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Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications.
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Peach varieties that differ in red coloration due to varied anthocyanin accumulation result from transcriptional regulation by PpMYB10s, a group of specific R2R3 MYBs. Here we investigated the mechanisms driving a lack of anthocyanin in yellow-skinned 'Jinxiu' peach peel, as well as accumulation induced by UV irradiance. It was found that PpMYB10.1, PpMYB10.2 and PpMYB10.3 were positive regulators of anthocyanin accumulation, but the stimulation by PpMYB10.2 was weak. Low expression of PpMYB10.1 causes natural anthocyanin deficiency in 'Jinxiu' peel. However, the promoter sequences of PpMYB10.1 were identical in 'Jinxiu' and a naturally red-coloured peach 'Hujingmilu'. Therefore, potential negative regulator(s) upstream of PpMYB10.1 were explored. A novel R2R3-MYB repressor termed PpMYB80 was identified through comparative transcriptomic analysis and then functionally confirmed via transiently overexpressing and silencing in peach fruit, as well as transformation in tobacco. PpMYB80 directly binds to the promoter of PpMYB10.1 and inhibits its expression, but does not affect PpMYB10.3. In UV-exposed 'Jinxiu' fruit, expression of PpMYB10.3 was upregulated, while PpMYB10.1 remained low and PpMYB80 enhanced, which results in accumulation of anthocyanin in peel. This study revealed a transcriptional cascade involving PpMYB activators and repressors in regulating basal and UV-induced anthocyanin accumulation in peach peel.
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A promising mid-infrared (MIR) laser crystal with Er, Sm co-doped SrLaAlO4 (Er,Sm:SLA) crystal was successfully grown using the Czochralski (CZ) method. It was the first time that co-doped Sm3+ ion as deactivator for Er3+ activated â¼ 3.0 µm laser. The crystal structure, absorption spectra, emission spectra, and energy level lifetime were discussed in detail. The band structure and density of states were calculated by the density functional theory. The spectral parameters were calculated using Judd-Ofelt (J-O) theory and the deactivate effect of Sm3+ was systematically studied. The introduction of Sm3+ ions enhance the 2.7 µm mid infrared emission intensity by three times, and decrease the lifetime of 4I13/2 energy level of Er3+ ion from 4.35 ms to 0.98 ms. The lifetime ratio of upper and lower levels for 2.7 µm emission was calculated to be 0.63, which is 2.6 times of Er:SLA crystal and comparable to some commercial crystals. All the results indicate that the Sm3+ ion is an effective deactivator for â¼3 µm laser emission. The long upper level lifetime, as well as the large lifetime ratio, the broadening spectra characteristics and the appropriate emission cross-section show the Er,Sm:SLA crystal a good gain material for ultrafast and tunable lasers at â¼3.0 µm.
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Micro/nanomotors represent a promising class of drug delivery carriers capable of converting surrounding chemical or external energy into mechanical power, enabling autonomous movement. Their distinct autonomous propulsive force distinguishes them from other carriers, offering significant potential for enhancing drug penetration across cellular and tissue barriers. A comprehensive understanding of micro/nanomotor dynamics with various power sources is crucial to facilitate their transition from proof-of-concept to clinical application. In this review, micro/nanomotors are categorized into three classes based on their energy sources: endogenously stimulated, exogenously stimulated, and live cell-driven. The review summarizes the mechanisms governing micro/nanomotor movements under these energy sources and explores factors influencing autonomous motion. Furthermore, it discusses methods for controlling micro/nanomotor movement, encompassing aspects related to their structure, composition, and environmental factors. The remarkable propulsive force exhibited by micro/nanomotors makes them valuable for significant biomedical applications, including tumor therapy, bio-detection, bacterial infection therapy, inflammation therapy, gastrointestinal disease therapy, and environmental remediation. Finally, the review addresses the challenges and prospects for the application of micro/nanomotors. Overall, this review emphasizes the transformative potential of micro/nanomotors in overcoming biological barriers and enhancing therapeutic efficacy, highlighting their promising clinical applications across various biomedical fields.
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Hydrogels, as an emerging biomaterial, have found extensive use in the healing of wounds due to their distinctive physicochemical structure and functional properties. Moreover, hydrogels can be made to match a range of therapeutic requirements for materials used in wound healing through specific functional modifications. This review provides a step-by-step explanation of the processes involved in cutaneous wound healing, including hemostasis, inflammation, proliferation, and reconstitution, along with an investigation of the factors that impact these processes. Furthermore, a thorough analysis is conducted on the various stages of the wound healing process at which functional hydrogels are implemented, including hemostasis, anti-infection measures, encouraging regeneration, scar reduction, and wound monitoring. Next, the latest progress of multifunctional hydrogels for wound healing and the methods to achieve these functions are discussed in depth and categorized for elucidation. Finally, perspectives and challenges associated with the clinical applications of multifunctional hydrogels are discussed.
