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Long-term inflammation and impaired angiogenesis are the main reasons for the difficulty of diabetic wound healing. What to do to effectively promote vascular endothelial cell response and immune cell reprogramming is the key to diabetic skin healing. However, contemporary therapies cannot simultaneously coordinate the promotion of vascular endothelial cells and macrophage polarization, which leads to an increased rate of disability in patients with chronic diabetes. Therefore, we developed a method of repair composed of self-assembling Prussian blue nanoenzymes, which achieved synergistic support for the immune microenvironment, and also contributed to macrophage polarization in the tissue regeneration cycle, and enhanced vascular endothelial cell activity. The template hydrothermal synthesis PB-Zr nanoplatform was prepared and locally applied to wounds to accelerate wound healing through the synergistic effect of reactive oxygen species (ROS). PB-Zr significantly normalized the wound microenvironment, thereby inhibiting ROS production and inflammatory response, which may be because it inhibited the M1 polarization of macrophages in a rat model of wound. PB-Zr treatment significantly promoted the activity of vascular endothelial cells, which better promoted the growth and regeneration of other tissues in the body. The results confirmed the disease microenvironment of PB-Zr-mediated wound therapy and indicated its application in other inflammation-related diseases.
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Whiplash injury, commonly occurring as a result of car accidents, represents a significant public health concern. However, to date, no comprehensive study has utilized bibliometric approaches to analyze all published research on whiplash injury. Therefore, our study aims to provide an overview of current trends and the global research landscape using bibliometrics and visualization software. We performed a bibliometric analysis of the data retrieved and extracted from the Web of Science Core Collection database in whiplash injury research up to December 31, 2022. Research articles were assessed for specific characteristics, such as year of publication, country/region, institution, author, journal, field of study, references, and keywords. We identified 1751 research articles in the analysis and observed a gradual growth in the number of publications and references. The United States (379 articles, 21.64%), Canada (309 articles, 17.65%), and Australia (280 articles, 16.00%) emerged as the top-contributing countries/regions. Among institutions, the University of Queensland (169 articles, 9.65%) and the University of Alberta (106 articles, 6.05%) demonstrated the highest productivity. "Whiplash," "Neck Pain," "Cervical Spine Disease," and "Whiplash-associated Disorders" are high-frequency keywords. Furthermore, emerging areas of research interest included traumatic brain injury and mental health issues following whiplash injury. The number of papers and citations has increased significantly over the past 2 decades. Whiplash injury research is characteristically multidisciplinary in approach, involving the fields of rehabilitation, neuroscience, and spinal disciplines. By identifying current research trends, our study offers valuable insights to guide future research endeavors in this field.
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Bibliometría , Lesiones por Latigazo Cervical , Lesiones por Latigazo Cervical/epidemiología , Humanos , Salud Global , Accidentes de Tránsito/estadística & datos numéricosRESUMEN
Traumatic spinal cord injury (SCI), often resulting from external physical trauma, initiates a series of complex pathophysiological cascades, with severe cases leading to paralysis and presenting significant clinical challenges. Traditional diagnostic and therapeutic approaches, particularly X-ray imaging, are prevalent in clinical practice, yet the limited efficacy and notable side effects of pharmacological treatments at the injury site continue to pose substantial hurdles. Addressing these challenges, recent advancements have been made in the development of multifunctional nanotechnology and synergistic therapies, enhancing both the efficacy and safety of radiographic techniques. In this context, we have developed an innovative nerve regeneration and neuroprotection nanoplatform utilizing an X-ray-triggered, on-demand RuFe metal-organic framework (P-RuFe) for SCI recovery. This platform is designed to simulate the enzymatic activities of catalase and superoxide dismutase, effectively reducing the production of reactive oxygen species, and to remove free radicals and reactive nitrogen species, thereby protecting cells from oxidative stress-induced damage. In vivo studies have shown that the combination of P-RuFe and X-ray treatment significantly reduces mortality in SCI mouse models and promotes spinal cord repair by inhibiting glial cell proliferation and neuroinflammation. P-RuFe demonstrates excellent potential as a safe, effective scavenger of reactive oxygen and nitrogen species, offering good stability, biocompatibility, and high catalytic activity, and thus holds promise for the treatment of inflammation-related diseases.
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Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H2O2-induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible.
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Exosomas , Inmunoterapia , Macrófagos , Nanopartículas , Traumatismos de la Médula Espinal , Animales , Exosomas/trasplante , Exosomas/metabolismo , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/inmunología , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Ratones , Nanopartículas/química , Inmunoterapia/métodos , Ferrocianuros/química , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Humanos , Microglía/inmunología , Células RAW 264.7 , Apoptosis/efectos de los fármacosRESUMEN
Mitochondrial injury, neuronal apoptosis and phenotypic transformation of macrophages are the main mechanisms of spinal cord injury. Based on the Prussian blue nanomase's strong ability to clear free radicals, the treatment of spinal cord injury with nano-zirconium (Pb-Zr) was carried out. The disease treatment strategy based on nanomaterials has excellent therapeutic effect, and Prussian blue analogs have good therapeutic properties, so the application prospects of Prussian blue analogs is broad. From the point of view of Prussian blue content, improving the presence of zirconium in the microenvironment significantly increased the activity of Prussian blue. Prussian Blue zirconium significantly improved lipopolysaccharide (LPS) and interferon (IFN-γ) induced neuronal cell (pc12 cells) and macrophage dysfunction by improving oxidative stress, inflammation, and apoptosis in the microenvironment. It can promote the recovery of motor function after spinal cord injury. In vivo experiments, it shows that Prussian blue zirconium can improve inflammation, apoptosis and oxidative stress of spinal cord tissue, promote regenerative therapy after spinal cord injury, and improve motor function. Moreover, it has been reported that high-priced Zr4+ cations can regulate the deposition and nucleation behavior of Zn2+ in high-performance zinc metal anodes. Therefore, we propose the hypothesis that Pb-Zr modulates Zn2+ be used to promote recovery from spinal cord injury. The results show that nanomaterial is beneficial in the treatment of spinal cord injury. This study provides a good prospect for the application of spinal cord injury treatment. It also provides an important feasibility for subsequent clinical conversions.
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Ferrocianuros , Plomo , Traumatismos de la Médula Espinal , Ratas , Animales , Plomo/farmacología , Plomo/uso terapéutico , Circonio/uso terapéutico , Circonio/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Médula Espinal , Inflamación/tratamiento farmacológico , Zinc/uso terapéutico , Zinc/farmacologíaRESUMEN
Most legumes can form an endosymbiotic association with soil bacteria called rhizobia, which colonize specialized root structures called nodules where they fix nitrogen. To colonize nodule cells, rhizobia must first traverse the epidermis and outer cortical cell layers of the root. In most legumes, this involves formation of the infection thread, an intracellular structure that becomes colonized by rhizobia, guiding their passage through the outer cell layers of the root and into the newly formed nodule cells. In this brief review, we recount the early research milestones relating to the rhizobial infection thread and highlight two relatively recent advances in the symbiotic infection mechanism, the eukaryotically conserved 'MYB-AUR1-MAP' mitotic module, which links cytokinesis mechanisms to intracellular infection, and the discovery of the 'infectosome' complex, which guides infection thread growth. We also discuss the potential intertwining of the two modules and the hypothesis that cytokinesis served as a foundation for intracellular infection of symbiotic microbes.
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Fabaceae , Rhizobium , Fabaceae/microbiología , Bacterias , Simbiosis , Nódulos de las Raíces de las PlantasRESUMEN
Amphiphilic copolymers comprising hydrophilic segments of poly(ethylene glycol) and hydrophobic domains that are able to adhere to solid/liquid interfaces have proven to be versatile ingredients in formulated products for various types of applications. Recently, we have reported the successful synthesis of a copolymer designed for modifying the surface properties of polyesters as mimics for synthetic textiles. Using sum frequency generation (SFG) spectroscopy, it was shown that the newly developed copolymer adsorbs effectively on the targeted substrates even in the presence of surfactants as supplied by common detergents. In the present work, these studies were extended to evaluate the ability of the formed copolymer adlayers to passivate polyester surfaces against undesired deposition of bio(macro)molecules, as represented by fibrinogen as model protein foulants. In addition, SFG spectroscopy was used to elucidate the structure of fibrinogen at the interface between polyester and water. To complement the obtained data with an independent technique, analogous experiments were performed using quartz-crystal microbalance with dissipation monitoring for the detection of the relevant interfacial processes. Both methods give consistent results and deliver a holistic picture of brush copolymer adsorption on polyester surfaces and subsequent antiadhesive effects against proteins under different conditions representing the targeted application in home care products.
