Trade-offs between diaspore dispersal and dormancy within a spike of the invasive annual grass Aegilops tauschii.

MAIN CONCLUSION: Differences in dispersal and dormancy of heteromorphic diaspores of Aegilos tauschii may increase its flexibility to invade/occupy weedy unpredictable habitats by spreading risk in space and time. In plant species that produce dimorphic seeds, there often is a negative relationship between dispersal and dormancy, with high dispersal-low dormancy in one morph and low dispersal-high dormancy in the other, which may function as a bet-hedging strategy that spreads the risk of survival and ensures reproductive success. However, the relationship between dispersal and dormancy and its ecological consequences in invasive annual grasses that produce heteromorphic diaspores is not well studied. We compared dispersal and dormancy responses of diaspores from the basal (proximal) to the distal position on compound spikes of Aegilops tauschii, an invasive grass with heteromorphic diaspores. Dispersal ability increased and degree of dormancy decreased as diaspore position on a spike increased from basal to distal. There was a significant positive correlation between length of awns and dispersal ability, and awn removal significantly promoted seed germination. Germination was positively correlated with GA concentration and negatively correlated with ABA concentration, and the ABA: GA ratio was high in seeds with low germination/high dormancy. Thus, there was a continuous inverse-linear relationship between diaspore dispersal ability and degree of dormancy. This negative relationship between diaspore dispersal and degree of dormancy at different positions on a spike of Aegilops tauschii may facilitate seedling survival in space and time.

Real-time monitoring of atmospheric ammonia based on modifier-enhanced vacuum ultraviolet photoionization ion mobility spectrometry.

Ammonia (NH3) plays an important role in the atmospheric environment such as the formation of PM2.5, the concentration monitoring of which could hence help in the air quality assessment. In this study, a method for quantitative monitoring of atmospheric NH3 was developed based on modifier-enhanced selectivity detection using a homemade vacuum ultraviolet photoionization ion mobility spectrometry (VUV-PI-IMS). To enhance the resolution and sensitivity of measuring NH3, 2-butanone as the gas modifier was introduced into the drift tube with the drift gas. Atmospheric NH3 can be selectively detected, where the peak-to-peak resolution (RP-P) of 7.69 was obtained. The product ions were identified to be [C4H8O]2NH4+ by using a homemade time-of-flight mass spectrometer. The calculated limit of detection (LOD) was 0.39 ppbv improving about 10 times. For the most common concentration variation of atmospheric NH3 in the range of 10-100 ppbv, the linear curve was obtained with R2 of 0.997. Lastly, the VUV-PI-IMS was used to monitor the evolution of atmospheric NH3 near our laboratory and mounted on a car for monitoring the regional distribution of atmospheric NH3 in Dalian, China. The results also showed that VUV-PI-IMS has a promising application prospect in monitoring the concentration of atmospheric NH3 and supporting the air quality assessment.

Ductile machining of optical micro-structures on single crystal germanium by elliptical vibration assisted sculpturing.

Microstructure surfaces are widely and deeply applied in optical fields to decrease the volume of an optical system and realize sophisticated optical requirements. This paper studies the machining of optical micro-structures with micro-scale height on single crystal germanium by elliptical vibration assisted sculpturing (EVAS) method in which two vibration amplitudes keep constant. Due to the superimposition of low-frequency sculpture path and high-frequency elliptical locus, the investigations are focused on cutting plane to describe motion trajectory of the tool tip of cutting tool for desired complex motion path and to calculate the sculpture path of elliptical vibration cutting device to make corresponding path of tool tip be the envelope of target profile. A comparative experiment is firstly conducted to verify that elliptical locus would deteriorate machining accuracy without accurate compensation for the ellipse. Following that, 2D and 3D sinusoidal surfaces and a picture, whose structural heights are all not less than 2.0µm, are experimentally machined on single crystal germanium. Satisfying experimental results demonstrate the feasibility of EVAS method for fabricating optical micro-structures on germanium.

Influence in core training on physical fitness of college athletes / Influência do treinamento do core na aptidão física de atletas universitários / Influencia del entrenamiento del core en la aptitud física de los deportistas universitarios

