Determination of zinc pyrithione in shampoos by HPLC and HPLC-MS/MS.

Methods have been developed for the determination of zinc pyrithione (ZPT) in shampoos using high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS). Samples were washed by water first to remove surfactant and water-soluble impurities, then ultrasonic-extracted by acetonitrile-methanol for 30 min, and finally analyzed by MG C18 column (250 mm x 4.6 mm, 5 µm) or RP-18e (100 mm x 3 mm, 2 µm) plus APCI-MS/MS. Limits of detection were determined as 0.015% (HPLC) and 0.003% (HPLC-MS/MS), with a limit of quantization of 0.05% and 0.01%, respectively. The recoveries were 85.8-104% (HPLC) and 87.6-107% (HPLC-MS/MS). A good linear relationship was obtained from 3.20 µg·ml(-1) to 200 µg·ml(-1) (HPLC) and 1.00 µg·ml(-1) to 200 µg·ml(-1) (HPLC-MS/MS). The proposed methods have been successfully applied to the analysis of ZPT in many shampoos. The established two methods were rapid and reproducible with low interference.

[Synthesis and immunosuppressive effects of novel phthalazine ketone derivatives].

A series of phthalazine ketone compounds were synthesized and the structures were confirmed by H NMR and HR-MS spectrum. All target compounds were obtained through 7 steps, including selective reduction, nitration, bromination, ring enlargement, reduction, Knoevenagel and acylated reaction. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and inhibitory activity of IMPDH type II in vitro, as well as their structure-activity relationship were assessed. Several compounds exhibited strong immunosuppressive properties, especially compounds 7f and 7h, with IC50 values of 0.093 micromol x L(-1) and 0.14 micromol x L(-1) respectively, which were superior to mycophenolic acid. The information obtained from the studies may be useful for further research on the immunosuppressive agents.

The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives.

The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several compounds demonstrated highly efficacious immunosuppressive properties, especially compounds 2d, 2e, 2h and 2j, which were superior to MPA, while compounds 2k, 2m, 2n, 4c and 5d exhibited an equipotent inhibitory activity compared to MPA. Generally, it was obviously demonstrated that α,ß-unsaturated amides proved more potent than the diamide and urea series. The present study provides a guide for further research on development of safe and effective immunosuppressive agents.

[Effects of long-term fertilization on organic carbon functional groups in black soil as revealed by synchrotron radiation soft X-ray near-edge absorption spectroscopy].

A 20 years (1984-2004) stationary field experiment was conducted to evaluate the effects of long-term application of chemical fertilizers (N or NPK) alone or in combination with low (0.125 kg x hm(-2)) or high dose of corn stalk (0.25 kg x hm(-2)) on organic carbon functional groups in black soil using synchrotron radiation soft X-ray near-edge absorption spectroscopy (C-1s NEXAFS). Compared with the control (CK) treatment, the aromatic C and the carboxyl C of soil increased, whereas the aliphatic C, the carbonyl C and the aliphatic C/aromatic C ratio decreased after the application of chemical fertilizer alone. After the application of chemical fertilizations in combined with corn stalk, the aromatic C decreased while the aliphatic C and the aliphatic C/aromatic C ratio increased as compared to N or NPK fertilizer treatment. And the change tendency was more obvious with the increase in the dose of corn stalk applied. Regardless of corn stalk application, the aromatic C, the aliphatic C, and the aliphatic C/aromatic C ratio were all higher for NPK than for N fertilizer treatment. The above results indicated that, compared with the no-fertilizer control treatment, the application of chemical fertilizers alone resulted in the relative proportion of aromatic compounds increased whereas that of aliphatic hydrocarbon compounds decreased. On the other hand, the relative proportion of the aliphatic hydrocarbon compounds was higher after the application of chemical fertilizers with than without corn stalk, with high than with low dose of corn stalk, and with NPK than with N fertilization. C-1s NEXAFS spectroscopy could characterize in situ the changes of organic carbon functional groups in soil under long-term stationary fertilization.

Effects of Dietary Riboflavin Supplementation on the Growth Performance, Body Composition and Anti-Oxidative Capacity of Coho Salmon (Oncorhynchus kisutch) Post-Smolts.

