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OBJECTIVE: To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC. METHODS: A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model. RESULTS: The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P

Along with the rapid increase of China's energy demands, the energy engineering is facing more and more complex risks. The present research on the early warning methods of energy price risk mainly consider single prices and fail to analyze the energy price system integrally. In this paper, an early warning model of China's energy price is analyzed from the aspects of price fluctuation and price ratio structure through fitting the risk distributions of indices and applying the CGE model (Computable General Equilibrium). And Based on analyzing China's warning degrees of energy price ratios in the year 2015, it is found that the price ratios between electricity and crude oil are in the state of ‘dangerous’, while others are in the state of ‘highly dangerous’, including the price ratios between refined oil and crude oil, between the natural gas of resident and crude oil, between natural gas and coal and between electricity and coal.

Based on rock Mechanical theory under unloading, according to the analysis of rock mechanics state of pre and post excavation of the layered dip rocky slope, it was found that excavation unloading cause deterioration of rock constitutive relation and structure plane’s mechanical parameters, deformation mechanism of high layered dip rocky slope was analyses when rock is at unloading condition in this study. Its deformation consists of the two parts which are rock mass unloading rock mass springback displacement and bedding-slip displacement along the rock mass discontinuity, and deduced the calculating formula of slope displacement. Research results with great guide significance and practical engineering value to similar engineering construction afterward.

Firstly, general regression neural network (GRNN) was used for variable selection of key influencing factors of residential load (RL) forecasting. Secondly, the key influencing factors chosen by GRNN were used as the input and output terminals of urban and rural RL for simulating and learning. In addition, the suitable parameters of final model were obtained through applying the evidence theory to combine the optimization results which were calculated with the PSO method and the Bayes theory. Then, the model of PSO-Bayes least squares support vector machine (PSO-Bayes-LS-SVM) was established. A case study was then provided for the learning and testing. The empirical analysis results show that the mean square errors of urban and rural RL forecast are 0.02% and 0.04%, respectively. At last, taking a specific province RL in China as an example, the forecast results of RL from 2011 to 2015 were obtained.

The main cause of cement concrete pavement fracture is void beneath slab, while water is an important factor of void beneath slab. In order to clearly understand impact of water on void beneath cement concrete pavement, this paper analyzes penetration soaking role and scouring of water and studies the evolution process of void under slab. It is founded that the erosion of the grassroots and void beneath the plate influence each other. Conducting a Small-size simulation test by using Falling Weight Deflectometer (FWD), the movement condition of the water in empty area under concrete road and the effect of void size on current scour are got under the action of moving load.

The practice of urban power network planning in China is facing more and more complex risks. The nature of the risks themselves is unclear and uncertain. In order to ensure that urban power networks are planned in a scientific manner, a reasonable risk assessment needs to be performed. Based on extension analysis and the matter-element extension theory, a model of risk evaluation designed to be applied to urban power network planning is put forward in this paper. This model has the advantage that it conveniently quantifies the qualitative indices. At the same time, it also overcomes the main limitation of the matter-element method, namely, that if the risk index exceeds the risk grading standard, it can not be calculated using the correlation function. Finally, taking a specific urban power network as an example, the empirical analysis results show that this model is credible and practical.

Based on the CGE model, this paper simulates the impact of electricity price adjustment on demand for electricity, and the simulation results show the range of electricity elasticities of different consumers. The elasticities of the high power-consuming sectors are relatively larger. However, the absolute values of the price elasticities are less than one. Furthermore, this paper quantitatively analyses the price elasticity of different categories of users, which are classified according to the objectives of China’s electricity price reform. The elasticity absolute value of Industry & Commerce is around 0.018, that of Residents is around 0.300 and that of Agriculture is around 0.066. Finally, the price elasticities of different consumers in 2005 and 2007 are calculated through the CGE model, and it is discovered that the price elasticity absolute values in 2007 are less than that in 2005. The analytical results of this paper can provide corresponding support for the formulation of electricity pricing mechanisms for the developing countries.

Differential reactivity of the amine functionality in a number of common 1,2-diamine starting materials is exploited to undertake an expedient synthesis of unsymmetrical 2,3,6-trisubstituted quinoxaline and unsymmetrical 2,3,7-trisubstituted pyridopyrazine derivatives.

Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 microM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC(50)=7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents.

A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 cancer cells with EC(50) values in the single digit nanomolar range. Binding experiments demonstrated that representative active compounds of this class compete with colchicine for its binding site on tubulin. The syntheses and structure-activity relationship studies for the triazole derivatives are described herein.

