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Self-inhibition has been observed widely in hierarchical biochemical processes but has yet to be demonstrated in pure molecular physical rather than chemical or biological processes. Herein, we report an unprecedented example of self-inhibition during the supramolecular chirality induction, memory, erasure, and inversion processes of pillar[5]arene (P[5]) derivatives. The addition of chiral alanine ethyl ester to bulky substituent-modified P[5]s led to time-dependent chirality induction due to the shift in the equilibrium of the

The isomerization of glucose to fructose provides an important way to expand the utilization of biomass. Herein, an amidoximated polyacrylonitrile (PAO) with an amidoxime functional group was prepared and used as an active heterogeneous catalyst for the isomerization of glucose to fructose. The PAO was characterized by SEM, XPS, and FTIR. The yield of fructose reached 48.9% with a selectivity of 98.6% for a 5 h reaction in aqueous solution at an initial pH of 6.5 and 85 °C. The pH caused a great influence on the conversion of glucose and selectivity of fructose while a little effect on the yield of fructose in the range of pH 5-10. The activation energy of isomerization reaction was evaluated as 79.7 kJ·mol-1. The catalysis mechanism was proposed, and the synergistic effect of oxime and amino groups played an important role in the isomerization of glucose. PAO maintained good catalytic activity after four cycles.

This study focuses on the effective separation of cellulose from bamboo through a two-step process. Several organic alkalies 2-pyrrolidinone, ethylurea, dibutylamine, N-methylformamide and tetramethyl guanidine were used to remove lignin and isolate cellulose from massive bamboo. The results showed that tetramethyl guanidine can effectively remove lignin and hemicellulose while retaining almost all the cellulose in the residual solid. The removal of lignin and hemicellulose achieved 86.0% and 84.0% after heating for 3h at 150°C, respectively. Subsequently, the final remove of lignin and hemicellulose increased to 91.5% and 93.8%, respectively, after a simple alkaline H2O2 bleach treatment. Interestingly, the loss of cellulose was very small after two-step treatments, and 96.9% of the component was still retained. The crystalline increased from 61.3–68.4% in XRD graphs due to the remove of lignin and hemicellulose. The SEM images indicated that the diameter of cellulose bundles decreased from 80–100µm to about 50µm after organic alkali treatment, and then the fiber bundle was completely separated into a single long fiber with a diameter of about 10 µm after H2O2 bleaching. The FT-IR spectra confirmed the high selective removal of lignin and hemicellulose. Two-dimensional 1H-13C NMR (2D HSQC) spectra were analyzed to investigate the lignin structure, and found that only the signals of –OCH3, Cγ-Hγ in β-O-4' (Aγ) and β-β' (Cγ) structures and C5-H5 in guaiacyl (G5) did not disappear after two-step treatment.

A highly active iron (II) complex that catalyzed epoxidation of terminal olefins with hydrogen peroxide was described. The catalytic system displayed excellent catalytic ability for the selective oxidation of terminal olefins to epoxides with high selectivity (up to 97.8%) in CH3CN at 25 °C. The catalytic activity of three similarly structural iron (II) complexes was comparatively studied. The effect of various auxiliary ligands on epoxidation was investigated in detail.

Patients exhibit a wide heterogeneity in their responses to a drug treatment due to variations in the molecular determinants underlying this heterogeneity. Pharmacogenomics approaches can be used to integrate information on drug responsiveness with alterations in molecular entities, often on a genome-wide scale. However, most of the studies involving pharmacogenomics of specific therapeutics are in their early stages and thus are not ready for clinical utilization. Genotyping studies tackle around a candidate gene approach using genes known to be important in the pharmacokinetics and pharmacodynamics of the administered drugs. However, this approach could miss potentially important genes that influence drug sensitivity through unknown mechanisms. The way to get around this limiting approach is sought after. Here, we introduce and propose a novel concept of pharmacogenomics signature (PGx-S) for elucidating holistically the effects of genetic polymorphisms upon individual variations in drug responses in an attempt to boost the pharmacovigilant capacities of drug responses.

The selective oxidation of aromatic olefins 1,2-dimethoxy-4-vinylbenzene (DEVB) and 2-methoxy-4-vinylphenol (MOVP) by H2O2 into 1-(3,4-dime-thoxyphenyl)ethanol (MVA) and 1-(4-hydroxy-3-methoxyphenyl)ethanol (HMOPE) catalyzed by copper(II) complex CuL (L = 6,8,15,17-tetramethyl-7,16-dihydrodibenzo-1,4,8,11-tetraazacyclotetradecine) were achieved in cationic surfactant cetyl trimethylammonium bromide (CTAB), anionic surfactant sodium dodecyl benzene sulfonate (SDBS) and nonionic surfactant Triton X-100 (TX-100) micellar media, respectively. Micelle showed great influence on both reaction rate and selectivity of product. Aromatic olefins could be oxidized into corresponding aromatic ketones in aqueous solution, but into secondary alcohols in micellar media. The combination of TEMPO and CuL/H2O2 resulted in relatively fast reaction rate and S > 96% selectivity of aromatic ketones. The reaction rate constants, k 1, k 2 and k 3 for three oxidation reactions pathways: olefin to ketone, olefin to alcohol and alcohol to ketone were obtained, respectively. The kinetic study indicated that the CuL catalyzed oxidation of olefins by H2O2 to alcohols was a relatively rapid and major reaction and ketone was generated by the direct oxidation of olefins, not by further oxidation of alcohol in micellar media.

