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Coronaviruses have threatened humans repeatedly, especially COVID-19 caused by SARS-CoV-2, which has posed a substantial threat to global public health. SARS-CoV-2 continuously evolves through random mutation, resulting in a significant decrease in the efficacy of existing vaccines and neutralizing antibody drugs. It is critical to assess immune escape caused by viral mutations and develop broad-spectrum vaccines and neutralizing antibodies targeting conserved epitopes. Thus, we constructed CovEpiAb, a comprehensive database and analysis resource of human coronavirus (HCoVs) immune epitopes and antibodies. CovEpiAb contains information on over 60 000 experimentally validated epitopes and over 12 000 antibodies for HCoVs and SARS-CoV-2 variants. The database is unique in (1) classifying and annotating cross-reactive epitopes from different viruses and variants; (2) providing molecular and experimental interaction profiles of antibodies, including structure-based binding sites and around 70 000 data on binding affinity and neutralizing activity; (3) providing virological characteristics of current and past circulating SARS-CoV-2 variants and in vitro activity of various therapeutics; and (4) offering site-level annotations of key functional features, including antibody binding, immunological epitopes, SARS-CoV-2 mutations and conservation across HCoVs. In addition, we developed an integrated pipeline for epitope prediction named COVEP, which is available from the webpage of CovEpiAb. CovEpiAb is freely accessible at https://pgx.zju.edu.cn/covepiab/.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Epítopos , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Anticuerpos Neutralizantes/inmunología , Epítopos/inmunología , Epítopos/química , Epítopos/genética , Coronavirus/inmunología , Coronavirus/genética , Bases de Datos Factuales , Reacciones Cruzadas/inmunologíaRESUMEN
Stringent control of centrosome duplication and separation is important for preventing chromosome instability. Structural and numerical alterations in centrosomes are hallmarks of neoplastic cells and contribute to tumorigenesis. We show that a Centrosome Amplification 20 (CA20) gene signature is associated with high expression of the Tripartite Motif (TRIM) family member E3 ubiquitin ligase, TRIM69. TRIM69-ablation in cancer cells leads to centrosome scattering and chromosome segregation defects. We identify Serine/threonine-protein kinase 3 (MST2) as a new direct binding partner of TRIM69. TRIM69 redistributes MST2 to the perinuclear cytoskeleton, promotes its association with Polo-like kinase 1 (PLK1) and stimulates MST2 phosphorylation at S15 (a known PLK1 phosphorylation site that is critical for centrosome disjunction). TRIM69 also promotes microtubule bundling and centrosome segregation that requires PRC1 and DYNEIN. Taken together, we identify TRIM69 as a new proximal regulator of distinct signaling pathways that regulate centrosome dynamics and promote bipolar mitosis.
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Centrosoma , Segregación Cromosómica , Transducción de Señal , Proteínas de Ciclo Celular/metabolismo , Centrosoma/metabolismo , Mitosis/genética , Fosforilación , Huso Acromático/metabolismoRESUMEN
Long-wave infrared (LWIR) imaging, or thermal imaging, is widely applied in night vision and security monitoring. However, the widespread use of LWIR imagers is impeded by their bulky size, considerable weight, and high cost. While flat meta-optics present a potential solution to these limitations, existing pure LWIR meta-optics face constraints such as severe chromatic or coma aberrations. Here, we introduce an approach utilizing large-scale hybrid meta-optics to address these challenges and demonstrate the achromatic, coma-corrected, and polarization-insensitive thermal imaging. The hybrid metalens doublet is composed of a metasurface corrector and a refractive lens, featuring a full field-of-view angle surpassing 20° within the 8-12 µm wavelength range. Employing this hybrid metalens doublet, we showcase high-performance thermal imaging capabilities both indoors and outdoors, effectively capturing ambient thermal radiation. The proposed hybrid metalens doublet holds considerable promise for advancing miniaturized, lightweight, and cost-effective LWIR optical imaging systems.
