The relations between metabolic variations and genetic evolution of different species.

Metabonomics has been applied in many bio-related scientific fields. Nevertheless, some animal research works are shown to fail when they are extended to humans. Therefore, it is essential to figure out suitable animal modeling to mimic human metabolism so that animal findings can serve humans. In this study, two kinds of commonly selected body fluids, serum and urine, from humans and various experimental animals were characterized by integration of nuclear magnetic resonance (NMR) spectroscopy with multivariate statistical analysis to identify the interspecies metabolic differences and similarities at a baseline physiological status. Our results highlight that the dairy cow and pig may be an optimal choice for transportation and biodistribution studies of drugs and that the Kunming (KM) mouse model may be the most effective for excretion studies of drugs, whereas the Sprague-Dawley (SD) rat could be the most suitable candidate for animal modeling under overall considerations. The biochemical pathways analyses further provide an interconnection between genetic evolution and metabolic variations, where species evolution most strongly affects microbial biodiversity and, consequently, has effects on the species-specific biological substances of biosynthesis and corresponding biological activities. Knowledge of the metabolic effects from species difference will enable the construction of better models for disease diagnosis, drug metabolism, and toxicology research.

May-Thurner syndrome: correlation between digital subtraction and computed tomography venography.

BACKGROUND/PURPOSE: Digital subtraction venography (DSV) and computed tomography venography (CTV) are both recommended for diagnosing May-Thurner syndrome. The literature contains little information on the correlation between these imaging tools. We performed a retrospective case-series study to investigate this correlation. METHODS: From August 2009 to August 2010, 42 patients with May-Thurner syndrome (34 women, 8 men; mean age: 52.8 ± 13.5 years) received DSV followed by CTV. The DSV was used to evaluate the degree of venous reflux, reflux start-up time, and flow time. By CTV, the ratio of cross-sectional area and the ratio of diameter between the narrowest region to that of the caudal part of the left common iliac vein were calculated. The correlation between these variables for DSV versus CTV was calculated using Spearman's rank correlation coefficients. RESULTS: In DSV evaluation of the extent of reflux, 19.0% of cases were classified as Grade 0, 11.9% as Grade I, 28.6% as Grade II, and 40.5% as Grade III. The mean ± standard deviation flow times for these groups were 2.00 ± 0.38 seconds, 1.75 ± 0.29 seconds, 1.67 ± 0.72 seconds, and 1.81 ± 0.68 seconds, the mean time for total patients was 1.76 ± 0.78 seconds. The reflux start-up times for Grades I-III were 2.00 ± 1.00 seconds, 1.80 ± 1.23 seconds, and 1.40 ± 0.49 seconds, and the mean time was 1.6 ± 0.8 seconds. In CTV, the mean area ratio and diameter ratio were 0.78 ± 0.22 (range, 0.22-1.27) and 0.75 ± 0.24 (range, 0.33-1.25). The reflux start-up time showed a positive correlation with the cross-sectional area ratio (r = 0.518; p = 0.002) and diameter ratio (r = 0.413; p = 0.019). CONCLUSION: The cross-sectional area ratio and diameter ratio in CTV correlate with the reflux start-up time in DSV. For May-Thurner syndrome, both CTV and DSV provide essential information for diagnosis and evaluation of the disease. The positive correlation between anatomical and hemodynamic properties corresponds with the underlying pathophysiology.

Surface bonding of MN4 macrocyclic metal complexes with pyridine-functionalized multi-walled carbon nanotubes for non-aqueous Li-O2 batteries.

