Genome-wide analysis of MYB transcription factor family and AsMYB1R subfamily contribution to ROS homeostasis regulation in Avena sativa under PEG-induced drought stress.

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

Autophagy induced by Schwann cell-derived exosomes promotes recovery after spinal cord injury in rats.

Spinal cord injury (SCI) is catastrophic to humans and society. However, there is currently no effective treatment for SCI. Autophagy is known to serve critical roles in both the physiological and pathological processes of the body, but its facilitatory and/or deleterious effects in SCI are yet to be completely elucidated. This study aimed to use primary Schwann cell-derived exosomes (SCDEs) to treat rats after SCI. In the present study, SCDEs were purified and their efficacy in ameliorating the components of SCI was examined. Using both in vivo and in vitro experiments, it was demonstrated that SCDEs increased autophagy and decreased apoptosis after SCI, which promoted axonal protection and the recovery of motor function. Furthermore, it was discovered that an increased number of SCDEs resulted in a decreased expression level of EGFR, which subsequently inhibited the Akt/mTOR signaling pathway, which upregulated the level of autophagy to ultimately induce microtubule acetylation and polymerization. Collectively, the present study identified that SCDEs could induce axonal protection after SCI by increasing autophagy and decreasing apoptosis, and it was suggested that this may involve the EGFR/Akt/mTOR signaling pathway.

Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (SCI) is a severely disabling disease that leads to loss of sensation, motor, and autonomic function. As exosomes have great potential in diagnosis, prognosis, and treatment of SCI because of their ability to easily cross the blood-brain barrier, the function of Schwann cell-derived exosomes (SCDEs) is still largely unknown. METHODS: A T10 spinal cord contusion was established in adult female mice. SCDEs were injected into the tail veins of mice three times a week for 4 weeks after the induction of SCI, and the control group was injected with PBS. High-resolution transmission electron microscope and western blot were used to characterize the SCDEs. Toll-like receptor 2 (TLR2) expression on astrocytes, chondroitin sulfate proteoglycans (CSPGs) deposition and neurological function recovery were measured in the spinal cord tissues of each group by immunofluorescence staining of TLR2, GFAP, CS56, 5-HT, and ß-III-tublin, respectively. TLR2f/f mice were crossed to the GFAP-Cre strain to generate astrocyte specific TLR2 knockout mice (TLR2-/-). Finally, western blot analysis was used to determine the expression of signaling proteins and IKKß inhibitor SC-514 was used to validate the involved signaling pathway. RESULTS: Here, we found that TLR2 increased significantly on astrocytes post-SCI. SCDEs treatment can promote functional recovery and induce the expression of TLR2 on astrocytes accompanied with decreased CSPGs deposition. The specific knockout of TLR2 on astrocytes abolished the decreasing CSPGs deposition and neurological functional recovery post-SCI. In addition, the signaling pathway of NF-κB/PI3K involved in the TLR2 activation was validated by western blot. Furthermore, IKKß inhibitor SC-514 was also used to validate this signaling pathway. CONCLUSION: Thus, our results uncovered that SCDEs can promote functional recovery of mice post-SCI by decreasing the CSPGs deposition via increasing the TLR2 expression on astrocytes through NF-κB/PI3K signaling pathway.

Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury.

Exosomes are nanometer-sized vesicles involved in intercellular communication, and they are released by various cell types. To learn about exosomes produced by Schwann cells (SCs) and to explore their potential function in repairing the central nervous system (CNS), we isolated exosomes from supernatants of SCs by ultracentrifugation, characterized them by electron microscopy and immunoblotting and determined their protein profile using proteomic analysis. The results demonstrated that Schwann cell-derived exosomes (SCDEs) were, on average, 106.5 nm in diameter, round, and had cup-like concavity and expressed exosome markers CD9 and Alix but not tumor susceptibility gene (TSG) 101. We identified a total of 433 proteins, among which 398 proteins overlapped with the ExoCarta database. According to their specific functions, we identified 12 proteins that are closely related to CNS repair and classified them by different potential mechanisms, such as axon regeneration and inflammation inhibition. Gene Oncology analysis indicated that SCDEs are mainly involved in signal transduction and cell communication. Biological pathway analysis showed that pathways are mostly involved in exosome biogenesis, formation, uptake and axon regeneration. Among the pathways, the neurotrophin, PI3K-Akt and cAMP signaling pathways played important roles in CNS repair. Our study isolated SCDEs, unveiled their contents, presented potential neurorestorative proteins and pathways and provided a rich proteomics data resource that will be valuable for future studies of the functions of individual proteins in neurodegenerative diseases.