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Polímeros , Cuarzo , Adsorción , Análisis Espectral/métodos , Propiedades de Superficie , Poliésteres , Fibrinógeno/químicaRESUMEN
The purification and collection of various products from oil/water mixtures are routine procedures. However, the presence of emulsifiers that can displace other surface active components in the mixtures can significantly influence the efficiency of such procedures. Previously, we investigated interfacial mechanisms of zein protein-induced emulsification and the opposing surfactant-induced demulsification related to corn oil refinement. In this paper, we further investigated a different class of protein, glutelin, inside corn and proved that glutelin acts as an oil/water emulsifier in an acidic water environment. Furthermore, an extended surfactant's protein disordering and removal ability was tested and compared with a conventional surfactant. An extended surfactant contains a poly(propylene oxide) or poly(propylene oxide)-poly(ethylene oxide) chain inserted between the hydrophilic head and the hydrophobic tail. In this study, a nonlinear optical spectroscopic technique, sum frequency generation (SFG) vibration spectroscopy, was used to study the behavior of glutelin and extended as well as regular surfactants at the corn oil/water or aqueous solution interface. In most cases, the conventional surfactant shows better protein disordering or removal ability than the extended surfactant. However, with the addition of heat and salt to an extended surfactant solution, the experiment resulted in a substantial increase in the extended surfactant's protein disorder or removal ability.
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Surfactantes Pulmonares , Tensoactivos , Tensoactivos/química , Aceite de Maíz , Zea mays , Glútenes , Emulsionantes/química , LipoproteínasRESUMEN
AIM: To investigate the prevalence and factors associated with optic disc grey crescent (GC) in African Americans with glaucoma. METHODS: Stereo optic disc image features from subjects with glaucoma in the Primary Open-Angle African Ancestry Glaucoma Genetics Study were evaluated independently by non-physician graders and discrepancies adjudicated by an ophthalmologist. Risk factors for GC were evaluated by logistic regression models with intereye correlation accounted for by generalised estimating equations. Adjusted ORs (aORs) were generated. RESULTS: GC was present in 227 (15%) of 1491 glaucoma cases, with 57 (3.82%) bilateral and 170 (11.4%) unilateral. In multivariable analysis, factors associated with GC were younger age (aOR 1.27, 95% CI 1.11 to 1.43 for every decade younger in age, p=0.001), diabetes (aOR 1.46, 95% CI 1.09 to 1.96, p=0.01), optic disc tilt (aOR 1.84, 95% CI 1.36 to 2.48, p<0.0001), a sloping retinal region adjacent to the outer disc margin (aOR 2.37, 95% CI 1.74 to 3.32, p<0.0001) and beta peripapillary atrophy (aOR 2.32, 95% CI 1.60 to 3.37, p<0.0001). Subjects with GC had a lower mean (SD) value of the ancestral component q0 than those without GC (0.22 (0.15) vs 0.27 (0.20), p=0.001), consistent with higher degrees of African ancestry. CONCLUSIONS: More than 1 in 10 glaucoma cases with African ancestry have GC, occurring more frequently in younger subjects, higher degrees of African ancestry and diabetes. GC was associated with several ocular features, including optic disc tilt and beta peripapillary atrophy. These associations should be considered when evaluating black patients with primary open-angle glaucoma.