New “Magic Blue” reagent, namely, the blue solution in F113 (CClF 2 CCl 2 F) containing H-abstracting agent bis[ ω -fluorosulfonylperfluoroalkyl] nitroxide R F N(O )R F 2 and ω -fluorosulfonylperfluoronitrosoalkane spin trap R F NO 3 both generated in the reaction of ω -fluorosulfonylperfluorodiacyl peroxide [FO 2 SCF 2 CF 2 OCF(CF 3 )CF 2 OCF(CF 3 )COO] 2 1 with sodium nitrite in F113 (CClF 2 CCl 2 F) at room temperature, reacted with a series of p -substituted benzaldehydes 4 via regio-selective abstraction of the formyl hydrogen followed by spin trapping of the acyl radical intermediate 5 , thus led to the formation of stable spin adducts ω -fluorosulfonylperfluoroalkyl p -substituted benzoyl nitroxides 6 . The correlation analyses of a N values of nitroxides 6 with various substituent constants disclose that the polar effects are the major factors varying the spin density on the nitroxyl-nitrogen while the effect through spin-delocalization is felt slightly.

Reactions of pyrrole (2) or 1-methylpyrrole (4) with readily available N-acylbenzotriazoles 1a-g (RCOBt, where R = 4-tolyl, 4-nitrophenyl, 4-diethylaminophenyl, 2-furyl, 2-pyridyl, 2-indolyl, or 2-pyrrolyl) in the presence of TiCl(4) produced 2-acylpyrroles 3a-g and 5a-g in good to excellent yields. 1-Triisopropylsilylpyrrole (6) under the same conditions gave the respective 3-acylpyrroles 7a-g. Similarly, indole (9) and 1-methylindole (11) gave the corresponding 3-acylated derivatives 10a-g and 12a-g. These results demonstrate that N-acylbenzotriazoles such as 1c,f,g are mild, regioselective, and regiospecific C-acylating agents of particular utility when the corresponding acid chlorides are not readily available.

Chiral (3S,9bS)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones 11a–11f, 14b,14c and 17a,b were prepared in 78–93% yields with high stereoselectivities (d.e. >99%) by the intermolecular condensations of 2-formylbenzoic acids 10 or 13 or 2-acetylbenzoic acid 15 with chiral diamines 9a–9f and 9h. Compounds 9a–9f and 9h were readily prepared in three steps from optically active N-Boc-α-amino acids 5a–5d.

Unsymmetrical imidazolidines 10-14, optically active imidazolidines 20-22, and 2,3-dihydro-1H-benzimidazoles 28 and 29 were synthesized in good to excellent yields by Mannich reactions of 1,2-ethanediamines 8a-c, 18a-c, or N-methyl-1,2-benzenediamine (26a) with benzotriazole and formaldehyde, followed by the nucleophilic substitution of the benzotriazolyl group with C-nucleophiles (Grignard reagents, sodium cyanide), an S-nucleophile (benzenethiol), and a P-nucleophile (triethyl phosphite).

4-Benzotriazolylmethyl-2,3,4,5-tetrahydro-1,4-benzothiazepines 5a,b, -1,4-benzoxazepine (12) and -1,4-benzodiazepine (20) are obtained via aluminium chloride mediated intramolecular cyclizations of N,N-bis(1H-1,2,3-benzotriazol-1-ylmethyl)-2-(arylthio)ethan-1-amines 4a,b, -2-(phenoxy)ethan-1-amine (11) and -N-[2-(N′-methylanilino)ethyl]amine (19), respectively. Subsequent nucleophilic substitutions of the benzotriazolyl group in 5a,b, 12 and 20 succeeded with Grignard reagents, triethyl phosphite, sodium borohydride, and a silyl enol ether to give novel 2,3,4,5-tetrahydro-1,4-benzothiazepines 6–9, -1,4-benzoxazepines 13 and 14, and -1,4-benzodiazepines 21–23 in good yields.

Lithiation of 1,3-dialkoxybenzenes with n-BuLi, followed by formylation with DMF, furnished solely 2,6-dialkoxybenzaldehydes with high regioselectivity. Using this key step, different approaches have been developed for novel symmetrical and unsymmetrical 2,6dialkoxybenzaldehydes.

