Development and validation of a LASSO prediction model for cisplatin induced nephrotoxicity: a case-control study in China.

BACKGROUND: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy. METHODS: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike's information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model's performance. RESULTS: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9. CONCLUSIONS: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.

Organic-inorganic hybrid coating materials derived from renewable soybean oil and amino silanes.

Novel organic-inorganic hybrid coating materials were developed using amino silanes and acetoacetylated soybean oil. The acetoacetylated soybean oil was prepared from soybean oil (a renewable resource) using a solvent-free method involving a thiol-ene and transesterification reactions, and the chemical structure was characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), Fourier-transform infrared (FTIR) spectroscopy, and viscosity analyses. On the basis of the acetoacetylated soybean oil, several organic-inorganic hybrid coating materials were prepared using different amino silanes by a catalyst-free method involving one-step comprising two reactions (an amine-acetoacetate reaction and an in situ sol-gel technique), and their crosslinked structures were determined from their FT-IR and solid-state 29Si NMR spectra. The resulting coating materials have good mechanical/chemical performance. This method for preparing renewable organic-inorganic hybrid coating materials may have wide uses because plant oils contain many unsaturated C[double bond, length as m-dash]C bonds and easy access to acetoacetate functional groups.

Al and Zn complexes bearing N,N,N-tridentate quinolinyl anilido-imine ligands: synthesis, characterization and catalysis in L-lactide polymerization.

Reactions of N,N,N-tridentate quinolinyl anilido-imine ligands with AlMe(3) afford mononuclear aluminum complexes {κ(3)-[{2-[ArN=C(H)]C(6)H(4)}N(8-C(9)H(6)N)]}AlMe(2) (Ar = 2,6-Me(2)C(6)H(3) (1a), 2,6-Et(2)C(6)H(3) (1b), 2,6-(i)Pr(2)C(6)H(3) (1c)) or dinuclear complexes AlMe(3){κ(1)-[{2-[ArN=C(H)C(6)H(4)]N(8-C(9)H(6)N)}-κ(2)]AlMe(2) (R = 2,6-Me(2)C(6)H(3) (2a), 2,6-Et(2)C(6)H(3) (2b), 2,6-(i)Pr(2)C(6)H(3) (2c)) depending on the ratios of reactants used. Similar reactions of ZnEt(2) with these ligands give the monoligated ethyl zinc complexes {κ(3)-[{2-[ArN=C(H)]C(6)H(4)}N(8-C(9)H(6)N)]}ZnEt (Ar = 2,6-Me(2)C(6)H(3) (3a), 2,6-Et(2)C(6)H(3) (3b), 2,6-(i)Pr(2)C(6)H(3) (3c)) or bisligated complexes {κ(3)-[{2-[ArN=C(H)]C(6)H(4)}N(8-C(9)H(6)N)]}Zn{κ(2)-[{2-[ArN=C(H)]C(6)H(4)}N(8-C(9)H(6)N)]} (Ar = 2,6-Me(2)C(6)H(3) (4a), 2,6-Et(2)C(6)H(3) (4b), 2,6-(i)Pr(2)C(6)H(3) (4c)). These complexes were well characterized by NMR and the structures of 1a, 2a, 2c, 3b and 4c were confirmed by X-ray diffraction analysis. The aluminum and zinc complexes were tested to initiate lactide polymerization in which the zinc complexes show moderate to high activities in the presence of benzyl alcohol.

Synthesis of 4-methylcoumarin derivatives containing 4,5-dihydropyrazole moiety to scavenge radicals and to protect DNA.

A series of 4-methylcoumarin derivatives containing 4,5-dihydropyrazole moiety were synthesized and their antioxidant activities were evaluated in AAPH (2,2'-azobis(2-amidinopropane hydrochloride))-induced oxidation of DNA, and in trapping DPPH (2,2'-diphenyl-1-picrylhydrazyl) and ABTS(+•) (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical), respectively. Among coumarin derivatives, 3a-d and 4a-c exhibited the termination of radical propagation-chains in AAPH-induced oxidation of DNA. The ortho dihydroxyphenyl substitution at 5 position and 1-unsubstitution of the 4,5-dihydroxylpyrazole was found enhancing the antioxidant activities of these coumarin derivatives.

