Effect of Immunosuppressants Tacrolimus and Mycophenolate Mofetil on the Keratinocyte UVB Response

Nonmelanoma skin cancer, derived from epidermal keratinocytes, is the most common malignancy in organ transplant recipients, causes serious morbidity and mortality, and is strongly associated with solar ultraviolet (UV) exposure. Preventing and treating skin cancer in these individuals has been extraordinarily challenging. Following organ transplantation, the immunosuppressants are used to prevent graft rejection. Until now, immunosuppression has been assumed to be the major factor leading to skin cancer in this setting. However, the mechanism of skin carcinogenesis in organ transplant recipients has not been understood to date; specifically, it remains unknown whether these cancers are immunosuppression‐dependent or ‐independent. In particular, it remains poorly understood what is the mechanistic carcinogenic action of the newer generation of immunosuppressants including tacrolimus and mycophenolate mofetil (MMF). Here, we show that tacrolimus and MMF impairs UVB‐induced DNA damage repair and apoptosis in human epidermal keratinocytes. In addition, tacrolimus inhibits UVB‐induced checkpoint signaling. However, MMF had no effect. Our findings have demonstrated that tacrolimus and MMF compromises proper UVB response in keratinocytes, suggesting an immunosuppression‐independent mechanism in the tumor‐promoting action of these immunosuppressants.     

聚氯乙烯三乙撑四胺负载钯配合物的制备及对Heck反应的催化性能

以聚氯乙烯为原料, 通过胺化反应制得聚氯乙烯三乙撑四胺, 然后用较简单方法得到聚氯乙烯三乙撑四胺负载钯配合物(PVC-TETA-Pd), 利用XPS, TG, DTA和TEM等手段对其进行了表征. 热分析表明PVC-TETA-Pd在室温至250 ℃范围内有很好的热稳定性; TEM分析证实钯在PVC-TETA-Pd中分布比较均匀, 钯颗粒呈球形, 粒径在2～3 nm. PVC-TETA-Pd不需在惰性气体氛围中就能有效地催化丙烯酸、苯乙烯与芳基碘的Heck芳基化反应, 并且在较低的温度(40 ℃)或较少的催化剂用量(0.02%)下, 对Heck反应仍有较好的催化性能. PVC-TETA-Pd便于回收, 且有很好的重复使用性能, 对于碘苯与丙烯酸的反应, 重复使用十二次, 肉桂酸的产率仍达到80.1%.     

PREPARATION AND CHARACTERIZATION OF AFFINITY POLYMER BASIC MICROSPHERES BY SOAP-FREE EMULSION POLYMERIZATION

Poly(styrene-co-glycidyl methacrylate) latex microspheres with uniform size and high-density epoxy groups on the surface were prepared by soap-free emulsion polymerization with batch wise operation mode in the presence of 2.2′- azobis(2-methylpropionamidine) dihydrochloride as an initiator.The kinetics of soap-free emulsion polymerization and the effects of polymerization factors were examined.In addition,the optimum polymerization conditions of poly(styrene-co- glycidyl methacrylate) latex microspheres ...     

Synthesis and comparative spectroscopic analysis of two chenodeoxycholic acid (CDCA) derivatives with closely related 7α-ester moieties

3α-Hydroxyl-7α-(4-pentenoyloxy)-5β-cholanoic acid (5) has been synthesized in four step reactions starting from CDCA. The serendipitous synthesis of methyl 3α-(ethoxycarbonyloxy)-7α-(allyloxycarbonyloxy)-5β-cholanoate (7) has led us to compare the spectroscopic difference of the 7α-(allyloxycarbonyloxy) group versus the 7α-(4-pentenoyloxy) group. The molecular structures of these compounds were confirmed by X-ray crystallography. Methyl 3α-(ethoxycarbonyloxy)-7α-(allyloxycarbonyloxy)-5β-cholanoate was obtained by a method, which may prove useful in the synthesis of ¹⁴C-labeled derivatives for metabolic studies.     

Oxovanadium(IV) based hypocrellin B complexes with enhanced photodynamic activity

Hypocrellin B (HB), a naturally occurring photosensitizer, has been extensively and intensively studied as a promising photodynamic therapy (PDT) agent. In this work, three new oxovanadium(IV) complexes were designed and synthesized with HB as a bridging ligand and phen (1,10-phenanthroline, complex 1), tmp (3,4,7,8-tetramethyl-1,10-phenanthroline, complex 2) and dpq (dipyrido[3,2-f:2'3'-h]quinoxaline, complex 3) as terminal ligands. The use of a diimine terminal ligand avoids the formation of polymeric complexes and ensures the three VO(2+)-HB complexes possess a definite molecular formula and molecular weight to meet the single component requirement for an ideal PDT agent. Compared to HB, the VO(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window, increased binding affinity toward dsDNA, and similar singlet oxygen quantum yield, therefore advanced DNA photocleavage activity. Both the DNA binding constants and photo nuclease activities of the complexes follow the order 2 (tmp) > 3 (dpq) > 1 (phen), demonstrating the importance of the binding affinity to biomolecules, which improves the bioavailability of reactive oxygen species. Our work opens a new avenue for the development of HB-based PDT agents.     

