CX-6258 hydrochloride hydrate: A potential non-nucleoside inhibitor targeting the RNA-dependent RNA polymerase of norovirus.

Human norovirus (HuNoV), a primary cause of non-bacterial gastroenteritis, currently lacks approved treatment. RdRp is vital for virus replication, making it an attractive target for therapeutic intervention. By application of structure-based virtual screening procedure, we present CX-6258 hydrochloride hydrate as a potent RdRp non-nucleoside inhibitor, effectively inhibiting HuNoV RdRp activity with an IC50 of 3.61 µM. Importantly, this compound inhibits viral replication in cell culture, with an EC50 of 0.88 µM. In vitro binding assay validate that CX-6258 hydrochloride hydrate binds to RdRp through interaction with the "B-site" binding pocket. Interestingly, CX-6258-contacting residues such as R392, Q439, and Q414 are highly conserved among major norovirus GI and GII variants, suggesting that it may be a general inhibitor of norovirus RdRp. Given that CX-6258 hydrochloride hydrate is already utilized as an orally efficacious pan-Pim kinase inhibitor, it may serve as a potential lead compound in the effort to control HuNoV infections.

Associations between obesity and hyperuricemia combing mendelian randomization with network pharmacology.

Objective: Obesity has become a global health issue and a risk factor for hyperuricemia. However, the associations between obesity and hyperuricemia are sometimes confounding. In the present study, we performed mendelian randomization (MR) analysis to study their relationship and investigate the underlying mechanism by network pharmacology. Method: Body mass index (BMI) and uric acid related to single nucleotide polymorphism were selected as instrumental variables for MR analysis. Three robust analytical methods are used for bidirectional MR analysis such as inverse-variance weighting, weighted median and MR-Egger regression. Then, we further performed sensitivity analysis to evaluate the horizontal pleiotropy, heterogeneities, and stability. The targets related to obesity and hyperuricemia were collected, screened and further conducted for Kyoto Encyclopedia of Genes and Genomes pathway enrichment to explore the mechanism of obesity and hyperuricemia using network pharmacology. Results: The positive causality was indicated between BMI and hyperuricemia based on inverse variance-weighted analysis [odds ratio:1.23, 95% confidence interval: 1.11 to 1.30 for each standard deviation increase in BMI (4.6 kg/m2)]. Conversely, hyperuricemia did not influence BMI. 235 intersected targets from obesity and hyperuricemia were collected. Insulin resistance were the top 1 key target. The mechanism between obesity and hyperuricemia are associated with important pathways including adipocytokine signaling pathway, insulin resistance and cholesterol metabolism et al. Conclusions: Our MR analysis supported the causal association between obesity and hyperuricemia based on availablegenome-wide association analysis summary statistics. Obesity leads to hyperuricemia via insulin resistance, which is a key link in the huge network pathways using network pharmacology.

A Promising Target of Langchuangding Prescription Treating Systemic Lupus Erythaematosus Integrated Network Pharmacology with HPLC-MS and Molecular Docking.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder affecting almost any organ system without effective treatment. Based on accumulating evidence, activated T cells are key cause promoting the pathogenesis of SLE. A traditional clinic Langchuangding formula (LCD) is an effective clinical traditional Chinese medicine prescription for SLE with few side effects and good patient compliance. However, the mechanism of how LCD affects SLE remains unclear. METHODS: Targets related to LCD and SLE were predicted and overlapped to construct protein-protein interaction (PPI) for screening core target. Subsequently, flow cytometry analysis and Western-blot method were used to verify the expression levels of target gene in LCD serum treated-Jurkat T cells. The main compounds of LCD were identified by HPLC-MS and further docked with the core targe. RESULTS: 283 protein targets in LCD, 1498 SLE targets and 150 common targets were obtained to construct protein-protein interaction (PPI). Network pharmacology results suggested that LCD was closely related to CASP3 target. To verify the prediction of pharmacological mechanism of LCD treatment for SLE, we investigated the anti-proliferative effects of LCD-treated rat serum on ß-oestradiol (300 pg/mL)-activated Jurkat T cells in vitro using a CCK-8 kit and flow cytometry analysis and then analyzed the CASP3 expression levels. Vitro experiments confirmed that LCD serum could suppress the proliferation (p < 0.05) and induce apoptosis of the activated T cells through up-regulating CASP3 expression levels. Interactions between CASP3 target and LCD were further validated integrating HPLC-MS analysis and molecular docking. CONCLUSIONS: The results showed that LCD could relieve SLE, which might be attributed to inducing the activated T cells apoptosis by up-regulating CASP3 expression levels. The network pharmacology and molecular docking approach provide a new insight for deepening understanding about TCM. LCD potentially represents a promising therapeutic prescription for SLE supplement treatment with no adverse effects.

