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Many organic reactions are characterized by a complex mechanism with a variety of transition states and intermediates of different chemical natures. Their correct and accurate theoretical characterization critically depends on the accuracy of the computational method used. In this work, we study a complex ambimodal cycloaddition with five transition states, two intermediates, and three products, and we ask whether density functional theory (DFT) can provide a correct description of this type of complex and multifaceted reaction. Our work fills a gap in that most systematic benchmarks of DFT for chemical reactions have considered much simpler reactions. Our results show that many density functionals not only lead to seriously large errors but also differ from one another in predicting whether the reaction is ambimodal. Only a few of the available functionals provide a balanced description of the complex and multifaceted reactions. The parameters varied in the tested functionals are the ingredients, the treatment of medium-range and nonlocal correlation energy, and the inclusion of Hartree-Fock exchange. These results show a clear need for more benchmarks on the mechanisms of large molecules in complex reactions.
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In Chemistry, complexity is not necessarily associated to large systems, as illustrated by the textbook example of axial-equatorial equilibrium in mono-substituted cyclohexanes. The difficulty in modelling such a simple isomerization is related to the need for reproducing the delicate balance between two forces, with opposite effects, namely the attractive London dispersion and the repulsive steric interactions. Such balance is a stimulating challenge for density-functional approximations and it is systematically explored here by considering 20 mono-substituted cyclohexanes. In comparison to highly accurate CCSD(T) reference calculations, their axial-equatorial equilibrium is studied with a large set of 48 exchange-correlation approximations, spanning from semilocal to hybrid to more recent double hybrid functionals. This dataset, called SAV20 (as Steric A-values for 20 molecules), allows to highlight the difficulties encountered by common and more original DFT approaches, including those corrected for dispersion with empirical potentials, the 6-31G*-ACP model, and our cost-effective PBE-QIDH/DH-SVPD protocol, in modeling these challenging interactions. Interestingly, the performance of the approaches considered in this contribution on the SAV20 dataset does not correlate with that obtained with other more standard datasets, such as S66, IDISP or NC15, thus indicating that SAV20 covers physicochemical features not already considered in previous noncovalent interaction benchmarks.
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We present here an extension of our recently developed PBE-QIDH/DH-SVPD basis set to halogen atoms, with the aim of obtaining, for weakly interacting halogenated molecules, interaction energies close to those provided by a large basis set (def2-TZVPP) coupled to empirical dispersion potential. The core of our approach is the split-valence basis set, DH-SVPD, that has been developed for F, Cl, Br, and I atoms using a self-consistent formula, containing only energy terms computed for dimers and the corresponding monomers at the same level of theory. The basis set developed considering four systems, one for each halogen atoms, has been then tested on the X40, X4 × 10 benchmarks as well as on other two, less standard, data sets. Finally, a large system (380 atoms) has been also considered as a "crash" test. Our results show that the simple and nonempirical PBE-QIDH/DH-SVPD approach is able to provide accurate results for interaction energies of all the considered systems and can thus be considered as a cheaper alternative to DH functionals paired with empirical dispersion corrections and a large basis set of triple-ζ quality.
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BACKGROUND: Metal implants may affect the image quality, iodine concentration (IC), and CT Hounsfield unit (HU) quantification accuracy. PURPOSE: To investigate the quantitative accuracy of IC and HU from dual-layer spectral detector (DLCT) in the presence of metal artifacts. MATERIAL AND METHODS: An experimental cylindrical phantom containing eight iodine inserts and two metal inserts was designed. The phantom underwent scanning at three radiation dose levels and two tube voltage settings. A set of conventional images (CIs), virtual monoenergetic images (VMIs), and iodine concentration maps (ICMs) were generated and measured for all the eight iodine inserts. Quantitative indicators of mean absolute percentage error (MAPE), artifact index (AI), contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and standard deviation (SD) on CIs and VMIs were calculated for IC and HU. Subjective score evaluation was also conducted. RESULTS: The MAPEiodine values of all regions of interest across different scanning configurations were all <5%. Almost all APEiodine values were <5%, indicating that metal artifacts had little impact on IC measurements. When the tube voltage was fixed, the SD value of attenuation decreased with the increase of the tube current; this is also true when the tube current was fixed. The middle energy reconstructions seemed to give a good balance between reducing artifacts and improving contrast. CONCLUSION: VMIs from DLCT can reduce metal artifacts, the accuracy of IC quantification is not sensitive to imaging parameters. In summary, metal implants exhibit minimal impact on image quality and IC quantification accuracy in reconstructed images from DLCT.
