Mitoguardin 1 and 2 promote granulosa cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway.

Mitochondria have been identified to be involved in oxidative phosphorylation, lipid metabolism, cell death, and cell proliferation. Previous studies have demonstrated that mitoguardin (Miga), a mitochondrial protein that governs mitochondrial fusion, mitochondria-endoplasmic reticulum (ER) contacts, lipid formation, and autophagy, is crucial for ovarian endocrine and follicular development. Nevertheless, whether mammalian MIGA1 or MIGA2 (MIGA1,-2) regulates ovarian granulosa cell proliferation remains unclear. This study revealed that mammalian MIGA1,-2 promotes cell proliferation and regulates the phosphorylation and localization of Yes-associated protein 1 (YAP1) in ovarian granulosa cells. MIGA2 upregulation resulted in reduced YAP1 activity, while MIGA2 removal led to increased YAP1 activity. Further analysis indicated that MIGA1,-2 regulated YAP1 via the Hippo signaling pathway and regulated protein kinase B (AKT) activity in collaboration with YAP1. In addition, lysophosphatidic acid (LPA) regulated MIGA2 expression and AKT activity by activating YAP1. Briefly, we demonstrated that the mitochondrial MIGA1 and MIGA2, especially MIGA2, promoted cellular proliferation by activating AKT and regulating the Hippo/YAP1 signaling pathway in ovarian granulosa cells, which may contribute to the molecular pathogenesis of reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS).

Mitoguardin2 Is Associated With Hyperandrogenism and Regulates Steroidogenesis in Human Ovarian Granulosa Cells.

Polycystic ovary syndrome (PCOS) is an endocrinopathy characterized by hyperandrogenism, anovulation, and polycystic ovaries, in which hyperandrogenism manifests by excess androgen and other steroid hormone abnormalities. Mitochondrial fusion is essential in steroidogenesis, while the role of mitochondrial fusion in granulosa cells of hyperandrogenic PCOS patients remains unclear. In this study, mRNA expression of mitochondrial fusion genes mitoguardin1, -2 (MIGA 1, -2) was significantly increased in granulosa cells of hyperandrogenic PCOS but not PCOS with normal androgen levels, their mRNA expression positively correlated with testosterone levels. Dihydrotestosterone (DHT) treatment in mice led to high expression of MIGA2 in granulosa cells of ovulating follicles. Testosterone or forskolin/ phorbol 12-myristate 13-acetate treatments increased expression of MIGA2 and the steroidogenic acute regulatory protein (StAR) in KGN cells. MIGA2 interacted with StAR and induced StAR localization on mitochondria. Furthermore, MIGA2 overexpression significantly increased cAMP-activated protein kinase A (PKA) and phosphorylation of AMP-activated protein kinase (pAMPK) at T172 but inhibited StAR protein expression. However, MIGA2 overexpression increased CYP11A1, HSD3B2, and CYP19A1 mRNA expression. As a result, MIGA2 overexpression decreased progesterone but increased estradiol synthesis. Besides the androgen receptor, testosterone or DHT might also regulate MIGA2 and pAMPK (T172) through LH/choriogonadotropin receptor-mediated PKA signaling. Taken together, these findings indicate that testosterone regulates MIGA2 via PKA/AMP-activated protein kinase signaling in ovarian granulosa cells. It is suggested mitochondrial fusion in ovarian granulosa cells is associated with hyperandrogenism and potentially leads to abnormal steroidogenesis in PCOS.

Porous Single-Crystalline Monolith to Enhance Catalytic Activity and Stability.

Engineering the catalytic activity and stability of materials would require the identification of the structural features that can tailor active sites at surfaces. Porous single crystals combine the ordered lattice structures and disordered interconnected pores, and they would therefore provide the advantages of precise structure features to identify and engineer the active sites at surfaces. Herein, we fabricate porous single-crystalline vanadium nitride (VN) at centimeter scale and further dope Fe (Fe0.1V0.9N) and Co (Co0.1V0.9N) in lattice to engineer the active sites at surface. We demonstrate that the active surface is composed of unsaturated coordination of V-N, Fe-N, and Co-N structures which lead to the generation of high-density active sites at the porous single-crystalline monolith surface. The interconnected pores aid the pore-enhanced fluxion to facilitate species diffusion in the porous architectures. In the nonoxidative dehydrogenation of ethane to ethylene, we demonstrate the outstanding performance with ethane conversion of 36% and ethylene selectivity of 99% at 660°C. Remarkably stability as a result of their single-crystalline structure, the monoliths achieve the outstanding performance without degradation being observed even after 200 hours of a continuous operation in a monolithic reactor. This work not only demonstrates the effective structural engineering to simultaneously enhance the stability and overall performance for practically useful catalytic materials but also provide a new route for the element doping of porous single crystals at large scale for the potential application in other fields.

SLAMF6/Ly108 promotes the development of hepatocellular carcinoma via facilitating macrophage M2 polarization.

