Analyzing Gene Expression Profile in K562 Cells Exposed to Sodium Valproate Using Microarray Combined with the Connectivity Map Database

To explore the mechanism underlying antileukaemia effect of sodium valproate, the growth and survival of the K562 cell line were investigated. Global profiles of gene expression in K562 cells exposed to sodium valproate were assessed and validated. The differentially expressed genes identified were further used to query the connectivity map database to retrieve a ranked list of compounds that act on the same intracellular targets as sodium valproate. A significant increase in cell apoptosis and a change in gene expression profile were observed in valproate-exposed K562 cells. The significant enrichment analysis of gene ontology terms for the differentially expressed genes showed that these genes were involved in many important biological processes. Eight differentially expressed genes involved in apoptosis were verified by quantitative real-time PCR. The connectivity map analysis showed gene expression profile in K562 cells exposed to sodium valproate was most similar to that of HDACi and PI3K inhibitors, suggesting that sodium valproate might exert antileukaemic action by inhibiting HDAC as well as inhibiting PI3K pathway. In conclusion, our data might provide clues to elucidate the molecular and therapeutic potential of VPA in leukaemia treatment, and the connectivity map is a useful tool for exploring the molecular mechanism of drug action

Measurement-device-independent quantum key distribution over untrustful metropolitan network

Quantum cryptography holds the promise to establish an information-theoretically secure global network. All field tests of metropolitan-scale quantum networks to date are based on trusted relays. The security critically relies on the accountability of the trusted relays, which will break down if the relay is dishonest or compromised. Here, we construct a measurement-device-independent quantum key distribution (MDIQKD) network in a star topology over a 200 square kilometers metropolitan area, which is secure against untrustful relays and against all detection attacks. In the field test, our system continuously runs through one week with a secure key rate ten times larger than previous result. Our results demonstrate that the MDIQKD network, combining the best of both worlds --- security and practicality, constitutes an appealing solution to secure metropolitan communications.Comment: 17 pages, 4 figure

Experimental measurement-device-independent quantum digital signatures over a metropolitan network

Quantum digital signatures (QDS) provide a means for signing electronic communications with informationtheoretic security. However, all previous demonstrations of quantum digital signatures assume trusted measurement devices. This renders them vulnerable against detector side-channel attacks, just like quantum key distribution. Here, we exploit a measurement-device-independent (MDI) quantum network, over a 200-square-kilometer metropolitan area, to perform a field test of a three-party measurement-device-independent quantum digital signature (MDI-QDS) scheme that is secure against any detector side-channel attack. In so doing, we are able to successfully sign a binary message with a security level of about 1E-7. Remarkably, our work demonstrates the feasibility of MDI-QDS for practical applications.Comment: 5 pages, 1 figure, 2 tables, supplemental materials included as ancillary fil

[2,6-Bis(4,5-dihydro-1H-imidazol-2-yl)pyridine]dichloridomanganese(II)

In the title compound, [MnCl2(C11H13N5)], the MnII ion is five-coordinated in a distorted square-pyramidal geometry, with three N atoms from the neutral tridentate 2,6-bis­(4,5-dihydro-1H-imidazol-2-yl)pyridine ligand and one chloride ion forming the basal plane and the other chloride ion in the apical position. Both dihydro­imidazole rings adopt envelope conformations. In the crystal structure, mol­ecules are linked into a three-dimensional network by N—H⋯Cl and C—H⋯Cl hydrogen bonds

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment