RESUMEN
NK cell education, a term describing a process for NK cell acquisition of functional competence, is primarily achieved by self-MHC-I-specific inhibitory receptors. In this study, we have demonstrated that SLAM family receptors (SFRs) redundantly expressed on hematopoietic cells function as self-specific activation receptors critical for NK cell education. To overcome gene redundancy, we generated mice simultaneously lacking seven SFRs, revealing that NK-cell-mediated rejection of semi-allogeneic hematopoietic cells largely depended on the presence of SFRs on target cells. This stimulatory effect was determined by the presence of SFR-coupled adaptors; however, SFR-deficient mice displayed enhanced reactivity to hematopoietic cells. These findings demonstrate that SFRs endow NK cells with an ability to kill hematopoietic cells during the effector phase; however, the sustained engagement of SFRs can desensitize NK cell responses during an education process. Therefore, self-specific activating ligands may be "tolerogens" for NK cells, akin to self-antigens that induce T cell tolerance.
Asunto(s)
Rechazo de Injerto/inmunología , Trasplante de Células Madre Hematopoyéticas , Células Asesinas Naturales/inmunología , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismo , Tolerancia al Trasplante , Animales , Autoantígenos/inmunología , Diferenciación Celular , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Citotoxicidad Inmunológica , Humanos , Isoantígenos/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genéticaRESUMEN
Although the sources of molecular hydrogen (H2) synthesis in plants remain to be fully elucidated, ample evidence shows that plant-based H2 can regulate development and stress responses. Here, we present genetic and molecular evidence indicating that nitrate reductase (NR) might be a target of H2 sensing that positively regulates nitrogen use efficiency (NUE) and seed size in Arabidopsis (Arabidopsis thaliana). The expression level of NR and changes of NUE under control and, in particular, low nitrogen supply were positively associated with H2 addition supplied exogenously or through genetic manipulation. The improvement in nitrate assimilation achieved by H2 was also mediated via NR dephosphorylation. H2 control of seed size was impaired by NR mutation. Further genetic evidence revealed that H2, NR, and nitric oxide can synergistically regulate nitrate assimilation in response to N starvation conditions. Collectively, our data indicate that NR might be a target for H2 sensing, ultimately positively regulating nitrate uptake and seed size. These results provide insights into H2 signaling and its functions in plant metabolism.
Asunto(s)
Arabidopsis , Nitratos , Nitrato-Reductasa/genética , Nitrato-Reductasa/metabolismo , Nitratos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas/metabolismo , Semillas/genética , Semillas/metabolismo , Nitrógeno/metabolismo , HidrógenoRESUMEN
KEY MESSAGE: Endogenous cGMP operates downstream of CH4 control of adventitious rooting, following by the regulation in the expression of cell cycle regulatory and auxin signaling-related genes. Methane (CH4) is a natural product from plants and microorganisms. Although exogenously applied CH4 and cyclic guanosine monophosphate (cGMP) are separately confirmed to be involved in the control of adventitious root (AR) formation, the possible interaction still remains elusive. Here, we observed that exogenous CH4 not only rapidly promoted cGMP synthesis through increasing the activity of guanosine cyclase (GC), but also induced cucumber AR development. These responses were obviously impaired by the removal of endogenous cGMP with two GC inhibitors. Anatomical evidence showed that the emerged stage (V) among AR primordia development might be the main target of CH4-cGMP module. Genetic evidence revealed that the transgenic Arabidopsis that overexpressed the methyl-coenzyme M reductase gene (MtMCR) from Methanobacterium thermoautotrophicum not only increased-cGMP production, but also resulted in a pronounced AR development compared to wild-type (WT), especially with the addition of CH4 or the cell-permeable cGMP derivative 8-Br-cGMP. qPCR analysis confirmed that some marker genes associated with cell cycle regulatory and auxin signaling were closely related to the brand-new CH4-cGMP module in AR development. Overall, our results clearly revealed an important function of cGMP in CH4 governing AR formation by modulating auxin-dependent pathway and cell cycle regulation.
Asunto(s)
Arabidopsis , Cucumis sativus , Metano/metabolismo , Arabidopsis/genética , Ácidos Indolacéticos/farmacología , Ácidos Indolacéticos/metabolismo , Transducción de Señal , Cucumis sativus/genética , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND AND OBJECTIVE: In the process of robotic fracture reduction, there is a risk of unintended collision of broken bones, which is not conducive to ensuring the safety of the reduction system. In order to solve this problem, this paper proposed a vibration-based collision detection method for fracture reduction process. METHODS: Based on the two degree-of-freedom vibration response model, the factors affecting the respond of the vibration, including the excitation voltage, the clamping length at the proximal and distal ends, the mass and tensile force of the soft tissue, were obtained. The effects of these factors on the vibration transfer performance of broken bones and soft tissue were investigated by single factor experiments. RESULTS: The results showed that, in terms of peak value, the increase of excitation voltage would make the vibration amplitude increase linearly, and the increase of soft tissue mass and tension increased the vibration transmission capacity of soft tissue in the frequency range of 500-1000 Hz. In terms of peak frequency, the clamping length at the distal end had the greatest influence, which reached 74 Hz, followed by 45 Hz at the proximal end. While the influence of other factors was little. According to single factor experiments, the excitation frequency in the verification experiments was determined as 677 Hz. Under the vibration interference with the acceleration amplitude of 1.2 G, this method achieved correct detection. CONCLUSION: This research developed a broken bone collision detection method based on vibration excitation. The method can correctly detect the collision of broken bones with strong anti-interference ability. It is of great significance to improve the safety of fracture reduction process.
