DNMT3a in the hippocampal CA1 is crucial in the acquisition of morphine self‐administration in rats

Drug‐reinforced excessive operant responding is one fundamental feature of long-lasting addiction‐like behaviors and relapse in animals. However, the transcriptional regulatory mechanisms responsible for the persistent drug‐specific (not natural rewards) operant behavior are not entirely clear. In this study, we demonstrate a key role for one of the de novo DNA methyltransferase, DNMT3a, in the acquisition of morphine self‐administration (SA) in rats. The expression of DNMT3a in the hippocampal CA1 region but not in the nucleus accumbens shell was significantly up‐regulated after 1‐ and 7‐day morphine SA (0.3 mg/kg/infusion) but not after the yoked morphine injection. On the other hand, saccharin SA did not affect the expression of DNMT3a or DNMT3b. DNMT inhibitor 5‐aza‐2‐deoxycytidine (5‐aza) microinjected into the hippocampal CA1 significantly attenuated the acquisition of morphine SA. Knockdown of DNMT3a also impaired the ability to acquire the morphine SA. Overall, these findings suggest that DNMT3a in the hippocampus plays an important role in the acquisition of morphine SA and may be a valid target to prevent the development of morphine addiction. Includes Supplemental informatio

A Polyrotaxane-based pH-labile Drug Delivery System

A novel polyrotaxane (PR)-based triblock copolymer was exploited as polymeric carrier for doxorubicin (DOX). A sample holding a feed molar ratio of Pluronic F127 to β-CD to poly(ethylene glycol) methyl ether methacrylate (PEGMA) equal to 1:30:20 was synthesized via the in situ atom transfer radical polymerization (ATRP) and then conjugated with DOX using pH sensitive hydrazone linker. The resulting PR-DOX conjugates enabled to self-assemble into nano-particles of about 70 nm in diameter in aqueous solution as evidenced by TEM. The release of DOX was varied from 10 % to 37 % over 72 h at physiological and acidic pH, respectively. The PR-based triblock copolymer without DOX conjugation showed almost non toxicity, while these nano-particles with DOX conjugation presented increased toxicity

Mixing of X and Y states from QCD Sum Rules analysis

We study $\bar{Q}Q\bar{q}q$ and $\bar{Q}qQ\bar{q}$ states as mixed states in QCD sum rules. By calculating the two-point correlation functions of pure states of their corresponding currents, we review the mass and coupling constant predictions of $J^{PC}=1^{++}$, $1^{--}$, $1^{-+}$ states. By calculating the two-point mixed correlation functions of $\bar{Q}Q\bar{q}q$ and $\bar{Q}qQ\bar{q}$ currents, and we estimate the mass and coupling constants of the corresponding `"physical state" that couples to both $\bar{Q}Q\bar{q}q$ and $\bar{Q}qQ\bar{q}$ currents. Our results suggest that $1^{++}$ states are more likely mixing from $\bar{Q}Q\bar{q}q$ and $\bar{Q}qQ\bar{q}$ components, while for $1^{--}$ and $1^{-+}$ states, there is less mixing between $\bar{Q}Q\bar{q}q$ and $\bar{Q}qQ\bar{q}$. Our results suggest the $Y$ series of states have more complicated components.Comment: 14 pages,3 figs, 7 table

Error Mitigated Metasurface-Based Randomized Measurement Schemes

Estimating properties of quantum states via randomized measurements has come to play a significant role in quantum information science. In this paper, we design an innovative approach leveraging metasurfaces to perform randomized measurements on photonic qubits, together with error mitigation techniques that suppress realistic metasurface measurement noise. Through fidelity and purity estimation, we confirm the capability of metasurfaces to implement randomized measurements and the unbiased nature of our error-mitigated estimator. Our findings show the potential of metasurface-based randomized measurement schemes in achieving robust and resource-efficient estimation of quantum state properties

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

Study of RNA Interference Targeting NET-1 Combination with Sorafenib for Hepatocellular Carcinoma Therapy In Vitro

The aim of this study is to explore the inhibitory effects of RNA interference (RNAi) targeting NET-1 or combined with sorafenib on HCC in vitro and in vivo and the possible underlying mechanisms. The expressions of NET-1 mRNA and protein were detected by RT-QPCR and western blot. The ability of proliferation was determined by CCK-8 assay. Apoptosis was examined by flow cytometry (FCM). Abilities of migration and invasion were measured by scratch-wound assay and transwell assay. MHCC97H cells with stable transfection of NET-1shRNA were injected subcutaneously to prepare nude mice model of HCC and Caspase-3, Caspase-8, and Caspase-9 mRNAs of tumor tissues in different groups were examined. NET-1 mRNA and protein were reduced sharply in MHCC97H cells transfected with NET-1shRNA. The abilities of proliferation and migration were inhibited and apoptosis was promoted in either NET-1shRNA or sorafenib as compared with untreated cells in vitro and in vivo (P<0.05). The mRNA levels of caspase-3, caspase-8, and caspase-9 of tumor tissues were reduced in different treatment groups compared with untreated group, particularly in combination group. (P<0.05). The combination NET-1shRNA with sorafenib dramatically enhanced the effects of sorafenib antitumor ,which may involve in blocking ras signaling pathway and stimulating apoptotic pathways simultaneously