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Glaucoma de Ángulo Abierto , Glaucoma , Disco Óptico , Enfermedades del Nervio Óptico , Humanos , Disco Óptico/diagnóstico por imagen , Glaucoma de Ángulo Abierto/epidemiología , Enfermedades del Nervio Óptico/patología , Prevalencia , Glaucoma/patología , Atrofia/patologíaRESUMEN
Polymers containing poly(ethylene glycol) (PEG) units can exhibit excellent antifouling properties, which have been proposed/used for coating of biomedical implants, separation membranes, and structures in marine environments, as well as active ingredients in detergent formulations to avoid soil redepositioning in textile laundry. This study aimed to elucidate the molecular behavior of a copolymer poly(MMA-co-MPEGMA) containing antiadhesive PEG side chains and a backbone of poly(methyl methacrylate), at a buried polymer/solution interface. Polyethylene terephthalate (PET) was used as a substrate to model polyester textile surfaces. Sum frequency generation (SFG) vibrational spectroscopy was applied to examine the interfacial behavior of the copolymer at PET/solution interfaces in situ and in real time. Complementarily, copolymer adsorption on PET and subsequent antiadhesion against protein foulants were probed by quartz-crystal microbalance experiments with dissipation monitoring (QCM-D). Both applied techniques show that poly(MMA-co-MPEGMA) adsorbs significantly to the PET/solution interface at bulk polymer solution concentrations as low as 2 ppm, while saturation of the surface was reached at 20 ppm. The hydrophobic MMA segments provide an anchor for the copolymer to bind onto PET in an ordered way, while the pendant PEG segments are more disordered but contain ordered interfacial water. In the presence of considerable amounts of dissolved surfactants, poly(MMA-co-MPEGMA) could still effectively adsorb on the PET surface and remained stable at the surface upon washing with hot and cold water or surfactant solution. In addition, it was found that adsorbed poly(MMA-co-MPEGMA) provided the PET surface with antiadhesive properties and could prevent protein deposition, highlighting the superior surface affinity and antifouling performance of the copolymer. The results obtained in this work demonstrate that amphiphilic copolymers containing PMMA anchors and PEG side chains can be used in detergent formulations to modify polyester surfaces during laundry and reduce deposition of proteins (and likely also other soils) on the textile.
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One-part (1K) polyurethane (PU) adhesive has excellent bulk strength and environmental resistance. It is therefore widely used in many fields, such as construction, transportation, and flexible lamination. However, when contacting non-polar polymer materials, the poor adhesion of 1K PU adhesive may not be able to support its outdoor applications. To solve this problem, plasma treatment of the non-polar polymer surface has been utilized to improve adhesion between the polymer and 1K PU adhesive. The detailed mechanisms of adhesion enhancement of the 1K PU adhesive caused by plasma treatment on polymer substrates have not been studied extensively because adhesion is a property of buried interfaces which are difficult to probe. In this study, sum frequency generation (SFG) vibrational spectroscopy was used to investigate the buried PU/polypropylene (PP) interfaces in situ nondestructively. Fourier-transform infrared spectroscopy, the X-ray diffraction technique, and adhesion tests were used as supplemental methods to SFG in the study. The 1K PU adhesive is a moisture-curing adhesive and usually needs several days to be fully cured. Here, time-dependent SFG experiments were conducted to monitor the molecular behaviors at the buried 1K PU adhesive/PP interfaces during the curing process. It was found that the PU adhesives underwent rearrangement during the curing process with functional groups gradually becoming ordered at the interface. Stronger adhesion between the plasma-treated PP substrate and the 1K PU adhesive was observed, which was achieved by the interfacial chemical reactions and a more rigid interface. Annealing the samples increased the reaction speed and enhanced the bulk PU strength with higher crystallinity. In this research, molecular mechanisms of adhesion enhancement of the 1K PU adhesive caused by the plasma treatment on PP and by annealing the PU/PP samples were elucidated.
