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High-entropy alloys are a class of materials that contain five or more elements in near-equiatomic proportions1,2. Their unconventional compositions and chemical structures hold promise for achieving unprecedented combinations of mechanical properties3-8. Rational design of such alloys hinges on an understanding of the composition-structure-property relationships in a near-infinite compositional space9,10. Here we use atomic-resolution chemical mapping to reveal the element distribution of the widely studied face-centred cubic CrMnFeCoNi Cantor alloy2 and of a new face-centred cubic alloy, CrFeCoNiPd. In the Cantor alloy, the distribution of the five constituent elements is relatively random and uniform. By contrast, in the CrFeCoNiPd alloy, in which the palladium atoms have a markedly different atomic size and electronegativity from the other elements, the homogeneity decreases considerably; all five elements tend to show greater aggregation, with a wavelength of incipient concentration waves11,12 as small as 1 to 3 nanometres. The resulting nanoscale alternating tensile and compressive strain fields lead to considerable resistance to dislocation glide. In situ transmission electron microscopy during straining experiments reveals massive dislocation cross-slip from the early stage of plastic deformation, resulting in strong dislocation interactions between multiple slip systems. These deformation mechanisms in the CrFeCoNiPd alloy, which differ markedly from those in the Cantor alloy and other face-centred cubic high-entropy alloys, are promoted by pronounced fluctuations in composition and an increase in stacking-fault energy, leading to higher yield strength without compromising strain hardening and tensile ductility. Mapping atomic-scale element distributions opens opportunities for understanding chemical structures and thus providing a basis for tuning composition and atomic configurations to obtain outstanding mechanical properties.
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Background: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent. Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes. Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes. Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors. Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.
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Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.
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Transtorno Depressivo Maior , Humanos , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal , Função Executiva , Lobo Frontal , Imageamento por Ressonância Magnética , Mapeamento EncefálicoRESUMO
Two-phase titanium-based alloys are widely used in aerospace and biomedical applications, and they are obtained through phase transformations between a low-temperature hexagonal closed-packed α-phase and a high-temperature body-centred cubic ß-phase. Understanding how a new phase evolves from its parent phase is critical to controlling the transforming microstructures and thus material properties. Here, we report time-resolved experimental evidence, at sub-ångström resolution, of a non-classically nucleated metastable phase that bridges the α-phase and the ß-phase, in a technologically important titanium-molybdenum alloy. We observed a nanosized and chemically ordered superstructure in the α-phase matrix; its composition, chemical order and crystal structure are all found to be different from both the parent and the product phases, but instigating a vanishingly low energy barrier for the transformation into the ß-phase. This latter phase transition can proceed instantly via vibrational switching when the molybdenum concentration in the superstructure exceeds a critical value. We expect that such a non-classical phase evolution mechanism is much more common than previously believed for solid-state transformations.
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Ligas , Titânio , Ligas/química , Temperatura Alta , Molibdênio/química , Transição de Fase , Titânio/químicaRESUMO
In the endometrium of women with recurrent implantation failure and unexplained recurrent miscarriage, the expression levels of homeobox A10 and E-cadherin were positively correlated. To explore whether homeobox A10 regulates E-cadherin during endometrial receptivity establishment, Ishikawa and RL95-2 cells were transfected with target-specific small interfering RNA (siRNA) and overexpression plasmid of homeobox A10. The expression levels of homeobox A10 and E-cadherin were measured by western blot and quantitative Real-time Polymerase Chain Reaction (qRT-PCR). Attachment assay of JEG-3 spheroids to endometrial cells were conducted to explore the adhesive functions after homeobox A10 interfered. Chromatin immunoprecipitation assays and dual luciferase reporter were used to investigate the regulatory mechanism of homeobox A10. The CD1 mice were transfected with si-homeobox A10 to confirm these results in vivo. In Ishikawa and RL95-2 cells, the expression of E-cadherin was positively correlated with homeobox A10 when it was silenced/overexpressed. Consistently, the adhesion of endometrial epithelium cells and trophoblast cells was inhibited after homeobox A10 was silenced, and exogenous restoration of E-cadherin expression reversed this effect to some extent. Homeobox A10 regulates the expression of E-cadherin by directly binding to a conserved motif (TGTACTAAAAA) located in the E-cadherin promoter region. In addition, after knockdown of homeobox A10 in CD1 mice, both the implantation and live birth rates were decreased. In conclusion, homeobox A10 can bind to the E-cadherin promoter region and directly regulate its expression, thereby improving endometrial receptivity and subsequently increasing the embryo adhesion and implantation.
