Dual role of dissolved black carbon in sensitized ofloxacin photooxidation: Mechanism and influential factors.

Dissolved black carbon (DBC) is the more photoactive component of dissolved organic matter (DOM) pool, which plays a dual role in the photoconversion of aquatic contaminants, acting as both a photosensitizer and an inhibitor. However, little is known about the more systematic mechanism by which DBC exhibits a dual effect, which is closely related to the structure composition of DBC. In this study, the differences in characteristics of DBC obtained from 300 °C and 500 °C were compared via UV-vis absorption spectrum, Fluorescence excitation emission matrix spectra (3D-EEM), Fourier transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS), and evaluated the promoting and inhibiting effects of DBC on ofloxacin (OFL) photodegradation. It was found that higher pyrolysis temperature reduced the UV absorbance, molecular weight, aromaticity, and phenolics of DBC while increasing the content of quinone/aromatic ketone and humic substances. Photochemical data showed that 3DBC*, 1O2 and ·OH were all participated in the DBC-mediated OFL photodegradation. Wherein, DBC300 (DBCT, where T = pyrolysis temperature) had strong light screening and dynamic quenching effect, but the formation ability of 3DBC*, 1O2 and ·OH was poor, which significantly retarded the photodegradation of OFL. While DBC500 exhibited a slight promotion effect due to its higher formation ability of reactive species and weak light screening effect. Moreover, DBC500 had higher steady-state concentration and (kOFL,3DBC⁎) than DBC300, which might be due to the higher contents of quinone/aromatic ketone and the lower contents of phenol in DBC500, thus enhancing the reactivity of 3DBC* and OFL. Our research systematically revealed the trade-off mechanism of DBC on the photodegradation of fluoroquinolones, and provided an important theoretical guidance for the photodegradation of fluoroquinolones under the evolution of DBC composition.

[A new biosynthesis route for production of 5-aminovalanoic acid, a biobased plastic monomer].

5-aminovalanoic acid (5AVA) can be used as the precursor of new plastics nylon 5 and nylon 56, and is a promising platform compound for the synthesis of polyimides. At present, the biosynthesis of 5-aminovalanoic acid generally is of low yield, complex synthesis process and high cost, which hampers large-scale industrial production. In order to achieve efficient biosynthesis of 5AVA, we developed a new pathway mediated by 2-keto-6-aminohexanoate. By combinatory expression of L-lysine α-oxidase from Scomber japonicus, α-ketoacid decarcarboxylase from Lactococcus lactis and aldehyde dehydrogenase from Escherichia coli, the synthesis of 5AVA from L-lysine in Escherichia coli was achieved. Under the initial conditions of glucose concentration of 55 g/L and lysine hydrochloride of 40 g/L, the final consumption of 158 g/L glucose and 144 g/L lysine hydrochloride, feeding batch fermentation to produce 57.52 g/L of 5AVA, and the molar yield is 0.62 mol/mol. The new 5AVA biosynthetic pathway does not require ethanol and H2O2, and achieved a higher production efficiency as compared to the previously reported Bio-Chem hybrid pathway mediated by 2-keto-6-aminohexanoate.

Hirsutine, a novel megakaryopoiesis inducer, promotes thrombopoiesis via MEK/ERK/FOG1/TAL1 signaling.

