Structural insights into the ubiquitylation strategy of the oligomeric CRL2FEM1B E3 ubiquitin ligase.

Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2FEM1B in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2FEM1B is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2FEM1B. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2FEM1B according to substrates with different scales.

Microstructural Insights into Performance Loss of High-Voltage Spinel Cathodes for Lithium-ion Batteries.

Spinel-structured LiNix Mn2-x O4 (LNMO), with low-cost earth-abundant constituents, is a promising high-voltage cathode material for lithium-ion batteries. Even though extensive electrochemical investigations have been conducted on these materials, few studies have explored correlations between their loss in performance and associated changes in microstructure. Here, down to the atomic scale, the structural evolution of these materials is investigated upon the progressive cycling of lithium-ion cells. Transgranular cracking is revealed to be a key feature during cycling; this cracking is initiated at the particle surface and leads to the penetration of electrolytes along the crack path, thereby increasing particle exposure to the electrolyte. The lattice structure on the crack surface shows spatial variances, featuring a top layer of rock-salt, a sublayer of a Mn3 O4 -like arrangement, and then a mixed-cation region adjacent to the bulk lattice. The transgranular cracking, along with the emergence of local lattice distortion, becomes more evident with extended cycling. Further, phase transformation at primary particle surfaces and void formation through vacancy condensation is found in the cycled samples. All these features collectively contribute to the performance degradation of the battery cells during electrochemical cycling.

Supramolecular Modifying Nafion with Fluoroalkyl-Functionalized Polyoxometalate Nanoclusters for High-Selective Proton Conduction.

Proton exchange membranes with high selectivity are urgently required in energy and electronic technologies. Nafion, a state-of-the-art commercial proton exchange membrane material, faces significant challenges. It suffers from the permeation of undesirable substances, like hydrogen in fuel cells and vanadium ions in redox flow batteries, due to the unmatched sizes between its ionic domains (3~5 nm) and these substances. In this work, we present a supramolecular modification strategy that simultaneously enhances the proton conductivity and selectivity of Nafion. We employ fluoroalkyl-grafted polyoxometalate (POMs) nanoclusters as supramolecular additives to modify Nafion via co-assembly. These POMs can precisely and robustly decorate at Nafion ionic domains, with their fluoroalkyl chains anchoring into the perfluorinated matrix while their inorganic clusters stay in the ionic regions. The hybrid membranes, with continuous proton hopping sites and nanoscale steric hindrance offered by POMs, exhibit a 56% increase in proton conductivity and a 100% improvement in proton/vanadium selectivity. This leads to significantly enhanced power density and energy efficiency in fuel cells and vanadium flow batteries, respectively. These results underscore the intriguing potential of molecular cluster additives in improving the functions of ion-conducting membranes.

Linearly Arranged Multi-π-Stacked Structure for Efficient Through-Space Charge-Transfer Emitters.

Noncovalent spatial interaction has become an intriguing and important tool for constructing optoelectronic molecules. In this study, we linearly attached three conjugated units in a multi π-stacked manner by using just one trident bridge based on indeno[2,1-b]fluorene. To achieve this structure, we improved the synthetic approach through double C-H activation, significantly simplifying the preparation process. Due to the proximity of the C10, C11, and C12 sites in indeno[2,1-b]fluorene, we derived two novel donor|acceptor|donor (D|A|D) type molecules, 2DMB and 2DMFB, which exhibited closely packed intramolecular stacking, enabling efficient through-space charge transfer. This molecular construction is particularly suitable for developing high-performance thermally activated delayed fluorescence materials. With donor(s) and acceptor(s) constrained and separated within this spatially rigid structure, elevated radiative transition rates, and high photoluminescence quantum yields were achieved. Organic light-emitting diodes incorporating 2DMB and 2DMFB demonstrated superior efficiency, achieving maximum external quantum efficiencies of 28.6% and 16.2%, respectively.