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The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.
Assuntos
Arecaceae , Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Flavonoides/análise , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Objective: The prediction of RR intervals in hypertensive patients can help clinicians to analyze and warn patients' heart condition. Methods: Using 8 patients' data as samples, the RR intervals of patients were predicted by long short-term memory network (LSTM) and gradient lift tree (XGBoost), and the prediction results of the two models were combined by the inverse variance method to overcome the disadvantage of single model prediction. Results: Compared with the single model, the proposed combined model had a different degree of improvement in the prediction of RR intervals in 8 patients. Conclusion: LSTM-XGBoost model provides a method for predicting RR intervals in hypertensive patients, which has potential clinical feasibility.
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Hipertensão , Humanos , Redes Neurais de Computação , Frequência Cardíaca , AlgoritmosRESUMO
As alcohol consumption increases, alcoholic liver disease (ALD) has become more popular and is threating our human life. In this study, we found mulberry fruit extract (MFE) repaired alcohol-caused liver diseases by regulating hepatic lipid biosynthesis pathway and oxidative singling in alcoholically liver injured (ALI) rats. MFE administration inhibited hepatic lipid accumulation and improved liver steatosis in ALI rats. MFE also enhanced the antioxidant capacity and alleviated the inflammatory response by increasing the activities of antioxidant enzymes and decreasing the contents of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. Additionally, MFE regulated the expression of miRNA-155 and lipid metabolism-related PPARα protein in rats. Both miR-155 and PPARα play important roles in liver function. The results indicate that MFE has hepatoprotective effects against ALI in rats.
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Hepatopatias Alcoólicas , MicroRNAs , Morus , Humanos , Ratos , Animais , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR alfa/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Morus/metabolismo , Metabolismo dos Lipídeos , Frutas/metabolismo , Fígado/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Lipídeos , Estresse OxidativoRESUMO
Grapevine leafroll-associated virus 2 (GLRaV-2) is a prevalent virus associated with grapevine leafroll disease, but the molecular mechanism underlying GLRaV-2 infection is largely unclear. Here, we report that 24-kDa protein (p24), an RNA-silencing suppressor (RSS) encoded by GLRaV-2, promotes GLRaV-2 accumulation via interaction with the B3 DNA-binding domain of grapevine (Vitis vinifera) RELATED TO ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 (VvRAV1), a transcription factor belonging to the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) superfamily. Salicylic acid-inducible VvRAV1 positively regulates the grapevine pathogenesis-related protein 1 (VvPR1) gene by directly binding its promoter, indicating that VvRAV1 may function in the regulation of host basal defense responses. p24 hijacks VvRAV1 to the cytoplasm and employs the protein to sequester 21-nt double-stranded siRNA together, thereby enhancing its own RSS activity. Moreover, p24 enters the nucleus via interaction with VvRAV1 and weakens the latter's binding affinity to the VvPR1 promoter, leading to decreased expression of VvPR1. Our results provide a mechanism by which a viral RSS interferes with both the antiviral RNA silencing and the AP2/ERF-mediated defense responses via the targeting of one specific host factor.
