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The bioactive peptide has wide functions, such as lowering blood glucose levels and reducing inflammation. Meanwhile, computational methods such as machine learning are becoming more and more important for peptide functions prediction. Most of the previous studies concentrate on the single-functional bioactive peptides prediction. However, the number of multi-functional peptides is on the increase; therefore, novel computational methods are needed. In this study, we develop a method MLBP (Multi-Label deep learning approach for determining the multi-functionalities of Bioactive Peptides), which can predict multiple functions including anti-cancer, anti-diabetic, anti-hypertensive, anti-inflammatory and anti-microbial simultaneously. MLBP model takes the peptide sequence vector as input to replace the biological and physiochemical features used in other peptides predictors. Using the embedding layer, the dense continuous feature vector is learnt from the sequence vector. Then, we extract convolution features from the feature vector through the convolutional neural network layer and combine with the bidirectional gated recurrent unit layer to improve the prediction performance. The 5-fold cross-validation experiments are conducted on the training dataset, and the results show that Accuracy and Absolute true are 0.695 and 0.685, respectively. On the test dataset, Accuracy and Absolute true of MLBP are 0.709 and 0.697, with 5.0 and 4.7% higher than those of the suboptimum method, respectively. The results indicate MLBP has superior prediction performance on the multi-functional peptides identification. MLBP is available at https://github.com/xialab-ahu/MLBP and http://bioinfo.ahu.edu.cn/MLBP/.
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Aprendizado Profundo , Aprendizado de Máquina , Redes Neurais de Computação , PeptídeosRESUMO
MOTIVATION: With the great number of peptide sequences produced in the postgenomic era, it is highly desirable to identify the various functions of therapeutic peptides quickly. Furthermore, it is a great challenge to predict accurate multi-functional therapeutic peptides (MFTP) via sequence-based computational tools. RESULTS: Here, we propose a novel multi-label-based method, named ETFC, to predict 21 categories of therapeutic peptides. The method utilizes a deep learning-based model architecture, which consists of four blocks: embedding, text convolutional neural network, feed-forward network, and classification blocks. This method also adopts an imbalanced learning strategy with a novel multi-label focal dice loss function. multi-label focal dice loss is applied in the ETFC method to solve the inherent imbalance problem in the multi-label dataset and achieve competitive performance. The experimental results state that the ETFC method is significantly better than the existing methods for MFTP prediction. With the established framework, we use the teacher-student-based knowledge distillation to obtain the attention weight from the self-attention mechanism in the MFTP prediction and quantify their contributions toward each of the investigated activities. AVAILABILITY AND IMPLEMENTATION: The source code and dataset are available via: https://github.com/xialab-ahu/ETFC.
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Aprendizado Profundo , Humanos , Redes Neurais de Computação , Peptídeos/uso terapêutico , SoftwareRESUMO
The design and application of molecular photoswitches have attracted much attention. Herein, we performed a detailed computational study on the photoswitch benzylidene-oxazolone system based on static electronic structure calculations and on-the-fly excited-state dynamic simulations. For the Z and E isomer, we located six and four minimum energy conical intersections (MECIs) between the first excited state (S1) and the ground state (S0), respectively. Among them, the relaxation pathway driven by ring-puckering motion is the most competitive channel with the photoisomeization process, leading to the low photoisomerization quantum yield. In the dynamic simulations, about 88 % and 66 % trajectories decay from S1 to S0 for Z and E isomer, respectively, within the total simulation time of ~2â ps. The photoisomeization quantum yields obtained in our study (0.20 for ZâE and 0.12 for EâZ) agree well with the experimental measured values (0.25 and 0.11), even though the number of trajectories is limited to 50. Our study sheds light on the complexity of the benzylidene-oxazolone system 's deactivation process and the competitive mechanisms among different reaction channels, which provides theoretical guidance for further design and development of benzylidene-oxazolone based molecular photoswitches.
