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1.
Nat Commun ; 15(1): 8940, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39414826

RESUMEN

The kagome lattice is a versatile platform for investigating correlated electronic states. However, its realization in two-dimensional (2D) semiconductors for tunable device applications is still challenging. An alternative strategy to create kagome-like bands is to realize a coloring-triangle (CT) lattice in semiconductors through a distortion of a modified triangular lattice. Here, we report the observation of low-energy kagome-like bands in a semiconducting 2D transition metal chalcogenide-Cr8Se12 with a thickness of 7 atomic layers-which exhibits a CT lattice and a bandgap of 0.8 eV. The Cr-deficient layer beneath the topmost Se-full layer is partially occupied with 2/3 occupancy, yielding a √3 × âˆš3 Cr honeycomb network. Angle-resolved photoemission spectroscopy measurements and first-principles investigations reveal the surface kagome-like bands near the valence band maximum, which are attributed to topmost Se pz orbitals modulated by the honeycomb Cr.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39425549

RESUMEN

Tumor-associated macrophages (TAMs) constitute the largest number of immune cells in the tumor microenvironment (TME). They play an essential role in promoting tumor progression and metastasis, which makes them a potential therapeutic target for cancer treatment. TAMs are usually divided into two categories: pro-tumoral M2-like TAMs and antitumoral M1 phenotypes at either extreme. The reprogramming of M2-like TAMs toward a tumoricidal M1 phenotype is of particular interest for the restoration of antitumor immunity in cancer immunotherapy. Notably, nanomedicines have shown great potential for cancer therapy due to their unique structures and properties. This review will briefly describe the biological features and roles of TAMs in tumor, and then discuss recent advances in nanomedicine-mediated repolarization of TAMs for cancer immunotherapy. Finally, perspectives on nanomedicine-mediated repolarization of TAMs for effective cancer immunotherapy are also presented.


Asunto(s)
Inmunoterapia , Nanomedicina , Neoplasias , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Macrófagos Asociados a Tumores/inmunología , Neoplasias/terapia , Neoplasias/inmunología , Animales
3.
Sci Rep ; 14(1): 24433, 2024 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-39424950

RESUMEN

This large community-based cohort study investigates the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), specifically Liraglutide and Semaglutide, on the risk of developing psychiatric conditions such as depression, anxiety, and suicidal behaviors in patients with obesity. Utilizing post-marketing data, this research compares patients prescribed GLP-1 RAs (cases) with those not taking these medications (controls). The analysis spanned data from January 1, 2015, to December 31, 2023. To minimize selection bias, we employed 1:1 propensity score matching to account for demographic factors such as age, sex, race, and comorbidities. After matching, the study included 162,253 case and control patients. This study showed a significant association between GLP-1 RA treatment and an 98% increased risk of any psychiatric disorders. Notably, patients on GLP-1 RAs exhibited a 195% higher risk of major depression, a 108% increased risk for anxiety, and a 106% elevated risk for suicidal behavior. These findings underscore the critical need for physicians to thoroughly assess patient history before prescribing GLP-1 RAs and highlight the urgent requirement for further prospective clinical trials to fully understand the implications of GLP-1 RA use on mental health in the obese patient population.


Asunto(s)
Ansiedad , Depresión , Receptor del Péptido 1 Similar al Glucagón , Liraglutida , Obesidad , Humanos , Masculino , Femenino , Obesidad/epidemiología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Persona de Mediana Edad , Ansiedad/epidemiología , Adulto , Depresión/tratamiento farmacológico , Depresión/epidemiología , Liraglutida/uso terapéutico , Anciano , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Factores de Riesgo , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Estudios de Cohortes
4.
Vet Res ; 55(1): 132, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39375803