Synthesis, characterization, and catalytic properties of new half-sandwich zirconium(IV) complexes.

A number of new half-sandwich zirconium(IV) complexes bearing N,N-dimethylaniline-amido ligands with the general formula Cp*ZrCl(2)[ortho-(RNCH(2))(Me(2)N)C(6)H(4)] [R = 2,6-Me(2)C(6)H(3) (1), 2,6-(i)Pr(2)C(6)H(3) (2), (i)Pr (3), (t)Bu (4)] were synthesized by the reaction of Cp*ZrCl(3) with the corresponding ortho-(Me(2)N)C(6)H(4)CH(2)NRLi. All new zirconium complexes were characterized by (1)H and (13)C NMR, elemental analyses and single crystal X-ray diffraction analysis. The molecular structural analysis reveals that the NMe(2) group does not coordinate to the zirconium atom in all cases. Complexes 1-4 all have a pseudo-tetrahedral coordination environment in their solid state structures and adopt a three-legged piano stool geometry for the zirconium atoms with the amide N atom and the two Cl atoms being the three legs and the Cp* ring being the seat. Variable-temperature (1)H NMR experiments for all complexes 1-4 were performed to investigate the possible intramolecular interaction between the N atom in the NMe(2) group and the central zirconium atom in solution. Upon activation with Al(i)Bu(3) and Ph(3)CB(C(6)F(5))(4), complexes 1-4 all exhibit moderate to good catalytic activity for ethylene polymerization and copolymerization with 1-hexene, producing linear polyethylene or poly(ethylene-co-1-hexene) with moderate molecular weight and reasonable 1-hexene incorporation.

N,N'-Bis(2,6-diethyl-phen-yl)acenaphthyl-ene-1,2-diimine.

The title compound, C(32)H(32)N(2), has crystallographic twofold rotation symmetry, with two C atoms lying on the rotation axis. The dihedral angle between the substituted benzene ring and the naphthalene ring system is 79.8 (1)°. The crystal structure is stabilized by C-H⋯N inter-actions, which form a chain motif along the b-axis direction.

Chromium complexes supported by phenanthrene-imine derivative ligands: synthesis, characterization and catalysis on isoprene cis-1,4 polymerization.

Reactions of CrCl(2)(THF)(2) with N-aryl-9,10-iminophenanthraquinone in CH(2)Cl(2) give the monoimine chromium complexes (Ar)IPQCrCl(2)(THF)(2) (1, Ar = 2,6-Me(2)C(6)H(3); 2, Ar = 2,6-Et(2)C(6)H(3); 3, Ar = 2,6-(i)Pr(2)C(6)H(3)). Molecular structures of 1 and 3 were revealed to be monomeric with the chromium atoms in distorted octahedral geometries. Similar reactions of CrCl(2)(THF)(2) with N,N-bis(arylimino)phenanthrene ligands afford the diimine complexes (Ar1,Ar2)BIPCrCl(µ-Cl)(3)Cr(THF)(Ar1,Ar2)BIP (4, Ar(1) = Ar(2) = 2,6-Me(2)C(6)H(3); 5, Ar(1) = Ar(2) = 2,6-Et(2)C(6)H(3); 6, Ar(1) = Ar(2) = 2,6-(i)Pr(2)C(6)H(3); 7, Ar(1) = 2,6-Me(2)C(6)H(3), Ar(2) = 2,6-(i)Pr(2)C(6)H(3)). The X-ray diffraction analysis shows that 4, 5, and 7 are chlorine-bridged dimers with each chromium atom in a distorted octahedral geometry. Upon activation with MAO, all these complexes exhibit good catalytic activities for isoprene polymerization affording polyisoprene with predominantly a cis-1,4 unit.

Trichlorido-1κCl,2κCl-(2,6-dimethyl-phenolato-2κO)-µ-oxido-bis{1,2(η)-2,3,4,5-tetra-methyl-1-[4-(trimethyl-silyl)phen-yl]cyclo-penta-dien-yl}dititanium(IV).