ABSTRACT Introduction: Recent research shows the CORE is the central link in the kinetic chain of aerobic gymnastics. The athlete's synchronized performances depend not only on strength but also on the balance and precision of the movements that start from this area. Although the importance of this muscle group is recognized, there is no consensus about the most effective protocol to increase performance in aerobic gymnastics athletes. Objective: Develop and verify the influence of a protocol for CORE training on the aerobic gymnasts' balance. Methods: This paper selects high-level aerobic gymnastics athletes and randomly divides them into experimental and control groups. The experiment was conducted over eight weeks. The experimental group adopted systematic core strength training methods, and the control group continued with traditional conventional strength training methods. Volunteers were tested for physical fitness before and after the experiment. Results: Aerobic gymnastics athletes' physical fitness and athletic abilities were significantly improved after training. Conclusion: The CORE training protocol in aerobic gymnastics athletes increased the execution quality in complex movements. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução: Pesquisas recentes demonstram que o CORE é o elo central na cadeia cinética da ginástica aeróbica. As apresentações sincronizadas dos atletas dependem não só da força quanto também do equilíbrio e precisão dos movimentos que partem dessa área. Embora reconheça-se a importância desse grupo muscular, não há um consenso sobre o protocolo mais eficaz para aumentar o desempenho em atletas de ginástica aeróbica. Objetivo: Desenvolver um protocolo de treinamento do CORE e verificar sua influência sobre o equilíbrio dos atletas em ginástica aeróbica. Métodos: Este artigo seleciona atletas de ginástica aeróbica de alto nível e os divide aleatoriamente em grupos experimentais e de controle. A experiência foi conduzida em 8 semanas. O grupo experimental adotou métodos sistemáticos de treinamento de força central, e o grupo de controle continuou com os métodos tradicionais de treinamento de força convencional. Os voluntários foram testados quanto à aptidão física antes e depois do experimento. Resultados: A aptidão física e as habilidades atléticas dos atletas de ginástica aeróbica foram significativamente aprimoradas após o treinamento. Conclusão: O protocolo de treinamento do CORE em atletas de ginástica aeróbica elevou a qualidade de execução nos movimentos complexos. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción: Investigaciones recientes demuestran que el CORE es el eslabón central de la cadena cinética de la gimnasia aeróbica. Las presentaciones sincronizadas de las atletas dependen no sólo de la fuerza sino también del equilibrio y la precisión de los movimientos que parten de esta zona. Aunque se reconoce la importancia de este grupo muscular, no hay consenso sobre el protocolo más eficaz para aumentar el rendimiento de las gimnastas aeróbicas. Objetivo: Desarrollar un protocolo de entrenamiento del CORE y comprobar su influencia en el equilibrio de los atletas en la gimnasia aeróbica. Métodos: Este trabajo selecciona a atletas de gimnasia aeróbica de alto nivel y los divide aleatoriamente en grupos experimental y de control. El experimento se realizó durante 8 semanas. El grupo experimental adoptó métodos sistemáticos de entrenamiento de la fuerza central, y el grupo de control continuó con los métodos tradicionales de entrenamiento de la fuerza convencional. Los voluntarios fueron sometidos a pruebas de aptitud física antes y después del experimento. Resultados: La aptitud física y las capacidades atléticas de los atletas de gimnasia aeróbica mejoraron significativamente después del entrenamiento. Conclusión: El protocolo de entrenamiento CORE en atletas de gimnasia aeróbica elevó la calidad de ejecución en movimientos complejos. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Seed position in spikelet as a contributing factor to the success of the winter annual invasive grass Aegilops tauschii.

Seed position - dependent effects on seed dormancy/germination are well documented at the inflorescence/infructescence level, but less is known about seeds at different positions within a dispersal unit. For the invasive winter annual grass Aegilops tauschii, we quantified morphology, mass and dormancy/germination of seeds from basal (1), middle (2), and distal (3) positions in two spikelet types (Left and Right). We also investigated seedling emergence, survival, plant size and seed production of plants from seeds in different spikelet positions of two spikelet types under different soil nutrient and water conditions. We found that these seed, seedling and plant traits performed as mirror images between the Left and Right spikelet types. The middle seed was significantly the longest and had the maximum mass, while the basal seed was the shortest and had medium mass. Middle seeds had the highest increase in mass during imbibition and the highest germination percentages and rates, while basal seeds had the lowest. Seedling emergence and survival, plant size and seed production for each position of seeds were highest in the added fertilizer combined with regular watering treatment and lowest in the no fertilizer combined with natural moisture, while height of plants derived from the middle and the distal seeds was significantly higher than that of plants derived from the basal seeds under all soil nutrient and water conditions. Seedling survival, number of tillers per plant and seed production per plant from the middle and distal seeds were significantly lower than those from basal seeds under all soil nutrient and water treatments. The considerable variation in seedling emergence and survival, plant size and seed production between seeds in different positions in the spikelet results in much flexibility in all stages of the life cycle, thereby likely contributing to the invasiveness of A. tauschii.

Evaluation of the Glymphatic System With Diffusion Tensor Imaging-Along the Perivascular Space in Cancer Pain.

