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In this work, the hypoglycemic components in Platycladi Cacumen, an essential traditional Chinese medicine, were evaluated by combining phytochemical investigation, spectrum-effect relationship analysis, and chemometric methods. The phytochemical studies on Platycladi Cacumen extract lead to the isolation of 21 potential bioactive compounds. The chromatographic fingerprints of Platycladi Cacumen samples were established by high-performance liquid chromatography. The hypoglycemic effects of Platycladi Cacumen samples were further evaluated by inhibition of α-glucosidase and detected by the high-performance liquid chromatography method. The spectrum-effect relationship study by bivariate correlations analysis and orthogonal partial least squares regression revealed that myricitrin (P9), quercitrin (P13), afzelin (P18), and amentoflavone (P24) were more relevant to the α-glucosidase inhibitory activity. The results of α-glucosidase inhibitory activity of 21 isolated compounds and molecular docking studies also indicated these flavonoids had potent α-glucosidase inhibitory activity. Collectively, the present study established the spectrum-effect relationship mode of Platycladi Cacumen and discovered the major hypoglycemic components, which provides a feasible method for screening bioactive components.

Since the combinatorial components responsible for the antihyperlipidemic activity of Citrus reticulata 'Chachi' (CRC) peels remains unclear, we herein developed a bioactive equivalence oriented feedback screening method to discover the bioactive equivalent combinatorial components (BECCs) from CRC peels. Using palmitic acid (PA)-stimulated hepatocyte model, a combination of 5 polymethoxyflavones (PMFs) including tangeretin, sinensetin, nobiletin, 5,7,8,4'-tetramethoxyflavone and 3,5,6,7,8,3',4'-heptamethoxyflavone was identified to be responsible for the antihyperlipidemic effect of CRC peels. Via evaluation of combination effect by combination index (CI), these 5 PMFs were found to take effect via a synergistic mode. Our data indicated that the antihyperlipidemic mechanism of PMF combination was associated with the inhibition of fatty acid and cholesterol synthesis, and inflammation. Also, the PMF combination exhibited robust antihyperlipidemic effects in HFD-fed rats in vivo. Our study offers evidence-based data to uncover the pharmacological effect of CRC peels.

Four-stranded G-quadruplex (G4) structures formed by guanine-rich nucleic acids play a role in many essential physiological processes. To date, studies have focused almost exclusively on monomeric intramolecular G4s with three or more G-tetrads. Based on the analysis of Okazaki fragment syntheses and G4 probing, we report here a massive genome-wide formation of a hybrid type of G4s (hG4s), composed of G-tracts from both DNA and RNA, in the genome of live yeast cells. We found that hG4s can form with as few as one G-tract in DNA, increasing the total number of G4 sites from 38 to 127841. Furthermore, we also effectively detected hG4s of two G-tetrads, bringing the total number of G4 sites to a final of 587694, an increase of >15,000-fold. We even found that hG4s dominate in DNAs capable of forming the canonical intramolecular DNA G4s by themselves. Taken together, our results reveal a previously unrecognized rule governing G4 formation in eukaryotic genomes that makes hG4s the overwhelmingly dominant G4 species. They are present in all genes, with greater structural diversity and a wider dynamic range. More importantly, the involvement of RNA gives hG4s the ability to function in a transcription-dependent manner. These new findings thus emphasize a complete renewal and expansion of our current perspective on the existence and functional role of G4s in eukaryotic cells.SignificanceOur work reveals a massive and genome-wide formation of a virtually unnoticed, but in reality overwhelmingly dominant type of G-quadruplexes (G4s), i.e. DNA:RNA hybrid G-quadruplexes (hG4s), in living yeast cells. The involvement of RNA confers several unique properties to hG4s: 1) it allows genomic DNA to form G4s with as few as one G-tract, resulting in complete hG4 dominance over canonical monomeric DNA G4s (dG4s) and their ubiquitous presence in genes; 2) it increases the structural diversity of G4s by offering different combinations of DNA and RNA G-tracts; and 3) it couples G4 formation to transcription, such that hG4s function in a transcription-dependent manner. The discovery of hG4s reveals the physiological reality of the prevalence and functionality of G4s in the context of transcription.

Background: Given that severe inflammatory reaction is an important manifestation of asthma, it would be helpful to understand the pathological mechanism of asthma to determine the endogenous anti-inflammatory events of asthma. Recent studies have found that energy metabolites in the body are related to some inflammatory diseases, but little is known about their role in asthma. Method: In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene–knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5’-(α, β-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect. Result: PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic destruction of CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C-C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis. Conclusion: Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma.

Additional file 1: Table S1. Primers used for real-time PCR.

Additional file 2: Supplemental Figure 1. The neutrophil cells characterized by CD11b+Ly6G+. Supplemental Figure 2. The levels of cytokines and chemokines in BALF of mice with administered 20mg/Kg APCP and 40mg/Kg APCP to wild type mice followed by A.f. Supplemental Figure 3. Eosinophil cells number and eosinophil chemokines expression in BALF. Supplemental Figure 4. The expression of other adenosine receptor subtypes. Supplemental Figure 5. The airway resistance of the WT and KO groups. Supplemental Figure 6. A2aR expression of wild-type mice and CD73 knockout mice. Supplemental Figure 7. Wild-type mice treated with adenosine, adenosine and A.f. induced inflammation.

