Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the ...effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy. In vitro, Rb2 (50 µmol/L) obviously increased autophagic flux in HepG2 cells and primary mouse hepatocytes, and consequently reduced the lipid accumulation induced by oleic acid in combination with high glucose. Western blotting analysis showed that Rb2 partly reversed the high fatty acid in combination with high glucose (OA)-induced repression of autophagic pathways including AMP-activated protein kinase (AMPK) and silent information regulator 1 (sirt1). Furthermore, pharmacological inhibition of the sirt1 or AMPK pathways attenuated these beneficial effects of Rb2 on hepatic autophagy and lipid accumulation. Taken together, these results suggested that Rb2 alleviated hepatic lipid accumulation by restoring autophagy via the induction of sirt1 and activation of AMPK, and resulted in improved nonalcoholic fatty liver disease (NAFLD) and glucose tolerance.
With the improvement of gene vectors, the rise of chimeric antigen receptor T cell immunotherapy and breakthroughs in the genome editing technology, gene therapy had once again returned to the ...central stage of disease treatment. It had brought new choices to clinical therapy of diseases such as tumors and genetic diseases, and had changed the status quo of treatment for monogenic disorders and diffuse large B-cell lymphoma. Until August 2019, 22 gene medicines had been approved by the drug regulatory agencies from various countries, but there were few relevant reviews of combing these drugs systematically. Consequently, this review summarizes the gene therapy drugs approved worldwide from 1998 to 2019 in details, including names, indications, dates of approval, companies, vectors, the applied technologies and mechanisms of gene therapy drugs, etc. Furthermore, the gene therapy drugs were classified and addressed in accordance with the employed vectors. Gene therapy had gradually been accepted by the government and the public since 1980s, and have become a new and important alternative to existing treatments for human diseases in the past few years. Therefore, gene therapy drugs, with safe vectors and advanced biotechnologies, would play a greater role in the prevention and treatment of human diseases in future.
The interplay between thermal and quantum fluctuations controls the competition between phases of matter in strongly correlated electron systems. We study finite-temperature properties of the ...strongly coupled two-dimensional doped Hubbard model using the minimally entangled typical thermal states method on width-four cylinders. We discover that a phase characterized by commensurate short-range antiferromagnetic correlations and no charge ordering occurs at temperatures above the half-filled stripe phase extending to zero temperature. The transition from the antiferromagnetic phase to the stripe phase takes place at temperatureT/t≈0.05and is accompanied by a steplike feature of the specific heat. We find the single-particle gap to be smallest close to the nodal point atk=(π/2,π/2)and detect a maximum in the magnetic susceptibility. These features bear a strong resemblance to the pseudogap phase of high-temperature cuprate superconductors. The simulations are verified using a variety of different unbiased numerical methods in the three limiting cases of zero temperature, small lattice sizes, and half filling. Moreover, we compare to and confirm previous determinantal quantum Monte Carlo results on incommensurate spin-density waves at finite doping and temperature.
Recently, significant progress has been made in (2+1 )-dimensional conformal field theories without supersymmetry. In particular, it was realized that different Lagrangians may be related by hidden ...dualities; i.e., seemingly different field theories may actually be identical in the infrared limit. Among all the proposed dualities, one has attracted particular interest in the field of strongly correlated quantum-matter systems: the one relating the easy-plane noncompact CP1 model (NCCP1 ) and noncompact quantum electrodynamics (QED) with two flavors (N=2 ) of massless two-component Dirac fermions. The easy-plane NCCP1 model is the field theory of the putative deconfined quantum-critical point separating a planar (XY ) antiferromagnet and a dimerized (valence-bond solid) ground state, while N=2 noncompact QED is the theory for the transition between a bosonic symmetry-protected topological phase and a trivial Mott insulator. In this work, we present strong numerical support for the proposed duality. We realize the N=2 noncompact QED at a critical point of an interacting fermion model on the bilayer honeycomb lattice and study it using determinant quantum Monte Carlo (QMC) simulations. Using stochastic series expansion QMC simulations, we study a planar version of the S=1/2 J−Q spin Hamiltonian (a quantum XY model with additional multispin couplings) and show that it hosts a continuous transition between the XY magnet and the valence-bond solid. The duality between the two systems, following from a mapping of their phase diagrams extending from their respective critical points, is supported by the good agreement between the critical exponents according to the proposed duality relationships. In the J−Q model, we find both continuous and first-order transitions, depending on the degree of planar anisotropy, with deconfined quantum criticality surviving only up to moderate strengths of the anisotropy. This explains previous claims of no deconfined quantum criticality in planar two-component spin models, which were in the strong-anisotropy regime, and opens doors to further investigations of the global phase diagram of systems hosting deconfined quantum-critical points.
