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Introduction: Hearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan. Methods: Organs of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively. Results: The first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOC-OHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age. Discussion: This study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses.
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BACKGROUND: Aged sarcopenia is characterized by loss of skeletal muscle mass and strength, and mitochondrial dysregulation in skeletal myocyte is considered as a major factor. Here, we aimed to analyze the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on mitochondrial reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) in aged skeletal muscles. METHODS: C2C12 cells were stimulated by 50 µM 7ß-hydroxycholesterol (7ß-OHC) to observe the changes of cellular ROS, mitochondrial ROS, and expression of PGC-1α and Nrf2. Different PGC-1α expression in cells was established by transfection with small interfering RNA (siRNA) or plasmids overexpressing PGC-1α (pEX-3-PGC-1α). The effects of different PGC-1α expression on cellular ROS, mitochondrial ROS and Nrf2 expression were measured in cells. Wild type (WT) mice and PGC-1α conditional knockout (CKO) mice were used to analyze the effects of PGC-1α on aged sarcopenia and expression of Nrf2 and CD38 in gastrocnemius muscles. Diethylmaleate, a Nrf2 activator, was used to analyze the connection between PGC-1α and Nrf2 in cells and in mice. RESULTS: In C2C12 cells, the expressions of PGC-1α and Nrf2 were declined by the 7ß-OHC treatment or PGC-1α silence. Moreover, PGC-1α silence increased the harmful ROS and decreased the Nrf2 protein expression in the 7ß-OHC-treated cells. PGC-1α overexpression decreased the harmful ROS and increased the Nrf2 protein expression in the 7ß-OHC-treated cells. Diethylmaleate treatment decreased the harmful ROS in the 7ß-OHC-treated or PGC-1α siRNA-transfected cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia, decreased Nrf2 expression and increased CD38 expression in gastrocnemius muscles compared with the WT mice. Diethylmaleate treatment improved the muscle function and decreased the CD38 expression in the old two genotypes. CONCLUSIONS: Our study demonstrated that PGC-1α modulated mitochondrial oxidative stress in aged sarcopenia through regulating Nrf2.
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Ratones Noqueados , Músculo Esquelético , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Especies Reactivas de Oxígeno , Sarcopenia , Animales , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Sarcopenia/metabolismo , Sarcopenia/patología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Masculino , Envejecimiento/metabolismo , Ratones Endogámicos C57BL , Línea Celular , Mitocondrias Musculares/metabolismo , Mitocondrias/metabolismoRESUMEN
OBJECTIVE: Study the efficacy of digital health interventions in enhancing patient activation and identify the distinct features of these interventions using the WHO classification system. METHODS: Asystematic reviewand meta-analysis were carried out according to the PRISMA guidelines. A search was conducted in Scopus, PubMed, and ProQuest. Randomized controlled trials (RCT), quasi-randomized controlled trials, and before-and-after studies enrolling patients ≥ 18 years of age with the Patient Activation Measure (PAM) score measurement and contain digital intervention with any aspects of health education or health-related behavior were included. The Downs and Black quality assessment tool was used to assess the quality of the articles. RESULTS: In the three different types of meta-analyses, implementing the intervention led to a PAM score increase (Mean Difference (M.D.)), ranging from a minimum of (MD = 0.2014, 95 % CI = 0.0871-0.3158) and a highly significant p-value 0.0006 to a maximum of (MD = 2.7882, 95 % CI = 1.5558-4.0206) and a p-value < .0001. While the M.D. score of 0.2014 may seem relatively low, it is enough to elevate the patient from one activation level to a higher one out of the four activation levels. CONCLUSION AND PRACTICE IMPLICATIONS: The results suggest the effectiveness of digital health interventions on patient activation across diverse settings and contexts, implying potential generalizability. Using WHO classification, all examined digital interventions addressed the challenges of information, utilization, and efficiency in the health system, but not equity-related challenges. The study recognized online health communities (OHCs) as a subset of digital interventions that enhance patient activation through social support.
