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Dual-ion batteries (DIBs) present great application potential in low-temperature energy storage scenarios due to their unique dual-ion working mechanism. However, at low temperatures, the insufficient electrochemical oxidation stability of electrolytes and depressed interfacial compatibility impair the DIB performance. Here, we design a variant-localized high-concentration solvation structure for universal low-temperature electrolytes (ν-LHCE) without the phase separation via introducing an extremely weak-solvating solvent with low energy levels. The unique solvation structure gives the ν-LHCE enhanced electrochemical oxidation stability. Meanwhile, the extremely weak-solvating solvent can competitively participate in the Li+-solvated coordination, which improves the Li+ transfer kinetics and boosts the formation of robust interphases. Thus, the ν-LHCE electrolyte not only has a good high-voltage stability of >5.5â V and proper Li+ transference number of 0.51 but also shows high ionic conductivities of 1 mS/cm at low temperatures. Consequently, the ν-LHCE electrolyte enables different types of batteries to achieve excellent long-term cycling stability and good rate capability at both room and low temperatures. Especially, the capacity retentions of the DIB are 77.7 % and 51.6 %, at -40 °C and -60 °C, respectively, indicating great potential for low-temperature energy storage applications, such as polar exploration, emergency communication equipment, and energy storage station in cold regions.
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The alluring correlations of cellular behaviors with viscoelastic extracellular matrices have driven increasing endeavors directed toward the understanding of mechanical cues on cell growth and differentiation via preparing biomimetic scaffolds/gels with viscoelastic controllability. Indeed, systematic investigations, especially into calcium phosphate-containing biomimetics, are relatively rare. Here, oxidized hyaluronic acid/hydroxyapatite hybrids (OHAHs) were synthesized by hyaluronan-mediated biomimetic mineralization with confined ion diffusion and subsequent oxidization treatment. The collagen self-assembly was applied to fabricate tunable stress relaxing fibrillar matrices in the presence of OHAHs in which the incorporated hyaluronic acid with aldehyde groups acted to improve the component compatibility as well as to supplement the molecular interactions with the occurrence of a Schiff-base reaction. With the addition of varying OHAH contents, the self-assembly behavior of collagen was altered, and the obtained collagen-hybrid (CH) matrices presented a heterogeneous fibrillar structure interspersed with OHAHs, characterized by large fibrillar bundles coexisting with small fibrils. The OHAHs improved the hydrogel stability of pure collagen, and according to rheological and nanoindentation measurements, CH matrices also exhibited tunable stress relaxation rates, following an OHAH concentration-dependent fashion. The proliferation and spreading of MC3T3-E1 cells cultured onto such CH matrices were further found to increase with the stress relaxing rate of the matrices. The present study showed that the introduction of hydroxyapatite incorporated with active hyaluronic acid during collagen reconstitution was a simple and effective strategy to realize the preparation of tunable stress relaxing biomimetic matrices potentially used for further appraising the regulation of mechanical cues on cell behaviors.
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Durapatita , Ácido Hialurónico , Ácido Hialurónico/química , Durapatita/química , Biomimética , Colágeno/química , Matriz Extracelular , Hidrogeles/químicaRESUMEN
Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.
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Trastorno Autístico/inducido químicamente , Glicina/análogos & derivados , Exposición Materna , Efectos Tardíos de la Exposición Prenatal , Animales , Conducta Animal/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Modelos Animales de Enfermedad , Epóxido Hidrolasas/metabolismo , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Glicina/efectos adversos , Masculino , Ratones , Embarazo , GlifosatoRESUMEN
Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. We recently reported that the new antidepressant (R)-ketamine could ameliorate the disease progression in experimental autoimmune encephalomyelitis model of MS. Cuprizone (CPZ) has been used to produce demyelination which resembles demyelination in MS patients. This study was undertaken to investigate whether (R)-ketamine could affect demyelination in CPZ-treated mice and remyelination after CPZ withdrawal. Repeated treatment with (R)-ketamine (10 mg/kg/day, twice weekly, for 6 weeks) significantly ameliorated demyelination and activated microglia in the brain compared with saline-treated mice. Furthermore, pretreatment with ANA-12 (TrkB antagonist) significantly blocked the beneficial effects of (R)-ketamine on the demyelination and activated microglia in the brain of CPZ-treated mice. The 16S rRNA analysis showed that (R)-ketamine significantly improved abnormal composition of gut-microbiota and decreased levels of lactic acid of CPZ-treated mice. In addition, there were significant correlations between demyelination (or microglial activation) in the brain and the relative abundance of several microbiome, suggesting a link between gut microbiota and brain. Interestingly, (R)-ketamine could facilitate remyelination in the brain after CPZ withdrawal. In conclusion, the study suggests that (R)-ketamine could ameliorate demyelination in the brain of CPZ-treated mice through TrkB activation, and that gut-microbiota-microglia crosstalk may play a role in the demyelination of CPZ-treated mice. Therefore, it is likely that (R)-ketamine could be a new therapeutic drug for MS.