RESUMEN

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine viral infectious diseases worldwide. Vaccination is a key strategy for the control and prevention of PRRS. At present, the NADC30-like PRRSV strain has become the predominant epidemic strain in China, superseding the HP-PRRSV strain. The existing commercial vaccines offer substantial protection against HP-PRRSV, but their efficacy against NADC30-like PRRSV is limited. The development of a novel vaccine that can provide valuable cross-protection against both NADC30-like PRRSV and HP-PRRSV is highly important. In this study, an infectious clone of a commercial MLV vaccine strain, GD (HP-PRRSV), was first generated (named rGD). A recombinant chimeric PRRSV strain, rGD-SX-5U2, was subsequently constructed by using rGD as a backbone and embedding several dominant immune genes, including the NSP2, ORF5, ORF6, and ORF7 genes, from an NADC30-like PRRSV isolate. In vitro experiments demonstrated that chimeric PRRSV rGD-SX-5U2 exhibited high tropism for MARC-145 cells, which is of paramount importance in the production of PRRSV vaccines. Moreover, subsequent in vivo inoculation and challenge experiments demonstrated that rGD-SX-5U2 confers cross-protection against both HP-PRRSV and NADC30-like PRRSV, including an improvement in ADG levels and a reduction in viremia and lung tissue lesions. In conclusion, our research demonstrated that the chimeric PRRSV strain rGD-SX-5U2 is a novel approach that can provide broad-spectrum protection against both HP-PRRSV and NADC30-like PRRSV. This may be a significant improvement over previous MLV vaccinations.


Asunto(s)
Protección Cruzada , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Vacunas Virales , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/inmunología , Animales , Síndrome Respiratorio y de la Reproducción Porcina/prevención & control , Síndrome Respiratorio y de la Reproducción Porcina/virología , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Porcinos , Vacunas Virales/inmunología , China
5.
Natl Sci Rev ; 11(9): nwae286, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39350936
6.
Macromol Rapid Commun ; : e2400698, 2024 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-39470628

RESUMEN

Fluorosilicone rubber is essential for sealing in extreme temperatures and non-polar environments due to its exceptional adaptability. However, achieving a high yield of fluorosilicone polymers with medium and high fluorine content remains a challenge. Herein, a facile gradient strategy is developed that involves modifying the method of cyclic monomer addition based on the rate of ring-opening polymerization (ROP), to improve yield and adjust fluorine content precisely. The polymerization process is designed and tailored based on the reaction rates of anionic ring-opening polymerization (AROP) and cationic ring-opening polymerization (CROP) via an efficient gradient strategy. The effects of the polymerization process on the viscosity and yield of vinyl fluorosilicone polymers and hydrofluorosilicone polymers are investigated and optimized. Notably, the as-prepared vinyl-terminated fluoromethylsilane with 60% fluorine content (FMS-Vi-60F) has a high yield (86.6%) and high viscosity (150 000 mPa·s) in a short reaction time, which is superior to previous methods. Clearly, the gradient ring-opening method developed in this work provides a facile and efficient synthesis for fabricating fluorosilicone polymers with a high yield and tunable fluorine content.

7.
Sci Total Environ ; 955: 177041, 2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-39437919

RESUMEN

This study aims to investigate effects of dissolved oxygen (DO) levels and aerated hydrodynamic retention time (HRT) on nitrogen removal and nitrous oxide (N2O) emissions in a novel anaerobic-swing-anoxic-oxic (ASAO) continuous plug-flow system for treating low carbon to nitrogen ratio municipal wastewater. The swing zones had varying DO levels and volumes, deciding the aerated HRT of the ASAO system. Results showed that low DO level (0.8-1.0 mg/L) and short aerated HRT led to high nitrogen removal performance (91.4 %-96.3 %) and low N2O emission factor (2.8 %). The simultaneous nitrification and denitrification (SND) in swing zones and endogenous denitrification in anoxic zones contributed to the nitrogen removal. Meanwhile, the SND and autotrophic denitrification processes were identified as the N2O sources. Low DO level enriched ammonia-oxidizing bacteria and enhanced the SND and autotrophic denitrification pathway. These findings suggest that the ASAO system is promising for reducing carbon emissions in municipal wastewater treatment.