IL-33/ST2 Axis Regulates Vasculogenic Mimicry via ERK1/2-MMP-2/9 Pathway in Melanoma.

BACKGROUND: Melanoma, an extremely malignant form of cancer, poses a significant health risk. Vasculogenic mimicry (VM), blood vessels formed by tumor cells instead of endothelial cells, is an important factor for the rapid progression of melanoma. Interleukin (IL)-33 is an inflammatory factor commonly found in the tumor microenvironment and plays an important role in the progression of many tumors. IL-33 acts on immune cells and tumor cells through its receptor ST2. This study hypothesized that IL-33 directly affects the progression of melanoma. OBJECTIVES: This study was designed to investigate the effect of IL-33 on VM of melanoma and its potential mechanism of action. METHODS: The expression of ST2 was evaluated in 66 cases of melanoma collected from human patients, and the differences were analyzed. In vitro experiments were conducted to study the effects of the IL-33/ST2 axis on cell migration and invasion and to elucidate possible mechanisms. RESULTS: ST2 expression is associated with that of matrix metalloproteinase (MMP)-2 and VM in melanoma of patients. IL-33 increases the abilities of proliferation, migration and invasion of melanoma cells and VM tube formation through ST2. IL-33 induces the production of MMP-2/9 via ERK1/2 phosphorylation. CONCLUSION: IL-33 can directly act on melanoma cells and promote its development.

Ketamine versus ketamine pluses atropine for pediatric sedation: A meta-analysis.

OBJECTIVES: The application of atropine for pediatric sedation in the emergency department remains controversial. Our objective was to perform a comprehensive review of the literature and assess the clinical indexes in groups with and without atropine use. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized and non-randomized studies that compared ketamine and ketamine plus atropine for pediatric sedation. The risk ratio with 95% confidence interval was calculated using either a fixed- or random-effects model according to the value of I2. RESULTS: One retrospective study and four randomized controlled trials were identified to compare the clinical indexes. For the clinical indexes, the ketamine plus atropine group had better outcomes than the ketamine group in hypersalivation (P<0.05), but indexes of rash and tachycardia were worse. The two methods of sedation were comparable for nausea, vomiting, desaturation, agitation and laryngospasm (P>0.05). CONCLUSIONS: Based on the current evidence, the group receiving atropine had reduced hypersalivation and increased rash and tachycardia; no differences were observed in nausea, vomiting, desaturation, agitation and laryngospasm between the two groups. Given that some of the studies were of low quality, additional high-quality randomized controlled trials should be conducted to further verify these findings.

Endoskeleton Soft Multi-Fingered Hand with Variable Stiffness.

The use of a soft multi-fingered hand in handling fragile objects has been widely acknowledged. Nevertheless, high flexibility often results in decreased load capacity, necessitating the need for variable stiffness. This article introduces a new soft multi-fingered hand featuring variable stiffness. The finger of the hand has three chambers and an endoskeleton mechanism. Two chambers facilitate bending and swinging motions, whereas the third adjusts stiffness. An endoskeleton mechanism is embedded in the third chamber, and the friction between its moving parts increases as negative air pressure rises, causing the finger's stiffness to increase. This mechanism can alter its stiffness in any configuration, which is particularly useful in manipulating irregular-shaped fragile objects post-grasping. The effectiveness of the proposed soft multi-fingered hand is validated through five experiments: stiffness adjustment, finger stiffening under a specific orientation, bulb screwing, heavy object lifting, and bean curd grasping. The results demonstrate that the proposed soft multi-fingered hand exhibits robust grasping capabilities for various fragile objects.

Senescence of endplate osteoclasts induces sensory innervation and spinal pain.

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

Senescence of endplate osteoclasts induces sensory innervation and spinal pain.

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

Maize plant height automatic reading of measurement scale based on improved YOLOv5 lightweight model.