It is essential to develop bifunctional catalysts with high activity and stability for reversible oxygen reduction reactions (ORRs) and oxygen evolution reactions (OERs) in lithium-oxygen (Li-O2) batteries. In this work, pyridine (Py) functionalized multi-walled carbon nanotubes (MWCNTs) were prepared to immobilize various solid MN4 macrocyclic metal complexes (MN4-MC) as cathode electrocatalysts for Li-O2 batteries. Three types of MN4-MC molecules, including iron phthalocyanine (FePc), cobalt phthalocyanine (CoPc) and iron protoporphyrin IX (Heme) were examined to evaluate the influence of central metal atoms and ligand substituents found in MN4-MC molecules on the electrocatalytic performance of the study samples. The order of the ORR/OER catalytic activity of the bifunctional catalysts is FePc > Heme > CoPc. The central metal atom in FePc molecule has the highest occupied molecular orbital (HOMO) energy than the corresponding metal atoms in CoPc and Heme molecules. This made the molecule to have better dioxygen-binding ability and higher catalytic activity in the ORR process; it also made it to easily lose electrons that were oxidized in the OER process. This study proposed a simplified scheme of the electrode surface route to assist in understanding the diverse ORR/OER performances of MN4-MC. It is discovered that the positive core of the MN5 coordination sphere in MN4-MC/Py/MWCNTs composite is the primary active site that can influence the formation of MN5···O2* and MN5-LOOLi cluster in the ORR process. The interfacial electron could be easily delivered between MWCNTs and MN5 active site through the Py bridge. This facilitated the formation and decomposition of MN5-LOOLi species during the ORRs/OERs, leading to the enhancement of its catalytic performance. This work provides a new insight into the effects of the molecular structure and organization of MN4-MC on the catalytic activity of O2 electrodes in Li-O2 batteries.

Genetic background influences pig responses to porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly infectious and economically significant virus that causes respiratory and reproductive diseases in pigs. It results in reduced productivity and increased mortality in pigs, causing substantial economic losses in the industry. Understanding the factors affecting pig responses to PRRSV is crucial to develop effective control strategies. Genetic background has emerged as a significant determinant of susceptibility and resistance to PRRSV in pigs. This review provides an overview of the basic infection process of PRRSV in pigs, associated symptoms, underlying immune mechanisms, and roles of noncoding RNA and alternative splicing in PRRSV infection. Moreover, it emphasized breed-specific variations in these aspects that may have implications for individual treatment options.

Differences in histomorphology and expression of key lipid regulated genes of four adipose tissues from Tibetan pigs.

Tibetan pigs, an indigenous pig breed in China, have high overall fat deposition and flavorful and tasty meat. They are thus good models for studying adipogenesis. Few studies have been conducted focusing on expression of lipid regulated genes in different adipose tissues of Tibetan pigs. Therefore, we compared the difference of histomorphology and expression level of lipid regulated genes through qPCR and western blot in subcutaneous fat, perirenal fat, omental adipose tissue, and inguinal fat of Tibetan pigs. Our results showed that the area of subcutaneous adipocytes in Tibetan pigs was smaller, while the other three adipose tissues (perirenal fat, greater omentum fat, inguinal fat) had cell areas of similar size. The gene expression of FABP4, FASN, FABP3, and ME1 in subcutaneous fat was significantly higher than that in perirenal fat. Furthermore, the protein expression of FABP4 was significantly lower in subcutaneous fat than in perirenal fat (p < 0.05), and the expression of FASN was higher in greater omentum fat than in subcutaneous fat (p = 0.084). The difference in adipocyte cell size and expression of lipid-regulated genes in adipose tissues from the various parts of the pig body is likely due to the different cellular lipid metabolic processes. Specially, FABP4 and FASN may be involved in the regulation of fat deposition in different adipose tissues of Tibetan pigs.

PRRSV alters m6A methylation and alternative splicing to regulate immune, extracellular matrix-associated function.

The alternative splicing and N6-methyladenosine (m6A) modifications occurring during porcine reproductive and respiratory syndrome virus (PRRSV) infections remain poorly understood. Transcriptome and MeRIP-seq analyses were performed to identify the gene expression changes, splicing and m6A modifications in the lungs of PRRSV-infected pigs. In total, 1624 differentially expressed genes (DEGs) were observed between PRRSV-infected and uninfected pigs. We observed significant alterations in alternative splicing (54,367 events) and m6A modifications (2265 DASEs) in numerous genes, including LMO7, SLC25A27, ZNF185, and ECM1, during PRRSV infection. LMO7 and ZNF185 exhibited alternative splicing variants and reduced mRNA expression levels following PRRSV infection. Notably, LMO7 inhibited c-JUN, SMAD3, and FAK expression, whereas ZNF185 affected the expression of FAK, CDH1, and GSK3ß downstream. Additionally, ECM1 influenced FAK expression by targeting ITGB3 and AKT2, suggesting its involvement in extracellular matrix accumulation through the ITGB3-AKT2/FAK pathway. These changes may facilitate viral invasion and replication by modulating the expression of genes and proteins participating in crucial cellular processes associated with immunity and the extracellular matrix. We highlight the importance of these genes and their associated pathways in PRRSV infections and suggest that targeting these may be a promising therapeutic approach for treating viral infections.