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Closterovirus , Proteínas Virais/metabolismo , Vitis , Closterovirus/genética , Closterovirus/metabolismo , Doenças das Plantas/genética , Interferência de RNA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Vitis/genética , Vitis/metabolismoRESUMO
The accurate evaluation of weak noncovalent interactions in large, that is those containing up to thousand atoms, molecular systems represents a difficult challenge for any quantum chemical method. Indeed, some approximations are often introduced to render affordable these calculations. Here, we consider the PBE-QIDH/DH-SVPD protocol, combining a nonempirical double hybrid functional (PBE-QIDH) with a small basis set (DH-SVPD) tailored for noncovalent interactions with a double aim: (i) explore the robustness and accuracy of this protocol with respect to other Density Functional Approximations; (ii) illustrate how its performances are affected by the computational parameters underlying the calculation of the exact exchange and the Coulomb contribution, as well as the perturbative term. To this end, we consider three data sets, namely S66, L7, and CiM13, incorporating molecules of increasing size. On the bright side, our results suggest that the PBE-QIDH/DH-SVPD protocol is particularly accurate for large systems such as those contained in the CiM13 set (up to more than 1000 atoms and 14â¯000 basis functions), for which the DLPNO approximation leads to a significant speed-up for the evaluation of the perturbative correlation term. However, our analysis also points out the limit of this statistical exercise, when the quality of the reference data cannot be easily assessed, due to the size of the molecular complexes involved, and when the number of molecules is limited.
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Teoria QuânticaRESUMO
In this Communication, we assess a panel of 18 double-hybrid density functionals for the modeling of the thermochemical and kinetic properties of an extended dataset of 449 organic chemistry reactions belonging to the BH9 database. We show that most of DHs provide a statistically robust performance to model barrier height and reaction energies in reaching the "chemical accuracy." In particular, we show that nonempirical DHs, such as PBE0-DH and PBE-QIDH, or minimally parameterized alternatives, such as ωB2PLYP and B2K-PLYP, succeed to accurately model both properties in a balanced fashion. We demonstrate, however, that parameterized approaches, such as ωB97X-2 or DSD-like DHs, are more biased to only one of both properties.
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Thromboxane (TX) A2 has been identified as an important intrahepatic vasoconstrictor upon Kupffer cell (KC) activation during infections such as spontaneous bacterial peritonitis (SBP). The study aimed to investigate the role of TLRs in the TXA2 increase in liver nonparenchymal cells and their related mechanisms. Here, we identified TLR-2 as a common pathway for different microbials: microbial lysates including Gram-positive bacteria, Gram-negative bacteria, and fungi all increased TXA2 secretion via activation of TLR-2 in human KCs, accompanied by increased expression and phosphorylation of Myd88-related pathway. Of all TLR agonists, only TLR-1, -2, and -4 agonists increased TXA2 in human KCs. These results were further confirmed by mouse liver nonparenchymal cells. Comparing the effects of TLR-1, -2, and -4 antagonists, only TLR-2 antagonist showed inhibitory effects with all tested microbial lysates. Pretreatment with TLR-2 antagonist in human KCs blocked the secretion of IL-10, CXCL-10, TNF-α, and IL-6 induced by Gram-positive and Gram-negative bacterial stimulation. IL-23 and IL-1ß were only induced by Gram-negative bacteria. Thus, TLR-2 might be a potential marker and an attractive target for future treatment of patients with SBP. In addition, IL-23 and IL-1ß might distinguish early between Gram-positive and Gram-negative SBP.