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Encefalomielitis Autoinmune Experimental , Ketamina , Microbiota , Remielinización , Animales , Encéfalo , Cuprizona/toxicidad , Modelos Animales de Enfermedad , Humanos , Ketamina/farmacología , Ratones , Ratones Endogámicos C57BL , Microglía , Vaina de Mielina , Oligodendroglía , ARN Ribosómico 16SRESUMEN
Red swamp crayfish (Procambarus clarkii) is an important aquaculture species in China. With increasing crayfish culture, a number of outbreaks of various diseases have been identified in crayfish. Despite this, there are no reports on the application of disease resistance genes in the molecular breeding of crayfish. In this study, transcriptome analysis was performed to explore the disease resistance genes in crayfish, with a focus on investigating the genetic variations in the open reading frames of these genes, for subsequent haplotype analysis. Furthermore, pathogen-challenge experiments were carried out in the crayfish, to identify the favoured haplotypes. A novel disease resistance gene, R (Resistance), was identified by means of transcriptome analysis. In total, two, four, and five haplotypes of the three disease resistance genes, ALF, R, and crustin2, respectively, were detected. ALF1, R1, and Cru1 were the favoured haplotypes of ALF, R, and crustin2, respectively. Subsequently, the favoured haplotype combinations of the different genes were obtained, and a series of molecular markers were developed to identify them. Finally, we propose a molecular breeding strategy to enhance the disease resistance of crayfish, and thus, improve its production.
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Astacoidea , Resistencia a la Enfermedad , Animales , Astacoidea/genética , Resistencia a la Enfermedad/genética , Perfilación de la Expresión Génica , Sistemas de Lectura Abierta , Alimentos MarinosRESUMEN
Maternal immune activation (MIA) plays a role in the etiology of schizophrenia. MIA by prenatal exposure of polyinosinic:polycytidylic acid [poly(I:C)] in rodents caused behavioral and neurobiological changes relevant to schizophrenia in adult offspring. We investigated whether the novel antidepressant (R)-ketamine could prevent the development of psychosis-like phenotypes in adult offspring after MIA. We examined the effects of (R)-ketamine (10 mg/kg/day, twice weekly for 4 weeks) during juvenile and adolescent stages (P28-P56) on the development of cognitive deficits, loss of parvalbumin (PV)-immunoreactivity in the medial prefrontal cortex (mPFC), and decreased dendritic spine density in the mPFC and hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, we examined the role of TrkB in the prophylactic effects of (R)-ketamine. Repeated intermittent administration of (R)-ketamine during juvenile and adolescent stages significantly blocked the development of cognitive deficits, reduced PV-immunoreactivity in the prelimbic (PrL) of mPFC, and decreased dendritic spine density in the PrL of mPFC, CA3 and dentate gyrus of the hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, pretreatment with ANA-12 (TrkB antagonist: twice weekly for 4 weeks) significantly blocked the beneficial effects of (R)-ketamine on cognitive deficits of adult offspring after prenatal poly(I:C) exposure. These data suggest that repeated intermittent administration of (R)-ketamine during juvenile and adolescent stages could prevent the development of psychosis in adult offspring after MIA. Therefore, (R)-ketamine would be a potential prophylactic drug for young subjects with high-risk for psychosis.