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Chemical pressure generated through ion doping into crystal lattices has been proven to be conducive to exploration of new matter, development of novel functionalities, and realization of unprecedented performances. However, studies are focusing on one-time doping, and there is a lack of both advanced investigations for multiple doping and sophisticated strategies to precisely and quantitatively track the gradual functionality evolution along with progressive chemical pressure implementation. Herein, high-valent Y3+ and equal-valent Mg2+ is successively doped to replace multiple Ca sites in Ca10.5(PO4)7:Eu2+. The luminescence evolution of Eu2+ serves as an optical probe, allowing step-by-step and atomic-level tracking of the site occupation of Y3+ and Mg2+, interassociation of Ca sites, and ultimately functionality improvement. The resulting Ca8MgY(PO4)7:Eu2+ displays a record-high relative sensitivity for optical thermometry. Utilization of the environment-sensitive emission of Eu2+ as a luminescent probe has offered a unique approach to monitoring structure-functionality evolution in vivo with atomic precision, which shall also be extended to optimization of other functionalities such as ferroelectricity, conductivity, thermoelectricity, and catalytic activity through precise control over atomic diffusion in other types of substances.
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Soluble redox-active polymers (RAPs) enable size-exclusion nonaqueous redox flow batteries (NaRFBs) which promise high energy density. Pendants along the RAPs not only store charge but also engage in electron transfer to varying extents based on their designs. Here, we explore these phenomena in Metal-containing Redox Active Polymers (M-RAPs, M = Ru, Fe, Co). We assess by using cyclic voltammetry and chronoamperometry with ultramicroelectrodes the current response to electrolyte concentration spanning 3 orders of magnitude. Currents scaled as Ru-RAP > Fe-RAP â« Co-RAP, consistent with electron self-exchange trends in the small molecule analogues of the MII/III redox pair. Varying the ionic strength of the electrolyte also revealed nonmonotonic behavior, evidencing the impact of polyelectrolytic dynamics on M-RAP redox response. We developed a model to account for the behavior by combining kinetic Monte Carlo and Brownian dynamics near a boundary representing an electrode. While 1D pendant-to-pendant charge transfer along the chain is not a strong function of electrolyte concentration, the microstructure of the RAP at different electrolyte concentrations is decisively impacted, yielding qualitative trends to those observed experimentally. M-RAP size-exclusion NaRFBs using a poly viologen as negolyte varied in average potential with â¼1.54 V for Ru-RAP, â¼1.37 V for Fe-RAP, and â¼0.52 V for Co-RAP. Comparison of batteries at their optimal and suboptimal solution conditions as gauged from analytical experiments showed clear correlations in performance. This work provides a blueprint for understanding the factors underpinning charge transfer in solutions of RAPs for batteries and beyond.
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Thermal quenching (TQ) has been naturally entangling with luminescence since its discovery, and lattice vibration, which is characterized as multiphonon relaxation (MPR), plays a critical role. Considering that MPR may be suppressed under exterior pressure, we have designed a core/shell upconversion luminescence (UCL) system of α-NaYF4:Yb/Ln@ScF3 (Ln = Ho, Er, and Tm) with positive/negative thermal expansion behavior so that positive thermal expansion of the core will be restrained by negative thermal expansion of the shell when heated. This imposed pressure on the crystal lattice of the core suppresses MPR, reduces the amount of energy depleted by TQ, and eventually saves more energy for luminescing, so that anti-TQ or even thermally enhanced UCL is obtained.
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Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.
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Enfermedades de los Pequeños Vasos Cerebrales , Arteria Cerebral Posterior , Humanos , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Sustancia Gris , Imagen por Resonancia Magnética , Tálamo/diagnóstico por imagenRESUMEN
OBJECTIVE: This study aimed to explore the association between kidney function and the risk of relapse as well as prognosis in patients with aquaporin-4 (AQP4)-immunoglobulin G (IgG)-seropositive neuromyelitis optica spectrum disorder (NMOSD). METHODS: We focused on patients experiencing their first onset of AQP4-IgG-seropositive NMOSD. Data on demographics, disease characteristics, and kidney function were collected, with the primary assessment utilizing the estimated glomerular filtration rate (eGFR). Associations between eGFR and relapse risk were examined using multivariate Cox proportional hazards regression models. Additionally, logistic regression models were employed to evaluate the impact of eGFR on clinical prognosis. RESULTS: Our analysis revealed glomerular hyperfiltration and impaired urine concentrating ability in patients with AQP4-IgG-seropositive NMOSD. Multivariate Cox proportional hazards regression demonstrated a positive correlation between eGFR and the risk of relapse. Logistic regression analysis further identified higher eGFR as an independent predictor of disease relapse and prognosis in AQP4-IgG-seropositive NMOSD patients. CONCLUSIONS: The eGFR of patients with AQP4-IgG-seropositive NMOSD emerges as a potential diagnostic biomarker for this condition, indicating its significance in predicting both relapse risk and clinical prognosis.