The present study investigated the effects of dietary riboflavin on growth performance, body composition and anti-oxidative capacity of coho salmon (Oncorhynchus kisutch) post-smolts. Seven experimental diets were formulated with graded riboflavin levels of 0.00, 3.96, 8.07, 16.11, 31.81, 63.67 and 126.69 mg/kg, respectively. Each diet was fed to triplicate groups of 10 fish with an individually initial mean body weight of 186.22 ± 0.41 g in 21 cages (water volume, 1000-L/cage) and fed three times daily (7:30, 12:30 and 17:30) to apparent satiation for 12 weeks. Fish fed a diet with 31.81 mg/kg riboflavin had the highest specific growth rate (SGR), which was significantly higher than fish-fed diets with 0.00, 3.96, 8.07 and 126.69 mg/kg riboflavin (p < 0.05). Feed conversion ratio showed an inverse trend with SGR. No significant differences were observed in condition factor, hepatosomatic index, viscerosomatic index, muscle moisture, crude protein and ash contents among dietary groups. Muscle lipid had the highest content in the 31.81 mg/kg group and was significantly higher (p < 0.05) than those in the 0.00, 3.96 and 8.07 mg/kg groups. The alanine aminotransferase, aspartate aminotransferase and malondialdehyde contents in the liver and serum of fish were significantly decreased with the increase in dietary riboflavin level up to 31.81 mg/kg, and then increased as dietary riboflavin level further increased. An inverse trend was observed for total superoxide dismutase and catalase activities. Serum total cholesterol and triglyceride levels were significantly decreased with the dietary of riboflavin levels up to 31.81 and 63.67 mg/kg, respectively. The cubic curve regression analysis based on SGR indicated that the optimum dietary riboflavin level was estimated to be 35.26 mg/kg for coho salmon post-smolts.

Comparison of Clinical Effects of the Modified Masquelet Technique and Kirschner Wire External Fixation-Assisted Autogenous Bone Transplantation in the Treatment of Segmental Metacarpophalangeal Bone Defects.

OBJECTIVE: The present study aims to explore the (1) clinical effects of the modified Masquelet technique, whose improved Masquelet technique innovates the in vitro plasticity of the bone cement module and prefabricated hollow design, and the Kirschner wire external fixation-assisted autologous bone transplantation technique in the treatment of segmental metacarpophalangeal bone defects and (2) the differences between the two techniques. METHODS: The clinical data of 32 patients with segmental metacarpophalangeal bone defects (15 patients treated with the modified Masquelet technique and 17 patients treated with the self-made Kirschner wire external fixation technique) admitted to our department between January 2012 and January 2020 were retrospectively analyzed. The postoperative bone healing time, hand function, and complications were compared between the two groups. RESULTS: The two groups were comparable; there were no significant differences in age, sex, length of bone defect, and time from injury to operation between the two groups (P > 0.05). All patients were followed up with for 6-24 months (average = 13.7 months), and all patients with segmental metacarpophalangeal bone defects achieved fracture healing. The postoperative hospital stay, fracture healing time, functionary scores of the affected limb, and incidence of severe complications were better in the modified group than in the external fixation group (P < 0.05). CONCLUSION: Compared with the Kirschner wire external fixation stent assisted autologous bone transplantation, the improved Masquelet technique has the advantages of simple operation, fast healing, accurate effect, wide indications, and less complications, making it more worthy of clinical promotion.

Synthesis, biological evaluation, and modeling of dimeric PPI analogues as novel DNA minor groove binders.

A series of symmetrical dimeric proton pump inhibitor (PPI) analogues, designed as novel type DNA minor groove binders, was synthesized and evaluated for anti-tumor activity. Some of these new compounds showed IC(50) values below 10 microM in an in vitro anti-tumor test. A molecular modeling study was performed to confirm the sequence selectivity of these compounds towards AT base pairs in DNA. Two effective compounds were selected and docked into the minor groove of DNA. The snug binding may be responsible for their cytotoxic and anti-tumor effects.

[Studies on triterpenoids from Potentilla chinensis].