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Bactérias/metabolismo , Células de Kupffer/metabolismo , Tromboxano A2/metabolismo , Receptor 2 Toll-Like/metabolismo , Animais , Quimiocina CXCL10/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The so-called protobranching phenomenon, that is the greater stability of branched alkanes with respect to their linear isomers, represents an interesting challenge for approaches based on density functional theory (DFT), since it requires a balanced description of several electronic effects, including (intramolecular) dispersion forces. Here, we investigate this problem using a protocol recently developed based on double-hybrid functionals and a small basis set, DH-SVPD, suited for noncovalent interactions. The energies of bond separation reactions (BSR), defined on the basis of an isodesmic principle, are taken as reference properties for the evaluation of 15 DFT approaches. The obtained results show that error lower than the so-called "chemical accuracy" (<1.0 kcal/mol) can be obtained by the proposed protocol on both relative reaction energies and enthalpies. These results are then verified on the standard BSR36 data set and support the proposition of our computational protocol, named DHthermo, where any DH functional, such as PBE-QIDH or B2PLYP, provides accurate results when coupled to an empirical dispersion correction and the DH-SVPD basis set. This protocol not only gives subchemical accuracy on the thermochemistry of alkanes but it is extremely easy to use with common quantum-chemistry codes.
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ABSTACTA chemical investigation of the whole plant of traditional Chinese medicine, Chrysanthemum indicum L., led to the discovery of six guaianolide-type sesquiterpenoids 1-6 with a 1,10-splited skeleton. The structure of the new compound 1 was established by extensive analysis of UV, IR, MS, NMR and ECD data. Compounds 3-6 are mutually stereoisomers with four chiral centers and their absolute configurations were determined by comparison of ECD spectra. The anti-inflammatory effects of these isolates on lipopolysaccharide (LPS)-induced nitric oxide (NO) were investigated in RAW 264.7 cells. Results showed that most of the compounds displayed NO production inhibitory activities with IC50 values ranged from 3.54 to 8.17 µM.
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Chrysanthemum , Sesquiterpenos , Animais , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico , Células RAW 264.7 , Sesquiterpenos/farmacologiaRESUMO
BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with liver cirrhosis. In recent years, it has been postulated that the rate of multidrug-resistant organisms (MDROs) is increasing, especially in nosocomial SBP patients. Aim of the present work was to investigate this hypothesis and its possible clinical consequences. MATERIALS AND METHODS: One hundred and three culture-positive patients between 2007 and 2014 were compared with 81 patients between 2015 and 2017, to study the change of microbiological profiles and their clinical consequences. The cirrhosis patients with bacterascites requiring treatment were included as well. RESULTS: The most prevalent Gram-negative bacteria isolated from ascites were Enterobacterales (31.6%) and in Gram-positive pathogens Staphylococci (22.8%). There was a significant increase in MDROs (22.3% ICU 40.7%, P = .048), accompanied by an increased incidence of sepsis (from 21.4% to 37.0%, P = .021), hepatorenal syndrome (from 40.8% to 58.0%, P = .007) and the need of catecholamine therapy (from 21.4% to 38.8%, P = .036). Nosocomial origin correlated with higher MDRO proportion, more complications and lower antimicrobial susceptibility rates in 12 commonly used antibiotics. MDROs were confirmed as an isolated predictor for inpatient mortality and complications in multivariable logistic regression. CONCLUSIONS: The feeling in clinical practice that MDROs have increased in the last 11 years could be confirmed in our study in Munich, Germany. Nosocomial SBP correlated with significantly higher MDRO rates (nearly 50%) and complication rates. In our opinion, an antibiotic combination with comprehensive effect should be taken into account in nosocomial SBP patients in this region.