Simultaneous determination of catecholamines and amino acids by micellar electrokinetic chromatography with laser-induced fluorescence detection

A selective and sensitive method was developed for separation and simultaneous determination of catecholamines and amino acids by MEKC with LIF. Interestingly enough, such work has been firstly performed on catecholamines derivatized with 4-chloro-7-nitro-2,1,3-benzoxadiazole and the detailed derivatization mechanism was discussed. After derivatization at 60 degrees C for 20 min, NBD-labeled catecholamines and amino acids were separated in a buffer system containing 10 mM sodium tetraborate-Na2HPO4, 20 mM SDS, and 10% v/v ACN at pH 9.75. SDS micelles were employed to improve the fluorescence intensity of catecholamine derivatives efficiently. Under optimum conditions, two catecholamines and 11 amino acids were separated in a short 13 min analysis time and the RSDs for migration time and peak area were less than 0.60 and 6.50%, respectively. The method was successfully applied for the quantification of catecholamines and amino acids in Portulaca oleracea L., human urine sample, and mixed injection sample.     

Interaction between cucurbit[6]uril and bispyridinecarboxamide

The interaction between cucurbit[6]uril and N,N′-(m-bispyridinecarboxamide)-1,n-alkane (m = 2, 3, 4; n = 4, 6, 8) has been investigated by ¹H-NMR, ESI-MS and single crystal X-ray diffraction method. The results show that cucurbit[6]uril can form pseudorotaxanes with N,N′-(m-bispyridinecarboxamide)-1,6-hexane (m = 2, 3, 4) easily. When the alkyl chain length increases (n = 8), the binding mode is identical, but the binding ability of the host towards guest decreases. In both two cases cucurbit[6]uril shows no selectivity towards positional isomers. However, in the case of n = 4, the binding mode is different, having relations with positional substitution of the guest. Only N,N′-(m-bispyridinecarboxamide)-1,4-butane (m = 2) can form pseudorotaxane with cucurbit[6]uril, while the other two (m = 3, m = 4) form external complex with cucurbit[6]uril. The possible reason for the difference has been discussed.     

Analogy in the adsorption of random copolymers and homopolymers at solid-liquid interface: a Monte Carlo simulation study

The adsorption of random copolymers at solid-liquid interface from a nonselective solvent has been studied by Monte Carlo simulation in a cubic lattice. The polymeric molecules are modeled as self-avoiding linear chains composed of two types of segments A and B. The effects of copolymer composition (A/B ratio), segment-surface interaction, and bulk concentration are examined on the thermodynamic and structural adsorption properties including surface coverage, adsorption amount, adsorption layer thickness, and microscopic density distribution. At a given newly introduced effective adsorption energy, random copolymers are found to behave quantitatively as homopolymers regardless of the copolymer composition and surface affinity. This remarkable analogy provides an efficient way in predicting the adsorption of random copolymers from homopolymers.     

Simple Silole‐Containing Polyfluorene for White Electroluminescence with Simultaneous Blue,Green, and Red Emission

Novel conjugated silole‐containing polyfluorenes, with green‐ and red‐emissive siloles on the backbone of the blue‐emissive polyfluorene are synthesized for white light electroluminescence (EL) from a single polymer with simultaneous red, green, and blue (RGB) emission. The CIE coordinates (0.33, 0.36) of the white light EL spectra are very close to that for pure white light (0.33, 0.33). The EL spectra are also quite stable at different applied voltages or brightness. The relative intensities for the three RGB peaks, at 450, 505, and 574 nm, were 0.94, 1, and 0.97, respectively, which demonstrates a balanced simultaneous RGB emission. A maximum luminous efficiency of 2.03 cd · A⁻¹ for a brightness of 344 cd · m⁻², and a luminous efficiency of 1.86 cd · A⁻¹ for a more practical brightness of 2 703 cd · m⁻², were achieved.

     

A facile two-step etching method to fabricate porous hollow silica particles

We report here the fabrication of hollow silica particles with mesopores larger than 10 nm on their wall via a facile two-step etching method. Different from the conventional template method, the new method uses the silica particles as starting materials, which were synthesized using the well-known Stöber method. In the hollow silica preparation, first, we gently etch the silica particles with a NaOH solution without using template molecules to make them porous. Then, we coat the porous silica particles with poly-dimethyldiallylammonium chloride (PDDA) and treat the PDDA-coated porous silica with an ammonia solution to form the hollow silica nanospheres. In this study, we found that the NaOH dosage and ammonia concentration have significant impact on the morphology of the final products. Adsorption was also studied and results show that the hollow nanospheres can effectively uptake protein-based biomolecules (hemoglobin).