Tumor-associated macrophages (TAMs) are capable of worsening hepatocellular carcinoma (HCC) prognosis by accelerating tumor growth and progression. Signaling lymphocyte activation molecule family member 6 (SLAMF6; Ly108 in mice) is an immune regulator that is involved in numerous diseases. However, whether SLAMF6 might affect macrophage function in HCC has not yet been reported. Therefore, the present study aimed to determine the relationship between SLAMF6 expression on macrophages and HCC progression. In the present study, the expression of SLAMF6 in human blood samples and mice was analyzed by flow cytometry. Furthermore, macrophage-related polarization markers were detected via reverse transcription quantitative PCR. Clonogenic formation and Transwell assay were performed to determine the proliferation, migration and invasion of HCC cells. In addition, a murine HCC model was established to detect the function of SLAMF6 in vivo. The results demonstrated that SLAMF6 expression was increased in CD14+ cells obtained from patients with HCC. It was also determined that this increase was associated with a positive hepatitis B virus DNA status and high levels of α-fetoprotein. Polarized TAMs from THP-1 cells, murine peritoneal macrophages and murine bone marrow-derived macrophages all exhibited higher levels of SLAMF6 compared with M1 cells. Furthermore, an increased expression of Ly108 was detected in macrophages obtained from mice tumor tissues, indicating that the tumor microenvironment may promote Ly108 expression and macrophage M2 polarization. Ly108 small interfering RNA was applied to macrophages, which resulted in the suppression of M2 polarization. Ly108-silenced macrophages attenuated HCC cell migration and invasion and prevented tumor growth by inhibiting the nuclear factor-κB pathway. Altogether, the results from the present study suggested that SLAMF6/Ly108 was upregulated in TAMs, which may in turn accelerate the development of HCC.

An Efficient Symmetric Electrolyzer Based On Bifunctional Perovskite Catalyst for Ammonia Electrolysis.

Ammonia is a natural pollutant in wastewater and removal technique such as ammonia electro-oxidation is of paramount importance. The development of highly efficient and low-costing electrocatalysts for the ammonia oxidation reaction (AOR) and hydrogen evolution reaction (HER) associated with ammonia removal is subsequently crucial. In this study, for the first time, the authors demonstrate that a perovskite oxide LaNi0.5 Cu0.5 O3-δ after being annealed in Ar (LNCO55-Ar), is an excellent non-noble bifunctional catalyst towards both AOR and HER, making it suitable as a symmetric ammonia electrolyser (SAE) in alkaline medium. In contrast, the LNCO55 sample fired in air (LNCO55-Air) is inactive towards AOR and shows very poor HER activity. Through combined experimental results and theoretical calculations, it is found that the superior AOR and HER activities are attributed to the increased active sites, the introduction of oxygen vacancies, the synergistic effect of B-site cations and the different active sites in LNCO55-Ar. At 1.23 V, the assembled SAE demonstrates ≈100% removal efficiency in 2210 ppm ammonia solution and >70% in real landfill leachate. This work opens the door for developments towards bifunctional catalysts, and also takes a profound step towards the development of low-costing and simple device configuration for ammonia electrolysers.

Electrochemical Oxidative Dehydrogenation of Ethane to Ethylene in a Solid Oxide Electrolyzer.

Oxidative dehydrogenation of ethane to ethylene is an important process in light olefin industry; however, the over-oxidation of ethane leads to low ethylene selectivity. Here, we report a novel approach to electrochemical oxidative dehydrogenation of ethane in anode in conjunction with CO2 reduction at cathode in a solid oxide electrolyser using a porous single-crystalline CeO2 electrode at 600 °C. We identify and engineer the flux and chemical states of active oxygen species that evolve from the lattice at anode surface to activate and dehydrogenate ethane to ethylene via the reaction of epoxy species. Active oxygen species (O2- , O2 2- and O2 - ) at the anode surface effectively dehydrogenate ethane to ethylene, but O- species tend to induce deep oxidation. We demonstrate exceptionally high ethylene selectivity of 95 % and an ethane conversion of 10 % with a durable operation of 300 h.

Dry Reforming of CH4 /CO2 by Stable Ni Nanocrystals on Porous Single-Crystalline MgO Monoliths at Reduced Temperature.

Dry reforming of CH4 /CO2 provides a promising and economically feasible route for the large-scale carbon fixation; however, the coking and sintering of catalysts remain a fundamental challenge. Here we stabilize single-crystalline Ni nanoparticles at the surface of porous single-crystalline MgO monoliths and show the quantitative production of syngas from dry reforming of CH4 /CO2 . We show the complete conversion of CH4 /CO2 even only at 700 °C with excellent performance durability after a continuous operation of 500 hours. The well-defined and catalytically active Ni-MgO interfaces facilitate the reforming reaction and enhance the coking resistance. Our findings would enable an industrially and economically viable path for carbon reclamation, and the "Nanocrystal On Porous Single-crystalline Monoliths" technique could lead to stable catalyst designs for many challenging reactions.

High-Density Lewis Acid Sites in Porous Single-Crystalline Monoliths to Enhance Propane Dehydrogenation at Reduced Temperatures.

The non-oxidative dehydrogenation of propane to propylene plays an important role in the light-olefin chemical industry. However, the conversion and selectivity remain a fundamental challenge at low temperatures. Here we create and engineer high-density Lewis acid sites at well-defined surfaces in porous single-crystalline Mo2 N and MoN monoliths to enhance the non-oxidative dehydrogenation of propane to propylene. The top-layer Mo ions with unsaturated Mo-N1/6 and Mo-N1/3 coordination structures provide high-density Lewis acid sites at the surface, leading to the effective activation of C-H bonds without the overcracking of C-C bonds during the non-oxidative dehydrogenation of propane. We demonstrate a propane conversion of ≈11 % and a propylene selectivity of ≈95 % with porous single-crystalline Mo2 N and MoN monoliths at 500 °C.