Metabolic Disturbance and Th17/Treg Imbalance Are Associated With Progression of Gingivitis.

Objective: This study sought to explore the role of metabolic disturbance in immunoregulation of gingivitis targeting T helper 17 cells (Th17)/regulatory T cell (Treg). Materials and Methods: A total of 20 gingivitis patients and 19 healthy volunteers were recruited. Quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate expression patterns of Forkhead box protein P3 (Foxp3), transforming growth factor-ß (TGF-ß), retinoid-related orphan receptor-gammat (RORγt) and interleukin 17A (IL-17A) in the peripheral blood lymphocytes of subjects across the two groups. Moreover, the enzyme-linked immunosorbent assay (ELISA) technique was used to detect levels of TGF-ß, IL-4, IL-6,TL-10 and L-17A secreted in the plasma as well as the SIgA secreted in saliva. Flow cytometry was used to detect the percentage of CD4+CD25+ Foxp3+Treg cells and the percentage of CD4+IL-17A+ Th17 cells in whole blood of subjects in both groups. Gas chromatography-mass spectrometry (GC-MS) was employed to analyze the plasma metabolites in the gingivitis patient group. Statistical analysis was applied to determine whether the plasma metabolites and related metabolic pathways significantly differed between gingivitis patients and healthy controls. Ingenuity pathway analysis (IPA) was employed to identify the potential relation between the metabolites and the Th17 and Treg related pathway. Results: The percentages of CD4+IL17A+Th17 cells and IL-17 significantly increased in the peripheral blood in the gingivitis group. Moreover, the upregulation of IL-17A mRNA and RORγt mRNA were also found in the gingivitis group. However, the percentage of CD4+CD25+ Foxp3+Treg cells and Foxp3 mRNA in the whole blood did not significantly change. However, TGF-ß mRNA as well as TGF-ß, IL-4, IL-6, IL-10 in the periperial blood and SIgA in the saliva were higher in the gingivitis group. Notably, that the ratio of Th17/Treg cells was significantly increased during peripheral circulation. Furthermore, we identified 18 different metabolites which were differentially expressed in plasma between the gingivitis and healthy control groups. Notably, the levels of cholesterol, glycerol 1-octadecanoate, d-glucose, uric acid, cyclohexaneacetic acid, 3-pyridine, tryptophan, and undecane 2,4-dimethyl were significantly up-regulated. whereas the levels of lactic acid, glycine, linoleic acid, monopalmitic acid, glycerol, palmitic acid, pyruvate, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, 1 5-anhydro d-altrol, and boric acid were down-regulated in the gingivitis group, relative to healthy controls. IPA showed that these metabolites are connected to IL17 signaling, TGF-B signaling, and IL10 signaling, which are related closely to Th17 and Treg pathway. Conclusion: Overall, these results showed that disturbance to glycolysis as well as amino and fatty acid metabolism are associated with Th17/Treg balance in gingivitis. Impaired immunometabolism may influence some periodontally involved systemic diseases, hence it is a promising strategy in targeted development of treatment therapies.

Drug screening and development from the affinity of S protein of new coronavirus with ACE2.

