氟西汀总活性成分在抑郁患者中的群体药动学研究

目的建立抑郁患者氟西汀(fluoxetine,FLX)总活性成分(total active moiety,TAM)的群体药动学(PPK)模型并研究其影响因素,为个体化用药提供参考。方法回顾性收集2020年1月-2023年12月深圳市康宁医院154例服用FLX治疗住院患者的用药情况、FLX和去甲氟西汀(norfluoxetine,NFLX)血药浓度、肝肾功能水平、血脂水平及细胞色素P4502D6酶(CYP2D6)基因型等临床资料,计算FLX和NFLX浓度之和为血浆TAM浓度,采用非线性混合效应模型法(NONMEM)建立TAM浓度PPK模型,采用拟合优度图(GOF)、正态化预测分布误差法(NPDE)和自举法(Bootstrap)对模型的稳定性和预测性能进行评估。基于最终模型的显著协变量,模拟不同人群不同剂量TAM浓度的变化情况,拟合达稳态时间并推荐给药剂量。结果154例住院患者570个血药浓度数据包括FLX(n=285)和NFLX(n=285),建立了TAM的一阶吸收和消除的一房室模型,体重(WT)是影响表观清除率(CL/F)的显著协变量,最终模型参数CL/F、表观分布容积(V/F)和吸收速率常数(Ka)的群体典型值分别为2.91 L/h、734 L和0.3 h^(-1),模型表示为:CL/F(L·h^(-1))=2.91×(WT/55)0.531,V/F(L)=734,Ka(h^(-1))=0.3(固定值)。蒙特卡洛模拟结果显示,TAM浓度达稳态时间为6~11周,给药剂量相同,体重越轻达稳时间越长,体重小于70 kg的患者,最佳给药方案为10~30 mg,大于70 kg为20~40 mg。结论成功建立了服用FLX治疗的抑郁患者TAM浓度的PPK模型,最终模型稳定可靠,低体重人群应选择较低剂量的FLX,避免药物蓄积产生不良反应。

Tuning Structural and Electronic Configuration of FeN_(4) via External S for Enhanced Oxygen Reduction Reaction

The Fe-N-C material represents an attractive oxygen reduction reaction electrocatalyst,and the FeN_(4)moiety has been identified as a very competitive catalytic active site.Fine tuning of the coordination structure of FeN_(4)has an essential impact on the catalytic performance.Herein,we construct a sulfur-modified Fe-N-C catalyst with controllable local coordination environment,where the Fe is coordinated with four in-plane N and an axial external S.The external S atom affects not only the electron distribution but also the spin state of Fe in the FeN_(4)active site.The appearance of higher valence states and spin states for Fe demonstrates the increase in unpaired electrons.With the above characteristics,the adsorption and desorption of the reactants at FeN_(4)active sites are optimized,thus promoting the oxygen reduction reaction activity.This work explores the key point in electronic configuration and coordination environment tuning of FeN_(4)through S doping and provides new insight into the construction of M-N-C-based oxygen reduction reaction catalysts.

以苯硼酸为载体的前药及其类似物的研究进展

ROS是机体重要的信号分子,对机体的代谢过程中起着重要的作用。研究发现,在癌症、炎症和神经退行性疾病等疾病组织出现了ROS异常升高的现象。这一现象为治疗以上相关疾病提供了靶点,ROS型敏感型前药应运而生,近年来将苯硼酸基团作为载体引入原药中设计ROS敏感型前药成为基于ROS开发新药的有效途径。本文作者对近年来开发出含苯硼酸结构的前药的设计思路及药效进行综述,所涉及的药物包括传统的化疗药物,生物小分子以及光动力疗法的光敏剂。以上药物均有良好的疗效,但此类前药也面临一些问题。本文作者探讨了这类前药连接臂的选择、合成方法以及释放效果等相关问题。希望为设计更好更合理含苯硼酸结构的前药和提出新的思路。

