APP substrate ectodomain defines amyloid-ß peptide length by restraining γ-secretase processivity and facilitating product release.

Sequential proteolysis of the amyloid precursor protein (APP) by γ-secretases generates amyloid-ß (Aß) peptides and defines the proportion of short-to-long Aß peptides, which is tightly connected to Alzheimer's disease (AD) pathogenesis. Here, we study the mechanism that controls substrate processing by γ-secretases and Aß peptide length. We found that polar interactions established by the APPC99 ectodomain (ECD), involving but not limited to its juxtamembrane region, restrain both the extent and degree of γ-secretases processive cleavage by destabilizing enzyme-substrate interactions. We show that increasing hydrophobicity, via mutation or ligand binding, at APPC99 -ECD attenuates substrate-driven product release and rescues the effects of Alzheimer's disease-associated pathogenic γ-secretase and APP variants on Aß length. In addition, our study reveals that APPC99 -ECD facilitates the paradoxical production of longer Aßs caused by some γ-secretase inhibitors, which act as high-affinity competitors of the substrate. These findings assign a pivotal role to the substrate ECD in the sequential proteolysis by γ-secretases and suggest it as a sweet spot for the potential design of APP-targeting compounds selectively promoting its processing by these enzymes.

p110CUX1 promotes acute myeloid leukemia progression via regulating pyridoxal phosphatase expression and activating PI3K/AKT/mTOR signaling pathway.

As an evolutionarily conserved transcription factor, Cut-like homeobox 1 (CUX1) plays crucial roles in embryonic and nervous system development, cell differentiation, and DNA damage repair. One of its major isoforms, p110CUX1, exhibits stable DNA binding capabilities and contributes to the regulation of cell cycle progression, proliferation, migration, and invasion. While p110CUX1 has been implicated in the progression of various malignant tumors, its involvement in acute myeloid leukemia (AML) remains uncertain. This study aims to elucidate the role of p110CUX1 in AML. Our findings reveal heightened expression levels of both p110CUX1 and pyridoxal phosphatase (PDXP) in AML cell lines. Overexpression of p110CUX1 promotes AML cell proliferation while inhibiting apoptosis and differentiation, whereas knockdown of PDXP yields contrasting effects. Mechanistically, p110CUX1 appears to facilitate AML development by upregulating PDXP expression and activating the PI3K/AKT/mTOR signaling pathway. Animal experimental corroborate the pro-AML effect of p110CUX1. These results provide experimental evidence supporting the involvement of the p110CUX1-PDXP-PI3K/AKT/mTOR axis in AML progression. Hence, targeting p110CUX1 may hold promise as a therapeutic strategy for AML.

Longitudinal reciprocal association between rheumatoid arthritis and chronic obstructive pulmonary disease and mediation of inflammation.

OBJECTIVES: To elucidate the longitudinal reciprocal association between rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD), and the mediating role of systemic inflammation in the association. METHODS: 403045 participants from UK Biobank were enrolled in this study. A cross-lagged panel model was used to investigate the longitudinal reciprocal association between RA and COPD. Cox-proportional hazard regression and logistic regression models were also conducted to examine the association between baseline RA and COPD during follow-up, and vice versa. Causal mediation analysis was then performed to explore the mediating roles of 160 systemic inflammatory biomarkers in the bidirectional association. RESULTS: At baseline, 4755 (1.2%) and 6989 (1.7%) individuals were diagnosed with RA and COPD, respectively. After adjusting for the covariates, the result of cross-lagged panel model revealed a bidirectional association between RA and COPD (ß = 0.018, P < 0.001 for RA→COPD path; ß = 0.010, P < 0.001 for COPD→RA path). In the non-COPD population, the risk of future COPD was increased in RA patients (Cox: HR = 1.65, 95% CI, 1.50-1.83; logistic: OR = 1.85, 95% CI, 1.66-2.07). In the non-RA population, baseline COPD was associated with a higher risk of RA during follow-up (Cox: HR = 1.67, 95% CI, 1.44-1.92; logistic: OR = 1.70, 95% CI, 1.47-1.97). Five inflammatory factors mediated the RA→COPD path, and C-reactive protein mediated the COPD→RA path (FDR < 0.05). CONCLUSIONS: A significant bidirectional association exists between RA and COPD, and it is partially mediated by systemic inflammation.