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In recent years, 3-hydroxychromone (3-HC) and its derivatives have attracted much interest for their applications as molecular photoswitches and fluorescent probes. A clear understanding of their excited-state dynamics is essential for their applications and further development of new functional 3-HC derivatives. However, the deactivation mechanism of the photoexcited 3-HC family is still puzzling as their spectral properties are sensitive to the surrounding medium and substituents. The excited-state relaxation channels of 3-HC have been a matter of intense debate. In the current work, we thoroughly investigated the excited-state decay process of the 3-HC system in the gas phase using high-level electronic structure calculations and on-the-fly excited-state dynamic simulations intending to provide insight into the intrinsic photochemical properties of the 3-HC system. A new deactivation mechanism is proposed in the gas phase, which is different from that in solvents. The excited-state intramolecular proton transfer (ESIPT) process that occurs in solutions is not preferred in the gas phase due to the existence of a sizable energy barrier (â¼0.8 eV), and thus, no dual fluorescence is found. On the contrary, the non-radiative decay process is the dominant decay channel, which is driven by photoisomerization combined with ring-puckering and ring-opening processes. The results coincide with the observations of an experiment performed in a supersonic jet by Itoh (M. Itoh, Pure Appl. Chem., 1993, 65(8), 1629-1634). The current work indicates that the solution environment plays an important role in regulating the excited-state dynamic behaviour of the 3-HC system. This study thus provides theoretical guidance for the rational design and improvement of the photochemical properties of the 3-HC system and paves the way for further investigation into its photochemical properties in complex environments.
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Spectroscopic characterization of carbon monoxide activation by neutral metal carbides is of essential importance for understanding the structure-reactivity relationships of catalytic sites, but has been proven to be very challenging owing to the difficulty in size selection. Here, we report a size-specific infrared-vacuum ultraviolet spectroscopic study of the reactions between carbon monoxide with neutral chromium carbides. Quantum chemical calculations were carried out to identify the low-lying structures and to interpret the experimental features. The results reveal that the most stable structure of CrC3(CO)2 consists of a CCO ketenylidene unit and that of CrC4(CO)2 has a semi-bridging CO with a very low CO stretching vibrational frequency at 1821 cm-1. The electron structure analyses show that this semi-bridging CO is highly activated through the delocalized Cr-C-C three-center two-electron (3c-2e) interaction between the antibonding orbitals of CO and the metal carbide skeleton. The formation of these metal carbide carbonyls is found to be both thermodynamically exothermic and kinetically facile in the gas phase. The present findings have important implications for the mechanical understanding of the catalytic processes with isolated metal atoms/clusters dispersed on supports.
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Spectroscopic characterization of highly excited neutral transition-metal complexes is important for understanding the multifaceted reaction mechanisms between metals and ligands. In this work, the reactions of neutral chromium atoms with carbon monoxide were probed by size-specific infrared spectroscopy. Interestingly, Cr(CO)3 was found to have an unprecedented 7A2â³ septet excited state rather than the singlet ground state. A combination of experiment and theory shows that the gas-phase formation of this highly excited Cr(CO)3 is facile both thermodynamically and kinetically. Electronic structure and bonding analyses indicate that the valence electrons of Cr atoms in the septet Cr(CO)3 are in a relatively stable configuration, which facilitate the highly excited structure and the planar geometric shape (D3h symmetry). The observed septet Cr(CO)3 affords a paradigm for exploring the structure, properties, and formation mechanism of a large variety of excited neutral compounds.
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An endophytic bacterium Paenibacillus polymyxa DS-R5 which can effectively inhibit the growth of pathogenic fungi was isolated from Salvia miltiorrhiza in our previous study. By using hydrochloric acid precipitation, methanol extraction, silica gel column isolation, dextran gel chromatography column, and HPLC, 3 compounds with antifungal activity were isolated. To further improve the production of antifungal compounds produced by this strain, fermentation medium was optimized using one-factor-at-a-time, Plackett-Burman design, and Box-Behnken design experiments. Through statistical optimization, the optimal medium composition was determined to be as follows: 14.7 g/l sucrose, 20.0 g/l soluble starch, 7.0 g/l corn steep liquor, 10.0 g/l (NH4)2SO4, and 0.7 g/l KH2PO4. In this optimized medium, the highest titer of antifungal compounds reached 3452 U/ml, which was 123% higher than that in the initial medium. In addition, in order to guide scale-up for production, logistic and Luedeking-Piret equations were proposed to predict the cell growth and antifungal compounds production. The fermentation kinetics and empirical equations of the coefficients (X0, Xm, µm, α, and ß) for the two models were reported, which will aid the design and optimization of industrial processes. The degrees of fit between calculated values of the model and the experimental data were 0.989 and 0.973, respectively. The results show that the cell growth and product synthesis models established in this study may better reflect the dynamic process of antifungal compounds production and provide a theoretical basis for further optimization and on-line monitoring of the fermentation process.