BACKGROUND: Thrombocytopenia (TP) remains a challenge in clinical hematology. TP may have serious consequences, such as recurrent skin and mucosal bleeding and increased risk of intracranial and internal organ hemorrhage. However, effective and safe therapeutic drugs for the long-term management of TP are still lacking. PURPOSE: This study aimed to identify more effective active compounds for TP therapy. METHODS: Liquid chromatography-mass spectrometry-nuclear magnetic resonance analysis was used to confirm the medicinal species and chemical structure of Hirsutine (HS). The proliferation of HS was examined by Cell Counting Kit (CCK-8) assay on cells lines. The effect of HS on megakaryocyte differentiation was analyzed by evaluating the expression of CD41, CD42b, and DNA ploidy via flow cytometry (FCM). The morphology of megakaryocytes and intermediate cells was observed using an optical microscope. K562 cells were then stained with Giemsa and benzidine. qRT-PCR was used to examine the mRNA expression of GATA-1, GATA-2, FOG-1, TAL-1, RUNX-1, NF-E2, and KLF-1 in K562 cells. Protein levels of the transcription factors were analyzed by western blotting. An MEK inhibitor was used to verify the relationship between the MEK/ERK signaling pathway and CD41/CD42b (FCM), FOG-1, and TAL-1. The Kunming thrombocytopenia mouse model was established by X-ray irradiation (4 Gy) and used to test HS activity and related hematopoietic organ index in vivo. Finally, computer simulations of molecular docking were used to predict the binding energies between HS-MEK and HS-ERK. RESULTS: We preliminarily identified HS by screening a plant-sourced compound library for natural compounds with megakaryocytic differentiation and maturation (MKD/MKM)-promoting activity. We found that HS not only enhanced MKD/MKM of K562 and Meg01 cells, but also suppressed the decline of peripheral platelet levels in X-ray-induced myelosuppressive mice. In addition, HS promoted MKD via activation of MEK-ERK-FOG1/TAL1 signaling, which may be the key molecular mechanism of HS action in TP treatment. Molecular docking simulations further verified that HS targets the signaling protein MEK with high-affinity. CONCLUSION: In this study, we report for the first time that hirsutine boosts MKD/MKM through the MEK/ERK/FOG1/TAL1 signaling pathway and thus represents a promising treatment option for TP.

Tandospirone enhances the anti-myocardial fibrosis effect of valsartan in spontaneously hypertensive rats.

PURPOSE: Myocardial fibrosis (MF) is an unavoidable complication in patients with hypertensive heart disease. Valsartan, a widely used antihypertensive drug, was reported to inhibit MF. Deficiency in the 5-hydroxytryptamine (5-HT, serotonin) transporter gene has been proven to cause MF. Long-term sympathetic nerve excitability activates renin angiotensin aldosterone system leading to MF. Tandospirone, a partial agonist of the 5-HT1A receptor, has been commonly used to relieve psychiatric symptoms. However, there is limited evidence on the combination of valsartan and tandospirone for the treatment of MF. Therefore, we investigated the synergistic effect of tandospirone on the anti-MF activity of valsartan in spontaneously hypertensive rats (SHRs). METHODS: Systolic blood pressure (SBP) of SHRs (12-week-old) was measured weekly using the tail-cuff method for eight weeks; the left ventricular was collected and weighted for calculation of the left ventricular mass index (LVMI). The myocardial histopathology of left ventricle was evaluated in rats by hematoxylin and eosin (H&E) and Mason's trichrome staining assays. The mRNA and protein expressions of transforming growth factor ß (TGF-ß1), Sma- and Mad-related protein 3 (Smad3), and fibronectin (Fn) were investigated by real time PCR, immunohistochemistry, and Western blotting analysis, respectively. RESULTS: Tandospirone (40 mg/kg) could significantly improve the effect of valsartan (30 mg/kg) in decreasing the SBP of SHRs and lower the ratio of the LVMI in SHRs, compared to that of rats treated with valsartan or tandospirone alone. Tandospirone could also enhance the valsartan-induced reduction in collagen deposition in the myocardial tissues of SHRs. Furthermore, tandospirone could enhance the effect of valsartan on downregulating the expression levels of TGF-ß1, Smad3, and Fn at both mRNA and protein levels. CONCLUSION: We report for the first time that tandospirone could improve the anti-MF efficacy of valsartan via the TGF-ß1/Smad3 signaling pathway in SHRs. Our findings may provide valuable insight into the scientific rationale for combining tandospirone and valsartan in the treatment of MF clinically.

