Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans. © 2005 Nature Publishing Group

Transcriptome Profile Analysis of Intestinal Upper Villus Epithelial Cells and Crypt Epithelial Cells of Suckling Piglets

It is well known that the small intestinal epithelial cells of mammals rapidly undergo differentiation, maturation, and apoptosis. However, few studies have defined the physiological state and gene expression changes of enterocytes along the crypt-villus axis in suckling piglets. In the present study, we obtained the intestinal upper villus epithelial cells (F1) and crypt epithelial cells (F3) of 21-day suckling piglets using the divalent chelation and precipitation technique. The activities of alkaline phosphatase, sucrase, and lactase of F1 were significantly higher (p < 0.05) than those of F3. To explore the differences at the gene transcription level, we compared the global transcriptional profiles of F1 and F3 using RNA-seq analysis technology. A total of 672 differentially expressed genes (DEGs) were identified between F1 and F3, including 224 highly expressed and 448 minimally expressed unigenes. Functional analyses indicated that some DEGs were involved in the transcriptional regulation of nutrient transportation (SLC15A1, SLC5A1, and SLC3A1), cell differentiation (LGR5, HOXA5 and KLF4), cell proliferation (PLK2 and TGFB3), transcriptional regulation (JUN, FOS and ATF3), and signaling transduction (WNT10B and BMP1), suggesting that these genes were related to intestinal epithelial cell maturation and cell renewal. Gene Ontology (GO) enrichment analysis showed that the DEGs were mainly associated with binding, catalytic activity, enzyme regulator activity, and molecular transducer activity. Furthermore, KEGG pathway analysis revealed that the DGEs were categorized into 284 significantly enriched pathways. The greatest number of DEGs enriched in signal transduction, some of which (Wnt, Hippo, TGF-beta, mTOR, PI3K-Akt, and MAPK signaling pathways) were closely related to the differentiation, proliferation, maturation and apoptosis of intestinal epithelial cells. We validated the expression levels of eight DEGs in F1 and F3 using qRT-PCR. The present study revealed temporal and regional changes in mRNA expression between F1 and F3 of suckling piglets, which provides insights into the regulatory mechanisms underlying intestinal epithelial cell renewal and the rapid repair of intestinal mucosal damage

Early assessment of the efficacy of noninvasive ventilation tested by HACOR score to avoid delayed intubation in patients with moderate to severe ARDS

Background: Use of noninvasive ventilation (NIV) in patients with moderate to severe ARDS is controversial. We aimed to use HACOR (combination of heart rate, acidosis, consciousness, oxygenation and respiratory rate) score to comprehensively assess the efficacy of NIV in ARDS patients with PaO 2 /FiO 2  ⩽ 150 mmHg. Methods: Secondary analysis was performed using the data collected from two databases. We screened the ARDS patients who used NIV as a first-line therapy. Patients with PaO 2 /FiO 2  ⩽ 150 mmHg were enrolled. NIV failure was defined as requirement of intubation. Results: A total of 224 moderate to severe ARDS patients who used NIV as a first-line therapy were enrolled. Of them, 125 patients (56%) experienced NIV failure and received intubation. Among the intubated patients, the survivor had shorter time from initiation of NIV to intubation than nonsurvivors (median 10 vs 22 h, p  1 as responders (n  = 102) and the rest to non-responders (n  = 122). Compared to non-responders, the responders had higher HACOR score before NIV. However, the HACOR score was lower in the responders than non-responders after 1–2 h, 12 h, and 24 h of NIV. The responders also had lower NIV failure rate (36% vs 72%, p  < 0.01) and lower 28-day mortality (32% vs 47%, p  = 0.04) than non-responders. Conclusions: NIV failure was high among patients with moderate to severe ARDS. Delayed intubation is associated with increased mortality. The reduction of HACOR score after 1–2 h of NIV can identify the patients who respond well to NIV

Heterogeneous Phases Reaction Equilibrium in an Oxy-Thermal Carbide Furnace

This work focuses on revealing the chemical reaction equilibrium behaviors of gas&ndash;liquid&ndash;solid heterogeneous phases in an oxy-thermal carbide furnace. From a CaC2 formation mechanism investigation, it was determined that a one-step mechanism occurs when there is an excess of C and a high CO partial pressure, which inhibits the formation of Ca in the system, and a two-step mechanism occurs when there is insufficient C and a low CO partial pressure, which promotes the formation of Ca. Based on the calculated results of the equilibrium compositions at 100 kPa and different temperature conditions, the chemical reaction equilibrium behaviors of gas&ndash;liquid&ndash;solid heterogeneous phases in an oxy-thermal carbide furnace were analyzed at conditions of excess C and insufficient C

Revealing the Effects of Water Imbibition on Gas Production in a Coalbed Matrix Using Affected Pore Pressure and Permeability

The effect of water imbibition on characteristics of coalbed methane reservoirs, such as permeability, gas occurrence state, and gas production, is controversial. According to the mechanism of imbibition, gas and water distribution in blind pores is reconfigured during the fracturing process. Therefore, a new comprehensive model of pore pressure and permeability, based on the perfect gas equation and the weighted superposition of viscous flow and Knudsen diffusion, was established for micro- and nanoscale blind pores during water drainage. Using the numerical simulation module in the Harmony software, the effects of imbibition on coal pore pressure, permeability, and gas production were analyzed. The results showed that (1) water imbibition can increase pore pressure and reduce permeability, and (2) water imbibition is not always deleterious to gas production and estimated ultimate reserve (EUR), when the imbibition is constant, the thicker water film is deleterious to coalbed methane wells; when the thickness of water film is constant, more imbibition is beneficial to gas production and EUR. This research is beneficial to optimize the operation of well shut-ins after fracturing and provides methods for optimizing key parameters of gas reservoirs and insights into understanding the production mechanism of coalbed methane wells

