PoRVA G9P[23] and G5P[7] infections differentially promote PEDV replication by reprogramming glutamine metabolism.

PoRVA and PEDV coinfections are extremely common in clinical practice. Although coinfections of PoRVA and PEDV are known to result in increased mortality, the underlying mechanism remains unknown. Here, we found that PoRVA infection promoted PEDV infection in vivo and in vitro and that PoRVA G9P[23] (RVA-HNNY strain) enhanced PEDV replication more significantly than did PoRVA G5P[7] (RVA-SXXA strain). Metabolomic analysis revealed that RVA-HNNY more efficiently induced an increase in the intracellular glutamine content in porcine small intestinal epithelial cells than did RVA-SXXA, which more markedly promoted ATP production to facilitate PEDV replication, whereas glutamine deprivation abrogated the effect of PoRVA infection on promoting PEDV replication. Further studies showed that PoRVA infection promoted glutamine uptake by upregulating the expression of the glutamine transporter protein SLC1A5. In SLC1A5 knockout cells, PoRVA infection neither elevated intracellular glutamine nor promoted PEDV replication. During PoRVA infection, the activity and protein expression levels of glutamine catabolism-related enzymes (GLS1 and GLUD1) were also significantly increased promoting ATP production through glutamine anaplerosis into the TCA cycle. Consistent with that, siRNAs or inhibitors of GLS1 and GLUD1 significantly inhibited the promotion of PEDV replication by PoRVA. Notably, RVA-HNNY infection more markedly promoted SLC1A5, GLS1 and GLUD1 expression to more significantly increase the uptake and catabolism of glutamine than RVA-SXXA infection. Collectively, our findings illuminate a novel mechanism by which PoRVA infection promotes PEDV infection and reveal that the modulation of glutamine uptake is key for the different efficiencies of PoRVA G9P[23] and PoRVA G5P[7] in promoting PEDV replication.

Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic ß cells.

Pancreatic ß cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as ß cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in ß cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in ß cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in ß cells.

Preparation of Novel C/N-Doped LaFeO3 Type Perovskite for Efficient Photocatalytic Degradation of Sodium Humate.

LaFeO3 chalcocite precursor was prepared by solid-phase milling method, and LaFeO3-type chalcocite composite catalyst, referred to as LFCN catalyst, was synthesized by in situ doping of carbon and nitrogen (urea, melamine, dicyandiamide, and carbon powder), The catalytic performance of the catalysts was investigated by the different mass ratios of LaFeO3 chalcocite precursor and carbon and nitrogen (1:1, 1:2, and 2:1) and the degradation mechanism. Various characterization analyses, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET), showed that the doped composite LFCN catalysts exhibited a hemispherical network structure with a larger specific surface area than that of the pure phase LaFeO3 material. In addition, the LaFeO3 material adjusted the electronic structure of the original LaFeO3 chalcogenide material to a certain extent after in situ doping with organic C and N elements, which enhanced its lattice oxygen oxidation ability. In the study of the catalytic degradation of sodium humate solution under natural light conditions, the catalytic performance was significantly improved compared to that of the pure phase LaFeO3, and 10 mg of the catalyst degraded 30 mg/L of sodium humate solution in 50 min, with a degradation rate increasing from 40 to 98%. The degradation rate increased from 40 to 98% after 4 applications, indicating that the LFCN catalyst has good stability and significant catalytic degradation performance.

Endoscopy image enhancement method by generalized imaging defect models based adversarial training.

Objective.Smoke, uneven lighting, and color deviation are common issues in endoscopic surgery, which have increased the risk of surgery and even lead to failure.Approach.In this study, we present a new physics model driven semi-supervised learning framework for high-quality pixel-wise endoscopic image enhancement, which is generalizable for smoke removal, light adjustment, and color correction. To improve the authenticity of the generated images, and thereby improve the network performance, we integrated specific physical imaging defect models with the CycleGAN framework. No ground-truth data in pairs are required. In addition, we propose a transfer learning framework to address the data scarcity in several endoscope enhancement tasks and improve the network performance.Main results.Qualitative and quantitative studies reveal that the proposed network outperforms the state-of-the-art image enhancement methods. In particular, the proposed method performs much better than the original CycleGAN, for example, the structural similarity improved from 0.7925 to 0.8648, feature similarity for color images from 0.8917 to 0.9283, and quaternion structural similarity from 0.8097 to 0.8800 in the smoke removal task. Experimental results of the proposed transfer learning method also reveal its superior performance when trained with small datasets of target tasks.Significance.Experimental results on endoscopic images prove the effectiveness of the proposed network in smoke removal, light adjustment, and color correction, showing excellent clinical usefulness.

