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1.
Angew Chem Int Ed Engl ; 63(1): e202316097, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37985423

RESUMO

Electrocatalytic nitrogen oxidation reaction (NOR) offers an efficient and sustainable approach for conversion of widespread nitrogen (N2 ) into high-value-added nitrate (NO3 - ) under mild conditions, representing a promising alternative to the traditional approach that involves harsh Haber-Bosch and Ostwald oxidation processes. Unfortunately, due to the weak absorption/activation of N2 and the competitive oxygen evolution reaction, the kinetics of NOR process is extremely sluggish accompanied with low Faradaic efficiencies and NO3 - yield rates. In this work, an oxygen-vacancy-enriched perovskite oxide with nonstoichiometric ratio of strontium and ruthenium (denoted as Sr0.9 RuO3 ) was synthesized and explored as NOR electrocatalyst, which can exhibit a high Faradaic efficiency (38.6 %) with a high NO3 - yield rate (17.9 µmol mg-1 h-1 ). The experimental results show that the amount of oxygen vacancies in Sr0.9 RuO3 is greatly higher than that of SrRuO3 , following the same trend as their NOR performance. Theoretical simulations unravel that the presence of oxygen vacancies in the Sr0.9 RuO3 can render a decreased thermodynamic barrier toward the oxidation of *N2 to *N2 OH at the rate-determining step, leading to its enhanced NOR performance.

2.
Phys Chem Chem Phys ; 26(1): 144-152, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38063043

RESUMO

With favorable colour purity, multi-resonance thermally activated delayed fluorescence (MR-TADF) molecules exhibit enormous potential in high-definition displays. Due to the relatively small chemical space of MR-TADF molecules, it is challenging to improve molecular performance through domain-specific expertise alone. To address this problem, we focused on optimizing the classic molecule, DABNA-1, using machine learning (ML). Molecular morphing operations were initially employed to generate the adjacent chemical space of DABNA-1. Subsequently, a machine learning model was trained with a limited database and used to predict the properties throughout the generated chemical space. It was confirmed that the top 100 molecules suggested by machine learning present excellent electronic structures, characterized by small reorganization energy and singlet-triplet energy gaps. Our results indicate that the improvement in electronic structures can be elucidated through the view of the molecular orbital (MO). The results also reveal that the top 5 molecules present weaker vibronic peaks of the emission spectrum, demonstrating higher colour purity when compared to DABNA-1. Notably, the M2 molecule presents a high RISC rate, indicating its promising future as a high-efficiency MR-TADF molecule. Our machine-learning-assisted approach facilitates the rapid optimization of classical molecules, addressing a crucial requirement within the organic optoelectronic materials community.

3.
Sensors (Basel) ; 23(19)2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37836868

RESUMO

Ciphertext policy-attribute-based encryption (CP-ABE), which provides fine-grained access control and ensures data confidentiality, is widely used in data sharing. However, traditional CP-ABE schemes often choose to outsource data to untrusted third-party cloud service providers for storage or to verify users' access rights through third parties, which increases the risk of privacy leakage and also suffers from the problem of opaque permission verification. This paper proposes an access control scheme based on blockchain and CP-ABE, which is based on multiple authorization centers and supports policy updating. In addition, blockchain technology's distributed, decentralized, and tamper-proof features are utilized to solve the trust crisis problem in the data-sharing process. Security analysis and performance evaluation show that the proposed scheme improves the computational efficiency by 18%, 26%, and 68% compared to previous references. The proposed scheme also satisfies the indistinguishability under chosen-plaintext attack (IND-CPA).

