New adsorbent materials based on PILs for Freon refrigerants.

The development of refrigerant adsorbent materials is not only essential for enhancing the efficiency of refrigeration systems but also plays a pivotal role in environmental conservation and addressing global warming challenges. However, traditional adsorbent materials are often limited in widespread applications in industrial scales due to various disadvantages, such as low adsorption efficiency, difficulties in desorption, and poor reusability. In this context, three distinct PILs, P[EVIM][PF6], P[BVIM][PF6] and P[HVIM][PF6], were synthesized and characterized. In addition, their structure as well as adsorption capacities towards three different Freon refrigerants (R12, R22 and R134a) were explored. The results indicated that the synthesized PILs had high thermal stability and exceptional adsorption capabilities, with P[EVIM][PF6] demonstrating the best adsorption performance. These PILs consistently maintain a stable saturated adsorption capacity throughout nine consecutive adsorption-desorption cycles, and the desorption rate of the adsorbent tubes consistently exceeded 96%. Thus, the superior recyclability of these PILs was verified. These PILs provide a promising route for efficient adsorption of Freon refrigerants, highlighting their potential significance in pertinent industries and environmental conservation efforts.

Comparative Tandem Mass Tag-Based Quantitative Proteomics Analysis of Liver Against Chronic Hypoxia: Molecular Insights Into Metabolism in Rats.

Xu, Jin, Shenhan Gao, Mingyuan Xin, Wenjie Chen, Kaikun Wang, Wenjing Liu, Xinzong Yan, Sinan Peng, and Yanming Ren. Comparative tandem mass tag-based quantitative proteomics analysis of liver against chronic hypoxia: molecular insights into metabolism in rats. High Alt Med Biol. 24:49-58, 2023. Objective: Using a metabolomic approach, we uncovered key regulators in metabolism from tandem mass tag (TMT)-based proteomic analysis in animals chronically exposed to hypoxia. Methods: Sixteen Sprague-Dawley rats (n = 8 per group) were exposed to chronic normoxia or hypoxia (380 mmHg corresponding to a simulated altitude of 5,500 m) for 35 consecutive days. Hypoxia-induced alterations in metabolic pathways were analyzed from TMT-based proteomic analysis, complemented by western blot validation of key regulators. Results: We profiled biochemical parameters and serum lipids, found that serum alanine aminotransferase and blood glucose were not significantly changed due to chronic hypoxia. However, serum triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) were significantly affected by chronic hypoxia. And the levels of LDL nearly doubled (p < 0.05) after hypoxia exposure for 35 days. Through Kyoto Encyclopedia of Genes and Genomes classification, we found several metabolic pathways were enriched, including lipid metabolism, cofactor and vitamin metabolism, amino acids metabolism, carbohydrate metabolism, and energy metabolism. To explore the potential functions of proteins in metabolic pathways that become a coordinated shift under chronic hypoxic conditions, Gene Ontology and pathway analysis were carried out on differentially expressed proteins. As the co-expression network shown in Figure, we identified the most significant differentially expressed proteins after chronic hypoxic changes in the livers of rats. Furthermore, we validated the gene expression profiles at the protein level using western blot. Results of western blot were in accordance with our quantitative polymerase chain reaction findings. The levels of fatty acid synthase and aquaporin 1 were significantly downregulated after 35 days and the levels of ATP citrate lyase, 2'-5'-oligoadenylate synthetase 1A, aldehyde dehydrogenase 2, and Ras-related protein Rap-1A were significantly upregulated after 35 days. Conclusions: Although this study cannot completely account for all the molecular mechanisms in rats, we provide a good analysis of protein expression and profiling of rats under chronic hypoxia conditions.

Profiles of transcriptome and metabolic pathways after hypobaric hypoxia exposure.

BACKGROUND: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive. METHODS: In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia. RESULTS: The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist. CONCLUSIONS: Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.

Luteolin ameliorates hypoxia-induced pulmonary hypertension via regulating HIF-2α-Arg-NO axis and PI3K-AKT-eNOS-NO signaling pathway.