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Participación del Paciente , Humanos , Conductas Relacionadas con la Salud , Participación del Paciente/estadística & datos numéricos , TelemedicinaRESUMEN
The cilia of the outer hair cells (OHCs) are the key microstructures involved in cochlear acoustic function, and their interactions with lymph in the cochlea involve complex, highly nonlinear, coupled motion and energy conversions, including macroscopic fluid-solid coupling. Recent optical measurements have shown that the frequency selectivity of the cochlea at high sound levels is entirely mechanical and is determined by the interactions of the hair bundles with the surrounding fluid. In this paper, an analytical mathematical model of the spiral cochlea containing macro- and micromeasurements was developed to investigate how the phonosensitive function of OHCs' motions is influenced by the macrostructural and microstructural fluid-solid coupling in the spiral cochlea. The results showed that the macrostructural and microstructural fluid-solid coupling exerted the radial forces of OHCs through the flow field, deflecting the cilia and generating frequency-selective properties of the microstructures. This finding showed that microstructural frequency selectivity arises from the radial motions of stereocilia hair bundles and enhances the hearing of sound signals at specific frequencies. It also implied that the macrostructural and microstructural fluid-solid couplings influence the OHCs' radial forces and that this is a key factor in the excitation of ion channels that enables their activity in helping the brain to detect sound.
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Cóclea , Audición , Células Ciliadas Auditivas Externas , Movimiento (Física) , Modelos TeóricosRESUMEN
Purpose/significance: Humans understand, think, and express themselves through metaphors. The current paper emphasizes the importance of identifying the metaphorical language used in online health communities (OHC) to understand how users frame and make sense of their experiences, which can boost the effectiveness of counseling and interventions for this population. Methods/process: We used a web crawler to obtain a corpus of an online depression community. We introduced a three-stage procedure for metaphor identification in a Chinese Corpus: (1) combine MIPVU to identify metaphorical expressions (ME) bottom-up and formulate preliminary working hypotheses; (2) collect more ME top-down in the corpus by performing semantic domain analysis on identified ME; and (3) analyze ME and categorize conceptual metaphors using a reference list. In this way, we have gained a greater understanding of how depression sufferers conceptualize their experience metaphorically in an under-represented language in the literature (Chinese) of a new genre (online health community). Results/conclusion: Main conceptual metaphors for depression are classified into PERSONAL LIFE, INTERPERSONAL RELATIONSHIP, TIME, and CYBERCULTURE metaphors. Identifying depression metaphors in the Chinese corpus pinpoints the sociocultural environment people with depression are experiencing: lack of offline support, social stigmatization, and substitutability of offline support with online support. We confirm a number of depression metaphors found in other languages, providing a theoretical basis for researching, identifying, and treating depression in multilingual settings. Our study also identifies new metaphors with source-target connections based on embodied, sociocultural, and idiosyncratic levels. From these three levels, we analyze metaphor research's theoretical and practical implications, finding ways to emphasize its inherent cross-disciplinarity meaningfully.
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Introduction: With the enhancement of people's health awareness and the impact of the coronavirus pandemic in recent years, people's demand for online health information continues to expand, and online health communities (OHCs) have developed rapidly. However, the service quality of OHCs is uneven, and problems such as content quality, privacy disclosure are increasingly prominent. It's of great significance to establish normalized OHC service quality evaluation standards and develop effective evaluation tools and methods for the improvement of OHC service quality. Material and Methods: Based on the grounded theory, the raw materials obtained from semi-structured interviews were coded in three stages to construct a service quality evaluation system for OHC. Through empirical analysis, the rationality and effectiveness of the evaluation system were verified. Then six representative Chinese OHCs were selected and their service quality was evaluated by the entropy weight TOPSIS method. Results: The service quality evaluation system of OHC was constructed which includes 4 first-level indicators and 16 second-level indicators. The weights of the first-level indicators from large to small are content quality, emotional experience quality, interaction quality and function quality. Among the second-level indicator weights, the top three are perceived cost reasonableness, content professionalism and effectiveness of interactive content. Conclusions: The indicator system is reasonable and effective and the evaluation method has strong applicability and operability. This study will provide theoretical guidance for community platform operators and relevant departments to design effective evaluation mechanism of OHC service quality, offering a reference for decisions and policymakers.
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The role of 27-hydroxycholesterol (27-OHC) in autoimmune diseases has become a subject of intense research in recent years. This oxysterol, derived from cholesterol, has been identified as a significant player in modulating immune responses and inflammation. Its involvement in autoimmune pathogenesis has drawn attention to its potential as a therapeutic target for managing autoimmune disorders effectively. 27-OHC, an oxysterol derived from cholesterol, has emerged as a key player in modulating immune responses and inflammatory processes. It exerts its effects through various mechanisms, including activation of nuclear receptors, interaction with immune cells, and modulation of neuroinflammation. Additionally, 27-OHC has been implicated in the dysregulation of lipid metabolism, neurotoxicity, and blood-brain barrier (BBB) disruption. Understanding the intricate interplay between 27-OHC and autoimmune diseases, particularly neurodegenerative disorders, holds promise for developing targeted therapeutic strategies. Additionally, emerging evidence suggests that 27-OHC may interact with specific receptors and transcription factors, thus influencing gene expression and cellular processes in autoimmune disorders. Understanding the intricate mechanisms by which 27-OHC influences immune dysregulation and tissue damage in autoimmune diseases is crucial for developing targeted therapeutic interventions. Further investigations into the molecular pathways and signaling networks involving 27-OHC are warranted to unravel its full potential as a therapeutic target in autoimmune diseases, thereby offering new avenues for disease intervention and management.