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Neuromielitis Óptica , Humanos , Acuaporina 4 , Autoanticuerpos , Tasa de Filtración Glomerular , Inmunoglobulina G , PronósticoRESUMEN
In this work, multi-layer Ti3C2 - carbon nanotubes - gold nanoparticles (Ti3C2-CNTs-Au) and cyclodextrin metal-organic framework - carbon nanotubes (CD-MOF-CNTs) have been prepared by in situ growth method and used to construct the ultra-sensitive rutin electrochemical sensor for the first time. Among them, the large number of metal active sites of Ti3C2, the high electron transfer efficiency of CNTS, and the good catalytic properties of AuNPs significantly enhance the electrochemical properties of the composite carbon nanomaterials. Interestingly, CD-MOF has a unique host-guest recognition and a large number of cavities, molecular gaps, and surface reactive groups, which gives the composite outstanding accumulation properties and selectivity for rutin. Under the optimized conditions, the constructed novel sensor has satisfactory detection performance for rutin in the range of 2 × 10-9 to 8 × 10-7 M with a limit of detection of 6.5 × 10-10 M. In addition, the sensor exhibits amazing anti-interference performance against rutin in some flavonoid compounds and can be used to test natural plant samples (buckwheat, Cymbopogon distans, and flos sophorae immaturus). This work has promising applications in the field of environmental and food analysis, and exploring new directions for the application of Mxene-based composites.
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Ciclodextrinas , Oro , Nanotubos de Carbono , Rutina , Titanio , Rutina/química , Rutina/análisis , Oro/química , Ciclodextrinas/química , Nanotubos de Carbono/química , Titanio/química , Estructuras Metalorgánicas/química , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodosRESUMEN
Protein side chains are vitally important to many biological processes such as protein-protein interaction. In this study, we evaluate the performance of our previous released side-chain modeling method OPUS-Mut, together with some other methods, on three oligomer datasets, CASP14 (11), CAMEO-Homo (65) and CAMEO-Hetero (21). The results show that OPUS-Mut outperforms other methods measured by all residues or by the interfacial residues. We also demonstrate our method on evaluating protein-protein docking pose on a dataset Oligomer-Dock (75) created using the top 10 predictions from ZDOCK 3.0.2. Our scoring function correctly identifies the native pose as the top-1 in 45 out of 75 targets. Different from traditional scoring functions, our method is based on the overall side-chain packing favorableness in accordance with the local packing environment. It emphasizes the significance of side chains and provides a new and effective scoring term for studying protein-protein interaction.
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Proteínas , Programas Informáticos , Algoritmos , Unión Proteica , Conformación Proteica , Proteínas/químicaRESUMEN
Plasmonic nanosensors and the dynamic control of light fields are of the utmost significance in the field of micro- and nano-optics. Here, our study successfully demonstrates a plasmonic nanosensor in a compact coupled resonator system and obtains the pressure-induced transparency phenomenon for the first time to our knowledge. The proposed structure consists of a groove and slot cavity coupled in the metal-insulator-metal waveguide, whose mechanical and optical characteristics are investigated in detail using the finite element method. Simulation results show that we construct a quantitative relationship among the resonator deformation quantity, the applied pressure variation, and the resonant wavelength offset by combining the mechanical and optical properties of the proposed system. The physical features contribute to highly efficient plasmonic nanosensors for refractive index and optical pressure sensing with sensitivity of 1800â nm/RIU and 7.4â nm/MPa, respectively. Furthermore, the light waves are coupled to each other in the resonators, which are detuned due to the presence of pressure, resulting in the pressure-induced transparency phenomenon. It is noteworthy to emphasize that, unlike previously published works, our numerical results take structural deformation-induced changes in optical properties into account, making them trustworthy and practical. The proposed structure introduces a novel, to the best of our knowledge, approach for the dynamic control of light fields and has special properties that can be utilized for the realization of various integrated components.
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We propose a plasmonic nanolaser based on a metal-insulator-semiconductor-insulator-metal (MISIM) structure, which effectively confines light on a subwavelength scale (â¼λ/14). As the pump power increases, the proposed plasmonic nanolaser exhibits broadband output characteristics of 20â nm, and the maximum output power can reach 20â µW. Furthermore, the carrier lifetime at the upper energy level in our proposed structure is measured to be about 400â fs using a double pump-probe excitation. The ultrafast characteristic is attributed to the inherent Purcell effect of plasmonic systems. Our work paves the way toward deep-subwavelength mode confinement and ultrafast femtosecond plasmonic lasers in spaser-based interconnected, eigenmode engineering of plasmonic nanolasers, nano-LEDs, and spontaneous emission control.