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Hidrogeles , Piel , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Humanos , Animales , Piel/efectos de los fármacos , Piel/lesiones , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Hemostasis/efectos de los fármacosRESUMEN
The comorbidity of anxiety and depression frequently occurs in patients with neuropathic pain. The ventrolateral orbital cortex (VLO) plays a critical role in mediating neuropathic pain and anxiodepression in rodents. Previous studies suggested that 5-HT6 receptors in the VLO are involved in neuropathic pain. Strong evidence supports a close link between 5-HT6 receptors and affective disorders such as depression and anxiety disorders. However, it remains unclear whether the 5-HT6 receptors in the VLO are involved in neuropathic pain-induced anxiodepression. Using a rat neuropathic pain model of spared nerve injury (SNI), we demonstrated that rats exhibited significant anxiodepression-like behaviors and the expression of VLO 5-HT6 receptors obviously decreased four weeks after SNI surgery. Microinjection of the 5-HT6 receptor agonist EMD-386088 into the VLO or overexpression of VLO 5-HT6 receptors alleviated anxiodepression-like behaviors. These effects were blocked by pre-microinjection of a selective 5-HT6 receptor antagonist (SB-258585) or inhibitors of AC (SQ-22536), PKA (H89), and MEK1/2 (U0126) respectively. Meanwhile, the expression of p-ERK, p-CREB, and BDNF in the VLO decreased four weeks after SNI surgery. Furthermore, administration of EMD-386088 upregulated the expression of BDNF, p-ERK, and p-CREB in the VLO of SNI rats, which were reversed by pre-injection of SB-258585. These findings suggest that activating 5-HT6 receptors in the VLO has anti-anxiodepressive effects in rats with neuropathic pain via activating AC-cAMP-PKA-MERK-CREB-BDNF signaling pathway. Accordingly, 5-HT6 receptor in the VLO could be a potential target for the treatment of the comorbidity of neuropathic pain and anxiodepression.
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BACKGROUND: Hepatitis is a systemic disease that often results in various comorbidities. Meta-bolic disorders, the most common comorbidities in clinical practice, were selected for this study. AIM: To investigate the causal relationship between comorbidities and hepatitis trea-tment outcomes. METHODS: A total of 23583378 single nucleotide polymorphisms from 1248743 cases and related summaries of genome-wide association studies were obtained from online public databases. A two-sample Mendelian randomization (MR) was performed to investigate causality between exposure [type 2 diabetes mellitus (T2D), hyperlipidemia, and hypertension] and outcome (chronic hepatitis B or C in-fections). RESULTS: The data supported the causal relationship between comorbidities and hepatitis infections, which will affect the severity of hepatitis progression and will also provide a reference for clinical researchers. All three exposures showed a link with progression of both hepatitis B (T2D, P = 0.851; hyperlipidemia, P = 0.596; and hypertension, P = 0.346) and hepatitis C (T2D, P = 0.298; hyperlipidemia, P = 0.141; and hypertension, P = 0.035). CONCLUSION: The results of MR support a possible causal relationship between different ex-posures (T2D, hyperlipidemia, and hypertension) and chronic hepatitis progression; however, the potential mechanisms still need to be elucidated.
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Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.
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Depresión , Estrés del Retículo Endoplásmico , Retículo Endoplásmico , Ratones Endogámicos C57BL , Microglía , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR , Derrota Social , Estrés Psicológico , Canal Aniónico 1 Dependiente del Voltaje , Animales , Mitocondrias/metabolismo , Depresión/metabolismo , Microglía/metabolismo , Microglía/patología , Ratones , Masculino , Retículo Endoplásmico/metabolismo , Estrés Psicológico/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/genética , Hipocampo/metabolismo , Hipocampo/patología , Adenosina Trifosfato/metabolismo , Inflamasomas/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Calcio/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Conducta Animal , Membranas Asociadas a Mitocondrias , Proteínas HSP70 de Choque TérmicoRESUMEN
BACKGROUND: Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression. METHODS: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS. RESULTS: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice. LIMITATION: The cellular specificity of MAMs related protein changes in CSDS mice was not explored. CONCLUSIONS: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses.
