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BACKGROUND: This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. METHODS: Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10-4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period. RESULTS: Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I. CONCLUSION: The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.
With advancements in science and technology, ovarian transplantation techniques have become increasingly mature. However, there are still many questions that need to be addressed. For instance, the large size of the transplanted ovarian tissues may cause over-recruitment of the primordial follicles. When the transplanted ovarian tissue is too small, it can only exert limited functionality and may not meet the patient's needs. This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function in rats after oophorectomy, and to provide a theoretical basis for determining the minimum effective volume of heterotopic ovarian tissue transplantation.
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Ciclo Estral , Ovariectomía , Ovario , Trasplante Heterotópico , Animales , Femenino , Ovario/trasplante , Ratas , Hormona Antimülleriana/sangre , Hormona Folículo Estimulante/sangre , Estradiol/sangre , Ratas Sprague-Dawley , Tamaño de los Órganos , Folículo Ovárico , Reproducción/fisiologíaRESUMEN
This paper introduces the Least Increase aversion (LIA) protocol to investigate the relative impact of factors that may trigger cybersickness. The protocol is inspired by the Subjective Matching methodology (SMT) from which it borrows the incremental construction of a richer VR experience, except that the full-blown target experience may cause undesired discomfort. In the first session, the participant briefly encounter all factors at the maximum level. Then in the second session they start with the minimum level of all factors as a Baseline. Subsequently, we expect the participant to minimize their exposure to the most adverse factors. This approach ranks the factors from mildest to worst and helps detect individual susceptibility to cybersickness triggers.To validate the applicability of LIA protocol, we further evaluate it with an experiment to identify individual susceptibility to three rotational axes (Yaw, Pitch, and Roll). The findings not only confirm the protocol's capability to accurately discern individual rankings of various factors to cybersickness but also indicate that individual susceptibility is more intricate and multifaceted than initially anticipated.
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In this research paper, we conducted a study to investigate the connection between three objective measures: Electrocardio-gram(EGG), Electrogastrogram (EGG), and Electroencephalogram (EEG), and individuals' susceptibility to cybersickness. Our primary objective was to identify which of these factors plays a central role in causing discomfort when experiencing rotations along three different axes: Roll, Pitch, and Yaw. This study involved 35 participants who were tasked with destroying asteroids using their eye gaze while undergoing passive rotations in four separate sessions. The results, when combined with subjective measurements (specifically, Fast motion sickness questionnaire (FMS) and Simulator sickness questionnaire (SSQ) score), demonstrated that EGG measurements were superior in detecting symptoms associated with nausea. As for ECG measurements, our observations did reveal significant changes in Heart Rate Variability (HRV) parameters. However, we caution against relying solely on ECG as a dependable indicator for assessing the extent of cybersickness. Most notably, EEG signals emerged as a crucial resource for discerning individual differences related to these rotational axes. Our findings were significant not only in the context of periodic activities but also underscored the potential of aperiodic activities in detecting the severity of cybersickness and an individual's susceptibility to rotational triggers.
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Gráficos por Computador , Mareo por Movimiento , Humanos , Fijación Ocular , Electroencefalografía , Mareo por Movimiento/diagnóstico , Electrocardiografía/efectos adversosRESUMEN
Hepatocellular carcinoma (HCC) is significantly associated with adverse prognostic outcomes. The development and progression of different types of human tumors are significantly influenced by APOB. Nevertheless, the significance and pathomechanisms of APOB in HCC have not been conclusively determined. We assessed APOB expression levels in HCC using three publicly available databases of TIMER2.0, UALCAN and Human Protein Atlas. To identify the biological function of APOB, we conducted enrichment analysis via LinkedOmics. Moreover, UALCAN was employed to assess the relationship between APOB expression and clinicopathological features among HCC patients. Additionally, the Kaplan-Meier plotter was utilized to investigate the prognostic relevance of APOB in HCC. To explore potential regulatory ncRNAs that could bind to APOB, we utilized StarBase and GEPIA. Furthermore, the correlation between APOB expression and immune cell infiltration, as well as immune checkpoint genes, was investigated using Spearman's correlation analysis in TISIDB, GEPIA, and TIMER2.0. The findings of our investigation showed a notable decrease in the expression levels of APOB among individuals diagnosed with HCC. Moreover, a noteworthy correlation was observed between the expression of APOB and immune checkpoint genes, alongside the occurrence of immune cell infiltration. The levels of APOB expression in HCC tissues also showed correlations with various clinicopathological features. According to Cox regression analysis, decreased APOB expression emerged as a potential autonomous predictor for OS, RFS, DSS, and PFS among HCC patients. Furthermore, we identified six potential pathways associated with non-coding RNA (ncRNA) as the most promising pathway for APOB in HCC. Our results illuminate the possible involvement of APOB in HCC and offer understanding into its governing mechanisms and medical importance.