The purpose of this paper is to assess the relationship between gene polymorphism in angiogenesis-related genes and radiation responses in nasopharyngeal carcinoma (NPC) patients. The genotypes of 180 NPC patients were analyzed by Sequenom MassARRAY. The response evaluation criteria in solid tumours were used for assessing efficacies, and the criteria of the Radiation Therapy Oncology Group or European Organization for Research & Treatment of Cancer were utilized for evaluating acute toxic reactions in response to radiation. Statistical methods included chi-square test, uni- and multivariate logistic regression analyses. Genotypic carriers of rs1800541 GT were at an elevated risk of developing grade 3+ oral mucositis, and a genetic variant of rs5333 was a predictor for a lower occurring risk of grade 2+ radiation-induced xerostomia. EDN1 rs1800541, rs2071942 and rs5370 variants were associated with a significantly higher risk of severe myelosuppression. SNPs in such angiogenesis-related genes as EDN1 rs1800541, rs2071942 & rs5370 and EDNRA rs5333 may serve as useful biomarkers for predicting the outcomes of NPC patients.

Background COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. Methods A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. Results Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). Conclusions Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. Trial registration Chinese Clinical Trial Registry (chictr.org.cn) identifier: ChiCTR2000030464.

Additional file 1: Supplementary Table S1. The distribution and clinical type of confirmed cases in mainland China.

A series of bimetel organic framework MnxCu1−x-MOF were prepared. The MOFs was characterized and analyzed by powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The catalytic activity of the developed catalyst was tested on various olefins by H2O2 as oxidant. The MOFs catalyst exhibits excellent catalytic activity for the epoxidations of various aromatic and cyclic olefins. Particularly, Mn0.1Cu0.9-MOF can achieve 90.2% conversion of styrene with 94.3% selectivity of styrene oxide at 0 °C after reaction 6 h. The MOF exhibited the catalytic activity of inverse temperature effect on epoxidation of styrene. The introduction of copper component can stabilize H2O2 and inhibit its decomposition to a certain extent. The catalyst can be reused at least five cycles without significant loss in activity towards epoxidation.

Complete or partial inactivity of UGT1A1, the unique enzyme responsible for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We investigated the dynamic expression of UGT1A1, and that of the transcription factors (TFs) involved in its developmental regulation, during human hepatic growth in Han Chinese individuals.Eighty-eight prenatal, pediatric, and adult liver samples were obtained from Han Chinese individuals. Quantitative real-time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc. UGT1A1 protein levels and metabolic activity were determined by western blotting and high-performance liquid chromatography. Direct sequencing was employed to genotype UGT1A1*6 (211G˃A) and UGT1A1*28 (TA6˃TA7) polymorphisms.UGT1A1 expression was minimal in prenatal samples, but significantly elevated during pediatric and adult stages. mRNA and protein levels and metabolic activity were prominently increased (120-, 20-, and 10-fold, respectively) in pediatric and adult livers compared to prenatal samples. Furthermore, expression did not differ appreciably between pediatric and adult periods. Dynamic expression of TFs, including PXR, CAR, HNF1A, HNF4A, and PPARA, was consistent with UGT1A1 levels at each developmental stage. A pronounced correlation between expression of these TFs and that of UGT1A1 (P 0.001) was observed. Moreover, UGT1A1*6 and UGT1A1*28 polymorphisms reduced levels of UGT1A1 by up to 40-60 %.Hepatic expression of transcription factors is associated with developmental regulation of UGT1A1 in the Han Chinese population. Moreover, UGT1A1 polymorphisms are associated with reduced expression of UGT1A1 mRNA and protein, as well as enzyme activity.

An efficient method for selective oxidation of unsaturated hydrocarbons to carbonyl compounds was established by using oxidant [bis(acetoxy)iodo]benene and catalyst ruthenium trichloride (0.1 mol %) in a CH 2 Cl 2 /H 2 O two phase system at 30 °C. Both aromatic and aliphatic olefins could be oxidized via direct carbon carbon bond cleavage to the corresponding aryl or alkyl aldehydes with good selectivity (up to 100%). Further, diketone could be obtained from alkyne in high yields with this method.