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Depresión , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico , Hipocampo , Ratones Endogámicos C57BL , Estrés Psicológico , Animales , Hipocampo/patología , Hipocampo/fisiopatología , Ratones , Estrés del Retículo Endoplásmico/fisiología , Masculino , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Mitocondrias , Electroacupuntura , Membranas Mitocondriales/metabolismo , Derrota Social , Conducta Animal/fisiología , Membranas Asociadas a MitocondriasRESUMEN
The CUL3-RING E3 ubiquitin ligases (CRL3s) play an essential role in response to extracellular nutrition and stress stimuli. The ubiquitin ligase function of CRL3s is activated through dimerization. However, how and why such a dimeric assembly is required for its ligase activity remains elusive. Here, we report the cryo-EM structure of the dimeric CRL3KLHL22 complex and reveal a conserved N-terminal motif in CUL3 that contributes to the dimerization assembly and the E3 ligase activity of CRL3KLHL22. We show that deletion of the CUL3 N-terminal motif impairs dimeric assembly and the E3 ligase activity of both CRL3KLHL22 and several other CRL3s. In addition, we found that the dynamics of dimeric assembly of CRL3KLHL22 generates a variable ubiquitination zone, potentially facilitating substrate recognition and ubiquitination. These findings demonstrate that a CUL3 N-terminal motif participates in the assembly process and provide insights into the assembly and activation of CRL3s.
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Secuencias de Aminoácidos , Microscopía por Crioelectrón , Proteínas Cullin , Receptores de Interleucina-17 , Ubiquitina-Proteína Ligasas , Ubiquitinación , Proteínas Cullin/metabolismo , Proteínas Cullin/química , Proteínas Cullin/genética , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genética , Células HEK293 , Multimerización de Proteína , Secuencia Conservada , Unión Proteica , Modelos MolecularesRESUMEN
Nanozyme-based colorimetric sensing has drawn immense attention due to the rapid development of nanozyme in recent years. However, the selectivity of nanozyme-based colorimetric sensing greatly limits its subsequent practical application. It is well known that sample pretreatment can not only improve selectivity by eliminating the sample matrix interference, but also improve sensitivity by enriching trace targets. Based on the easy facile surface modification properties of nanozyme, we rationally designed nanozyme combined with sample pretreatment for colorimetric biosensing, through separation and enrichment, thereby improving the selectivity and sensitivity of the nanozyme colorimetric biosensing. As a proof of concept, the detection of Hg2+ by nanozyme-based colorimetric sensing was used as an example. Magnetic peroxidase-like nanozyme Fe3S4 was designed and synthesized. The selectivity is improved by the specific adsorption of S-Hg bond and the interference elimination after magnetic separation. In addition, the sensitivity is improved by magnetic solid-phase extraction enrichment. Our established colorimetric sensing based on Fe3S4 nanozyme integrated sample pretreatment with an enrichment factor of 100 and the limit of detection (LOD) is 26 nM. In addition, this strategy was successfully applied to detect Hg2+ in environmental water samples. Overall, the strategy showed good selectivity and sensitivity, providing a new practical method for the application of nanozyme-based biosensing in sample pretreatment.
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Colorimetría , Límite de Detección , Mercurio , Estructuras Metalorgánicas , Extracción en Fase Sólida , Mercurio/análisis , Mercurio/aislamiento & purificación , Colorimetría/métodos , Extracción en Fase Sólida/métodos , Estructuras Metalorgánicas/química , Catálisis , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/aislamiento & purificación , Peroxidasa/química , Técnicas Biosensibles/métodosRESUMEN
LC-MS is widely utilized in identifying and tracing plant-derived food varieties but quality control markers screening and accurate identification remain challenging. The adulteration and confusion of Chrysanthemum flowers highlight the need for robust quality control markers. This study established an efficient workflow by integrating UHPLC-Orbitrap-MS/MS with Compound Discoverer and chemometrics. This workflow enabled the systematic screening of 21 markers from 10,540 molecular features, which effectively discriminated Chrysanthemum flowers of different species and cultivars. The workflow incorporated targeted and untargeted methods by employing diagnostic product ions, fragmentation patterns, mzCloud, mzVault, and in-house databases to identify 206 compounds in the flowers, including 17 screened markers. This approach improved identification accuracy by reducing false positives, eliminating in-source fragmentation interference, and incorporating partial verification utilizing our established compound bank. Practically, this workflow can be instrumental in quality control, geolocation determination, and varietal tracing of Chrysanthemum flowers, offering prospective use in other plant-derived foods.
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Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-DTT as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the near-infrared (NIR), it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable reactive oxygen species scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 days. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.