Development of a two-beveled-fiber polarized fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy.

We report on the development of a two-beveled-fiber polarized (TBFP) fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy. The two-beveled fibers positioned symmetrically along a ball lens, in synergy with paired parallel-polarized polarizers integrated between the fibers and the ball lens, maximize the Raman signal excitation and collection from the superficial epithelium where gastrointestinal (GI) precancer arises. Monte Carlo (MC) simulations and two-layer tissue phantom experiments show that the probe developed detects ∼90% of the Raman signal from the superficial epithelium. The suitability of the probe developed for rapid (<3 s) superficial epithelial Raman measurements is demonstrated on fresh swine esophagus, stomach, and colon tissues, followed by their differentiation with high accuracies (92.1% for esophagus [sensitivity: 89.3%, specificity: 93.2%], 94.1% for stomach [sensitivity: 86.2%, specificity: 97.2%], and 94.1% for colon [sensitivity: 93.2%, specificity: 94.7%]). The presented results suggest the great potential of the developed probe for enhancing in vivo superficial epithelial Raman measurements in endoscopy.

ZNF460-regulated COMMD7 Promotes Acute Myeloid Leukemia Proliferation Via the NF-κB Signaling Pathway.

Acute myeloid leukemia (AML) is a malignancy of the hematological system, for which there remains an urgent need for new therapeutic and diagnostic targets. COMM domain containing 7 (COMMD7) is a recently-identified oncogene linked to poor prognosis in AML. COMMD7 regulates multiple signaling pathways, including nuclear factor-kappa B (NF-κB) signaling. Here, we report that COMMD7 is highly expressed in the AML cell lines KG1a and U937 and that its inhibition by shRNA reduced proliferation, promoted apoptosis and facilitated cell cycle arrest in the G2/M phase in relation to depression of the NF-κB pathway. Furthermore, zinc finger protein 460 (ZNF460) is overexpressed in AML and regulates COMMD7. We found that knockdown of ZNF460 downregulated the expression of COMMD7 while the NF-κB pathway was also inhibited. In addition, we noticed that knockdown of ZNF460 reduced proliferation and increased apoptosis rate of AML cells and that the cell cycle was blocked in the G2/M phase. In brief, our results revealed a critical effect of the ZNF460-COMMD7-NF-κB axis for the proliferation of AML cells. Therefore, COMMD7 may be a possible therapeutic target for AML.

Centroid Optimization of DNN Classification in DOA Estimation for UAV.

Classifications based on deep learning have been widely applied in the estimation of the direction of arrival (DOA) of signal. Due to the limited number of classes, the classification of DOA cannot satisfy the required prediction accuracy of signals from random azimuth in real applications. This paper presents a Centroid Optimization of deep neural network classification (CO-DNNC) to improve the estimation accuracy of DOA. CO-DNNC includes signal preprocessing, classification network, and Centroid Optimization. The DNN classification network adopts a convolutional neural network, including convolutional layers and fully connected layers. The Centroid Optimization takes the classified labels as the coordinates and calculates the azimuth of received signal according to the probabilities of the Softmax output. The experimental results show that CO-DNNC is capable of acquiring precise and accurate estimation of DOA, especially in the cases of low SNRs. In addition, CO-DNNC requires lower numbers of classes under the same condition of prediction accuracy and SNR, which reduces the complexity of the DNN network and saves training and processing time.

A Chemical Proteomic Strategy Reveals Inhibitors of Lipoate Salvage in Bacteria and Parasites.