BACKGROUND: Pulmonary hypertension (PH) is a devastating disease with poor prognosis and high mortality. Hypoxia induced pulmonary hypertension (HPH) is a persistent threat to human health, especially to people who live on high altitude plateau. Pulmonary vascular endothelial cell is involved in numerous pathophysiological processes, including in vasoconstriction, oxidative stress, cell growth and differentiation. Endothelial cells (ECs) are the first layer to be exposed to changed oxygen levels and hypoxia could lead to ECs dysfunction. Endothelial-derived nitric oxide (NO) is the most important bioactive molecule, which could regulate endothelial homeostasis. PH pathophysiology has been linked to the disruption of NO pathways. PURPOSE: Luteolin is a kind of plant active ingredient with multiple pharmacological activities. The purpose of this study is to detect the effect of luteolin on HPH with in vivo, ex vivo and in vitro analyses and to further elucidate luteolin's pharmaceutical mechanism with NO related signaling pathway regulation. METHODS: Hypobaric chamber was used to establish HPH animal model. Rats were intragastrically administrated luteolin for 28 days. Then hemodynamic indexes, histopathological changes, pulmonary artery endothelial function, NO content and arginase activity in lung tissue, NO related pathway proteins expression were measured to evaluate the effect of luteolin on HPH. PAECs were treated with 1% O2 and incubated with or without luteolin. PAECs vitality, NO content in cells supernatant, and NO related pathway proteins expression were tested to reveal the protective mechanism of luteolin. RESULTS: Luteolin decreased mean pulmonary hypertension of HPH rats, alleviated right ventricular and pulmonary vascular remodeling. Immunofluorescence staining (vWF), isolated perfused/ventilated rat lung experiment indicated that luteolin protected pulmonary vascular endothelial function of HPH rats. Luteolin increased NO content in PAECs supernatant while decreased NO level in lung tissues of HPH rats. Further, it was demonstrated that luteolin inhibited HIF-2α-Arg axis in PAECs and HPH rats. PI3K-AKT-eNOS signaling pathway was upregulated in PAECs, but which was downregulated in lung tissues of HPH rats. Pharmacological effect of luteolin was equivalent or better than sildenafil. CONCLUSION: Luteolin ameliorated HPH in rats by protecting pulmonary vascular endothelial function via regulating HIF-2α-Arg-NO axis and PI3K-AKT-eNOS-NO signaling pathway. This study may provide a novel perspective and approach to alleviate the devastating disease of HPH.

A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice.

Introduction: The objective of this study is to construct a multi-epitope vaccine GILE containing B-cell and T-cell epitopes against Echinococcus Multilocularis (E. multilocularis) infection based on the dominant epitopes of E. multilocularis EMY162, LAP, and GLUT1. Methods: The structure and hydrophobicity of GILE were predicted by SWISSMODEL, pyMOL, SOPMA and VMD, and its sequence was optimized by Optimum™ Codon. The GILE gene was inserted into pCzn1 and transformed into Escherichia coli Arctic express competent cells. IPTG was added to induce the expression of recombinant proteins. High-purity GILE recombinant protein was obtained by Ni-NTA Resin. BALB/c mice were immunized with GILE mixed with Freund's adjuvant, and the antibody levels and dynamic changes in the serum were detected by ELISA. Lymphocyte proliferation was detected by MTS. The levels of IFN-g and IL-4 were detected by ELISpot and flow cytometry (FCM). T cells were detected by FCM. The growth of hepatic cysts was evaluated by Ultrasound and their weights were measured to evaluate the immune protective effect of GILE. Results: The SWISS-MODEL analysis showed that the optimal model was EMY162 95-104-LAP464-479-LAP495-510-LAP396-410-LAP504-518-EMY162112-126. The SOPMA results showed that there were Alpha helix (14.88%), Extended strand (26.25%), Beta turn (3.73%) and Random coil (45.82%) in the secondary structure of GILE. The restriction enzyme digestion and sequencing results suggested that the plasmid pCzn1-GILE was successfully constructed. The SDSPAGE results indicated that the recombinant protein was 44.68 KD. The ELISA results indicated that mice immunized with GILE showed higher levels of serum antibodies compared to the PBS group. The FCM and ELISpot results indicated that mice immunized with GILE secreted more IFN-g and IL-4. Immunization with GILE also led to a significant decrease in the maximum diameter and weight of cysts and stimulated the production of CD4+ and CD8+ T Cell. Discussion: A multi-epitope vaccine GILE with good immunogenicity and antigenicity has been successfully constructed in this study, which may provide important theoretical and experimental bases for the prevention and treatment of E. multilocularis infection.