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Ketamina , Trastornos Psicóticos , Esquizofrenia , Adolescente , Hijos Adultos , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ketamina/farmacología , Glicoproteínas de Membrana/metabolismo , Fenotipo , Poli I-C/farmacología , Embarazo , Receptor trkB/metabolismo , Esquizofrenia/prevención & controlRESUMEN
The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) regulates the cholinergic ascending anti-inflammatory pathway involved in depression. We previously reported that Chrna7 knock-out (KO) mice show depression-like phenotypes through systemic inflammation. In this study, we investigated whether fecal microbiota transplantation (FMT) from Chrna7 KO mice causes depression-like phenotypes in mice treated with an antibiotic cocktail (ABX). Chrna7 KO mice with depression-like phenotypes show an abnormal gut microbiota composition, although the alpha diversity and beta diversity were not altered. FMT from Chrna7 KO mice caused depression-like phenotypes, systemic inflammation, and downregulation of synaptic proteins in the prefrontal cortex (PFC) in the ABX-treated mice compared to FMT from the control mice. The Principal component analysis based on the OTU level showed that the FMT group from the KO mice were different from the FMT group from the control mice. We found differences in abundance for several bacteria in the FMT group from the KO mice at the taxonomic level when compared with the other group. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of depression-like phenotypes in the ABX-treated mice after FMT from Chrna7 KO mice. These data suggest that FMT from Chrna7 KO mice produce depression-like phenotypes in ABX-treated mice via the subdiaphragmatic vagus nerve. The brain-gut-microbiota axis association with the subdiaphragmatic vagus nerve plays an important role in the development of depression.
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Depresión , Trasplante de Microbiota Fecal , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Nervio Vago , Receptor Nicotínico de Acetilcolina alfa 7/genéticaRESUMEN
The transcription nuclear factor-erythroid factor 2-related factor 2 (Nrf2) plays a key role in inflammation that is involved in depression. We previously reported that Nrf2 knock-out (KO) mice exhibit depression-like phenotypes through systemic inflammation. (R)-ketamine, an enantiomer of ketamine, has rapid-acting and long-lasting antidepressant-like effects in rodents. We investigated whether (R)-ketamine can produce antidepressant-like effects in Nrf2 KO mice. Effects of (R)-ketamine on the depression-like phenotypes in Nrf2 KO mice were examined. Furthermore, the role of TrkB in the antidepressant-like actions of (R)-ketamine was also examined. In the tail-suspension test (TST) and forced swimming test (FST), (R)-ketamine (10 mg/kg) significantly attenuated the increased immobility times of TST and FST in the Nrf2 KO mice. In the sucrose preference test (SPT), (R)-ketamine significantly ameliorated the reduced preference of SPT in Nrf2 KO mice. Decreased expression of synaptic proteins (i.e., GluA1 and PSD-95) in the medial prefrontal cortex (mPFC) of Nrf2 KO mice was significantly ameliorated after a single injection of (R)-ketamine. Furthermore, the pre-treatment with the TrkB antagonist ANA-12 (0.5 mg/kg) significantly blocked the rapid and long-lasting antidepressant-like effects of (R)-ketamine in Nrf2 KO mice. Furthermore, ANA-12 significantly antagonized the beneficial effects of (R)-ketamine on decreased expression of synaptic proteins in the mPFC of Nrf2 KO mice. These findings suggest that (R)-ketamine can produce rapid and long-lasting antidepressant-like actions in Nrf2 KO mice via TrkB signaling.