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Carbon-based materials that process a wide bandgap, high mechanical performance, thermal stability and adjustable characteristics are in high demand. Auxeticity is one of the factors that helps enhances the mechanical performance. Based on this concept, two stable layered carbon-based materials, namely α-C2O and ß-C2O, are proposed. A new mechanism (multi-directional negative Poisson's ratio (NPR) effect) is induced, which is attributed to the interaction of modified pz orbitals between interfacial layers. This effect introduces high mechanical properties into materials. Besides, all layered materials are ultrawide bandgap semiconductors, which endows them comparable dielectric properties to those of diamond. Furthermore, α-BK-C2O would maintain its configuration over 2000 K, thereby guaranteeing extremely high thermodynamic stability. So far, these advantages suggested that these carbon-based layer materials could be used in nanoelectronics, especially in electromechanical devices.
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The Cu0-Cu+ interfaces play a key role in the electrochemical CO2 reduction reaction (CO2RR) to produce multi-carbon products (C2+), however, it is difficult for Cu+ to exist stably under reducing conditions. Herein, we construct highly dispersed and stable Cu-Cu2O-CeOx interface on reduced graphene oxide (rGO) for CO2 electroreduction to C2+ products. During the synthesis process, utilizing strong electrostatic interactions, the complex ions of Cu2+ and Ce3+ are uniformly adsorbed on the surface of graphene oxide. Then, under the solvothermal reaction of ethylene glycol and thiourea, the two metal complex ions are converted into highly dispersed and ultrafine Cu2S-CeOx nanocomposites on rGO. Interestingly, CeOx and thiourea synergistically regulate the generation of only Cu+. Under the CO2RR process, the reconstruction of Cu2S promotes the formation of Cu0 and Cu2O species. CeOx stabilizes partial Cu+ species and promotes the formation of Cu-Cu2O-CeOx composite interface. With the help of synergistic effect of Cu0, Cu+ and CeOx, the optimized reaction interface achieves the Faradaic efficiency (FE) of 74.5 % for C2+ products with the current density of 230 mA cm-2 at -0.9 V versus the reversible hydrogen electrode. In situ attenuate total reflectance-infrared absorption spectroscopy (ATR-IRAS) spectra show that the composite interfaces promote the adsorption and activation of H2O and CO2, improve the surface coverage of CO intermediates (*CO), and thus accelerate the CC coupling process.
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BACKGROUND: The epidermal growth factor receptor (EGFR) protein has been intensively studied as a therapeutic target for non-small cell lung cancer (NSCLC). The aminobenzimidazole derivatives as the fourth-generation EGFR inhibitors have achieved promising results and overcame EGFR mutations at C797S, del19 and T790M in NSCLC. OBJECTIVE: In order to understand the quantitative structure-activity relationship (QSAR) of aminobenzimidazole derivatives as EGFRdel19 T790M C797S inhibitors, the four-dimensional QSAR (4D-QSAR) and multivariate image analysis (MIA-QSAR) have been performed on the data of 45 known aminobenzimidazole derivatives. METHODS: The 4D-QSAR descriptors were acquired by calculating the association energies between probes and aligned conformational ensemble profiles (CEP), and the regression models were established by partial least squares (PLS). In order to further understand and verify the 4D-QSAR model, MIA-QSAR was constructed by using chemical structure pictures to generate descriptors and PLS regression. Furthermore, the molecular docking and averaged noncovalent interactions (aNCI) analysis were also performed to further understand the interactions between ligands and the EGFR targets, which was in good agreement with the 4D-QSAR model. RESULTS: The established 4D-QSAR and MIA-QSAR models have strong stability and good external prediction ability. CONCLUSION: These results will provide theoretical guidance for the research and development of aminobenzimidazole derivatives as new EGFRdel19 T790M C797S inhibitors.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Relación Estructura-Actividad Cuantitativa , Simulación del Acoplamiento Molecular , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Mutación , Resistencia a AntineoplásicosRESUMEN
Feral swine (FS) (Sus scrofa) are an invasive species that has spread widely across the southern United States, including the West Gulf region. With their rapidly increasing population, they have caused severe damage to landowners. To better understand private landowners' knowledge and attitudes toward FS, we conducted a mail survey in the West Gulf region including Arkansas, Louisiana, and East Texas in 2021. The results indicated that the majority of landowners are familiar with, have overall negative opinions of, and are concerned about the presence and future population growth of FS in this region. Nearly 70% of the private landowners surveyed supported stricter FS control regulations. Logistic regression results further revealed that landowners' supportiveness for FS control regulations is associated with their perceived FS-induced economic damage and ownership characteristics (i.e., age and tenure). These findings shed new light on private landowners' perspectives on FS invasions and control regulations, aiding in developing and implementing FS control/management policies and programs in the West Gulf region and beyond.