4.
Nanotechnology ; 34(9)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36541478

RESUMO

Au-n-octanedithiol-Au molecular junction (Au-SC8S-Au) has been investigated using density functional theory combined with the nonequilibrium Green's function approach. Theoretically calculated results are used to build the relationship between the interface binding structures and single-molecule quantum conductance of n-octanedithiol (SC8S) embodied in a gold nanogap with or without stretching forces. To understand the electron transport mechanism in the single molecular nanojunction, we designed three types of Au-SC8S-Au nanogaps, including flat electrode through an Au atom connecting (Model I), top-pyramidal or flat electrodes with the molecule adsorbing directly (Model II), and top-pyramidal Au electrodes with Au atomic chains (Model III). We first determined the optimized structures of different Au-SC8S-Au nanogaps, and then predicted the distance-dependent stretching force and conductance in each case. Our calculated results show that in the Model I with an Au atom bridging the flat Au (111) gold electrodes and the SC8S molecule, the conductance decreases exponentially before the fracture of Au-Au bond, in a good agreement with the experimental conductance in the literature. For the top-pyramidal electrode Models II and III, the magnitudes of molecular conductance are larger than that in Model I. Our theoretical calculations also show that the Au-Au bond fracture takes place in Models I and III, while the Au-S bond fracture appears in Model II. This is explained due to the total strength of three synergetic Au-Au bonds stronger than an Au-S bond in Model II. This is supported from the broken force about 2 nN for the Au-Au bond and 3 nN for the Au-S bond.

5.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142144

RESUMO

Southern corn leaf blight is one of the most widespread foliar diseases in maize-producing areas worldwide and can seriously reduce the yield and quality of sweet corn. However, the molecular mechanisms underlying the disease in sweet corn have not been widely reported. In this study, two sweet corn inbred lines, resistant K13 (RK13) and susceptible K39 (SK39), were used to explore the disease resistance mechanism of southern leaf blight. We observed morphological characteristics and assessed the changes in protective enzymatic activity in sweet corn leaves after inoculation of C. heterostrophus. RNA-seq was performed to elucidate the transcriptional dynamics and reveal the key pathways involved in southern leaf blight resistance without pathogens (Mock) and at 1 and 3 days post inoculation (1 and 3 dpi). Differentially expressed genes (DEGs) were identified in the SK39 group (including three pairwise combinations: SK39-0d_vs_SK39-1d, SK39-1d_vs_SK39-3d and SK39-1d_vs_SK39-3d), the RK13 group (including three pairwise combinations: RK13-0d_vs_RK13-1d, RK13-1d_vs_RK13-3d and RK13-1d_vs_RK13-3d), and the SK39_vs_RK13 group (including three pairwise combinations: SK39-0d_vs_RK13-0d, SK39-1d_vs_RK13-1d, and SK39-3d_vs_RK13-3d). In our study, 9455 DEGs from the RK13 group, 9626 from the SK39 group, and 9051 DEGs from the SK39_vs_RK13 group were obtained. Furthermore, 2775, 163, and 185 DEGs were co-expressed at SK39_vs_RK13, RK13, and SK39, respectively. A functional analysis of the DEGs revealed that five pathways-i.e., photosynthesis, plant hormone signal transduction, MAPK signaling pathway, phenylpropanoid biosynthesis, and biosynthesis of secondary metabolites-and transcription factor families play crucial roles in disease resistance. The results from the present study enabled the identification of the JA and SA signaling pathways, which are potentially involved in the response to southern leaf blight in maize. Our findings also highlight the significance of ZIM transcription factors and pathogenesis-related (PR) genes during pathogen infection. This study preliminarily explored the molecular mechanisms of the interaction between sweet corn and C. heterostrophus and provides a reference for identifying southern leaf blight resistance genes in the future.


Assuntos
Resistência à Doença , Zea mays , Resistência à Doença/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/genética , Reguladores de Crescimento de Plantas , Fatores de Transcrição/genética , Zea mays/genética
6.
Inorg Chem ; 60(13): 9757-9761, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34115470

RESUMO

The development of nonprecious catalysts for hydrogenation of organic molecules is of great importance in heterogeneous catalysis. Herein, we report a series of N-doped hollow carbon frameworks encompassing cobalt nanoparticles (denoted as Co@NHF-900) constructed as a new kind of reusable catalyst for this purpose by pyrolysis of ZIF-8@Co-dopamine under Ar atmospheres. Notably, the framework of ZIF-8 is essential for efficient catalyst by providing a carbon framework to support Co-dopamine. The experimental results reveal that the ZIF-8 renders a large hollow place within the catalysts, allowing the enrichment of the substrate and windows of the hollow structure and the ease of mass transfer of products during the reaction. All of the virtues made Co@NHF-900 a good candidate for hydrogenation of quinolines with high activity (TOF value of 119 h-1, which is several times than that of akin catalysts) and chemoselectivity.

