BackgroundIn the People’s Republic of China, outpatients have limited time with their physicians. Thus, compared to inpatients, outpatients have lower medication adherence and are less knowledgeable about their disease.ObjectiveThe objective of this study was to evaluate the effect of pharmaceutical care on clinical outcomes of outpatients with type 2 diabetes mellitus (T2DM).Patients and methodsA randomized, controlled, prospective clinical trial was conducted recruiting a total of 240 T2DM outpatients from Zhongda Hospital, Southeast University. The control group (CG) received only common care from medical staff, whereas the inter vention group (IG) received extra pharmaceutical care from clinical pharmacists. Biochemical data such as blood pressure (BP), fasting blood glucose (FBG), glycosylated hemoglobin A1 (HbA1c), and blood lipid were collected before and after 6-month intervention. The primary end points in this study were FBG and HbA1c.ResultsAfter the intervention, most of the baseline clinical outcomes of the patients in IG significantly improved, while only body mass index, diastolic BP, low-density lipoprotein cholesterol, and total cholesterol (TC) improved significantly in patients in the CG. Compared to CG, in IG, there were significant improvements in FBG, HbA1c, TC, the target attainment rates of HbA1c, and BP.ConclusionPharmaceutical care provided by clinical pharmacists could improve the control of diabetes of outpatients, and clinical pharmacists could play an important role in diabetes management.

BTK is a member of the TEC family of non-receptor tyrosine kinases whose deregulation has been implicated in a variety of B-cell-related diseases. We have used structure-based drug design in conjunction with kinome profiling and cellular assays to develop a potent, selective, and irreversible BTK kinase inhibitor, QL47, which covalently modifies Cys481. QL47 inhibits BTK kinase activity with an IC50 of 7 nM, inhibits autophosphorylation of BTK on Tyr223 in cells with an EC50 of 475 nM, and inhibits phosphorylation of a downstream effector PLCγ2 (Tyr759) with an EC50 of 318 nM. In Ramos cells QL47 induces a G1 cell cycle arrest that is associated with pronounced degradation of BTK protein. QL47 inhibits the proliferation of B-cell lymphoma cancer cell lines at submicromolar concentrations.

A series of 1,2,3-triazole phenylhydrazone derivatives were designed and synthesized as antifungal agents. Their structures were determined based on (1)H-NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction. The antifungal activities were evaluated against four phytopathogenic fungi including Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, by the mycelium growth inhibition method in vitro. Compound 5p exhibited significant anti-phytopathogenic activity, with the EC50 values of 0.18, 2.28, 1.01, and 1.85 μg mL(-1), respectively. In vivo testing demonstrated that 5p was effective in the control of rice sheath blight, rape sclerotinia rot and fusarium head blight. A 3D-QSAR model was built for a systematic SAR profile to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel fungicides.

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The knowledge of solubility and solution thermodynamics for 1-(3-nitrophenyl)ethanone and 1-(4-nitrophenyl)ethenone in different solvents is essential for their purification and further theoretical study. In this work, the solid−liquid equilibrium for 1-(3-nitrophenyl)ethanone and 1-(4-nitrophenyl)ethenone in nine pure solvents (methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, ethyl acetate, toluene, and cyclohexane) was established with the isothermal saturation method at temperatures T = (278.15 to 318.15) K under pressure of 101.2 kPa. The mole fraction solubility of 1-(3-nitrophenyl)ethanone obeys the following order from high to low in different solvents: acetone > acetonitrile, ethyl acetate > toluene > methanol > ethanol > n-propanol, isopropanol > cyclohexane. While in 1-(4-nitrophenyl)ethanone + solvents, the order of the data from high to low is acetone > acetonitrile > ethyl acetate > toluene > methanol > ethanol > n-propanol > isopropanol > cyclohexane. The modified Apelblat equation, λh equation, Wilson model, and nonrandom two-liquid model were employed to correlate the measured solubility data of 1-(3-nitrophenyl)ethanone and 1-(4-nitrophenyl)ethanone in the selected solvents. Results showed that the largest values of relative average deviation and root-mean-square deviation obtained with the four models were no greater than 2.78% and 7.59 × 10 −3 , respectively. The modified Apelblat equation provided better results than the other three models. Furthermore, the mixing properties, including Gibbs energy, mixing enthalpy, mixing entropy, activity coefficient at infinitesimal concentration (γ 1 ∞ ), and reduced excess enthalpy (H 1 E,∞ ) were computed. The mixing processes of 1-(3-nitrophenyl)ethanone and 1-(4-nitrophenyl)ethenone in the studied solvents are all spontaneous and endothermic. The obtained solubility and thermodynamic studies are very helpful for optimizing the purification process of 1-(3-nitrophenyl)ethanone and 1-(4-nitrophenyl)ethenone.

STK16, a serine/threonine protein kinase, is ubiquitously expressed and is conserved among all eukaryotes. STK16 has been implicated to function in a variety of cellular processes such as VEGF and cargo secretion, but the pathways through which these effects are mediated remain to be elucidated. Through screening of our focused library of kinase inhibitors, we discovered a highly selective ATP competitive inhibitor, STK16-IN-1, which exhibits potent inhibitory activity against STK16 kinase (IC50: 0.295 μM) with excellent selectivity across the kinome as assessed using the KinomeScan profiling assay (S score (1) = 0.0). In MCF-7 cells, treatment with STK16-IN-1 results in a reduction in cell number and accumulation of binucleated cells, which can be recapitulated by RNAi knockdown of STK16. Co-treatment of STK16-IN-1 with chemotherapeutics such as cisplatin, doxorubicin, colchicine, and paclitaxel results in a slight potentiation of the antiproliferative effects of the chemotherapeutics. STK16-IN-1 provides a useful tool compound for further elucidating the biological functions of STK16.

The first example of diastereo- and enantioselective aza-MBH-type reaction was accomplished by the asymmetric synthesis of beta-nitro-gamma-enamines via a (1R,2R)-diaminocyclohexane thiourea derivative mediated tandem Michael addition and aza-Henry reaction in good yields (up to 95%) and high enantioselectivities (up to 91% ee) and diastereoselectivities (up to 1:99 dr).

A series of benzimidazole phenylhydrazone derivatives (6a-6ai) were synthesized and characterized by 1 H-NMR, ESI-MS, and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction as (E)-configuration. All the compounds were screened for antifungal activity against Rhizoctonia solani and Magnaporthe oryzae employing a mycelium growth rate method. Compound 6f exhibited significant inhibitory activity against R. solani and M. oryzae with the EC 50 values of 1.20 and 1.85 µg/mL, respectively. In vivo testing demonstrated that 6f could effectively control the development of rice sheath blight (RSB) and rice blast (RB) caused by the above two phytopathogens. This work indicated that the compound 6f with a benzimidazole phenylhydrazone scaffold could be considered as a leading structure for the development of novel fungicides.