Cancer pain (CP) is one of the most common symptoms affecting life quality, and there is considerable variation in pain experience among patients with malignant tumors. Previously, it has been found that the fluid drainage function in the brain can be regulated by peripheral pain stimulation. However, the relationship between cancer pain and functional changes of the glymphatic system (an important pathway for fluid drainage in the brain) remains unclear. In this study, 97 participants were enrolled, which included 40 participants in the cancer pain (CP) group, 27 participants in the painless cancer (PLC) group and 30 participants in the control (NC) group. Differences in glymphatic system function among the three groups and between before and after pain pharmacological intervention were analyzed by measuring diffusivity and the index along the perivascular space (ALPS index) using diffusion tensor imaging. We found that diffusivity and the ALPS index were significantly lower in the CP group than in the PLC and NC group and increased following intervention with pain relief. Moreover, the ALPS index was negatively correlated with the degree of pain in the CP group. The present study verified that alterations in glymphatic function are closely related to cancer pain, and the quantification of functional changes reflects pain severity. Our findings support the use of neuroimaging biomarkers for cancer pain assessment and indicate that pain can be alleviated by regulating brain function status.

Research on the influence of sport dance on physical health in national fitness exercise / Pesquisa sobre a influência da dança esportiva na saúde física no exercício de condicionamento físico nacional / Investigación sobre la influencia de la danza deportiva en la salud física en el ejercicio de acondicionamiento físico nacional

ABSTRACT Introduction: Sports dance is widely known as a competitive game, but as a leisure activity, there is little research on the efficacy of human health and fitness. Sports dance, as a popular national fitness exercise, has sound health promotion effects. At present, domestic and foreign researches mostly focus on the impact of sports dance on young men and women. Objective: This study will explore the influence of regular physical dance exercises on the body shape, function, and quality of middle-aged and older adults, provide a scientific basis for the role of physical dance in national fitness. Methods: This study recruited 20 healthy middle-aged and elderly members of a leisure sports dance club without professional dance experience for three months of dance training. The first two weeks are pre-experiments five times a week. Each exercise time is 60 minutes. The last ten weeks are formal experiments, two times a week, 90 minutes each time, and no other physical exercises are involved in everyday life. By comparing part of the body shape, physical function, and physical fitness index before and after the experiment, the impact of sports dance on middle-aged and older adults' healthy physical fitness is evaluated. Results: After three months of physical dance exercise with different dance styles, in male, BMI index, body fat percentage, waist circumference, hip circumference, and thigh circumference indicators all decreased, but there was no significant difference. In women, BMI index, body fat percentage (P<0.01), waist circumference (P<0.05), diastolic blood pressure (P<0.01), sitting body forward bending (P<0.05), and standing with one foot and closed eyes all increased. In women, the indexes of grip strength (P<0.01), forward bending in sitting position (P<0.055), and standing with eyes closed on one foot all increased. Conclusions: It is suggested that long-term moderate-intensity aerobic sport dance exercise can improve the body shape of middle-aged and older adults and help increase physical fitness; meanwhile, sports dance can effectively improve the cardiovascular function of middle-aged and elderly subjects. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A dança esportiva é amplamente conhecida como um jogo competitivo, mas como atividade de lazer, existem poucas pesquisas sobre sua eficácia na saúde e forma física humana. A dança esportiva, como exercício físico popular em âmbito nacional, tem importantes efeitos na promoção da saúde. Atualmente, a pesquisa nacional e estrangeira está focada principalmente no impacto da dança esportiva em jovens de ambos os sexos. Objetivo: Este estudo irá explorar a influência dos exercícios regulares de dança física na forma, função e qualidade do corpo de adultos mais velhos e de meia-idade, e fornecerá uma base científica para o papel da dança física no fitness nacional. Métodos: Este estudo recrutou 20 pessoas saudáveis, de meia-idade e idosos de um clube esportivo sem experiência profissional em dança durante três meses de treinamento. As primeiras duas semanas foram pré-experimentos cinco vezes por semana. Cada tempo de exercício foi de 60 minutos. As últimas dez semanas foram experimentos formais, duas vezes por semana, 90 minutos cada vez, sem nenhum outro exercício físico na vida cotidiana. Ao comparar a forma corporal, a função física e o índice de aptidão física antes e depois do experimento, o impacto da dança esportiva na aptidão física saudável de adultos mais velhos e de meia-idade é avaliado. Resultados: Após três meses de exercício físico de dança com diferentes estilos de dança, nos homens, o índice de IMC, o percentual de gordura corporal, a circunferência da cintura, a circunferência do quadril e a circunferência da coxa diminuíram, mas não houve diferença significativa. Nas mulheres, o índice de IMC, o percentual de gordura corporal (P <0,01), a circunferência da cintura (P <0,05), a pressão arterial diastólica (P <0,01), o corpo sentado inclinado para frente (P <0,05) e com um pés e olhos fechados aumentaram. Nas mulheres, os índices de força de preensão (P <0,01), de inclinação para a frente na posição sentada (P <0,055) e com um pé com os olhos fechados aumentaram. Conclusões: Sugere-se que o exercício de dança esportiva aeróbica de intensidade moderada de longa duração pode melhorar a forma corporal de adultos mais velhos e de meia idade e ajudar a aumentar a aptidão física; enquanto isso, a dança esportiva pode efetivamente melhorar a função cardiovascular de indivíduos de meia-idade e idosos. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.