7.
Sensors (Basel) ; 20(17)2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32872595

RESUMO

The intrinsic heterogeneity property of concrete causes strong multiple scatterings during wave propagation, forming coda wave that follows very complex trajectories. As a superposition of multiply scattered waves, coda wave shows great sensitivity to subtle changes, but meanwhile lose spatial resolution. To make use of its sensitivity and turn the limitation into advantage, this paper presents an experimental study of three-dimensionally imaging local changes in concrete by application of inverse algorithms to coda wave measurements. Load tests are performed on a large reinforced concrete beam that contains multiple pre-existing millimeter-scale cracks in order to match real life situation. The joint effects of cracks and stresses on coda waves have been monitored using a network of fixed transducers placed at the surface. The global waveform decorrelations and velocity variations are firstly quantified through coda wave interferometry technique. Subsequently, two inverse algorithms are independently applied to map the densities of changes at each localized position. Using this methodology, the stress changes and subtle cracks in the concrete beam are detected and imaged for both temporal and spatial domains.

8.
BMC Ophthalmol ; 19(1): 132, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226955

RESUMO

BACKGROUND: Although the pathogenesis of glaucoma is not fully understood,an elevated intraocular pressure (IOP) is a major factor contributing to its development and progression. The aim of this study was to investigate the changes in the vessel densities of the macula and optic nerve head (ONH) after an acute elevation in the intraocular pressure (IOP) observed using optical coherence tomography angiography (OCTA). METHODS: This was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and one hour after the LPI. The retinal vessel densities of the macula and ONH were measured using OCTA at the baseline and one hour after the LPI. RESULTS: A total of 64 eyes of 51 individuals were enrolled in this study, and 58 eyes of 43 individuals finally completed the study with a mean IOP rise of 10.5 ± 7.6 mmHg after the LPI. Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤10 mmHg, group B = 10 mmHg < IOP rise ≤20 mmHg, and group C = IOP rise > 20 mmHg. The vessel density did not differ after the acute IOP elevation in either the macular region or papillary region in group A or group B (p > 0.05), but there was a significant difference in group C (p < 0.05). However, when the subjects were not separated into groups, the vessel densities of the ONH and macular region did not differ between the measurements obtained at the baseline and one hour after the LPI (p > 0.05). The correlation existed in peripapillary and macular vessel density (p < 0.05). CONCLUSION: In these subjects with narrow antenior chamber, an acute mild or moderate IOP elevation for one hour after the LPI did not affect the vessel density in the macula or ONH, as examined using OCTA. However, when the IOP rise was greater than 20 mmHg, the macular and papillary vessel density decreased significantly.


Assuntos
Câmara Anterior/patologia , Hipertensão Ocular/patologia , Vasos Retinianos/patologia , Doença Aguda , Idoso , Feminino , Humanos , Pressão Intraocular/fisiologia , Macula Lutea/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Disco Óptico/irrigação sanguínea , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos
10.
PLoS One ; 19(3): e0300975, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547074

RESUMO

Android malware is becoming more common, and its invasion of smart devices has brought immeasurable losses to people's lives. Most existing Android malware detection methods extract Android features from the original application files without considering the high-order hidden information behind them, but these hidden information can reflect malicious behaviors. To solve this problem, this paper proposes Z2F, a detection framework based on multidimensional Android feature extraction and graph neural networks for Android applications. Z2F first extracts seven types of Android features from the original Android application and then embeds them into a heterogeneous graph. On this basis, we design 12 kinds of meta-structures to analyze different semantic spaces of heterogeneous graphs, mine high-order hidden semantic information, and adopt a multi-layer graph attention mechanism to iteratively embed and update information. In this paper, a total of 14429 Android applications were detected and 1039726 Android features were extracted, with a detection accuracy of 99.7%.