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We established an efficient method using high-speed countercurrent chromatography (HSCCC) combined with preparative high-performance liquid chromatography (prep-HPLC) for isolating and purifying Gelsemium elegans (G. elegans) alkaloids. First, the two-phase solvent system composed of 1% triethylamine aqueous solution/n-hexane/ethyl acetate/ethanol (volume ratio 4:2:3:2) was employed to separate the crude extract (350 mg) using HSCCC. Subsequently, the mixture that resulted from HSCCC was further separated by Prep-HPLC, resulting in seven pure compounds including: 14-hydroxygelsenicine (1, 12.1 mg), sempervirine (2, 20.8 mg), 19-(R)-hydroxydihydrogelelsevirine (3, 10.1 mg), koumine (4, 50.5 mg), gelsemine (5, 32.2 mg), gelselvirine (6, 50.5 mg), and 11-hydroxyhumanmantenine (7, 12.5 mg). The purity of these seven compounds were 97.4, 98.9, 98.5, 99, 99.5, 96.8, and 85.5%, as determined by HPLC. The chemical structures of the seven compounds were analyzed and confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear magnetic resonance (1H NMR), and 13 C-nuclear magnetic resonance (13 C NMR) spectra. The results indicate that the HSCCC-prep-HPLC method can effectively separate the major alkaloids from the purified G. elegans, holding promising prospects for potential applications in the separation and identification of other traditional Chinese medicines.
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We previously demonstrated a positive relation of secretory phospholipase A2 group IIA (sPLA2-IIA) with circulating high-density lipoprotein cholesterol (HDL-C) in patients with coronary artery disease, and sPLA2-IIA increased cholesterol efflux in THP-1 cells through peroxisome proliferator-activated receptor-γ (PPAR-γ)/liver X receptor α/ATP-binding cassette transporter A1 (ABCA1) signaling pathway. The aim of the present study was to examine the role of sPLA2-IIA over-expression on lipid profile in a transgenic mouse model. Fifteen apoE-/- and C57BL/7 female mice received bone marrow transplantation from transgenic SPLA2-IIA mice, and treated with specific PPAR-γ inhibitor GW9662. High fat diet was given after one week of bone marrow transplantation, and animals were sacrificed after twelve weeks. Immunohistochemical staining showed over-expression of sPLA2-IIA protein in the lung and spleen. The circulating level of HDL-C, but not that of low-density lipoprotein cholesterol (LDL-C), total cholesterol, or total triglyceride, was increased by sPLA2-IIA over-expression, and was subsequently reversed by GW9662 treatment. Over-expression of sPLA2-IIA resulted in augmented expression of cholesterol transporter ABCA1 at mRNA level in the aortas, and at protein level in macrophages, co-localized with macrophage specific antigen CD68. GW9662 exerted potent inhibitory effects on sPLA2-IIA-induced ABCA1 expression. Conclusively, we demonstrated the effects of sPLA2-IIA on circulating HDL-C level and the expression of ABCA1, possibly through regulation of PPAR-γ signaling in transgenic mouse model, that is in concert with the conditions in patients with coronary artery disease.
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Transportador 1 de Casete de Unión a ATP , Molécula CD68 , Ratones Endogámicos C57BL , Ratones Transgénicos , Animales , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador 1 de Casete de Unión a ATP/genética , Femenino , Ratones , Fosfolipasas A2 Grupo II/metabolismo , Fosfolipasas A2 Grupo II/genética , PPAR gamma/metabolismo , HDL-Colesterol/sangre , HDL-Colesterol/metabolismo , Pulmón/metabolismo , Pulmón/patología , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD/metabolismo , Antígenos CD/genética , Bazo/metabolismo , Trasplante de Médula Ósea , Humanos , Lípidos/sangreRESUMEN
Nanozymes have been widely used in the field of biosensing owing to their high stability, low cost, adjustable catalytic activity, and convenient modification. However, achieving high selectivity and sensitivity simultaneously in nanozyme-based colorimetric sensing remains a major challenge. Nanozymes are nanomaterials with enzyme-simulating activity that are often used as solid-phase adsorbents for sample pretreatment. Our design strategy integrated sample pretreatment function into the nanozyme through separation and enrichment, thereby improving the selectivity and sensitivity of nanozyme-based colorimetric biosensing. As a proof-of-concept, glucose was used as the model analyte in this study. A phenylboric acid-modified magnetic nanozyme (Cu/Fe3O4@BA) was rationally designed and synthesized. Selectivity was enhanced by boronate-affinity specific adsorption and the elimination of interference after magnetic separation. In addition, magnetic solid-phase extraction enrichment was used to improve the sensitivity. A recovery rate of more than 80% was reached when the enrichment factor was 50. The synthesized magnetic Cu/Fe3O4@BA was recyclable at least five times. The proposed method exhibited excellent selectivity and sensitivity, simple operation, and recyclability, providing a novel and practical strategy for designing multifunctional nanozymes for biosensing.