RESUMEN Introducción: La danza deportiva es ampliamente conocida como un juego competitivo, pero como actividad de ocio hay poca investigación sobre la eficacia en la salud y el estado físico humanos. La danza deportiva, como ejercicio físico popular a nivel nacional, tiene importantes efectos en la promoción de la salud. En la actualidad, las investigaciones nacionales y extranjeras se centran principalmente en el impacto de la danza deportiva en hombres y mujeres jóvenes. Objetivo: Este estudio explorará la influencia de los ejercicios regulares de danza física en la forma, función y calidad del cuerpo de los adultos mayores y de mediana edad, y proporcionará una base científica para el papel de la danza física en la aptitud nacional. Métodos: Este estudio reclutó a 20 miembros sanos de mediana edad y ancianos de un club deportivo sin experiencia profesional en danza durante tres meses de entrenamiento. Las dos primeras semanas eran experimentos previos cinco veces por semana. Cada tiempo de ejercicio fue de 60 minutos. Las últimas diez semanas eran experimentos formales, dos veces por semana, 90 minutos cada vez, sin otros ejercicios físicos en la vida cotidiana. Al comparar la forma del cuerpo, la función física y el índice de aptitud física antes y después del experimento, se evalúa el impacto de la danza deportiva en la aptitud física saludable de los adultos mayores y de mediana edad. Resultados: Después de tres meses de ejercicio físico de baile con diferentes estilos de baile, en los hombres, el índice de IMC, el porcentaje de grasa corporal, la circunferencia de la cintura, la circunferencia de la cadera y la circunferencia del muslo disminuyeron, pero no hubo diferencia significativa. En las mujeres, el índice de IMC, el porcentaje de grasa corporal (P <0.01), la circunferencia de la cintura (P <0.05), la presión arterial diastólica (P <0.01), el cuerpo sentado inclinado hacia adelante (P <0.05) y con un pie y ojos cerrados aumentaron. En las mujeres, aumentaron los índices de fuerza de agarre (P <0.01), de inclinación hacia adelante en posición sentada (P <0.055) y con un pie con los ojos cerrados. Conclusiones: Se sugiere que el ejercicio de danza deportiva aeróbica de intensidad moderada a largo plazo puede mejorar la forma del cuerpo de los adultos mayores y de mediana edad y ayudar a aumentar la aptitud física; mientras tanto, la danza deportiva puede mejorar eficazmente la función cardiovascular de sujetos de mediana edad y ancianos. Nivel de evidencia II;Estudios terapéuticos: investigación de los resultados del tratamiento.

Research on the application of sport dance in colleges and universities in the healthy development of sports / Pesquisa sobre a aplicação da dança esportiva nas universidades no desenvolvimento saudável dos esportes / Estudio sobre la aplicación de la danza deportiva en las universidades en el desarrollo saludable de los deportes