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Antígenos CD , Caderinas , Implantação do Embrião , Endométrio , Proteínas Homeobox A10 , Animais , Antígenos CD/genética , Caderinas/genética , Linhagem Celular Tumoral , Implantação do Embrião/fisiologia , Endométrio/metabolismo , Feminino , Proteínas Homeobox A10/genética , Humanos , Camundongos , RNA Interferente Pequeno/genéticaRESUMO
The advancement of recombinant virus-like particle-based vaccines has attracted global attention owing to substantially safety and high efficacy in provoking a protective immunity against various chronic and infectious diseases in humans and animals. A robust, low-cost, and scalability separation and purification technology is of utmost importance in the downstream processing of recombinant virus-like particles to produce affordable and safe vaccines. Being a relatively simple, environmentally friendly, and efficient biomolecules recovery approach, aqueous two-phase systems have received great attention from researchers worldwide. This review aims to highlight the challenges and outlook in addition to the current applications of aqueous two-phase systems in downstream processing of virus-like particles. The efforts will confidently reinforce scholars' knowledge and fill in the valuable research gap in the aspect of concerning recombinant virus-like particle-based vaccines development, particularly related to the virus-like particles downstream production processes.
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Vacinas de Partículas Semelhantes a Vírus , AnimaisRESUMO
BACKGROUND: Schizophrenia is a severe, heritable, and refractory psychiatric disorder. Several studies have shown that the disrupted in schizophrenia 1 (DISC1) gene is closely associated with schizophrenia by its role in neuronal morphology, synaptic function, brain development, and dopamine homeostasis etc. This study intended to investigate the expression levels of DISC1 gene in schizophrenia patients compared with healthy controls, and the expression variation of DISC1 gene before and after antipsychotic treatment in schizophrenia patients. METHODS: In this study, we compared DISC1 expression levels in blood of 48 healthy controls, and 32 schizophrenia patients before and after 12 weeks of antipsychotic treatment using real-time quantitative PCR (RT-qPCR) analysis. RESULTS: The expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients before antipsychotic treatment were higher than those in healthy controls (P < 0.01); whereas after antipsychotic treatment, the expression levels of DISC1 gene in peripheral blood mononuclear cells of schizophrenia patients still remained increased (P < 0.01). CONCLUSIONS: Our study provided further support for the involvement of DISC1 in the development of schizophrenia.
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Expressão Gênica , Leucócitos Mononucleares/efeitos dos fármacos , Proteínas do Tecido Nervoso/genética , Esquizofrenia/genética , Adulto , Antipsicóticos/uso terapêutico , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/sangue , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: Schizophrenia (SCZ) is a heritable, refractory, and devastating psychiatric disorder. Previous studies have shown that the variants of CUB and sushi multiple domains 1 (CSMD1) demonstrate significant genome-wide association with SCZ. However, few studies have been conducted on the effect of antipsychotics on the expression levels of CSMD1. This study explored whether a change occurs in the expression of the CSMD1 gene before and after antipsychotic treatment in SCZ patients. METHODS: The study population comprised Han Chinese patients from eastern China, including 32 SCZ patients and 48 healthy controls. The expression of CSMD1 before and after treatment in the SCZ group and between the two groups was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expression levels of the CSMD1 gene in the peripheral blood mononuclear cells (PBMCs) of SCZ patients were lower than those in the healthy controls. The expression levels of the CSMD1 gene in the PBMCs of the SCZ patients after antipsychotic treatment were higher than those in the baseline SCZ patients (all P < 0.05). CONCLUSIONS: Our results showed that the expression levels of CSMD1 are correlated with the development and treatment of SCZ, providing further evidence for the involvement of CSMD1 in SCZ.