[The mediating role of emotion regulation strategies between symptoms and anxiety problems in children with attention deficit hyperactivity disorder]. / æƒ ç»ªè°ƒèŠ‚ç­–ç•¥åœ¨æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥ç—‡çŠ¶ä¸Žç„¦è™‘é—®é¢˜ä¹‹é—´çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To study the mediating role of emotion regulation strategies between symptoms and anxiety problems in children with attention deficit hyperactivity disorder (ADHD). METHODS: Convenience cluster sampling was performed to select 435 eligible children with ADHD from 10 211 students in 10 elementary schools in Kashgar of Xinjiang Uygur Autonomous Region. SNAP-IV Assessment Scale, Emotion Regulation Questionnaire for Children and Adolescents, and Conners Parent Symptoms Questionnaire were used to obtain relevant information. The Spearman correlation analysis and the moderated mediation method were used for data analysis. RESULTS: For the children with ADHD, the score of cognitive reappraisal was negatively correlated with the scores of symptoms and anxiety problems (rs=-0.254 and -0.270 respectively, P<0.001), and the score of symptoms was positively correlated with the score of anxiety problems (rs=0.329, P<0.001). The analysis of mediating effect showed that cognitive reappraisal played a partial mediating role between symptoms and anxiety problems, with a 95% confidence interval of 0.008-0.027, and the mediating effect accounted for 16.10% of the total effect. In addition, sex played a regulatory role in this mediation model (P<0.001). CONCLUSIONS: Cognitive reappraisal plays a mediating role between symptoms and anxiety problems in children with ADHD, while sex regulates the relationship of symptoms with cognitive reappraisal and anxiety problems in these children.

Rapid On-Chip Isolation of Cancer-Associated Exosomes and Combined Analysis of Exosomes and Exosomal Proteins.

Exosomes are lipid bilayer extracellular vesicles secreted by various types of cells and inherit abundant molecular information from parental cells. Tumor-derived exosomes have been widely recognized as noninvasive biomarkers for early cancer diagnosis and surveillance, but the separation of intact exosomes and detection of exosomal proteins remain challenging. Herein, we proposed a microfluidic chip for specific exosome isolation, integrated with sensitive quantification by a novel PTCDI-aptamer signal switch strategy. To enhance the capture efficiency, an alternating drop-shaped micropillar array was designed to assist the capture of tumor-derived exosomes by Tim4-modified magnetic beads (Tim4 beads) on the chip. Following capture, a chelating agent can easily elute intact exosomes which were further used for profiling exosomal surface proteins by the multiplexed fluorescence turn-on approach. Profiting from the efficient on-chip enrichment of the Tim4 beads and superior fluorescence signal transduction strategy, the detection limit of the analysis platform for HepG2 exosomes is as low as 8.69 × 103 particles/mL with a wide linear range spanning 6 orders of magnitude. Meanwhile, the proposed platform could recognize subtle changes in protein levels on the exosomal surface from various cell lines. More importantly, this strategy is successfully applied to analyze exosomes in human serum to distinguish liver cancer patients from healthy individuals. Combined analysis of different types of biomarkers on the exosomal membrane surface can greatly improve the accuracy of cancer type identification and disease monitoring. We hope that this convenient, rapid, and sensitive platform may become a powerful tool in the field of exosome analysis and early cancer screening.

Genome-wide unraveling SNP pairwise epistatic effects associated with sheep body weight.

Epistatic effects are an important part of the genetic effect of complex traits in livestock. In this study, we used 218 synthetic ewes from the Xinjiang Academy of Agricultural Reclamation in China to identify interacting paired with genome-wide single nucleotide polymorphisms (SNPs) associated with birth weight, weaning weight, and one-yearling weight. We detected 2 and 66 SNP-SNP interactions of sheep birth weight and weaning weight, respectively. No significant epistatic interaction of one-year-old body weight was detected. The genetic interaction of sheep body weight is dynamic and time-dependent. Most significant interactions of weaning body weight contributed 1% or higher. In the weaning weight trait, 66 significant SNP pairs consisted of 98 single SNPs covering 23 chromosomes, 5 of which were nonsynonymous SNPs (nsSNPs), resulting in single amino acid substitution. We found that genes that interact with transcription factors (TFs) are target genes for the corresponding TFs. Four epitron networks affecting weaning weight, including subnetworks of HIVEP3 and BACH2 transcription factors, constructed using significant SNP pairs, were also analyzed and annotated. These results suggest that transcription factors may play an important role in explaining epistatic effects. It provides a new idea to study the genetic mechanism of weight developing.

[Androgen Insensitivity Syndrome with Bilateral Cryptorchidism and Seminoma in Tibet:Report of One Case].

Androgen insensitivity syndrome(AIS)with bilateral testicular malignant transformation is very rare,and its diagnosis should be based on clinical manifestations,physical examination,serological findings,karyotype analysis,and pathological findings.This study reported a case of complete androgen insensitivity syndrome among Tibetan in Tibet.It took 17 years from the discovery of congenital absence of uterus to bilateral pelvic mass resection.Pathological examination confirmed that bilateral pelvic space occupying lesions were dysplastic testicular tissue with seminoma and sertoli cell adenoma-like nodules.This study summarized the clinicopathological features to deepen the understanding of the disease.