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Infecções Bacterianas/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Peritonite/microbiologia , Sepse/microbiologia , Idoso , Ascite/epidemiologia , Ascite/microbiologia , Infecções Bacterianas/epidemiologia , Translocação Bacteriana , Catecolaminas/uso terapêutico , Infecção Hospitalar/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Enterococcus , Feminino , Alemanha/epidemiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Síndrome Hepatorrenal/epidemiologia , Mortalidade Hospitalar , Humanos , Cirrose Hepática/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Peritonite/epidemiologia , Terapia de Substituição Renal , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Sepse/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Vasoconstritores/uso terapêuticoRESUMO
BACKGROUND: Endoscopic biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is the most common form of palliation for malignant hilar obstruction. However, ERCP in such cases is associated with a risk of cholangitis. The incidence of post-ERCP cholangitis is particularly high in Bismuth type IV hilar obstruction, and this risk is further increased when the contrast injected for cholangiography is not drained. The present study aims to compare the incidence of cholangitis associated with the use of a contrast agent, air and CO2 for cholangiography in type IV hilar biliary lesions. METHODS: The clinical data of consecutive 70 patients with type IV hilar obstruction, who underwent ERCP from October 2013 to November 2017, were retrospectively analyzed. These patients were divided into three groups based on the agent used for cholangiography: group A, contrast (n = 22); group B, air (n = 18); group C, CO2 (n = 30). These three methods of cholangiography were chronologically separated. Prior to the ERCP, MRCP was obtained from all patients to guide the endoscopic intervention. RESULTS: At baseline, there was no significant difference in terms of the patient's age, gender, symptoms and liver function tests among the three groups (P > 0.05). The complication rates were significantly higher in group A than in groups B and C (63.6% vs. 26.7 and 27.8%, P < 0.05). The incidence of post-ERCP cholangitis was significantly higher in group A (P < 0.05), while the incidence of post-ERCP pancreatitis and bleeding were similar in the three groups. After the ERCP, the mean hospital stay was shorter in groups B and C, when compared to group A (P < 0.05). However, there was no significant difference in the 30-day mortality rate among the three groups (P > 0.05). Furthermore, there was no significant difference between groups B and C in terms of primary end points. CONCLUSION: CO2 or air cholangiography during ERCP for type IV hilar obstruction is associated with reduced risk of post-ERCP cholangitis, when compared to conventional contrast agents.
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Dióxido de Carbono/efeitos adversos , Colangiografia/efeitos adversos , Colangite/epidemiologia , Meios de Contraste/efeitos adversos , Pneumorradiografia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Neoplasias dos Ductos Biliares/cirurgia , Colangiografia/métodos , Colangite/etiologia , Feminino , Humanos , Incidência , Tumor de Klatskin/cirurgia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Pneumorradiografia/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI. METHODS: In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated. RESULTS: The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues. CONCLUSIONS: Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.
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Lesão Pulmonar Aguda/metabolismo , Cicloexilaminas/uso terapêutico , Ferroptose/efeitos dos fármacos , Fenilenodiaminas/uso terapêutico , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Aldeídos/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cicloexilaminas/farmacologia , Ferroptose/imunologia , Humanos , Ferro/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fenilenodiaminas/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismoRESUMO
CONTEXT: Lilium davidii var. unicolour Cotton (Lilium genus, Liliaceae) is an edible plant and a herb used in China to alleviate insomnia. OBJECTIVE: To investigate the alleviating insomnia mechanism of L. davidii (LD). MATERIALS AND METHODS: Wistar rats were intraperitoneally injected with p-chlorophenylalanine (PCPA) to establish an insomnia model. Rats were divided into six groups (n = 8): Control, PCPA, Estazolam (0.5 mg/kg), LD extract in low, medium and high doses (185.22, 370.44, 740.88 mg/kg). Serum hormone levels of the HPA axis, levels of 5-HT, NE and MT, and the expression of GABAA and 5-HT1A receptors in hypothalamus were determined. Moreover, behavioural and pathological changes in the hypothalamus were evaluated. RESULTS: After LD administration, body weight and brain coefficient increased by 2.74% and 8.22%, respectively, and the adrenal coefficient decreased by 25%, compared with PCPA group. Elevation of the serum hypothalamic-pituitary-adrenal (HPA) axis hormone CRH (11.24 ± 3.16 ng/mL), ACTH (565.87 ± 103.44 pg/mL) and CORT (44.28 ± 8.73 ng/mL) in the PCPA group was reversed after LD treatment. Furthermore, abnormal excitatory behaviour [5 min movement distance (2096.34 ± 259.51 cm), central exercise time (5.28 ± 1.08 s)] of insomnia rats in the PCPA group was also relieved. LD extract increased 5-HT and MT levels, reduced NE level in the hypothalamus, and upregulated the expression of GABAA R and 5-HT1A. Moreover, LD extract may improve the pathology of neurons in the hypothalamus. CONCLUSIONS: LD can be considered to develop health-care food or novel drugs to cope with the increasing number of insomniacs.