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Paenibacillus polymyxa , Salvia miltiorrhiza , Antifúngicos/farmacologia , Fermentação , Líquido AmnióticoRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well as genetic and environmental factors. Liraglutide has been used to control blood sugar. But the impact of liraglutide on T2DM-associated NAFLD remains unclear. In this study, we investigated the impact and potential molecular mechanisms of inhibiting ferroptosis for liraglutide improves T2DM-associated NAFLD. METHODS: Mice were fed on high-fat-diet and injected with streptozotocin to mimic T2DM-associated NAFLD and gene expression in liver was analysed by RNA-seq. The fast blood glucose was measured during the period of liraglutide and ferrostatin-1 administration. Hematoxylin and eosin staining was used to evaluate the pathological changes in the liver. The occurrence of hepatic ferroptosis was measured by lipid peroxidation in vivo. The mechanism of liraglutide inhibition ferroptosis was investigated by in vitro cell culture. RESULTS: Liraglutide not only improved glucose metabolism, but also ameliorated tissue damage in the livers. Transcriptomic analysis indicated that liraglutide regulates lipid metabolism related signaling including AMPK and ACC. Furthermore, ferroptosis inhibitor rather than other cell death inhibitors rescued liver cell viability in the presence of high glucose. Mechanistically, liraglutide-induced activation of AMPK phosphorylated ACC, while AMPK inhibitor compound C blocked the liraglutide-mediated suppression of ferroptosis. Moreover, ferroptosis inhibitor restored liver function in T2DM mice in vivo. CONCLUSIONS: These findings indicate that liraglutide ameliorates the T2DM-associated NAFLD, which possibly through the activation of AMPK/ACC pathway and inhibition of ferroptosis.
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Diabetes Mellitus Tipo 2 , Ferroptose , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Prediction of therapeutic peptide is a significant step for the discovery of promising therapeutic drugs. Most of the existing studies have focused on the mono-functional therapeutic peptide prediction. However, the number of multi-functional therapeutic peptides (MFTP) is growing rapidly, which requires new computational schemes to be proposed to facilitate MFTP discovery. In this study, based on multi-head self-attention mechanism and class weight optimization algorithm, we propose a novel model called PrMFTP for MFTP prediction. PrMFTP exploits multi-scale convolutional neural network, bi-directional long short-term memory, and multi-head self-attention mechanisms to fully extract and learn informative features of peptide sequence to predict MFTP. In addition, we design a class weight optimization scheme to address the problem of label imbalanced data. Comprehensive evaluation demonstrate that PrMFTP is superior to other state-of-the-art computational methods for predicting MFTP. We provide a user-friendly web server of PrMFTP, which is available at http://bioinfo.ahu.edu.cn/PrMFTP.
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Algoritmos , Peptídeos , Peptídeos/uso terapêuticoRESUMO
Structural characterization of neutral water clusters is crucial to understanding the structures and properties of water, but it has been proven to be a challenging experimental target due to the difficulty in size selection. Here, we report the size-specific infrared spectra of confinement-free neutral water nonamer (H2O)9 based on threshold photoionization, using a tunable vacuum ultraviolet free-electron laser. Distinct OH stretch vibrational fundamentals in the 3200-3350 cm-1 region are observed, providing unique spectral signatures for the formation of an unprecedented (H2O)9 structure evolved by adding a ninth water molecule onto a hydrogen bond-unbroken edge of the (H2O)8 octamer with D2d symmetry. This nonamer structure coexists with the five previously identified structures that can be viewed as derived by inserting a ninth water molecule into a hydrogen bond-broken edge of the D2d/S4 octamer. These findings provide key microscopic information for systematic understanding of the formation and growth mechanism of dynamical hydrogen-bonding networks that are responsible for the structure and properties of condensed-phase water.