The development of novel anti-infectives requires unprecedented strategies targeting pathways which are solely present in pathogens but absent in humans. Following this principle, we developed inhibitors of lipoic acid (LA) salvage, a crucial pathway for the survival of LA auxotrophic bacteria and parasites but non-essential in human cells. An LA-based probe was selectively transferred onto substrate proteins via lipoate protein ligase (LPL) in intact cells, and their binding sites were determined by mass spectrometry. Probe labeling served as a proxy of LPL activity, enabling in situ screenings for cell-permeable LPL inhibitors. Profiling a focused compound library revealed two substrate analogs (LAMe and C3) as inhibitors, which were further validated by binding studies and co-crystallography. Importantly, LAMe exhibited low toxicity in human cells and achieved killing of Plasmodium falciparum in erythrocytes with an EC50 value of 15 µM, making it the most effective LPL inhibitor reported to date.

An internal docking site stabilizes substrate binding to γ-secretase: Analysis by molecular dynamics simulations.

Amyloid precursor protein (APP) is cleaved and processed sequentially by γ-secretase yielding amyloid ß (Aß) peptides of different lengths. Longer Aß peptides are associated with the formation of neurotoxic plaques related to Alzheimer's disease. Based on the APP substrate-bound structure of γ-secretase, we investigated the enzyme-substrate interaction using molecular dynamics simulations and generated model structures that represent the sequentially cleaved intermediates during the processing reaction. The simulations indicated an internal docking site providing strong enzyme-substrate packing interaction. In the enzyme-substrate complex, it is located close to the region where the helical conformation of the substrate is interrupted and continues toward the active site in an extended conformation. The internal docking site consists of two non-polar pockets that are preferentially filled by large hydrophobic or aromatic substrate side chains to stabilize binding. Placement of smaller residues such as glycine can trigger a shift in the cleavage pattern during the simulations or results in destabilization of substrate binding. The reduced packing by smaller residues also influences the hydration of the active site and the formation of a catalytically active state. The simulations on processed substrate intermediates and a substrate G33I mutation offer an explanation of the experimentally observed relative increase of short Aß fragment production for this mutation. In addition, studies on a substrate K28A mutation indicate that the internal docking site opposes the tendency of substrate dissociation due to a hydrophobic mismatch at the membrane boundary caused by K28 during processing and substrate movement toward the enzyme active site. The proposed internal docking site could also be useful for the specific design of new γ-secretase modulators.

DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway.

BACKGROUND: DNA methyltransferase 3A (DNMT3A) often mutate on arginine 882 (DNMT3AR882) in acute myeloid leukemia (AML). AML patients with DNMT3A R882 mutation are usually resistant to daunorubicin treatment; however, the associated mechanism is still unclear. Therefore, it is urgent to investigate daunorubicin resistance in AML patients with DNMT3A R882 mutant. METHOD: AML cell lines with DNMT3A-wild type (DNMT3A-WT), and DNMT3A-Arg882His (DNMT3A-R882H) mutation were constructed to investigate the role of DNMT3A R882H mutation on cell proliferation, apoptosis and cells' sensitivity to Danunorubin. Bioinformatics was used to analyze the role of nuclear factor-E2-related factor (NRF2) in AML patients with DNMT3A R882 mutation. The regulatory mechanism of DNMT3A R882H mutation on NRF2 was studied by Bisulfite Sequencing and CO-IP. NRF2 inhibitor Brusatol (Bru) was used to explore the role of NRF2 in  AML cells carried DNMT3A R882H mutation. RESULTS: AML cells with a DNMT3A R882H mutation showed high proliferative and anti-apoptotic activities. In addition, mutant cells were less sensitive to daunorubicin and had a higher NRF2 expression compared with those in WT cells. Furthermore, the NRF2/NQO1 pathway was activated in mutant cells in response to daunorubicin treatment. DNMT3A R882H mutation regulated the expression of NRF2 via influencing protein stability rather than decreasing methylation of NRF2 promoter. Also, NRF2/NQO1 pathway inhibition improved mutant cells' sensitivity to daunorubicin significantly. CONCLUSION: Our findings identified NRF2 as an important player in the regulation of cell apoptosis through which helps mediate chemoresistance to daunorubicin in AML cells with DNMT3A R882H mutation. Targeting NRF2 might be a novel therapeutic approach to treat AML patients with a DNMT3A R882H mutation. Video abstract.