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Medicago truncatula , Rhizobium , Sinorhizobium meliloti , Giberelinas , Rhizobium/fisiología , Nódulos de las Raíces de las Plantas/metabolismo , Nodulación de la Raíz de la Planta/genética , Medicago truncatula/genética , Simbiosis/genética , Proteínas de Plantas/metabolismo , Sinorhizobium meliloti/fisiología , Regulación de la Expresión Génica de las Plantas , Fijación del Nitrógeno/genéticaRESUMEN
The subcellular events occurring in cells of legume plants as they form transcellular symbiotic-infection structures have been compared with those occurring in premitotic cells. Here, we demonstrate that Aurora kinase 1 (AUR1), a highly conserved mitotic regulator, is required for intracellular infection by rhizobia in Medicago truncatula. AUR1 interacts with microtubule-associated proteins of the TPXL and MAP65 families, which, respectively, activate and are phosphorylated by AUR1, and localizes with them within preinfection structures. MYB3R1, a rhizobia-induced mitotic transcription factor, directly regulates AUR1 through two closely spaced, mitosis-specific activator cis elements. Our data are consistent with a model in which the MYB3R1-AUR1 regulatory module serves to properly orient preinfection structures to direct the transcellular deposition of cell wall material for the growing infection thread, analogous to its role in cell plate formation. Our findings indicate that the eukaryotically conserved MYB3R1-TPXL-AUR1-MAP65 mitotic module was conscripted to support endosymbiotic infection in legumes.
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Aurora Quinasas , Medicago truncatula , Proteínas de Plantas , Rhizobium , Simbiosis , Aurora Quinasas/genética , Aurora Quinasas/metabolismo , Regulación de la Expresión Génica de las Plantas , Medicago truncatula/genética , Medicago truncatula/microbiología , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Rhizobium/metabolismo , Factores de Transcripción/metabolismoRESUMEN
(1) Background: Vertical cup-to-disc ratio (CDR) is an important measure for evaluating damage to the optic nerve head (ONH) in glaucoma patients. However, this measure often does not fully capture the irregular cupping observed in glaucomatous nerves. We developed and evaluated a method to measure cup-to-disc ratio (CDR) at all 360 degrees of the ONH. (2) Methods: Non-physician graders from the Scheie Reading Center outlined the cup and disc on digital stereo color disc images from African American patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. After converting the resultant coordinates into polar representation, the CDR at each 360-degree location of the ONH was obtained. We compared grader VCDR values with clinical VCDR values, using Spearman correlation analysis, and validated significant genetic associations with clinical VCDR, using grader VCDR values. (3) Results: Graders delineated outlines of the cup contour and disc boundaries twice in each of 1815 stereo disc images. For both cases and controls, the mean CDR was highest at the horizontal bisector, particularly in the temporal region, as compared to other degree locations. There was a good correlation between grader CDR at the vertical bisector and clinical VCDR (Spearman Correlation OD: r = 0.78 [95% CI: 0.76-0.79]). An SNP in the MPDZ gene, associated with clinical VCDR in a prior genome-wide association study, showed a significant association with grader VCDR (p = 0.01) and grader CDR area ratio (p = 0.02). (4) Conclusions: The CDR of both glaucomatous and non-glaucomatous eyes varies by degree location, with the highest measurements in the temporal region of the eye. This method can be useful for capturing innate eccentric ONH morphology, tracking disease progression, and identifying genetic associations.
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Negro o Afroamericano/estadística & datos numéricos , Glaucoma de Ángulo Abierto/diagnóstico , Tamizaje Masivo/métodos , Proteínas de la Membrana/genética , Disco Óptico/patología , Nervio Óptico/patología , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Técnicas de Diagnóstico Oftalmológico/estadística & datos numéricos , Femenino , Glaucoma de Ángulo Abierto/genética , Humanos , Masculino , Disco Óptico/diagnóstico por imagen , Nervio Óptico/diagnóstico por imagen , Campos VisualesRESUMEN
Leghemoglobins enable the endosymbiotic fixation of molecular nitrogen (N2) in legume nodules by channeling O2 for bacterial respiration while maintaining a micro-oxic environment to protect O2-sensitive nitrogenase. We found that the NIN-like protein (NLP) transcription factors NLP2 and NIN directly activate the expression of leghemoglobins through a promoter motif, resembling a "double" version of the nitrate-responsive elements (NREs) targeted by other NLPs, that has conserved orientation and position across legumes. CRISPR knockout of the NRE-like element resulted in strongly decreased expression of the associated leghemoglobin. Our findings indicate that the origins of the NLP-leghemoglobin module for O2 buffering in nodules can be traced to an ancient pairing of NLPs with nonsymbiotic hemoglobins that function in hypoxia.