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Povo Asiático/genética , Predisposição Genética para Doença/genética , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Esquizofrenia/sangue , Esquizofrenia/genética , Proteínas Supressoras de Tumor/sangue , Proteínas Supressoras de Tumor/genética , Adulto , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Biomarcadores/sangue , China/epidemiologia , Feminino , Expressão Gênica , Predisposição Genética para Doença/epidemiologia , Estudo de Associação Genômica Ampla/métodos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esquizofrenia/tratamento farmacológicoRESUMO
Sublimation is an important endothermic phase transition in which the atoms break away from their neighbors in the crystal lattice and are removed into the gas phase. Such debonding process may be significantly influenced by dislocations, the crystal defect that changes the bonding environment of local atoms. By performing systematic defects characterization and in situ transmission electron microscopy (TEM) tests on a core--shell MgO-Mg system, which enables us to "modulate" the internal dislocation density, we investigated the role of dislocations on materials' sublimation with particular focus on the sublimation kinetics and mechanism. It was observed that the sublimation rate increases significantly with dislocation density. As the density of screw dislocations is high, the intersection of screw dislocation spirals creates a large number of monatomic ledges, resulting in a "liquid-like" motion of solid-gas interface, which significantly deviates from the theoretically predicted sublimation plane. Our calculation based on density functional theory demonstrated that the remarkable change of sublimation rate with dislocation density is due to the dramatic reduction in binding energy of the monatomic ledges. This study provides direct observation to improve our understanding on this fundamental phase transition as well as to shed light on tuning materials' sublimation by "engineering" dislocation density in applications.
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Using the modulation transfer function obtained by establishing and solving the two-dimensional continuity equation, we have calculated and comparatively analyzed the resolution characteristics of transmission-mode exponential-doping and uniform-doping Ga0.37Al0.63As photocathodes. The calculations show that compared with a uniform-doping Ga0.37Al0.63As photocathode, the exponential-doping structure can significantly improve not only the resolution, but also the quantum efficiency of the photocathode. This improvement is different from the approach for high resolution by reducing the emission layer thickness Te and electron diffusion length LD, or by increasing the recombination velocity of the back-interface, SV, which results in low quantum efficiency. Furthermore, the improvement in resolution and quantum efficiency for the transmission-mode exponential-doping Ga0.37Al0.63As photocathodes is the result of the effect of the built-in electric field on electron transport and lateral diffusion.
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Internal strain and its distribution within the crystal lattice play crucial roles in modulating dislocation activities, thereby affecting mechanical properties of materials. Through the synergistic application of integrated differential phase contrast, in situ transmission electron microscopy characterizations, and computational simulations, a method is unveiled for homogenizing dislocation pinning in NiCoCr multi-principal element alloy (MPEA) through the introduction of a high concentration of oxygen atoms with high diffusion mobility. The doping of massive oxygen atoms creates a high density of strong local pinning points for dislocation motion. Notably, oxygen interstitials exhibit remarkable diffusion and mobility across different octahedral and tetrahedral sites within the distorted crystal lattice of NiCoCrO alloy, even at room temperature. The capability allows for the release of severe stress concentrations arising from dislocation entanglement and the establishment of new strong local pinning points at alternative locations in a uniform way, enabling the material with high strength and outstanding deformability. These findings suggest that interstitial atoms can exhibit significant mobility, even at ambient temperature, in complex MPEAs with spreading lattice distortion, opening new possibilities for dislocation engineering.