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Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Ketamina/farmacología , Glicoproteínas de Membrana/efectos de los fármacos , Proteínas Tirosina Quinasas/efectos de los fármacos , Receptor trkB/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Animales , Antidepresivos/administración & dosificación , Azepinas/farmacología , Benzamidas/farmacología , Modelos Animales de Enfermedad , Ketamina/administración & dosificación , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 2 Relacionado con NF-E2/genéticaRESUMEN
The spleen is a large immune organ that plays a key role in the immune system. The precise molecular mechanisms underlying the relationship between the spleen and stress-related psychiatric disorders are unknown. Here we investigated the role of spleen in stress-related psychiatric disorders. FACS analysis was applied to determine the contribution of the spleen to susceptibility and resilience in mice that were subjected to chronic social defeat stress (CSDS). We found a notable increase in splenic volume and weight in CSDS-susceptible mice compared to control (no CSDS) mice and CSDS-resilient mice. The number of granulocytes, but not of T cells and B cells, in the spleen of susceptible mice was higher than in the spleen of both control and resilient mice. Interestingly, NKG2D (natural killer group 2, member D) expression in the spleen of CSDS-susceptible mice was higher than that in control mice and CSDS-resilient mice. In addition, NKG2D expression in the spleen of patients with depression was higher than that in controls. Both increased splenic weight and increased splenic NKG2D expression in CSDS-susceptible mice were ameliorated after a subsequent administration of (R)-ketamine. The present findings indicate a novel role of splenic NKG2D in stress susceptibility versus resilience in mice subjected to CSDS. Furthermore, abnormalities in splenic functions in CSDS-susceptible mice were ameliorated after subsequent injection of (R)-ketamine. Thus, the brain-spleen axis might, at least in part, contribute to the pathogenesis of stress-related psychiatric disorders such as depression.
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Antidepresivos/farmacología , Trastorno Depresivo Mayor/inmunología , Susceptibilidad a Enfermedades/inmunología , Ketamina/farmacología , Subfamilia K de Receptores Similares a Lectina de Células NK/efectos de los fármacos , Resiliencia Psicológica , Derrota Social , Bazo/efectos de los fármacos , Bazo/inmunología , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/inmunología , Animales , Antidepresivos/administración & dosificación , Autopsia , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Ketamina/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Lóbulo Parietal/inmunología , Bazo/patologíaRESUMEN
BACKGROUND: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotic-treated microbiota depletion. METHODS: The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined. RESULTS: The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (Lactobacillus intestinalis and Lactobacillus reuteri) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14 days led to depression- and anhedonia-like phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotic-treated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes. CONCLUSIONS: These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of L. intestinalis and L. reuteri. Therefore, it is likely that the brain-gut-microbiota axis participates in the pathogenesis of depression via the vagus nerve.
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Anhedonia/efectos de los fármacos , Antibacterianos/farmacología , Depresión/microbiología , Lactobacillus , Limosilactobacillus reuteri , Nervio Vago/microbiología , Animales , Depresión/sangre , Microbioma Gastrointestinal , Interleucina-6/sangre , Ratones , Actividad Motora/efectos de los fármacos , Estrés Psicológico/sangre , Estrés Psicológico/microbiologíaRESUMEN
Objective This study aimed to identify misdiagnosed or undiagnosed psychiatric disorders and the factors associated with these disorders in patients with sleep problems who are referred to a consultation-liaison service. Method Records of all inpatients receiving a consultation from the Psychiatry Department between January and December 2016 were retrospectively reviewed. Psychiatric diagnoses were analyzed using descriptive statistics, and the factors associated with the risk of these disorders in patients with sleep problems were determined by multiple logistic regression analysis. Results Of the 331 referral patients whose referral reason was simply having trouble in sleeping, only 97 patients were diagnosed with primary sleep disorder after consultation. The recognition rate of psychiatric disorders in inpatients with sleep problems among nonpsychiatric physicians was 29.3%. Anxiety (107, 45.7%) was the most common psychiatric diagnosis in patients with sleep problems followed by organic mental disorder (83, 35.5%), depression (37, 15.8%), and other mental disorders (8, 3.4%). Multiple logistic regression analysis revealed that a course >1 month (OR = 3.656, 95% CI = 2.171-6.156, p = 0.000) and sleep-wake rhythm disturbances (OR = 25.008, 95% CI = 5.826-107.341, p = 0.000) were associated with increased risks of psychiatric disorders. Conclusions The study showed that recognition rate of psychiatric disorders in inpatients with sleep problems was very low. A course >1 month and sleep-wake rhythm disturbances were associated with increased risks of disorders and could be used as indicators by nonpsychiatric physicians to improve diagnoses.