A novel functional surfactant N α-dodecyl-l-histidine (NDH) was synthesized and its micelle was used as mimic of β-1,4-endoglucanase to catalyzed the hydrolysis of methyl-β-d-cellobioside (MCB) under relatively low temperatures (80–110 °C). The results showed that the micelle of NDH displayed excellent catalytic activity for the cleavage of β-1,4-glycosidic bond and the formation of l-histidine-5-d-glucopyranosyl. The micelle-catalyzed first-order reaction rate constant k m of degradation of MCB was calculated. The conversion of MCB and selectivity of reducing sugars (glucose and fructose) could reach 58.9 and 87.1 %, respectively, for a reaction time of 10 h at pH 4.0 and 110 °C. In NDH micelle-catalyzed reaction sugar ester was deduced as the chief product. The reaction pathways of MCB hydrolysis were proposed and the activation energy Ea for the hydrolysis was calculated.

A novel zwitterionic catalyst containing imidazole, carboxyl and amino functional groups was synthesized to catalyze the retro-aldol condensation of fructose. The catalyst displayed efficiently catalytic activity for the conversion of fructose to 1,3-dihydroxyacetone (DHA). The yield of DHA and selectivity of DHA achieved 27.9% and 46.5% after reaction 2 h, respectively, at pH 9.5, 85 °C. A possible catalytic mechanism was suggested. The charged functional groups on the catalyst exhibited synergistic effect and played role in electron induction and proton transfer, which leaded to a good selectivity of DHA in the conversion of fructose under mild conditions.

The narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped for CYP3A4 20230T>C (rs2242480), CYP3A4 T>C (rs4646437), CYP3A5*3 6898A>G (rs776746), ABCB1 129T>C (rs3213619); ABCB1 c.1236C>T (rs01128503), ABCB1 c.2677G>T/A (rs2032582) and ABCB1 c.3435C>T (rs1045642) polymorphisms, and the effects of gene-gene and gene-environment interactions on the predictive accuracy of algorithm were evaluated. In wild-type CYP3A4 rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (P < 1 × 10-4 ). In contrast, there was no significant difference in mutant type patients. Similarly, the tacrolimus stable doses in wild-type CYP3A5 rs776746 carriers who had hypertension were higher than those without hypertension (P = 4.10 × 10-3 ). More importantly, dose-predictive algorithms with interaction terms showed higher accuracy and better performance than those without interaction terms. Our finding suggested that wild-type CYP3A4 rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, and CYP3A5 rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension.

Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the "derivation cohort" to develop dose-prediction algorithm, while the remaining 20% constituted the "validation cohort" to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

Eukaryotic translation initiation factor 3 subunit A (eIF3a) plays critical roles in regulating the initiation of protein translation, and eIF3a is highly expressed in lung cancer. In this study, we investigated the association of the positively selected SNPs of eIF3a with the response to and toxicity of platinum-based chemotherapy in Chinese patients with non-small cell lung cancer (NSCLC). SNP data for eIF3a locus were downloaded from HapMap database. For each SNP, haplotype, LD profile and population differentiation were analyzed. The long-range haplotype (LRH) test was employed to identify positively selected SNPs of eIF3a. A total of 325 NSCLC patients were enrolled and genotyped for these SNPs. Five positively selected (rs1409314, rs4752219, rs4752220, rs7091672 and rs10510050) and 5 non-positively selected SNPs (rs10886342, rs11198804, rs2275112, rs10787899 and rs4752269) were identified in the LRH test. However, none of them was correlated with the platinum-based chemotherapy response. In contrast, 4 of the positively selected SNPs (rs1409314, rs4752219, rs4752220 and rs7091672) were significantly correlated with the toxicities tested (neutropenia, anemia, thrombocytopenia, emesis and hepatotoxicity). In addition, rs10510050 was significantly correlated with thrombocytopenia, emesis and hepatotoxicity. None of the 5 non-positively selected SNPs was correlated with the 5 toxicities. The positively selected SNPs of eIF3a are significantly correlated with platinum-based chemotherapy toxicities in Chinese NSCLC patients.

A simple method for oxidative CC bond cleavage of terminal olefins to aldehydes with H2O2 catalyzed by copper(II) complex LCu consisted of copper(II) and macrocyclic ligand 5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradeca-4,7,11,14-tetraene (L) was described. This study indicated that the copper(II) complex displayed excellent catalytic ability for the selective oxidation of terminal olefins to aldehydes with high selectivity (S > 90%) in CH3CN at 30 °C. The possible catalytic reaction mechanism of oxidation of terminal olefins was discussed.