Recently, various studies have shown that angiotensin-converting enzyme 2 (ACE2) acts as the "doorknob" that can be bound by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which conduces to its entrance to the host cells, and plays an important role in corona virus disease 2019 (COVID-19). This paper aims to collect and sorts out the existing drugs, which exert the ability to block the binding of S protein and ACE2 so as to provide directions for the later drug development. By reviewing the existing literature, we expound the pathogenesis of SARS-CoV-2 from the perspective of S protein and ACE2 binding, and summarize the drugs and compounds that can interfere with the interaction of spike protein and ACE2 receptor from different ways. We summarized five kinds of substances, including peptide P6, griffithsin, hr2p analogs, EK1, vaccine, monoclonal antibody, cholesterol-depleting agents, and extracts from traditional Chinese medicine. They can fight SARS-CoV-2 by specifically binding to ACE2 receptor, S protein, or blocking membrane fusion between the host and virus. ACE2 is the key point for SARS-CoV-2 to enter the cells, and it is also the focus of drug intervention. Our drug summary on this pathomechanism is expected to provide ideas for the drug research on SARS-CoV-2 and help to develop anti-coronavirus drugs of broad spectrum for future epidemics.

Innovated formulation of TCM pangolin scales to develop a nova therapy of rheumatoid arthritis.

Pangolin scale (PS) is a traditional Chinese medicine (TCM) for treating rheumatic arthritis (RA), and diverse medicinal formulations and therapeutic properties of PS have proved great potential to supplement conventional treatments in integrative medicine-based strategies. However, few studies have investigated how different PS formulations can impact the management of RA. Herein, we developed an innovative formulation of PS processed with vinegar (PSP) and evaluated it by comparing with the traditional decoction of PS (PSD) and non-steroidal anti-inflammatory drug (NASID) (i.e., meloxicam) in a RA Sprague Dawley rat model, which is induced with a complete Freund's adjuvant (CFA). The anti-inflammatory activities were evaluated by paw edema measurement, arthritic score, histopathological examination, pro-inflammatory cytokines (IL-1ß and TNF-α) production and the whole blood viscosity. PSP treatments (249.0 mg/kg.bw) from day 14-42 alleviated paw edema (P < 0.001), arthritic index (score 0-1.5) and the inflammatory cell infiltration in the ankle joint, which may be attributed to inhibiting the production of TNF-α (P < 0.01) and IL-1ß (P < 0.05) in the serum. Although PSP is with fewer efficacies than meloxicam, it outperformed traditional formulation PSD (830 mg/kg.bw) in all above mentioned metrics. Furthermore, PSP exhibited a unique effect on reducing whole blood viscosity (P < 0.05) unobserved in meloxicam intervention. The present study demonstrates that PSP showed more efficient anti-inflammatory activity than PSD in CFA-induced RA rats, possibly due to the presence of higher levels of active ingredients. Thus, PSP may be a promising therapy for anti-inflammation in RA and can be integrated with conventional treatments, particularly for long-term RA management in an integrative treatment strategy.

Purification, characterization and anti-tumor activity of a pectic-type polysaccharide isolated from Ficus pandurata H.

A homogeneous polysaccharide (FP2) with 83.3 kDa molecular weight was obtained from the aerial parts of Ficus pandurata H. (Moraceae) by Sevag, anion-exchange chromatography and gel-filtration chromatography. On the basis of composition analysis, infrared spectra (IR) and nuclear magnetic resonance (NMR) experiments, FP2 is a linear pectin with a main chain composed of →4)-α-D-GalpA-(1→. We investigated the anti-proliferative activity and its underlying mechanism of FP2 in HeLa cancer cells, using MTT assay and western blot analysis, respectively. Treatment with FP2 in HeLa cancer cells showed anti-proliferation effect and up-regulated the expression levels of caspase-3 and cleaved-PARP. IC50 values were 31.50 and 22.62 µg/ml for 24 h and 48 h, respectively. FP2 has potential of antitumor possibly due to apoptosis induction mediated through caspase-3 activation and cleavage of PARP. The results suggest that FP2 may be a promising plant polysaccharide targeting for anticancer therapy through activating the apoptotic pathway.