N- Benzotriazolylmethyl- N -phenethylamines 5a – 5c and 11a – 11c cyclize in the presence of aluminum chloride to produce 1,2,3,4-tetrahydroisoquinolines 6a – 6c and 12a – 12c (70–89%) via electrophilic attack of a transient iminium cation X on the tethered phenyl ring. The Bt group in 2 - benzotriazolylmethyl-1,2,3,4-tetrahydroisoquinolines 6a – 6b was replaced (i) with hydrogen by sodium borohydride to afford N -methyl-1,2,3,4-tetrahydroisoquinolines 7a – 7b or (ii) by nucleophiles, such as Grignard reagents, a silyl enol ether or triethyl phosphite, to furnish novel N -substituted-1,2,3,4-tetrahydroisoquinolines 13a – 13c , 14 or 15 , respectively. Optically active 3-substituted-1,2,3,4-tetrahydroisoquinolines 12a – 12c were similarly prepared in high yields without racemization.

1H-Imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones 6a–i are synthesized in 67–96% yields with high stereoselectivities (de 88–99%, except 6e with a 58% de value) via intermolecular condensation of 2-formylbenzoic acid (5) and α-amino amides 4a–i in the presence of a catalytic amount of toluene-p-sulfonic acid. Intermediates 4 are obtained in two steps from easily available chiral N-Boc-α-amino acids 1.

Direct O-alkylation of 2-hydroxy-5-methoxybenzaldehyde (1) with alkyl bromides or iodides gave nine 2-alkoxy-5-methoxybenzaldehydes 2a-i in high yields, six of which are novel compounds. Treatment of 2-ethoxy-5-bromobenzaldehydes (3) with n-BuLi, morpholine and nitrobenzene afforded 2-ethoxy-5-hydroxybenzaldehyde (4), which easily underwent Oalkylation to furnish 2-ethoxy-5-alkoxybenzaldehydes 5a-b in total moderate yields.

Heteroaromatic α- and β-carboxaldehydes were prepared by the formylation with DMF of α- lithio benzofuran, benzothiophene, N-methylbenzimidazole and 10-methylphenothiazine obtained by direct lithiation and β-lithio compounds from lithium-bromine exchange. Dialkoxybenzaldehydes were prepared by the formylation of dialkoxybenzenes with hexamethylenetetramine (HMTA) or by the alkylation of dihydroxybenzaldehydes with alkyl bromides or iodides.

Facile electron transfer reactions between linear triblock copolymer SBS (polystyrene–polybutadiene–polystyrene) and per(poly)fluorodiacyl peroxides at room temperature (∼20°C) in dichloromethane produced high yields of olefmic per(poly)fluoroalkylated SBS with excellent water and oil repellency, chemical resistance and much lowered refractive indices.

1-Phenyl-5-(benzotriazol-1-yl)hexahydro-1H-pyrrolo[1,2-a]ĭmidazole (18) and 1-phenyl-5-benzotriazolyloctahydroimidazo[1,2-a]pyridine (27) were readily prepared from succindialdehyde or glutaraldehyde, benzotriazole, and N-phenylethylenediamine. Synthons 18 and 27 reacted with Grignard reagents, allylsilanes, silyl ethers, and triethyl phosphite to produce 1-phenyl-5-substituted-hexahydro-1H-pyrrolo[1,2-a]ĭmidazoles 20a-f, 22, 24a,b, and 25 and 1-phenyl-5-substituted-octahydroimidazo[1, 2-a]pyridines 28a-e, 32, 33a,b, and 34 in good to excellent yields. The configurations of 20, 22, 24, and 25 were determined to be cis isomers by NOE experiment, while the configurations and conformations of 28a-e, 32, 33a,b, and 34 were elucidated by (1)H-(1)H COSY and (1)H-(13)C COSY.

Indolizines and pyrrolo[2,1-a]isoquinolines are synthesized by 1,3-dipolar cycloadditions of pyridinium benzotriazolylmethylides or isoquinolinium benzotriazolylmethylides with ethylenes and acetylenes.

The 2-alkyl-5-tert-butyl-1,4-dimethoxybenzene radical cations 1+·a–e (2-alkyl = Me, Et, i-Pr, c-PrCH2 and PhCH2) generated in one-electron oxidation of their parent compounds 1a–e by pentafluorobenzoyl peroxide or cerium(IV) sulfate were characterized by EPR spectrometry. The product analysis shows that under certain conditions 1+·a–e may collapse through two competitive pathways, i.e. deprotonation and de-tert-butylation. The deprotonation of 1+·a–e is further assured by EPR observations of the corresponding benzyl radical intermediates. The relative importance of the two pathways is greatly dependent on the structure of the alkyl substituents, the nature of the solvents and the reaction temperature. For deprotonation, the reactivity order is found to be c-PrCH2 >Me >PhCH2 >Et ≫ i-Pr. Copyright © 1999 John Wiley & Sons, Ltd.