A novel surfactant, 3-(dodecylimino)butan-2-one-oxime (DMBO), was synthesized. The metallomicelle La(DMBO)2 was prepared and used as a mimic of β-glucosidase to catalyze the hydrolysis of cellobiose in weakly alkaline aqueous solution at relative low temperature (80–110 °C). This study indicated that the functional metallomicelle displayed effective catalytic activity for hydrolysis of cellobiose to monosaccharide (glucose, fructose and 1,6-anhydroglucose) and glucosyl-erythrose. The conversion of cellobiose and selectivity of monosaccharide could reach 38.5% and 71.1%, respectively, for a reaction time of 10 h at pH 9.0 and 95 °C. The possible reaction pathways of cellobiose hydrolysis are proposed and the catalysis reaction rate constant kcat and Michaelis constant Km for the cellobiose hydrolysis were calculated. The apparent activation energy (Ea = 84.6 kJ mol−1) of cellobiose to monosaccharide was evaluated.

Human UDP-glucuronosyltransferase 1A1 (UGT1A1) is a unique enzyme involved in bilirubin conjugation. We previously characterized the hepatic expression of transcription factors affecting UGT1A1 expression during development. Accordingly, in this study, we characterized the ontogenetic expression of hepatic UGT1A1 from the perspective of epigenetic regulation. We observed significant histone-3-lysine-4 dimethylation (H3K4me2) enrichment in the adult liver and histone-3-lysine-27 trimethylation (H3K27me3) enrichment in the fetal liver, indicating that dynamic alterations of histone methylation were associated with ontogenetic UGT1A1 expression. We further showed that the transcription factor hepatocyte nuclear factor 1α (HNF1A) affects histone modifications around the UGT1A1 locus. In particular, we demonstrated that by recruiting HNF1A the cofactors mixed-lineage leukemia 1, the transcriptional coactivator p300, and nuclear receptor coactivator 6 aggregate at the UGT1A1 promoter, thereby regulating histone modifications and subsequent UGT1A1 expression. In this study, we proposed new ideas for the developmental regulation of metabolic enzymes via histone modifications, and our findings will potentially contribute to the development of age-specific therapies.

A novel chemically modified chitosan CS-SA-CD with phenol and β-cyclodextrin groups was prepared. The adsorptions of phenol, 2-chlorophenol (2-CP), 4-chlorophenol (4-CP), 2,4-dichlorophenol (DCP) and 2,4,6-trichlorophenol (TCP) on the functional chitosan from aqueous solution were investigated. CS-SA-CD exhibited excellent adsorption ability for chlorophenols especially for DCP and TCP. The maximum adsorption capacities of phenol, 2-CP, 4-CP, DCP and TCP on CS-SA-CD were 59.74, 70.52, 96.43, 315.46 and 375.94 mg/g, respectively. The scanning electron microscope and Brunauer–Emmett–Teller analyses revealed that the introduction of phenol group changed the surface morphology and surface properties of chitosan. The modified chitosan CS-SA-CD possesses larger surface areas (4.72 m2/g), pore volume (7.29 × 10−3 mL/g) and average pore diameter (59.99 A) as compared to those of chitosan 3.27 m2/g, 2.00 × 10−3 mL/g and 15.95 A, respectively. The enhanced adsorption of chlorophenols was also attributed to the interaction of hydrogen bond between Cl atom and OH group. The adsorption of chlorophenols on CS-SA-CD followed the pseudo-second-order kinetic model. Adsorbent could be regenerated easily and the regenerated CS-SA-CD remained 80–91% adsorption efficiency.

Two copper (II) complexes L1Cu and L2Cu (H2L1 = 4,9-dimethyl-2,11-dioxy-5,8-diazacycldode-2,4,8,10-tetraene; H2L2 = diethyl-3,8-dimethyl-4,7-diazadeca-2,8-diene-1,10-dioat) were prepared and displayed good catalytic efficiency for the oxidations of Mandelic acid (MA), 4-hydroxymandelic acid (4-HMA) and 4-methoxymandelic acid (4-MMA) by H2O2 in aqueous solution at 35 °C. The apparent first-order rate constants kobs of oxidations of MA, 4-HMA and 4-MMA were obtained in the range of pH 2.5–4.5. It was great interesting that the complexes LCu displayed excellent catalytic ability for the selective oxidation of Mandelic acids into aromatic aldehydes (S > 98%). The active species generated by reacting copper (II) complexes LCu with H2O2 was characterized by UV–vis, electrospray ionization mass spectrometry (ESI-MS) and cyclic voltammetry (CV). The LCuI- OOH species was suggested as the possible active species. The geometric configurations of LCu and the LCuI- OOH species were calculated with Density Functional Theory (DFT) method. The LCuI- OOH species is stable and possesses relatively high oxidation potential in aqueous solution at ambient temperature. This study also provides a new insight for the degradation of lignin.