城市景观湖溶解性有机物特征及臭氧去除效能:以金海湖为例

分析城市景观湖溶解性有机物(DOM)的特征和可处理特性,有助于提高城市水环境质量,提出合理的有机污染控制策略。文章以金海湖水样为研究对象,通过紫外光谱、三维荧光光谱、液相色谱技术等分析方法探究其DOM特点,发现DOM具有强自生源、较低腐殖化程度、偏小有机物分子量的特征。随后对金海湖水样进行臭氧氧化处理,60 min后溶解性有机碳(DOC)、COD_(Mn)、UV_(254)、荧光强度(FI)、供电子官能团(EDM)的平均去除率分别为5.8%、13.1%、60.1%、70.0%、18.2%。结果表明,臭氧可以高效降解多种有机污染物,对金海湖DOM的紫外生色团、荧光团及大分子组分供电子官能团均有较强的去除能力,但对有机物的矿化能力和对小分子组分供电子官能团的去除能力较弱。臭氧通过将大分子有机物分解成小分子有机物,而非直接矿化,来实现对DOM的降解。

Synthesis of New Schiff Bases Containing Thiophene Moiety

Seven new Schiff bases, which are 4,4,4-trifluo-ro-1-(2-thienyl)-1-butanone-3-Z, Z =-thioseraicarbazone (a); -thiocarbohydrazone (b),-benzoic hydrazone (c), -( o-hydroxyphenyl) imine (d) ,-nicotinic hydrazone (e),-salicylic hydrazone (f), and -(p-fluoro-m-chlorophenyl) imine (g), have been synthesized by reaction of 4, 4, 4-trifluoro-1-(2-thienyl)-1,3-butanedione (TFTBD) with corresponding hy-drazides or anilines, acetic acid or p-toluence sulfonic acid as catalyst, and characterized by Elemental analysis, IR, UV-Vis,1H NMR and MS. The MS spectra confirmed that the -C3=O condensed with primary amino group. Tauto-merism of the compounds is discussed.

Polyimide-silver nanocomposite containing phosphine oxide moieties in the main chain:Synthesis and properties

New flame-retardant polyimide-silver nanocomposite containing phosphine oxide moiety in the main chain was synthesized by a convenient ultraviolet irradiation technique.A precursor such as AgNO_3 was used as the source of the silver particles.Polyimide 6 as a source of polymer was synthesized by polycondensation reaction of bis（3-aminophenyl） phenyl phosphine oxide 4 with pyromellitic anhydride 5 in the presence of iso-quinoline as base and in m-cresol solution.The resulting composite film was characterized by FTIR spectroscopy,X-ray diffraction（XRD）,transmission electron microscopy（TEM）,thermogravimetry（TGA） and differential scanning calorimetry（DSC）.The average size of the nanometer Ag particles is about 10 nm.The temperature of 5 and 10%weight loss and also the char yield at 600℃of polyimide-silver nanocomposite 6a were higher than the pure PI 6.

Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients

BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.

Ion shielding functional separator using halloysite containing a negative functional moiety for stability improvement of Li–S batteries

Lithium–sulfur batteries are one of the attractive next-generation energy storage systems owing to theienvironmental friendliness,low cost,and high specific energy densities.However,the low electrical conductivity of sulfur,shuttling of soluble intermediate polysulfides between electrodes,and low capacitretention have hampered their commercial use.To address these issues,we use a halloysitemodulated(H-M)separator in a lithium–sulfur battery to mitigate the shuttling problem.The H-M separator acts as a mutual Coulombic repulsion in lithium-sulfur batteries,thereby selectively permitting Lions and efficiently suppressing the transfer of undesired lithium polysulfides to the Li anode sideMoreover,the use of halloysite switches the surface of the separator from hydrophobic to hydrophilicconsequently improving the electrolyte wettability and adhesion between the separator and cathodeWhen sulfur-multi-walled carbon nanotube(S-MWCNT)composites are used as cathode active materialsa lithium–sulfur battery with an H-M separator exhibits first discharge and charge capacities of 1587 an1527 m Ah g-1,respectively.Moreover,there is a consistent capacity retention up to 100 cyclesAccordingly,our approach demonstrates an economical and easily accessible strategy for commercialization of lithium–sulfur batteries.