8.
Angew Chem Int Ed Engl ; : e202417548, 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39445657

RESUMEN

Heterometallic cluster-based materials offer the potential to incorporate multiple functionalities, leveraging the aggregation effects of clusters and translating this heterogeneity and complexity into unexpected properties that are more than just the sum of their components. However, the rational construction of heterometallic cluster-based materials remains challenging due to the complexity of metal cation coordination and structural unpredictability. This minireview provides insights into a general synthetic strategy based on Hard and Soft Acids and Bases (HSAB) theory, summarizing its advantages in the designed synthesis of discrete heterometallic clusters (intracluster assembly) and infinite heterometallic cluster-based materials (intercluster assembly). Furthermore, it emphasizes the potential to exploit the intrinsic properties of mixed components to achieve breakthroughs across a broad range of applications. The insights from this review are expected to drive the progress of heterometallic cluster-based materials in a controllable and predictable manner.

9.
Opt Lett ; 49(20): 5913-5916, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39404570

RESUMEN

High Al content (60%) p-AlGaN with different NH3 flow rates was grown using metal-organic chemical vapor deposition (MOCVD), and changes in its photoelectric properties were studied using the Hall effect tester (Hall) and cathodoluminescence (CL) spectrometer. The results show that the film resistivity increases from 3.8â€…Ω·cm to 46.5â€…Ω·cm with increasing NH3 flow rate. The impurity peak intensity of p-AlGaN grown under high NH3 flow conditions is particularly high, indicating numerous point defects. The results of high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) show a large number of Ga interstitial atoms (Gai) at the interface. As Gai acts as a donor, this may be the main reason for the increase in resistivity. And under high NH3 flow conditions, a lattice distortion and a high density of dislocation occur between p-AlGaN and p-GaN, which can lead to enhanced carrier scattering and decreased mobility. Additional validation via LED growth experiments indicates that the luminescence intensity of samples with low ammonia concentration increased by more than 13000 times.

10.
Front Nutr ; 11: 1432283, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39399526

RESUMEN

Background: Observational studies indicate a correlation between food intake and allergic rhinitis. The potential interplay between the immune system and allergic rhinitis might contribute causally to both food intake and allergic rhinitis, providing promising therapeutic avenues. However, elucidating the causal relationship and immune-mediated mechanisms between food intake and allergic rhinitis remains a pending task. Methods: We utilized a two-sample Mendelian randomization (MR) methodology to explore the causal relationship between food intake and allergic rhinitis. Furthermore, we investigated the potential causal relationship of immune cell signals with allergic rhinitis, as well as the potential causal relationship between food intake and immune cell signals. Moreover, employing both two-step Mendelian randomization and multivariable Mendelian randomization, we delved into the mediating role of immune cell signals in the causal relationship between food intake and allergic rhinitis. Leveraging publicly accessible genetic datasets, our analysis encompassed 903 traits, comprising 171 food intake features, 731 immune cell features, and one trait related to allergic rhinitis. Result: We found causal relationships between seven types of food intake and allergic rhinitis, as well as between 30 immune cell phenotypes and allergic rhinitis. Furthermore, our two-step Mendelian randomization analysis and multivariable Mendelian randomization analysis indicate that immune cells do not mediate the causal relationship between food intake and allergic rhinitis. Conclusion: To the best of our knowledge, we are the first to incorporate a large-scale dataset integrating immune cell features, food intake features, and allergic rhinitis into Mendelian randomization analysis. Our research findings indicate that there are causal relationships between six types of food intake and allergic rhinitis, as well as between 30 immune cell phenotypes and allergic rhinitis. Additionally, immune cells do not mediate these relationships.