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In response to increasing antibiotic resistance and the pressing demand for safer infected wound care, probiotics have emerged as promising bioactive agents. To address the challenges associated with the safe and efficient application of probiotics, this study successfully loaded metabolites from Lacticaseibacillus rhamnosus GG (LGG) into a gelatin cross-linked macromolecular network by an in situ blending and photopolymerization method. The obtained LM-GelMA possesses injectability and autonomous healing capabilities. Importantly, the incorporation of LGG metabolites endows LM-GelMA with excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, while maintaining good biocompatibility. In vivo assessments revealed that LM-GelMA can accelerate wound healing by mitigating infections induced by pathogenic bacteria. This is accompanied by a reduction in the expression of key proinflammatory cytokines such as TNF-α, IL-6, VEGFR2, and TGF-ß, leading to increased re-epithelialization and collagen formation. Moreover, microbiological analysis confirmed that LM-GelMA can modulate the abundance of beneficial wound microbiota at family and genus levels. This study provides a facile strategy and insights into the functional design of hydrogels from the perspective of wound microenvironment regulation.
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Lacticaseibacillus rhamnosus , Cicatrización de Heridas , Antibacterianos/farmacología , Citocinas , Escherichia coli , Hidrogeles/farmacologíaRESUMEN
Peptide stapling, by employing a stable, preformed alpha-helical conformation, results in the production of peptides with improved membrane permeability and enhanced proteolytic stability, compared to the original peptides, and provides an effective solution to accelerate the rapid development of peptide drugs. Various reviews present peptide stapling chemistries, anchoring residues and one- or two-component cyclization, however, therapeutic stapled peptides have not been systematically summarized, especially focusing on various disease-related targets. This review highlights the latest advances in therapeutic peptide drug development facilitated by the application of stapling technology, including different stapling techniques, synthetic accessibility, applicability to biological targets, potential for solving biological problems, as well as the current status of development. Stapled peptides as therapeutic drug candidates have been classified and analysed mainly by receptor- and ligand-based stapled peptide design against various diseases, including cancer, infectious diseases, inflammation, and diabetes. This review is expected to provide a comprehensive reference for the rational design of stapled peptides for different diseases and targets to facilitate the development of therapeutic peptides with enhanced pharmacokinetic and biological properties.
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Péptidos , Humanos , Animales , Péptidos/uso terapéutico , Péptidos/química , Péptidos/farmacología , Diseño de FármacosRESUMEN
Interfacial strain engineering can induce structural transformation and introduce new physical properties into materials, which is an effective method to prepare new multifunctional materials. However, interfacial strain has a limited spatial impact size. For example, in 2D thin films, the critical thickness of biaxial strain is typically less than 20 nm, which is not conducive to the maintenance of a strained structure and properties in thick film materials. The construction of a 3D interface can solve this problem. The large lattice mismatch between the BaZrO3 thin film and the substrate can induce the out-of-phase boundary (OPB) structure, which can extend along the thickness direction with the stacking of atoms. The lattice distortion at the OPB structure can provide a clamping effect for each layer of atoms, thus expanding the spatial influence range of biaxial strain. As a result, the uniform in-plane strain distribution and strain-induced ferroelectricity (Pr = 13 µC/cm2) are maintained along the thickness direction in BaZrO3 films.
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BACKGROUND: The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. METHODS: A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan-Meier analysis were used to assess poor prognosis. RESULTS: During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54-5.66]; p = 0.001) and CAD-RADS categories 3-5 (HR = 16.31[6.34-41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan-Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786-0.911). CONCLUSION: The severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3-5 categories on CCTA.