First report of branch blight caused by Diaporthe ueckerae on Eucalyptus citriodora in China.

Eucalyptus citriodora is a wood and oil dual-purpose tree with strong growth adaptability and high ornamental value. Recent years, it has been widely planted in Guangxi in China. In Nov. 2021, branch blight was found to be widespread on E. citriodora in Qinzhou in China (21°57'57"N, 108°42'6"E). The occurrence area was over 7000 m2, and the disease incidence was 23% (23/100). Twigs were withered in most of infected plants, and only top branch died in few plants. The lesions started from branch tips, then expanded and caused 5-20 cm branches died in final. The lesions were tiny and brown at early stage, then turned dark brown or black. Ten diseased branches were sampled randomly in field and were cut into 1 cm pieces. After surface disinfecting with 75% ethanol for 3 min, 0.1% HgCl2 for 5 min, washing with sterile water three times, samples were placed onto Potato Dextrose Agar (PDA) medium. Hyphae appeared after incubating for 5 days at 28 ℃. The diameter of colonies reached 64-71 mm after 7 days incubation. The colonies were white and felt-like, and then turned yellowish gradually with flourish aerial hyphae. Two weeks later, pycnidia appeared, which were nearly spherical, initial pale yellow and later black. Sometimes secretions overflowed from the aperture on pycnidia. There were 2 types of conidia (α and ß type), which were unicellular and hyaline. The α type was spindle to ellipse and had 1-2 oil globule, with 5.56±0.50 × 2.67±0.39 µm (n=100) in size. The ß type was linear and one end bent in hook shape, with 17.10±2.54 × 1.55±0.32 µm (n=50) in size. Three isolates (LEQZ01, LEQZ02, LEQZ03) were selected for further study. The internal transcribed spacers (ITS) region of rDNA, translation elongation factor 1-α (tef1 α) and ß-tubulin (tub2) genes were amplified using primer pairs ITS1/ITS4 (White et al. 1990), EF1-983F/EF1-1567R (Rehner et al. 2005) and Tub1/ Tub2 (Chauhan et al. 2007), respectively. BLASTn searches showed that the ITS (OM339849, ON075781, ON075782), tef1 α (ON093807-ON093809) and tub2 (ON093810-ON093812) sequences had the highest similarity with Diaporthe ueckerae strains, with 99% (543/549, 544/549, 544/549) identity for ITS (NR 147543.1), with 99% (350/351, 353/353, 349/350) identity for tef1 α (KY569388.1), with 99% (754/754, 753/754, 754/754) identity for tub2 (MW514128.1). A neighbor-joining tree constructed by combining 3 sequenced loci. Three isolates clustered in the D. ueckerae clade with 100% bootstrap support. Based on morphological (Yi et al. 2018) and molecular evidences, the pathogen was identified as D. ueckerae. In a pathogenicity test, 20 healthy E. citriodora seedlings were divided into 4 groups. Before inoculation, twigs were surface disinfected with 75% ethanol followed by washing 3 times using sterile water. Tiny artificial wounds at 5 cm below the seedling top were inoculated by hyphae taken from colonies incubated for 7 days at 25 ℃ in the dark, and covered with damp cotton in 1-3 groups (Yi et al. 2018). Yet the wounds were covered with damp cotton in control group. Two days later, wounds started to turn brown in test groups, and symptoms similar to field were obtained after 10 days. But no lesion emerged in control group. Then germs were re-isolated from symptomatic twigs and identified as D. ueckerae following the methods above. To our knowledge, this is the first report of branch blight caused by D. ueckerae on E. citriodora in China. Further researches on disease epidemiology would help to prevent spread to more locations.

Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma.

BACKGROUND: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma. METHODS: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control. RESULTS: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment. CONCLUSIONS: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.