Effect of a Traditional Chinese Medicine Formula (CoTOL) on Serum Uric Acid and Intestinal Flora in Obese Hyperuricemic Mice Inoculated with Intestinal Bacteria.

CoTOL is a traditional Chinese medicine (TCM) formula in clinics for treating gout and hyperuricemia, especially in obese patients with recurrent attacks. However, fewer studies have investigated how CoTOL impacts the intestinal flora in reducing uric acid. In the present, we analyze the bacteria targeted by ingredients of CoTOL and evaluate the effects of CoTOL on uric acid and intestinal flora in a mice model of obese hyperuricemia inoculated with xanthine dehydrogenase- (XOD-) producing bacteria, Streptococcus faecalis. Firstly, ingredients of herbs in CoTOL and gene target by these ingredients were retrieved from TCMID 2.0, and these genes were screened by DAVID Bioinformatics Resources 6.8, deciphered to retrieve the bacteria. Then, 3-4-week-old male C57bl/6j mice were randomly divided into 6 groups and fed with high fat diet for 8 weeks up to obesity standard. The mice were inoculated intragastrically with 5 × 109 CFU Streptococcus faecalis 3 times at the 5th, 6th, and 7th week and intragastrically administrated with uricase inhibitor, potassium-oxonate (PO, 250 mg/kg), to induce hyperuricemia at the 8th week, once a day for 7 consecutive days, respectively (IB model). IB model plus CoTOL (0.4 ml/20g) and allopurinol (40 mg/kg) were administrated by gavage at the 5th week, once a day for 4 weeks. The feces and blood in each group were sampled at the 4th and 8th week. With no bacteria inoculation, CoTOL, allopurinol, and blank group were treated with CoTOL and allopurinol or water, respectively. 44 species of bacteria (i.e., Enterococcus faecalis, Streptococcus, etc.) genes were targeted by 6 ingredients of 6 herbs in CoTOL. Inoculation with Streptococcus faecalis significantly caused the elevation of uric acid and the change of intestinal flora structure, whereas treatment with CoTOL significantly increased the abundance of Akkermansia and those of Bacteroides and Alloprevotella decreased. Furthermore, CoTOL exhibited a unique effect on reducing weight unobserved in allopurinol intervention. The present study, for the first time, demonstrated that CoTOL has beneficial effects on hyperuricemia and overweight, which may be attributed to regulating material metabolism and improving the structure or function of intestinal flora. Thus, CoTOL may be a promising therapy for hyperuricemia and overweight in chronic gout management and can be integrated with conventional treatments.

A Traditional Clinic Chinese Medicine Prescription Qu-Zhuo-Tong-Bi (QZTB) Alleviates Gouty Arthritis in Model Rats.

Qu-Zhuo-Tong-Bi (QZTB) is an empirical traditional Chinese medicine prescription for treating acute gouty arthritis clinically without serious adverse effects in mainland China. However, the biochemical mechanism underlying the therapeutic action produced by QZTB treatment against acute gouty arthritis and the effect on recurrent attack remain unknown. In this study, we investigated the anti-inflammatory and analgesic effects of QZTB on acute gouty arthritis and the recurrent attack in rats, as well as the underlying mechanisms. The gouty arthritis model was established by intra-articular injection of monosodium urate (MSU) crystal suspension (2 mg/50 µL) into the right ankle joint of Sprague Dawley (SD) male rats. QZTB (500 mg/kg) and the positive control drug meloxicam were administrated by gavages twice a day for 7 days before, or 3 days after, first MSU injection in different experiments, respectively. The analgesic effects were evaluated by pain-like behaviors and hind paw mechanical withdrawal threshold testing. The anti-inflammatory activities were evaluated by ankle swelling measurement, histologic examination, NLRP3 inflammasome, and inflammatory cytokine expression. Western blot and quantitative real-time PCR were used to detect the protein and mRNA expressions of NLRP3. IL-1ß and TNF-α level in the blood serum were detected by enzyme-linked immunosorbent assay (ELISA). QZTB can suppress ankle swelling and synovial inflammation in the MSU-induced gouty arthritis rat model. QZTB alleviated the acute attack and prevented the recurrent attack of gouty arthritis. In addition, QZTB treatment significantly decreased both mRNA and protein levels of NLRP3, as well as the production of IL-1 and TNF-α in the ankle joint of model rats. Taken together, these results suggest that QZTB may be a promising herbal formula for the prevention and treatment of gouty arthritis in humans.

