Artemisia argyi ethanol extract ameliorates nonalcoholic steatohepatitis-induced liver fibrosis by modulating gut microbiota and hepatic signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear. AIM: This study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model. METHODS: Male C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-ß-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways. RESULTS: Treatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC. CONCLUSION: The AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis.

Sanguisorba officinalis L. Ameliorates Hepatic Steatosis and Fibrosis by Modulating Oxidative Stress, Fatty Acid Oxidation, and Gut Microbiota in CDAHFD-Induced Mice.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases and encompasses non-alcoholic steatosis, steatohepatitis, and fibrosis. Sanguisorba officinalis L. (SO) roots have traditionally been used for their antioxidant properties and have beneficial effects on metabolic disorders, including diabetes and obesity. However, its effects on hepatic steatosis and fibrosis remain unclear. In this study, we explored the effects of a 95% ethanolic SO extract (SOEE) on NAFLD and fibrosis in vivo and in vitro. The SOEE was orally administered to C57BL/6J mice fed a choline-deficient, L-amino-acid-defined, high-fat diet for 10 weeks. The SOEE inhibited hepatic steatosis by modulating hepatic malondialdehyde levels and the expression of oxidative stress-associated genes, regulating fatty-acid-oxidation-related genes, and inhibiting the expression of genes that are responsible for fibrosis. The SOEE suppressed the deposition of extracellular matrix hydroxyproline and mRNA expression of fibrosis-associated genes. The SOEE decreased the expression of fibrosis-related genes in vitro by inhibiting SMAD2/3 phosphorylation. Furthermore, the SOEE restored the gut microbial diversity and modulated specific bacterial genera associated with NAFLD and fibrosis. This study suggests that SOEE might be the potential candidate for inhibiting hepatic steatosis and fibrosis by modulating oxidative stress, fatty acid oxidation, and gut microbiota composition.

Constant-Cost Implementations of Clifford Operations and Multiply-Controlled Gates Using Global Interactions.

We consider quantum circuits composed of single-qubit operations and global entangling gates generated by Ising-type Hamiltonians. It is shown that such circuits can implement a large class of unitary operators commonly used in quantum algorithms at a very low cost-using a constant or effectively constant number of global entangling gates. Specifically, we report constant-cost implementations of Clifford operations with and without ancillae, constant-cost implementation of the multiply-controlled gates with linearly many ancillae, and an O(log^{*}(n)) cost implementation of the n-controlled single-target gates using logarithmically many ancillae. This shows a significant asymptotic advantage of circuits enabled by the global entangling gates.

Efficient Stabilized Two-Qubit Gates on a Trapped-Ion Quantum Computer.

In order to scale up quantum processors and achieve a quantum advantage, it is crucial to economize on the power requirement of two-qubit gates, make them robust to drift in experimental parameters, and shorten the gate times. Applicable to all quantum computer architectures whose two-qubit gates rely on phase-space closure, we present here a new gate-optimizing principle according to which negligible amounts of gate fidelity are traded for substantial savings in power, which, in turn, can be traded for substantial increases in gate speed and/or qubit connectivity. As a concrete example, we illustrate the method by constructing optimal pulses for entangling gates on a pair of ions within a trapped-ion chain, one of the leading quantum computing architectures. Our method is direct, noniterative, and linear, and, in some parameter regimes, constructs gate-steering pulses requiring up to an order of magnitude less power than the standard method. Additionally, our method provides increased robustness to mode drift. We verify the new trade-off principle experimentally on our trapped-ion quantum computer.

Efficient arbitrary simultaneously entangling gates on a trapped-ion quantum computer.

Efficiently entangling pairs of qubits is essential to fully harness the power of quantum computing. Here, we devise an exact protocol that simultaneously entangles arbitrary pairs of qubits on a trapped-ion quantum computer. The protocol requires classical computational resources polynomial in the system size, and very little overhead in the quantum control compared to a single-pair case. We demonstrate an exponential improvement in both classical and quantum resources over the current state of the art. We implement the protocol on a software-defined trapped-ion quantum computer, where we reconfigure the quantum computer architecture on demand. Our protocol may also be extended to a wide variety of other quantum computing platforms.

Toward the first quantum simulation with quantum speedup.

With quantum computers of significant size now on the horizon, we should understand how to best exploit their initially limited abilities. To this end, we aim to identify a practical problem that is beyond the reach of current classical computers, but that requires the fewest resources for a quantum computer. We consider quantum simulation of spin systems, which could be applied to understand condensed matter phenomena. We synthesize explicit circuits for three leading quantum simulation algorithms, using diverse techniques to tighten error bounds and optimize circuit implementations. Quantum signal processing appears to be preferred among algorithms with rigorous performance guarantees, whereas higher-order product formulas prevail if empirical error estimates suffice. Our circuits are orders of magnitude smaller than those for the simplest classically infeasible instances of factoring and quantum chemistry, bringing practical quantum computation closer to reality.