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Hidroxicolesteroles , Oxiesteroles , Humanos , Hidroxicolesteroles/metabolismo , Colesterol , Factores de TranscripciónRESUMEN
Oxysterols are oxidized derivatives of cholesterol that are formed by enzymatic processes or through the action of reactive oxygen species. Several of these bioactive lipids have been shown to be affected and/or play a role in inflammatory processes. 4ß-hydroxycholesterol is one of the major oxysterols in mice and humans and its levels are affected by inflammatory diseases. However, apart from its long half-life, little is known about its catabolism. By incubating 4ß-hydroxycholesterol with mouse mitochondria-enriched liver fractions, as well as 25-hydroxycholesterol and 27-hydroxycholesterol with recombinant CYP3A4, we identified 4ß,25-dihydroxycholesterol and 4ß,27-dihydroxycholesterol as 4ß-hydroxycholesterol metabolites. Supporting the biological relevance of this metabolism, we detected both metabolites after incubation of J774, primary mouse peritoneal macrophages and PMA-differentiated THP-1 cells with 4ß-hydroxycholesterol. Across our experiments, the incubation of cells with lipopolysaccharides differentially affected the levels of the 25- and 27-hydroxylated metabolites of 4ß-hydroxycholesterol. Finally, 4ß,27-dihydroxycholesterol was also detected in mice liver and plasma after intraperitoneal administration of 4ß-hydroxycholesterol. To our knowledge, this is the first report of the in vitro and in vivo detection and quantification of 4ß-hydroxycholesterol metabolites.
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Hidroxicolesteroles , Oxiesteroles , Humanos , Animales , Ratones , Hidroxicolesteroles/metabolismo , Colesterol , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , SemividaRESUMEN
Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca2+ activity in both sensory and non-sensory cells. Calcium signalling in neonatal OHCs can be modulated by oncomodulin (OCM, ß-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca2+ activity and afferent connectivity during development. Using a genetically encoded Ca2+ sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm+/+ ) and Ocm knockout (Ocm-/- ) littermates, we found increased spontaneous Ca2+ activity and upregulation of purinergic receptors in OHCs from Ocm-/- cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibres on Ocm-/- OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca2+ signalling in the developing cochlea and the maturation of OHC afferent innervation. KEY POINTS: Cochlear outer hair cells (OHCs) exhibit spontaneous Ca2+ activity during a narrow period of neonatal development. OHC afferent maturation and connectivity requires spontaneous Ca2+ activity. Oncomodulin (OCM, ß-parvalbumin), an EF-hand calcium-binding protein, modulates Ca2+ signals in immature OHCs. Using transgenic mice that endogenously expressed a Ca2+ sensor, GCaMP6s, we found increased spontaneous Ca2+ activity and upregulated purinergic receptors in Ocm-/- OHCs. The maturation of afferent synapses in Ocm-/- OHCs was also delayed, leading to an upregulation of ribbon synapses and afferent fibres in Ocm-/- OHCs before hearing onset. We propose that OCM plays an important role in modulating Ca2+ activity, expression of Ca2+ channels and afferent innervation in developing OHCs.
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Calcio , Células Ciliadas Auditivas Externas , Ratones , Animales , Células Ciliadas Auditivas Externas/fisiología , Calcio/metabolismo , Parvalbúminas/metabolismo , Cóclea/fisiología , Proteínas de Unión al Calcio/metabolismo , Ratones Transgénicos , Receptores Purinérgicos/metabolismo , Mamíferos/metabolismoRESUMEN
Given the many challenges facing healthcare access in many developing countries and the added limitations observed in emergencies like COVID-19 pandemic, the authors here discuss an alternative and feasible approach to overcome all these limitations.