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Especies Introducidas , Conocimiento , Porcinos , Animales , Arkansas , Texas , LouisianaRESUMEN
The photocycloaddition of 1,4-dihydropyridines (1,4-DHPs) is a main approach to synthesize structurally complex compounds, which are important intermediates for the preparation of cage compounds, such as 3,9-diazatetraasterane, 3,6-diazatetraasterane, 3,9-diazatetracyclododecane, and 6,12-diazaterakishomocubanes. The acquisition of different cage compounds depended on the chemoselectivity, which is mainly caused by the reaction conditions and structural characteristics of 1,4-DHPs. This study aimed to investigate the effect of the structural characteristics on chemoselectivity in [2 + 2]/[3 + 2] photocycloaddition of 1,4-DHPs. The photocycloadditions were conducted on the 1,4-diaryl-1,4-dihydropyridine-3-carboxylic ester with steric hindrance groups at the C3 position or chirality at the C4 position irradiated by a 430 nm blue LED lamp. When the 1,4-DHPs contained high steric hindrance groups at the C3 position, [2 + 2] photocycloaddition was the main reaction, resulting in 3,9-diazatetraasteranes with a yield of 57%. Conversely, when the 1,4-DHPs were resolved to a chiral isomer, the main reaction was [3 + 2] photocycloaddition, producing 6,12-diazaterakishomocubanes with a yield of 87%. To investigate the chemoselectivity and understand the photocycloaddition of 1,4-DHPs, density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed at the B3LYP-D3/def-SVP//M06-2X-D3/def2-TZVP level. The steric hindrance and excitation energy modulated by substituents at the C3 position and chiral carbon at the C4 position were crucial for the chemoselectivity in [2 + 2]/[3 + 2] photocycloaddition of 1,4-DHPs.
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Polyoxometalates (POMs), as a class of multinuclear metal oxygen clusters, have promising biological activities. And their amino acid derivatives will lead to better pharmacological activity by the diversity in structures and properties. With reference to the anti-HIV-1 activities of PM-19 (K7PTi2W10O40) and its pyridinium derivatives, a series of novel Keggin-type POMs with amino acid as organic cations (A7PTi2W10O40) were synthesized by hydrothermal synthetic method. The final products were characterized by 1H NMR, Elemental analyzes and single crystal X-ray diffraction. All the synthesized compounds were obtained in the yields of 44.3-61.7% and evaluated the cytotoxicity and anti-HIV-1 activity in vitro. Compared with the reference compound PM-19, the target compounds had a lower toxicity to TZM-bl cells and a higher inhibitory activity against HIV-1. Among them, compound A3 showed higher anti-HIV-1 activity with IC50 of 0.11 nM than that of PM-19 with 4.68 nM. This study demonstrated that combination of Keggin-type POMs and amino acids can be a new strategy to enhance the anti-HIV-1 biological activity of POMs. All results will be expected to helpful for developing more potent and effective HIV-1 inhibitors.