Single-cell RNA sequencing (scRNA-seq) is generally used for profiling transcriptome of individual cells. The droplet-based 10X Genomics Chromium (10X) approach and the plate-based Smart-seq2 ...full-length method are two frequently used scRNA-seq platforms, yet there are only a few thorough and systematic comparisons of their advantages and limitations. Here, by directly comparing the scRNA-seq data generated by these two platforms from the same samples of CD45− cells, we systematically evaluated their features using a wide spectrum of analyses. Smart-seq2 detected more genes in a cell, especially low abundance transcripts as well as alternatively spliced transcripts, but captured higher proportion of mitochondrial genes. The composite of Smart-seq2 data also resembled bulk RNA-seq data more. For 10X-based data, we observed higher noise for mRNAs with low expression levels. Approximately 10%−30% of all detected transcripts by both platforms were from non-coding genes, with long non-coding RNAs (lncRNAs) accounting for a higher proportion in 10X. 10X-based data displayed more severe dropout problem, especially for genes with lower expression levels. However, 10X-data can detect rare cell types given its ability to cover a large number of cells. In addition, each platform detected distinct groups of differentially expressed genes between cell clusters, indicating the different characteristics of these technologies. Our study promotes better understanding of these two platforms and offers the basis for an informed choice of these widely used technologies.
Chuanxiong Rhizome (called Chuanxiong, CX in Chinese), the dried rhizome of Ligusticum chuanxiong Hort, is an extremely common traditional edible-medicinal herb. As a widely used ethnomedicine in ...Asia including China, Japan and Korea, CX possesses ideal therapeutic effect on cardiovascular and cerebrovascular diseases, and is also used as a major ingredient in soups for regular consumption to benefit health. Based on the traditional perception, amounts of investigations on different aspects have been done for CX in the past decades. However, no literature systematic review about these achievements have been compiled. Herein, the aim of this review is to present the up-to-date information on the ethnobotany, ethnopharmacological uses, phytochemicals, pharmacological activities, toxicology of this plant to identify their therapeutic potential and directs future research opportunities. So far, about 174 compounds has been isolated and identified from CX, in which phthalides and alkaloids would be the main bioactive ingredients for its pharmacological properties, such as anti-cerebral ischemia, anti-myocardial ischemia, blood vessel protection, anti-thrombotic, anti-hypertensive, anti-atherosclerosis, anti-spasmodic, anti-inflammatory, anti-cancer, anti-oxidant, and anti-asthma effects. Even so, due to the incomplete standardized planting, unstable herbal quality, and outdated preparation techniques, the industrial progress of CX is still less developed.
•About 174 compounds has been isolates and identified from CX.•Phthalides and alkaloids in CX would be the main bioactive ingredients for its various pharmacological properties.•Ethnobotany, ethnopharmacological uses, phytochemicals, pharmacological activities, etc. of CX were systematically presented.
► Co-pyrolysis presented three stages. ► Interaction between solid phases inhibited the thermal decomposition. ► Kinetic triplets were obtained.