OBJECTIVE: To investigate the chemical constituents of Potentilla chinensis. METHOD: Silica gel column chromatography and Sephadex LH - 20 gel column chromatography were employed for the isolation and purfication. The structures were identified on the basis of spectral data and chemical evidence. RESULT: Six compounds were isolated and identified as follows: 3-hydroxy-11-ursen-28, 13-olide, 11, 12-dehydroursolic acid lactone (1), 3-O-acetyl pomolic acid (2), betulinic acid (3), 3-oxo-12-ursen-28-oic acid (4), ursolic acid (5), oleanic acid (6). CONCLOUSION: All these compounds were isolated from P. chinensis for the first time, compound 1, 2, 4 were isolated from this genus for the first time.

[Study on chemical constituents of Potentilla chinensis Ser].

Five compounds (I - V) were isolated from Potentilla chinensis Ser. On the basis of spectral data and chemical evidence. I - V were identified as 2alpha-hydroxyoleanolic acid (I), 2alpha-hydroxyursolic acid (II), 5, 7, 4'-trihydroxyflavone (IIl), beta-sitosterol (IV), daucostarine (V). All these compounds were isolated from Potentilla chinensis Ser for the first time.

In silico design of human IMPDH inhibitors using pharmacophore mapping and molecular docking approaches.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is one of the crucial enzymes in the de novo biosynthesis of guanosine nucleotides. It has served as an attractive target in immunosuppressive, anticancer, antiviral, and antiparasitic therapeutic strategies. In this study, pharmacophore mapping and molecular docking approaches were employed to discover novel Homo sapiens IMPDH (hIMPDH) inhibitors. The Güner-Henry (GH) scoring method was used to evaluate the quality of generated pharmacophore hypotheses. One of the generated pharmacophore hypotheses was found to possess a GH score of 0.67. Ten potential compounds were selected from the ZINC database using a pharmacophore mapping approach and docked into the IMPDH active site. We find two hits (i.e., ZINC02090792 and ZINC00048033) that match well the optimal pharmacophore features used in this investigation, and it is found that they form interactions with key residues of IMPDH. We propose that these two hits are lead compounds for the development of novel hIMPDH inhibitors.

Computational insights into the inhibition of inosine 5'-monophosphate dehydrogenase by mycophenolic acid analogs: three-dimensional quantitative structure-activity relationship and molecular docking studies.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo synthesis of guanosine nucleotides. It is considered as an important target in the quest for drugs in the immunosuppressive, antiviral, antibacterial, and anticancer therapeutic areas. Herein, we report the 3D-QSAR analyses using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking on mycophenolic acid derivates for the first time. We obtained cross-validated q(2) value of 0.805 for CoMFA and 0.620 for CoMSIA, while the non-cross-validated r(2) values for them were 0.969 and 0.935, respectively. Based on the CoMFA and CoMSIA contour maps and docking analyses, some key structural factors responsible for inhibitory activity were revealed. The results obtained from this study could be used for the rational design of potent inhibitors against IMPDH.

A three-dimensional pharmacophore model for IMPDH inhibitors.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo synthesis of guanosine nucleotides. It is considered an important target in the quest for drugs in the immunosuppressive, antiviral, antibacterial and anticancer therapeutic areas. In this study, a chemical feature-based pharmacophore model of IMPDH inhibitors has been firstly developed with the aid of the HypoRefine protocol within Discovery Studio 2.5. The best model for IMPDH inhibitors, Hypo1-1, was characterized by the best correlation coefficient (0.97595) and the lowest RMSD (0.582058). It consisted of one hydrogen-bond donor, one hydrogen-bond acceptor, one aromatic ring and one hydrophobic feature, as well as two excluded volumes. The model was validated using a wide range of test molecules and a cross-validation. Furthermore, the pharmacophore features were confirmed by molecular docking studies. The pharmacophore model could quantitatively predict inhibitor activity and identify highly potent molecules. Therefore, the present results could be valuable for the discovery and development of specific IMPDH inhibitors.

Design, synthesis, and anti-tumor evaluation of novel symmetrical bis-benzimidazoles.

A novel symmetrical bis-benzimidazole was designed as DNA minor groove binder. Molecular modeling study showed that it could dock into the minor groove of DNA. Several derivatives were synthesized and confirmed by IR, MS, and (1)H NMR. All these novel compounds were screened for cytotoxic activity on SKOV-3, HeLa, and BGC-823 cell lines in vitro. Some compounds showed IC(50)s in the single-digit micromolar range for cytotoxicity in several tumor cell lines.