11.
Physiol Plant ; 176(5): e14548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39318054

RESUMEN

Reactive oxygen species (ROS) have been extensively suggested to stimulate ethylene production. However, the molecular mechanism by which ROS stimulate ethylene production remains largely unclear. Here, transcriptome profiling was used to verify if ROS could stimulate ethylene production via direct formation of ethylene from ROS. Trichloroisocyanuric acid (TCICA) can stimulate seed germination in rice. When transcriptome profiling was performed to determine the molecular responsiveness of rice seeds to TCICA, TCICA was initially proven to be a ROS-generating reagent. A total of 300 genes potentially responsive to TCICA treatment were significantly annotated to cysteine, and the expression of these genes was significantly upregulated. Nonetheless, the levels of cystine did not exhibit significant changes upon TCICA exposure. Cystine was then proven to be a substrate that reacted with TCICA to form ethylene under FeSO4 conditions. Moreover, 7 of 22 genes responsive to TCICA were common with the hydrogen peroxide (H2O2)-responsive genes. Ethylene was then proven to be produced from cysteine or cystine by reacting with H2O2 under FeSO4 condition, and the hydroxyl radical (OH-) was proposed to be the free radical species responsible for ethylene formation under FeSO4 condition. These results provide the first line of evidence that ethylene can be produced from ROS in a non-enzymatic manner, thereby unveiling one new molecular mechanism by which ROS stimulate ethylene production and offering novel insights into the crosstalk between ethylene and ROS.


Asunto(s)
Etilenos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Oryza , Especies Reactivas de Oxígeno , Semillas , Especies Reactivas de Oxígeno/metabolismo , Oryza/genética , Oryza/metabolismo , Oryza/efectos de los fármacos , Semillas/efectos de los fármacos , Semillas/genética , Semillas/metabolismo , Etilenos/metabolismo , Etilenos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Germinación/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Triazinas/farmacología
12.
Heliyon ; 10(16): e36232, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253252

RESUMEN

This paper presents an innovative fusion model called "CALSE-LSTM," which integrates Convolutional Neural Networks (CNNs), Long Short-Term Memory Networks (LSTMs), self-attention mechanisms, and squeeze-and-excitation attention mechanisms to optimize the estimation accuracy of the State of Charge (SoC). The model incorporates battery historical data as input and employs a dual-attention mechanism based on CNN-LSTM to extract diverse features from the input data, thereby enhancing the model's ability to learn hidden information. To further improve model performance, we fine-tune the model parameters using the Pelican algorithm. Experiments conducted under Urban Dynamometer Driving Schedule (UDDS) conditions show that the CALSE-LSTM model achieves a Root Mean Squared Error (RMSE) of only 1.73 % in lithium battery SoC estimation, significantly better than GRU, LSTM, and CNN-LSTM models, reducing errors by 31.9 %, 31.3 %, and 15 %, respectively. Ablation experiments further confirm the effectiveness of the dual-attention mechanism and its potential to improve SoC estimation performance. Additionally, we validate the learning efficiency of CALSE-LSTM by comparing model training time with the number of iterations. Finally, in the comparative experiment with the Kalman filtering method, the model in this paper significantly improved its performance by incorporating power consumption as an additional feature input. This further verifies the accuracy of CALSE-LSTM in estimating the State of Charge (SoC) of lithium batteries.

13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 592-602, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39223024

RESUMEN

Alzheimer's disease (AD) is a common neurodegenerative disease with the main manifestations of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an important role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory storage,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major pathological factor in the occurrence and development of AD.This article reviews the role and research progress in intracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloid ß,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling pathways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflammation.


Asunto(s)
Enfermedad de Alzheimer , Calcio , Homeostasis , Enfermedad de Alzheimer/metabolismo , Humanos , Calcio/metabolismo , Péptidos beta-Amiloides/metabolismo , Señalización del Calcio/fisiología , Mitocondrias/metabolismo , Proteínas tau/metabolismo , Autofagia/fisiología , Animales , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Neuronas/metabolismo , Fosforilación
14.
Small ; : e2405358, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291888