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Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Enfermedad del Hígado Graso no Alcohólico , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Medición de Riesgo , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/complicaciones , Anciano , Pronóstico , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/mortalidad , Estudios Retrospectivos , Factores de TiempoRESUMEN
Objectives: This research aimed to study the expression of PRDX6 mRNA in hepatocellular carcinoma (HCC) and its effect on the prognosis of HCC. Moreover, the effect of PRDX6 gene knockdown on the proliferation, migration, and invasion of HepG2 cells mediated by lentivirus was also examined. This study offers a theoretical and experimental basis for further research on the mechanism of PRDX6 in liver cancer and new methods for clinical diagnosis and treatment. Methods: RNA sequence data of 369 HCC patients were screened through the TCGA database, and the expression and clinical characteristics of PRDX6 mRNA were analyzed based on high-throughput RNA sequencing data. HepG2 cells were divided into WT, sh-NC and sh-PRDX6 groups. Real-time PCR and Western blot were used to detect the expression levels of the PRDX6 gene and protein, respectively. CCK8 method was used to detect the proliferation activity of HepG2 cells, scratch healing test was used to detect the migration ability, Transwell chamber was used to detect the invasion ability, and Western blot was used to detect the expression levels of PI3K/Akt/mTOR signaling pathway and Notch signaling pathway-related proteins. Results: The expression of PRDX6 was significantly correlated with the gender, race, clinical stage, histological grade, and survival time of HCC patients (P < 0.05). Compared with that in WT and sh-NC groups, the expression level of PRDX6 protein in HCC patients was significantly lower (P < 0.01), the proliferation activity of HCC cells was significantly decreased (P < 0.05), and the migration and invasion ability was significantly decreased (P < 0.05) in the sh-PRDX6 group. The expression levels of PI3K, p-Akt, p-mTOR, Notch1, and Hes1 proteins in the sh-PRDX6 group were significantly lower than those in WT and sh-NC groups (P < 0.05). Conclusion: The expression of PRDX6 may be closely related to the prognosis of HCC. Lentivirus-mediated PRDX6 knockdown can inhibit the proliferation, migration and invasion of HCC cells, which may be related to its regulating the PI3K/Akt/mTOR and Notch1 signaling pathways. PRDX6 is expected to be a new target for the diagnosis and treatment of liver cancer.
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PURPOSE: This study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke. MATERIALS AND METHODS: This retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke. RESULTS: Serum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098-4.770), SVD (aOR = 4.471, 95% CI = 1.110-4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733-5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954-6.449), CEI (aOR = 2.809, 95% CI = 1.073-4.991), SVD (aOR = 5.376, 95% CI = 1.708-6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535-7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008-5.148), CEI (aOR = 2.212, 95% CI = 1.247-5.946), SVD (aOR = 2.957, 95% CI = 1.324-6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586-4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR. CONCLUSIONS: Vitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD.
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Ácido Fólico , Homocisteína , Accidente Cerebrovascular Isquémico , Vitamina B 12 , Humanos , Vitamina B 12/sangre , Ácido Fólico/sangre , Homocisteína/sangre , Estudios Retrospectivos , Femenino , Masculino , Estudios de Casos y Controles , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/epidemiología , Anciano , Factores de Riesgo , Curva ROC , Accidente Cerebrovascular/sangreRESUMEN
The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Exosomas , Ferroptosis , Flores , Mucosa Gástrica , Subunidad alfa del Factor 1 Inducible por Hipoxia , Mucosa Intestinal , Intestino Delgado , Peroxidación de Lípido , Nanopartículas , Animales , Ferroptosis/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Exosomas/metabolismo , Exosomas/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patología , Administración Oral , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Flores/química , Nanopartículas/química , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Humanos , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: This study sought to investigate the potential risk factors associated with weak and asymmetric handgrip strength (HGS) in older Chinese adults. METHODS: A total of 2702 participants aged ≥65 years from the two waves of data (2011 and 2013) from the China Health and Retirement Longitudinal Study were analyzed. The highest recorded HGS values (Method A) or the average HGS values (Method B) for the dominant hand were used to compute the HGS asymmetry (nondominant HGS/dominant HGS out of 0.9-1.1) and HGS weakness (male <28 kg, female <18 kg). Risk factors associated with the weak and asymmetric HGS were identified by logistic regression analysis. RESULTS: Risk factors associated with weak and asymmetric HGS of varying severity differed between the two methods. Both methods identified age and illiteracy as risk factors for weak HGS with 10%-20% asymmetry. Method A also identified speech impediment, stroke, and sleep duration as additional risk factors. Similarly, both methods identified age, illiteracy, primary school education and below, diabetes, and stroke as risk factors for weak HGS and asymmetry over 30.1%. Method B additionally identified a history of falls as a risk factor. However, apart from age, the risk factors for weak HGS with 20.1%-30% asymmetry differed between the two methods-Method A identified kidney disease, while Method B identified illiteracy and asthma. CONCLUSIONS: The results revealed that risk factors associated with the abnormal HGS in older adults varied based on the methods used to define these conditions.