Two series of ω-hydroperfluoroalkyl 1-methyl-2-substituted-pyrrolyl-5-carbonyl nitroxides, i.e., 5 and 6 generated in the H-abstraction/spin trapping reaction of twelve 1-methyl-2-substituted-pyrrolyl-5-carbaldehydes 1 with the H-abstracting agent RfN(O⋅)Rf (2) and the spin-trapping agent RfNO (4), were studied by ESR. Correlation analysis of the aN values of 5 and 6 with polar and spin-delocalization substituent constants shows that aN values are mainly affected by the polar effect, but the spin-delocalization effect also exists.

Three series of new 1-methyl-2-substituted-5-pyrrolylcarbonyl fluorinated nitroxides, i.e., 3 (R f =C 2 F 5 ), 4 (R f = n -C 3 F 7 ) and 5 (R f = n -C 7 F 15 ), generated by the H-abstraction/spin-trapping reaction of eleven 1 -methyl-2-substituted-pyrrole-5-carbaldehydes ( 6 ) with the H-abstracting agent [R f N(O • )R f ] 1 and the spin-trapping agent R f NO 2 , were studied by EPR. Correlation analysis of their a N values with polar and spin-delocalization substituent constants shows that a N values are mainly affected by the polar effect of the 2-substituent, but the spin-delocalization effect also exists.

Previous work has shown that postmitotic, differentiating fiber cells of the embryonic chicken lens express cyclin B and Cdc2. The present study explores the possible physiological role of these proteins in lens differentiation by examining the developmental regulation of cyclin B/Cdc2 expression and activity in lens fiber cells of embryonic and newborn rats. Cyclin B mRNA and protein were detected not only in the lens epithelium, which contains proliferating cells, but also in postmitotic, differentiating fiber cells. In contrast, cyclin A mRNA and protein were detected only in epithelial cells. Immunoprecipitation with cyclin B antibody coprecipitated Cdc2 from both epithelial and fiber cell extracts. Immunoprecipitates of cyclin B from both epithelial cells and fiber cells showed H1 kinase activity when assayed in vitro, but the developmental pattern of cyclin B-associated kinase activity in these two lens fractions was markedly different. In the epithelium, H1 kinase activity decreased gradually with developmental age in parallel with the decrease in epithelial cell proliferation, whereas, in the fiber cells, kinase activity peaked sharply at embryonic day 18 (E18) and E19. Microscopic examination of rat lenses indicated that peak cyclin B/Cdc2 activity was correlated with changes in chromatin structure and nuclear envelope breakdown in the terminally differentiating primary lens fiber cells. These findings suggest that cyclin B/Cdc2 activity may play an active role in nuclear changes leading to primary fiber cell denucleation.

The H-abstraction from benzyl silicanes (3–6), alkoxy silicanes (7–18), phenyl alkoxy silicanes (19–22), and polybenzylsiloxane (23) by “magic blue” solution (in F113, CClF2-CCl2F) containing the H-abstracting agent [H(CF2)4]2NO· (1) and spin trap H(CF2)4 NO (2) was studied by EPR detection of the F, Si-nitroxides (a total of 24 from 21 silicon substrates) generated in the reactions. From the EPR spectra of the nitroxides, we have gained information about the position of H-abstraction, the subsequent radical steps after the H-abstraction, as well as the structures of the transient radical intermediates. This technique may serve as a new method for making multi-and polynitroxides under very mild conditions.

We have investigated the expression of Cdk5 and its regulatory subunit, p35, in the developing rat lens from embryonic day 16 (E16) to postnatal day 8 (P8). Reverse transcription and polymerase chain reaction (RT/PCR) detected Cdk5 and p35 mRNA expression in lens epithelial cells and in differentiating lens fibers throughout this developmental period. Subsequent sequencing of the RT/PCR products confirmed their identifies. In sity hybridization with Cdk5 and p35 riboprobes showed especially high expression of both mRNAs in the newly formed lens fiber cells in the bow region of the lens. Immunocytochemistry at E18 showed that Cdk5 was present in the cytoplasm of lens epithelial cells and fiber cells, with especially strong immunostaining at the anterior ends of the fibers. Fiber cells in the final stages of maturation, immediately prior to nuclear degeneration, showed positive staining for Cdk5 in the nucleus. Immunoprecipitation of proteins with Cdk5 antibody followed by immunoblotting with either N-terminal specific or C-terminal specific p35 antibodies demonstrated that p35 is complexed with Cdk5 in lens epithelial cells and lens fibers. Immunoprecipitates of Cdk5 from epithelia and fibers showed kinase activity in vitro using histone H1 as a substrate. These findings demonstrate that p35/Cdk5 activity is not restricted to neurons and raise the possibility that this kinase may play a role in lens fiber cell differentiation.