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Trastornos Mentales/complicaciones , Trastornos del Sueño-Vigilia/complicaciones , Adulto , Anciano , Femenino , Humanos , Pacientes Internos/psicología , Masculino , Trastornos Mentales/psicología , Persona de Mediana Edad , Derivación y Consulta , Estudios Retrospectivos , Trastornos del Sueño-Vigilia/psicologíaRESUMEN
BACKGROUND: The Illness Attitude Scales (IAS) are considered as one of the most suitable instruments to screen hypochondriasis. PURPOSE: Whether it has cross-cultural validity in China remains to be determined. METHODS: In Chinese university students (141 women and 141 men), we have administered the IAS, the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ), and the Plutchik-van Praag Depression Inventory (PVP). RESULTS: For the first time in Chinese culture, we have identified a four-factor structure of the IAS: patho-thanatophobia, symptom effect, treatment seeking, and hypochondriacal belief. Women scored significantly higher on IAS patho-thanatophobia and treatment seeking, on ZKPQ neuroticism-anxiety and activity, and on PVP than men did. The neuroticism-anxiety was significantly correlated with patho-thanatophobia and symptom effect, and PVP was positively correlated with symptom effect in women. Neuroticism-anxiety was significantly correlated with patho-thanatophobia, and impulsive sensation seeking and activity were significantly correlated with symptom effect in men. CONCLUSION: In Chinese students, we have found a stable four-factor IAS structure.
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Trastornos de Ansiedad/diagnóstico , Ansiedad/diagnóstico , Hipocondriasis/diagnóstico , Encuestas y Cuestionarios , Adolescente , Adulto , Pueblo Asiatico , China , Cultura , Depresión/diagnóstico , Femenino , Humanos , Masculino , Neuroticismo , Inventario de Personalidad , Estudiantes/psicología , Universidades , Adulto JovenRESUMEN
Autophagy, a cellular process where cells degrade and recycle their own components, has garnered attention for its potential role in psychiatric disorders, including schizophrenia (SCZ). This study aimed to construct and validate a new autophagy-related gene (ARG) risk model for SCZ. First, we analyzed differential expressions in the GSE38484 training set, identifying 4,754 differentially expressed genes (DEGs) between SCZ and control groups. Using the Human Autophagy Database (HADb) database, we cataloged 232 ARGs and pinpointed 80 autophagy-related DEGs (AR-DEGs) after intersecting them with DEGs. Subsequent analyses, including metascape gene annotation, pathway and process enrichment, and protein-protein interaction enrichment, were performed on the 80 AR-DEGs to delve deeper into their biological roles and associated molecular pathways. From this, we identified 34 candidate risk AR-DEGs (RAR-DEGs) and honed this list to final RAR-DEGs via a constructed and optimized logistic regression model. These genes include VAMP7, PTEN, WIPI2, PARP1, DNAJB9, SH3GLB1, ATF4, EIF4G1, EGFR, CDKN1A, CFLAR, FAS, BCL2L1 and BNIP3. Using these findings, we crafted a nomogram to predict SCZ risk for individual samples. In summary, our study offers deeper insights into SCZ's molecular pathogenesis and paves the way for innovative approaches in risk prediction, gene-targeted diagnosis, and community-based SCZ treatments.
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Esquizofrenia , Humanos , Esquizofrenia/genética , Autofagia/genética , Bases de Datos Factuales , Modelos Logísticos , Proteínas de la Membrana , Chaperonas Moleculares , Proteínas del Choque Térmico HSP40RESUMEN
BACKGROUND: Hearing loss is a prevalent issue resulting from loud noise exposure, aging, diseases, and genetic differences. As individuals age, the likelihood of experiencing hearing loss and depression escalates; yet, the link between hearing loss and the risk of depression remains ambiguous. This study explores the relationship between hearing and depression risk, taking into account sociodemographic and health-related factors. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018, a cross-sectional analysis was conducted, focusing on adult participants. It evaluated their hearing status and depression levels using the Patient Health Questionnaire-9 (PHQ-9). The study examined a range of variables, such as age, gender, socioeconomic status, lifestyle choices, and comorbidities, to understand their influence on the link between hearing loss and depression. RESULTS: Analysis indicated a significant association between moderate to severe hearing loss and an increased risk of depression, notably in older adults. This relationship remained significant even after adjusting for a variety of sociodemographic and health factors. LIMITATIONS: This is a study using the NHANES database using self-reported surveys. CONCLUSION: The findings of this study emphasize the need to integrate hearing health in the holistic assessment and treatment of depression, particularly advocating for combined care strategies for the elderly.