RESUMEN

The replacement of oxygen evolution reactions with organic molecule oxidation reactions to enable energy-efficient hydrogen production has been a subject of interest. However, further reducing reaction energy consumption and releasing hydrogen from organic molecules continue to pose significant challenges. Herein, a strategy is proposed to produce hydrogen and formic acid from formaldehyde using Ag/Co3O4 interface catalysts at the anode. The key to improving the performance of Ag-based catalysts for formaldehyde oxidation lies in the strong SMSI achieved through the well-designed "spontaneous redox reaction" between Ag and Co3O4 precursors. Nano-sized Ag particles are uniformly dispersed on Co3O4 nanosheets, and electron-deficient Agδ+ are formed by the SMSI between Ag and Co3O4. Ag/Co3O4 demonstrates exceptional formaldehyde oxidation activity at low potentials of 0.32 V versus RHE and 0.65 V versus RHE, achieving current densities of 10 and 100 mA cm-2, respectively. The electrolyzer "Ag/Co3O4||20% Pt/C" achieves over 195% hydrogen efficiency and over 98% formic acid selectivity, maintaining stable operation for 60 hours. This work not only presents a novel approach to precisely modulate Ag particle size and interface electronic structure via SMSI, but also provides a promising approach to efficient and energy-saving hydrogen production and the transformation of harmful formaldehyde.

15.
Microorganisms ; 12(9)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39338421

RESUMEN

Colorectal cancer (CRC) is a prevalent and escalating health issue in Taiwan. This nationwide study delves into the relationship between Human Papillomavirus (HPV) infection and CRC risk, employing population datasets from 2007 to 2017. Cox regression analyses revealed a statistically significant hazard ratio (HR) of 1.73 (95% CI: 1.63-1.83) for CRC in HPV-positive patients, indicating a considerably elevated risk compared to non-infected individuals. Further, stratification by sex showed males with HPV have a higher CRC risk (HR = 1.49, 95% CI: 1.40-1.58) compared to females. Age-related analysis uncovered a progressive increase in CRC risk with advancing age (HR = 34.69 for over 80 years). The study of specific CRC subtypes showed varying risks: HR = 1.74 for the colon, HR = 1.64 for the rectum, and a notably higher HR = 4.72 for the anus. Comorbid conditions such as hypertension (HR = 1.26), diabetes mellitus (HR = 1.32), and abnormal liver function (HR = 1.18) also correlate with significantly increased CRC risks. These findings suggest that HPV is a significant risk factor for CRC, with disparities in risk based on anatomical location, demographic characteristics, and comorbidities, highlighting the need for intervention strategies and targeted prevention.

16.
Zhongguo Gu Shang ; 37(9): 899-904, 2024 Sep 25.
Artículo en Chino | MEDLINE | ID: mdl-39342474

RESUMEN

OBJECTIVE: To explore clinical effect of closed reduction percutaneous elastic intramedullary nail assisted by arthrography in the treatment of radial neck fracture in children. METHODS: A retrospective analysis was performed on 23 children with radial neck fracture treated with arthrography assisted closed reduction and percutaneous elastic intramedullary nail internal fixation (arthrography with elastic nail group) from January 2019 to December 2022, including 12 males and 11 females, aged from 2 to 12 years old with an average of (7.36±1.89) years old;According to Judet fracture types, 14 children were type Ⅲ and 9 children were type Ⅳ. In addition, 23 children with radial neck fracture were selected from January 2015 to December 2018 who were treated with closed reduction and percutaneous elastic intramedullary nail fixation (elastic nail group), including 11 males and 12 females, aged from 2 to 14 years old with an average of (7.50±1.91) years old;Judet classification included 15 children were type Ⅲ and 8 children were type Ⅳ. Operative time and intraoperative fluoroscopy times were compared between two groups. Metaizeau evaluation criteria was used to evaluate fracture reduction, and Tibone-Stoltz evaluation criteria was used to evaluate functional recovery of elbow between two groups. RESULTS: Both groups were followed up for 12 to 24 months with an average of (16.56±6.34) months. Operative time and intraoperative fluoroscopy times of elastic nail group were (56.64±19.27) min and (21.13±7.87) times, while those of joint angiography with elastic nail group were (40.33±11.50) min and (12.10±3.52) times;there were difference between two groups (P<0.05). According to Metaizeau evaluation, 11 patients got excellent result, 9 good and 3 fair in joint angiography with elastic nail group, while in elastic nail group, 5 excellent, 13 good, 4 acceptable, and 1 poor;the difference between two groups was statistically significant (P<0.05). According to Tibone-Stoltz criteria, 14 patients got excellent result, 8 good, and 1 fair in joint arthrography with elastic nail group;while in elastic nail group, 12 patients got excellent result, 9 good, 1 fair and 1 poor;there was no significant difference between two groups (P>0.05). CONCLUSION: Compared to percutaneous elastic intramedullary nail fixation, closed reduction assisted by arthrography has advantages of reduced operation time, decreased intraoperative fluoroscopy frequency, and improved fracture reduction. Arthrography enables clear visualization of the anatomical structures of radius, head, neck, bone, and cartilage in children, facilitating comprehensive display of fracture reduction and brachioradial joint alignment. This technique more precisely guides the depth of elastic intramedullary nail implantation in radius neck, thereby enhancing surgical efficiency and success rate.


