Cardiovascular and metabolic disease (CMD) remains a main cause of premature death worldwide. Berberine (BBR), a lipid-lowering botanic compound with diversified potency against metabolic disorders, ...is a promising candidate for ameliorating CMD. The liver is the target of BBR so that liver-site accumulation could be important for fulfilling its therapeutic effect. In this study a rational designed micelle (CTA-Mic) consisting of α-tocopheryl hydrophobic core and on-site detachable polyethylene glycol-thiol shell is developed for effective liver deposition of BBR. The bio-distribution analysis proves that the accumulation of BBR in liver is increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes is detectable in the HepG2 cells and in vivo. In the high fat diet-fed mice, BBR-CTA-Mic intervention remarkably improves metabolic profiles and reduces the formation of aortic arch plaque. Our results provide proof-of-concept for a liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.
A novel biscinchona alkaloid-catalyzed highly enantioselective desymmetrization reaction of bisphenol compounds with achiral Morita-Baylis-Hillman carbonate agents was developed. Through the ...asymmetric allylic alkylation strategy, a broad range of optically active P-stereogenic phosphine oxides were generated with excellent to good yields (up to 99%) and high enantioselectivities (up to 98.5 : 1.5 e.r.). The reaction was further investigated by the linear free energy relationship (LFER) analysis. A possible transition state was proposed and furthered verified by theoretical calculations.
Fungal pathogens secrete effector proteins to suppress plant basal defense for successful colonization. Resistant plants, however, can recognize effectors by cognate R proteins to induce ...effector-triggered immunity (ETI). By analyzing secretomes of the vascular fungal pathogen Verticillium dahliae, we identified a novel secreted protein VdSCP7 that targets the plant nucleus.
The green fluorescent protein (GFP)-tagged VdSCP7 gene with either a mutated nuclear localization signal motif or with additional nuclear export signal was transiently expressed in Nicotiana benthamiana, and investigated for induction of plant immunity. The role of VdSCP7 in V. dahliae pathogenicity was characterized by gene knockout and complementation, and GFP labeling.
Expression of the VdSCP7 gene in N. benthamiana activated both salicylic acid and jasmonate signaling, and altered the plant’s susceptibility to the pathogens Botrytis cinerea and Phytophthora capsici. The immune response activated by VdSCP7 was highly dependent on its initial extracellular secretion and subsequent nuclear localization in plants. Knockout of the VdSCP7 gene significantly enhanced V. dahliae aggressiveness on cotton. GFP-labeled VdSCP7 is secreted by V. dahliae and accumulates in the plant nucleus.
We conclude that VdSCP7 is a novel effector protein that targets the host nucleus to modulate plant immunity, and suggest that plants can recognize VdSCP7 to activate ETI during fungal infection.
In conventional electron trapping optical storage phosphor, both short‐ and long‐wavelength light are needed for information write‐in and read‐out, respectively, complicating the optical storage ...system. Here, a Y3Al2Ga3O12:Pr3+,Eu3+ optical storage phosphor with Pr3+ as an electron donor and Eu3+ as an electron trap is designed, and a single wavelength write‐read scheme is demonstrated, which employs the same blue laser diode (LD) light source for both optical write‐in through two‐photon up‐conversion charging and for read‐out based on photostimulated luminescence (PSL), originated from 4f15d1→4f2 transition of Pr3+ peaked at 315 nm in UV region. A deep electron trap with the mean depth of 1.42 eV and a narrow distribution of 0.3 eV is observed in the presence of Eu3+ in Y3Al2Ga3O12:Pr3+, implying its long‐term storage potential. The write‐in and read‐out experiments are conducted using 450 nm blue LD light with the power density of 1 W cm−2 for write‐in and that with a low power density of 0.02 W cm−2 for read‐out in order to avoid the effect of up‐conversion luminescence on PSL signal. These results will advance the electron trapping optical storage scheme.