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Zero thermal expansion (ZTE) alloys with high mechanical response are crucial for their practical usage. Yet, unifying the ZTE behavior and mechanical response in one material is a grand obstacle, especially in multicomponent ZTE alloys. Herein, we report a near isotropic zero thermal expansion (αl = 1.10 × 10-6 K-1, 260-310 K) in the natural heterogeneous LaFe54Co3.5Si3.35 alloy, which exhibits a super-high toughness of 277.8 ± 14.7 J cm-3. Chemical partition, in the dual-phase structure, assumes the role of not only modulating thermal expansion through magnetic interaction but also enhancing mechanical properties via interface bonding. The comprehensive analysis reveals that the hierarchically synergistic enhancement among lattice, phase interface, and heterogeneous structure is significant for strong toughness. Our findings pave the way to tailor thermal expansion and obtain prominent mechanical properties in multicomponent alloys, which is essential to ultra-stable functional materials.
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To research the attenuation performance of the AlGaN photocathode, three samples with the same structures grown by metalorganic chemical vapor deposition were activated with three different activation methods, which are called Cs-only, Cs-O, and Cs-O-Cs activation, respectively. The spectral responses and attenuated photocurrents of the three AlGaN photocathodes were measured. The results show that the Cs-O activated AlGaN photocathode exhibits the lowest attenuation speed in the first few hours, and the attenuation speed of the Cs-only activated one is fastest. After attenuating for 90 min, the attenuation photocurrent curve of the Cs-O-Cs activated sample is coincident with that of the Cs-O activated one. The main factor affecting the photocurrent attenuation is related to Cs atoms desorbed from the photocathode surface.
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Understanding the coordinated deformation of multiple phases under applied stress is crucial for the structural design of dual-phase or multiphase advanced alloys. In this study, in-situ transmission electron microscope tensile tests were performed to investigate the dislocation behaviors and the transportation of dislocation plasticity during the deformation of a dual-phase Ti-10(wt.%) Mo alloy having hexagonal close-packed α phase and body-centered cubic ß phase. We demonstrated that the dislocation plasticity preferred to transmit from alpha to alpha phase along the longitudinal axis of each plate, regardless of where dislocations were formed. The intersections of different α plates provided local stress concentration that facilitated the initiation of dislocation activities from there. Dislocations then migrated along the longitudinal axis of α plates and carried dislocation plasticity from one plate to another through these intersections as well. Since the α plates distributed in various orientations, dislocation slips occurred in multiple directions, which is beneficial for uniform plastic deformation of the material. Our micropillar mechanical testing further quantitatively demonstrated that the distribution of α plates and the α-α plates' intersections plays important role in tuning the mechanical properties of the material.
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MicroRNA-9-5p (miR-9-5p) is highly expressed in the brain and has been implicated in the risk of schizophrenia. We compared the expression levels of miR-9-5p in schizophrenia cases and healthy controls and evaluated whether regulatory targets of miR-9-5p are enriched in schizophrenia genome-wide risk genes. Literature-based analysis was conducted to construct molecular pathways connecting miR-9-5p and schizophrenia. We found that the expression levels of miR-9-5p were down-regulated in the peripheral blood of schizophrenia patients compared with those in healthy controls. miR-9-5p can regulate 24 out of the 1136 genome-wide risk genes of schizophrenia, which was higher than by chance (hypergeometric test P = 4.09E-06). The literature-based analysis showed that quantitative genetic changes driven by miR-9 exert more inhibitory (the IL1B, ABCB1, FGFR1 genes) than promoting (the INS gene) effects on schizophrenia, suggesting that miR-9 may protect against schizophrenia. Our results suggest that miR-9-5p deficiency may contribute to the development of schizophrenia.
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MicroRNAs , Esquizofrenia , Humanos , Esquizofrenia/genética , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Layered double hydroxides (LDHs) can be used as catalysts and adsorbents due to their high stability, safety, and reusability. The preparation of modified LDHs mainly includes coprecipitation, hydrothermal, ion exchange, calcination recovery, and sol-gel methods. LDH-based materials have high anion exchange capacity, good thermal stability, and a large specific surface area, which can effectively adsorb and remove heavy metal ions, inorganic anions, organic pollutants, and oil pollutants from wastewater. Additionally, they are heterogeneous catalysts and have excellent catalytic effect in the Fenton system, persulfate-based advanced oxidation processes, and electrocatalytic system. This review ends with a discussion of the challenges and future trends of the application of LDHs in wastewater treatment.