SYNTHESIS AND CHARACTERIZATION OF NOVEL MULTIFUNCTIONAL HOST COMPOUNDS.1.β-CYCLODEXTRIN DERIVATIVE BEARING DIETHANOLAMINE MOIETY

A novel β-cyclodextrin(β-CD)derivative bearing diethanolamine moiety was synthesized by a convenient method with 63% yield,and the new host compound was characterized by (13)~C-NMR,FT-IR spectra etc,

SUPPRESSION OF CELL ADHESION ON POLYACRYLONITRILE-BASED MEMBRANES BY THE ANCHORING OF PHOSPHOLIPID MOIETIES

In this work, the membrane surface of poly（acrylonitrile-co-2-hydroxyethyl methacrylate） （PANCHEMA） was chemically modified by anchoring of phospholipid moieties. The process involved the reaction of hydroxyl groups on the membrane surface with 2-chloro-2-oxo-1,3,2-dioxaphospholane （COP） followed by the ring-opening reaction of COP with trimethylamine. Chemical differences between the original and the modified membranes were characterized by FT-IR and XPS, It was found that the amount of macrophage adhered on the modified membrane surface is substantially lower than that on polyacrylonitrile （PAN） and PANCHEMA membranes under the same condition, The morphological change of the adherent cell is also suppressed by the generation ofphospholipid moieties on the membrane surface.

IMMOBILIZATION OF POTENTIALLY BIOACTIVE MOIETIES ONTO POLYETHER WITH POLY(ETHYLENE GLYCOL)-SULFONATE SPACER

A new reactive graft copolymer, poly(tetramethylene glycol)-graft-omega-propyl sodium sulfonate-poly(ethylene glycol) (PTMG-g-PEG-CH2CH2CH2SO3-Na+), was synthesized by the cationic polymerization of alpha-omega-bifunctional PEG macromonomer ((sic)CH2-PEG-CH2CH2CH2SO3Na) and THF. The obtained copolymer exhibits the expected structure as indicated by the result of characterization. Two amino acids (L-arginine, L-tyrosine) were covalently attached to the copolymer after converting the sulfonate group, to sulfonyl chloride. So the new reactive graft copolymer (PTMG-g-PEG-CH2CH2CH2SO3-Na+) is expected to be very useful in attachment of potentially bioactive moieties to polymer via a hydrophilic PEG spacer.

Synthesis and characterization of novel poly(aryl ether)s containing naphthyl moieties

Two poly（aryl ether）s containing naphthyl moieties were prepared from bis（3,5-dimethyl-4-hydroxyphenyl）naphthyl methane （monomer 1） via nucleophilic aromatic substitution polycondensation with bis（4-fluorophenyl） ketone and bis（4-fluorophenyl） sulfone. The structures of these polymers were confirmed by 1H NMR. The Mn values of the two polymers were 96,200 and 88,600, respectively. The polymers exhibited good thermal stabilities with 5% mass loss at T 〉 400 and high glass-transition temperature （Ts） of T 〉 250 ℃. Moreover, the resultant polymers were amorphous determined by wide angle X-ray diffraction （WAXD）. ？2009 Lei Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All fights reserved.

STUDIES ON STEROIDAL PLANT GROWTH REGULATOR 24. STEREOCONTROLLED CONSTRUCTION OF THE SIDE CHAIN OF BRASSINOLIDE AND HOMOBRASSINOLIDE VIA A TANDEM VICINAL DIALKYLATION OF PYRANONE MOIETY

A stereocontrolled construction of the side chain of brassinclide and homobrassinolide has been achieved via the tandem vicinal dialkylation of the pyranone moiety as a key step.

Synthetic Approach for Novel Fluorine Substituted <i>α</i>-Aminophosphonic Acids Containing 1,2,4-Triazin-5-One Moiety as Antioxidant Agents

Novel fluorine substituted α-amino phosphonic acids containing 1,2,4-triazin- 5-one (6a-f) have been obtained from fluoroacylation of 6-(2&prime;-amino-5&prime;-nitrophenyl)-3-thioxo-1,2,4-triazin-5(4H)-one (1) followed by ammonilysis to give the corresponding 3-amino-derivative 3. Condensation of compound 3 with nitro/halogenated aromatic aldehydes yielded the Schiff bases 4. The simple addition of diethyl phosphonate to compound 4 produced the α-amino phosphonates 5. Acidic hydrolysis of compound 5 produced the fluorine substituted α-amino acids derivatives 6. Structures of the new compounds have been established with the help of elemental analysis and spectral measurements. Also, the products evaluated as antioxidants, where the fluorinated α-amino phosphonic acids 6 are more active than the other synthesized systems.

