First Organic–Inorganic Hybrid Compounds Formed by Ge-V-O Clusters and Transition Metal Complexes of Aromatic Organic Ligands

Three compounds based on Ge-V-O clusters were hydrothermally synthesized and characterized by IR, UV-Vis, XRD, ESR, elemental analysis and X-ray crystal structural analysis. Both [Cd(phen)(en)]₂[Cd₂(phen)₂V₁₂O₄₀Ge₈(OH)₈(H₂O)]∙12.5H₂O (1) and [Cd(DETA)]₂[Cd(DETA)₂]_0.5[Cd₂(phen)₂V₁₂O₄₁Ge₈(OH)₇(0.5H₂O)]∙7.5H₂O (2) (1,10-phen = 1,10-phenanthroline, en = ethylenediamine, DETA = diethylenetriamine) are the first Ge-V-O cluster compounds containing aromatic organic ligands. Compound 1 is the first dimer of Ge-V-O clusters, which is linked by a double bridge of two [Cd(phen)(en)]²⁺. Compound 2 exhibits an unprecedented 1-D chain structure formed by Ge-V-O clusters and [Cd₂(DETA)₂]⁴⁺ transition metal complexes (TMCs). [Cd(en)₃]{[Cd(η₂-en)₂]₃[Cd(η₂-en)(η₂-μ₂-en)(η₂-en)Cd][Ge₆V₁₅O₄₈(H₂O)]}∙5.5H₂O (3) is a novel 3-D structure which is constructed from [Ge₆V₁₅O₄₈(H₂O)]¹²⁻ and four different types of TMCs. We also synthesized [Zn₂(enMe)₃][Zn(enMe)]₂[Zn(enMe)₂(H₂O)]₂[Ge₆V₁₅O₄₈(H₂O)]∙3H₂O (4) and [Cd(en)₂]₂{H₈[Cd(en)]₂Ge₈V₁₂O₄₈(H₂O)}∙6H₂O (5) (enMe = 1,2-propanediamine), which have been reported previously. In addition, the catalytic properties of these five compounds for styrene epoxidation have been assessed.     

荧光光谱法研究奥美拉唑和埃索美拉唑与牛血清白蛋白的相互作用

首次应用荧光光谱法研究外消旋体奥美拉唑和其中的一个单体S-奥美拉唑(埃索美拉唑)分别与牛血清白蛋白(BSA)的相互作用机制的异同.利用荧光猝灭反应求出了在pH7.4、pH8.0、pH9.0这三种环境中两个药物结合常数KA和结合位点数n,进一步根据热力学参数判断出它们的主要作用力类型.发现两个药物引起的BSA内源荧光的猝灭均是由静态猝灭引起的.在相同情况下埃索美拉唑对BSA的结合能力强于奥美拉唑,结合位点数部是1.两种药物分子与BSA之间的作用力类型主要为疏水作用力和静电作用力.可以得出结论:两个药物除了结合常数的差异外并无不同.     

原子吸收光谱法测定TG6钛合金中痕量镍不确定度的分析

通过对原子吸收光谱法测定TG6钛合金中痕量镍的不确定度的系统分析,阐述了测量结果不确定度主要来源于测量试液中镍的浓度、试液定容体积及样品质量产生的不确定度,并对这些分量进行了量化计算,最后计算出合成标准不确定度和扩展不确定度.同时通过评估,得出影响镍含量测定不确定度的主要因素是测量试液中镍浓度引起的不确定度.     

A Docosahexaenoic Acid Derivative (N-Benzyl Docosahexaenamide) as a Potential Therapeutic Candidate for Treatment of Ovarian Injury in the Mouse Model

Commonly used clinical chemotherapy drugs, such as cyclophosphamide (CTX), may cause injury to the ovaries. Hormone therapies can reduce the ovarian injury risk; however, they do not achieve the desired effect and have obvious side effects. Therefore, it is necessary to find a potential therapeutic candidate for ovarian injury after chemotherapy. N-Benzyl docosahexaenamide (NB-DHA) is a docosahexaenoic acid derivative. It was recently identified as the specific macamide with a high degree of unsaturation in maca (Lepidium meyenii). In this study, the purified NB-DHA was administered intragastrically to the mice with CTX-induced ovarian injury at three dose levels. Blood and tissue samples were collected to assess the regulation of NB-DHA on ovarian function. The results indicated that NB-DHA was effective in improving the disorder of estrous cycle, and the CTX+NB-H group can be recovered to normal levels. NB-DHA also significantly increased the number of primordial follicles, especially in the CTX+NB-M and CTX+NB-H groups. Follicle-stimulating hormone and luteinizing hormone levels in all treatment groups and estradiol levels in the CTX+NB-H group returned to normal. mRNA expression of ovarian development-related genes was positive regulated. The proportion of granulosa cell apoptosis decreased significantly, especially in the CTX+NB-H group. The expression of anti-Müllerian hormone and follicle-stimulating hormone receptor significantly increased in ovarian tissues after NB-DHA treatment. NB-DHA may be a promising agent for treating ovarian injury.     