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Métodos Epidemiológicos , Redes Sociales en Línea , Sistema de Registros , Sistema de Registros/normas , Países en Desarrollo , Internet/normas , Accesibilidad a los Servicios de Salud , Brotes de Enfermedades/prevención & controlRESUMEN
Objective: To determine the circadian influence on sound sensitivity produced by temporal hearing deprivation in healthy normal human subjects. Design: Participants underwent bilateral earplugging before completion of anthropometry, the author's developed questionnaire, the Hamilton Anxiety and Depression Inventory, pure tone audiometry (PTA), stapedial reflex thresholds (SRT), distortion products otoacoustic emissions input/output (DPOAE-I/O), and uncomfortable loudness levels (ULLs). Afterward, the participants were randomly divided into group A, starting at 8:00 a.m. and finishing at 8:00 p.m., and group B, starting at 4:00 p.m. and ending at 4:00 a.m. Serum cortisol levels and audiological test results were obtained at the beginning and end of the session and 24-h free urinary cortisol levels were measured. Study sample: Thirty healthy volunteers. Results: PTA was 2.68 and 3.33 dB HL in groups A and B, respectively, with no statistical difference between them. ULLs were significantly lower in group A compared to group B, with an average of 8.1 dB SPL in group A and 3.3 dB SPL in group B (p < 0.0001). A SRT shift was observed in group A, with no difference in group B, and a night shift in DPOAE-I/O in group B. Conclusions: Reduced loudness tolerance is demonstrated during daytime hearing deprivation in contrast to nighttime; this may be due to increased central gain in the awake cortex.
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In cochlear outer hair cells (OHCs), a network of Ca2+ channels, pumps and Ca2+-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), α-parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm-/-) gives rise to progressive cochlear dysfunction in young adult mice. Here, we show that changes in Ca2+ signaling begin early in postnatal development of Ocm-/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca2+ transients in OHCs and leads to slower KCl-induced Ca2+ transients than those elicited in cells from Ocm-/- littermates. We compared OCM buffering kinetics with other CaBPs in animal models and cultured cells. In a double knockout of Ocm and Apv (Ocm-/-;Apv-/-), mutant OHCs show even faster Ca2+ kinetics, suggesting that APV may also contribute to early postnatal Ca2+ signaling. In transfected HEK293T cells, OCM slows Ca2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca2+ environment by lowering the amount of freely available [Ca2+]i in OHCs and transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca2+ signals through its inimitable Ca2+ buffering capacity.
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Señalización del Calcio , Células Ciliadas Auditivas Externas , Animales , Calcio/metabolismo , Proteínas de Unión al Calcio/metabolismo , Células HEK293 , Células Ciliadas Auditivas Externas/metabolismo , Humanos , Ratones , Parvalbúminas/metabolismoRESUMEN
The impact of yellow pumpkin powder (YP) substitution (5, 10, and 15%) on wheat flour's physico-functional, pasting, gel texture, and dough rheology was studied. Moreover, the nutritional, organoleptic properties and bioactivity of the composite pan and pita bread were evaluated. An improved water holding capacity was noticed for the blended flour than for control. The pasting parameters were declined significantly (p < 0.05) with increasing YP. Composite flours presented a softer gel texture in the presence of YP. Reduced water absorption, increased dough development time, and lower stability for combined flour dough. The bread with YP depicted increased protein, fat, fiber, and mineral contents, while a reduced volume and specific volume were noticed for pan bread. YP incorporated 5% and did not compromise pan and pita bread's color and overall acceptability. Additionally, composite bread depicted higher total phenolics with enhanced antioxidant activities at the higher substitution of YP.
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The progressive motor neuropathy (PMN) mouse is a model of an inherited motor neuropathy disease with progressive neurodegeneration. Axon degeneration associates with homozygous mutations of the TBCE gene encoding the tubulin chaperone E protein. TBCE is responsible for the correct dimerization of alpha and beta-tubulin. Strikingly, the PMN mouse also develops a progressive hearing loss after normal hearing onset, characterized by degeneration of the auditory nerve and outer hair cell (OHC) loss. However, the development of this neuronal and cochlear pathology is not fully understood yet. Previous studies with pegylated insulin-like growth factor 1 (peg-IGF-1) treatment in this mouse model have been shown to expand lifespan, weight, muscle strength, and motor coordination. Accordingly, peg-IGF-1 was evaluated for an otoprotective effect. We investigated the effect of peg-IGF-1 on the auditory system by treatment starting at postnatal day 15 (p15). Histological analysis revealed positive effects on OHC synapses of medial olivocochlear (MOC) neuronal fibers and a short-term attenuation of OHC loss. Peg-IGF-1 was able to conditionally restore the disorganization of OHC synapses and maintain the provision of cholinergic acetyltransferase in presynapses. To assess auditory function, frequency-specific auditory brainstem responses and distortion product otoacoustic emissions were recorded in animals on p21 and p28. However, despite the positive effect on MOC fibers and OHC, no restoration of hearing could be achieved. The present work demonstrates that the synaptic pathology of efferent MOC fibers in PMN mice represents a particular form of "efferent auditory neuropathy." Peg-IGF-1 showed an otoprotective effect by preventing the degeneration of OHCs and efferent synapses. However, enhanced efforts are needed to optimize the treatment to obtain detectable improvements in hearing performances.