Background: Plant height is a significant indicator of maize phenotypic morphology, and is closely related to crop growth, biomass, and lodging resistance. Obtaining the maize plant height accurately is of great significance for cultivating high-yielding maize varieties. Traditional measurement methods are labor-intensive and not conducive to data recording and storage. Therefore, it is very essential to implement the automated reading of maize plant height from measurement scales using object detection algorithms. Method: This study proposed a lightweight detection model based on the improved YOLOv5. The MobileNetv3 network replaced the YOLOv5 backbone network, and the Normalization-based Attention Module attention mechanism module was introduced into the neck network. The CioU loss function was replaced with the EioU loss function. Finally, a combined algorithm was used to achieve the automatic reading of maize plant height from measurement scales. Results: The improved model achieved an average precision of 98.6%, a computational complexity of 1.2 GFLOPs, and occupied 1.8 MB of memory. The detection frame rate on the computer was 54.1 fps. Through comparisons with models such as YOLOv5s, YOLOv7 and YOLOv8s, it was evident that the comprehensive performance of the improved model in this study was superior. Finally, a comparison between the algorithm's 160 plant height data obtained from the test set and manual readings demonstrated that the relative error between the algorithm's results and manual readings was within 0.2 cm, meeting the requirements of automatic reading of maize height measuring scale.

Flexible and wearable sensor for in situ monitoring of gallic acid in plant leaves.

Gallic acid (GA) is one of the main phenolic components naturally occurring in many plants and foods and has been a subject of increasing interest owing to its antioxidant and anti-mutagenic properties. This study introduces a novel flexible sensor designed for in situ detecting GA in plant leaves. The sensor employs a laser-induced graphene (LIG) flexible electrode, enhanced with MXene and molybdenum disulfide (MoS2) nanosheets. The MXene/MoS2/LIG flexible sensor not only demonstrates exceptional mechanical properties, covering a wide detection range of 1-1000 µM for GA, but also exhibits remarkable selectivity and stability. The as-prepared sensor was successfully applied to in situ determination of GA content in strawberry leaves under salt stress. This innovative sensor opens an attractive avenue for in situ measurement of metabolites in plant bodies with flexible electronics.

A fully automatic MRI-guided decision support system for lumbar disc herniation using machine learning.

Background: Normalized decision support system for lumbar disc herniation (LDH) will improve reproducibility compared with subjective clinical diagnosis and treatment. Magnetic resonance imaging (MRI) plays an essential role in the evaluation of LDH. This study aimed to develop an MRI-based decision support system for LDH, which evaluates lumbar discs in a reproducible, consistent, and reliable manner. Methods: The research team proposed a system based on machine learning that was trained and tested by a large, manually labeled data set comprising 217 patients' MRI scans (3255 lumbar discs). The system analyzes the radiological features of identified discs to diagnose herniation and classifies discs by Pfirrmann grade and MSU classification. Based on the assessment, the system provides clinical advice. Results: Eventually, the accuracy of the diagnosis process reached 95.83%. An 83.5% agreement was observed between the system's prediction and the ground-truth in the Pfirrmann grade. In the case of MSU classification, 95.0% precision was achieved. With the assistance of this system, the accuracy, interpretation efficiency and interrater agreement among surgeons were improved substantially. Conclusion: This system showed considerable accuracy and efficiency, and therefore could serve as an objective reference for the diagnosis and treatment procedure in clinical practice.

LF-NMR/MRI Determination of Different 6-Benzylaminopurine Concentrations and Their Effects on Soybean Moisture.

In this study, we aimed to clarify the distribution and dynamics of water in the Xudou 20 soybean cultivar post-germination after culturing plants with various concentrations of 6-benzylaminopurine (6-BA). Low-field nuclear magnetic resonance and magnetic resonance imaging (LF-NMR/MRI), as well as principal component analysis (PCA), were used for the investigation. Results showed that low concentrations of 6-BA promoted soybean germination and high concentrations inhibited soybean germination, with 5 mg/l of 6-BA producing the most optimal conditions for growth. Moreover, the T 22 determination of weakly bound water increased with increasing 6-BA concentration, and the PCA effectively distinguished soybeans cultured at different 6-BA concentrations. This study provides a method for the rapid detection of 6-BA concentration in bean sprouts and provides theoretical support and bean sprout quality assessment.

Silencing ATF3 Might Delay TBHP-Induced Intervertebral Disc Degeneration by Repressing NPC Ferroptosis, Apoptosis, and ECM Degradation.