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OBJECTIVE: Repeated pregnancy loss has been shown to be related to decidual immune imbalance. Metformin has been found to promote a shift in the Th17/Treg balance towards immune tolerance. Our research aims to evaluate and obtain further information on the role and potential mechanism of metformin on Th17/Treg balance in the early pregnancy decidua. METHODS: Decidual immune cells from normal pregnancy women were treated with metformin, pro-inflammatory cytokines or metformin + cytokines respectively. The mRNA expression levels of STAT3, STAT5, RORC and Foxp3 were detected by qRT-PCR. The proportions of Th17 and Treg cells, the stability of Treg cells, and the STATs phosphorylation levels of T cells were evaluated by flow cytometry. The cytokine concentrations in the culture medium were detected by ELISA. RESULTS: After treated with metformin, indicators related to immune tolerance, including the mRNA expression and phosphorylation levels of STAT5, mRNA expression level of Foxp3, the proportion of Treg cell, and the IL-10 concentration increased significantly. Indicators related to immune rejection including the mRNA expression level of STAT3, the proportion of Th17 cell, and the IL-17A concentration showed a significant decrease. In inflammatory conditions, the proportion of Th-like Treg cells increased. Metformin promoted CD25 expression to maintain Treg cell stability. CONCLUSION: Metformin has beneficial effects on immunological tolerance at the maternal-foetal interface in early pregnancy. The underlying mechanism may be that metformin restores the Th17/Treg balance by changing the expression of STATs, which is conducive to establishing maternal-foetal immune tolerance.
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Background: The metabolic characteristics of premature ovarian insufficiency (POI), a reproductive endocrine disease characterized by abnormal sex hormone metabolism and follicle depletion, remain unclear. Metabolomics is a powerful tool for exploring disease phenotypes and biomarkers. This study aims to identify metabolic markers and construct diagnostic models, and elucidate the underlying pathological mechanisms for POI. Methods: Non-targeted metabolomics was utilized to characterize the plasma metabolic profile of 40 patients. The metabolic markers were identified through bioinformatics and machine learning, and constructed an optimal diagnostic model by classified multi-model analysis. Enzyme-linked immunosorbent assay (ELISA) was used to verify antioxidant indexes, mitochondrial enzyme complexes, and ATP levels. Finally, integrated transcriptomics and metabolomics were used to reveal the dysregulated pathways and molecular regulatory mechanisms of POI. Results: The study identified eight metabolic markers significantly correlated with ovarian reserve function. The XGBoost diagnostic model was developed based on six machine learning models, demonstrating its robust diagnostic performance and clinical applicability through the evaluation of receiver operating characteristic (ROC) curve, decision curve analysis (DCA), calibration curve, and precise recall (PR) curve. Multi-omics analysis showed that mitochondrial respiratory chain electron carrier (CoQ10) and enzyme complex subunits were down-regulated in POI. ELISA validation revealed an elevation in oxidative stress markers and a reduction in the activities of antioxidant enzymes, CoQ10, and mitochondrial enzyme complexes in POI. Conclusion: Our findings highlight that mitochondrial dysfunction and energy metabolism disorders are closely related to the pathogenesis of POI. The identification of metabolic markers and predictive models holds significant implications for the diagnosis, treatment, and monitoring of POI.
