RESUMEN
Largemouth bass virus (LMBV) infections has resulted in high mortality and economic losses to the global largemouth bass industry and has seriously restricted the healthy development of the bass aquaculture industry. There are currently no antiviral therapies available for the control of this disease. In this study, we developed three types of vaccine against LMBV; whole virus inactivated vaccine (I), a subunit vaccine composed of the major viral capsid protein MCP (S) as well as an MCP DNA vaccine(D), These were employed using differing immunization and booster strategies spaced 2 weeks apart as follows: II, SS, DD and DS. We found that all vaccine groups induced humoral and cellular immune responses and protected largemouth bass from a lethal LMBV challenge to varying degrees and DD produced the best overall effect. Specifically, the levels of specific IgM in serum in all immunized groups were elevated and significantly higher than those in the control group. Moreover, the expression of humoral immunity (CD4 and IgM) and cellular immunity (MHCI-α) as well as cytokines (IL-1ß) was increased, and the activity of immunity-related enzymes ACP, AKP, LZM, and T-SOD in the serum was significantly enhanced. In addition, the relative percent survival of fish following an LMBV lethal challenge 4 weeks after the initial immunizations were high for each group: DD(89.5 %),DS(63.2 %),SS(50 %) and II (44.7 %). These results indicated that the MCP DNA vaccine is the most suitable and promising vaccine candidate for the effective control of LMBV disease.
RESUMEN
An increasing number of studies have shown that cross-modal interaction can occur in early sensory cortices. Yet, how neurons in sensory cortices integrate multisensory cues in perceptual tasks and to what extent this influences behavior is largely unclear. To investigate, we examined visual modulation of auditory responses in the primary auditory cortex (A1) in a two-alternative forced-choice task. During the task, male rats were required to make a behavioral choice based on the pure tone frequency (low vs high) of the self-triggered stimulus to get a water reward. The result showed that the presence of a noninformative visual cue did not uniformly influence auditory response, with frequently enhancing just one of them. Closely correlated with behavioral choice, the visual cue mainly enhanced responsiveness to the auditory cue indicating a movement direction contralateral to A1 being recorded. Operating in this fashion provided A1 neurons a superior capability to discriminate sound during multisensory trials. Concomitantly, behavioral data and decoding analysis revealed that visual cue presence could speed the process of sound discrimination. We also observed this differential multisensory integration effect in well-trained rats when tested with passive stimulation and under anesthesia, albeit to a much lesser extent. We did not see this differentially integrative effect while recording in A1 in another similar group of rats performing a free-choice task. These data suggest that auditory cortex can engage in meaningful audiovisual processing, and perceptual learning can modify its multisensory integration mechanism to meet task requirements.SIGNIFICANCE STATEMENT In the natural environment, visual stimuli are frequently accompanied by auditory cues. Although multisensory integration has traditionally been seen as a feature of associational cortices, recent studies have shown that cross-modal inputs can also influence neuronal activity in primary sensory cortices. However, exactly how neurons in sensory cortices integrate multisensory cues to guide behavioral choice is still unclear. Here, we describe a novel model of multisensory integration used by A1 neurons to shape auditory representations when rats performed a cue-guided task. We found that a task-irrelevant visual cue could specifically enhance the response of neurons in sound guiding to the contralateral choice. This differentially integrative model facilitated sound discrimination and behavioral choice. This result indicates that task engagement can modulate multisensory integration.
Asunto(s)
Corteza Auditiva , Masculino , Ratas , Animales , Corteza Auditiva/fisiología , Estimulación Acústica , Estimulación Luminosa , Percepción Auditiva/fisiología , Discriminación en Psicología , Percepción Visual/fisiologíaRESUMEN
Data on the dynamic changes in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD) during antiviral therapy are scarce. We aimed to investigate the evolution of NAFLD status change in CHB patients treated with nucleos(t)ide analogues (NAs) and its influence on therapeutic outcomes. This retrospective study included 164 HBeAg-positive CHB patients from a randomized controlled trial who were treated with NAs for 104 weeks and underwent paired liver biopsies. Histological evaluation was performed at baseline and Week 104. The patients were divided into four groups according to NAFLD status changes. From baseline to Week 104, the overall percentage of CHB patients with concurrent NAFLD increased from 17.1% to 26.2% (p = 0.044). Among them, 7 of 28 patients (25.0%) with NAFLD at baseline showed NAFLD remission at week 104, while 22 of 136 patients (16.2%) without NAFLD at baseline developed new-onset NAFLD. In subgroup analyses, the new-onset and sustained NAFLD groups showed significantly lower rates of biochemical response at week 104 as compared to the sustained non-NAFLD group (77.3% and 57.1% vs. 93.9%, respectively; all p < 0.05), as well as fibrosis improvement (31.8% and 42.9% vs. 69.3%, respectively; all p < 0.05). NAFLD status changes did not influence the virological response, HBeAg seroconversion, and necroinflammation improvement (all p > 0.05). In HBeAg-positive CHB patients receiving NAs therapy, new-onset and sustained NAFLD may counteract the benefits of antiviral therapy, reducing the rate of biochemical response and fibrosis improvement.