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BACKGROUND: The aim of this retrospective study was to compare the clinical outcomes of total endoscopic transaxillary (TET) breast augmentation with those of non-TET (NTET) breast augmentation. For the purposes of this study, the term NTET refers to the combination of blunt dissection and endoscopic techniques, whereas TET did not involve blunt dissection. METHODS: We conducted a retrospective review of 119 consecutive cases of primary breast augmentation from May 1, 2020, to August 31, 2020. The primary outcomes were the number of drainage days and pain scores as assessed using the visual analog scale on the first postoperative day. The secondary outcomes were the daily drainage volume recorded during the postoperative drainage days, the presence of postoperative daily pain that required the administration of tramadol for relief, reoperation rate, and operative time. RESULTS: The number of drainage days was significantly lower in the TET group than in the NTET group (TET vs NTET: 2.56 ± 0.57 vs 3.78 ± 1.30 days, P = 0.000). The visual analog scale score on the first postoperative day was significantly lower in the TET group than in the NTET group (TET vs NTET: 4.96 ± 0.63 vs 5.93 ± 0.93, P = 0.000). CONCLUSIONS: We observed that the major outcomes of the TET group were more favorable than those of the NTET group. Based on our results, we recommend the avoidance of blunt dissection during endoscopic transaxillary breast augmentation. LEVEL OF EVIDENCE: III.
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Implante Mamário , Humanos , Implante Mamário/métodos , Implantes de Mama , Endoscopia/métodos , Mamoplastia , Dor Pós-Operatória/etiologia , Estudos RetrospectivosRESUMO
The separation of light hydrocarbon compounds is an important process in the chemical industry. Currently, its separation methods mainly include distillation, membrane separation, and physical adsorption. However, these traditional methods or materials have some drawbacks and disadvantages, such as expensive equipment costs and high energy consumption, poor selectivity, low separation ratios, and separation efficiencies. Therefore, it is important to develop novel separation materials for light hydrocarbon separation. As a new type of organic-inorganic hybrid crystalline material, metal-organic frameworks (MOFs) are promising materials for light hydrocarbon separation due to their designability of structure and easy modulation of function. This review provides an overview of recent advances in the design, synthesis, and application of MOFs for light hydrocarbon separation in recent years, with a focus on the separation of alkane, alkene, and alkyne. We discuss strategies for improving the adsorption selectivity and capacity of MOFs, including pore size limitation, physical adsorption, and chemisorption. In addition, we discuss the advantages/disadvantages, challenges, and prospects of MOFs in the separation of light hydrocarbon.
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Spectroscopic characterization of neutral highly-coordinated compounds is essential in fundamental and applied research, but has been proven to be a challenging experimental target because of the difficulty in mass selection. Here, we report the preparation and size-specific infrared-vacuum ultraviolet (IR-VUV) spectroscopic identification of group-3 transition metal carbonyls Sc(CO)7 and TM(CO)8 (TM=Y, La) in the gas phase, which are the first confinement-free neutral heptacarbonyl and octacarbonyl complexes. The results indicate that Sc(CO)7 has a C2v structure and TM(CO)8 (TM=Y, La) have a D4h structure. Theoretical calculations predict that the formation of Sc(CO)7 and TM(CO)8 (TM=Y, La) is both thermodynamically exothermic and kinetically facile in the gas phase. These highly-coordinated carbonyls are 17-electron complexes when only those valence electrons that occupy metal-CO bonding orbitals are considered, in which the ligand-only 4b1u molecular orbital is ignored. This work opens new avenues toward the design and chemical control of a large variety of compounds with unique structures and properties.
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A neutral boron carbonyl complex B4 (CO)3 is generated in the gas phase and is characterized by infrared plus vacuum ultraviolet (IR+VUV) two-color ionization spectroscopy and quantum chemical calculations. The complex is identified to have a planar C2v structure with three CO ligands terminally coordinated to a rhombus B4 core. It has a closed-shell singlet ground state that correlates to an excited state of B4 . Bonding analyses on B4 (CO)3 as well as the previously reported B4 and B4 (CO)2 indicate that the electronic structure of rhombus tetraboron cluster changes from a close-shell singlet to an open-shell singlet in B4 (CO)2 and to a close-shell singlet in B4 (CO)3 , demonstrating that the electronic structures of boron clusters can be effectively tuned via sequential CO ligand coordination.