A new 2-amino-N-dodecyl-3-(1H-imidazole-4-yl)propanamide (L2) surfactant was synthesized and its metallomicelles made of La(III), Cu(II), Co(II) and Zn(II) complexes were used as hydrolytic metalloenzyme mimics to catalyze the hydrolysis of phosphodiester bis(p-nitrophenyl) phosphate (BNPP) in buffer solution at 35 °C. The effects of long alkyl ligand, metal ions, temperature and pH on the catalytic hydrolysis of phosphodiester were investigated. The ternary complex kinetic model for metallomicellar catalysis was suggested to analyze the experimental data. The kinetic and thermodynamic parameters k ′ N , KM, KT, Km and pKa were obtained. The effect of pH was especially analyzed. The pH-independent rate constant of the reaction catalyzed by metallomicelles LaL2, CuL2, CoL2 and ZnL2 was evaluated as 7.03 × 10−4, 6.51 × 10−5, 4.28 × 10−5 and 1.78 × 10−5 s−1, respectively. The different association manners between metallomicelles and substrate were proposed. A hydroxide ion OH− associated metallomicelle, which was detected by ESI-MS spectral analysis, was suggested as the real active species to catalyze the hydrolysis of phosphodiester. Imidazole group might accelerate the hydrolysis by activating H2O associated the metal into metal-OH−. Effect of microenvironment of micelle on the catalysis hydrolysis of BNPP was also discussed.

To investigate the influence of cytochrome P450 oxidoreductase (POR) polymorphisms (A503V and rs2868177) on warfarin stable dosage (WSD) in Han-Chinese patients with mechanical heart valve replacement (MHVR).Three hundred and seventeen Han-Chinese MHVR patients on stable maintenance dose of warfarin were enrolled. Blood samples were collected for genotyping analyses of VKORC1 -1639GA, CYP2C9 *3, CYP4F2 rs2108622 and POR (A503V and rs2868177). Average WSD of carriers with variant POR genotypes or haplotypes were compared. Association analyses were performed by single and multiple linear regression analysis.The variant allele frequencies of POR polymorphisms (A503V and rs2868177) were 38.8 % and 44.8 %, respectively. D' between POR A503V and rs2868177 was 0.855, r(2) was 0.375, and the frequencies of the four POR haplotypes were 42.3 % for CG, 36.3 % for TA, 18.9 % for CA, and 2.5 % for TG, respectively. There were no significant differences in average WSD among carriers with three variant POR A503V genotypes or among carriers with three variant POR rs2868177 genotypes (both P 0.05). Similarly, there were no significant differences in average WSD among carriers with variant POR haplotypes (all P 0.05). Neither single nor multiple linear regression analyses showed significant effects of POR A503V or POR rs2868177 polymorphisms on WSD.POR polymorphisms (A503V and rs2868177) do not appear to significantly influence WSD in Han-Chinese patients with MHVR.

Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the “derivation cohort” to develop dose-prediction algorithm, while the remaining 20% constituted the “validation cohort” to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67–0.76)] and validation cohorts [0.73 (0.63–0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients.One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clinical indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4*1G, CYP3A5*3C, ABCB1 1236 CT, ABCB1 2677 GT/A, and ABCB1 3435 CT polymorphisms. Whole blood trough concentrations of CsA at time zero (C(0)) were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted C(0) (C(0)/dose) based on several clinical indices.The CYP3A5*3C polymorphism influenced the C(0) and C(0)/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs (CYP3A4*1G, ABCB1 1236 CT, ABCB1 2677 GT/A, and ABCB1 3435 CT). In a univariate analysis using Pearson's correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA C(0)/dose. In the multiple regression model, CYP3A5*3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA C(0)/dose.CYP3A5*3C correlates with the C(0)/dose of CsA on the seventh day after renal transplantation. The allele is a putative indicator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.

The Baeyer-Villiger (B-V) reactions of 3,4-dimethoxy acetophenone (DMOAP), 4-methyl acetophenone (MAP), and acetophenone (AP) with performic acid (PFA) in formic acid (FA) solvent have been studied by density functional theory (DFT) method. The noncatalyzed and the formic acid-catalyzed reaction paths have been calculated at the MPWB1K/6-311++G(d,p)-IEF-PCM// MPWB1K/6-311G(d,p) level of theory. On the basis of the calculations, the attack of peracid to the carbonyl carbon is rate-determining in both the noncatalyzed and acid-catalyzed paths. The selective oxidation of 3,4-dimethoxy acetophenone and 4-methyl acetophenone by performic acid into aromatic esters have been experimentally investigated. The kinetic rate constants were obtained in the temperature range of 303 to 323 K. The selectivity of product was also explained by the NBO electric charge analysis. The calculated activation energy barriers of the B-V reaction of DMOAP and MAP were in good agreement with those of experiment.