The title dinuclear titanocene, [Ti(2)(C(8)H(9)O)(C(18)H(25)Si)(2)Cl(3)O], contains one Ti atom tetra-hedrally coordinated by two Cl atoms, a bridging O atom and the substituted cyclo-penta-dienyl ligand, and another Ti atom tetra-hedrally coordinated by a Cl atom, a bridging O atom, the 2,6-dimethyl-phenolate ligand and the substituted cyclo-penta-dienyl ligand. The bridging O atom lies on a twofold rotation axis.

New titanium complexes with symmetric or asymmetric cis-9,10-dihydrophenanthrenediamide ligands formed through sequential intramolecular C-C bond-forming reactions.

A series of new titanium(IV) complexes with symmetric or asymmetric cis-9,10-dihydrophenanthrenediamide ligands, cis-9,10-PhenH(2)(NR)(2)Ti(O(i)Pr)(2) [PhenH(2) = 9,10-dihydrophenanthrene, R = 2,6-(i)Pr(2)C(6)H(3) (2a), 2,6-Et(2)C(6)H(3) (2b), 2,6-Me(2)C(6)H(3) (2c)], cis-9,10-PhenH(2)(NR(1))(NR(2))Ti(O(i)Pr)(2) [R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Et(2)C(6)H(3) (2d); R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Me(2)C(6)H(3) (2e)], and [cis-9,10-PhenH(2)(NR(1))(2)][o-C(6)H(4)(CH=NR(2))]TiO(i)Pr [R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Et(2)C(6)H(3) (3a); R(1) = 2,6-(i)Pr(2)C(6)H(3), 2,6-Me(2)C(6)H(3) (3b)], have been synthesized from the reactions of TiCl(2)(O(i)Pr)(2) with o-C(6)H(4)(CH=NR)Li [R = 2,6-(i)Pr(2)C(6)H(3), 2,6-Et(2)C(6)H(3), 2,6-Me(2)C(6)H(3)]. The symmetric complexes 2a-2c were obtained from the reactions of TiCl(2)(O(i)Pr)(2) with 2 equiv of the corresponding o-C(6)H(4)(CH=NR)Li followed by intramolecular C-C bond-forming reductive elimination and oxidative coupling processes, while the asymmetric complexes 2d-2e were formed from the reaction of TiCl(2)(O(i)Pr)(2) with two different types of o-C(6)H(4)(CH=NR)Li sequentially. The complexes 3a and 3b were also isolated from the reactions for complexes 2d and 2e. All complexes were characterized by (1)H and (13)C NMR spectroscopy, and the molecular structures of 2a, 2b, 2e, and 3a were determined by X-ray crystallography.

Properties of synthetic homoisoflavonoids to reduce oxidants and to protect linoleic acid and dna against oxidation.

3-(2'-, 3'-, and 4'-Hydroxybenzylidene)-7-methoxychroman-4-one (o-, m-, and p-HBMC) was synthesized for the clarification of the influence of the hydroxyl group at the B ring on the antioxidant activity of homoisoflavonoid. The three homoisoflavonoids used herein can reduce peroxynitrite. p-HBMC exhibited high activity to reduce singlet oxygen. Furthermore, o-, m-, and p-HBMC can scavenge the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(*+)) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and galvinoxyl radicals. The rates of o-HBMC trapping of DPPH and galvinoxyl radicals were higher than those of m- and p-HBMC, whereas m-HBMC can trap ABTS(*+) rapidly. o-HBMC was found to possess high activity in the beta-carotene-linoleic acid bleaching test and to protect methyl linoleate against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation efficiently. Finally, o-HBMC served as a prooxidant in Cu(2+)/glutathione (GSH)- and hydroxyl radical-mediated oxidations of DNA. m- and p-HBMC protected DNA against hydroxyl radical-mediated oxidation of DNA effectively, and o- and p-HBMC behaved as antioxidants to protect DNA against AAPH-induced oxidation. Thus, the hydroxyl group attaching to the ortho- and para-positions in the B ring was of importance for the homoisoflavonoid's enhancement of antioxidant activity.