Intervertebral disc degeneration (IDD), being the predominant root cause of lower back pain, has led to an enormous socioeconomic burden in the world. Ferroptosis is an iron-dependent nonapoptotic and nonpyroptotic programmed cell death associated with an increase in reactive oxygen species (ROS), which has been implicated in the pathogenesis of IDD. Activation transcription factor 3 (ATF3) is widely reported to promote ferroptosis and apoptosis in multiple diseases, but its roles and underlying regulatory mechanism in IDD have not been identified. FAoptosis is defined as a mixed cell death consisting of ferroptosis and apoptosis. The loss- and gain-of-function experiments demonstrated that ATF3 positively regulated tert-butyl hydroperoxide- (TBHP-) induced nucleus pulposus cell (NPC) FAoptosis, ROS production, inflammatory response, and extracellular matrix (ECM) degradation. Furthermore, silencing ATF3 ameliorated the progression of IDD in vivo, whereas its overexpression showed the opposite phenotype. Bioinformatics analysis and molecular experiments corroborated that ATF3 is a direct target of miR-874-3p, suggesting that the upregulation of ATF3 in IDD might be caused at least in part due to the downregulation of miR-874-3p in IDD, thereby relieving the inhibition of ATF3 by miR-874-3p. The findings revealed that ATF3 has the potential to be used as a promising therapeutic target against IDD.

Periosteal CD68+ F4/80+ Macrophages Are Mechanosensitive for Cortical Bone Formation by Secretion and Activation of TGF-ß1.

Mechanical force regulates bone density, modeling, and homeostasis. Substantial periosteal bone formation is generated by external mechanical stimuli, yet its mechanism is poorly understood. Here, it is shown that myeloid-lineage cells differentiate into subgroups and regulate periosteal bone formation in response to mechanical loading. Mechanical loading on tibiae significantly increases the number of periosteal myeloid-lineage cells and the levels of active transforming growth factor ß (TGF-ß), resulting in cortical bone formation. Knockout of Tgfb1 in myeloid-lineage cells attenuates mechanical loading-induced periosteal bone formation in mice. Moreover, CD68+ F4/80+ macrophages, a subtype of myeloid-lineage cells, express and activate TGF-ß1 for recruitment of osteoprogenitors. Particularly, mechanical loading induces the differentiation of periosteal CD68+ F4/80- myeloid-lineage cells to the CD68+ F4/80+ macrophages via signaling of piezo-type mechanosensitive ion channel component 1 (Piezo1) for TGF-ß1 secretion. Importantly, CD68+ F4/80+ macrophages activate TGF-ß1 by expression and secretion of thrombospondin-1 (Thbs1). Administration of Thbs1 inhibitor significantly impairs loading-induced TGF-ß activation and recruitment of osteoprogenitors in the periosteum. The results suggest that periosteal myeloid-lineage cells respond to mechanical forces and consequently produce and activate TGF-ß1 for periosteal bone formation.

Inhibition of Integrin αvß6 Activation of TGF-ß Attenuates Tendinopathy.

Tendinopathy is a common tendon disorder that causes pain and impairs function. It is the most common reason for consultation with musculoskeletal specialists. The available therapies for tendinopathy are limited in number and efficacy and have unclear cellular and molecular mechanisms. Here it is shown that transforming growth factor-beta (TGF-ß) activated by integrin αvß6 promotes tendinopathy in mice. Excessive active TGF-ß is found during tendinopathy progression, which led to tenocytes' phenotype transition to chondrocytes. Transgenic expression of active TGF-ß in tendons induced spontaneous tendinopathy, whereas systemic injection of a TGF-ß neutralizing antibody attenuated tendinopathy. Inducible knockout of the TGF-ß type 2 receptor gene (Tgfbr2) in tenocytes inhibited tendinopathy progression in mice. Moreover, it is found that integrin αvß6 induces TGF-ß activation in response to mechanical load in tendons. Conditional knockout of the integrin αv gene in tendons prevented tendinopathy in mice. The study suggests that integrin αvß6 activation of TGF-ß is the mechanism of tendinopathy, and that integrin αvß6 may be a therapeutic target in tendinopathy.

Circ_0004354 might compete with circ_0040039 to induce NPCs death and inflammatory response by targeting miR-345-3p-FAF1/TP73 axis in intervertebral disc degeneration.