A novel optical storage scheme with two‐photon write‐in and one‐photon read‐out using a single‐wavelength light source is developed and demonstrated in Y3Al2Ga3O12:Pr3+,Eu3+ storage phosphor. Pr3+ and Eu3+ provide the energy‐level structure for two‐photon write‐in and deep traps for long‐term storage, respectively. This scheme simplifies conventional optical storage systems based on electron‐trapping media.
Patients with obsessive compulsive disorder (OCD) exhibit tremendous heterogeneity in structural and functional neuroimaging aberrance. However, most previous studies just focus on group‐level ...aberrance of a single modality ignoring heterogeneity and multimodal features. On that account, we aimed to uncover OCD subtypes integrating structural and functional neuroimaging features with the help of a multiview learning method and examined multimodal aberrance for each subtype. Ninety‐nine first‐episode untreated patients with OCD and 104 matched healthy controls (HCs) undergoing structural and functional MRI were included in this study. Voxel‐based morphometric and amplitude of low‐frequency fluctuation (ALFF) were adopted to assess gray matter volumes (GMVs) and the spontaneous neuronal fluctuations respectively. Structural/functional distance network was obtained by calculating Euclidean distance between pairs of regional GMVs/ALFF values across patients. Similarity network fusion, one of multiview learning methods capturing shared and complementary information from multimodal data sources, was used to fuse multimodal distance networks into one fused network. Then spectral clustering was adopted to categorize patients into subtypes. As a result, two robust subtypes were identified. These two subtypes presented opposite GMV aberrance and distinct ALFF aberrance compared with HCs while shared indistinguishable clinical and demographic features. In addition, these two subtypes exhibited opposite structure–function difference correlation reflecting distinct adaptive modifications between multimodal aberrance. Altogether, these results uncover two objective subtypes with distinct multimodal aberrance and provide a new insight into taxonomy of OCD.
With the help of a multiview learning method named SNF, we proposed a novel framework integrating structural and functional information and successfully uncovered two subject subtypes of OCD. These two subtypes presented totally opposite GMV difference and distinct ALFF aberrance compared with HCs while shared indistinguishable clinical and demographic features.
In this paper, the historical power load data from the National Electricity Market (Australia) is used to analyze the characteristics and regulations of electricity (the average value of every eight ...hours). Then, considering the inverse of Euclidean distance as the weight, this paper proposes a novel short-term load forecasting model based on the weighted k-nearest neighbor algorithm to receive higher satisfied accuracy. In addition, the forecasting errors are compared with the back-propagation neural network model and the autoregressive moving average model. The comparison results demonstrate that the proposed forecasting model could reflect variation trend and has good fitting ability in short-term load forecasting.
Gut dysbiosis has been found to be involved in the pathogenesis of energy metabolic disorders and might be a new strategy for these ailments. Berberine (BBR), a botanical medicine, shows therapeutic ...efficacy in patients with metabolic diseases. Numerous reports have shown BBR's modulating effect on gut microbiota, opening a new avenue to understand BBR's mechanism. In this study, a colon‐specific delivery system, BBR‐CS/PT‐NP, is investigated by the assembly of pH/gut microflora dual stimuli‐responsive nanoparticles for enhancing the interaction between BBR and gut microbiota. After oral administration, the delivering system remains stable in the stomach and small intestine, followed by a burst release of BBR after reaching the colon segment rich in intestinal bacteria. The enzymes produced by bacteria degrade the nanoparticle, causing direct exposure of BBR to gut microbiota. In the high fat diet‐induced obese hamsters, BBR‐CS/PT‐NP intervention inhibits weight‐gain and fat deposition, decreases plasma lipids and glucose levels, improves inflammation condition and insulin resistance, alleviates hepatic steatosis, at a level significantly higher than the pure BBR does. The mechanisms might be attributable to the enhanced interaction between BBR and the gut flora. The results provide a novel proof‐of‐concept for drug delivery targeting gut microbiota to ameliorate metabolic disorders.