Asunto(s)
Artrografía , Clavos Ortopédicos , Fijación Intramedular de Fracturas , Fracturas del Radio , Humanos , Femenino , Masculino , Niño , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/instrumentación , Preescolar , Estudios Retrospectivos , Fracturas del Radio/cirugía , Fracturas del Radio/diagnóstico por imagen , Artrografía/métodos , Adolescente , Resultado del Tratamiento , Fracturas Radiales de Cabeza y Cuello
17.
Phytomedicine ; 135: 156091, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39332101

RESUMEN

BACKGROUND: ß-Amyloid (Aß) fibrillation is critical for Aß deposition and cytotoxicity during the progression of Alzheimer's disease (AD). Consequently, anti-Aß monoclonal antibody drugs targeting Aß oligomers and aggregation are considered potential therapeutic strategies for AD treatment. Similar to the working mechanisms of anti-Aß monoclonal antibody drugs, our study identified osmundacetone (OAC), a small-molecule compound isolated from the traditional Chinese medicine Rhizoma Osmundae, as exerting anti-AD effects by targeting Aß. PURPOSE: This study sought to determine whether OAC influences the Aß burden in APP/PS1 mice and to identify potential regulatory mechanisms. METHODS: Five-month-old APP/PS1 mice were injected intraperitoneally with OAC at a dose of 1 mg/kg for 12 weeks. The cognitive functions of the mice were assessed via the Morris water maze test and the open field test. Osmundacetone was analyzed via molecular docking, an isothermal dose‒response fingerprint-cellular context thermal shift assay, a thioflavine T fluorescence assay, and an atomic force microscopy assay to analyze the effects of OAC on Aß fibrillation. Immunofluorescence, immunoblotting, and immunohistochemistry were used to assess Aß clearance, AD pathology, oxidative stress, and inflammatory responses. RESULTS: The innovative biochemical and physical data illustrated that the ability of OAC to inhibit Aß fibrillation was accomplished by binding directly to Aß, which differed from the majority of previously reported natural polyphenols that modulate the Aß content and structure in an indirect manner. The inhibition of Aß fibrosis by OAC subsequently promoted Aß lysosomal degradation, resulting in a decreased Aß burden in APP/PS1 mice. Furthermore, OAC treatment inhibited oxidative damage by upregulating glutathione peroxidase expression and attenuated the production of inflammatory factors by downregulating nuclear factor-kB phosphorylation in APP/PS1 mice. CONCLUSION: These findings demonstrate, for the first time, that OAC could reduce the brain Aß burden in APP/PS1 mice by inhibiting Aß fibrillation through direct binding to Aß and improve cognitive dysfunction by attenuating oxidative damage and neuroinflammation. These findings indicate that OAC may be a promising candidate for the treatment of AD.