Dichloro-4-quinolinol-3-carboxylic acid: synthesis and antioxidant abilities to scavenge radicals and to protect methyl linoleate and DNA.

5,7-, 5,8-, 6,8-, 7,8-dichloro-4-quinolinol-3-carboxylic acid (5,7-, 5,8-, 6,8-, 7,8-DCQA) together with 7-chloro-4-quinolinol-3-carboxylic acid (7-CQA) and 4-quinolinol-3-carboxylic acid (QA) were synthesized to investigate the antioxidant properties. 5,7-DCQA exhibited the highest ability to scavenge 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+.), 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and galvinoxyl radicals. 6,8-DCQA possessed the highest efficacy to protect methyl linoleate against 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH)-induced oxidation. 5,7-, 5,8-DCQA and QA were able to retard the beta-carotene-bleaching in beta-carotene-linoleic acid emulsion. In addition, 5,8- and 6,8-DCQA efficiently protected DNA against hydroxyl radical (.OH)-mediated oxidation, and 5,8-DCQA and 7-CQA were active to protect DNA against AAPH-induced oxidation. Furthermore, only 7-CQA can protect DNA against Cu2+/glutathione (GSH)-mediated oxidation. Dichloro-4-quinolinol-3-carboxylic acids were potent to be antiradical drugs, and were worthy to be researched pharmacologically.

The antioxidative effect of icariin in human erythrocytes against free-radical-induced haemolysis.

Icariin (2-(4'-methoxyl phenyl)-3-rhamnosido-5-hydroxyl-7-glucosido-8-(3'-methyl-2-butylenyl)-4-chromanone) is the major component in Herba Epimedii used in traditional Chinese medicine for the treatment of atherosclerosis. This work focuses on the antioxidative effect of icariin on free-radical-induced haemolysis of human erythrocytes, in which the initial free radical derives from the decomposition of 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) at physiological temperature. To reveal the structure-activity relationship of icariin, the antioxidant effects of two structural analogues of icariin, acacetin (2-(4'-methoxylphenyl)-5,7-dihydroxylchromone) and norwogonin (2-phenyl-5,7,8-trihydroxylchromone), on the same experimental system were examined as well. It was found that all these chromone derivatives (Chm-OHs) dose-dependently protected human erythrocytes against free-radical-induced haemolysis. The order of antioxidative activity was norwogonin > acacetin > icariin by the analysis of the relationship between the concentration of Chm-OHs and the prolongation percentage of the lag time of haemolysis (PP%). It was also proved that the phenyl hydroxyl group attached to the chromone ring at 7-position cannot trap the free radical. On the contrary, phenyl hydroxyl groups at the 5- and 8-position in norwogonin made it a significant antioxidant in AAPH-induced haemolysis. The more hydroxyl groups attached to the chromone ring, the higher the antioxidative activity in protecting erythrocytes against free-radical-induced peroxidation.

In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes.

Ginsenoside, the major active component in Panax ginseng, which has been used in traditional Chinese medicine, contains a series of derivatives of the triterpene dammarane being attached by some sugar moieties. To clarify the relationship between the structure of ginsenoside and its properties, 11 individual ginsenosides, along with the central structures of ginsenoside, protopanaxadiol and protopanaxatriol, are used in 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) induced hemolysis of human erythrocytes, a good experimental model to research free radical induced membrane damage and to evaluate the antioxidative or prooxidative activities of various antioxidants conveniently. It is found that the central structures of ginsenosides, either protopanaxadiol or protopanaxatriol, play a prooxidative role in AAPH-induced hemolysis of erythrocytes. As to the individual ginsenoside, if there are no sugar moieties attached to the 20-position of the triterpene dammarane, the ginsenoside acts as a prooxidant, that is, Rg3, Rh2, and Rg2. A glucose attached to the 6-position instead of the 20-position sugar moieties can make the ginsenoside an antioxidant, that is, Rh1. The antioxidants among ginsenosides follow two different mechanisms that can be expressed mathematically by the Boltzmann equation, that is, Rc and Rb1, and a polynomial equation, that is, Re, Rd, R1, Rg1, Rb3, and Rh1. The orders of antioxidative ability are Rc > Rb1 and Re > Rd > R1 > Rg1 > Rb3 > Rh1, respectively.