[Influence of sleep quality on symptoms in children with attention deficit hyperactivity disorder: the mediating role of working memory]. / ç¡çœ è´¨é‡å¯¹æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å„¿ç«¥ç—‡çŠ¶çš„å½±å“ï¼šå·¥ä½œè®°å¿†çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To study the mediating role of working memory between sleep quality and symptoms in children with attention deficit hyperactivity disorder (ADHD). METHODS: The cluster random sampling method was used to select 110 ADHD children and 124 normal children as subjects from grade 3-5 students in two primary schools in Kashgar, Xinjiang Uygur Autonomous Region, China. SNAP-IV, Pittsburgh Sleep Quality Index (PSQI), and visual-spatial working memory paradigm were used for investigation and comparison. RESULTS: Compared with the normal group, the ADHD group had a significantly higher total score of PSQI and scores of subjective sleep quality, sleep latency, sleep efficiency, sleep disturbance, and a higher incidence of sleep quality problems (P<0.001). The working memory score in the ADHD group was significantly lower than that in the normal group (P<0.001). In the ADHD group, the working memory score was negatively correlated with the total score of PSQI (rs=-0.271, P<0.001) and the score of symptoms (rs=-0.439, P<0.001), and the total score of PSQI was positively correlated with the score of symptoms (rs=0.540, P<0.001). Working memory had a partial mediating effect in the influence of sleep quality on symptoms in children with ADHD, accounting for 18.10% of the total effect. CONCLUSIONS: Sleep quality issues are observed in some children with ADHD, and working memory plays a mediating role between sleep quality and symptoms in ADHD children.

An aptamer biosensor based dual signal amplification system for the detection of salmonella typhimurium.

Salmonella, a typical foodborne pathogen, always seriously threatens the health and even life of both humans and animals. However, highly sensitive and fast quantitative methods for its detection are remaining to be challenged. Herein, we presented an efficient method with dual signal amplification strategy by combining immune hybridization chain reaction (HCR) with surface enhanced Raman scattering (SERS) to high sensitively detect Salmonella typhimurium in food. After sample preparation, S. typhimurium were specifically captured by immunomagnetic beads (IMBs), then aptamers and hairpin-probes were added to trigger HCR to form nicked dsDNA, finally 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) was incubated with HCR products and then the whole system was mixed with AgNP colloid to detect the SERS intensity at 1610 cm-1. As a result, a good linear relationship was achieved between SERS intensities and corresponding concentrations of S. typhimurium ranging from 10 to 105 CFU/mL, with a limit of detection (LOD) of 6 CFU/mL in 3.5 h. The proposed method has been successfully applied to capture and detect the S. typhimurium in spiked milk samples, and the results were consistent with those of the traditional plate counting method. The method, with combination of HCR and SERS, achieves double amplification of the detection signal and significantly improves the detection sensitivity of S. typhimurium. And it also shows good application potential for the highly sensitive detection of other contaminants in food.

Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives.

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the "tail approach" and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

Association of PNPLA3 rs738409 G/C gene polymorphism with nonalcoholic fatty liver disease in children: a meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Current studies have shown that PNPLA3 (Patatin-like phospholipase domain containing 3) rs738409 G/C gene polymorphism is associated with adult nonalcoholic fatty liver disease [1, 2].But there is no consensus on the relationship between PNPLA3 rs738409 G/C gene polymorphism and children NAFLD due to differences in population samples. To this end, a meta-analysis of published research is conducted to comprehensively assess the relationship between PNPLA3 gene polymorphism and NAFLD in children. METHODS: We searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children's NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. The Stata 12.0 software was employed for data analysis. RESULTS: A total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children's NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR = 3.343, 95% CI = 1.524-7.334; GG + GC vs CC,OR = 3.157, 95% CI = 1.446-6.892;GG vs GC + CC,OR = 5.692, 95% CI = 1.941-16.689; GG + CC vs GC,OR = 2.756, 95% CI = 1.729-4.392). Four case-control studies compared Children with nonalcoholic fatty liver (NAFL) and children with nonalcoholic steatohepatitis (NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model (GG vs GC + CC,OR = 14.43, 95% CI = 5.985-34.997); The Egger's test revealed no significant publication bias. CONCLUSIONS: Meta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children.

Xanthine Oxidase Inhibition and Anti-LDL Oxidation by Prenylated Isoflavones from Flemingia philippinensis Root.

