vertebrate reproduction. GnIH acts via the novel G protein-coupled receptor 147 (GPR147) to inhibit gonadotropin release and synthesis. To determine the physiological functions of GnIH in the pig, a study was conducted to clone and sequence the cDNA of the GnIH precursor and GPR147. Our results demonstrated that the cloned pig GnIH precursor cDNA encoded three LPXRF and that its receptor possessed typical transmembrane features. Subsequently, tissue expression studies revealed that GnIH was mainly expressed in the brain, corresponding largely with the tissue expression patterns of GPR147 in the pig. The expression patterns in the reproductive axis of the female pig across the estrous cycle were also systemically investigated. The hypothalamic levels of both GnIH and its receptor mRNA were lowest in estrus and peaked in the proestrus and diestrus phases. The highest pituitary GnIH mRNA level was detected in the metestrus, and its receptor displayed a somewhat similar pattern of expression to that of the ligand. However, the expression patterns of GnIH and GPR147 were negatively correlated in the ovary. Immunolocalization in the ovary during the estrous cycle revealed that the immunoreactivities of GnIH and GPR147 were mainly localized in the granulosa and theca cells of the antral follicles during proestrus and estrus and in the luteal cells during metestrus and diestrus. Taken together, this research provided molecular and morphological data for further study of GnIH in the pig.