Controllable Preparation of Spherical Molybdenum Nano-Powders by One-Step Reduction of APM in Radio Frequency Hydrogen Plasma.

Spherical molybdenum nano-powders were in-situ ultrafast synthesized from ammonium paramolybdate (APM) raw materials in a one-step reduction method by radio frequency (RF) hydrogen plasma. Due to the extreme conditions of the RF plasma torch such as its high temperature and large temperature gradient, the injected raw APM powder was quickly gasified and then reduced into nano-sized metal molybdenum (Mo) powder. The influences of APM powder delivery rate and H2 concentration on the properties of the obtained powders were investigated. Field-emission scanning electron microscope (FESEM), transmission electron microscope (TEM), X-ray diffraction (XRD), nanolaser particle analyzer, and specific surface area method were used to characterize the morphology, phase, and particle size distribution of the powders. The results showed that the nano-sized Mo powder obtained by hydrogen plasma treatment had a quasi-spherical morphology and an average particle size of about 30 nm. The particle size could be successfully adjusted by varying H2 concentrations. In addition, spherical nano-sized MoO3 powder could be obtained when no H2 was added into the RF plasma.

Copper and palladium bimetallic sub-nanoparticles were stabilized on modified polyaniline materials as an efficient catalyst to promote C-C coupling reactions in aqueous solution.

Modified polyaniline self-stabilizing Cu/Pd bimetallic sub-nanocluster composite materials (Cu/Pd@Mod-PANI-3OH) are obtained through the three steps of oxidative polymerization, structural modification, and metal self-trapping. Palladium and copper are confined and coordinated in the composite material by participating in the reaction and are highly uniformly dispersed in the carrier in the form of sub-nano clusters. The Cu/Pd@Mod-PANI-3OH micro-nano reactor catalyst formed by the self-assembly of copper, palladium and polyaniline has excellent electronic effects, including a tunable microenvironment, metal-carrier and metal-metal synergy, and the stabilizing effect of metal by polyaniline materials. It can efficiently catalyse C-C coupling (Sonogashira and Suzuki) reactions in aqueous solution with high catalytic activity and a wide range of applications (40 substrates). The characterization test results show that the Cu/Pd@Mod-PANI-3OH composite material obtained by self-trapping metal is a kind of prefabricated catalyst. During the reaction process, the high-valent metals in the pre-catalyst are in situ converted into active zero-valent metals. The catalyst's pre-fabrication strategy well protects the catalytic active centre, largely prevents agglomeration of the metal particles (can be recycled 8 times) and exhibits excellent interfacial domain-limited catalysis. The research strategy of modulation of catalytic active sites to improve the properties of materials at the molecular and atomic level reported in this article will open a new door in the research of polyaniline materials.

The new life of traditional water treatment flocculant polyaluminum chloride (PAC): a green and efficient micro-nano reactor catalyst in alcohol solvents.

Polyaluminum chloride (PAC) is an inorganic polymer material that has the advantages of a simple preparation process and special electronic structure. It is considered to be the most efficient and widely used flocculation material for water treatment. In this work, PAC has been used as a Lewis acid catalyst in interdisciplinary fields because of its polynuclear Al-O cation structure. Further, its catalytic mechanism in green organic synthesis has been studied in detail by using the multicomponent Biginelli reaction as the probe. The effect of solvent on the self-assembly and aggregation process of PAC materials was investigated using optical microscopy, UV-Vis spectrophotometry, particle size analysis, XPS, IR, SEM and HR-TEM. The results show that the PAC materials have different morphological characteristics in different solvents. The Al-O-Al cations were transformed in the ethanol solvent to form new multi-nuclear cation aggregates Alb, which could be used as inorganic micro-nano reactors with unique synergistic catalysis in catalytic reactions. This is the first time the role of PAC in the Biginelli reaction has been analyzed with a liquid in situ infrared instrument, which provided favorable evidence for the speculated reaction mechanism. The PAC-ethanol system is, therefore, considered to be a green, efficient (best yield >99%), economic and recyclable catalyst for catalyzing organic synthesis reactions. The development and utilization of PAC materials in organic synthesis will bring new vitality to this cheap material, which is widely used in industries.