Efficacy and Safety of Multiple Dosages of Fostamatinib in Adult Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Background: Rheumatoid arthritis is a type of systemic and complex autoimmune other disease characterized by chronic joint inflammation. Spleen tyrosine kinase (Syk) inhibitors are regarded as an effective alternative to existing drugs for the treatment of this disease. However, studies evaluating fostamatinib, a new Syk inhibitor, are either invalid or insufficient. Through a systematic review and meta-analysis, we evaluated the efficacy and safety of fostamatinib at different dosages in rheumatoid arthritis patients that display an inadequate response to methotrexate or disease-modifying antirheumatic drugs. Methods: Randomized controlled trials published between January 2000 and November 2018 were retrieved from PubMed, Embase, Medline, Web of Science, and The Cochrane Library. We also searched a relevant website (www.clinicaltrials.gov) for retrieval of unpublished data. These studies compared different dosages of fostamatinib to placebo, including the intake of 100 mg fostamatinib twice per day (bid) for 4 weeks followed by 150 mg once per day (qd) vs. the intake of 100 mg bid. Results: Two investigators analyzed 11 randomized placebo-controlled trials consisting of 3,680 patients. Compared to placebo, fostamatinib resulted in an obvious reduction in the American College of Rheumatology 20% response standard [weighted mean difference (WMD) 1.96, 95% confidence interval (CI) [1.46, 2.61], P < 0.001] and disease activity score < 2.6 (WMD 4.70, 95% CI [3.14, 7.03], P < 0.001). Regarding safety, the incidence of serious adverse reactions was higher in the fostamatinib group than in the placebo group [risk ratio (RR) 2.10, 95% CI [1.57, 2.80], P < 0.001]. The same was true for other adverse events [RR 1.63, 95%CI [1.33, 2.01], P < 0.001]. Conclusions: Fostamatinib is an effective and safe therapeutic medicine administered to patients with rheumatoid arthritis over 24 weeks. It can alleviate the degree of swelling and inflammation of the joints. Furthermore, 100 mg bid can be considered the most beneficial regimen over a 24-week period. More data are however needed to clarify the incidence of other adverse events and serious adverse reactions.

Polyacetylated labdane-type diterpenoids, ptychantins P-R from Chinese liverwort Ptychanthus striatus.

Three new polyacetylated labdane diterpenoids ptychantins P-R (1-3) and four known compounds (4-7) were isolated from an EtOH extract of the Chinese liverwort Ptychanthus striatus (Lehm. & Lindenb.) Nees. Their structures were established by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR).

Scapaundulin C, a novel labdane diterpenoid isolated from Chinese liverwort Scapania undulate, inhibits acetylcholinesterase activity.

In the present study, scapaundulin C (1), a new labdane diterpenoid, and four related known compounds scapaundulin A (2), 5α, 8α, 9α-trihydroxy-13E-labden-12-one (3), 5α, 8α-dihydroxy-13E-labden-12-one (4), and (13S)-15-hydroxylabd-8 (17)-en-19-oic acid (5), were isolated from the Chinese liverwort Scapania undulate (L.) Dum., using column chromatography. The structures of these compounds were determined on the basis of 1D- and 2D-NMR analyses. The acetylcholinesterase (AchE) inhibitory activity was evaluated using a bioautographic TLC assay and the cytotoxic activity was evaluated by the MTT method. All the compounds were reported for the first time to exhibit moderate AchE inhibitory activity with minimal inhibitory quantities ranging from 250 to 500 ng. All the compounds were tested for their cytotoxicity against five human tumor cell lines, A549, K562, A2780, Hela, and HT29, and compounds 3 and 4 exhibited moderate inhibitory effects on the growth of A2780 cells.

Notolutesins A-J, dolabrane-type diterpenoids from the Chinese liverwort Notoscyphus lutescens.

Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 µM against the PC3 human prostate cancer cell line.

Cembrane-type diterpenoids from the Chinese liverworts Chandonanthus hirtellus and C. birmensis.

Six new cembrane-type diterpenoids (1-6) were isolated from two species of Chandonanthus: Chandonanones A, B, and D-F (1, 2, and 4-6) were isolated from C. hirtellus, and chandonanones B, C, E, and F (2, 3, 5, and 6) from C. birmensis. Five known diterpenoids, (8E)-4α-acetoxy-12α,13α-epoxycembra-1(15),8-diene (7), isochandonanthone (8), chandonanthone (9), anadensin (10), and 2,10,14-triacetoxy-7,8,18,19-diepoxydolabell-3(E)-ene (11), were also obtained. The structures of the new metabolites were established by analyses of their spectroscopic data (1D NMR, 2D NMR, HRESIMS, and IR). The absolute configurations of compounds 1 and 2 were unequivocally confirmed using single-crystal X-ray diffraction analysis with Cu Kα radiation. Cytotoxicity tests of the isolated diterpenoids against seven cancer cell lines (DU145, PC3, A549, PC12, NCI-H292, NCI-H1299, and A172) revealed that some of the diterpenoids had weak activity.