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The incidence of diabetes-associated cognitive dysfunction is increasing. However, few clinical interventions are available to prevent the disorder. Several researches have shown that liraglutide, as a glucagon-like peptide-1 analog, has protective effects on various neurodegenerative diseases, but its roles in diabetic cognitive dysfunction are rarely reported. This study aims to investigate the protective effects of liraglutide on diabetic cognitive dysfunction and its underlying mechanisms. In vivo, the effects of liraglutide treatment were investigated in a mouse model of type 2 diabetes mellitus (T2DM). In vitro, we investigated the effects of liraglutide on the high-glucose-induced rat primary neurons. The results showed that liraglutide reduced the escape latency and increased the time in effective area in the Morris water maze test, improved the damage of hippocampal and synaptic ultrastructure, and decreased the accumulation of amyloid ß protein in hippocampus of T2DM mice. Furthermore, liraglutide increased the ratio of microtubule-associated protein light 1 chain â ¡/â , the expression of Beclin1 protein and Lysosome-associated membrane protein 2 in vivo and vitro. Additionally, Bafilomycin A1 which can inhibit the fusion of autophagosome and lysosome partially abolished the effects of liraglutide. These findings indicate liraglutide ameliorates diabetes-associated cognitive dysfunction by rescuing autophagic flux.
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Autofagia/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Animais , Proteína Beclina-1/metabolismo , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/ultraestrutura , Proteínas de Membrana Lisossomal/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Ratos , Sinapses/patologia , Sinapses/ultraestruturaRESUMO
BACKGROUND: While recent studies have reported modest to no difference in breast aesthetics for shaped and round implant types in breast augmentations, the anatomy and biomechanics in the setting of breast reconstruction is different. OBJECTIVES: Accordingly, we endeavored to evaluate whether two implant types impacted nipple position and aesthetic features in prosthetic breast reconstruction. METHODS: A retrospective chart review was carried out on patients who underwent nipple-sparing mastectomy (NSM) with immediate tissue expander breast reconstruction. Patients were divided into two cohorts: smooth round implants and textured shaped implants. Postoperative photographs were evaluated to assess nipple displacement vis-à-vis a vector of maximal projection and aesthetic outcome for features of breast shape. RESULTS: Of 102 breasts meeting the inclusion criteria, 41 had tissue expander-implant reconstruction with anatomical shaped implants, and 61 had reconstruction with smooth round implants. The shaped implant cohort had less nipple deviation from the point of maximal projection (3.69 ± 6.24 vs 7.52 ± 10.50; P < 0.0001). Graded semi-quantitative aesthetic scores were also higher (4.04 ± 0.67 vs 3.72 ± 0.93; P = 0.0044) in the shaped implants than in the round cohort. CONCLUSIONS: Unlike breast augmentation, there is a paucity of overlying breast tissue and larger dissected spaces in prosthetic breast reconstruction. Our analysis suggests that in this setting, textured anatomic implants result in less nipple deviation from the point of maximum projection and improved aesthetic outcomes compared to round implants. When considering implant choice in NSM reconstruction, the manifold risks of shaped textured implants must thus be informed by potential aesthetic benefits with respect to shape and enhanced nipple sensation.
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Implante Mamário/instrumentação , Implantes de Mama , Neoplasias da Mama/cirurgia , Mastectomia Subcutânea/efeitos adversos , Dispositivos para Expansão de Tecidos , Adulto , Idoso , Implante Mamário/métodos , Estética , Feminino , Humanos , Pessoa de Meia-Idade , Mamilos/anatomia & histologia , Satisfação do Paciente , Estudos Retrospectivos , Propriedades de Superfície , Resultado do TratamentoRESUMO
Metabotropic glutamate receptor 5 (mGluR5) is extensively involved in neural survival, differentiation, dendritic morphology, synaptic plasticity, and neural circuit formation. However, little is known about its role in neuronal polarization and axon outgrowth. In this study, we applied the selective agonist (RS)-2-chloro-5-hydroxyphenylglycine sodium salt and antagonist 3-[(2-methyl-4-thaizolyl) ethynyl] pyridine (MTEP) of mGluR5 to the cultured hippocampal neurons to observe the neuronal polarization and axon outgrowth, and further explored the possible intracellular signal transduction pathway. The results demonstrated that MTEP administration significantly attenuates the proportion of polarized neurons and the length of the axon, indicated by SMI312 (an axon marker) and Tuj-1 (a marker of all the neurites) double-labeling immunofluorescence. Western blot analysis showed that MTEP administration also inhibited the activation of AKT and nuclear translocation of nuclear factor-κB (NF-κB) p65, and decreased the phosphorylation of p65 as well. Furthermore, Akt inhibitor LY294002 treatment resulted in neuronal polarization delay and axon outgrowth retardation, while suppressing the phosphorylation and nuclear translocation of p65. We concluded that mGluR5 could regulate neuronal polarity and axon outgrowth during the morphological differentiation of rat developing neurons, and the intracellular signaling pathway of Akt-NF-κB might be involved in the action of mGluR5. © 2016 Wiley Periodicals, Inc.