Facile electron-transfer reactions between polystyrene and per(poly)fluorodiacyl peroxides at ~ 20 °C in dichloromethane produced high yields of ring-peer(poly)fluoroalkylated polystyrenes with excellent water- and oil-repellency, chemical resistance and much lowered refractive indices.

A large number of fluorinated nitroxides with a wide variety of structures have been synthesized by mainly making use of the electron-transfer reactions of fluorinated oxidants, such as (R f COO) 2 , R f I and R f SO 2 Br with nitrogen-containing substrates. The nitroxides are spin-adducts of the radical intermediates and both nitroso traps (R f NO or RNO) are formed in these reactions. Such ‘in situ spin trapping reactions’ have served as a useful technique in the mechanistic studies of these radical reactions of N-substrates. The reaction mixtures — blue solutions (called ‘magic blue’) containing very reactive fluorinated nitroxides such as R f N(O·)R f and effective spin traps such as R f NO — have been applied successfully to the study of H-abstraction reactions from very many kinds of substrates and thereby producing a much larger number of fluorinated nitroxides. Much valuable information about the electronegativity of various fluorinated functional groups, substituent effects through spin-delocalization (σ scale), solvation, the temperature dependence of α N and α F values, as well as selective line broadening have been gained from EPR studies of these new fluorinated nitroxides.

Twenty-two polysubstituted 2-aminopyrimidines dissolved in F1 13 (CC1F2-CCl2F) solutions containing ([H(CF2CF2)nCO2]2 n = 1,2) and H(CF2CF2)nNO [↔ H(CF2CF2)n • + NO] have been oxidized into detectable ω-H-perfluoroalkyl pyrimidinyl nitroxides along with neutral products. A mechanism involving Habstraction from the amino groups by H(CF2CF2)nN(O•)(CF2CF2)nH and the subsequent radical steps was suggested for the generation of the nitroxides. Some relationships between aN values and the nature of the ring substituents are discussed.

1-Benzotriazolylmethyl-3-propylhexahydropyrimidine (1) and 1,3-bis(1H-1,2,3-benzotriazol-1-ylmethyl)-1,2,3,4-tetrahydroquinazoline (3) were readily prepared by reactions of N-propyl-1,3-propanediamine or 2-aminobenzylamine with benzotriazole and formaldehyde, respectively. Intermediate 1 reacted with alkyl and aryl Grignard reagents to produce N,N'-unsymmetrically substituted hexahydropyrimidines 2a,b in 90 and 92% yields, respectively. Nucleophilic substitutions of 3 with Grignard reagents, allylsilane, and triethyl phosphite gave N,N'-disubstituted 1,2,3,4-tetrahydroquinazolines 4a-f, 5, and 6 in good to excellent yields. Successive treatment of 3 with two different Grignard reagents in one-pot reaction led regiospecifically to N,N'-unsymmetrically substituted tetrahydroquinazoline derivatives 8a,b.

Dihydropyrrolo[2′,1′:3,4]pyrazino[2,1-a]isoindolones 10a–10c were obtained in 76–81% yields by the reaction of 2-(1H-pyrrol-1-yl)ethylamine 8 with 2-formylbenzoic acids 9a , 9b or 2-acetylbenzoic acid 9c via N-acyliminium cation aromatic cyclizations. Similarly, dihydropyrrolo[2′,1′:3,4][1,4]diazepino[2,1-a]isoindolones 12a , 12b were prepared in one-pot reactions from 3-(1H-pyrrol-1-yl)propylamine 11 and 2-formylbenzoic acids 9a , 9b .

1-Methyl-2-formyl-5-bromopyrrole 1 was prepared in 48% total yield by initial bromination of the intermediate 1-methyl-2-(5,5-dimethyl-1,3-dioxan-2-yl)pyrrole 5 with N-bromosuccinimide to give the intermediate 1-methyl-2-(5,5-dimethyl-1,3-dioxan-2-yl)-5-bromopyrrole 6, which was finally hydrolyzed to the product 1.