Qualitative and quantitative analysis of saponins in the flower bud of Panax ginseng (Ginseng Flos) by UFLC-Triple TOF-MS/MS and UFLC-QTRAP-MS/MS.

INTRODUCTION: Ginseng Flos (GF), the flower bud of Panax ginseng, is a worthy functional food with medicinal potential. A few studies have focused on the comprehensive and systematic analysis of its major bioactive constituents. OBJECTIVE: The aims are to develop the methods of ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS) and ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UFLC-QTRAP-MS/MS) for the qualitative and quantitative analysis of the saponins in GF. METHODOLOGY: UFLC-Triple TOF-MS/MS and UFLC-QTRAP-MS/MS were established for the qualitative and quantitative analysis of the saponins in GF, separately. RESULTS: Fifty-one saponins were identified in GF using UFLC-Triple TOF-MS/MS method; among them, 21 saponins were characterized by comparing with standards. Furthermore, 12 ginsenosides (ginsenoside Re, Rg1 , Rf, 20(S)-Rg2 , 20(R)-Rg2 , Rb1 , Rc, Ro, Rb2 , F1 , Rd, and F2 ) were synchronously determined by UFLC-QTRAP-MS/MS method after the extraction with 70% methanol. This UFLC-QTRAP-MS/MS method showed good linearity (r >0.9991), the interday and intraday precision, repeatability and stability were all satisfied, the average recoveries of standard addition for the compounds were between 94.01% and 105.16%, and the relative standard deviations were less than 5%. CONCLUSION: The results are available for the comprehensive quality control and assessment of GF and its relative products.

Chemically Controlled Helical Polymorphism in Protein Tubes by Selective Modulation of Supramolecular Interactions.

Polymorphism has been the subject of investigation across different research disciplines. In biology, polymorphism could be interpreted in such a way that discrete biomacromolecules can adopt diversiform specific conformations/packing arrangement, and this polymorph-dependent property is essential for many biochemical processes. For example, bacterial flagellar filament, composed of flagellin, switches between different supercoiled state allowing the bacteria to swim and tumble. However, in artificial supramolecular systems, it is often challenging to achieve polymorph control and prediction, and in most cases, two or more concomitant polymorphs of similar formation energies coexist. Here, we show that a tetrameric protein with properly oriented binding sites on its surface can arrange into diverse protein tubes with distinct helical parameters by adding specifically designed inducing ligands. We examined several parameters of the ligand that would influence the protein tube formation and found that the flexibility of the ligand linker and the dimerization pose of the ligand complex is critical for the successful production of the tubes and eventually influence the specific helical polymorphs of the formed tubes. A surface lattice accommodation model was further developed to rationalize the geometrical relationship between each helical tube type. Molecular simulation was used to elucidate the interactions between ligands and SBA and molecular basis for polymorphic switching of the protein tubes. Moreover, the kinetics of structural formation was studied and the ligand design was found that can affect the kinetics of the protein polymerization pathway. In short, our designed protein tubes serves as an enlightening system for understanding how a protein polymer composed of a single protein switches among different helical states.

IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model.

Steroid insensitivity constitutes a major problem for asthma management. Toluene diisocyanate (TDI) is one of the leading allergens of asthma that induces both T-helper Th2 and Th17 responses, and is often associated with poor responsiveness to steroid treatment in the clinic.We sought to evaluate the effects of inhaled and systemic steroids on a TDI-induced asthma model and to find how interleukin (IL)-17A and IL-17F function in this model. BALB/c mice were exposed to TDI for generating an asthma model and were treated with inhaled fluticasone propionate, systemic prednisone, anti-IL-17A, anti-IL-17F, recombinant IL-17A or IL-17F.Both fluticasone propionate and prednisone showed no effects on TDI-induced airway hyperresponsiveness (AHR), bronchial neutrophilia and eosinophilia, and epithelial goblet cell metaplasia. TDI-induced Th2 and Th17 signatures were not suppressed by fluticasone propionate or prednisone. Treatment with anti-IL-17A after TDI exposure led to increased AHR, aggravated mucus production and airway eosinophil recruitment, accompanied by amplified Th2 responses, whereas anti-IL-17F ameliorated TDI-induced AHR and airway neutrophilia, with decreased Th17 responses. Recombinant IL-17A and IL-17F showed opposite effects to the monoclonal antibodies.IL-17A and IL-17F exert distinct biological effects during airway inflammation of a TDI-induced asthma model, which is unresponsive to both inhaled and systemic steroids.