ABSTRACT Introduction: Immunity is closely related to health. When the body's immunity is strong, it is healthy. On the contrary, various diseases appear. Sports dance is an entertainment and fitness sports project that integrates sports, music, aesthetics, and dance, the body movement dance as the necessary content and two-person or collective exercises as the primary form of exercise. Studies have shown that long-term adherence to Tai Chi exercise can significantly increase the serum immunoglobulin IgA, IgG, and IgM levels. Objective: The paper explores the effect of physical dance exercise on serum immunoglobulin and T lymphocyte subsets of college students. Methods: The thesis randomly selected 16 male and female students in the first-grade physical dance optional course of public physical education as the experimental group. They performed physical dance exercises three times a week, 40 minutes each time, and the training intensity was controlled at a heart rate of 135-150 beats/min. Ten weeks; besides, 16 male and female students in the first grade were selected as the control group, and no physical dance exercise was performed; all the subjects were drawn from the elbow venous blood on an empty stomach at the same time before and after the experiment to measure serum immunoglobulin and T lymph Cell subpopulation content. Results: After ten weeks of sports dance training, the serum immunoglobulin IgG of both men and women in the experimental group increased significantly (P<0.01), and the CD4+% and CD4+/CD8+ ratio of T lymphocyte subgroups showed extremely significant and significant increases (P <0.01, P<0.05), serum IgM tended to increase, IgA, CD8+% tended to decrease, but there was no significant change. Conclusions: Long-term physical dance exercise can improve the body's immune function. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: la inmunidad está estrechamente relacionado con la salud. Cuando la inmunidad del cuerpo es fuerte éste está sano. En caso contrario, aparecen diversas enfermedades. La danza deportiva é um projeto de entretenimiento y fitness que integra el deporte, la música, la estética y la danza, el movimiento corporal como contenido necesario y los ejercicios de das personas ou colectivos como forma principal de ejercicio. Los estudios han demonstraram que a adesão a largo plazo al ejercicio de Tai Chi pode aumentar também os niveles séricos de imunoglobulina IgA, IgG e IgM. Objetivo: O artigo explora o efeito do exercício físico de danza em subconjuntos de imunoglobulina sérica e linfocitos T de estudiantes universitários. Métodos: Para que a tese seja selecionada aleatoriamente, 16 ex-alunos e ex-alunos do curso optativo de danza física de primer grado de educação física pública como grupo experimental. Realizaron ejercicios de danza física tres veces por semana, 40 minutes cada vez, y la intensidad del entrenamiento se controló a una frecuencia cardíaca de 135-150 latidos/min. durante as semanas; además, se selecionar 16 alumnos y alumnas de primer grado como group de control, el que no realizó ningún ejercicio físico de danza. A todos os sujetos se les extrajo sangre venosa del codo com o estómago vacío, durante, antes e depois do experimento para medir o conteúdo da subpoblación de células T y de imunoglobulina sérica. Resultados: Después de diez semanas de entrenamiento de danza deportiva, la imunoglobulina IgG sérica de hombres y mujeres en el grupo experimental aumentó complementar (P <0,01), y la proporción CD4 +% y CD4 +/CD8 + de los subgrupos de linfocitos T mostró incrementos extremadamente provados. (P <0,01,P <0,05), la IgM sérica tendió a aumentar, la IgA, CD8 +% tendió a disminuir, mas nenhum hubo cambio projetado. Conclusiones: El ejercicio de danza física a largo plazo puede mejorar la función inmunológica del cuerpo. Nivel de evidencia II; Estudios terapéuticos: investigación de los results del tratamiento.

RESUMEN Introducción: la inmunidad está estrechamente relacionada con la salud. Cuando la inmunidad del cuerpo es fuerte éste está sano. En caso contrario, aparecen diversas enfermedades. La danza deportiva es un proyecto de entretenimiento y fitness que integra el deporte, la música, la estética y la danza, el movimiento corporal como contenido necesario y los ejercicios de dos personas o colectivos como forma principal de ejercicio. Los estudios han demostrado que la adherencia a largo plazo al ejercicio de Tai Chi puede aumentar significativamente los niveles séricos de inmunoglobulina IgA, IgG e IgM. Objetivo: El artículo explora el efecto del ejercicio físico de danza en subconjuntos de inmunoglobulina sérica y linfocitos T de estudiantes universitarios. Métodos: Para la tesis se seleccionaron aleatoriamente a 16 alumnos y alumnas del curso optativo de danza física de primer grado de educación física pública como grupo experimental. Realizaron ejercicios de danza física tres veces por semana, 40 minutos cada vez, y la intensidad del entrenamiento se controló a una frecuencia cardíaca de 135-150 latidos/min. durante diez semanas; además, se seleccionaron 16 alumnos y alumnas de primer grado como grupo de control, el que no realizó ningún ejercicio físico de danza. A todos los sujetos se les extrajo sangre venosa del codo con el estómago vacío, durante, antes y después del experimento para medir el contenido de la subpoblación de células T y de inmunoglobulina sérica. Resultados: Después de diez semanas de entrenamiento de danza deportiva, la inmunoglobulina IgG sérica de hombres y mujeres en el grupo experimental aumentó significativamente (P <0.01), y la proporción CD4 +% y CD4 + / CD8 + de los subgrupos de linfocitos T mostró incrementos extremadamente significativos. (P <0.01, P <0.05), la IgM sérica tendió a aumentar, la IgA, CD8 +% tendió a disminuir, pero no hubo cambios significativos. Conclusiones: El ejercicio de danza física a largo plazo puede mejorar la función inmunológica del cuerpo. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Physical development monitoring of primary school students in the Oroqen Inhabited Area from 2013 to 2018 / 中国学校卫生

