Synthetic studies toward a total synthesis of paeoniflorigenin

A new approach towards a total synthesis of paeoniflorigenin is discussed. The approach involves the application of regio- and stereoselective [2+2] photocycloaddition for the preparation of a key intermediate, cyclobutanone 86, and model studies on diiodosamarium (Sm12) mediated pinacol coupling of a diketone. Intermolecular [2+2] photocycloaddition of a,13unsaturated lactam 33 to ketene acetal 34 generated exclusively a head-to-tail and endo cyclobutanone derivative 35. Singlet oxygen oxidation generated butenolide 76, which is a precursor for preparation of photosubstrate 78. Intramolecular [2+2] photocycloaddition using a siloxane as temporary tether, a key step in this synthetic sequence, resulted in tricyclic siloxane intermediate 79. A stepwise oxidative cleavage of O-Si and C-Si bonds in 79 according to Tamao's procedure afforded cyclobutanol 85. Swern oxidation of 85 resulted in highly oxygenated cyclobutanone 86. Overall, a total of eleven steps from the commercial available 3-furaldehyde allowed us to prepare this highly functionalized intermediate 86. Diiodosamarium (SmI2) mediated pinacol coupling of diketone 92 formed a diastereomeric mixture of vicinal bis-tertiary diols 93a and 93b

The Properties of The Wood-Polystyrene Interphase Determined by Inverse Gas Chromatography

The properties of the interphase in wood-polymer composites are important determinants of the properties of the final composite. This study used inverse gas chromatography (IGC) to measure interphasal properties of composites of polystyrene and two types of wood fiber fillers and an inorganic substrate (CW) with varying amounts of surface coverage of polystyrene. Glass transition temperatures, thermodynamic parameters, and the London component of the surface free energy (YsL) were deter mined. Values for YsL became constant at higher coverages, allowing the thickness of the interphase to be estimated

Computational Identification of Gene Networks as a Biomarker of Neuroblastoma Risk

Neuroblastoma is a common cancer in children, affected by a number of genes that interact with each other through intricate but coordinated networks. Traditional approaches can only reconstruct a single regulatory network that is topologically not informative enough to explain the complexity of neuroblastoma risk. We implemented and modified an advanced model for recovering informative, omnidirectional, dynamic, and personalized networks (idopNetworks) from static gene expression data for neuroblastoma risk. We analyzed 3439 immune genes of neuroblastoma for 217 high-risk patients and 30 low-risk patients by which to reconstruct large patient-specific idopNetworks. By converting these networks into risk-specific representations, we found that the shift in patients from a low to high risk or from a high to low risk might be due to the reciprocal change of hub regulators. By altering the directions of regulation exerted by these hubs, it may be possible to reduce a high risk to a low risk. Results from a holistic, systems-oriented paradigm through idopNetworks can potentially enable oncologists to experimentally identify the biomarkers of neuroblastoma and other cancers

Autoinducer-2 Facilitates Pseudomonas aeruginosa PAO1 Pathogenicity in Vitro and in Vivo

Bacterial communication systems, such as quorum sensing (QS), have provided new insights of alternative approaches in antimicrobial treatment. We recently reported that one QS signal, named as autoinducer-2 (AI-2), can affect the behaviors of Pseudomonas aeruginosa PAO1 in a dose-dependent manner. In this study, we aimed to investigate the effects of AI-2 on P. aeruginosa PAO1 biofilm formation and virulence factors production in vitro, and in vivo using a pulmonary infection mouse model. Exogenous AI-2 resulted in increased biofilms architecture, the number of viable cells, and the yield of pyocyanin and elastase virulence factors in wild type P. aeruginosa PAO1. However, no such effect was observed in P. aeruginosa lasR rhlR mutant strain. In vivo, the use of AI-2 significantly increased the mortality, lung bacterial count and histological lung damage of mice with acute P. aeruginosa PAO1 infection. Our data suggest that AI-2 promotes the formation of P. aeruginosa PAO1 biofilms and the production of virulence factors by interfering with P. aeruginosa QS systems, resulting in decreased host survival. AI-2 may be a therapeutic target for the clinical treatment of a co-infection of P. aeruginosa and AI-2 producing bacteria

Low thyroid function is associated with metabolic dysfunction‐associated steatotic liver disease