To find out an alternative of coal saving, a kind of ...microalgae, Chlorella vulgaris (C. vulgaris) which is widespread in fresh water was introduced into coal pyrolysis process. In this work, the pyrolysis experiments of C. vulgaris and coal blend (CCB) were carried out by TGA, and those of C. vulgaris and coal were also taken respectively as control groups. It was found that: the TG and DTG profiles of CCB were similar to C. vulgaris, but different from coal under various blending ratios; DTG profiles of CCB were different at several heating rates; interaction was observed between the solid phases of CCB; kinetic triplets were determined by the Kissinger–Akahira–Sunose (KAS), Flynn–Wall–Ozawa (FWO), and master-plots method, respectively. The results provide a reference for further study on co-pyrolysis of microalgae and coal to a certain extent.
Competing and intertwined orders including inhomogeneous patterns of spin and charge are observed in many correlated electron materials, such as high-temperature superconductors. Introducing a new ...development of the constrained-path auxiliary-field quantum Monte Carlo method, we study the interplay between thermal and quantum fluctuations in the two-dimensional Hubbard model. We obtain an accurate and systematic characterization of the evolution of the spin and charge correlations as a function of temperatureTand how it connects to the ground state, at three representative hole doping levelsδ=1/5,1/8, and1/10. We find increasing short-range commensurate antiferromagnetic correlations asTis lowered. As the correlation length grows sufficiently large, a modulated spin-density wave (SDW) appears. Atδ=1/5andU/t=6, the SDW saturates and remains short-ranged asT→0. In contrast, atδ=1/8,1/10andU/t=8, this evolves into a ground-state stripe phase. We study the relation between spin and charge orders and find that formation of charge order appears to be driven by that of the spin order. We identify a finite-temperature phase transition below which charge ordering sets in and discuss the implications of our results for the nature of this transition.
Numerous substrates have been identified for Type I and II arginine methyltransferases (PRMTs). However, the full substrate spectrum of the only type III PRMT, PRMT7, and its connection to type I and ...II PRMT substrates remains unknown. Here, we use mass spectrometry to reveal features of PRMT7-regulated methylation. We find that PRMT7 predominantly methylates a glycine and arginine motif; multiple PRMT7-regulated arginine methylation sites are close to phosphorylations sites; methylation sites and proximal sequences are vulnerable to cancer mutations; and methylation is enriched in proteins associated with spliceosome and RNA-related pathways. We show that PRMT4/5/7-mediated arginine methylation regulates hnRNPA1 binding to RNA and several alternative splicing events. In breast, colorectal and prostate cancer cells, PRMT4/5/7 are upregulated and associated with high levels of hnRNPA1 arginine methylation and aberrant alternative splicing. Pharmacological inhibition of PRMT4/5/7 suppresses cancer cell growth and their co-inhibition shows synergistic effects, suggesting them as targets for cancer therapy.
Simultaneous imaging and treatment of infections remains a major challenge, with most current approaches being effective against only one specific group of bacteria or not being useful for diagnosis. ...Here we develop multifunctional nanoagents that can potentially be used for imaging and treatment of infections caused by diverse bacterial pathogens. The nanoagents are made of fluorescent silicon nanoparticles (SiNPs) functionalized with a glucose polymer (e.g., poly4-O-(α-D-glucopyranosyl)-D-glucopyranose) and loaded with chlorin e6 (Ce6). They are rapidly internalized into Gram-negative and Gram-positive bacteria by a mechanism dependent on an ATP-binding cassette (ABC) transporter pathway. The nanoagents can be used for imaging bacteria by tracking the green fluorescence of SiNPs and the red fluorescence of Ce6, allowing in vivo detection of as few as 10
colony-forming units. The nanoagents exhibit in vivo photodynamic antibacterial efficiencies of 98% against Staphylococcus aureus and 96% against Pseudomonas aeruginosa under 660 nm irradiation.
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