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Aminoácidos , Aminoácidos/farmacología , Cristalografía por Rayos XRESUMEN
Despite advancements made in the therapeutic strategies on hepatocellular carcinoma (HCC), the survival rate of HCC patient is not satisfactory enough. Therefore, there is an urgent need for the valuable prognostic biomarkers in HCC therapy. In this study, we aimed to screen hub genes correlated with prognosis of HCC via multiple databases. 117 HCC-related genes were obtained from the intersection of the four databases. We subsequently identify 10 hub genes (JUN, IL10, CD34, MTOR, PTGS2, PTPRC, SELE, CSF1, APOB, MUC1) from PPI network by Cytoscape software analysis. Significant differential expression of hub genes between HCC tissues and adjacent tissues were observed in UALCAN, HCCDB and HPA databases. These hub genes were significantly associated with immune cell infiltrations and immune checkpoints. The hub genes were correlated with clinical parameters and survival probability of HCC patients. 147 potential targeted therapeutic drugs for HCC were identified through the DGIdb database. These hub genes could be used as novel prognostic biomarkers for HCC therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores/metabolismo , Carcinoma Hepatocelular/patología , Biología Computacional , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/patología , Pronóstico , Mapas de Interacción de Proteínas/genéticaRESUMEN
We examined the distribution characteristics of melanin in different tissues and organs of Triplophysa stenura and T. orientalis by using histological method. The results showed that melanin was distributed in the head skin, dorsal skin, lateral skin, peritoneal kidney layer, spinal cord cavity wall, peritoneal wall layer, pericardial cavity wall, neurocranial cavity wall and eyes of both Triplophysa species. Melanin was not found in the abdomen skin, liver chorion, gonad capsule and spleen capsule. Melanin was distributed in the dermis layer and subcutaneous layer in the skin, and in the endothelial layer or wall layer in other tissues and organs. Melanin was mainly distributed on the back, with sparse and symmetrical distribution on both sides of the body. Melanin was more abundant and densely distributed on the dorsal and lateral skin with stripes than areas without stripes. Melanin in the no stripes skin was only partially aggregated or formed intermittently distributed melanin patches. The distribution of melanin in different tissues and organs of the same Triplophysa species was different, and the percentage of distribution area and thickness of melanin layer were significantly different. However, the distribution characteristics of melanin in the same tissues and organs were similar in two Triplophysa species. The distribution of melanin in the tissues and organs of both species were related to the intensity of ultraviolet radiation they received, which was an adaptation to the intense ultraviolet radiation environment of the plateau.
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Cipriniformes , Melaninas , Animales , Rayos UltravioletaRESUMEN
In this paper, an Nb alloying layer on a TC4 alloy was fabricated by using high-current pulsed electron beam (HCPEB) irradiation to improve surface performance. X-ray diffraction (XRD), optical microscopy (OM), laser surface microscope (LSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the phase composition and microstructure of the surface layer. The microhardness, wear tests and corrosion resistance were also examined. The results show that after HCPEB alloying, a Nb-alloyed layer was formed with about 3.6 µm in thickness on the surface of the sample, which was mainly composed of α'-Ti martensite, ß-Ti equiaxial crystals, and NbTi4 particles. After HCPEB irradiation, the surface hardness, wear resistance and corrosion resistance of Nb alloying layer on TC4 alloy were improved compared to the initial samples.
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We examined the distribution of melanin during the development of the larvae of Schizothorax o'connori except the eyes with histological method. The results showed that after hatching, the appearance sequence of melanin in different organs were following an order of the outer membrane of neurocranium, the pericardial cavity and the dorsal skin, and the peritoneum and the spinal cord. Specifically, melanin appeared in the outer membrane of neurocranium around 5 DAH (days after hatching), in the pericardial cavity and the back skin at 7 DAH, and in the peritoneum and the spinal cord at 10 DAH. Melanin was found in the skin and internal organs (the outer membrane of neurocranium, the pericardial cavity, the peritoneum, the spinal cord) of S. o'connori at 10 DAH, which was mainly distributed on the back. The appearance and distribution of melanin in the postembryonic development of S. o'connori might be related to the high ultraviolet radiation. Our results could provide reference for further research on the UV protection mechanism of melanin for fish and provide theoretical support for the optimization of rearing conditions for larvae in the plateau.