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Regulación de la Expresión Génica de las Plantas , Leghemoglobina/genética , Medicago truncatula/genética , Nódulos de las Raíces de las Plantas/metabolismo , Factores de Transcripción/metabolismo , Fabaceae/genética , Fabaceae/metabolismo , Leghemoglobina/química , Medicago truncatula/metabolismo , Fijación del Nitrógeno , Oxígeno/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nodulación de la Raíz de la Planta , Regiones Promotoras Genéticas , Simbiosis , Factores de Transcripción/genéticaRESUMEN
The formation of nitrogen-fixing no dules on legume roots requires the coordination of infection by rhizobia at the root epidermis with the initiation of cell divisions in the root cortex. During infection, rhizobia attach to the tip of elongating root hairs which then curl to entrap the rhizobia. However, the mechanism of root hair deformation and curling in response to symbiotic signals is still elusive. Here, we found that small GTPases (MtRac1/MtROP9 and its homologs) are required for root hair development and rhizobial infection in Medicago truncatula. Our results show that the Nod factor receptor LYK3 phosphorylates the guanine nucleotide exchange factor MtRopGEF2 at S73 which is critical for the polar growth of root hairs. In turn, phosphorylated MtRopGEF2 can activate MtRac1. Activated MtRac1 was found to localize at the tips of root hairs and to strongly interact with LYK3 and NFP. Taken together, our results support the hypothesis that MtRac1, LYK3, and NFP form a polarly localized receptor complex that regulates root hair deformation during rhizobial infection.
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Factores de Intercambio de Guanina Nucleótido/metabolismo , Medicago truncatula/enzimología , Proteínas de Plantas/metabolismo , Nodulación de la Raíz de la Planta , Proteína de Unión al GTP rac1/metabolismo , Medicago truncatula/crecimiento & desarrollo , Medicago truncatula/microbiología , Fosforilación , Raíces de Plantas/enzimología , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/microbiología , SimbiosisRESUMEN
The establishment of the symbiotic interaction between rhizobia and legumes involves the Nod factor signaling pathway. Nod factor recognition occurs through two plant receptors, NFR1 and NFR5. However, the signal transduction mechanisms downstream of NFR1-NFR5-mediated Nod factor perception remain largely unknown. Here, we report that a small guanosine triphosphatase (GTPase), GmROP9, and a guanine nucleotide exchange factor, GmGEF2, are involved in the soybean-rhizobium symbiosis. We show that GmNFR1α phosphorylates GmGEF2a at its N-terminal S86, which stimulates guanosine diphosphate (GDP)-to-GTP exchange to activate GmROP9 and that the active form of GmROP9 can associate with both GmNFR1α and GmNFR5α. We further show that a scaffold protein, GmRACK1, interacts with active GmROP9 and contributes to root nodule symbiosis. Collectively, our results highlight the symbiotic role of GmROP9-GmRACK1 and support the hypothesis that rhizobial signals promote the formation of a protein complex comprising GmNFR1, GmNFR5, GmROP9, and GmRACK1 for symbiotic signal transduction in soybean.
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Glycine max , Nodulación de la Raíz de la Planta , Rhizobium , Transducción de Señal , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Rhizobium/fisiología , Glycine max/microbiología , Glycine max/fisiología , SimbiosisRESUMEN
OBJECTIVE: Ferroptosis plays an important role in traumatic brain injury (TBI). The p53 protein is a major mediator of ferroptosis. However, the role of p53-mediated ferroptosis in TBI has not been studied. Sirtuin 2 (SIRT2) exerts a protective effects role in TBI, although the underlying mechanism of this protection remains unclear. In the present study, we tested the hypothesis that that SIRT2 mitigates TBI by regulating p53-mediated ferroptosis. METHODS AND RESULTS: To model TBI in mice, we used the controlled cortical impact (CCI) injury method. We found that ferroptosis was significantly activated by CCI, and peaked 3 days following CCI, as evidenced by upregulation of GPX4 and SLC7A11, increased content of decreases glutathione, lipid peroxidation, malondialdehyde and ferrous ion. Inhibition of ferroptosis significantly alleviated neurological indications and brain edema. In addition, knockout of p53 significantly blocked ferroptosis following CCI. Furthermore, we found that inhibition of SIRT2 upregulated the acetylation of p53, as well as p53 expression, and exacerbated ferroptosis following CCI. Interestingly, knockout of p53 rescued the SIRT2 inhibition-induced exacerbation of ferroptosis. CONCLUSIONS: These findings indicate that p53-mediated ferroptosis contributes to the pathogenesis of TBI. Furthermore, we demonstrate that SIRT2 exerts a neuroprotective effect against TBI by suppressing p53-mediated ferroptosis.