18.
Aging Cell ; : e14336, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287420

RESUMEN

Glycogen synthase kinase-3α/ß (GSK3α/ß) is a critical kinase for Tau hyperphosphorylation which contributes to neurodegeneration. Despite the termination of clinical trials for GSK3α/ß inhibitors in Alzheimer's disease (AD) treatment, there is a pressing need for novel therapeutic strategies targeting GSK3α/ß. Here, we identified the compound AS1842856 (AS), a specific forkhead box protein O1 (FOXO1) inhibitor, reduced intracellular GSK3α/ß content in a FOXO1-independent manner. Specifically, AS directly bound to GSK3α/ß, promoting its translocation to the multivesicular bodies (MVBs) and accelerating exocytosis, ultimately decreasing intracellular GSK3α/ß content. Expectedly, AS treatment effectively suppressed Tau hyperphosphorylation in cells exposed to okadaic acid or expressing the TauP301S mutant. Furthermore, AS was visualized to penetrate the blood-brain barrier (BBB) using an imaging mass microscope. Long-term treatment of AS enhanced cognitive function in P301S transgenic mice by mitigating Tau hyperphosphorylation through downregulation of GSK3α/ß expression in the brain. Altogether, AS represents a novel small-molecule GSK3α/ß inhibitor that facilitates GSK3α/ß exocytosis, holding promise as a therapeutic agent for GSK3α/ß hyperactivation-associated disorders.

19.
Ecotoxicol Environ Saf ; 285: 117081, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39341135

RESUMEN

The co-occurrence of glyphosate (GPS), a commonly used organophosphorus herbicide, and cadmium (Cd), a neurotoxic metal, in agricultural environments prompts concerns about their combined toxic effects on ecosystems. This study explores the combined effects of GPS and Cd on the model organism Caenorhabditis elegans (C. elegans), to understand their cumulative effects in organismal living environments. We investigated the interaction between GPS and Cd over 24 hours using a comprehensive approach that included a variety of toxicity endpoints as well as the novel Automated Recognition and Statistics Tool (NCLE) for body bend measurement. Our data show a concentration-dependent interplay in which antagonistic effects at lower concentrations reduce phenotypic damage while synergistic effects emerge at higher concentrations, particularly at GPS's LC50. Transcriptome analysis under antagonistic conditions revealed significant downregulation of Cd toxicity-related genes and identified Y22D7AL.16, which has a C2H2-type zinc finger domain, as a novel gene involved in metal stress response, implying an alternative Cd-resilience mechanism. The expression profile of this gene shows that it plays a larger role in both development and metal stress adaption. These findings highlight the complexities of compound pollutant interactions, emphasizing the importance of including such dynamics in environmental risk assessments and control techniques.


Asunto(s)
Cadmio , Caenorhabditis elegans , Glicina , Glifosato , Herbicidas , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Glicina/análogos & derivados , Glicina/toxicidad , Cadmio/toxicidad , Herbicidas/toxicidad , Relación Dosis-Respuesta a Droga
20.
Sci Rep ; 14(1): 22224, 2024 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333584

RESUMEN

To evaluate the efficiency, predictability, and residual astigmatism between first- and second-generation keratorefractive lenticule extraction (KLEx) surgeries in a prominent astigmatism population. A retrospective cohort study was conducted, and individuals who underwent first- and second-generation KLEx surgeries were enrolled. A total of 31 and 35 eyes were categorized into first and second KLEx groups, respectively. Visual acuity, refraction, topographic parameters, and surgical indices were recorded. Independent t tests were used to compare the postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and residual astigmatism between the two groups. The difference in UDVA was not significant three months after KLEx surgery (P = 0.509), and the SEs three months after surgery also presented similar values between the two groups (P = 0.552). The first KLEx group demonstrated greater residual astigmatism than did the second KLEx group throughout the three-month follow-up period (all P < 0.05). The values of surgically induced astigmatism (SIA), difference vector (DV), magnitude of error (ME) and correction index (CoI) were significantly better in the second KLEx group via vector analysis (all P < 0.05). Old age, high steep keratometry (K), high topographic cylinder, large angle kappa, and a small optic zone were correlated with greater residual astigmatism in the first KLEx group (all P < 0.05), whereas only a small optic zone was significantly correlated with greater residual astigmatism in the second KLEx group (P = 0.047). The second-generation KLEx is correlated with a lower risk of residual astigmatism.


Asunto(s)
Astigmatismo , Refracción Ocular , Agudeza Visual , Humanos , Astigmatismo/cirugía , Astigmatismo/fisiopatología , Masculino , Femenino , Adulto , Estudios Retrospectivos , Refracción Ocular/fisiología , Resultado del Tratamiento , Topografía de la Córnea , Adulto Joven , Persona de Mediana Edad
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