The abnormal function of nucleus pulposus cells (NPCs) plays a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Recent studies have demonstrated that circular RNAs (circRNAs) are involved in the pathological process of IVDD by regulating NPCs' function. Nevertheless, the investigation on circRNA-circRNA interaction has not yet been reported. Here, we identified the top upregulated circ_0040039 and circ_0004354 in IVDD, derived from the syntrophin beta 2 gene but had different degrees of biological functions. Accumulating studies have reported PANoptosis is composed of apoptosis, pyroptosis, and necroptosis. Based on this, we think there should be a new pro-inflammatory cell death PAoptosis in the form of apoptosis and pyroptosis. Circ_0004354 might compete with circ_0040039 to induce the development of IVDD by modulating miR-345-3p-FAF1/TP73 axis-mediated PAoptosis, inflammatory response, growth inhibition, and ECM degradation of NPCs. Thus, these findings offer a novel insight into the circRNAs-mediated posttranscriptional regulatory network in IVDD, contributing to further clarification of the pathological mechanism of IVDD to develop a promising therapeutic target for IVDD diseases.

Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models.

Bone formation induced by divalent metal cations has been widely reported; however, the underlying mechanism is unclear. Here we report that these cations stimulate skeleton interoception by promoting prostaglandin E2 secretion from macrophages. This immune response is accompanied by the sprouting and arborization of calcitonin gene-related polypeptide-α+ nerve fibers, which sense the inflammatory cue with PGE2 receptor 4 and convey the interoceptive signals to the central nervous system. Activating skeleton interoception downregulates sympathetic tone for new bone formation. Moreover, either macrophage depletion or knockout of cyclooxygenase-2 in the macrophage abolishes divalent cation-induced skeleton interoception. Furthermore, sensory denervation or knockout of EP4 in the sensory nerves eliminates the osteogenic effects of divalent cations. Thus, our study reveals that divalent cations promote bone formation through the skeleton interoceptive circuit, a finding which could prompt the development of novel biomaterials to elicit the therapeutic power of these divalent cations.

Inhibition of TGF-ß repairs spinal cord injury by attenuating EphrinB2 expressing through inducing miR-484 from fibroblast.

Spinal cord injury (SCI) can lead to severe loss of motor and sensory function with high disability and mortality. The effective treatment of SCI remains unknown. Here we find systemic injection of TGF-ß neutralizing antibody induces the protection of axon growth, survival of neurons, and functional recovery, whereas erythropoietin-producing hepatoma interactor B2 (EphrinB2) expression and fibroblasts distribution are attenuated. Knockout of TGF-ß type II receptor in fibroblasts can also decrease EphrinB2 expression and improve spinal cord injury recovery. Moreover, miR-488 was confirmed to be the most upregulated gene related to EphrinB2 releasing in fibroblasts after SCI and miR-488 initiates EphrinB2 expression and physical barrier building through MAPK signaling after SCI. Our study points toward elevated levels of active TGF-ß as inducer and promoters of fibroblasts distribution, fibrotic scar formation, and EphrinB2 expression, and deletion of global TGF-ß or the receptor of TGF-ß in Col1α2 lineage fibroblasts significantly improve functional recovery after SCI, which suggest that TGF-ß might be a therapeutic target in SCI.

Potential of different cells-derived exosomal microRNA cargos for treating spinal cord injury.

Spinal cord injury (SCI) is a disastrous situation that affects many patients worldwide. A profound understanding of the pathology and etiology of SCI is of great importance in inspiring new therapeutic concepts and treatment. In recent years, exosomes, which are complex lipid membrane structures secreted nearly by all kinds of plants and animal cells, can transport their valuable cargoes (e.g., proteins, lipids, RNAs) to the targeted cells and exert their communication and regulation functions, which open up a new field of treatment of SCI. Notably, the exosome's advantage is transporting the carried material to the target cells across the blood-brain barrier and exerting regulatory functions. Among the cargoes of exosomes, microRNAs, through the modulation of their mRNA targets, emerges with great potentiality in the pathological process, diagnosis and treatment of SCI. In this review, we discuss the role of miRNAs transported by different cell-derived exosomes in SCI that are poised to enhance SCI-specific therapeutic capabilities of exosomes.