Computational Insight into Biotransformation Profiles of Organophosphorus Flame Retardants to Their Diester Metabolites by Cytochrome P450

Biotransformation of organophosphorus flame retardants (OPFRs) mediated by cytochrome P450 enzymes (CYPs) has a potential correlation with their toxicological effects on humans. In this work, we employed five typical OPFRs including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri(2-chloroethyl) phosphate (TCEP), triethyl phosphate (TEP), and 2-ethylhexyl diphenyl phosphate (EHDPHP), and performed density functional theory (DFT) calculations to clarify the CYP-catalyzed biotransformation of five OPFRs to their diester metabolites. The DFT results show that the reaction mechanism consists of Cα-hydroxylation and O-dealkylation steps, and the biotransformation activities of five OPFRs may follow the order of TCEP ≈ TEP ≈ EHDPHP > TCIPP > TDCIPP. We further performed molecular dynamics (MD) simulations to unravel the binding interactions of five OPFRs in the CYP3A4 isoform. Binding mode analyses demonstrate that CYP3A4-mediated metabolism of TDCIPP, TCIPP, TCEP, and TEP can produce the diester metabolites, while EHDPHP metabolism may generate para-hydroxyEHDPHP as the primary metabolite. Moreover, the EHDPHP and TDCIPP have higher binding potential to CYP3A4 than TCIPP, TCEP, and TEP. This work reports the biotransformation profiles and binding features of five OPFRs in CYP, which can provide meaningful clues for the further studies of the metabolic fates of OPFRs and toxicological effects associated with the relevant metabolites.     

Bioavailability Enhancement of Cepharanthine via Pulmonary Administration in Rats and Its Therapeutic Potential for Pulmonary Fibrosis Associated with COVID-19 Infection

Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-β1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.     

Non-Invasive Detection of Anti-Inflammatory Bioactivity and Key Chemical Indicators of the Commercial Lanqin Oral Solution by Near Infrared Spectroscopy

Quality control methods of current traditional Chinese medicine (TCM) preparation is time-consuming and difficult to assess in terms of overall efficiency of the drug. A non-destructive rapid near-infrared spectroscopy detection system for key chemical components and biological activity of Lanqin oral solution (LOS), one of the best-selling TCM formulations, was established for comprehensive quality evaluation. Near infrared spectral scanning was carried out on 101 batches of commercial LOS under the penetrated vial state and traditional state. RAW 264.7 cells were cultured to detect the anti-inflammatory ability of LOS, and the reference concentrations of epigoitrin, geniposide, and baicalin were obtained by HPLC. The quantitative models were optimized by three kinds of variable selection methods. The correlation coefficients of prediction value of the models were greater than 0.94. The system also passed the external validation. The performance of the non-invasive models was similar to the traditional models. The established non-destructive system can be applied to the rapid quality inspection of LOS to avoid unqualified drugs from entering the market and ensure drug effectiveness. The biological activity index of LOS was introduced and predicted by NIRs for the first time, which provides a new idea about the quality control of TCM formulations.     

Effects of Organic Acids on the Release of Fruity Esters in Water: An Insight at the Molecular Level

It is well known that organic acids (OAs) could affect the flavour of fruit juices and beverages. However, the molecular mechanism of aroma release is still unclear. In this study, the effects of citric acid (CA), L-(-)-malic acid (MA) and L-lactic acid (LA) on the release of six selected esters and their sensory perception were investigated by means of HS-GC-MS analyses and odour detection threshold determination, respectively. Meanwhile, the density functional theory (DFT) calculation was employed to explore the interaction modes between esters and OAs. HS-GC-MS analyses showed that the concentration and the type of OAs regulated the release of esters. The results were basically consistent with the detection threshold change of those esters. The DFT calculation suggested that the main intermolecular interaction was hydrogen bonds, and several esters could form a ternary ring structure with OAs through hydrogen bonds. The interactions can induce the different release behaviours of esters in OAs water solution. The number of carboxyl functional groups in OAs and the spatial conformation of esters appeared to influence the magnitude of the interaction. The above results demonstrated the mechanism of OAs affecting the release of esters and indicated a possible flavour control way by using different OAs and OA concentrations.     

Estimation of biophysical properties of cell exposed to electric field

Excitable media,such as cells,can be polarized and magnetized in the presence of an external electromagnetic field.In fact,distinct geometric deformation can be induced by the external electromagnetic field,and also the capacitance of the membrane of cell can be changed to pump the field energy.Furthermore,the distribution of ion concentration inside and outside the cell can also be greatly adjusted.Based on the theory of bio-electromagnetism,the distribution of field energy and intracellular and extracellular ion concentrations in a single shell cell can be estimated in the case with or without external electric field.Also,the dependence of shape of cell on the applied electronic field is calculated.From the viewpoint of physics,the involvement of external electric field will change the gradient distribution of field energy blocked by the membrane.And the intracellular and extracellular ion concentration show a certain difference in generating timevarying membrane potential in the presence of electric field.When a constant electric field is applied to the cell,distinct geometric deformation is induced,and the cell triggers a transition from prolate to spherical and then to oblate ellipsoid shape.It is found that the critical frequency in the applied electric field for triggering the distinct transition from prolate to oblate ellipsoid shape obtains smaller value when larger dielectric constant of the cell membrane and intracellular medium,and smaller conductivity for the intracellular medium are used.Furthermore,the effect of cell deformation is estimated by analyzing the capacitance per unit area,the density of field energy,and the change of ion concentration on one side of cell membrane.The intensity of external applied electric field is further increased to detect the change of ion concentration.And the biophysical effect in the cell is discussed.So the deformation effect of cells in electric field should be considered when regulating and preventing harm to normal neural activities occurs in a nervous system.