Notoginsenoside R1 significantly promotes in vitro osteoblastogenesis.

Notoginsenoside R1 (NGR1), one of the main effective components of Panax notoginseng, appears to be effective in promoting osteogenesis and treating osteoporosis. However, hitherto, whether NGR1 can directly promote osteoblastogenesis remains to be elucidated. In the present study, we hereby examined the effects of NGR1 on the osteoblastogenesis of a pre-osteoblast cell line (MC3T3-E1) in in vitro time-course and dose-dependent experiments. Its efficacy was evaluated by assessing cell viability (indicator of proliferation), alkaline phosphatase (ALP) activity (a marker of early osteoblastic differentiation), levels of osteocalcin (OCN; a marker of late osteoblastic differentiation), calcium deposition (a marker of final mineralization) and the expression of a series of osteoblastogenic marker genes (such as collagen Iα, Runx2, ALP and OCN) at different time points. When examining the proliferation of and ALP activity in the pre-osteoblasts, a bell-shaped dose-response pattern was observed when the cells were treated with various concentrations of NGR1, with a peak being observed at the concentration of 50 µg/ml. NGR1 markedly increased the expression of OCN at the concentration of 1,000 µg/ml in a dose­dependent manner. Furthermore, treatment with 1,000 µg/ml NGR1 resulted in the highest mineralization by 4.3- and 5.9-fold on the 21st and 28th day, respectively compared with the control group (no treatment). On the whole, our findings indicate that NGR1 significantly promotes the osteoblastogenesis of pre-osteoblasts, which suggests that NGR1 has potential for use as a bone regeneration agent.

MicroRNA-92a Promotes Colorectal Cancer Cell Growth and Migration by Inhibiting KLF4.

Colorectal cancer (CRC) is the third most common malignancy with high mortality around the world. However, the biological mechanism of CRC carcinogenesis is not completely known. In the present study, we determined the role of miR-92a in the regulation of CRC cell motility. Expression of miR-92a is aberrantly upregulated in human CRC tissues and cultured cells, as shown by RT-PCR analysis. The effects of miR-92a on the proliferation and migration of human CRC SW620 and LoVo cells were measured by CCK-8 and Transwell assay, respectively. Results showed that the proliferation and migration capacity of both SW620 and LoVo cells were significantly increased by miR-92a mimic transfection but reduced by miR-92a inhibition. Additionally, KLF4 was identified as a direct target of miR-92a in CRC cells through bioinformatics and luciferase reporter analysis. KLF4 overexpression attenuated the effects of miR-92a on the regulation of CRC cell motility. Further studies suggested that the cell cycle inhibitor p21 was aberrantly downregulated in CRC cells, whereas this inhibition was reversed by miR-92a inhibitor. In conclusion, our data demonstrated that miR-92a may play a positive role in the colorectal carcinogenesis by promoting the proliferation and migration of CRC cells through targeting KLF4 as well as downstream p21. This could be an alternative therapeutic target for CRC.

Preclinical Evaluation of Liposomal C8 Ceramide as a Potent anti-Hepatocellular Carcinoma Agent.