Asunto(s)
Hepatitis B Crónica , Enfermedad del Hígado Graso no Alcohólico , Humanos , Antivirales/uso terapéutico , Antígenos e de la Hepatitis B/análisis , Hepatitis B Crónica/tratamiento farmacológico , Resultado del Tratamiento , Estudios Retrospectivos , Fibrosis , Virus de la Hepatitis BRESUMEN
BACKGROUND: Growing evidence suggests that gut microbiota can affect depression-like behavior, and electroacupuncture (EA) can regulate the composition and abundance of gut microbiota. At the same time, not a lot of research has been done on how EA affects gut microbiota to depression-like behavior. The objective of this study was to study the associated mechanisms by which EA exerts antidepressant effects by modulating gut microbiota. METHODS: Twenty-four C57BL/6 male mice were randomly divided into three groups, one group (n = 8) was the normal control group (NC). And the other two groups was chronic unpredictable mild stress for modeling + electroacupuncture group (CUMS + EA) (n = 8) and chronic unpredictable mild stress for modeling group (CUMS) (n = 8). Both CUMS and EA groups were subjected to 28 days of CUMS, but only the EA group received an additional 14 days of EA procedure. Behavior tests were used to determine the antidepressant effect of EA. Sequencing of the 16S ribosomal RNA (rRNA) gene was applied to examine alterations in the intestinal microbiome between groups. RESULTS: The findings were compared to those of the NC group, the sucrose preference rate and the total distance of Open Field Test (OFT) in CUMS group decreased, the abundance of Lactobacillus decreased, while the abundance of staphylococci increased. After the intervention of EA, the sucrose preference index and the total distance of OFT increased, the abundance of Lactobacillus increased, while the abundance of staphylococci decreased. CONCLUSIONS: These findings indicated EA may play an antidepressant effect by adjusting the abundance of Lactobacillus and staphylococci.
Asunto(s)
Depresión , Electroacupuntura , Ratones , Masculino , Animales , Depresión/terapia , Lactobacillus , Staphylococcus , Ratones Endogámicos C57BL , Antidepresivos/farmacología , Estrés Psicológico , Modelos Animales de Enfermedad , Conducta AnimalRESUMEN
Interventions for extrinsic aging can be implemented, but these must address photoaging, which is the primary cause of extrinsic aging. Pigmentation due to photoaging depends on the duration and intensity of sun exposure. This study investigated the relationship between adipose-derived mesenchymal stem cells (ASCs) and photoaging pigmentation, and the underlying mechanism of action by establishing a photoaging pigmentation model using various treatments and exposure options in a guinea pigs. The energy dose of each UVB irradiation was 120 mJ/cm2 and the total dose of irradiation was 360 mJ/cm2. After successfully establishing the photoaging model, ASCs (1×106) in an balanced salt solution (0.9 ml), balanced salt solution (0.9 ml), and bFGF (9 µg) mixed with an balanced salt solution (0.9 ml) were injected intradermally in ten guinea pigs. ELISA, macroscopic skin and histological observations, and Masson-Fontana staining were done. At 2 and 4 weeks post-injection, noticeable changes were observed. Guinea pigs receiving ASCs injections displayed significantly lower visible skin scores while the melanin content continued to decrease. Somewhat improved histopathological morphology, including epidermal thinning, dermal thickening, and little inflammatory cell infiltration was observed immediately after and up to 4 weeks of ASCs injection. Melanocortin 1 receptor (MC1R) and alpha-melanocyte test hormone (alpha-MSH) levels reduced significantly, and basic fibroblast growth factor (bFGF) levels increased significantly immediately after and up to 4 weeks of ASCs injection. The MC1R and alpha-MSH levels reduced significantly immediately after and up to 4 weeks of bFGF injection. Briefly, intradermal ASCs injection can notably eliminate pigmentation in a guinea pig photoaging pigmentation model. This may be related to the fact that bFGF secreted by ASCs lowers MC1R and alpha-MSH levels, blocks the cAMP signalling pathway, and inhibits melanin synthesis. This finding may present new options for treating photoaging pigmentation.Level of Evidence: N/A.