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Skin injury is a common health problem worldwide, and the highly complex healing process poses critical challenges for its management. Therefore, wound dressings with salutary effects are urgently needed for wound care. However, traditional wound dressing with a single function often fails to meet the needs of wound repair, and the integration of multiple functions has been required for wound repair. Herein, Cu2+-chelated epigallocatechin gallate nanoparticles (EAC NPs), with radical scavenging, inflammation relieving, bacteria restraining, and vascularization accelerating capacities, are adopted to functionalize collagen scaffold, aiming to promote wound healing. Radical scavenging experiments verify that EAC NPs could efficiently scavenge radicals. Additionally, EAC NPs could effectively remove Escherichia coli and Staphylococcus aureus. H2O2 stimuli-responsive EAC NPs show slow and sustained release properties of Cu2+. Furthermore, EAC NPs exhibit protective effects against H2O2-induced oxidative-stress damage and anti-inflammatory activity in vivo. Physicochemical characterizations show that the introduction of EAC NPs does not disrupt the gelation behavior of collagen, and the composite scaffolds (CS) remain porous structure similar to collagen scaffold. Animal experiments demonstrate that CS could promote wound healing through improving the thickness of renascent epidermis and number of new vessels. CS with multiple salutary functions is a promising dressing for wound care.
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Antibacterianos , Antiinflamatorios , Catequina , Catequina/análogos & derivados , Colágeno , Cobre , Nanopartículas , Cicatrización de Heridas , Catequina/química , Catequina/farmacología , Cicatrización de Heridas/efectos de los fármacos , Cobre/química , Cobre/farmacología , Animales , Antibacterianos/química , Antibacterianos/farmacología , Colágeno/química , Nanopartículas/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ratones , Antioxidantes/farmacología , Antioxidantes/química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Andamios del Tejido/química , Masculino , Neovascularización Fisiológica/efectos de los fármacosRESUMEN
Encapsulation of plant polyphenols with micro-/nano-carriers for enhanced bioavailability has been well documented, but the preparation of these carriers and subsequent loading of polyphenols is a multiple process, which is generally complicated with potentially unexpected negative effects on the bioactivity of the polyphenols. Here, we reported a convenient method to assemble carrier-free polyphenol nanoparticles (NPs) based on oxidative coupling polymerization. The effectiveness was assessed with five different polyphenols including pyrocatechol (PY), catechin (CA), epigallocatechin gallate (EGCG), tannic acid (TA), and proanthocyanidin (PC). The structural characteristics of these assembled nanoparticles (PY NPs, CA NPs, EG NPs, TA NPs, and PC NPs) were systematically analyzed with dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR). All NPs were colloidally stable with varying NaCl concentrations from 0 to 300 mM, were acid-resistant and alkali-intolerant, and were suitable for oral administration. An array of antioxidant assays further confirmed the superior antioxidant capabilities of NPs over Trolox and polyphenol monomers, indicating that the oxidative polymerization of polyphenols did not compromise the polyphenol activity of NPs. The in vitro simulated digestion studies validated that these responsive NPs were actually gastrointestinal pH-responsive and applicable to the gastrointestinal physiological environment. The bioaccessibility assessments by using a static in vitro digestion model revealed that better results were achieved with NPs than polyphenol monomers, with TA NPs showing about 1.5-fold higher bioaccessibility than other polyphenol nanoparticles. The present study with five polyphenols demonstrated that the oxidative polymerization of polyphenols provides an effective platform to assemble various carrier-free NPs with enhanced antioxidant activity, favorable stability, and improved bioaccessibility, which could be used promisingly as a functional food ingredient in food matrices or as oral drug delivery candidates for helping to manage human health or treating various gastrointestinal disorders in both the pharmaceutical and nutritional fields.