Gut dysbiosis is involved in the pathogenesis of energy metabolic disorders and represents a new strategy for treating these ailments. In this study, a pH/gut microflora dual stimuli‐responsive system, berberine (BBR)‐CS/PT‐NP with colon‐homing and microbiota‐targeting characteristics, is investigated to enhance the interaction between BBR and the gut microbiota. It provides a novel proof‐of‐concept for drug delivery targeting gut microbiota to ameliorate metabolic diseases.
The lncRNA nuclear enriched abundant transcript 1 (NEAT1) promotes sepsis-inflammatory responses and acute kidney injury (AKI), but little known about the underlying mechanisms. This study aims to ...investigate the roles of NEAT1 in regulating macrophage polarization and its potential for alleviating inflammatory responses during sepsis pathogenesis. Mouse RAW264.7 macrophages were treated with lipopolysaccharide (LPS) as a cellular inflammatory model. NEAT1 shRNA, miR-125a-5p mimics, and TRAF6-overexpressing vector were used to transfect RAW264.7 cells. NEAT1, miR-125a-5p, and mRNA levels of functional genes were detected by quantitative RT-PCR. Protein abundances were analyzed by western blotting. Macrophage polarization was evaluated by flow cytometry. The bindings of miR-125a-5p with NEAT1 or TRAF6 gene were validated by dual luciferase reporter assay. LPS treatment promoted NEAT1 and suppressed miR-125a-5p expression in mouse macrophage cells. NEAT1 silencing by shRNAs promoted macrophage M2 polarization under LPS treatment, which upregulated miR-125a-5p expression, repressed TRAF6 expression and TAK1 protein phosphorylation in macrophages. These cellular and molecular changes induced by NEAT1 shRNAs were abrogated by miR-125a-5p inhibitors. Moreover, miR-125a-5p mimics suppressed TRAF6 expression and TAK1 protein phosphorylation in LPS-treated macrophages, thus causing macrophage M2 polarization under LPS treatment. TRAF6 overexpression abrogated the miR-125a-5p mimics-induced macrophage M2 polarization. miR-125a-5p could directly bind to NEAT1 or TRAF6 gene in macrophages. lncRNA NEAT1 knockdown ameliorates LPS-induced inflammation by promoting macrophage M2 polarization
via
miR-125a-5p/TRAF6/TAK1 axis.
A modified projective synchronization is proposed to acquire a general kind of proportional relationships between the drive and response systems. From rigorously control theory, a sufficient ...condition is attained for the stability of the error dynamics, and is applied to guiding the design of the controllers. Finally, we take Lorenz system as an example for illustration and verification.
Reactive oxygen species (ROS) production is one of the earliest responses when plants percept pathogens and acts as antimicrobials to block pathogen entry. However, whether and how pathogens tolerate ...ROS stress remains elusive. Here, we report the chromatin remodeling in Verticillium dahliae, a soil-borne pathogenic fungus that causes vascular wilts of a wide range of plants, facilitates the DNA damage repair in response to plant ROS stress. We identified VdDpb4, encoding a histone-fold protein of the ISW2 chromatin remodeling complex in V. dahliae, is a virulence gene. The reduced virulence in wild type Arabidopsis plants arising from VdDpb4 deletion was impaired in the rbohd mutant plants that did not produce ROS. Further characterization of VdDpb4 and its interacting protein, VdIsw2, an ATP-dependent chromatin-remodeling factor, we show that while the depletion of VdIsw2 led to the decondensing of chromatin, the depletion of VdDpb4 resulted in a more compact chromatin structure and affected the VdIsw2-dependent transcriptional effect on gene expression, including genes involved in DNA damage repair. A knockout mutant of either VdDpb4 or VdIsw2 reduced the efficiency of DNA repair in the presence of DNA-damaging agents and virulence during plant infection. Together, our data demonstrate that VdDpb4 and VdIsw2 play roles in maintaining chromatin structure for positioning nucleosomes and transcription regulation, including genes involved in DNA repair in response to ROS stress during development and plant infection.
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