Asunto(s)
Células Madre Mesenquimatosas , Receptor de Melanocortina Tipo 1 , Animales , Factor 2 de Crecimiento de Fibroblastos/farmacología , Cobayas , Melaninas , Células Madre Mesenquimatosas/metabolismo , Pigmentación , Receptor de Melanocortina Tipo 1/metabolismo , alfa-MSH/farmacologíaRESUMEN
Autophagy is confirmed to be involved in the onset and development of depression, and some antidepressants took effect by influencing the autophagic process. Electroacupuncture (EA), as a common complementary treatment for depression, may share the mechanism of influencing autophagy in the hippocampus like antidepressants. To investigate that, sixty Sprague-Dawley rats firstly went through chronic unpredictable mild stress (CUMS) model establishment, and 15 rats were assigned to a control group. After modeling, 45 successfully CUMS-induced rats were randomly divided to 3 groups: CUMS, selective serotonin reuptake inhibitor (SSRI), and EA groups (15 rats per group), to accept different interventions for 2 weeks. A sucrose preference test (SPT), weighing, and open field test (OFT) were measurement for depressive behaviors of rats. Transmission electron microscope (TEM), immunohistochemistry (IHC), and western blot analysis were used to evaluate the autophagic changes. After that, depression-like behaviors were successfully induced in CUMS models and reversed by SSRI and EA treatments (both p < 0.05), but these two therapies had nonsignificant difference between each other (p > 0.05). Autolysosomes observed through TEM in the CUMS group were more than that in the control group. Their number and size in the SSRI and EA groups also decreased significantly. From IHC, the CUMS group showed enhanced positive expression of both Beclin1 and LC3 in CA1 after modeling (p < 0.05), and the LC3 level declined after EA treatments, which was verified by decreased LC3-II/LC3-I in western blot analysis. We speculated that CUMS-induced depression-like behavior was interacted with an autophagy process in the hippocampus, and EA demonstrated antidepressant effects by partly inhibiting autophagy with a decreased number of autolysosomes and level of LC3 along with LC3-II/LC3-I.
Asunto(s)
Autofagia , Depresión/prevención & control , Depresión/fisiopatología , Electroacupuntura , Hipocampo/fisiopatología , Animales , Depresión/etiología , Masculino , Neuronas/fisiología , Ratas Sprague-Dawley , Estrés Psicológico/complicacionesRESUMEN
BACKGROUND & AIMS: Polygonum Multiflorum Thumb (PMT), an ancient anti-aging Chinese herb known traditionally as He Shou Wu, has side effects of liver toxicity. To determine the main clinical and pathological characteristics of liver toxicity induced by PMT and the clinical course after its cessation. METHODS: Data of patients, diagnosed as drug-induced liver injury and hospitalised in Beijing Friendship Hospital from August 2005 to August 2017, were retrospectively reviewed. Clinical, pathological data and outcome after cessation of He Shou Wu were obtained and analysed. Kruskal-Wallis and Chi-square (χ2 ) tests were performed. RESULTS: Twenty-nine patients with He Shou Wu-induced liver injury were enrolled. The median age was 53 years (range 15-74) and 75.9% (22/29) were women. The most common symptom was jaundice (79.3%, 23/29). Of nine patients with liver biopsies, six showed acute cholestatic hepatitis, two acute, and one chronic hepatocellular injury pattern. The latency, liver chemistries and outcomes were comparable between pure He Shou Wu (5 patients) and its compounds (24 patients). Twenty-five of 29 patients (86.2%) had normal serum alanine aminotransferase levels after 45 days (range: 10-138 days) and total bilirubin of 46 days (range: 0-551 days). One patient was rechallenged with He Shou Wu and two developed autoimmune features. One patient died of liver failure and three had chronic persistent liver injury. CONCLUSIONS: The main clinicopathological injury pattern of He Shou Wu-induced liver injury is moderate to severe hepatitis with or without cholestasis. Most patients recover completely; however, chronic disease and death do occur.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colestasis/inducido químicamente , Medicamentos Herbarios Chinos/toxicidad , Polygonum/toxicidad , Adolescente , Adulto , Anciano , Beijing , Enfermedad Hepática Inducida por Sustancias y Drogas/mortalidad , Femenino , Humanos , Ictericia/etiología , Hígado/patología , Fallo Hepático/inducido químicamente , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Extractos Vegetales/toxicidad , Estudios Retrospectivos , Adulto JovenRESUMEN
Hippocampal atrophy is one of the key changes in the brain implicated in the biology of depression. However, the precise molecular mechanism remains poorly understood due to a lack of biomarkers. In this research, we used behavioral experiments to evaluate anxiety and anhedonia levels in depressed rats using chronic unpredictable mild stress (CUMS) modeling. We also used isobaric tag for relative and absolute quantitation (iTRAQ) to identify the differentially expressed hippocampal proteins between depressed and normal rats. Bioinformatics analyses were also performed for a better understanding. The results showed that CUMS rats had higher anxiety and anhedonia levels than control rats, along with hippocampal lesions. Through iTRAQ and bioinformatics analyses, we found that ribosome proteins were significantly downregulated and Ras proteins exhibited a mixed change in the hippocampus of depressed rats. These findings suggest that the expression of hippocampal ribosome lesions and Ras proteins is significantly different in depressed rats than in control rats, providing new insights into the neurobiology of depression.