Integrated lipidomics and RNA sequencing analysis reveal novel changes during 3T3-L1 cell adipogenesis.

After adipogenic differentiation, key regulators of adipogenesis are stimulated and cells begin to accumulate lipids. To identify specific changes in lipid composition and gene expression patterns during 3T3-L1 cell adipogenesis, we carried out lipidomics and RNA sequencing analysis of undifferentiated and differentiated 3T3-L1 cells. The analysis revealed significant changes in lipid content and gene expression patterns during adipogenesis. Slc2a4 was up-regulated, which may enhance glucose transport; Gpat3, Agpat2, Lipin1 and Dgat were also up-regulated, potentially to enrich intracellular triacylglycerol (TG). Increased expression levels of Pnpla2, Lipe, Acsl1 and Lpl likely increase intracellular free fatty acids, which can then be used for subsequent synthesis of other lipids, such as sphingomyelin (SM) and ceramide (Cer). Enriched intracellular diacylglycerol (DG) can also provide more raw materials for the synthesis of phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), ether-PE, and ether-PC, whereas high expression of Pla3 may enhance the formation of lysophophatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Therefore, in the process of adipogenesis of 3T3-L1 cells, a series of genes are activated, resulting in large changes in the contents of various lipid metabolites in the cells, especially TG, DG, SM, Cer, PI, PC, PE, etherPE, etherPC, LPC and LPE. These findings provide a theoretical basis for our understanding the pathophysiology of obesity.

Specific biological responses following dextran-coated ultra-small superparamagnetic particles of iron oxides administration.

Aim: The potential bio-related risks of dextran-coated ultra-small superparamagnetic particles of iron oxides (D-USPIO) were assessed. Materials & methods: Metabolic responses of D-USPIO in BALB/C mice were obtained using 1H-NMR-based metabolomic strategy combined with the traditional biochemical assay. Results: The metabolomic analyses of biological fluids (plasma and urine) and organs (liver, kidney and spleen) indicated that the disturbance, impairment and recovery of the physiological functions were related to the metabolic response to D-USPIO. The correlations between the biofluids and tissue metabolomes described the specific metabolic information of D-USPIO on their in vivo transportation, absorption, biodistribution and excretion. Conclusion: Metabolomic analysis provides preliminary validation for the use of D-USPIO in clinical medicine, and the results help to understand the potential adverse effects of the similar bio-nanomaterials further serve to their synthesis optimization and biocompatibility improvement.

Label-free DNA sensor by boron-doped diamond electrode using an ac impedimetric approach.

An electrochemical biosensor using a boron-doped diamond (BDD) electrode is described for differentiating between gene sequences according to DNA hybridization events using an ac impedimetric approach. BDD electrodes were dipped into a 1% solution of polyethylenimine (PEI) to adsorb a thin layer of positively charged PEI on the surface of BDD, then PEI-modified BDD electrodes were used to immobilize negatively charged single-stranded PCR fragments from Exon 7 of human p53 gene. Alternating current impedimetric measurements were first performed on these systems in phosphate buffered saline (PBS) and then upon exposure to single-stranded DNA (ssDNA). When the ssDNA-immobilized BDD electrode and solution ssDNA were completely complementary, a large drop in impedance was measured. Complementary DNA could be clearly detected at concentrations down to 10 (-19) g mL (-1) at a fixed frequency (10 Hz). Higher concentrations of DNA gave faster hybridization with saturation occurring at levels above 1.0 pg mL (-1.) Responses were much lower upon exposure to noncDNA, even at higher concentrations. The results show it is possible to directly detect target DNA at a fixed frequency and without additional labeling.