Toxic Prediction of Pyrrolizidine Alkaloids and Structure-Dependent Induction of Apoptosis in HepaRG Cells

Pyrrolizidine alkaloids (PAs) are common phytotoxins and could cause liver genotoxicity/carcinogenicity following metabolic activation. However, the toxicity of different structures remains unclear due to the wide variety of PAs. In this study, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of 40 PAs were analyzed, and their toxicity was predicted by Komputer Assisted Technology (TOPKAT) using Discovery Studio software. The in silico results showed that all PAs except retronecine had good intestinal absorption, and all PAs were predicted to have different toxicity ranges. To verify the predictive results, 4 PAs were selected to investigate cell injury and possible mechanisms of the differentiation in HepaRG cells, including retronecine type of twelve-membered cyclic diester (retrorsine), eleven-membered cyclic diester (monocrotaline), noncyclic diester (retronecine), and platynecine type (platyphylline). After 24 h exposure, retronecine-type PAs exhibited concentration-dependent cytotoxicity. The high-content screening assay showed that cell oxidative stress, mitochondrial damage, endoplasmic reticulum stress, and the concentration of calcium ions increased, and neutral lipid metabolism was changed notably in HepaRG cells. Induced apoptosis by PAs was indicated by cell cycle arrest in the G2/M phase, disrupting the mitochondrial membrane potential. Overall, our study revealed structure-dependent cytotoxicity and apoptosis after PA exposure, suggesting that the prediction results of in silico have certain reference values for compound toxicity. A 1,2-membered cyclic diester seems to be a more potent apoptosis inducer than other PAs

Electrospun TiO₂/C Nanofibers As a High-Capacity and Cycle-Stable Anode for Sodium-Ion Batteries

Nanosized TiO₂ is now actively developed as a low-cost and potentially high capacity anode material of Na-ion batteries, but its poor capacity utilization and insufficient cyclability remains an obstacle for battery applications. To overcome these drawbacks, we synthesized electrospun TiO₂/C nanofibers, where anatase TiO₂ nanocrystals with a diameter of ∼12 nm were densely embedded in the conductive carbon fibers, thus preventing them from aggregating and attacking by electrolyte. Due to its abundant active surfaces of well-dispersed TiO₂ nanocrytals and high electronic conductivity of the carbon matrix, the TiO₂/C anode shows a high redox capacity of ∼302.4 mA h g^–1 and a high-rate capability of 164.9 mAh g^–1 at a very high current of 2000 mA g^–1. More significantly, this TiO₂/C anode can be cycled with nearly 100% capacity retention over 1000 cycles, showing a sufficiently long cycle life for battery applications. The nanofibrous architecture of the TiO₂/C composite and its superior electrochemical performance may provide new insights for development of better host materials for practical Na-ion batteries

Polypropylene Glycol-Polyoxytetramethylene Glycol Multiblock Copolymers with High Molecular Weight: Synthesis, Characterization, and Silanization

The high crystallization at room temperature and high cost of polyoxytetramethylene glycol (PTMG) have become obstacles to its application. To overcome these problems, a segment of PTMG can be incorporated into a block copolymer. In this work, polypropylene (PPO) glycol-polyoxytetramethylene (PPO-PTMG) multiblock copolymers were designed and synthesized through a chain extension between hydroxyl (OH)-terminated PPO and PTMG oligomers. The chain extenders, feed ratios of the catalyst/chain extender/OH groups, reaction temperature, and time were optimized several times to obtain a PPO-PTMG with low crystallization and high molecular weight. Multiblock copolymers with low crystallization and high average molecular weight (Mn = 1.0&ndash;1.4 &times; 104 Dalton) were harvested using m-phthaloyl chloride as the chain extender. The OH-terminated PPO-PTMG multiblock copolymer with high Mn and a functionality near two was further siliconized by 3-isocyanatopropyltrimethoxysilane to synthesize a novel silyl-terminated polyether. This polyether has an appropriate vulcanizing property and potential applications in sealants/adhesive fields

Synergistic Na-Storage Reactions in Sn₄P₃ as a High-Capacity, Cycle-stable Anode of Na-Ion Batteries

Room-temperature Na-ion batteries have attracted great interest as a low cost and environmentally benign technology for large scale electric energy storage, however their development is hindered by the lack of suitable anodic host materials. In this paper, we described a green approach for the synthesis of Sn₄P₃/C nanocomposite and demonstrated its excellent Na-storage performance as a novel anode of Na-ion batteries. This Sn₄P₃/C anode can deliver a very high reversible capacity of 850 mA h g^–1 with a remarkable rate capability with 50% capacity output at 500 mA g^–1 and can also be cycled with 86% capacity retention over 150 cycles due to a synergistic Na-storage mechanism in the Sn₄P₃ anode, where the Sn nanoparticles act as electronic channels to enable electrochemical activation of the P component, while the elemental P and its sodiated product Na₃P serve as a host matrix to alleviate the aggregation of the Sn particles during Na insertion reaction. This mechanism may offer a new approach to create high capacity and cycle-stable alloy anodes for Na-ion batteries and other electrochemical energy storage applications