Sub-pm linewidth, high pulse energy, high beam quality microsecond-pulse Ti:sapphire laser at 766.699†nm.

In this letter, a sub-pm linewidth, high pulse energy and high beam quality microsecond-pulse 766.699 nm Ti:sapphire laser pumped by a frequency-doubled Nd:YAG laser is demonstrated. At an incident pump energy of 824 mJ, the maximum output energy of 132.5 mJ at 766.699 nm with linewidth of 0.66 pm and a pulse width of 100 µs is achieved at a repetition rate of 5 Hz. To the best of our knowledge, this is the highest pulse energy at 766.699 nm with pulse width of hundred micro-seconds for a Ti:sapphire laser. The beam quality factor M2 is measured to be 1.21. It could be precisely tuned from 766.623 to 766.755 nm with a tuning resolution of 0.8 pm. The wavelength stability is measured to be less than ±0.7 pm over 30 min. The sub-pm linewidth, high pulse energy and high beam quality Ti:sapphire laser at 766.699 nm can be used to create a polychromatic laser guide star together with a home-made 589 nm laser in the mesospheric sodium and potassium layer for the tip-tilt correction resulting in the near-diffraction limited imagery on a large telescope.

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism.

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)-induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666-1 cells through regulating PARP-2/SIRT1/AMPK signaling pathway.

BACKGROUND/AIM: Nobiletin, a major polymethoxyflavones (PMFs) from citri reticulatae pericarpium (CRP), can inhibit several forms of cancer proliferation. However, the effects of nobiletin on nasopharyngeal carcinoma (NPC) C666-1 cells remain largely unknown. MATERIALS AND METHODS: Cell counting kit 8 (CCK8) assay was used to measure cell vitality. Flow cytometry was performed to measure the apoptosis rate. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were applied to determine the expression of mRNA and protein, respectively. RESULTS: We showed that the proliferation rate of C666-1 cells was inhibited and the apoptosis rate was raised after treating with nobiletin. Moreover, nobiletin inhibited the expression of poly(ADP-ribose)polymerase-2 (PARP-2), and the tumor suppression effect of nobiletin on C666-1 is associated with PARP-2-dependent pathway. CONCLUSION: We demonstrated for the first time that nobiletin inhibited the growth of C666-1 cells, which may be relative to its regulation on PARP-2/SIRT1/AMPK signaling pathway. Our result implied that nobiletin may serve as a strategy to treat nasopharyngeal carcinoma.

Cultivar differentiation of Citri Reticulatae Pericarpium by a combination of hierarchical three-step filtering metabolomics analysis, DNA barcoding and electronic nose.

The traditional Chinese medicine Citri Reticulatae Pericarpium (CRP) was mainly originated from the dried pericarp of Citrus reticulata 'Chachi' (Crc), Citrus reticulata 'Dahongpao' (Crd), Citrus reticulata 'Unshiu' (Cru) and Citrus reticulata 'Tangerina' (Crt) in China. Since these four cultivars have great similarities in morphology, reliable methods to differentiate CRP cultivars have rarely been reported. To discriminate the differences of these CRP cultivars, herein an efficient and reliable method by combining metabolomics, DNA barcoding and electronic nose was first established. The hierarchical three-step filtering metabolomics analysis based on liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) indicated that 9 species-specific chemical markers including 6 flavanone glycosides and 3 polymethoxyflavones could be considered as marker metabolites for discrimination of the geoherb Crc from other cultivars. A total of 19 single nucleotide polymorphism (SNP) sites were found in nuclear internal transcribed spacer 2 (ITS2) of CRP, and three stable SNP sites (33, 128 and 174) in the ITS2 region can distinguish the four CRP cultivars. The electronic nose coupled with chemometrics could also be used to effectively distinguish Crc from other CRP cultivars. Therefore, our results indicated that the integrated method will be an effective strategy for discrimination of similar herbal medicines.

Evaluation of anti-lipase activity and bioactive flavonoids in the Citri Reticulatae Pericarpium from different harvest time.

BACKGROUND: Inhibition of pancreatic lipase is an attractive approach to the treatment of obesity and other metabolic disorders. Naturally occurring phytochemicals are promising sources of lipase inhibitors. PURPOSE: In the present study, the anti-lipase activity of Citri Reticulatae Pericarpium (CRP) extracts was firstly evaluated in vitro. Moreover, the dynamic alteration of bioactive flavonoids in CRP collected at different time and its correlation with anti-lipase activities was investigated. STUDY DESIGN/METHODS: Quantitative analysis of multi-components by a single-marker (QAMS) method was developed and validated for simultaneous determination of six flavonoids including narirutin, hesperidin, didymin, nobiletin, 3,5,6,7,8,3',4'-heptamethoxyflavone and tangeretin. Anti-lipase activity evaluation and docking studies of the flavonoids was also carried out to screen out the candidate lipase inhibitors. RESULTS: The QAMS method validation results exhibited that the developed method had desirable specificity, linearity, precision and accuracy. CRP collected in early months contained higher concentrations of bioactive flavonoids, and exhibited more potent anti-lipase activity. CONCLUSION: Harvest timing had a significant impact on the amounts of bioactive flavonoids and the anti-lipase activities of CRP extracts. The contents of total flavonoids were positively correlated with the anti-lipase activities of CRP, and polymethoxyflavones played a significant role in the hypolipidemic effect of CRP. Nobiletin might be the most potential lipase inhibitor in CRP.

Chemicalome and metabolome profiling of polymethoxylated flavonoids in Citri Reticulatae Pericarpium based on an integrated strategy combining background subtraction and modified mass defect filter in a Microsoft Excel Platform.

Detection of metabolites in complex biological matrixes is a great challenge because of the background noise and endogenous components. Herein, we proposed an integrated strategy that combined background subtraction program and modified mass defect filter (MMDF) data mining in a Microsoft Excel platform for chemicalome and metabolome profiling of the polymethoxylated flavonoids (PMFs) in Citri Reticulatae Pericarpium (CRP). The exogenously-sourced ions were firstly filtered out by the developed Visual Basic for Applications (VBA) program incorporated in the Microsoft Office. The novel MMDF strategy was proposed for detecting both target and untarget constituents and metabolites based on narrow, well-defined mass defect ranges. The approach was validated to be powerful, and potentially useful for the metabolite identification of both single compound and homologous compound mixture. We successfully identified 30 and 31 metabolites from rat biosamples after oral administration of nobiletin and tangeretin, respectively. A total of 56 PMFs compounds were chemically characterized and 125 metabolites were captured. This work demonstrated the feasibility of the integrated approach for reliable characterization of the constituents and metabolites in herbal medicines.