Integral absorbance measurement for a non-uniform flow field using wavelength modulation absorption spectroscopy.

Combined with computed tomography (CT), the laser absorption spectroscopy technique is used to measure the two-dimensional distribution information of the flow field. The CT method needs an "integral parameter" as a known quantity. The integrated absorbance satisfies the criterion in the laser absorption spectral measurement. The direct absorption spectroscopy method directly measures the integrated absorbance. However, fitting the absorbance curve is difficult due to the distorted baseline in harsh environments. By contrast, the wavelength modulation spectroscopy (WMS) method has satisfactory noise rejection capability. The difficulty that introduces WMS method to measure the non-uniform flow distribution is the integrated absorbance cannot be written in a mathematical expression. Previous efforts focused on solving the average temperature, concentration, and pressure and recalculating the integrated absorbance. This paper aims to develop an integrated absorbance measurement based on the calibration-free WMS method for non-uniform flow, which is called the calibration-free WMS-A method. First, the relationship between the transmissivity and integrated absorbance was established. Then, integrated absorbance was written into the WMS harmonic signals and solved by comparing the measured and simulated signals. The systematic comparison between the WMS-A and the previous WMS method showed the effectivity of the WMS-A method for non-uniform flow measurement. The reliable integrated absorbance can considerably improve the two-dimensional reconstruction quality.

Exploration and analysis of drug modes of action through feature integration.

Identifying drug modes of action (MoA) is of paramount importance for having a good grasp of drug indications in clinical tests. Anticipating MoA can help to discover new uses for approved drugs. Here we first used a drug-set enrichment analysis method to discover significant biological activities in every mode of action category. Then, we proposed a new computational model, a probability ensemble approach based on Bayesian network theory, which integrated chemical, therapeutic, genomic and phenotypic properties of over a thousand of FDA approved drugs to assist with the prediction of MoA. 10-fold cross validation tests demonstrate that this method can achieve better performances than four other methods with the area under the receiver operating characteristic (ROC) curves. Finally, we further conducted a large-scale prediction for drug-MoA pairs. Using the Cardiovascular Agents category as an example, several predicted drug-MoA pairs were supported by literature resources.

Identification of Genes Involved in Breast Cancer Metastasis by Integrating Protein-Protein Interaction Information with Expression Data.

The selection of relevant genes for breast cancer metastasis is critical for the treatment and prognosis of cancer patients. Although much effort has been devoted to the gene selection procedures by use of different statistical analysis methods or computational techniques, the interpretation of the variables in the resulting survival models has been limited so far. This article proposes a new Random Forest (RF)-based algorithm to identify important variables highly related with breast cancer metastasis, which is based on the important scores of two variable selection algorithms, including the mean decrease Gini (MDG) criteria of Random Forest and the GeneRank algorithm with protein-protein interaction (PPI) information. The new gene selection algorithm can be called PPIRF. The improved prediction accuracy fully illustrated the reliability and high interpretability of gene list selected by the PPIRF approach.

DSEP: A Tool Implementing Novel Method to Predict Side Effects of Drugs.

Drug side effects, or adverse drug reactions, have become a focus of public health concern. Anticipating side effects before the drugs are granted marketing authorization for clinical use can help reduce health threats. An increasing need for methods and tools that facilitate side-effect prediction still remains. Here, we present DSEP, which is a tool that is able to analyze chemistry files to predict side effects of drugs that are under development and have not been included into any database. Meanwhile, DSEP provides three computational methods, one of which is a novel method proposed by us. The method can obtain higher AUC(0.8927) and AUPR(0.4143) scores than previous work. The advantage characteristic and method made DSEP a useful tool to predict potential side effects for a given drug or compound. We use DSEP to conduct uncharacterized drugs' side-effect prediction and confirm interesting results.