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Cyprinidae , Melaninas , Animales , Larva , Rayos UltravioletaRESUMEN
Two series of novel N 6 derivatives of 8-azapurine I and II were designed as antiplatelet agents. Series I and II were N 6 amino derivatives and N 6 hydrazone derivatives of 8-azapurine, respectively. The compounds were synthesized in acceptable yields via conventional procedures, including nucleophilic substitution, diazotization, and amination or hydrazonation with amino alcohol and 4,6-dichloropyrimidine as starting materials. To assess the ability of the synthesized compounds as antiplatelet agents, the ADP-induced platelet aggregation assay of Born was performed both in vitro and in vivo using ticagrelor as a reference control substance. The analysis of the structure-activity relationship and molecular docking were also discussed in detail. The results demonstrated that series I and II compounds exhibited antiplatelet activity in vitro and IIh was the most active compound (IC50 = 0.20 µM) among the target compounds, being almost 4-fold better than ticagrelor (IC50 = 0.74 µM). For a preliminary assessment of the safety profile, a bleeding test (mouse tail) and a single-dose toxicity test were conducted. The use of compound IIh resulted in a shorter bleeding time, less blood loss and lower acute toxicity compared to ticagrelor. In addition, a molecular docking study was performed to investigate the binding capacity and binding mode between IIh and P2Y12.
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To obtain new anticancer agents with antimetastatic adjunct efficacy, a series of novel N4 -hydrazone derivatives of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one were designed and synthesized by an eight-step reaction, with appropriate yields. All the synthesized compounds were evaluated for their antiproliferative activity against A549 and MCF-7 cells and for antiplatelet aggregation activity in vitro. The results showed that compounds 25 and 35 not only showed potent antiproliferative activity against the A549 (IC50 = 15.3 and 21.4 µM) and MCF-7 (IC50 = 15.6 and 10.9 µM) cell lines but also showed certain antiplatelet aggregation activity (inhibition rates: 47.0% and 45.8%). These results indicated that the structural modification on the N4 -hydrazone moiety of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one is promising to obtain novel anticancer compounds with antimetastatic adjunct efficacy. In addition, a molecular docking study was performed to investigate the possible targets, and these results indicated that compounds 25 and 35 have the potential to target EGFR, HER2, and P2Y12 .
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Antineoplásicos/farmacología , Hidrazonas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Pirimidinas/farmacología , Células A549 , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Humanos , Hidrazonas/síntesis química , Hidrazonas/química , Concentración 50 Inhibidora , Células MCF-7 , Simulación del Acoplamiento Molecular , Metástasis de la Neoplasia/prevención & control , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/química , Pirimidinas/síntesis química , Pirimidinas/química , Relación Estructura-ActividadRESUMEN
AIDS, caused by HIV-1, is one of the most dangerous infectious diseases in the world. Therefore, it is necessary to develop new drugs with more potent bioactivities, less toxicity and higher tolerability for controlling the viral load, particularly by using the raw materials that are widely available. Agaricus blazei Murill (AbM), known in China as jisongrong, is of great importance as a food source and as a health-promoting supplement for immunomodulation. The polysaccharides of AbM exhibit various biological activities, such as regulating cellular immunity and providing anti-oxidative, anti-infective, and anti-inflammatory effects. At present, to our knowledge, no report has explored the chemically sulfated and anti-HIV-1 activity of AbM polysaccharides. Herein, the sulfated AbM polysaccharides with different sulfur contents were prepared by the chlorosulfonic acid-pyridine method. The characteristics of sulfated derivatives were established by the determination of the sulfur content, the relative molecular weight, and the Fourier-transform infrared spectroscopy. The anti-HIV activities of the sulfated AbM polysaccharides were evaluated by CCK-8 and the single-cycle pseudovirus infection (TZM-bl) assay. The sulfated AbM polysaccharides had strong antiviral properties, and the half-maximal inhibitory concentrations approached that of the positive control, azidothymidine. Sulfated modification of AbM polysaccharides can increase their anti-HIV pharmacological activity, which makes them promising alternative candidates as bioactive macromolecules for biomedical applications in HIV/AIDS.