Growing evidence suggests that fine particulate matter (PM 2.5 ) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM 2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO 3 − ), sulfate (SO 4 2− ), ammonium (NH 4 + ), and soil dust (DUST). To investigate the impact of long-term exposure to PM 2.5 constituents on incident all-cause dementia and Alzheimer’s disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration–response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM 2.5 and its major constituents. An interquartile range increase in PM 2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM 2.5 constituents, associations remained significant for BC, OM, SO 4 2− , and NH 4 + for both end points (even after adjustments of other constituents), among which BC and SO 4 2− showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM 2.5 is significantly associated with higher rates of incident dementia and AD and that SO 4 2− , BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.

The imaginal disc growth factor (IDGF), belonging to the glycoside hydrolase 18 family, plays an important role in various physiological processes in insects. However, the detail physiological function of IDGF is still unclear. In this study, transcriptome analysis was performed on the fatbody isolated from staged control and BmIDGF mutant silkworm larvae. Transcriptional profiling revealed that the absence of BmIDGF significantly affected differentially expressed genes involved in tyrosine and purine metabolism, as well as multiple energy metabolism pathways, including glycolysis, galactose, starch, and sucrose metabolism. The interruption of BmIDGF caused similar and specific gene expression changes to male and female fatbody. Furthermore, a genome-scale metabolic network integrating metabolomic and transcriptomic datasets revealed 11 pathways significantly altered at the transcriptional and metabolic levels, including amino acid, carbohydrate, uric acid metabolism pathways, insect hormone biosynthesis, and ABC transporters. In conclusion, this multiomics analysis suggests that IDGF is involved in gene-metabolism interactions, revealing its unique role in melanin synthesis and energy metabolism. This study provides new insights into the physiological function of IDGF in insects.

Invasive alien plants threaten biodiversity across the world. Erigeron canadensis (horseweed) is one of the most problematic agricultural weeds and represents a classic example of intercontinental invasion. Here, we studied the genetic diversity and population structure of invasive alien populations from the Jiangsu and Zhejiang Provinces in China and native populations from Alabama, in the USA. We used 10 polymorphic SSR loci to genotype 312 individuals from 5 native and 5 invasive populations to estimate the genetic diversity and structure. Invasive populations from Jiangsu and Zhejiang Provinces showed, on average, similar genetic diversity to native populations from Alabama, indicating no severe genetic bottlenecks during the invasion. STRUCTURE revealed that low population differentiation occurred, and that only two genetic groupings were detected in both native and invaded ranges. The high diversity observed in the invasive populations suggested multiple introductions and/or the introduction of genetically diverse propagules during initial colonization. Our study provides new insights toward understanding the invasion dynamics of this globally noxious weed in Eastern China. Preventing gene flow via seed dispersal between invasive and native populations should be examined to prevent the introduction and dispersal of herbicide-resistant individuals and inform management practices.

Hermansky-Pudlak syndrome (HPS) is characterized by defects of multiple tissue-specific lysosome-related organelles (LROs), typically manifesting with oculocutaneous albinism or ocular albinism, bleeding tendency, and in some cases with pulmonary fibrosis, inflammatory bowel disease or immunodeficiency, neuropsychological disorders. Eleven HPS subtypes in humans and at least 15 subtypes in mice have been molecularly identified. Current understanding of the underlying mechanisms of HPS is focusing on the defective biogenesis of LROs. Compelling evidences have shown that HPS protein-associated complexes (HPACs) function in cargo transport, cargo recycling, and cargo removal to maintain LRO homeostasis. Further investigation on the molecular and cellular mechanism of LRO biogenesis and secretion will be helpful for better understanding of its pathogenesis and for the precise intervention of HPS.

The destructive quantum interference (DQI) effect in molecular devices, as characterized by a sharp valley in the transmission function and conductance suppression with several orders of magnitude, is of great interest for both fundamental reasons and technical applications. Planar π conjugated systems, such as benzene, graphene molecules and graphene nanoribbons, are typical examples showing DQI and have been studied most frequently. Carbon nanotubes (CNTs) can be considered as extended planar π conjugated systems, but with a different topology from graphene. In this work, using the Hückel analytical theory, we investigated the transport properties of molecular junctions constructed with armchair CNTs which are weakly coupled to the leads with single site connections. It is found that the transport properties demonstrate obvious oscillation with a period of 3 in nanotube length as defined by the number (

Recently, NaNbO3-based ceramics with excellent energy storage performances (ESPs) and fast charge-discharge characteristics have attracted great attention. In this case, BaTiO3 modified 0.85NaNbO3-0.15Bi(Zn2/3Nb1/3)O3 (0.85NN-0.15BZN-yBT) ceramics were designed and successfully fabricated using solid state synthesis. The discharge storage density of the ceramics increases from 1.22 J/cm3 at y = 0–1.84 J/cm3 at y = 8%, which is 1.5 times higher than pure 0.85NN-0.15BZN ceramics. This ceramic reveals excellent temperature stability up to 150 °C, good discharge cycling after 105 cycles and high discharge speed of 2.0 μs, broadening the scope of NaNbO3-based ceramics for energy storage applications.