Objective@#To understand physical development of children aged 7 to 12 in the oroqen autonomous banner experimental primary school in the oroqen settlement area from 2013 to 2018, and to provide scientific basis for their physical fitness and health.@*Methods@#According to the standards of "National Student Physical Health Standards (2014 Revised Edition)" and the standards of "Overweight and Obesity Screening for School age Children and Adolescents" issued by the National Health and Family Planning Commission in 2018, the Oroqen Autonomous Banner Experimental Primary School was 7-12 years old. The average value and growth rate of children s height, weight and BMI in the past 6 years.@*Results@#From 2013 to 2018, the height and weight of boys and girls aged 7 to 12 showed an increasing trend, with height growth values of boys were 1.8,1.7,1.9,2.6,5.7,5.9 cm,girls were 2.8,4.5,1.9,1.8,3.6,2.9 cm.And the weight groups values of boys were 2.2,2.5,5.1,6.3,6.4,7.2 kg,girls were 2.4,3.6,3.1,1.3,4.6,3.0 kg. The growth rate of girls aged 7 to 8 was higher than that of boys, and the growth rate of boys aged 9 to 12 was higher than that of girls. With the increase of age, the average BMI of boys and girls aged 7 to 12 showed an upward trend, and the BMI of boys of the same age was always higher than that of girls. Among them, the average BMI of boys aged 7 to 12 in 2018 exceeded the critical value of overweight BMI.@*Conclusion@#The physical shape of children aged 7-12 years increases with age, but the development tends to be overweight and obese, which is related to the natural environment of life, lifestyle, and reduction in physical activity.

Aquaporin4 Knockout Aggravates Early Brain Injury Following Subarachnoid Hemorrhage Through Impairment of the Glymphatic System in Rat Brain.

BACKGROUND: It is reported that the expression of aquaporin4 (AQP4) in the brain is increased and leads to the brain edema after subarachnoid hemorrhage (SAH). In this study, by using AQP4 knockout rat model, the opposite role of AQP4 in early brain injury following SAH through modulation of interstitial fluid (ISF) transportation in the brain glymphatic system had been explored. METHODS: The SAH model was established using endovascular perforation method, the AQP4 knockout rat model was generated using TALENs (transcription activator-like (TAL) effector nucleases) technique. The animals were randomly divided into four groups: sham (n = 16), AQP4-/-sham (n = 16), SAH (n = 24), and AQP4-/-SAH groups (n = 27). The roles of AQP4 in the brain water content and neurological function were detected. In addition, immunohistochemistry and Nissl staining were applied to observe the effects of AQP4 on the blood-brain barrier (BBB) integrity and the loss of neurons in the hippocampus. To explore the potential mechanism of these effects, the distribution of Gd-DTPA (interstitial fluid indicator) injected from cisterna magna was evaluated with MRI. RESULTS: Following SAH, AQP4 knockout could significantly increase the water content in the whole brain and aggravate the neurological deficits. Furthermore, the loss of neuron and BBB disruption in hippocampus were also exacerbated. The MRI results indicated that the ISF transportation in the glymphatic system of AQP4 deficit rat was significantly injured. CONCLUSION: AQP4 facilitates the ISF transportation in the brain to eliminate the toxic factors; AQP4 knockout will aggravate the early brain injury following SAH through impairment of the glymphatic system.

Erratum: Publisher Correction: Endogenous formaldehyde is a memory-related molecule in mice and humans.

[This corrects the article DOI: 10.1038/s42003-019-0694-x.].

Endogenous formaldehyde is a memory-related molecule in mice and humans.

Gaseous formaldehyde is an organic small molecule formed in the early stages of earth's evolution. Although toxic in high concentrations, formaldehyde plays an important role in cellular metabolism and, unexpectedly, is found even in the healthy brain. However, its pathophysiological functions in the brain are unknown. Here, we report that under physiological conditions, spatial learning activity elicits rapid formaldehyde generation from mitochondrial sarcosine dehydrogenase (SARDH). We find that elevated formaldehyde levels facilitate spatial memory formation by enhancing N-methyl-D-aspartate (NMDA) currents, but that high formaldehyde concentrations gradually inactivate the NMDA receptor by cross-linking NR1 subunits to NR2B via the C232 residue. We also report that in mice with aldehyde dehydrogenase-2 (ALDH2) knockout, formaldehyde accumulation due to hypofunctional ALDH2 impairs memory, consistent with observations of Alzheimer's disease patients. We also find that formaldehyde deficiency caused by mutation of the mitochondrial SARDH gene in children with sarcosinemia or in mice with Sardh deletion leads to cognitive deficits. Hence, we conclude that endogenous formaldehyde regulates learning and memory via the NMDA receptor.