Asunto(s)
Depresión/metabolismo , Hipocampo/metabolismo , Plasticidad Neuronal/fisiología , Ribosomas/metabolismo , Proteínas ras/metabolismo , Animales , Ansiedad/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Masculino , Análisis por Matrices de Proteínas , Ratas , Ratas Wistar , Estrés Psicológico/metabolismoRESUMEN
KEY POINTS: It has been known for some time that sensory information of one type can bias the spatial perception of another modality. However, there is a lack of evidence of this occurring in individual neurons. In the present study, we found that the spatial receptive field of superior colliculus multisensory neurons could be dynamically shifted by a preceding stimulus in a different modality. The extent to which the receptive field shifted was dependent on both temporal and spatial gaps between the preceding and following stimuli, as well as the salience of the preceding stimulus. This result provides a neural mechanism that could underlie the process of cross-modal spatial calibration. ABSTRACT: Psychophysical studies have shown that the different senses can be spatially entrained by each other. This can be observed in certain phenomena, such as ventriloquism, in which a visual stimulus can attract the perceived location of a spatially discordant sound. However, the neural mechanism underlying this cross-modal spatial recalibration has remained unclear, as has whether it takes place dynamically. We explored these issues in multisensory neurons of the cat superior colliculus (SC), a midbrain structure that involves both cross-modal and sensorimotor integration. Sequential cross-modal stimulation showed that the preceding stimulus can shift the receptive field (RF) of the lagging response. This cross-modal spatial calibration took place in both auditory and visual RFs, although auditory RFs shifted slightly more. By contrast, if a preceding stimulus was from the same modality, it failed to induce a similarly substantial RF shift. The extent of the RF shift was dependent on both temporal and spatial gaps between the preceding and following stimuli, as well as the salience of the preceding stimulus. A narrow time gap and high stimulus salience were able to induce larger RF shifts. In addition, when both visual and auditory stimuli were presented simultaneously, a substantial RF shift toward the location-fixed stimulus was also induced. These results, taken together, reveal an online cross-modal process and reflect the details of the organization of SC inter-sensory spatial calibration.
Asunto(s)
Colículos Superiores/fisiología , Animales , Percepción Auditiva , Gatos , Potenciales Evocados , Masculino , Colículos Superiores/citología , Percepción VisualRESUMEN
In natural conditions, human and animals need to extract target sound information from noisy acoustic environments for communication and survival. However, how the contextual environmental sounds impact the tuning of central auditory neurons to target sound source azimuth over a wide range of sound levels is not fully understood. Here, we determined the azimuth-level response areas (ALRAs) of rat auditory cortex neurons by recording their responses to probe tones varying with levels and sound source azimuths under both quiet (probe alone) and forward masking conditions (preceding noise + probe). In quiet, cortical neurons responded stronger to their preferred stimuli than to their nonpreferred stimuli. In forward masking conditions, an effective preceding noise reduced the extents of the ALRAs and suppressed the neural responses across the ALRAs by decreasing the response strength and lengthening the first-spike latency. The forward suppressive effect on neural response strength was increased with increasing masker level and decreased with prolonging the time interval between masker and probe. For a portion of cortical neurons studied, the effects of forward suppression on the response strength to preferred stimuli was weaker than those to nonpreferred stimuli, and the recovery from forward suppression of the response strength to preferred stimuli was earlier than that to nonpreferred stimuli. We suggest that this nonuniform forward suppression of neural responses to preferred stimuli and to nonpreferred stimuli is important for cortical neurons to maintain their relative stable preferences for target sound source azimuth and level in noisy acoustic environments.