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Agaricus/química , Fármacos Anti-VIH/farmacología , VIH/efectos de los fármacos , Polisacáridos/farmacología , Sulfatos/química , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Conformación de Carbohidratos , Pruebas de Sensibilidad Microbiana , Polisacáridos/síntesis química , Polisacáridos/químicaRESUMEN
Flavonoids are potential strikingly natural compounds with antioxidant activity and acetylcholinesterase (AChE) inhibitory activity for treating Alzheimer's disease (AD). In present study, in line with our interests in flavonoid derivatives as AChE inhibitors, a four-dimensional quantitative structure-activity relationship (4D-QSAR) molecular model was proposed. The data required to perform 4D-QSAR analysis includes 52 compounds reported in the literature, usually analogs, and their measured biological activities in a common assay. The model was generated by a complete set of 4D-QSAR program which was written by our group. The best model was found after trying multiple experiments. It had a good predictive ability with the cross-validation correlation coefficient Q2 = 0.77, the internal validation correlation coefficient R2 = 0.954, and the external validation correlation coefficient R2pred = 0.715. The molecular docking analysis was also carried out to understand exceedingly the interactions between flavonoids and the AChE targets, which was in good agreement with the 4D-QSAR model. Based on the information provided by the 4D-QSAR model and molecular docking analysis, the idea for optimizing the structures of flavonoids as AChE inhibitors was put forward which maybe provide theoretical guidance for the research and development of new AChE inhibitors.
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Inhibidores de la Colinesterasa/química , Flavonoides/química , Modelos Moleculares , Relación Estructura-Actividad CuantitativaRESUMEN
In the experimental process of preparing diethyl 3,5-dicarboxylate-1,4-dihydropyridine (1,4-DHP) by a Hantzsch-like reaction, it was found that a by-product named diethyl 3,5-dicarboxylate-1,2-dihydropyridine (1,2-DHP) was produced in the reaction. To discuss this phenomenon, the effects of the reaction conditions on the yield ratio of 1,4-DHP and 1,2-DHP were studied by using aromatic amines, aromatic aldehydes and ethyl propiolate as raw materials. The mechanisms for the formation of 1,4-DHP and 1,2-DHP were proposed based on the isolated intermediate named diethyl 4-((phenylamino)methylene)pent-2-enedioate generated by the Michael addition of aniline and ethyl propiolate. The transition state structures were optimized and the reaction energy barriers of intermediates in the speculated mechanisms were calculated by DFT calculations at the M062X/def2TZVP//B3LYP-D3/def-SVP level. It was found that the reaction energy barriers and dominant configurations of intermediates IM2 and IM3' are the determinants for the chemoselectivity. Together, these results demonstrate a high chemoselectivity in the synthesis of 1,4-DHPs and 1,2-DHPs by a Hantzsch-like reaction and that 1,4-DHPs and 1,2-DHPs can be easily obtained under different conditions.
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Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) rs12427129 and rs3816153 in HOX transcript antisense intergenic RNA (HOTAIR) might interact with hepatitis B virus (HBV) infection to increase the risk of hepatocellular carcinoma (HCC). However, it is unclear whether HBV infection is a potential mediator between HOTAIR rs12427129, rs3816153, and HCC. This study, including 1262 HCC cases and 1559 controls, aimed to use a four-way decomposition method to quantify the interaction and mediation effects of HBV infection in the association between rs12427129, rs3816153, and HCC. We found that rs12427129 and rs3816153 were associated with a risk of HBV infection among the controls (CC: CT+TT, adjusted odds ratio (OR)=1.77, 95% confidence interval (CI)=1.32-2.36 and GG: GT+TT, adjusted OR=0.63, 95% CI=0.48-0.82). The four-way decomposition revealed that rs12427129, rs3816153, and HBV infection had statistically significant reference interaction on HCC (excess risk (95% CI): -0.362 (-0.530, -0.195), p<0.001 and excess risk (95% CI): 0.433 (0.059, 0.808), p=0.023), and the proportion attributed to reference interaction were 110.82% and 125.27%, respectively. The pure indirect effect suggested that the rs3816153 GT + TT genotype can reduce the risk of HCC by 21.79% (excess risk (95% CI): -0.075 (-0.142, -0.009), p=0.026) when HBV infection as a mediator. Our findings suggested that HBV infection interacts or mediates with the association between rs12427129, rs3816153, and HCC. This would provide a new perspective for exploring the underlying biological mechanism between HOTAIR SNPs, HBV infection, and HCC.