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Lesiones Traumáticas del Encéfalo/metabolismo , Ferroptosis/fisiología , Sirtuina 2/antagonistas & inhibidores , Sirtuina 2/metabolismo , Proteína p53 Supresora de Tumor/deficiencia , Animales , Benzamidas/farmacología , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/patología , Femenino , Ferroptosis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Sulfonamidas/farmacología , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Thermophilic fungi are eukaryotic species that grow at high temperatures, but little is known about the underlying basis of thermophily at cell and molecular levels. Here the proteome and N-glycoproteome of Chaetomium thermophilum at varying culture temperatures (30, 50, and 55°C) were studied using hydrophilic interaction liquid chromatography enrichment and high-resolution liquid chromatography-tandem mass spectroscopy analysis. With respect to the proteome, the numbers of differentially expressed proteins were 1,274, 1,374, and 1,063 in T50/T30, T55/T30, and T55/T50, respectively. The upregulated proteins were involved in biological processes, such as protein folding and carbohydrate metabolism. Most downregulated proteins were involved in molecular functions, including structural constituents of the ribosome and other protein complexes. For the N-glycoproteome, the numbers of differentially expressed N-glycoproteins were 160, 176, and 128 in T50/T30, T55/T30, and T55/T50, respectively. The differential glycoproteins were mainly involved in various types of N-glycan biosynthesis, mRNA surveillance pathway, and protein processing in the endoplasmic reticulum. These results indicated that an efficient protein homeostasis pathway plays an essential role in the thermophily of C. thermophilum, and N-glycosylation is involved by affecting related proteins. This is the novel study to reveal thermophilic fungi's physiological response to high-temperature adaptation using omics analysis, facilitating the exploration of the thermophily mechanism of thermophilic fungi.
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Carbon fiber-reinforced plastics (CFRPs) are widely used materials with outstanding mechanical properties. The wettability between the polymer matrix and carbon fiber in the interphase region significantly influences the strength of the composite. Sizing agents consisting of multiple components are therefore frequently applied to improve wetting and interfacial adhesion between polymers and carbon fiber in CFRPs. However, the complex compositions of sizing solutions make detailed interpretations of their impacts on interfacial wetting difficult. In this work, surface-sensitive sum frequency generation (SFG) spectroscopy was utilized to characterize the sizing/polymer and sizing/carbon fiber interfacial structures to gain molecular-level understandings of the wetting improvements afforded by sizing. A mixture sizing solution containing polyethylenimine (PEI, adhesion promoter) and Lutensol (surfactant) was investigated when contacting nylon (model plastics), polypropylene (model plastics), and graphite (model carbon fiber). Our results demonstrated that although the addition of the surfactant led to an interfacial tension decrease (in comparison to pure PEI solution) on nylon and polypropylene, the interfacial tension was surprisingly increased on graphite, contrasting with the commonly accepted function of surfactants. SFG characterizations revealed the multilayer molecular structures at these buried interfaces. The peculiar interfacial tension increase at the graphite/sizing interface was then correlated to the strong amine-π interactions between PEI and graphite. PEI was therefore demonstrated to be an effective adhesion promoter for carbon fiber. This article reports the first investigation of (polymer + surfactant) complex structures at solid-liquid interfaces. The valuable structural insights obtained by SFG analysis enable more accurate understandings of the composition-wettability (structure-function) relationship. These detailed understandings of interactions between sizing and the substrates promote more informed and optimized selections of sizing formulae.