Ginkgo biloba extract (GBE) is one of the most widely used herbal medicines in the world. It is often administered in combination with statins to treat diseases, especially some nervous system disorders. We aimed to investigate the influences of GBE on pharmacokinetics and efficacy of atorvastatin, which are currently unclear. Sixteen volunteers received a single oral dose of 40 mg atorvastatin, followed by a wash-out period of at least 5 days. Then the volunteers took 360 mg GBE daily for 14 days, followed by a single dose of 40 mg atorvastatin. Serial blood samples obtained over a period of 48 h after atorvastatin ingestion were subjected to determination of atorvastatin plasma concentrations and markers of cholesterol synthesis (lathosterol) and cholesterol absorption (sitosterol). With GBE administration, AUC₀₋₄₈, AUC(₀-∞) and C(max) of atorvastatin were reduced by 14.27% (p = 0.005), 10.00% (p = 0.03) and 28.93% (p = 0.002), respectively; Vd/F and CL/F of atorvastatin were increased by 31.95% (p = 0.017) and 6.48% (p = 0.044). After 14 days of treatment, GBE has no significant effects on cholesterol-lowering efficacy of atorvastatin. This study suggests that GBE slightly decreases the plasma atorvastatin concentrations, but has no meaningful effect on the cholesterol-lowering efficacy of atorvastatin.

Based on the thermokinetic theory, a novel thermokinetic research method-self-function regression method, which could be used to determine the kinetic parameters kl. k2 and k-1 of the complex reaction: B + , was proposed in this paper. The kinetics of the reaction of ascorbic acid (H2A) with hydrogen peroxide was investigated at pH=5-7 and T=298.15 K, and the kinetic parameters k1 k2 and k-1 were obtained with this method. The kinetics of the reaction was investigated in detail. The kinetic parameters of the oxidation of ascorbic monoanion (HA−) and ascorbic dianion (A2-) with hydrogen peroxide were 3.33×10−3 s−1 and 25.48 s−1 at 298.15 K, respectively. The molar enthalpy change for the reaction was -554.64 kJ · mol−1 in phosphate buffer solution at pH 7 and at 298. 15 K.

The oxidative coupling reaction of 2,6-dimethylphenol (DMP) with H 2 O 2 catalyzed by two copper(II) complexes (2,2′-dipyridylamine copper(II), L 1 Cu and N,N′-bis (2-pyridinecarbonyl) ethylenediamine copper(II), L 2 Cu) in cationic surfactant cetyl trimethylammonium bromide (CTAB), gemini surfactants ethanediyl-1,2-bis(dodecyldimethylammonium bromide) (12-2-12), dimethylene-1,2-bis(cetyltrimethylammonium bromide) (16-2-16), anionic surfactant sodium dodecyl benzene sulfornate (SDBS) and nonionic surfactant Triton X-100 (TX-100) micellar media were comparatively investigated at 25 °C. The kinetics of formation of 3,3′,5,5′-tetramethyl-4,4′-diphenoquinone (DPQ) was studied. The kinetic parameters k 2 and K m were obtained at pH 7.01. L 1 Cu displayed better catalytic activity than L 2 Cu in mentioned above systems. For L 1 Cu catalyzed systems, the cationic surfactant CTAB, 12-2-12 and 16-2-16 micellar media accelerated the oxidation of DMP. And the TX-100 and SDBS micelles showed little effect on reaction rate compared with the buffer solution. For the L 2 Cu catalyzed systems, these surfactants all inhibited the oxidation of DMP, and especially, the oxidation of DMP was not found in SDBS micellar solution in the catalyzed system at pH 7.01 and 25 °C. Micelles showed great influence on the yield of product and the selectivity of PPO. Under this work's conditions, DPQ was easily generated in aqueous solution, while PPO was remarkably promoted in micellar media, especially in SDBS micellar solution. As a green technology process, one outstanding advantage of this catalyzed system was that the products of polymer can be easily separated from the solution and the catalysts still remain in the micellar solution.

A kind of new functional surfactant with substituted long alkyl pyridine was synthesized and its Ce(IV), Zn(II), and Cu(II) complexes were used as hydrolytic metalloenzyme models. The hydrolysis of p-nitrophenyl picolinate (PNPP) catalyzed by the metallomicelles in CTAB micellar solution was investigated at different pH and 30°C. Kinetic parameters of catalytic hydrolysis were obtained by employing the ternary complex kinetic model for metallomicellar catalysis. Effects of the structure of ligands and microenvironment of reaction on the hydrolytic reaction of PNPP have been discussed in detail. From the apparent rate constants (k obsd ) of the catalytic hydrolysis of PNPP, it can be seen that the catalytic effect of complexes of ligand L2 with long hydrocarbon chain was stronger than that of ligand L1, and complex CuL2 showed higher catalytic efficacy on the hydrolytic reaction than those of ZnL2 and CeL2. However, experiment results in this article showed that ZnL2 and CeL2 are more susceptible to enviro...