Xanthine oxidase is a frontier enzyme to produce oxidants, which leads to inflammation in the blood. Prenylated isoflavones from Flemingia philippinensis were found to display potent inhibition against xanthine oxidase (XO). All isolates (1-9) inhibited XO enzyme with IC50 ranging 7.8~36.4 µM. The most active isoflavones (2-5, IC50 = 7.8~14.8 µM) have the structural feature of a catechol motif in B-ring. Inhibitory behaviors were disclosed as a mixed type I mode of inhibition with KI < KIS. Binding affinities to XO enzyme were evaluated. Fluorescence quenching effects agreed with inhibitory potencies (IC50s). The compounds (2-5) also showed potent anti-LDL oxidation effects in the thiobarbituric acid-reactive substances (TBARS) assay, the lag time of conjugated diene formation, relative electrophoretic mobility (REM), and fragmentation of apoB-100 on copper-mediated LDL oxidation. The compound 4 protected LDL oxidation with 0.7 µM in TBARS assay, which was 40-fold more active than genistein (IC50 = 30.4 µM).

Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth-most common malignancy worldwide. Multiple previous studies have assessed the relationship between TM6SF2 gene polymorphism and the risk of developing HCC, with discrepant conclusions reached. To assess the association of TM6SF2 rs58542926 T/C gene polymorphism with liver cancer, we performed the current meta-analysis. METHODS: This study queried the MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to April 2019. Case-control studies assessing the relationship between TM6SF2 rs5854292 locus polymorphism and liver cancer were selected according to inclusion and exclusion criteria. The Stata 12.0 software was employed for data analysis. RESULTS: A total of 5 articles, encompassing 6873 patients, met inclusion criteria and were included in the meta-analysis. Statistical analysis showed that the TM6SF2 gene polymorphism was significantly associated with liver cancer in the allele contrast, dominant, recessive and over dominant models (T vs C, OR = 1.621, 95%CI 1.379-1.905; CT + TT vs CC. OR = 1.541, 95%CI 1.351-1.758; TT vs CT + CC, OR = 2.897, 95%CI 1.690-4.966; CC + TT vs TC, OR = 0.693, 95%CI 0.576-0.834). The Egger's test revealed no significant publication bias. CONCLUSION: The present findings suggest a significant association of TM6SF2 gene polymorphism with HCC risk in the entire population studied.

Investigation of the Structure of the Modulated Doubly Ordered Perovskite NaLaCoWO6 and Its Reversible Phase Transition with a Colossal Temperature Hysteresis.

Transmission electron microscopy, neutron diffraction, and synchrotron powder X-ray diffraction reveal a complex modulated structure on the doubly ordered perovskite NaLaCoWO6. Electron diffraction patterns as well as high-resolution transmission electron microscopy images clearly show a periodicity of 12 ap, where ap is the cell parameter of the generic perovskite, along either the [100]p or [010]p direction. Annular bright-field scanning transmission electron microscopy of slightly tilted samples shows that there is no chemical origin for the superstructure but that it is caused by geometric rearrangements. An atomic model of the superstructure is proposed on the basis of octahedral tilt twinning. At low temperature, NaLaCoWO6 undergoes a phase transition and the superstructure disappears. The compound takes on the more usual monoclinic P21 structure below the transition. Neutron powder diffraction reveals and electron diffraction confirms an unusually large temperature hysteresis, where the transition takes place at ∼180 K on cooling and at ∼320 K on heating. This hysteresis can be attributed to the necessity of rearranging the oxygen octahedra and the thus induced energy barrier for the transition.

Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle).

Anti-melanogenesis effects of silymarin from milk thistle have been reported recently, but detailed tyrosinase inhibition properties of individual components have not been investigated. This study purported to substantiate tyrosinase inhibition and its mechanism based on a single metabolite. The responsible components for tyrosinase inhibition of target source were found out as flavonolignans which consist of isosilybin A (1), isosilybin B (2), silydianin (3), 2,3-dihydrosilychristin (4), silychristin A (5), silychristin B (6) and silybin (7), respectively. The isolated flavonolignans (1-7) inhibited both monophenolase (IC50 = 1.7-7.6 µM) and diphenolase (IC50 = 12.1-44.9 µM) of tyrosinase significantly. Their inhibitions were 10-fold effective in comparison with their mother skeletons (8-10). Inhibitory functions were also proved by HPLC analysis using N-acetyl-l-tyrosine as substrate. The predominant formation of Emet·I was confirmed from a long prolongation of lag time and a decrease of the static state activity of the enzyme. All tested compounds had a significant binding affinity to tyrosinase with KSV values of 0.06-0.27 × 104 L·mol-1, which are well correlated with IC50s. In kinetic study, all flavonolignan (1-7) were mixed type I (KI < KIS) inhibitors, whereas their mother skeletons (8-10) were competitive ones. The UPLC-ESI-TOF/MS analysis showed that the isolated inhibitors are the most abundant metabolites in the target plant.