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Técnicas Biosensibles , Colorimetría , Cobre , Glucosa , Técnicas Biosensibles/métodos , Colorimetría/métodos , Cobre/química , Glucosa/análisis , Glucosa/aislamiento & purificación , Glucosa/química , Nanoestructuras/química , Límite de Detección , Extracción en Fase Sólida/métodos , Ácidos Borónicos/química , AdsorciónRESUMEN
BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice. RESULTS: LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice. CONCLUSIONS: The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.
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Complemento C1q , Complemento C3 , Depresión , Modelos Animales de Enfermedad , Microglía , Fagocitosis , Transducción de Señal , Sinapsis , Animales , Complemento C1q/metabolismo , Microglía/metabolismo , Sinapsis/metabolismo , Ratones , Transducción de Señal/fisiología , Depresión/metabolismo , Fagocitosis/fisiología , Complemento C3/metabolismo , Masculino , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BLRESUMEN
Color is one of the vital components of product design and the choice of color combination is a critical factor that affects consumer reaction and purchase decisions. However, the impact of traditional colors on color extraction and product design has seldom been studied. The purpose of this study is to discover suitable colors from traditional patterns to create color schemes that will be used in the design of children's products. Colors were extracted from five major traditional ornaments obtained from Turkmenistan's national carpets, each representing one of the main Turkmen tribes, using tools like Photoshop, Adobe Color, and EasyRGB, with the objective of investigating psychological-emotional attachment, reaction, and attitudes towards the colors obtained. This initial extraction provided 124 color data points. Initially, extracted colors were refined and used to develop novel color schemes by two independent survey studies. The first survey, based on a sample of 104 parents of preschool children, identified colors that have a positive emotional effect on consumer preferences and provided the basis to develop color schemes. As a result, 25 colors were identified for use in developing 14 color schemes. The second survey, based on a sample of 48 parents of preschool children, identified which color schemes have an attraction for consumers. The survey indicated that 11 out of these 14 schemes were highly favored by the respondents. Based on these results, this study proposed new color schemes for children's products, extracted from traditional patterns of Turkmenistan and aligned with the psychological perception of the consumers.
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Actitud , Emociones , Preescolar , Humanos , Encuestas y Cuestionarios , Comportamiento del ConsumidorRESUMEN
INTRODUCTION: If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. METHODS: A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. RESULTS: Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. CONCLUSIONS: Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.
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Gota , Humanos , Gota/complicaciones , Factores de Riesgo , Fumar/efectos adversos , Índice de Masa Corporal , Tasa de Filtración GlomerularRESUMEN
OBJECTIVE: To identify the long non-coding RNA (lncRNA) expression profiling in exosomes derived from synovial fluid of rheumatoid arthritis (RA) patients, and carry out bioinformatics analysis on target genes of differentially expressed lncRNAs. METHODS: Exosomes were isolated from synovial fluid via ultracentrifugation. RNAs were extracted from exosomes by using HiPure Liquid RNA/miRNA kits, followed by lncRNA sequencing. Differentially expressed lncRNAs in RA were screened, and bioinformatics analysis of their target genes was carried out. qRT-PCR was used to verify the lncRNA expression levels. RESULTS: Compared with osteoarthritis (OA), 347 lncRNAs were found differentially expressed in RA. Compared with gout, 805 lncRNAs were found differentially expressed in RA. Compared with both OA and gout, 85 lncRNAs were found specially expressed in RA (65 were upregulated (including ENST00000433825.1)). Functional analysis of target genes of the specially expressed lncRNAs revealed significant enrichment of "autophagy" and "mTOR signaling pathway". The qRT-PCR results indicated that ENST00000433825.1 was highly expressed in RA, compared with both OA and gout (P < 0.05), which matched the lncRNA sequencing results. Correlation analysis showed that the level of ENST00000433825.1 in RA patients was significantly and positively correlated with the level of C-reactive protein (CRP) (P < 0.001). CONCLUSIONS: The lncRNA expression profiling in exosomes derived from synovial fluid of RA was significantly different from OA and gout. ENST00000433825.1 was highly and uniquely expressed in RA and significantly and positively correlated with CRP, which might provide a diagnostic and therapeutic biomarker for RA.