Synthesis and Characterization of a New Bifunctional Dye Containing Spirobenzopyran and Cinnamoyl Moiety

A novel bifunctional dye containing spirobenzopyran and cinnamoyl moiety has been prepared and its photochromic behavior following irradiation at different wavelengths of monochrome UV light was investigated. The colourless bifunctional dye in film or solution exhibits unusual photochromism through structural and geometrical transformation from spirobenzopyran to merocyanine accompanying with photocrosslinking reaction in cinnamoyl moieties. Two kinds of photochemical reaction were achieved by irradiation at the different wavelengths of monochrome UV light (275 nm, 365 nm) selectively. The photochromic process of the bifunctional dye was discussed and the dynamic behaviors of the decolorization process were investigated.

The origin and biosynthesis of the naphthalenoid moiety of juglone in black walnut

Several members of the Juglandaceae family produce juglone,a specialized 1,4-naphthoquinone(1,4-NQ)natural product that is responsible for the notorious allelopathic effects of black walnut(Juglans nigra).Despite its documented ecological roles and potential for being developed as a novel natural product-based herbicide,none of the genes involved in synthesizing juglone have been identified.Based on classical labeling studies,we hypothesized that biosynthesis of juglone’s naphthalenoid moiety is shared with biochemical steps of the phylloquinone pathway.Here,using comparative transcriptomics in combination with targeted metabolic profiling of 1,4-NQs in various black walnut organs,we provide evidence that phylloquinone pathway genes involved in 1,4-dihydroxynaphthoic acid(DHNA)formation are expressed in roots for synthesis of a compound other than phylloquinone.Feeding experiments using axenic black walnut root cultures revealed that stable isotopically labeled L-glutamate incorporates into juglone resulting in the same mass shift as that expected for labeling of the quinone ring in phylloquinone.Taken together,these results indicate that in planta,an intermediate from the phylloquinone pathway provides the naphthalenoid moiety of juglone.Moreover,this work shows that juglone can be de novo synthesized in roots without the contribution of immediate precursors translocated from aerial tissues.The present study illuminates all genes involved in synthesizing the juglone naphthoquinone ring and provides RNA-sequencing datasets that can be used with functional screening studies to elucidate the remaining juglone pathway genes.Translation of the generated knowledge is expected to inform future metabolic engineering strategies for harnessing juglone as a novel natural product-based herbicide.

A NEW SYNTHETIC APPROACH TO PHOSPHONOPEPTIDE WITH PHOSPHONAMIDE MOIETY

A novel tricomponental condensation leading to p-nitrophenyl- ethyl hydrogen substituted benzylphosphonates was described.The use of these compounds for the synthesis of phosphonopeptide with phosphonamide moiety was demonstrated.

SYNTHESIS OF FUNCTIONALIZED CALIX[4]ARENE BEARING [M]DAZOLE MOIETY TO SERVE AS CATALYTIC FUNCTION

Synthesis of catix[4]arene with one imidazolyl group on the upper rim is presented.

SYNTHESIS AND CHARACTERIZATION OF HETEROAROMATIC POLYMERS CONTAINING PYRIDINE MOIETIES

The progress on the molecular design, synthesis and characterizations of some kinds of pyridine-containing heteroaromatic polymers in main chain were reviewed in this paper, they would include polyimides （Pls）, polypyrrolones （PPYs）, poly（pyrrolane-imide）s （PPIs）, and poly（pyrrolane-benzimidazone）s （PPBs） containing pyridine moieties. The pyridine-cantaining polymers reported all exhibit good processability, excellent thermal properties and mechanical properties. However, the contribution of pyridine ring to polymers properties is still need to research further, the heteroaromatic polymers containing pyridine moieties have focused by more and more researchers.