Assuntos
Redes Neurais de Computação , Registros , Humanos , Diferencial Semântico , Semântica
11.
ACS Nano ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913550

RESUMO

Electrocatalytic nitrogen oxidation reaction (NOR) can convert nitrogen (N2) into nitrate (NO3-) under ambient conditions, providing an attractive approach for synthesis of NO3-, alternative to the current approach involving the harsh Haber-Bosch and Ostwald oxidation processes that necessitate high temperature, high pressure, and substantial carbon emission. Developing efficient NOR catalysts is a prerequisite, which remains a formidable challenge, owing to the weak activation/dissociation of N2. A variety of NOR electrocatalysts have been developed, but their NOR kinetics are still extremely sluggish, resulting in inferior Faradaic Efficiencies. Here, we report a high-entropy Ru-based perovskite oxide (denoted as Ru-HEP) that can function as a high-performance NOR catalyst and exhibit a high NO3- yield rate of 39.0 µmol mg-1 h-1 with a Faradaic Efficiency of 32.8%. Both our experimental results and theoretical calculations suggest that the high-entropy configuration of Ru-HEP perovskite oxide can markedly enhance the oxygen-vacancy concentration, where the Ru sites and their neighboring oxygen vacancies can serve as unsaturated centers and decrease the overall energy barrier for N2 electrooxidation, thereby leading to promoted NOR kinetics. This work presents an alternative avenue for promoting NOR catalysis on perovskite oxides through the high-entropy engineering strategy.

12.
ACS Chem Neurosci ; 15(9): 1893-1903, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38613492

RESUMO

Depression is a common mental disorder. In recent years, more and more attention has been paid to depression and its etiology and pathogenesis. This review aims to explore the neuroprotective and antidepressant effects of hop components. By establishing an in vitro cell damage model using PC12 cells induced by corticosterone (CORT) and an in vivo depression model through the intracranial injection of lipopolysaccharide (LPS) in mice, hop ethyl acetate extract (HEA) was used to study the protective effect and mechanism of HEA on neuronal cells in vitro and the antidepression effect and mechanism in vivo. The results showed that HEA increased the survival and decreased the rate of lactate dehydrogenase (LDH) release, apoptosis, and the ROS and NO content of CORT-induced PC12 cells. HEA alleviated depressive-like behavior, neuroinflammation, reduction of norepinephrine, and dendritic spines induced by intracerebroventricular injection of LPS in mice and increases the expression levels of BDNF, SNAP 25, and TrkB proteins without any significant side effects or toxicity. Hops demonstrated significant comprehensive utilization value, and this work provided an experimental basis for the role of hops in the treatment of depression and provided a basis for the development of HEA for antidepressant drugs or dietary therapy products.


Assuntos
Acetatos , Antidepressivos , Corticosterona , Depressão , Humulus , Fármacos Neuroprotetores , Extratos Vegetais , Animais , Células PC12 , Camundongos , Depressão/tratamento farmacológico , Extratos Vegetais/farmacologia , Acetatos/farmacologia , Antidepressivos/farmacologia , Ratos , Fármacos Neuroprotetores/farmacologia , Masculino , Humulus/química , Lipopolissacarídeos/farmacologia , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos
13.
Nanoscale ; 16(5): 2662-2671, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230765

RESUMO

Materials exhibiting X-ray-induced photochromism have consistently piqued the interest of researchers. Exploring the photochromic properties of such materials is valuable for understanding the structural changes and electron transfer processes that occur under high energy radiation, such as X-ray irradiation. Here, a crystalline silver(I) nanocluster synthesized from tert-butylacetylene silver was found to have the ability to exhibit color and photoluminescence changes upon exposure to X-ray radiation. The responsive behavior was observed across a wide temperature range of 100-300 K, with the ability to respond particularly well to soft X-rays (λ > 1 Å) and exhibit light responsiveness to hard X-rays (λ < 1 Å). By combining experimental findings including X-ray diffraction, X-ray photoelectron spectroscopy, electron spin resonance, etc. with theoretical calculations, we have proposed that X-ray irradiation induces electron transfer from chloride (Cl-) located in the center of the silver(I) nanocluster to the surrounding Ag14 in the skeleton. This represents the first documented example in which electron transfer induced by X-ray excitation has been observed, accompanied by a photochromism process, in silver nanoclusters. This study contributes to our understanding of X-ray-induced photochromism and the electron transfer process in silver cluster compounds. It also provides valuable insights and potential design strategies for applications such as photochromism, photoluminescence color change, and photoenergy conversion.