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Previous works showed that opioid peptides are produced by olivocochlear efferent neurons, while cochlear hair cells express opioid receptors. It has been proposed that opioids protect the auditory system from damage by intense stimulation, although their use for therapeutic or illicit purposes links to hearing impairment. Therefore, it is relevant to study the effect of opioids in the auditory system to define their functional expression and mechanism of action. This study investigated the modulation of the Ca2+ currents by opioid peptides in the rat outer hair cells (OHC) using the whole-cell patch-clamp technique. The influence of agonists of the three opioid receptor subtypes (µ, δ, and κ) was studied. The κ opioid receptor agonist U-50488 inhibits the Ca2+ currents in a partially reversible form. Coincidently, norbinaltorphimine (a κ receptor antagonist) blocked the U-50488 inhibitory effect on the Ca2+ current. The δ and the µ opioid receptor agonists did not significantly affect the Ca2+ currents. These results indicate that the κ opioid receptor activation inhibits the Ca2+ current in OHC, modulating the intracellular Ca2+ concentration when OHCs depolarize. The modulation of the auditory function by opioids constitutes a relevant mechanism with a potential role in the physiopathology of auditory disturbances.
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Receptores Opioides kappa , Receptores Opioides , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/farmacología , Analgésicos Opioides , Animales , Calcio/metabolismo , Encefalina Ala(2)-MeFe(4)-Gli(5) , Células Ciliadas Auditivas Externas/metabolismo , Péptidos Opioides , Ratas , Receptores Opioides mu/agonistasRESUMEN
A novel fluorescence sensor for successive detection of Cu2+and Fe3+based on anti-B18H22derivative which possesses 5-hydroxyisoquinoline as an ionophore was synthesized via a one-pot and its structure and photophysical properties were characterized by NMR, HRMS, FTIR, UV-vis, PL and theoretical calculation. The fluorophore displays two emission peaks at 460 nm and 670 nm in THF solution coming from the emission of the locally excited state and intramolecular charge transfer fluorescence, respectively. The complex exhibited obvious aggregation-induced emission enhancement (AIEE) characteristics in THF/H2O solution by increasing the aqueous concentration from 70% to 95%. The AIEE molecules showed a high selectivity towards Cu2+over other metal ions by forming a 2:1 metal-to-ligand complex in THF/H2O (fw = 20%) solution, the fluorescence intensity increased as a linear function of the Cu2+concentration at 460 nm due to the inhibition of PET effect. The fluorescent emission was quenched linearly by the addition of Fe3+, which provides a method for successive determination of Cu2+and Fe3+based on 'off-on-off' fluorescence of the fluorescent. The detection limit of Cu2+and Fe3+was 5.7 × 10-6M and 7.2 × 10-5M respectively. Morever, a rapid identification of Cu2+in the aqueous solution by naked eyes can be realized. In addition, the molecules were pH-sensitive, the fluorescence quenching can be observed in strongly alkaline environment. The method has been applied to the determination of copper ions in water samples with satisfactory results.
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Cobre , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Iones , Espectrometría de Fluorescencia , AguaRESUMEN
Age-related hearing loss (ARHL) is a common, increasing problem for older adults, affecting about 1 billion people by 2050. We aim to correlate the different reductions of hearing from cochlear hair cells (HCs), spiral ganglion neurons (SGNs), cochlear nuclei (CN), and superior olivary complex (SOC) with the analysis of various reasons for each one on the sensory deficit profiles. Outer HCs show a progressive loss in a basal-to-apical gradient, and inner HCs show a loss in a apex-to-base progression that results in ARHL at high frequencies after 70 years of age. In early neonates, SGNs innervation of cochlear HCs is maintained. Loss of SGNs results in a considerable decrease (~50% or more) of cochlear nuclei in neonates, though the loss is milder in older mice and humans. The dorsal cochlear nuclei (fusiform neurons) project directly to the inferior colliculi while most anterior cochlear nuclei reach the SOC. Reducing the number of neurons in the medial nucleus of the trapezoid body (MNTB) affects the interactions with the lateral superior olive to fine-tune ipsi- and contralateral projections that may remain normal in mice, possibly humans. The inferior colliculi receive direct cochlear fibers and second-order fibers from the superior olivary complex. Loss of the second-order fibers leads to hearing loss in mice and humans. Although ARHL may arise from many complex causes, HC degeneration remains the more significant problem of hearing restoration that would replace the cochlear implant. The review presents recent findings of older humans and mice with hearing loss.
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Outer hair cells (OHCs) are innervated by both medial olivocochlear (MOC) efferents and type II afferents, which also innervate supporting cells to form a local neural network. It has also been demonstrated that prestin provides the molecular basis for OHC somatic electromotility, amplifying movements within the organ of Corti. Although not anticipated, early-onset OHC loss was found in two prestin transgenic mouse models that either lack prestin protein or lack electromotility. To uncover the molecular pathways that evoke OHC death, we profiled the coding transcriptome of OHCs from wildtype (WT), prestin-knockout (KO), and 499-knockin (KI) mice using single-cell RNA sequencing (scRNA-seq). scRNA-Seq transcriptomics and pathway analyses did not reveal common pathways associated with OHC loss observed in prestin-KO and 499-KI mice. Clustering enrichment analysis showed that increased gene expression in OHCs from prestin-KO mice was associated with lipid metabolic processes and cell death pathways. These mRNA profiles likely contribute to the OHC loss observed in prestin-KO mice and support the notion that prestin is also a structural protein, important for the normal plasma membrane compartmentalization that is essential to establish MOC efferent synapses. In contrast, the mRNA profile of OHCs from 499-KI mice did not provide a rational explanation of the early-onset OHC loss in this mutant. OHCs from 499-KI mice have normal plasma membrane compartmentalization and normal OHC-MOC contacts. However, 499 prestin lacks electromotility and appears to change the local neural network around OHCs, as more synaptic markers were found near neighboring supporting cells when compared to WT and prestin-KO mice. Thus, OHCs in prestin-KOs (no prestin protein, no electromotility) and 499-KIs (prestin protein present, no electromotility) may influence local neuronal networks in different ways. Collectively, our data suggest that prestin and its motile properties are important for OHC survival and the maintenance of local afferent/efferent circuits, as well as for its role in cochlear amplification. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.
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Células Ciliadas Auditivas Externas , Proteínas Motoras Moleculares , Animales , Cóclea/metabolismo , Células Ciliadas Auditivas Externas/fisiología , Ratones , Ratones Noqueados , Ratones Transgénicos , Proteínas Motoras Moleculares/genética , Proteínas Motoras Moleculares/metabolismo , ARN Mensajero/metabolismoRESUMEN
In recent years, electromagnetic pollution has become more and more serious, resulting in a very negative impact on people's health. Therefore, it is important to develop efficient microwave absorbers to reduce electromagnetic pollution. Here, we construct a novel absorbing material of the polymer gel-derived porous carbon decorated by rare earth compounds (Ce (CO3) OH). When the thickness is 2.2 mm, the composite exhibits excellent microwave absorption performance with the optimal RLmin value and EAB reached up to -47.67 dB and 5.52 GHz, respectively, covering the Ku band. The high-efficiency microwave absorption is mainly attributed to the synergistic effect of dipole polarization, defect polarization and interfacial polarization. This work not only provides a new view for designing superior absorber materials, but also lay a foundation for their real applications.
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In the present work, NOx conversion efficiency of the hybrid catalysts at low temperatures was investigated. ANP-TVM and ANP-TVC-TVM hybrid catalysts for OHC-SCR performance were prepared by the impregnation method. The properties of catalysts were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) and X-ray diffraction (XRD) analyses. The NOx conversion ratios with real diesel exhaust gases were performed using oxygenated hydrocarbon reductants such as ethanol, propanol, n-butanol and n-penthanol. Performances of the hybrid catalysts at different engine loads and low temperatures were investigated. It was determined that ANP-TVC-TVM gave better results at all temperatures and loads. In general, the performance of ANP-TVC-TVM hybrid catalyst was superior with ethanol reductant except for at 1â kW engine load. The maximum NOx conversion ratio was 90.6% on the ANP-TVC-TVM hybrid catalyst with n-butanol at 1â kW engine load and 300°C.