Three synthetic copper(II) complexes exhibited remarkable catalytic activity for 4-chlorophenol (4-CP) oxidation by H 2 O 2 in neutral and weak alkaline solution at 25 °C. The decomposition of H 2 O 2 catalyzed by copper(II) complexes was investigated. The studies by fluorescence and UV–vis measurements proved that free hydroxyl radical was not the primary reactive species for the oxidation of 4-CP. “Associative radical” LCu I - OOH was suggested as the possible predominant reactive species in this work. The reaction kinetics of 4-CP oxidation catalyzed by copper(II) complexes was studied in detail. The pH effect was explicated by the catalytic kinetics model proposed in this paper. The catalysis involved not only the activation of H 2 O 2 by copper(II) complex to yield more reactive species LCu I - OOH, but also the formation of 4-chlorophenolate anion. A possible catalytic reaction mechanism of 4-CP oxidation was proposed.

Four short- and long-alkyl-multiamine ligands L1–L4 have been synthesized and characterized. The catalytic efficiency of complex CuL1 and functional metallomicelles CuL2–CuL4 were comparatively investigated for the hydrolysis of bis(p-nitrophenyl) phosphate (BNPP) in buffered solution at 30 °C. The ternary kinetic model for metallomicellar catalysis was suggested to analyze the experimental data. The kinetic and thermodynamic parameters k ′ N , KT and pKa were obtained. The results indicated that the complexes with 1:1 ratio of ligands L2–L4 to copper(II) ion were the kinetic active catalysts, and the deprotonized Cu(II) complex formed by activated water molecule was the real active species for BNPP catalytic hydrolysis. The real rate constant of the reaction catalyzed by CuL1–CuL4 was 4.00 × 10−6, 7.44 × 10−5, 1.42 × 10−4 and 4.10 × 10−4 s−1, respectively. The effects of ligand and microenvironment on the hydrolytic reaction of BNPP have been discussed in detail.

Dinuclear copper(II) and cobalt(II) complexes were prepared and investigated with respect to their effects on hydrolysis of bis(4-nitrophenyl) phosphate (BNPP). The kinetic data indicated that the mono-deprotonated oxime group could act as an effective intramolecular nucleophile in the reaction. The higher reactivity of dinuclear copper(II) complex than that of its mononuclear analogues illustrated the probability of double Lewis acid activation by two metal centers in the former complex.

CYP3A4 and CYP3A7 are generally served as the major adult and fetal liver forms, respectively, and exhibited a developmental switch during liver maturation. The objective of this study was to explore the potential mechanisms associated with the developmental switch of CYP3A4 and CYP3A7 in the Chinese Han population. We analyzed CYP3A4/7, nuclear receptors, and epigenetic modifications in human liver samples. We found that the expression levels of CYP3A4 mRNA in adults were significantly higher than the levels in fetus. In contrast, CYP3A7 mRNA expression reached a maximal level at an estimated gestational age of 25 weeks and then substantially decreased during the first year after birth. We also found that the expression level of hepatocyte nuclear factor 4 alpha (HNF4A) was most associated with CYP3A4 expression in adult liver; whereas the expression level of glucocorticoid receptor (GR) was intensively correlated with CYP3A7 expression in fetal liver. Furthermore, we illustrated the dynamic changes of H3K4me2 and H3K27me3 in the developmental switch of CYP3A7 and CYP3A4. In summary, our data suggested that HNF4A and GR, and epigenetic changes of H3K4me2 and H3K27me3 are associated with the ontogenic expressions of CYP3A4/3A7 in the livers of the Chinese Han population.

Terminal olefins are selectively converted into aldehydes with hydrogen peroxide using a copper complex as an highly active catalyst.

Two transitional metal ion macrocyclic Schiff base complexes, NiL and CuL were synthesized and characterized, and the metallomicelles made up of the nickel(II) and copper(II) complexes and surfactants(LSS, Brij35, CTAB), as mimic hydrolytic metalloenzyme, were used in catalytic hydrolysis of carboxylic ester (PNPP). The analysis of specific absorption spectrums of the hydrolytic reaction systems indicates that key intermediates, made up of PNPP and Ni(II) or Cu(II) complexes, have formed in the reaction processes of the PNPP catalytic hydrolysis. In this, based on the analytic result of specific absorption spectrum, the mechanism of PNPP catalytic hydrolysis has been proposed; a kinetic mathematical model, applied to the calculation of the kinetic parameter of PNPP catalytic hydrolysis has been established on the foundation of the mechanism proposed; the acid effect of reaction system, structure effect of the complexes, effect of temperature and effects of micelle on the rate of PNPP hydrolysis catalyzed ...

Three novel Schiff base cobalt(II) complexes containing benzoaza-15-crown-5, CoL1, CoL2 and CoL3 were synthesized and characterized, and these complexes were used in catalytic hydrolysis of carboxylic ester (PNPP, p-nitrophenyl picolinate) as mimic hydrolytic metalloenzyme. The analysis of specific absorption spectra of the hydrolytic reaction systems indicated that the catalytic hydrolysis involved the key intermediates formed by PNPP with cobalt(II) complexes. The CoL3 bearing the electron withdrawing group shows better catalytic activity due to its stabilization effect on active species MLS−. The catalytic mechanism of PNPP hydrolysis was also proposed. The kinetic parameter of PNPP catalytic hydrolysis has been calculated and the activation energy for the catalytic hydrolysis is 43.69, 39.76 and 35.44 kJ·mol−1, respectively.

