Adipose­derived mesenchymal stem cell­derived HCAR1 regulates immune response in the attenuation of sepsis.

Sepsis serves as a leading cause of admission to and death of patients in the intensive care unit (ICU) and is described as a systemic inflammatory response syndrome caused by abnormal host response to infection. Adipose­derived mesenchymal stem cells (ADSCs) have exhibited reliable and promising clinical application potential in multiple disorders. However, the function and the mechanism of ADSCs in sepsis remain elusive. In the present study, the crucial inhibitory effect of ADSC­derived hydroxy­carboxylic acid receptor 1 (HCAR1) on sepsis was identified. Reverse transcription quantitative­PCR determined that the mRNA expression of HCAR1 was reduced while the mRNA expression of Toll­like receptor 4 (TLR4), major histocompatibility complex class II (MHC II), NOD­like receptor family pyrin domain containing 3 (NLRP3), and the levels of interleukin­1ß (IL­1ß), tumor necrosis factor­α (TNF­α), interleukin­10 (IL­10), and interleukin­18 (IL­18) were enhanced in the peripheral blood of patients with sepsis. The expression of HCAR1 was negatively correlated with TLR4 (r=­0.666), MHC II (r=­0.587), and NLRP3 (r=­0.621) expression and the expression of TLR4 was positively correlated with NLRP3 (r=0.641), IL­1ß (r=0.666), TNF­α (r=0.606), and IL­18 (r=0.624) levels in the samples. Receiver operating characteristic (ROC) curve analysis revealed that the area under the ROC curve (AUC) of HCAR1, TLR4, MHC II and NLRP3 mRNA expression was 0.830, 0.853, 0.735 and 0.945, respectively, in which NLRP3 exhibited the highest diagnostic value, and the AUC values of IL­1ß, IL­18, TNF­α, and IL­10 were 0.751, 0.841, 0.924 and 0.729, respectively, in which TNF­α exhibited the highest diagnostic value. A sepsis rat model was established by injecting lipopolysaccharide (LPS) and the rats were randomly divided into 5 groups, including a normal control group (NC group; n=6), a sepsis model group (LPS group; n=6), an ADSC transplantation group (L + M group; n=6), a combined HCAR1 receptor agonist group [L + HCAR1 inducer (Gi) + M group; n=6], and a combined HCAR1 receptor inhibitor group [L + HCAR1 blocker (Gk) + M group; n=6]. Hematoxylin and eosin staining determined that ADSCs attenuated the lung injury of septic rats and ADSC­derived HCAR1 enhanced the effect of ADSCs. The expression of HCAR1, TLR4, MHC II, NLRP3, IL­1ß, IL­18 and TNF­α levels were suppressed by ADSCs and the effect was further induced by ADSC­derived HCAR1. However, ADSC­derived HCAR1 induced the levels of anti­inflammatory factor IL­10. The negative correlation of HCAR1 expression with TLR4, MHC II, and NLRP3 expression in the peripheral blood and lung tissues of the rats was then identified. It is thus concluded that ADSC­derived HCAR1 regulates immune response in the attenuation of sepsis. ADSC­derived HCAR1 may be a promising therapeutic strategy for sepsis.

Effect of Src tyrosine kinase on a rat model of asthma.

Src tyrosine kinase is a protein encoded by the Src gene. The present study aimed to determine the role of Src protein kinase in asthma using small interfering RNA (siRNA) technology. Several Src siRNAs were designed and the most effective siRNA pair was selected. A rat model of asthma was established using ovalbumin, and the rats were treated with Src siRNA, empty vector or phosphate-buffered saline (PBS). A non-asthmatic control group was also established. The rats were clinically observed and Src mRNA and protein levels were measured by reverse transcription-quantitative PCR and western blot analysis, respectively. Pathological observation of the lung tissue, counting of white blood cells (WBCs) and eosinophils (EOSs) and analysis of the concentrations of IL-5, IL-33 and IFN-γ in the bronchoalveolar lavage fluid were performed. The expression levels of Src mRNA in the control, PBS, empty vector and siRNA groups were 110±30.7x103, 253±55.4x103, 254±41.3x103 and 180±50.9x103, respectively. Histochemical analysis of the lung tissue of rats in the siRNA group exhibited a relatively complete lung structure and little damage to the alveolar cavity. Src protein expression and IL-5, IL-33 levels, WBC and EOS levels were positively correlated with Src mRNA expression, while the IFN-γ concentration was negatively correlated with Src mRNA expression. These results indicate that Src knockdown inhibits the release of tracheal inflammatory factors and significantly alleviates asthma in rats. In conclusion, the present study utilized a gene transfer technique to interfere with the expression of Src in rats, which decreased the levels of IL-5, IL-33, WBCs and EOSs and increased the level of IFN-γ; these changes effectively ameliorated the condition of the trachea in asthmatic rats.

