Improving the Accuracy of Density Functional Theory (DFT) Calculation for Homolysis Bond Dissociation Energies of Y-NO Bond: Generalized Regression Neural Network Based on Grey Relational Analysis and Principal Component Analysis

We propose a generalized regression neural network (GRNN) approach based on grey relational analysis (GRA) and principal component analysis (PCA) (GP-GRNN) to improve the accuracy of density functional theory (DFT) calculation for homolysis bond dissociation energies (BDE) of Y-NO bond. As a demonstration, this combined quantum chemistry calculation with the GP-GRNN approach has been applied to evaluate the homolysis BDE of 92 Y-NO organic molecules. The results show that the ull-descriptor GRNN without GRA and PCA (F-GRNN) and with GRA (G-GRNN) approaches reduce the root-mean-square (RMS) of the calculated homolysis BDE of 92 organic molecules from 5.31 to 0.49 and 0.39 kcal mol−1 for the B3LYP/6-31G (d) calculation. Then the newly developed GP-GRNN approach further reduces the RMS to 0.31 kcal mol−1. Thus, the GP-GRNN correction on top of B3LYP/6-31G (d) can improve the accuracy of calculating the homolysis BDE in quantum chemistry and can predict homolysis BDE which cannot be obtained experimentally

PI3K/Akt/mTOR pathway participates in neuroprotection by dexmedetomidine inhibits neuronic autophagy following traumatic brain injury in rats

Dexmedetomidine (Dex) has been demonstrated to provide neuroprotective effect against brain injury in the central nervous system. However, the underlying mechanism of this neuroprotection remains unclear. In this study, we explored whether Dex has the protective potential in rat models of traumatic brain injury(TBI). More importantly, our study further investigated the role of neuronic autophagy induced by PI3K/Akt/mTOR pathway in this neuroprotective action. Adult male Sprague-Dawley rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device and Dex (15ug/kg, i.v.) was administered immediately after TBI. Wet-dry weight method was used to evaluate brain edema. Motor function outcome was assessed by Neurologic Severity Score and the spatial learning ability was evaluated in a Morris water maze. The co-localization of microtubule-associated protein 1 light chain 3(LC3) and neuronal nuclei (NeuN), or LC3 and mammalian target of rapamycin (mTOR) were analyzed by immunofluorescence respectively. The expression of LC3, Phosphorylated protein kinase B (p-Akt) and p-mTOR were quantified using Western blot analysis. Our results showed treatment of rats exposed to TBI with Dex caused not only marked reduction in cerebral edema, motor and cognitive functions deficits, but also a decrease in LC3 levels and a increase in p-Akt and p-mTOR levels. Taken together, these findings indicated that treatment with Dex after TBI could inhibited neuronic autophagy in the hippocampus mediated by the activation of the PI3K/Akt/mTOR pathway, finally promoting neurological recovery.Abbreviations: TBI, Traumatic brain injury; Dex, Dexmedetomidine; LC3, Light chain 3; NeuN, Neuronal nuclei; mTOR, Mammalian target of rapamycin; Akt, Protein kinase

Motion of the hydrogen bond proton in cytosine and the transition between its normal and imino states

The potential energy surface of the H13 proton in base cytosine of the DNA molecules is calculated {\it ab initio} at the Gaussian98 MP2/6-311G(d,p) level. Two potential wells are found. One corresponds to the normal cytosine, while the other corresponds to its imino tautomer. The bindings of the proton in these wells are stable enough against the thermo-disturbance. The motions of the proton in these wells are oscillations around the nearest nitrogen atom like the pendula, and may move far away from the nitrogen atom to form the hydrogen bond with other bases. The estimated tunneling probability of the H13 proton from one well to another well shows that the life time of the proton staying in one of these wells is about 6$\times10^2$ yr. It is too long to let tautomers of cytosine be in thermodynamical equilibrium in a room temperature gas phase experiment. The biological significance of these result is discussed.Comment: 4 pages, 4 figures, replace the bmp files in figures 1 and 2 by corresponding eps files in tex

CD73 promotes proliferation and migration of human cervical cancer cells independent of its enzyme activity

100 ΟM Adenosine treatment did not change the expression of EGFR, VEGF and Akt. (JPG 335 kb

Burst expansion, distribution and diversification of MITEs in the silkworm genome

<p>Abstract</p> <p>Background</p> <p>Miniature inverted-repeat transposable elements (MITEs) are widespread in plants and animals. Although silkworm (<it>Bombyx mori</it>) has a large amount of and a variety of transposable elements, the genome-wide information of the silkworm MITEs is unknown.</p> <p>Results</p> <p>We used structure-based and homology approaches to search for MITEs in the silkworm genome. We identified 17 MITE families with a total of 5785 members, accounting for ~0.4% of the genome. 7 of 17 MITE families are completely novel based on the nucleotide composition of target site duplication (TSD) and/or terminal inverted repeats (TIR). Silkworm MITEs were widely and nonrandom distributed in the genome. One family named BmMITE-2 might experience a recent burst expansion. Network and diversity analyses for each family revealed different diversification patterns of the silkworm MITEs, reflecting the signatures of genome-shocks that silkworm experienced. Most silkworm MITEs preferentially inserted into or near genes and BmMITE-11 that encodes a germline-restricted small RNA might silence its the closest genes in silkworm ovary through a small RNA pathway.</p> <p>Conclusions</p> <p>Silkworm harbors 17 MITE families. The silkworm MITEs preferred to reside in or near genes and one MITE might be involved in gene silence. Our results emphasize the exceptional role of MITEs in transcriptional regulation of genes and have general implications to understand interaction between MITEs and their host genome.</p

Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma is difficult to diagnose early, and most patients are already in the late stages of the disease when they are admitted to hospital. The total 5-year survival rate is less than 5%. Recent studies have showed that brucine has a good anti-tumor effect, but high toxicity, poor water solubility, short half-life, narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study evaluated the effects of brucine immuno-nanoparticles (BIN) on hepatocellular carcinoma. MATERIALS AND METHODS: Anionic polymerization, chemical modification technology, and phacoemulsification technology were used to prepare a carboxylated polyethylene glycol-polylactic acid copolymer carrier material. Chemical coupling technology was utilized to develop antihuman AFP McAb-polyethylene glycol-polylactic acid copolymer BIN. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these immune-nanoparticles were studied in vitro. The targeting, and growth, invasion, and metastasis inhibitory effects of this treatment on liver cancer SMMC-7721 cells were tested. RESULTS: BIN were of uniform size with an average particle size of 249 ± 77 nm and zeta potential of -18.7 ± 4.19 mV. The encapsulation efficiency was 76.0% ± 2.3% and the drug load was 5.6% ± 0.2%. Complete uptake and even distribution around the liver cancer cell membrane were observed. CONCLUSION: BIN had even size distribution, was stable, and had a slow-releasing effect. BIN targeted the cell membrane of the liver cancer cell SMMC-7721 and significantly inhibited the growth, adhesion, invasion, and metastasis of SMMC-7721 cells. As a novel drug carrier system, BIN are a potentially promising targeting treatment for liver cancer