New insight into Alzheimer's disease: Light reverses Aß-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice.

INTRODUCTION: Pharmacological therapies to treat Alzheimer's disease (AD) targeting "Aß" have failed for over 100 years. Low levels of laser light can disassemble Aß. In this study, we investigated the mechanisms that Aß-blocked extracellular space (ECS) induces memory disorders in APP/PS1 transgenic mice and addressed whether red light (RL) at 630 nm rescues cognitive decline by reducing Aß-disturbed flow of interstitial fluid (ISF). METHODS: We compared the heating effects on the brains of rats illuminated with laser light at 630, 680, and 810 nm for 40 minutes, respectively. Then, a light-emitting diode with red light at 630 nm (LED-RL) was selected to illuminate AD mice. The changes in the structure of ECS in the cortex were examined by fluorescent double labeling. The volumes of ECS and flow speed of ISF were quantified by magnetic resonance imaging. Spatial memory behaviors in mice were evaluated by the Morris water maze. Then, the brains were sampled for biochemical analysis. RESULTS: RL at 630 nm had the least heating effects than other wavelengths associated with ~49% penetration ratio into the brains. For the molecular mechanisms, Aß could induce formaldehyde (FA) accumulation by inactivating FA dehydrogenase. Unexpectedly, in turn, FA accelerated Aß deposition in the ECS. However, LED-RL treatment not only directly destroyed Aß assembly in vitro and in vivo but also activated FA dehydrogenase to degrade FA and attenuated FA-facilitated Aß aggregation. Subsequently, LED-RL markedly smashed Aß deposition in the ECS, recovered the flow of ISF, and rescued cognitive functions in AD mice. DISCUSSION: Aß-obstructed ISF flow is the direct reason for the failure of the developed medicine delivery from superficial into the deep brain in the treatment of AD. The phototherapy of LED-RL improves memory by reducing Aß-blocked ECS and suggests that it is a promising noninvasive approach to treat AD.

The Drainage of Interstitial Fluid in the Deep Brain is Controlled by the Integrity of Myelination.

In searching for the drainage route of the interstitial fluid (ISF) in the deep brain, we discovered a regionalized ISF drainage system as well as a new function of myelin in regulating the drainage. The traced ISF from the caudate nucleus drained to the ipsilateral cortex along myelin fiber tracts, while in the opposite direction, its movement to the adjacent thalamus was completely impeded by a barrier structure, which was identified as the converged, compact myelin fascicle. The regulating and the barrier effects of myelin were unchanged in AQP4-knockout rats but were impaired as the integrity of boundary structure of drainage system was destroyed in a demyelinated rat model. We thus proposed that the brain homeostasis was maintained within each ISF drainage division locally, rather than across the brain as a whole. A new brain division system and a new pathogenic mechanism of demyelination are therefore proposed.

The olfactory stimulation slows down the substance clearance in the extracellular space of the hippocampus in rat brain.

Accelerating the clearance of toxin in the brain extracellular space (ECS) has grown a promising strategy for treating some central nervous system diseases. As oldest sensory system, we know little about the influence of olfaction on the brain, but preclinical studies such as treatment of neurological diseases through it are in the ascendant. This makes it important to clarify the effects of olfaction on brain ECS and interstitial fluid (ISF) drainage. In this study, the effect of olfactory stimulation (eugenol, EUG) on ISF flow in hippocampus and its association with aquaporin 4 (Aqp4) had been investigated. The results show that eugenol can significantly increase the activity of hippocampal neurons, but reduce the clearance and diffusion rates of Gd-DTPA and A-594 in hippocampus. Similarly, eugenol inhalation slows down the rate of Gd-DTPA in CSF entering the hippocampus and its clearance. And knockout of Aqp4 gene aggravated these processes. In vitro results showed that after Aqp4 gene silencing, astrocytes grew slowly, with significantly decreased cells number, less nuclei, atrophied bodies and shorter processes. These results concluded that olfactory stimulation can change the ECS structure of the hippocampus, slow down the ISF drainage, and improve the function of neurons, while Aqp4 plays important roles.

The effects of dihydroxyphenyl lactic acid on alleviating blood-brain barrier injury following subarachnoid hemorrhage in rats.