Human neutrophil elastase (HNE) inhibitory polyprenylated acylphloroglucinols from the flowers of Hypericum ascyron.

In the course of an investigation of human neutrophil elastase (HNE) associated with inflammation, the extract of the flower parts of Hypericum ascyron showed a significant influence to HNE. The responsible metabolites to HNE inhibition were found to be eight polyprenylated acylphloroglucinols, PPAPs (1-8) which showed IC50 ranges between 2.4 and 19.9 µM. This is the first report to demonstrate that PPAP skeleton exhibits potent HNE inhibition. The compounds 1-3 were characterized and newly named as ascyronone E (IC50 = 4.3 µM), ascyronone F (IC50 = 19.9 µM), ascyronone G (IC50 = 4.5 µM) based on 2D-NMR spectroscopic data. In the kinetic analysis of double reciprocal plots, all the compounds showed noncompetitive behaviors to HNE enzyme with the remaining of Km and the increase of Vmax. The binding affinity levels (KSV) by using fluorescence were sufficient to be able to prove that PPAPs (1-8) had compliant interaction with inhibitory potencies.

Competitive α-glucosidase inhibitors, dihydrobenzoxanthones, from the barks of Artocarpus elasticus.

This study aimed to search the α-glucosidase inhibitors from the barks part of Artocarpus elasticus. The responsible compounds for α-glucosidase inhibition were found out as dihydrobenzoxanthones (1-4) and alkylated flavones (5-6). All compounds showed a significant enzyme inhibition toward α-glucosidase with IC50s of 7.6-25.4 µM. Dihydrobenzoxanthones (1-4) exhibited a competitive inhibition to α-glucosidase. This competitive behaviour was fully characterised by double reciprocal plots, Yang's method, and time-dependent experiments. The compound 1 manifested as the competitive and reversible simple slow-binding, with kinetic parameters k3 = 0.0437 µM-1 min-1, k4 = 0.0166 min-1, and Kiapp = 0.3795 µM. Alkylated flavones (5-6) were mixed type I (KI < KIS) inhibitors. The binding affinities (KSV) represented by all inhibitors were correlated to their concentrations and inhibitory potencies (IC50). Moreover, compounds 1 and 5 were identified as new ones named as artoindonesianin W and artoflavone B, respectively. Molecular modelling study proposed the putative binding conformation of competitive inhibitors (1-4) to α-glucosidase at the atomic level.

Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism.

In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-ß) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR-DNA binding. It was observed that this regulatory function of acetylated GSI-ß enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and posttranslational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes.

Effectiveness of Prenyl Group on Flavonoids from Epimedium koreanum Nakai on Bacterial Neuraminidase Inhibition.

In this study, the inhibitory potential of bacterial neuraminidase (NA) was observed on the leaves of Epimedium koreanum Nakai, which is a popular ingredient in traditional herbal medicine. This study attempted to isolate the relevant, responsible metabolites and elucidate their inhibition mechanism. The methanol extraction process yielded eight flavonoids (1⁻8), of which compounds 7 and 8 were new compounds named koreanoside F and koreanoside G, respectively. All the compounds (1⁻8) showed a significant inhibition to bacterial NA with IC50 values of 0.17⁻106.3 µM. In particular, the prenyl group on the flavonoids played a critical role in bacterial NA inhibition. Epimedokoreanin B (compound 1, IC50 = 0.17 µM) with two prenyl groups on C8 and C5' of luteolin was 500 times more effective than luteolin (IC50 = 85.6 µM). A similar trend was observed on compound 2 (IC50 = 0.68 µM) versus dihydrokaempferol (IC50 = 500.4 µM) and compound 3 (IC50 = 12.6 µM) versus apigenin (IC50 = 107.5 µM). Kinetic parameters (Km, Vmax, and Kik/Kiv) evaluated that all the compounds apart from compound 5 showed noncompetitive inhibition. Compound 5 was proven to be a mixed type inhibitor. In an enzyme binding affinity experiment using fluorescence, affinity constants (KSV) were tightly related to inhibitory activities.