Synthesis of trifluoromethyl-containing isoindolinones from tertiary enamides via a cascade radical addition and cyclization process.

A radical trifluoromethylation reaction of tertiary enamides was investigated and trifluoromethyl-containing isoindolinones were prepared under mild conditions. Using TMSCF3 as a radical source, PhI(OAc)2 as an oxidant and KHF2 as an additive, tertiary enamides were converted to isoindolinones via a cascade addition and cyclization process in moderate to good yields.

The high-quality draft genome of peach (Prunus persica) identifies unique patterns of genetic diversity, domestication and genome evolution.

Rosaceae is the most important fruit-producing clade, and its key commercially relevant genera (Fragaria, Rosa, Rubus and Prunus) show broadly diverse growth habits, fruit types and compact diploid genomes. Peach, a diploid Prunus species, is one of the best genetically characterized deciduous trees. Here we describe the high-quality genome sequence of peach obtained from a completely homozygous genotype. We obtained a complete chromosome-scale assembly using Sanger whole-genome shotgun methods. We predicted 27,852 protein-coding genes, as well as noncoding RNAs. We investigated the path of peach domestication through whole-genome resequencing of 14 Prunus accessions. The analyses suggest major genetic bottlenecks that have substantially shaped peach genome diversity. Furthermore, comparative analyses showed that peach has not undergone recent whole-genome duplication, and even though the ancestral triplicated blocks in peach are fragmentary compared to those in grape, all seven paleosets of paralogs from the putative paleoancestor are detectable.

A quantitative structure-activity relationship (QSAR) study on glycan array data to determine the specificities of glycan-binding proteins.

Advances in glycan array technology have provided opportunities to automatically and systematically characterize the binding specificities of glycan-binding proteins. However, there is still a lack of robust methods for such analyses. In this study, we developed a novel quantitative structure-activity relationship (QSAR) method to analyze glycan array data. We first decomposed glycan chains into mono-, di-, tri- or tetrasaccharide subtrees. The bond information was incorporated into subtrees to help distinguish glycan chain structures. Then, we performed partial least-squares (PLS) regression on glycan array data using the subtrees as features. The application of QSAR to the glycan array data of different glycan-binding proteins demonstrated that PLS regression using subtree features can obtain higher R(2) values and a higher percentage of variance explained in glycan array intensities. Based on the regression coefficients of PLS, we were able to effectively identify subtrees that indicate the binding specificities of a glycan-binding protein. Our approach will facilitate the glycan-binding specificity analysis using the glycan array. A user-friendly web tool of the QSAR method is available at http://bci.clemson.edu/tools/glycan_array.

Three-photon absorption in anthracene-porphyrin-anthracene triads: a quantum-chemical study.

We have applied correlated quantum-chemical methods to investigate the three-photon absorption (3PA) response of a porphyrin triad derivative, where the central macrocycle is linked in mesopositions to two anthracene units via acetylenic bridges. The 3PA frequency-dependent spectrum of this derivative is dominated by a single resonance feature in the transparent region, associated with charge-transfer states between porphyrin and anthracene. The calculations indicate a two order of magnitude enhancement in the 3PA cross section in the triad molecule with respect to the individual entities, which is attributed to close one-, two-, and three-photon resonances together with strong electronic couplings among the units.