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Polaridade Celular/fisiologia , NF-kappa B/metabolismo , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Polaridade Celular/efeitos dos fármacos , Embrião de Mamíferos , Hipocampo/citologia , Hipocampo/embriologia , Hipocampo/metabolismo , Neurogênese/fisiologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tiazóis/farmacologiaRESUMO
BACKGROUND AND AIMS: Although a high viral load is an independent risk factor for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after surgery, the prognostic impact of viral load on advanced HCC is unclear. This study investigated the impact of baseline HBV load and antiviral therapy on survival of patients with advanced HCC treated with sorafenib. METHODS: Of 130 patients with advanced HBV-related HCC received first-line sorafenib therapy were evaluated in a multicenter, retrospective study. RESULTS: No patients experienced severe hepatic impairment because of HBV reactivation during sorafenib therapy. The median progression-free survival (PFS) and overall survival (OS) of all patients were 5.7 and 9.6 months respectively. Patients with a baseline HBV DNA ≤10(4) copies/ml had significantly better OS than those with >10(4) copies/ml (10.4 vs 6.6 months; P = 0.002), but PFS showed an increasing trend (5.8 vs 4.8 months; P = 0.068). Patients who received antiviral therapy had a better trend in OS than those who did not (12.0 vs 8.3 months; P = 0.058), but there was no difference in PFS (6.4 vs 4.1 months; P = 0.280). In a multivariate analysis, the baseline HBV DNA level >10(4) copies/ml (P = 0.001; hazard ration [HR] = 2.294; 95% CI 1.429-3.676) and antiviral therapy (P = 0.038; HR 0.617; 95% CI 0.390-0.975) were independent predictors of OS. CONCLUSION: In patients with advanced HBV-related HCC treated with sorafenib, a high baseline HBV load was an adverse prognostic factor for survival. However, survival was significantly improved with the use of antiviral therapy.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , DNA Viral/análise , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/virologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/virologia , Niacinamida/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sorafenibe , Análise de Sobrevida , Carga ViralRESUMO
Plastic additives such as the antioxidant 2,4-di-tert-butylphenol (2,4-DTBP) have been widely detected in aquatic environments, over a wide range of concentrations reaching 300 µg/L in surface water, potentially threatening the health of aquatic organisms and ecosystems. However, knowledge of the specific effects of 2,4-DTBP on aquatic vertebrates is still limited. In this study, adult zebrafish were exposed to different concentrations of 2,4-DTBP (0, 0.01, 0.1 and 1.0 mg/L) for 21 days in the laboratory. The amplicon sequencing results indicated that the diversity and composition of the zebrafish gut microbiota were significantly changed by 2,4-DTBP, with a shift in the dominant flora to more pathogenic genera. Exposure to 2,4-DTBP at 0.1 and 1.0 mg/L significantly increased the body weight and length of zebrafish, suggesting a biological stress response. Structural assembly defects were also observed in the intestinal tissues of zebrafish exposed to 2,4-DTBP, including autolysis of intestinal villi, adhesions and epithelial detachment of intestinal villi, as well as inflammation. The transcriptional expression of some genes showed that 2,4-DTBP adversely affected protein digestion and absorption, glucose metabolism and lipid metabolism. These results are consistent with the PICRUSt2 functional prediction analysis of intestinal microbiota of zebrafish exposed to 2,4-DTBP. This study improves our understanding of the effects of 2,4-DTBP on the health of aquatic vertebrates and ecosystems.
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Microbioma Gastrointestinal , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Ecossistema , Fenóis/químicaRESUMO
The BTB (broad-complex, tramtrack, and bric-à-brac) domain is a highly conserved protein interaction motif in eukaryotes. They are widely involved in transcriptional regulation, protein degradation and other processes. Recently, an increasing number of studies have shown that these genes play important roles in plant growth and development, biotic and abiotic stress processes. Here, we summarize the advances of these proteins ubiquitination-mediated development and abiotic stress responses in plants based on the protein structure, which may facilitate the study of this type of gene in plants.