Qualitative and Quantitative Analysis of the Saponins in Panacis Japonici Rhizoma Using Ultra-Fast Liquid Chromatography Coupled with Triple Quadrupole-Time of Flight Tandem Mass Spectrometry and Ultra-Fast Liquid Chromatography Coupled with Triple Quadrupole-Linear Ion Trap Tandem Mass Spectrometry.

Panacis Japonici Rhizoma (PJR) contains various kinds of saponins, which possesses extensive pharmacological activities, but studies of comprehensive analysis of its saponins were limited. Thus, ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS) and ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UFLC-QTRAP-MS/MS) methods were established for the qualitative and quantitative analysis of the saponins in PJR, separately. Fifty three saponins in PJR were identified by UFLC-Triple TOF-MS/MS method, 23 saponins of which were unequivocally identified by reference substances. In addition, fragmentation pathways of different types of saponins were preliminarily deduced by fragmentation behavior of 53 saponins. Furthermore, the simultaneous determination of the contents of 13 saponins in PJR samples harvested at different times were analyzed by UFLC-QTRAP-MS/MS method. Furthermore, the quality of the samples was evaluated by grey relational analysis. This study might be beneficial to the quality assessment and control of PJR. Meanwhile, it might provide the basic information for confirming its optimal harvested period.

Comparative Metabolite Profiling of Wild and Cultivated Licorice Based on Ultra-Fast Liquid Chromatography Coupled with Triple Quadrupole-Time of Flight Tandem Mass Spectrometry.

Licorice is one of the ancient and most frequently applied herbs for its diverse phytochemicals. At present, wild resources of licorice have rapidly declined with increasing demand and the proportion of cultivated products in the market is quickly growing. However, the different level in chemical composition between the wild and cultivated licorice may result in the discrepancy in quality and pharmacological activity. Therefore, an ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS) method combined with multivariate statistical analysis technology was employed to explore chemical composition differences. The result showed that total 63 components were identified from licorice samples. The wild and the cultivated licorice are obviously classified into two groups according to principal component analysis (PCA). PCA and partial least squared discrimination analysis (PLS-DA) were also introduced to rapidly find 14 candidate compounds between two ecotypes of licorice. Apart from glycyrrhizin, licorice saponin J2/G2, glyasperin D and dehydroglyasperin D also could be selected as chemical markers based on t-test and variable importance in the projection (VIP) value. Our study successfully established an effective method for exploring metabolite profiling between two ecotypes of licorice and laying the foundation for distinguishing wild and cultivated licorice.

Quality Evaluation of Wild and Cultivated Schisandrae Chinensis Fructus Based on Simultaneous Determination of Multiple Bioactive Constituents Combined with Multivariate Statistical Analysis.