BACKGROUND: In this study, the protective effects of 3,4-dihydroxyphenyl lactic acid (DLA) on blood-brain barrier (BBB) injury following subarachnoid hemorrhage (SAH) has been explored. METHODS: Male Sprague-Dawley rats (weight 300-350 g) were used to establish the SAH model using the endovascular perforation method. The animals were randomly divided into four groups: sham (n = 40), SAH (n = 46), SAH + vehicle (n = 44), and SAH + DLA (n = 40) treatment groups. At 1 h after SAH, either DLA (10 mg/kg) or normal saline (vehicle) was administered by femoral vein injection. The effects of DLA on mortality, neurological function, brain water content, and BBB were observed. Additionally, immunohistochemistry and western blot techniques were applied to investigate the mechanism of action of DLA. RESULTS: We found that the administration of DLA (10 mg/kg) following SAH could improve neurological functions, reduce brain water content, and maintain BBB integrity. The expression of pro-inflammatory and pro-apoptotic factors such as toll-like receptor 4 (TLR4), NF-κB (p-p65), tumor necrosis factor-α, p-p38 MAPK, p-p53, and caspase-3 were significantly increased after SAH. These same factors were markedly attenuated following treatment with DLA. CONCLUSIONS: These findings showed that DLA can alleviate BBB injury following SAH through its anti-inflammatory and anti-apoptotic effects via suppression of TLR4 and its downstream NF-κB and p38 MAPK pathways.

Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.

T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment1. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction2. However, the molecular mechanisms that underlie this dysfunction remain unclear. Here, using an in vitro T cell tolerance induction system in mice, we characterize genome-wide epigenetic and gene expression features in tolerant T cells, and show that they are distinct from effector and regulatory T cells. Notably, the transcription factor NR4A1 is stably expressed at high levels in tolerant T cells. Overexpression of NR4A1 inhibits effector T cell differentiation, whereas deletion of NR4A1 overcomes T cell tolerance and exaggerates effector function, as well as enhancing immunity against tumour and chronic virus. Mechanistically, NR4A1 is preferentially recruited to binding sites of the transcription factor AP-1, where it represses effector-gene expression by inhibiting AP-1 function. NR4A1 binding also promotes acetylation of histone 3 at lysine 27 (H3K27ac), leading to activation of tolerance-related genes. This study thus identifies NR4A1 as a key general regulator in the induction of T cell dysfunction, and a potential target for tumour immunotherapy.

Stimulation Modeling on Three-Dimensional Anisotropic Diffusion of MRI Tracer in the Brain Interstitial Space.

Purpose: To build a mathematical model based magnetic resonance (MR) method to simulate drug anisotropic distribution in vivo in the interstitial space (ISS) of the brain. Materials and Methods: An injection of signal intensity-related gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), which is an exogenous drug, was administered, and its diffusion was traced in the ISS of the brain using MRI. Dynamic MRI scans were performed to monitor and record the changes in signal intensity in each pixel of the region of interest. The transport parameters were calculated using the modified equation to simulate three-dimensional anisotropic diffusion, which was resolved using a Laplace transform and a linear regressive model. Results: After Gd-DTPA was introduced into the caudate nucleus, its distribution was demonstrated in real time. As the Gd-DTPA gradually cleared, the associated hyperintensity attenuated over time. The average diffusion coefficient (D) and the clearance rate constant (k) were (1.305 ± 0.364) × 10-4 mm2/s and (1.40 ± 0.206) × 10-5 s-1, respectively. Discussion: The combination of trace-based MRI and modified diffusion mathematical models can visualize and measure the three-dimensional anisotropic distribution of drugs in the ISS of the brain.

The Effect of Aquaporin-4 Knockout on Interstitial Fluid Flow and the Structure of the Extracellular Space in the Deep Brain.

It has been reported that aquaporin-4 (AQP4) deficiency impairs transportation between the cerebrospinal fluid and interstitial fluid (ISF) as well as the clearance of interstitial solutes in the superficial brain. However, the effect of AQP4 on ISF flow in the deep brain remains unclear. This study compared the brain ISF flow in the caudate nucleus and thalamus of normal rats (NO) and AQP4 knockout rats (KO) using tracer-based magnetic resonance imaging. The rate of brain ISF flow slowed to different degrees in the two regions of KO rats' brains. Compared with NO rats, the half-life of ISF in the thalamus of KO rats was significantly prolonged, with a corresponding decrease in the clearance coefficient. The tortuosity of the brain extracellular space (ECS) was unchanged in the thalamus of KO rats. In the caudate nucleus of KO rats, the volume fraction of the ECS and the diffusion coefficient were increased, with significantly decreased tortuosity; no significant changes in brain ISF flow were demonstrated. Combined with a change in the expression of glial fibrillary acidic protein and AQP4 in two brain regions, we found that the effect of AQP4 knockout on ISF flow and ECS structure in these two regions differed. This difference may be related to the distribution of astrocytes and the extent of AQP4 decline. This study provides evidence for the involvement of AQP4 in ISF transportation in the deep brain and provides a basis for the establishment of a pharmacokinetic model of the brain's interstitial pathway.