Asunto(s)
Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Neuronas/fisiología , Enmascaramiento Perceptual/fisiología , Animales , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-DawleyRESUMEN
Physiological and behavioral studies in cats show that corticotectal inputs play a critical role in the information-processing capabilities of neurons in the deeper layers of the superior colliculus (SC). Among them, the sensory inputs from functionally related associational cortices are especially critical for SC multisensory integration. However, the underlying mechanism supporting this influence is still unclear. Here, results demonstrate that deactivation of relevant cortices can both dislocate SC visual and auditory spatial receptive fields (RFs) and decrease their overall size, resulting in reduced alignment. Further analysis demonstrated that this RF separation is significantly correlated with the decrement of neurons' multisensory enhancement and is most pronounced in low stimulus intensity conditions. In addition, cortical deactivation could influence the degree of stimulus effectiveness, thereby illustrating the means by which higher order cortices may modify the multisensory activity of SC.
Asunto(s)
Percepción Auditiva/fisiología , Corteza Cerebral/fisiología , Neuronas/fisiología , Colículos Superiores/fisiología , Percepción Visual/fisiología , Estimulación Acústica , Potenciales de Acción , Animales , Gatos , Frío , Electrodos Implantados , Femenino , Masculino , Estimulación Luminosa , Campos Visuales/fisiología , AguaRESUMEN
Under the strong noise environment, the composite fault signal of gearbox is weak, which makes it difficult to extract fault features. For this problem, based on noise-assisted method, we propose a novel method called Modified Singular Spectrum Decomposition (MSSD). Singular Spectrum Decomposition (SSD) has many advantages such as high decomposition precision and strong ability to restrain mode mixing, etc. However, the ability of SSD to extract a weak signal is not ideal, the decomposition results usually contain a lot of redundant noise and mode mixing caused by intermittency, which is also a troubling problem. In order to improve the decomposition efficiency and make up for the defects of SSD, the new method MSSD adds an adaptive and particular noise in every SSD decomposition stage for each trial, and in addition, whenever the input signal is decomposed to obtain an intrinsic module function (IMF), a unique residual is obtained. After multiple decomposition, the average value of the residual is used as input to the next stage, until the residual cannot continue to decompose, which means that the residual component has, at most, one extreme value. Finally, analyzing simulated signals to explain the advantages of MSSD compared to ensemble empirical mode decomposition (EEMD) and complete ensemble local mean decomposition with adaptive noise (CEEMDAN). In order to further prove the effectiveness of MSSD, this new method, MSSD, is applied to the fault diagnosis of an engineering gearbox test stand in an actual engineer project case. The final results show that MSSD can extract more fault feature information, and mode mixing has been improved and suffers less interference compared to SSD.
RESUMEN
Conclusive evidence regarding the effect of statins on non-end stage chronic kidney disease (CKD) has not been reported previously. This meta-analysis evaluated the association between statins and microalbuminuria, proteinuria, progression, and all-cause mortality in patients with non-end stage CKD. Databases (e.g., PubMed, Embase and the Cochrane Library) were searched for randomized controlled trials (RCTs) with data on statins, microalbuminuria, proteinuria, renal health endpoints, and all-cause mortality patients with non-end stage CKD to perform this meta-analysis. The mean difference (MD) of the urine albumin excretion ratios (UAER), 24-h urine protein excretion, and risk ratios (RR) of all-cause mortality and renal health endpoints were calculated, and the results are presented with 95% confidence intervals (CI). A total of 23 RCTs with 39,419 participants were selected. The analysis demonstrated that statins statistically reduced UAER to 26.73 µg/min [95%CI (-51.04, -2.43), Z=2.16, P<0.05], 24-h urine protein excretion to 682.68 mg [95%CI (-886.72, -478.63), Z=6.56, P<0.01] and decreased all-cause mortality [RR=0.78, 95%CI (0.72, 0.84), Z=6.08, P<0.01]. However, the analysis results did not indicate that statins reduced the events of renal health endpoints [RR=0.96, 95%CI (0.91,1.01), Z=1.40, P>0.05]. In summary, our study indicates that statins statistically reduced microalbuminuria, proteinuria, and clinical deaths, but statins did not effectively slow the clinical progression of non-end stage CKD.