14.
J Anim Sci Biotechnol ; 15(1): 4, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38238856

RESUMO

BACKGROUND: The benefits of combining benzoic acid and essential oils (BAO) to mitigate intestinal impairment during the weaning process have been well established, while the detailed underlying mechanism has not been fully elucidated. Previous research has primarily focused on the reparative effects of BAO on intestinal injury, while neglecting its potential in enhancing intestinal stress resistance. METHODS: In this study, we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure. Piglets were pre-supplemented with BAO for 14 d, followed by a challenge with LPS or saline to collect blood and intestinal samples. RESULTS: Our findings demonstrated that BAO supplementation led to significant improvements in piglets' final weight, average daily gain, and feed intake/body gain ratio. Additionally, BAO supplementation positively influenced the composition of intestinal microbiota, increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota, Prevotella and Oscillospira. Furthermore, BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge. This was evidenced by elevated levels of T-AOC, SOD, and GSH, as well as decreased levels of MDA, TNF-α, and IL-6 in the plasma. Moreover, piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity, as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts. Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway. Additionally, the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO. CONCLUSIONS: In summary, our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition, reinforcing the intestinal barrier, and enhancing antioxidative and anti-inflammatory capabilities. These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.

15.
Antioxidants (Basel) ; 13(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38397739

RESUMO

This study aims to investigate the impact of dietary supplementation with selenium yeast (SeY) and glycerol monolaurate (GML) on the transfer of antioxidative capacity between the mother and fetus during pregnancy and its underlying mechanisms. A total of 160 sows with similar body weight and parity of 3-6 parity sows were randomly and uniformly allocated to four groups (n = 40) as follows: CON group, SeY group, GML group, and SG (SeY + GML) group. Animal feeding started from the 85th day of gestation and continued to the day of delivery. The supplementation of SeY and GML resulted in increased placental weight and reduced lipopolysaccharide (LPS) levels in sow plasma, placental tissues, and piglet plasma. Furthermore, the redox balance and inflammatory markers exhibited significant improvements in the plasma of sows fed with either SeY or GML, as well as in their offspring. Moreover, the addition of SeY and GML activated the Nrf2 signaling pathway, while downregulating the expression of pro-inflammatory genes and proteins associated with inflammatory pathways (MAPK and NF-κB). Vascular angiogenesis and nutrient transportation (amino acids, fatty acids, and glucose) were upregulated, whereas apoptosis signaling pathways within the placenta were downregulated with the supplementation of SeY and GML. The integrity of the intestinal and placental barriers significantly improved, as indicated by the increased expression of ZO-1, occludin, and claudin-1, along with reduced levels of DLA and DAO with dietary treatment. Moreover, supplementation of SeY and GML increased the abundance of Christensenellaceae_R-7_group, Clostridium_sensus_stricto_1, and Bacteroidota, while decreasing levels of gut microbiota metabolites LPS and trimethylamine N-oxide. Correlation analysis demonstrated a significant negative relationship between plasma LPS levels and placental weight, oxidative stress, and inflammation. In summary, dietary supplementation of SeY and GML enhanced the transfer of antioxidative capacity between maternal-fetal during pregnancy via gut-placenta axis through modulating sow microbiota composition.

16.
Int J Nanomedicine ; 18: 3125-3139, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333734

RESUMO

Introduction: Neutralizing antibodies (NAbs) are essential for preventing reinfection with SARS-CoV-2 and the recurrence of COVID-19; nonetheless, the formation of NAbs following vaccination and infection remains enigmatic due to the lack of a practical and effective NAb assay in routine laboratory settings. In this study, we developed a convenient lateral flow assay for the rapid and precise measurement of serum NAb levels within 20 minutes. Methods: Receptor-binding domain-fragment crystallizable (RBD-Fc) and angiotensin-converting enzyme 2-histidine tag (ACE2-His) were expressed by the eukaryotic expression systems of Spodoptera frugiperda clone 9 and human embryonic kidney 293T, respectively. Then, colloidal gold was synthesized and conjugated with ACE2. After optimizing various operating parameters, an NAb lateral flow assay was constructed. Subsequently, its detection limit, specificity, and stability were systematically evaluated, and clinical samples were analyzed to validate its clinical feasibility. Results: RBD-Fc and ACE2-His were obtained with 94.01% and 90.05% purity, respectively. The synthesized colloidal gold had a uniform distribution with an average diameter of 24.15 ± 2.56 nm. With a detection limit of 2 µg/mL, the proposed assay demonstrated a sensitivity of 97.80% and a specificity of 100% in 684 uninfected clinical samples. By evaluating 356 specimens from infected individuals, we observed that the overall concordance rate between the proposed assay and conventional enzyme-linked immunosorbent assay was 95.22%, and we noticed that 16.57% (59/356) of individuals still did not produce NAbs after infection (both by ELISA and the proposed assay). All the above tests by this assay can obtain results within 20 minutes by the naked eye without any additional instruments or equipment. Conclusion: The proposed assay can expediently and reliably detect anti-SARS-CoV-2 NAbs after infection, and the results provide valuable data to facilitate effective prevention and control of SARS-CoV-2. Clinical trial registration: Serum and blood samples were used under approval from the Biomedical Research Ethics Subcommittee of Henan University, and the clinical trial registration number was HUSOM-2022-052. We confirm that this study complies with the Declaration of Helsinki.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Anticorpos Neutralizantes , COVID-19/diagnóstico , Enzima de Conversão de Angiotensina 2 , Teste para COVID-19 , Anticorpos Antivirais
17.
Redox Biol ; 68: 102961, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38007983