Abstract Background and Aim Metabolic dysfunction‐associated steatotic liver disease (MASLD) is recently introduced to better highlight the pathogenic significance of cardiometabolic dysfunction, as compared with non‐alcoholic fatty liver disease. This study aimed to investigate the association between low thyroid function and MASLD in the new context. Methods We recruited 2901 participants for our retrospective cohort study from 2016 to 2021. Participants were divided into strict‐normal thyroid function and low thyroid function groups (low‐normal thyroid function, subclinical hypothyroidism) based on initial thyroid stimulating hormone (TSH) levels, respectively. Cox regression models were used to estimate the hazard ratios (HRs) and 95% CI. Results During a median follow‐up of 15.6 months, 165 (8.9%) strict‐normal thyroid function subjects and 141 (13.4%) low thyroid function subjects developed MASLD; this result was statistically relevant (P < 0.05). Univariate regression analysis showed that low thyroid function and subclinical hypothyroidism were statistically significantly associated with MASLD (low thyroid function: HR1.53; 95% CI 1.22–1.92; subclinical hypothyroidism: HR1.95; 95% CI 1.47–2.60). Conclusions MASLD is associated with low thyroid function and the relationship between MASLD and low thyroid function is independent

Expression Patterns of Immune Genes Reveal Heterogeneous Subtypes of High-Risk Neuroblastoma

High risk neuroblastoma (HR-NB) remains difficult to treat, and its overall survival (OS) is still below 50%. Although HR-NB is a heterogeneous disease, HR-NB patients are currently treated in a similar fashion. Through unsupervised biclustering, we further stratified HR-NB patients into two reproducible and clinically distinct subtypes, including an ultra-high risk neuroblastoma (UHR-NB) and high risk neuroblastoma (HR-NB). The UHR-NB subtype consistently had the worst OS in multiple independent cohorts ( p &lt; 0.008 ). Out of 283 neuroblastoma-specific immune genes that were used for stratification, 39 of them were differentiated in UHR-NB, including four upregulated and 35 downregulated, as compared to HR-NB. The four UHR-NB upregulated genes (ADAM22, GAL, KLHL13 and TWIST1) were all upregulated in MYCN amplified neuroblastoma in 5 additional cohorts. TWIST1 and ADAM22 were also positively correlated with cancer stage, while GAL was an independent OS predictor in addition to MYCN and age. Furthermore, we identified 26 commonly upregulated and 311 downregulated genes in UHR-NB from all 4723 immune-related genes. While 43 KEGG pathways with molecular functions were enriched in the downregulated immune-related genes, only the P53 signaling pathway was enriched in the upregulated ones, which suggested that UHR-NB was a TP53 related subtype with reduced immune activities

Cloning and Characterization of AabHLH1, a bHLH Transcription Factor that Positively Regulates Artemisinin Biosynthesis in Artemisia annua

Amorpha-4,11-diene synthase (ADS) and Cyt P450 monooxygenase (CYP71AV1) in Artemisia annua L. are two key enzymes involved in the biosynthesis of artemisinin. The promoters of ADS and CYP71AV1 contain E-box elements, which are putative binding sites for basic helix-loop-helix (bHLH) transcription factors. This study successfully isolated a bHLH transcription factor gene from A. annua, designated as AabHLH1, from a cDNA library of the glandular secretory trichomes (GSTs) in which artemisinin is synthesized and sequestered. AabHLH1 encodes a protein of 650 amino acids containing one putative bHLH domain. AabHLH1 and ADS genes were strongly induced by ABA and the fungal elicitor, chitosan. The transient expression analysis of the AabHLH1-green fluorescent protein (GFP) reporter gene revealed that AabHLH1 was targeted to nuclei. Biochemical analysis demonstrated that the AabHLH1 protein was capable of binding to the E-box cis-elements, present in both ADS and CYP71AV1 promoters, and possessed transactivation activity in yeast. In addition, transient co-transformation of AabHLH1 and CYP71AV1Pro::GUS in A. annua leaves showed a significant activation of the expression of the GUS (beta-glucuronidase) gene in transformed A. annua, but mutation of the E-boxes resulted in abolition of activation, suggesting that the E-box is important for the CYP71AV1 promoter activity. Furthermore, transient expression of AabHLH1 in A. annua leaves increased transcript levels of the genes involved in artemisinin biosynthesis, such as ADS, CYP71AV1 and HMGR. These results suggest that AabHLH1 can positively regulate the biosynthesis of artemisinin