Schisandrae Chinensis Fructus, also called wuweizi in China, was a widely used folk medicine in China, Korea, and Russia. Due to the limited natural resources and huge demand of wuweizi, people tend to cultivate wuweizi to protect this species. However, the quality of wild and cultivated herbs of the same species may change. Little attention has been paid to comparing wild and cultivated wuweizi based on simultaneous determination of its active components, such as lignans and organic acids. An analytical method based on UFLC-QTRAP-MS/MS was used for the simultaneous determination of 15 components, including 11 lignans (schisandrin, gomisin D, gomisin J, schisandrol B, angeloylgomisin H, schizantherin B, schisanhenol, deoxyschizandrin, γ-schisandrin, schizandrin C, and schisantherin) and 4 organic acids (quinic acid, d(-)-tartaric acid, l-(-)-malic acid, and protocatechuic acid) in wuweizi under different ecological environments. Principal components analysis (PCA), partial least squares discrimination analysis (PLS-DA), independent sample t-test, and gray relational analysis (GRA) have been applied to classify and evaluate samples from different ecological environments according to the content of 15 components. The results showed that the differential compounds (i.e., quinic acid, l-(-)-malic acid, protocatechuic acid, schisandrol B) were significantly related to the classification of wild and cultivated wuweizi. GRA results demonstrated that the quality of cultivated wuweizi was not as good as wild wuweizi. The protocol not just provided a new method for the comprehensive evaluation and quality control of wild and cultivated wuweizi, but paved the way to differentiate them at the chemistry level.

Quality Evaluation of Ophiopogonis Radix from Two Different Producing Areas.

Ophiopogonis Radix, also known as Mai-dong in Chinese, was a commonly used traditional Chinese medicine (TCM) and functional health food. Two products of Ophiopogonis Radix are largely produced in the Sichuan and Zhejiang province, which are called "Chuan maidong (CMD)" and "Zhe maidong (ZMD)" respectively. To distinguish and evaluate the quality of CMD and ZMD, an analytical method based on ultra-fast performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry (UFLC-QTRAP-MS/MS) was established for simultaneous determination of 32 constituents including 4 steroidal saponins, 3 homisoflavonoids, 15 amino acids, and 10 nucleosides in 27 Mai-dong samples from Sichuan and Zhejiang. Furthermore, principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA), t-test, and grey relational analysis (GRA) were applied to discriminate and evaluate the samples from Sichuan and Zhejiang based on the contents of 32 constituents. The results demonstrated that the bioactive constituents in CMD and ZMD were significantly different, and CMD performed better in the quality assessment than ZMD. This study not only provides a basic information for differentiating CMD and ZMD, but offers a new insight into comprehensive evaluation and quality control of Ophiopogonis Radix from two different producing areas.

Self-Assembly of Amphiphilic Schiff Base and Selectively Turn on Circularly Polarized Luminescence by Al3.

We designed glutamide-derived amphiphilic Schiff bases containing three different aldehyde moieties for the fabrication of circularly polarized luminescence (CPL) emitting materials. Upon self-assembly in acetonitrile, Schiff bases featuring 4-(dimethylamino)-2-hydroxylbenzaldehyde and 1-hydroxy-2-naphthaldehyde groups form supramolecular gels with twist and fiber structures, respectively, whereas Schiff bases featuring 2-hydroxy-1-naphthaldehyde groups form precipitation with flake structures. Although emission and circular dichroism signals can be detected from the supramolecular gels formed by amphiphilic Schiff bases, none of them exhibits a circularly polarized luminescence (CPL). Although Mg2+, Zn2+, and Al3+ can significantly enhance the fluorescence of the Schiff bases, interestingly, only Al3+ ion is able to turn on the CPL emission. This study on the one hand provides a simple method for the fabrication of CPL-emitting supramolecular materials and on the other hand offers a novel way for the sensing of aluminum ion with supramolecular materials.

Photoirradiation-generated radicals in two-component supramolecular gel for polymerization.

While supramolecular gels have been attracting great interest due to their easy design and fabrication, development of new applications based on these gels is always a challenging topic. Here, we report a two-component supramolecular gel that can generate and stabilize radicals through photo-irradiation, which can be subsequently used for polymerization. It has been found that the electrostatic interactions between a cationic amphiphile and anionic sulfonate could afford co-assembly into a two-component supramolecular gel. Upon photo-irradiation, the gel changed colour and produced the radicals, as verified from the EPR measurements. The radical thus formed in the supramolecular gel is relatively stable and could be used to polymerize acrylic acid directly without deoxygenation. In contrast, acrylic acid could not be polymerized in solution under the same conditions. This work expands the application scope of supramolecular gels.