A copper(II) complex 1 of a novel macrocyclic polyamine ligand with hydroxylethyl pendant groups, 4,11-bis(hydroxylethyl)-5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane (L) has been synthesized and characterized. Rate enhancement for hydrolysis of p-nitrophenyl picolinate (PNPP) catalyzed by 1 was studied kinetically under Brij35 micellar condition. For comparision, the catalytic activity of corresponding copper(II) complex 2 of non-substituted macrocyclic polyamine ligand, 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraaza-cyclote- tradecane (L′) toward the hydrolysis of PNPP was also investigated. The results indicate that the macrocyclic polyamine copper(II) complex 1 effectively catalyzed the hydrolysis of PNPP, and the pendant ligand hydroxyl group or deprotonated pendant ligand hydroxyl group can act as catalytically active species in the reaction. A ternary complex kinetic model involving metal ion, ligand and substrate has been proposed, and the results confirmed the reasonability of such kinetic model.

It has been reported that three aza crowned Schiff base cobalt (II) complexes were synthesized and characterized, and the metallomicelle made up of the cobalt (II) complexes and surfactants(Brij35, CTAB, LSS), as mimic hydrolytic metalloenzyme, was used in catalytic hydrolysis of bis(4‐nitrophenyl) phosphate (BNPP). The analysis of specific absorption spectrums of the hydrolytic reaction systems indicated that key intermediates made up of BNPP and Co (II) complexes are formed in the reaction process of BNPP catalytic hydrolysis. The mechanism of BNPP catalytic hydrolysis proposed is based on the analytic result of specific absorption spectra. Based on the mechanism proposed, a kinetic mathematical model for the calculation of the kinetic parameter of BNPP catalytic hydrolysis has been established. The acid effect of reaction system, structure effect of the complexes, effect of temperature and effect of micelles on the rate of BNPP hydrolysis catalyzed by the complexes have been discussed.

The kinetics of hydrolysis of p‐nitrophenyl picolinate(PNPP) catalyzed by metallomicelles formed from Cu (II), Ni (II) Schiff base complexes (CuL, NiL) and CTAB micelle were investigated in the pH range of 6.0–9.0 at 30°C. For the Cu (II) Schiff base complex CuL, the apparent rate constants (k obsd) of PNPP hydrolysis initially increased with the increasing pH of reaction media, then fell off. For the Ni (II) Schiff base complex NiL, the k obsd always increased with the increasing pH. The kinetic and thermodynamic parameters were calculated. The hydrolysis rate of PNPP catalyzed by Cu (II) complex was much larger than that by Ni (II) complex in CTAB micellar solution. The catalytic mechanism of the PNPP hydrolysis was discussed in detail, and the possibly active specie for the catalytic hydrolysis of PNPP was the monohydroxo metal complex.

Two symmetrical double aza‐crowned Schiff base cobalt(II) complexes were synthesized and characterized, and the metallomicelle made up of the cobalt(II) complexes and surfactant, as mimic hydrolytic metalloenzyme, was used in catalytic hydrolysis of bis(4‐nitrophenyl) phosphate (BNPP). The analysis of specific absorption spectrums of the hydrolytic reaction systems indicated that key intermediates made up of BNPP and Co(II) complexes are formed in reaction processes of the BNPP catalytic hydrolysis. In this article, the mechanism of BNPP catalytic hydrolysis has been proposed based on the analytic result of specific absorption spectrum. A kinetic mathematical model, for the calculation of the kinetic parameter of BNPP catalytic hydrolysis has been established based on the mechanism proposed. The acid effect of reaction system, the structural effect of the complexes, the effect of surfactant micelles and the effect of temperature on the rate of BNPP hydrolysis catalyzed by the complexes have been discussed.

Two cobalt(II) complexes of the Schiff base with morpholino or aza-crown ether pendants, CoL1 and CoL2, as mimic hydrolytic metalloenzyme, were used in catalytic hydrolysis of carboxylic ester (PNPP). The analysis of specific absorption spectra of the hydrolytic reaction systems indicates that key intermediates, made up of PNPP and Co(II) complexes, have been formed in reaction processes of the PNPP catalytic hydrolysis. The mechanism of PNPP catalytic hydrolysis has been proposed based on the analytic result of specific absorption spectrum. A kinetic mathematical model, applied to the calculation of the kinetic parameter of PNPP catalytic hydrolysis, has been established based on the mechanism proposed. The acid effect of buffer solution, structural effect of the complexes, and effect of temperature on the rate of PNPP hydrolysis catalyzed by the complexes have been also discussed.