Asunto(s)
Fracturas Óseas , Robótica , Humanos , Vibración , Huesos , Fijación de FracturaRESUMEN
In medical surgery, bone drilling is an inevitable procedure. The thermal necrosis in the drilling process can affect post-operative recovery. In this study, the method of drill bit precooling is proposed in bone drilling with robot assisted system. The influence of process parameters on the drilling temperature were investigated and analyzed. The results showed that the method of drill bit precooling could reduce the drilling temperature. The drill bit starting temperature and the feed rate were more important parameters on the drilling temperature compared with rotational speed and cooling length of the drill bit. The quadratic regression model obtained from response surface experiments can predicted the drilling temperature correctly under the range of process parameters in this study. The optimal parameter combination is rotational speed = 1610 rpm, feed rate = 0.5 mm/s, the starting temperature of drill bit = 8°C, and the cooling length = 34.8 mm. The results provide an effective method to reduce thermal necrosis of bone cells in drilling.
Asunto(s)
Procedimientos Ortopédicos , Procedimientos Quirúrgicos Robotizados , Robótica , Huesos/cirugía , Calor , Humanos , Necrosis , TemperaturaRESUMEN
Improvement of the storage quality of rice is a critical challenge for the scientific community. This study assesses the effects of the irrigation with hydrogen nanobubble water (HNW) on the storage quality of rice (Oryza sativa 'Huruan1212'). Compared with ditch water control, after one year of storage at 25 °C and 70% RH, the HNW-irrigated rice had higher contents of essential amino acids, especially lysine. Importantly, the generation of off-flavors in the stored rice was significantly decreased, which was confirmed by the lower levels of volatile substances, including pentanal, hexanal, heptanal, octanal, 1-octen-3-ol, and 2-heptanone. The subsequent results showed that the HNW-irrigated rice not only retained lower levels of free fatty acid values, but also had increased antioxidant capacity and decreased lipoxygenase activity and transcripts, thus resulting in decreased lipid peroxidation. This study opens a new window for the practical application of HNW irrigation in the production and subsequent storage of crops.
RESUMEN
Argon, a non-polar molecule, easily diffuses into deeper tissue and interacts with larger proteins, protein cavities, or even receptors. Some of the biological effects of argon, notably its activity as an antioxidant, have been revealed in animals. However, whether and how argon influences plant physiology remains elusive. Here, we provide the first report that argon can enable plants to cope with salinity toxicity. Considering the convenience of the application, argon gas was dissolved into water (argon-rich water (ARW)) to investigate the argon's functioning in phenotypes of alfalfa seed germination and seedling growth upon salinity stress. The biochemical evidence showed that NaCl-decreased α/ß-amylase activities were abolished by the application of ARW. The qPCR experiments confirmed that ARW increased NHX1 (Na+/H+ antiporter) transcript and decreased SKOR (responsible for root-to-shoot translocation of K+) mRNA abundance, the latter of which could be used to explain the lower net K+ efflux and higher K accumulation. Subsequent results using non-invasive micro-test technology showed that the argon-intensified net Na+ efflux and its reduced Na accumulation resulted in a lower Na+/K+ ratio. NaCl-triggered redox imbalance and oxidative stress were impaired by ARW, as confirmed by histochemical and confocal analyses, and increased antioxidant defense was also detected. Combined with the pot experiments in a greenhouse, the above results clearly demonstrated that argon can enable plants to cope with salinity toxicity via reestablishing ion and redox homeostasis. To our knowledge, this is the first report to address the function of argon in plant physiology, and together these findings might open a new window for the study of argon biology in plant kingdoms.
RESUMEN
BACKGROUND AND OBJECTIVE: The application of robot technology in fracture reduction ensures the minimal invasiveness and accurate operation process. Most of the existing robot assisted fracture reduction systems don't have the function of bone collision detection, which is very important for system safety. In view of the deficiencies in the research of this field, a broken bone collision detection method based on the slope ratio of force curve was proposed in this paper, which could realize the real-time detection. METHODS: In order to analyze the factors influencing the slope of force curve, a collision mechanical model based on three-element viscoelastic model was established. The effects of four factors on the slope ratio of the force curve were studied based on the mechanical model. The proposed collision detection model was analyzed in detail. By drawing slope ratio curves under various experimental conditions, the universality of the collision detection model was proved; by comparative simulation, the differences between the slope ratio curves before and after optimization were analyzed. The factors that affect the performance of the detection model were also analyzed. RESULTS: The results of collision experiments show that the increase of moving speed of distal bone and soft tissue mass reduces the slope ratio, while the increase of collision angle increases the slope ratio. In the verification experiment, the minimum main peak of KRopt curve is 14.16 and the maximum is 220.7, the maximum interference value before the peak is 6.1. When the detection threshold is 10, the model can detect the collision state of the broken bone. It is also proved that after optimization, the model can effectively filter out invalid waveforms and reduce the occurrence of false detections. When a=5 and b=40, the detection model has sufficient stability and a low detection time delay. CONCLUSION: This research developed a broken bone collision detection method based on the slope ratio of the force curve. After optimization, the method has good adaptability under a variety of experimental conditions. The collision of broken bones can be judged by setting an appropriate detection threshold. The application of this method in the robot fracture reduction system will improve the safety of the system.