Asunto(s)
Albuminuria/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Proteinuria/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Albuminuria/complicaciones , Albuminuria/epidemiología , Albuminuria/fisiopatología , Progresión de la Enfermedad , Humanos , Riñón/efectos de los fármacos , Riñón/fisiopatología , Proteinuria/complicaciones , Proteinuria/epidemiología , Proteinuria/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatologíaRESUMEN
OBJECTIVE: To conduct a systematic review and Meta-analysis of the effectiveness of acupuncture and common acupoint selection for postoperative ileus (POI). METHODS: Randomized controlled trials (RCTs) comparing acupuncture and non-acupuncture treatment were identified from the databases PubMed, Cochrane, EBSCO (Academic Source Premier and MEDLINE), Ovid (including Evidence-Based Medicine Reviews), China National Knowledge Infrastructure, and Wanfang Data. The data from eligible studies were extracted and a Meta-analysis performed using a fixed-effects model. Results were expressed as relative risk (RR) for dichotomous data, and 95% CI (confidence intervals) were calculated. Each trial was evaluated using the CONSORT (Consolidated Standards of Reporting Trials) and STRICTA (STandards for Reporting Interventions in Controlled Trials of Acupuncture) guideline . The quality of the study was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of the 69 studies screened, eight RCTs were included for review. Among these, four RCTs (with a total of 123 patients in the intervention groups and 124 patients in the control groups) met the criteria for Meta-analysis. The Meta-analysis results indicated that acupuncture combined with usual care showed a significantly higher total effective rate than the control condition (usual care) (RR 1.09, 95% CI 1.01, 1.18; P = 0.02). Zusanli (ST 36) and Shangjuxu (ST 37) were the most common acupoints selected. However, the quality of the studies was generally low, as they did not emphasize the use of blinding. CONCLUSION: The results suggested that acupuncture might be effective in improving POI; however, a definite conclusion could not be drawn because of the low quality of trials. Further large-scale, high-quality randomized clinical trials are needed to validate these findings and to develop a standardized method of treatment. We hope that the present results will lead to improved research, resulting in better patient care worldwide.
Asunto(s)
Terapia por Acupuntura , Enfermedades del Íleon/terapia , Complicaciones Posoperatorias/terapia , Puntos de Acupuntura , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The ability of the auditory system to resolve sound temporal information is crucial for the understanding of human speech and other species-specific communications. Gap detection threshold, i.e. the ability to detect the shortest duration of a silent interval in a sound, is commonly used to study the auditory temporal resolution. Behavioral studies in humans and rats have shown that normal developing infants have higher gap detection thresholds than adults; however, the underlying neural mechanism is not fully understood. In the present study, we determined and compared the neural gap detection thresholds in the primary auditory cortex of three age groups of rats: the juvenile group (postnatal day 20-30), adult group I (8-10 weeks), and adult group II (28-30 weeks). We found age-related changes in auditory temporal acuity in the auditory cortex, i.e. the proportion of cortical units with short neural gap detection thresholds (< 5 ms) was much lower in juvenile groups compared with that in both adult groups at a constant sound level, and no significant differences in neural gap detection thresholds were found between the two adult groups. In addition, units in the auditory cortex of each group generally showed better gap detection thresholds at higher sound levels than at lower sound levels, exhibiting a level-dependent temporal acuity. These results provided evidence for neural correlates of age-related changes in behavioral gap detection ability during postnatal hearing development.
Asunto(s)
Corteza Auditiva/crecimiento & desarrollo , Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Detección de Señal Psicológica/fisiología , Estimulación Acústica/métodos , Potenciales de Acción , Envejecimiento/fisiología , Animales , Potenciales Evocados Auditivos , Microelectrodos , Ratas Sprague-Dawley , Percepción del Tiempo/fisiologíaRESUMEN
The accurate processing of sound temporal information is crucial to human speech perception and other species-specific communication. During postnatal development, the auditory cortex shows environmental and experience-dependent plasticity. However, how the postnatal environment affects cortical processing of sound temporal information is not fully understood. The aim of the present study was to determine whether postnatal noise exposure impairs neural temporal resolution in the auditory cortex, and, if so, whether environmental enrichment can rescue this degraded neural temporal acuity. Using the neural gap detection threshold determined in anesthetized rats as an index of temporal acuity, we found that exposure of juvenile rats to moderate-level noise induced much higher neural gap detection thresholds in adulthood than exposure of adult rats to the same noise. Environmental enrichment did not affect cortical neural gap detection thresholds in normally developing rats. However, rearing of rats with early noise exposure in an enriched environment promoted recovery from the noise-induced degraded neural temporal resolution. In addition, the tonal stimuli in the enriched environment contributed to only a portion of the recovery. These results provide evidence for noise-induced developmental impairment in neural gap detection thresholds in the auditory cortex, and suggest a therapeutic potential for environmental enrichment as a non-invasive approach to rescue developmentally degraded auditory temporal processing.
Asunto(s)
Estimulación Acústica/efectos adversos , Corteza Auditiva/crecimiento & desarrollo , Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Vivienda para Animales , Neuronas/fisiología , Estimulación Acústica/métodos , Potenciales de Acción , Animales , Femenino , Masculino , Ratas Sprague-Dawley , Recuperación de la Función/fisiología , Detección de Señal Psicológica/fisiologíaRESUMEN
BACKGROUND: Using functional magnetic resonance imaging (fMRI), we determined brain regions that were activated/deactivated more by acupuncture at Taixi (KI3) than by non-acupoint or sham acupuncture. METHODS: A total of 30 healthy volunteers were randomly divided into a KI3 group (15 subjects) and non-acupoint group (15 subjects). Subjects in KI3 group received a sham acupuncture and then a real acupuncture, fMRI was performed before and after sham acupuncture as well as after ture acupuncture. Subjects in non-acupoint group received a ture acupuncture and the fMRI was performed before and after ture acupuncture. The fMRI data obtained were successively analyzed using DPARSF2.3 and REST1.8 software, yielding regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) values. RESULTS: Compared with sham acupuncture, ALFF values were higher in Brodmann area (BA) 10 and lower in BA7 and BA18. ReHo values after real acupuncture at KI3 were higher in the right sub-lobar region and BA10 and were lower in BA31. Compared with the changes before and after real acupuncture at non-acupoint, the changes at KI3 showed higher ALFF valued in the left cerebellum posterior lobe, BA10, BA39, BA31 and decreased ALFF was observed in the BA18, BA19 and BA40; and higher ReHo values were shown in left cerebellum posterior lobe pyramis, left cerebellum anterior lobe. BA37, BA10, BA39, BA31 and lower ReHo values were shown in BA18 and BA31. CONCLUSION: Acupuncture at KI3 has a specific effect on certain brain regions associated with perception, body movement, spirit, and association. Additionally, visual and auditory cortices were affected, which may be related to the clinical applications of KI3 acupuncture in auditory and cognitive disorders, hypomnesis, loss of concentration, and the loss of ability to work and learn. TRIAL REGISTRATION: The research ethics committee was achieved at 01/08/2012, the NO. was ChiECRCT-2012011. Website for Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=7123 . This study was registered at www.chictr.org, the Clinical Trial Registration Number was ChiCTR-TRC-12002427, and the registration number was achieved at 18/08/2012. The name of IRB that provided approval for the study and clearly state is Chinese Clinical Trail Registry.
Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura/métodos , Encéfalo/fisiopatología , Imagen por Resonancia Magnética , Adulto , Corteza Cerebral/fisiopatología , Trastornos del Conocimiento/terapia , Femenino , Voluntarios Sanos , Humanos , Aprendizaje , Masculino , Adulto JovenRESUMEN
Fibroblast activation protein (FAP) is a serine protease selectively expressed on tumor stromal fibroblasts in epithelial carcinomas and is important in cancer growth, adhesion, and metastases. As FAP enzymatic activity is a potent therapeutic target, we aimed to identify inhibitory antibodies. Using a competitive inhibition strategy, we used phage display techniques to identify 53 single-chain variable fragments (scFvs) after three rounds of panning against FAP. These scFvs were expressed and characterized for binding to FAP by surface plasmon resonance and flow cytometry. Functional assessment of these antibodies yielded an inhibitory scFv antibody, named E3, which could attenuate 35% of FAP cleavage of the fluorescent substrate Ala-Pro-7-amido-4-trifluoromethylcoumarin compared with nonfunctional scFv control. Furthermore, a mutant E3 scFv was identified by yeast affinity maturation. It had higher affinity (4-fold) and enhanced inhibitory effect on FAP enzyme activity (3-fold) than E3. The application of both inhibitory anti-FAP scFvs significantly affected the formation of 3-dimensional FAP-positive cell matrix, as demonstrated by reducing the fibronectin fiber orientation from 41.18% (negative antibody control) to 34.06% (E3) and 36.15% (mutant E3), respectively. Thus, we have identified and affinity-maturated the first scFv antibody capable of inhibiting FAP function. This scFv antibody has the potential to disrupt the role of FAP in tumor invasion and metastasis.
Asunto(s)
Gelatinasas/antagonistas & inhibidores , Gelatinasas/inmunología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/inmunología , Serina Endopeptidasas/inmunología , Anticuerpos de Cadena Única/inmunología , Animales , Afinidad de Anticuerpos , Endopeptidasas , Citometría de Flujo , Gelatinasas/genética , Gelatinasas/metabolismo , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Terapia Molecular Dirigida , Mutagénesis Sitio-Dirigida , Proteínas Mutantes/genética , Proteínas Mutantes/inmunología , Neoplasias/tratamiento farmacológico , Neoplasias/enzimología , Biblioteca de Péptidos , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/metabolismo , Resonancia por Plasmón de SuperficieRESUMEN
PURPOSE: Osteonecrosis of the femoral head (ONFH) is a severe bone disease that can progressively lead to hip dysfunction. Accurately segmenting the necrotic lesion helps in diagnosing and treating ONFH. This paper aims at enhancing deep learning models for necrosis segmentation. METHODS: Necrotic lesions of ONFH are confined to the femoral head. Considering this domain knowledge, we introduce a preprocessing procedure, termed the "subtracting-adding" strategy, which explicitly incorporates this domain knowledge into the downstream deep neural network input. This strategy first removes the voxels outside the predefined volume of interest to "subtract" irrelevant information, and then it concatenates the bone mask with raw data to "add" anatomical structure information. RESULTS: Each of the tested off-the-shelf networks performed better with the help of the "subtracting-adding" strategy. The dice similarity coefficients increased by 10.93%, 9.23%, 9.38% and 1.60% for FCN, HRNet, SegNet and UNet, respectively. The improvements in FCN and HRNet were statistically significant. CONCLUSIONS: The "subtracting-adding" strategy enhances the performance of general-purpose networks in necrotic lesion segmentation. This strategy is compatible with various semantic segmentation networks, alleviating the need to design task-specific models.
Asunto(s)
Necrosis de la Cabeza Femoral , Humanos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Aprendizaje Profundo , Redes Neurales de la Computación , Tomografía Computarizada por Rayos X/métodos , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/patología , Masculino , Femenino , Imagen por Resonancia Magnética/métodosRESUMEN
Background: Total joint arthroplasty (TJA) is an orthopedic procedure commonly used to treat damaged joints. Despite the efficacy of TJA, postoperative complications, including aseptic prosthesis loosening and infections, are common. Moreover, the effects of individual genetic susceptibility and modifiable risk factors on these complications are unclear. This study analyzed these effects to enhance patient prognosis and postoperative management. Methods: We conducted an extensive genome-wide association study (GWAS) and Mendelian randomization (MR) study using UK Biobank data. The cohort included 2964 patients with mechanical complications post-TJA, 957 with periprosthetic joint infection (PJI), and a control group of 398,708 individuals. Genetic loci associated with postoperative complications were identified by a GWAS analysis, and the causal relationships of 11 modifiable risk factors with complications were assessed using MR. Results: The GWAS analysis identified nine loci associated with post-TJA complications. Two loci near the PPP1R3B and RBM26 genes were significantly linked to mechanical complications and PJI, respectively. The MR analysis demonstrated that body mass index was positively associated with the risk of mechanical complications (odds ratio [OR]: 1.42; p < 0.001). Higher educational attainment was associated with a decreased risk of mechanical complications (OR: 0.55; p < 0.001) and PJI (OR: 0.43; p = 0.001). Type 2 diabetes was suggestively associated with mechanical complications (OR, 1.18, p = 0.02), and hypertension was suggestively associated with PJI (OR, 1.41, p = 0.008). Other lifestyle factors, including smoking and alcohol consumption, were not causally related to postoperative complications. Conclusions: The genetic loci near PPP1R3B and RBM26 influenced the risk of post-TJA mechanical complications and infections, respectively. The effects of genetic and modifiable risk factors, including body mass index and educational attainment, underscore the need to perform personalized preoperative assessments and the postoperative management of surgical patients. These results indicate that integrating genetic screening and lifestyle interventions into patient care can improve the outcomes of TJA and patient quality of life.