Can ginsenosides protect human erythrocytes against free-radical-induced hemolysis?

Many studies have focused on the free-radical-initiated peroxidation of membrane lipid, which is associated with a variety of pathological events. Panax ginseng is used in traditional Chinese medicine to enhance stamina and capacity to deal with fatigue and physical stress. Many reports have been devoted to the effects of ginsenosides, the major active components in P. ginseng, on the lipid metabolism, immune function and cardiovascular system. The results, however, are usually contradictory since the usage of mixture of ginsenosides cannot identify the function of every individual ginsenosides on the experimental system. On the other hand, every individual ginsenosides is not compared under the same experimental condition. These facts motivate us to evaluate the antioxidant effect of various individual ginsenosides on the experimental system of free-radical-initiated peroxidation: the hemolysis of human erythrocyte induced thermally by water-soluble initiator, 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the erythrocyte has been studied firstly and found that the order of IC(50) is Rb3 - Rb1<Rc>Re>Rh1>R1>Rg2>Rb3. Rg3, Rd and Rh2, however, act as synergistic prooxidants in the above experimental system. Rg1 does not show any synergistic antioxidative property. Although the antioxidative and prooxidative mechanism of various ginsenosides with or without TOH in AAPH-induced hemolysis of human erythrocytes will be further studied in detail, this information may be useful in the clinical usage of ginsenosides.

Antioxidative or prooxidative effect of 4-hydroxyquinoline derivatives on free-radical-initiated hemolysis of erythrocytes is due to its distributive status.

7-Chloro-4-hydroxyquinoline (CQ) is an antitumor drug but its efficiency is not very satisfactory. This fact motivates us to study the relationship between the structure of 4-hydroxyquinoline with various substituent and its antioxidant effect against free-radical-initiated peroxidation: the hemolysis of human erythrocyte initiated thermally by water-soluble initiator, 2,2'-azobis (2-amidinopropane hydrochloride) (AAPH), acts as an experimental system. 7-Fluoro-4-hydroxyquinoline (FQ) and CQ can be synthesized by decarboxylation of 7-fluoro-4-hydroxyquinoline-3-carboxylic acid (FQCA) and 7-chloro-4-hydroxyquinoline-3-carboxylic acid (CQCA), respectively, and FQCA and CQCA are prepared by hydrolysis of ethyl 7-fluoro-4-hydroxyquinoline-3-carboxylate (FQCE) and ethyl 7-chloro-4-hydroxyquinoline-3-carboxylate (CQCE), respectively. The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced hemolysis of the erythrocyte has been studied and found that all these chemicals dissolved in dimethyl sulfoxide (DMSO) can inhibit the free-radical-induced peroxidation. To clarify the relationship between the distributive status of the chemicals and their antioxidant effect, the chemical has been dissolved in the vesicle of dipalmitoyl phosphatidylcholine (DPPC) by sonication and suspended in the reaction system. It is found that FQCE, CQCE, FQCA and CQCA act as prooxidants either used alone or used in combination with alpha-tocopherol (TOH), demonstrating that FQCE, CQCE, FQCA and CQCA play a prooxidative role when they are packaged in the DPPC vesicle. This can be understood that the electron-attracting group, i.e. -COOC(2)H(5), -COOH, at the ortho position to the hydroxy group of quinoline makes the phenoxy radical of quinoline derivatives active by attracting negative charge from the electron-deficient radical site. These unstable free radicals preserved in DPPC vesicle can initiate additional propagation of lipid peroxidation and cause hemolysis. However, FQ and CQ without electron-attracting group are antioxidants even in DPPC vesicle either used alone, or mixed with TOH. Moreover, the antioxidative activity of FQ is much better than CQ either used alone or in combination with TOH, indicating that FQ has the potential to replace CQ to be an antioxidant drug. Therefore, the antioxidant/prooxidant effect is not only correlated with the molecular structure but also the distributive status in the reaction system.