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Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Extratos Vegetais/farmacologia , Distúrbios do Início e da Manutenção do Sono/prevenção & controle , Hormônio Adrenocorticotrópico/sangue , Animais , China , Corticosterona/sangue , Hormônio Liberador da Corticotropina/sangue , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Lilium , Masculino , Melatonina/metabolismo , Modelos Animais , Neurotransmissores/metabolismo , Teste de Campo Aberto/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patients treated with entecavir, virological measurement and biochemical measurement along with LSM were measured at baseline and every 6 months. Liver biopsies were conducted at baseline and month 18 of treatment. Fibrosis regression was defined by the following two criteria: (a) Ishak score decrease ≥1 stage, (b) Ishak score decrease ≥1 stage or predominantly regressive by post-treatment PIR classification. The dynamic changes of LSM and its predictive value for histological reversibility were evaluated with piecewise linear mixed-effects model and ROC analysis. We found that at month 18 of antiviral therapy, liver fibrosis was reserved in 86 of 212 (40.6%) CHB patients by Ishak reversal criterion. Overall, a decline in LSM was associated with attenuation of Ishak score. The rate of LSM decline in the first 6 months was significantly faster in patients with fibrosis reversal (ΔLSM%Ishak = -2.19%/month, P = 0.0025; ΔLSM%Ishak/PIR = -2.56%/month, P = 0.0004). The predictive model based on baseline FIB-4 and Ishak score as well as baseline LSM, PLT, albumin and their changes during the first 6 months could predict histological reversal (AUROCIshak = 0.74, 95% CI: 0.67-0.80; AUROCIshak/PIR = 0.81, 95% CI: 0.74-0.87). We conclude that in CHB patients, changes in LSM during the first 6 months of entecavir therapy can predict histological reversibility of liver fibrosis at month 18 of antiviral therapy.
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Antivirais/uso terapêutico , Elasticidade , Guanina/análogos & derivados , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/patologia , Adolescente , Adulto , Idoso , Biópsia , Regras de Decisão Clínica , Feminino , Guanina/uso terapêutico , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Resultado do Tratamento , Adulto JovemRESUMO
Methanol-to-olefins (MTO) is a very important industrial catalysis technique for the production of light olefins, which is of great economic value and strategic significance. However, it is a great challenge for the traditional analytical methods to obtain the real-time information of product variation during MTO reaction process, which is vital for the conversion process research and mechanism explanation. In this study, a single photon ionization time-of-flight mass spectrometry (SPI-TOFMS) based on a windowless RF-discharge (WLRF) lamp was developed for real-time measurement of catalytic product during the initial stage of MTO reaction. The vacuum ultraviolet (VUV) photon energy was easily adjusted by changing the discharge gas. Argon (Ar) gas was eventually adopted as the discharge gas, since it produces photons with appropriate energy of 11.6 eV and 11.8 eV for ionization of light olefin molecules. The detection sensitivities of ethylene and propylene were largely improved to a substantially similar level with limits of detection (LODs) down to 16.98 and 9.64 ppbv, respectively. The initial stage of MTO reaction was real-time monitored with a high temporal resolution of 0.5 s, revealing that ethylene was the first olefin product followed by propylene. The successful application of WLRF-SPI-TOFMS in the monitoring of MTO catalytic process indicated broad application prospects of this instrument in the industrial reaction process monitoring.
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The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.