Hepatocellular carcinoma (HCC) remains a global health threat. The search for novel anti-HCC agents is urgent. In the current study, we synthesized a liposomal C8 ceramide, and analyzed its anti-tumor activity in pre-clinical HCC models. The liposomal C8 (ceramide) potently inhibited HCC cell (HepG2, SMMC-7721 and Huh-7 lines) survival and proliferation, more efficiently than free C8 ceramide. Yet, non-cancerous HL7702 human hepatocytes were resistant to the liposomal C8 treatment. Liposomal C8 activated caspase-dependent apoptosis in HCC cells, and HCC cytotoxicity by liposomal C8 was significantly attenuated with co-treatment of caspase inhibitors. At the molecular level, we showed that liposomal C8 activated ASK1 (apoptosis signal-regulating kinase 1)-JNK (Jun N-terminal protein kinase) signaling in HCC cells. On the other hand, JNK pharmacological inhibition or dominant negative mutation, as well as ASK1 shRNA-knockdown remarkably inhibited liposomal C8-induced apoptosis in HCC cells. Further studies showed that liposomal C8 inhibited AKT-mTOR (mammalian target of rapamycin) activation in HCC cells. Restoring AKT-mTOR activation by introducing a constitutively-active AKT alleviated HepG2 cytotoxicity by liposomal C8. In vivo, intravenous (i.v.) injection of liposomal C8 significantly inhibited HepG2 xenograft growth in severe combined immuno-deficient (SCID) mice, and mice survival was significantly improved. These preclinical results suggest that liposomal C8 could be further studied as a valuable anti-HCC agent.

Observation of the intermediates of in-source aldolization reaction in electrospray ionization mass spectrometry analysis of heteroaromatic aldehydes.

Electrospray ionization mass spectrometry (ESI-MS) analyses of 2-(1,2,4-triazole-1-yl)-6-methyl-3- quinolinecarboxaldehyde were carried out by using an ion trap mass spectrometer in a positive-ion mode. Interestingly, several unusual [M + 15](+), [M + 33](+), and [M + 47](+) ions were observed with a high abundance in the ESI-MS spectrum when methanol was used as the ESI solvent. However, only the protonated molecule was obtained with acetonitrile as the ESI solvent. These unusual ions have been proposed as the intermediates of an aldolization reaction occurring in the ESI source, which have been validated by a tandem mass spectrometry experiment, high-performance liquid chromatography/mass spectrometry analysis, and theoretical calculations. A full understanding of this reaction can contribute to the avoidance of analysis errors in the ESI-MS analysis of unknown heteroaromatic aldehydes.

HPLC/QTOF-MS/MS application to investigate phenolic constituents from Ficus pandurata H. aerial roots.

Ficus pandurata H. aerial roots are used as a traditional Chinese medicine for the treatment of uarthritis, indigestion and hyperuricemia. However, the bioactive constituents responsible for the pharmacological effects of F. pandurata H. are unclear. A simple and efficient HPLC/QTOF-MS/MS (high-performance liquid chromatography/electrospray ionization with quadrupole time-of-flight tandem mass spectrometry) method was established to detect and identify active constituents in the n-butanol extract of F. pandurata H. aerial roots. Chemical constituents were separated and investigated by HPLC/QTOF-MS/MS in the negative-ion mode. Thirty-seven compounds, including hydroxycinnamic acid derivatives, hydroxybenzoic acid derivatives, hydroquinone glycosides, flavonoid glycosides, etc., were identified or tentatively characterized in the n-butanol extract of F. pandurata H. aerial roots by comparing the UV spectra, accurate mass spectra and fragmentation pathways and retrieving the reference literatures. Moreover, the flavonoid trisaccharides and hydroxybenzoic acid derivatives were tentatively characterized in F. pandurata H. for the first time. The analytical tool used here is very valuable in the rapid separation and identification of the multiple and minor constituents in the n-butanol extract of F. pandurata H. aerial roots.

Phytochemical Compositions and Antioxidant and Anti-Inflammatory Activities of Crude Extracts from Ficus pandurata H. (Moraceae).