RESUMO

BACKGROUND: Declining beneficial cardiovascular actions of estradiol (E2) have been associated with disproportionate susceptibility to takotsubo syndrome (TTS) in postmenopausal women. However, the underlying mechanisms between E2 and this marked disproportion remain unclear. SmgGDS (small GTP-binding protein GDP dissociation stimulator), as a key modulator of cardiovascular disease, plays protective roles in reducing oxidative stress and exerts pleiotropic effects of statins. Whether SmgGDS levels are influenced by E2 status and the effect of SmgGDS on sex differences in TTS are poorly understood. METHODS: Clinical data were reviewed from TTS inpatients. Echocardiography, immunofluorescence, and immunohistochemistry were performed together with expression analysis to uncover phenotypic and mechanism changes in sex differences in TTS-like wild-type (WT) and SmgGDS± mice. HL-1 cardiomyocytes were used to further examine and validate molecular mechanisms. RESULTS: In 14 TTS inpatients, TTS had a higher incidence in postmenopausal women as compared to premenopausal women and men. In murine TTS, female WT mice exhibited higher cardiac SmgGDS levels than male WT mice. Ovariectomy reduced SmgGDS expression in female WT mice similar to that observed in male mice, whereas E2 replacement in these ovariectomized (OVX) female mice reversed this effect. The physiological importance of this sex-specific E2-mediated SmgGDS response is underscored by the disparity in cardiac adaptation to isoproterenol (ISO) stimulation between both sexes of WT mice. E2-mediated SmgGDS induction conferred female protection against TTS-like acute cardiac injury involving ferritinophagy-mediated ferroptosis. No such cardioprotection was observed in male WT mice and OVX female. A causal role for SmgGDS in this sex-specific cardioprotective adaptation was indicated, inasmuch as SmgGDS deficiency abolished E2-modulated cardioprotection against ferritinophagy and aggravates TTS progression in both sexes. Consistently, knockdown of SmgGDS in HL-1 cardiomyocytes exacerbated ferroptosis in a ferritinophagy-dependent manner and abrogated the protective role of E2 against ferritinophagy. Mechanistically, our findings revealed that SmgGDS regulated E2-dependent cardioprotective effects via AMPK/mTOR signaling pathway. SmgGDS deficiency abolished E2-conferred protection against ferritinophagy through activating AMPK/mTOR pathway, while treatment with recombinant SmgGDS in HL-1 cells significantly mitigated this pathway-associated ferritinophagy activity. CONCLUSIONS: These results demonstrate that SmgGDS is a central mediator of E2-conferred female cardioprotection against ferritinophagy-mediated ferroptosis in TTS.