Generation of hypoimmunogenic human pluripotent stem cells via expression of membrane-bound and secreted ß2m-HLA-G fusion proteins.

Allogeneic immune rejection is a major barrier for the application of human pluripotent stem cells (hPSCs) in regenerative medicine. A broad spectrum of immune cells, including T cells, natural killer (NK) cells, and antigen-presenting cells, which either cause direct cell killing or constitute an immunogenic environment, are involved in allograft immune rejection. A strategy to protect donor cells from cytotoxicity while decreasing the secretion of inflammatory cytokines of lymphocytes is still lacking. Here, we engineered hPSCs with no surface expression of classical human leukocyte antigen (HLA) class I proteins via beta-2 microglobulin (B2M) knockout or biallelic knockin of HLA-G1 within the frame of endogenous B2M loci. Elimination of the surface expression of HLA class I proteins protected the engineered hPSCs from cytotoxicity mediated by T cells. However, this lack of surface expression also resulted in missing-self response and NK cell activation, which were largely compromised by expression of ß2m-HLA-G1 fusion proteins. We also proved that the engineered ß2m-HLA-G5 fusion proteins were soluble, secretable, and capable of safeguarding low immunogenic environments by lowering inflammatory cytokines secretion in allografts. Our current study reveals a novel strategy that may offer unique advantages to construct hypoimmunogenic hPSCs via the expression of membrane-bound and secreted ß2m-HLA-G fusion proteins. These engineered hPSCs are expected to serve as an unlimited cell source for generating universally compatible "off-the-shelf" cell grafts in the future.

Loss of Diacylglycerol Kinase-Ζ Inhibits Cell Proliferation and Survival in Human Gliomas.

Diacylglycerol kinases ζ (DGKζ) is a critical lipid kinase which is involved in phosphatidic acid (PA) generation via diacylglycerol (DAG) phosphorylation. DGKζ is highly expressed in central nervous system and essential for brain development. Studies have indicated that DGKζ is associated with colon cancer invasion and metastasis. However, the involvement of DGKζ in human glioma development remains elusive. Here, we explored the impact and possible mechanisms of DGKζ knockdown on the proliferation and survival of glioma cells. The relationship between DGKζ expression status and human glioma stages was explored in 111 specimens of human gliomas via immunohistochemistry technology. Then the impact of DGKζ on cell proliferation, cell cycle, survival, and colony formation ability was determined in U-87 MG glioma cell lines via lentiviral-mediated small interfering (shRNA) strategy. The influence of DGKζ knockdown on global gene expression in U-87 MGglioma cell lines was further analyzed by microarray platform to reveal the possible molecular mechanisms underlying DGKζ-mediated glioma development and progression. Immunohistochemistry analysis revealed that DGKζ expression is positively correlated with human gliomagrade. Lentiviral-mediated small interfering (shRNA) strategyefficiently reduced DGKζ expression and DGKζ knockdown impaired cell proliferation, inhibited colony formation ability, and induced cell cycle arrest and cell apoptosis in U-87 MG glioma cells. Finally, microarray analysis revealed that multiple cancer-associated pathways and oncogenes were regulated by DGKζ knockdown, which provides insights into underlying mechansims of DGKζ-associated glioma development and progression. Our results established the positive correlation between DGKζ expression and gliomagrade. Furthermore, DGKζ knockdown in human glioma cell lines U-87 MG impaired cell proliferation, inhibited colony formation ability, and induced cell cycle arrest and apoptosis which microarray analysis showed that DGKζ knockdown interrupted multiple oncogenes and cancer-associated pathways. Taken together, we provided confidential evidence for the causal role of DGKζ in glioma development and progression.