Asunto(s)
Fracturas Óseas , Robótica , Huesos , Simulación por Computador , Fijación de Fractura , HumanosRESUMEN
BACKGROUND AND OBJECTIVE: Percutaneous puncture with flexible needle has important value in clinical application for its low trauma and flexible path. However, it is difficult to guarantee accuracy and avoid obstacles in puncture process. Therefore, developing a viable path planning method is particularly important. In this research, the bending deformation law of flexible needles during puncture was studied and the puncture path was planned to provide a feasible method for clinical application of flexible needles. METHODS: According to the researchs that have been conducted, the path of the flexible needle in the tissue could be considered as a circular arc stitching. This research studied the calculation method of arc radius and obtained its actual value by the puncture experiments. Based on the arc model, the spatial transformation method of three-dimensional path planning was studied. In addition, a simplified particle swarm optimization (PSO) was applied into the process of path planning by changing the central angle of arc and the rotation angle of the needle body. RESULTS: The results of Experiment 1 showed that the path radius of the flexible needle pierced into gelatin prosthesis was influenced by four parameters, which were needle diameter, tip angle, puncture speed and the weight ratio of gelatin powder. As the needle diameter and tip angle increased, the radius of needle path tended to increase, but when the puncture speed and gelatin mass ratio increased, the radius of needle path decreased. The results of Experiment 2 showed that the distances of needle tip apart from target point were 3.2 mm (barrier-free experiments) and 1.8 mm (obstacle experiments). CONCLUSIONS: This research links the intelligent algorithm with the flexible needle puncture tissue process, which has high value in future clinical application. By setting the correct boundary conditions and parameters, the flexible needle can be planned to reach the target point accurately.
Asunto(s)
Agujas , Punciones , AlgoritmosRESUMEN
Classical signaling lymphocyte activating molecule (SLAM) family receptors are abundant within many types of immune cells, whereas the nonclassical SLAM family receptors SLAMF8 and SLAMF9, which uniquely lack cytoplasmic signaling motifs, are highly expressed by myeloid cells. Due to the potential redundancy, whether these two receptors regulate macrophage function remains largely unknown. Here, we show that SLAMF8 and SLAMF9 co-regulate macrophage-mediated liver inflammation. To overcome the redundancy, we generated mice that simultaneously lacked SLAMF8 and SLAMF9 using CRISPR-Cas9 technology. Although macrophage differentiation was not altered by the combined deficiency of SLAMF8 and SLAMF9, the loss of these two receptors significantly protected against lipopolysaccharide (LPS)-induced liver injury. SLAMF8 and SLAMF9 double-deficient mice had a prolonged survival rate and less infiltration of inflammatory cells. The depletion of macrophages using clodronate liposomes abolished the effects of SLAMF8 and SLAMF9 deficiencies on LPS-induced liver injury, which demonstrates that these receptors are required for macrophage activation following LPS challenge. Moreover, the deficiency of SLAMF8 and SLAMF9 suppressed the secretion of inflammatory cytokines by downregulating the expression of Toll-like receptor-4 (TLR4), a receptor that specifically binds LPS, which led to decreased mitogen-activated protein kinases (MAPK) signaling activation. Notably, combined injections of truncated extracellular SLAMF8 and SLAMF9 proteins significantly alleviated LPS-induced liver injury. Thus, our findings provide insights into the role of SLAMF8 and SLAMF9 in endotoxin-induced liver injury and suggest that SLAMF8 and SLAMF9 are potential therapeutic targets for acute hepatic injury.
Asunto(s)
Regulación hacia Abajo/genética , Hepatitis/etiología , Hepatitis/inmunología , Lipopolisacáridos/efectos adversos , Sistema de Señalización de MAP Quinasas/genética , Macrófagos/inmunología , Proteínas de la Membrana/deficiencia , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/deficiencia , Receptor Toll-Like 4/metabolismo , Animales , Sistemas CRISPR-Cas , Diferenciación Celular/genética , Citocinas/metabolismo , Hepatitis/metabolismo , Hepatitis/mortalidad , Activación de Macrófagos/genética , Macrófagos/metabolismo , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Células RAW 264.7 , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Tasa de Supervivencia , TransfecciónRESUMEN
Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (TFH) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in TFH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient TFH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP.