The blockade of the TGF-ß pathway alleviates abnormal glucose and lipid metabolism of lipodystrophy not obesity.

TGF-ß is thought to be involved in the physiological functions of early organ development and pathological changes in substantial organ fibrosis, while studies around adipose tissue function and systemic disorders of glucolipid metabolism are still scarce. In this investigation, two animal models, aP2-SREBP-1c mice and ob/ob mice, were used. TGF-ß pathway showed up-regulated in the inguinal white adipose tissue (iWAT) of the two models. SB431542, a TGF-ß inhibitor, successfully increased inguinal white adipocyte size by more than 1.5 times and decreased the weight of Peripheral organs including liver, Spleen and Kidney to 73.05%/62.18%/73.23% of pre-administration weights. The iWAT showed elevated expression of GLUTs and lipases, followed by a recovery of circulation GLU, TG, NEFA, and GLYCEROL to the wild-type levels in aP2-SREBP-1c mice. In contrast, TGF-ß inhibition did not have similar effects on that of ob/ob mice. In vitro, TGF-ß blocker treated mature adipocytes had considerably higher levels of glycerol and triglycerides than the control group, whereas GLUTs and lipases expression levels were unchanged. These findings show that inhibiting the abnormally upregulated TGF-ß pathway will only restore iWAT expansion and ameliorate the global metabolic malfunction of glucose and lipids in lipodystrophy, not obesity.

A quantum algorithm for heat conduction with symmetrization.

Heat conduction, driven by thermal non-equilibrium, is the transfer of internal thermal energy through physical contacts, and it exists widely in various engineering problems, such as spacecraft and state-of-the-art dilution refrigerators. The mathematical equation for heat conduction is a prototypical partial differential equation. Here we report a quantum algorithm for heat conduction (QHC) that significantly outperforms classical algorithms. We represent the original heat conduction system by a symmetric system with an ancilla qubit so that the quantum circuit complexity is polylogarithmic in the number of discretized grid points. Compared with the existing algorithms based on solving linear equations via the Harrow-Hassidim-Lloyd (HHL) algorithm, our method evolves the linear process directly without phase estimation, which involves complex quantum operations and large output error. Therefore, this algorithm is experimental-friendly and without output error after the discretization procedure. We experimentally implemented the algorithm for a one-dimensional thermal conduction process with two-edge constant temperatures and adiabatic conditions on a nuclear spin quantum processor. The spatial and temporal distributions of the temperature are accurately determined from the experimental results. Our work can be naturally applied to any physical processes that can be reduced to the heat equation.

A nanosystem loaded with perfluorohexane and rose bengal coupled upconversion nanoparticles for multimodal imaging and synergetic chemo-photodynamic therapy of cancer.

Theranostics is a new trend integrating diagnostic and therapeutic functions in tumour research. Theranostic nanoparticles enabling both tumour imaging and drug delivery are a promising platform for image-guided cancer therapy. Photodynamic therapy (PDT) has great potential in synergy with traditional chemotherapy but faces great challenges due to hypoxia, poor targeting ability and the limited penetration depth of visible light. To solve these problems, we presented a novel nanosystem of FA/UCNPs-RB/HCPT/PFH@lipid (denoted as FURH-PFH-NPs), with a perfluorohexane (PFH) carrying rich oxygen core and a folic acid-modified lipid shell. The shell contains 10-hydroxycamptothecin (HCPT) and self-fluorescing photosensitizer compounds, namely, upconversion nanoparticles and rose bengal (UCNPs-RB). In this study, FURH-PFH-NPs aggregated in SKOV3 cells (in vitro) and the nude xenograft tumour region when combined with folic acid receptors. When triggered by low-intensity focused ultrasound (LIFU), FURH-PFH-NPs released PFH, UCNPs-RB and HCPT. The above procedure was monitored through multimodal imaging, which simultaneously guided the tumour therapy. UCNPs-RB and PFH promoted the PDT effect under LIFU. Through PDT and HCPT, we obtained better therapeutic effects and good biosafety against SKOV3 nude xenograft tumours. FURH-PFH-NPs combined with LIFU and laser irradiation might be a promising strategy for ovarian cancer.

Rhizospheric soil fungal community patterns of Duchesnea indica in response to altitude gradient in Yunnan, southwest China.

The magnitude of the impact of altitude gradient on microbial community and diversity has been studied in recent decades. Whereas bacteria have been the focus of most studies, fungi have been given relatively less attention. As a vital part of the macro- and microscopic ecosystem, rhizosphere fungi play a key role in organic matter decomposition and relative abundance of plant species and have an impact on plant growth and development. Using Duchesnea indica as the host plant, we examined the rhizosphere soil fungal community patterns across the altitude gradient in 15 sites of Yunnan province by sequencing the fungal ITS2 region with the Illumina MiSeq platform. We determined the fungal community composition and structure. We found that, surprisingly, rhizosphere soil fungal diversity of D. indica increased with altitudinal gradient. There was a slight difference in diversity between samples from high- and medium-altitude sites, with medium-altitude sites having the greater diversity. Furthermore, the rhizosphere soil fungal community composition and structure kept changing along the altitudinal gradient. Taxonomic results showed that the extent of phylum diversity was greatest at high-altitude sites, with Ascomycota, Basidiomycota, Zygomycota, and Glomeromycota as the most dominant fungal phyla.

Duality quantum algorithm efficiently simulates open quantum systems.

Because of inevitable coupling with the environment, nearly all practical quantum systems are open system, where the evolution is not necessarily unitary. In this paper, we propose a duality quantum algorithm for simulating Hamiltonian evolution of an open quantum system. In contrast to unitary evolution in a usual quantum computer, the evolution operator in a duality quantum computer is a linear combination of unitary operators. In this duality quantum algorithm, the time evolution of the open quantum system is realized by using Kraus operators which is naturally implemented in duality quantum computer. This duality quantum algorithm has two distinct advantages compared to existing quantum simulation algorithms with unitary evolution operations. Firstly, the query complexity of the algorithm is O(d(3)) in contrast to O(d(4)) in existing unitary simulation algorithm, where d is the dimension of the open quantum system. Secondly, By using a truncated Taylor series of the evolution operators, this duality quantum algorithm provides an exponential improvement in precision compared with previous unitary simulation algorithm.

A self-contrast approach to evaluate the inhibitory effect of chrysosplenetin, in the absence and presence of artemisinin, on the in vivo P-glycoprotein-mediated digoxin transport activity.

In this study, we used a self-contrast method, which excluded the individual difference, to evaluate the inhibitory effect of chrysosplentin (CHR) in the presence or absence of artemisinin (ART) on the P-glycoprotein (P-gp) transport activity. A sensitive and rapid UHPLC-MS/MS method was applied for quantification of digoxin, a P-gp-specific substrate, in rat plasma. A pharmacokinetic study was carried out: first after an oral administration of digoxin at a dose of 0.09 mg/kg (first period), followed by a 20-day wash-out, then after another administration of digoxin (second period). During the second period, test compounds were orally given three times per day for seven consecutive days. Results showed that the t1/2 of digoxin in all the groups had no significant difference between the first and second periods. The AUC0-24 , Cmax , tmax , and Clz /F of the negative control and ART alone groups showed no difference. However, the AUC0-24 and Cmax in the CHR alone, CHR-ART (1:2) and verapamil (positive control) groups showed 2.34-, 3.04-, 1.79-, and 1.81-, 1.99-, 2.06-fold increases along with 3.50-, 3.84- and 4.76-fold decreases for CLz /F, respectively. The tmax in the CHR-ART (1:2) group increased 3.73-fold. In conclusion, our self-contrast study suggested that CHR, especially when combined with ART in a ratio of 1:2, inhibited P-gp activity while ART alone has no effect. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of genetic polymorphisms of CYP2C19*2/*3 and MDR1 C3435T on the pharmacokinetics of lansoprazole in healthy Chinese subjects.

OBJECTIVES: To evaluate the influence of CYP2C19*2/*3 and MDR1 C3435T polymorphisms on the pharmacokinetics of lansoprazole (LPZ) in healthy Chinese subjects. METHODS: All 24 subjects were from a study of bioequivalence. Plasma concentrations of LPZ were determined by liquid chromatography/mass spectrometry. Cytochrome P450 (CYP) 2C19*2/*3 and multidrug resistance transporter gene 1 (MDR1) C3435T of the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Significant differences were found in the area under the concentration-time curve from predose to T (AUC(0-T)), area under the concentration-time curve from predose to infinity (AUC(0-∞), t(1/2)), and apparent oral clearance (CL/F) of LPZ between CYP2C19 extensive metabolizers and intermediate metabolizers (p < 0.05). The AUC(0-T), AUC(0-∞), maximum plasma concentration, and CL/F of LPZ were significantly different between subjects with the MDR1 C3435T C/C, C/T, and T/T polymorphisms (p < 0.05). CONCLUSION: CYP2C19*2/*3 and MDR1 C3435T polymorphisms are important determinants of LPZ pharmacokinetics.

[Pharmacokinetics and tissue distribution of irinotecan hydrochloride nanoparticles].

To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.

[Determination of chrysosplenetin, metabolic inhibitor of artemisinin, in rat plasma by UPLC-ms/MS and study on its pharmacokinetics].

OBJECTIVE: The study aimed to develop the assay of chrysosplenetin (CHR), a metabolic inhibitor of artemisinin by UPLC-MS/MS in rat plasma and investigate the pharmacokinetics parameters of CHR. METHOD: The plasma samples were precipitated by acetonitrile to remove the proteins. Separation was carried out on a Shim-pack XR-ODS C,18(2. 0 mm x 100 mm, 2. 2 micromp.m) column using a mobile phase containing methanol-0. 1% formic acid (87:13) using by diazepam as internal standard. Mass spectrometer with electrospray ionization (ESI) operated in the positive ion mode was used for analysis. Total analysis time was 2 min. RESULT: The assay was linear in the range 5-5 000 microg L-1 (r =0. 999 3) with recoveries in the range from 69. 0% to 81.2% and satisfied inter-, intra- precision and accuracy. CHR after oral administration is not easy to absorb with double or multimodal peak phenomenon. The t1/2 of CHR after intravenous injection was very short and that of low, medium, and high dosage was (17. 01 +/- 8. 06) , (24. 62 +/- 4. 59), (28. 46+/- 4. 63) min, respectively. CONCLUSION: The developed method was special, rapid, and sensitive for determination of CHR pharmacokinetics. [Key words] UPLC-MS/MS; chrysosplenetin; pharmacokinetics; plasma; rat