Assuntos
Ferroptose , Cardiomiopatia de Takotsubo , Humanos , Feminino , Masculino , Camundongos , Animais , Caracteres Sexuais , Estradiol/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Ferroptose/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Serina-Treonina Quinases TOR/metabolismo
18.
J Agric Food Chem ; 71(49): 19592-19609, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38018895

RESUMO

The exacerbation of the greenhouse effect has made heat stress (HS) an important risk factor for the occurrence of intrauterine growth restriction (IUGR). The experiment aims to uncover the effects of maternal HS on IUGR and its mechanisms. The results showed that HS leads to decreased maternal and fetal birth weights, accompanied by increased serum oxidative stress and cortisol levels. Moreover, HS inflicted significant damage to both the intestinal and placental barriers, altering maternal gut microbiota and increasing intestinal LPS levels. As a result, LPS levels increased in maternal serum, placenta, and fetus. Furthermore, HS damaged the intestinal structure, intensifying inflammation and disrupting the redox balance. The placenta exposed to HS exhibited changes in the placental structure along with disrupted angiogenesis and decreased levels of nutritional transporters. Additionally, the leakage of LPS triggered placental JNK and ERK phosphorylation, ultimately inducing severe placental inflammation and oxidative stress. This study suggests that LPS translocation from the maternal intestine to the fetus, due to a disrupted gut microbiota balance and compromised intestinal and placental barrier integrity, may be the primary cause of HS-induced IUGR. Furthermore, increased LPS leakage leads to placental inflammation, redox imbalance, and impaired nutrient transport, further restricting fetal growth.


Assuntos
Retardo do Crescimento Fetal , Placenta , Humanos , Gravidez , Camundongos , Feminino , Animais , Retardo do Crescimento Fetal/etiologia , Lipopolissacarídeos/efeitos adversos , Feto , Intestinos , Inflamação/induzido quimicamente
19.
J Phys Chem Lett ; 14(43): 9539-9547, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37856238

RESUMO

Stereoelectronic effects in single-molecule junctions have been widely utilized to achieve a molecular switch, but high-efficiency and reproducible switching remain challenging. Here, we demonstrate that there are three stable intramolecular conformations in the 9,10-diphenyl-9,10-methanoanthracen-11-one (DPMAO) systems due to steric effect. Interestingly, different electronic coupling approaches including weak coupling (through-space), decoupling, and strong coupling (through-bond) between two terminal benzene rings are accomplished in the three stable conformations, respectively. Theoretical calculations show that the molecular conductance of three stable conformations differs by more than 1 order of magnitude. Furthermore, the populations of the three stable conformations are highly dependent on the solvent effect and the external electric field. Therefore, an excellent molecular switch can be achieved using the DPMAO molecule junctions and external stimuli. Our findings reveal that modulating intramolecular electronic coupling approaches may be a useful manner to enable molecular switches with high switching ratios. This opens up a new route for building high-efficiency molecular switches in single-molecular junctions.

20.
Drug Deliv Transl Res ; 12(1): 306-324, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33712991

RESUMO

Lipid-polymer hybrid nanoparticles (LPNs) are promising drug delivery systems in various of disease treatment areas, particularly for cancer treatments. Here, a water-insoluble antitumor agent, hydroxycamptothecin (HCPT), was successfully incorporated into LPNs formed from polylactic-co-glycolic acid (PLGA), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000) (DSPE-PEG2000), and lecithin, by a modified single emulsification-solvent evaporation method. Quality-by-design (QbD) strategy composed of Plackett-Burman and Box-Behnken designs were applied for optimizing HCPT-LPNs with desired properties. The optimized HCPT-loaded lipid-polymer hybrid nanoparticles (HCPT-LPNs) were on the nanoscale, with a final size of 220.9 nm, drug loading of 2.50%. HCPT-LPNs were highly stable in plasma and had pH- and drug loading-related sustained release characteristics. The in vitro cytotoxicity of HCPT-LPNs against MCF-7 and HepG2 cells showed that HCPT-LPNs had higher in vitro cytotoxicity than HCPT solution (HCPT-Sol) with reduced cell viability and IC50 values. In vivo pharmacokinetic assays demonstrated that the AUC of HCPT-LPNs was more than 3 times higher than that of HCPT-Sol after tail vein injection in SD rats. Tumor growth was significantly inhibited compared with HCPT-Sol after a single tail vein injection of HCPT-LPNs in murine LLC-GFP-luc lung cancer bearing mice at a dose of 6 mg/kg, without severe side effects. These results indicate that HCPT-LPNs are the promising drug delivery system for antitumor treatments.


Assuntos
Nanopartículas , Polímeros , Animais , Camptotecina/análogos & derivados , Linhagem Celular Tumoral , Portadores de Fármacos , Camundongos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley
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