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Menopausa Precoce , Insuficiência Ovariana Primária , Feminino , Humanos , Antioxidantes , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Biomarcadores , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Hepatitis B virus (HBV) infection remains a major global health burden, due to the increasing risk of complications, such as cirrhosis and hepatocellular carcinoma. Novel anti-HBV agents are critical required. Our previous study suggested that Artemisia argyi essential oil (AAEO) significantly inhibited the replication of HBV DNA and especially the secretion of hepatitis B antigen in vitro. PURPOSE: The aim of this study was to prepare AAEO loaded nanostructured lipid carriers (AAEO-NLCs) for the delivery of AAEO to the liver, investigated the therapeutic benefits of AAEO-NLCs against HBV in a duck HBV (DHBV) model and explored its potential mechanism. STUDY DESIGN AND METHODS: AAEO-NLCs were prepared by hot homogenization and ultrasonication method. The DHBV-infected ducks were treated with AAEO (4 mg/kg), AAEO-NLCs (0.8, 4, and 20 mg/kg of AAEO), and lamivudine (20 mg/kg) for 15 days. The DHBV DNA levels in the serum and liver were measured by quantitative Real-Time PCR. Pharmacokinetics and liver distribution were performed in rats after oral administration of AAEO-NLCs and AAEO suspension. The potential antiviral mechanism and active compounds of AAEO were investigated by network pharmacology and molecular docking. RESULTS: AAEO-NLCs markedly inhibited the replication of DHBV DNA in a dose-dependent manner and displayed a low virologic rebound following withdrawal the treatment in DHBV-infected ducks. Moreover, AAEO-NLCs led to a more pronounced reduction in viral DNA levels than AAEO suspension. Further investigations of pharmacokinetics and liver distribution in rats confirmed that NLCs improved the oral bioavailability and increased the liver exposure of AAEO. The potential mechanisms of AAEO against HBV explored by network pharmacology were associated with signaling pathways related to immune response, such as tumor necrosis factor, nuclear factor kappa B, and sphingolipid signaling pathways. Furthermore, a total of 16 potential targets were obtained, including prostaglandin-endoperoxide synthase-2 (PTGS2), caspase-3, progesterone receptor, etc. Compound-target docking results confirmed that four active compounds of AAEO had strong binding interactions with the active sites of PTGS2. CONCLUSIONS: AAEO-NLCs displayed potent anti-HBV activity with improved oral bioavailability and liver exposure of AAEO. Thus, it may be a potential therapeutic strategy for the treatment of HBV infection.
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Artemisia , Vírus da Hepatite B do Pato , Neoplasias Hepáticas , Óleos Voláteis , Ratos , Animais , Simulação de Acoplamento Molecular , Óleos Voláteis/farmacologia , Farmacologia em Rede , Ciclo-Oxigenase 2 , Antivirais/farmacologia , Vírus da Hepatite B/genética , Vírus da Hepatite B do Pato/genéticaRESUMO
Background: We previously reported that obese mice had significantly high lipid content in embryos, and excessive lipids are detrimental to embryonic development. However, whether maternal obesity has an effect on embryonic vitrification injury and subsequent pregnancy outcomes is still controversial. This study was conducted to clarify the influence of maternal obesity on embryonic vitrification injury and subsequent pregnancy outcomes by in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: We retrospectively collected medical record of IVF/ICSI patients from reproductive medicine centers in two tertiary hospitals. The patients were classified into a low-weight group (<18.5 kg/m2), normal-weight group (18.5-23.9 kg/m2), overweight group (24.0-27.9 kg/m2) and obese group (≥28.0 kg/m2) according to their body mass index (BMI). Multivariable logistic regression analysis was performed to compare pregnancy outcomes in fresh and frozen embryo transfer among different BMI groups to define the correlation between BMI and embryonic vitrification injury. Results: A total of 44 773 women among 20-40 years old were recruited in this study, of which 27 797 underwent their first fresh embryo transfer and 16 976 underwent their first frozen embryo transfer. For fresh embryo transfer, there was no significant difference in the clinical pregnancy rate, live birth rate, and miscarriage rate of 4 BMI groups. For frozen-thawed embryo transfer, there was a significant increase in the clinical pregnancy rate of the overweight group (AOR = 1.14, 95% CI: 1.05-1.25) and the obese group (AOR = 1.24, 95% CI: 1.03-1.50), while the miscarriage rate (AOR = 1.42, 95% CI: 1.05-1.92) also showed a significant increase in the obese group compared to the normal-weight group. Conclusion: This study provided a new understanding of the effect of maternal obesity on embryonic vitrification injury. Maternal obesity does not worsen the outcome of IVF/ICSI, particularly in the frozen-thawed group.