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Antioxidantes , Nanopartículas , Humanos , Antioxidantes/química , Polimerizacion , Polifenoles/química , Nanopartículas/química , Concentración de Iones de Hidrógeno , Estrés OxidativoRESUMEN
Multiphase Pickering emulsions, including two or more active agents, are of great importance to effectively manage complicated wounds. However, current strategies based on Pickering emulsions are still unsatisfying since they involve only stabilization by inactive particles and encapsulation of the hydrophobic drugs in the oil phase. Herein, thyme essential oil (TEO) was encapsulated in the shell of functional tea polyphenol (TP)-curcumin (Cur) nanoparticles (TC NPs) to exemplarily develop a novel Pickering emulsion (TEO/TC PE). Hydrophobic Cur was loaded with hydrophilic TP to obtain TC NPs, and under homogenization, these TC NPs adsorbed on the surface of TEO droplets to form a stable core-shell structure. Owing to such an oil-in-water (O/W) structure, the sequential release of the first Cur from pH-responsive disintegrated TC NPs and then the leaked TEO from the emulsion yielded synergetic functions of TEO/TC PE, leading to enhanced antibacterial, biofilm elimination, antioxidant, and anti-inflammatory activities. This injectable TEO/TC PE was applied to treat the infected full-thickness skin defects, and satisfactory wound healing effects were achieved with rapid angiogenesis, collagen deposition, and skin regeneration. The present TEO/TC PE constituted entirely of plant-sourced active products is biosafe and expected to spearhead the future development of novel wound dressings.
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The salient gelling feature of alginate via forming the egg-box structure with calcium ions has received extensive interests for different applications. Owing to the interfacial incompatibility of rigid inorganic solids with soft polymers, the requirement of overall stereocomplexation with calcium released from uniformly distributed solids in alginate remains a challenge. In this study, a novel alginate-incorporated calcium source was proposed to tackle the intractable dispersion for the preparation of injectable alginate hydrogels. Calcium phosphate synthesis in alginate solution yielded CaP-alginate hybrids as a calcium source. The physicochemical characterization confirmed the CaP-alginate hybrid was a nano-scale alginate-hydroxyapatite complex. The colloidally stable CaP-alginate hybrids were uniformly dispersed in alginate solutions even under centrifugation. The calcium-induced gelling of the CaP-alginate hybrids-loaded alginate solutions formed soft yet tough hydrogels including transparent sheets and knittable threads, confirming the homogeneous gelation of the hydrogel. The gelation time, injectability and mechanical properties of the hydrogels could be adjusted by changing preparation parameters. The prepared hydrogels showed uniform porous structure, excellent swelling, wetting properties and cytocompatibility, showing a great potential for applications in different fields. The present strategy with organic/inorganic hybridization could be exemplarily followed in the future development of functional hydrogels especially associated with the interface integration.
Asunto(s)
Alginatos , Durapatita , Hidrogeles , Hidrogeles/química , Alginatos/química , Durapatita/química , Materiales Biocompatibles/química , Inyecciones , Animales , Fenómenos Mecánicos , RatonesRESUMEN
The objective of this study was to investigate the effects of carboxymethyl chitosan (CMCS) on the stabilization and gelation of oil-in-water (O/W) Pickering emulsions (PEs) with polyphenol-amino acid particles in the presence of inorganic salts. The results revealed that the CMCS-induced depletion interactions contributed to improving the emulsification ability and interfacial adsorption efficiency of polyphenol-amino acid particles as well as constructing the network structures in the continuous phase. These relevant changes collectively resulted in elevating stability, viscosity and moduli of PEs. The additional effects of different inorganic salts with varying additions were further investigated, and the addition-dependent phenomena were observed. At low additions of inorganic salts, the occurrence of the chelation of inorganic salts with CMCS consolidated the constructed network structure, favorable to the gelation of PEs. With increasing additions, this chelation effect became stronger which compromised the CMCS-induced depletion, gradually leading to destabilization of PEs. In terms of ion species, the more pronounced effect on emulsion stability was achieved with calcium ions than with potassium and iron ions. This study expects to provide a new perspective on the extending application of cationic CMCS for improving the stability of O/W PEs in the food industry.