Highly Regio- and Stereoselective Cocyclotrimerization and Linear Cotrimerization of alpha,beta-Unsaturated Carbonyl Compounds with Alkynes Catalyzed by Nickel Complexes.

Cyclic enones 2-cyclohexen-1-one (1a), 4,4-dimethyl-2-cyclohexen-1-one (1b), 2-cyclopenten-1-one (1c), and 2-cyclohepten-1-one (1d) react with octa-1,7-diyne (2) in THF in the presence of Ni(PPh(3))(2)I(2), ZnI(2), and Zn powder at 62 degrees C to give [2 + 2 + 2] cycloaddition-dehydrogenation products 3a-d in 32-80% yields. alpha,beta-Unsaturated lactone 5a (5,6-dihydro-2H-pyran-2-one) undergoes [2 + 2 + 2] cycloaddition with 2 to give both the corresponding cyclohexadiene product 6 (29%) and dehydrogenation product 7 (39%). Under similar reaction conditions, 3-buten-2-one reacts with 2 and various substituted hepta-1,6-diynes 9a-c to give [2 + 2 + 2] cycloaddition-dehydrogenation products 11a-d in 68-80% yields. Diphenylacetylene also reacts with 1a-d, 5a, and 2(5H)-furanone (5b) to afford the corresponding [2 + 2 + 2] cocyclotrimerization products 13a-d and 14a-b. No dehydrogenation of products 13 and 14 was observed under the reaction and workup conditions. The reactions of acrylates with alkynes catalyzed by nickel complexes give products that depend greatly on the reaction conditions. Treating ethyl acrylate (15a) with 1-phenyl-1-propyne (16) in the presence of Ni(PPh(3))(2)Cl(2) and Zn at 90 degrees C in toluene affords cocyclotrimerization product 19aas the major product (54% yield). However, treatment of CH(2)CHCOOR (R = Et and t-Bu) with mono alkynes 16 and 12 in the presence of Ni(PPh(3))(2)X(2) (X = Cl and I) and Zn powder in toluene at 60 degrees C affords the corresponding conjugated trienes 17a-c in 82-92% yields. The MS data of 17firmly support an adduct of two molecules of alkyne and a molecule of acrylate. Similarly, the reaction of 15a with octa-1,7-diyne in the presence of Ni(PPh(3))(2)I(2), ZnI(2), and zinc gives triene derivative 21 in 68% yield. NOE and X-ray results indicate that in these trienes the substituents from each alkyne and alkene moiety are cis to each other. The unique stereoselectivity can be attributed to the exclusive formation of seven-membered nickelacycloheptadiene intermediate 25during the catalytic reaction.

Multifunctional core-shell upconverting nanoparticles for imaging and photodynamic therapy of liver cancer cells.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attention for their application in biomedicine. Here, silica-coated NaGdF(4):Yb,Er/NaGdF(4) nanoparticles with a tetrasubstituted carboxy aluminum phthalocyanine (AlC(4)Pc) photosensitizer covalently incorporated inside the silica shells were prepared and applied in the photodynamic therapy (PDT) and magnetic resonance imaging (MRI) of cancer cells. These UCNP@SiO(2)(AlC(4)Pc) nanoparticles were uniform in size, stable against photosensitizer leaching, and highly efficient in photogenerating cytotoxic singlet oxygen under near-infrared (NIR) light. In vitro studies indicated that these nanoparticles could effectively kill cancer cells upon NIR irradiation. Moreover, the nanoparticles also demonstrated good MR contrast, both in aqueous solution and inside cells. This is the first time that NaGdF(4):Yb,Er/NaGdF(4) upconversion-nanocrystal-based multifunctional nanomaterials have been synthesized and applied in PDT. Our results show that these multifunctional nanoparticles are very promising for applications in versatile imaging diagnosis and as a therapy tool in biomedical engineering.