Background. Ficus pandurata H. (Moraceae) is widely used in traditional Chinese medicine as a healthy food condiment or a medicine for treatment of various diseases including inflammation. Objective. The purpose of the present study is to investigate the phytochemical compositions and antioxidant and anti-inflammatory activities of crude water (FPW) and ethanolic extracts (FPE) from Ficus pandurata H. Methods. Phytochemical compositions were identified by a high-performance liquid chromatography-electrospray ionization-mass spectrometry method (HPLC-ESI-MS). The antioxidant activities were evaluated by diphenylpicrylhydrazyl (DPPH) and hydroxyl radical assays, and the anti-inflammatory activities were evaluated by paw edema and levels of inflammatory mediator TNF- α and PGE2 in monosodium urate (MSU) crystal-induced rats. Results. Six compounds were identified by HPLC-MS method, and abundance of phenolics was found in FPE. The FPE showed concentration-dependent-significant scavenging of DPPH and hydroxyl radicals with IC50 values 118.4 and 192.9 µ g/mL, respectively. The FPE treatment significantly inhibited the paw edema and the production of TNF- α and PGE2 in MSU crystal-induced rats. Conclusion. The FPE exerted stronger antioxidant and anti-inflammatory activities which may be attributed to its high phenolic content.

On the origin of the methyl radical loss from deprotonated ferulic and isoferulic acids: electronic excitation of a transient structure.

Formation of radical fragments from even-electron ions is an exception to the "even-electron rule". In this work, ferulic acid (FA) and isoferulic acid (IFA) were used as the model compounds to probe the fragmentation mechanisms and the isomeric effects on homolytic cleavage. Elimination of methyl radical and CO2 are the two competing reactions observed in the CID-MS of [FA - H](-) and [IFA - H](-), of which losing methyl radical violates the "even-electron rule". The relative intensity of their product ions is significantly different, and thereby the two isomeric compounds can be differentiated by tandem MS. Theoretical calculations indicate that both the singlet-triplet gap and the excitation energy decrease in the transient structures, as the breaking C-O bond is lengthened. The methyl radical elimination has been rationalized as the intramolecular electronic excitation of a transient structure with an elongating C-O bond. The potential energy diagrams, completed by the addition of the energy barrier of the radical elimination, have provided a reasonable explanation of the different CID-MS behaviors of [FA - H](-) and [IFA - H](-).

Optimization of technology for dietary fiber extraction from Maixiansan by response surface methodology.

BACKGROUND: Our study aims to determine whether response surface methodology can optimize the extraction of dietary fiber from Maixiansan. METHODS: A Box-Behnken design was employed to optimize the extraction parameters, including α-amylase concentration (X1: 0.3 - 0.5%), enzymolysis time (X2: 30 - 60 min) and NaOH content (X3: 1.0 - 5.0%), of dietary fiber from Maixiansan using an enzyme-alkali extraction technique. RESULTS: The optimal technological conditions were as follows: α-amylase concentration: 0.4%; enzymolysis time: 45 min; NaOH content: 4.0%. Under these conditions, the extraction yield reached 57.14%, which was well consistent with the predicted models with a coefficient of determination (R2) of 0.9818. An evaluation of the anti-inflammatory activity indicated that Maixiansan was able to significantly inhibit dextran sodium sulfate-induced ulcerative colitis in rats by increasing the concentration of short-chain fatty acids (acetate, propionate and butyrate), among which the butyrate content was significantly higher in the Maixiansan group than in the other groups. CONCLUSION: Our experiments showed that response surface methodology can optimize the extraction of dietary fiber from Maixiansan. Maixiansan could be explored as an anti-ulcerative colitis agent.

Brønsted acid-catalyzed decarboxylative redox amination: formation of N-alkylindoles from azomethine ylides by isomerization.

A Brønsted acid-catalyzed decarboxylative redox amination involving aldehydes with 2-carboxyindoline for the synthesis of N-alkylindoles is described. The decarboxylative condensations of aldehydes with 2-carboxyindoline produce azomethine ylides in situ, which then transform into N-alkylindoles by isomerization.