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Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the progression and exacerbation of various pathological states. Nevertheless, NETs exhibit dual functionalities in certain pathological contexts. While NETs may act as autoantigens, aggregated NET complexes can function as inflammatory mediators by degrading proinflammatory cytokines and chemokines. The delineation of molecules and signaling pathways governing NET formation aids in refining our appreciation of NETs' role in immune homeostasis, inflammation, autoimmune diseases, metabolic dysregulation, and cancer. In this comprehensive review, we delve into the multifaceted roles of NETs in both homeostasis and disease, whilst discussing their potential as therapeutic targets. Our aim is to enhance the understanding of the intricate functions of NETs across the spectrum from physiology to pathology.
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Doenças Autoimunes , Armadilhas Extracelulares , Homeostase , Inflamação , Neutrófilos , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/genética , Humanos , Homeostase/imunologia , Inflamação/imunologia , Inflamação/patologia , Inflamação/genética , Neutrófilos/imunologia , Neutrófilos/patologia , Neutrófilos/metabolismo , Doenças Autoimunes/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/genética , Citocinas/imunologia , Citocinas/metabolismo , Citocinas/genética , Transdução de Sinais/imunologia , AnimaisRESUMO
Articular cartilage is an avascular tissue with very limited capacity of self-regeneration. Trauma or injury-related defects, inflammation, or aging in articular cartilage can induce progressive degenerative joint diseases such as osteoarthritis. There are significant clinical demands for the development of effective therapeutic approaches to promote articular cartilage repair or regeneration. The current treatment modalities used for the repair of cartilage lesions mainly include cell-based therapy, small molecules, surgical approaches, and tissue engineering. However, these approaches remain unsatisfactory. With the advent of three-dimensional (3D) bioprinting technology, tissue engineering provides an opportunity to repair articular cartilage defects or degeneration through the construction of organized, living structures composed of biomaterials, chondrogenic cells, and bioactive factors. The bioprinted cartilage-like structures can mimic native articular cartilage, as opposed to traditional approaches, by allowing excellent control of chondrogenic cell distribution and the modulation of biomechanical and biochemical properties with high precision. This review focuses on various hydrogels, including natural and synthetic hydrogels, and their current developments as bioinks in 3D bioprinting for cartilage tissue engineering. In addition, the challenges and prospects of these hydrogels in cartilage tissue engineering applications are also discussed.
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Hepatic ischemia/reperfusion (I/R) injury is an important cause of liver function impairment following liver surgery. The ubiquitin-proteasome system (UPS) plays a crucial role in protein quality control and has substantial impact on the hepatic I/R process. Although OTU deubiquitinase 1 (OTUD1) is involved in diverse biological processes, its specific functional implications in hepatic I/R are not yet fully understood. This study demonstrates that OTUD1 alleviates oxidative stress, apoptosis, and inflammation induced by hepatic I/R injury. Mechanistically, OTUD1 deubiquitinates and activates nuclear factor erythroid 2-related factor 2 (NRF2) through its catalytic site cysteine 320 residue and ETGE motif, thereby attenuating hepatic I/R injury. Additionally, administration of a short peptide containing the ETGE motif significantly mitigates hepatic I/R injury in mice. Overall, our study elucidates the mechanism and role of OTUD1 in ameliorating hepatic I/R injury, providing a theoretical basis for potential treatment using ETGE-peptide.
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Fígado , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Traumatismo por Reperfusão , Animais , Humanos , Masculino , Camundongos , Apoptose , Enzimas Desubiquitinantes/metabolismo , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , UbiquitinaçãoRESUMO
Liver diseases contribute to ~2 million deaths each year and account for 4% of all deaths globally. Despite various treatment options, the management of liver diseases remains challenging. Physical exercise is a promising nonpharmacological approach to maintain and restore homeostasis and effectively prevent and mitigate liver diseases. In this review, we delve into the mechanisms of physical exercise in preventing and treating liver diseases, highlighting its effects on improving insulin sensitivity, regulating lipid homeostasis, and modulating immune function. In addition, we evaluate the impact of physical exercise on various liver diseases, including liver ischemia/reperfusion injury, cardiogenic liver disease, metabolic dysfunction-associated steatotic liver disease, portal hypertension, cirrhosis, and liver cancer. In conclusion, the review underscores the effectiveness of physical exercise as a beneficial intervention in combating liver diseases.
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The dissection of the genetic architecture and the detection of the loci for adaptive traits are important for marker-assisted selection (MAS) for breeding. A spring wheat diversity panel with 251 cultivars, mainly from China, was obtained to conduct a genome-wide association study (GWAS) to detect the new loci, including the heading date (HD), maturating date (MD), plant height (PH), and lodging resistance (LR). In total, 41 loci existing in all 21 chromosomes, except for 4A and 6B, were identified, and each explained 4.3-18.9% of the phenotypic variations existing in two or more environments. Of these, 13 loci are overlapped with the known genes or quantitative trait loci (QTLs), whereas the other 28 are likely to be novel. The 1A locus (296.9-297.7 Mb) is a multi-effect locus for LR and PH, whereas the locus on chromosome 6D (464.5-471.0 Mb) affects both the HD and MD. Furthermore, four candidate genes for adaptive traits were identified, involved in cell division, signal transduction, and plant development. Additionally, two competitive, allele-specific PCR (KASP) markers, Kasp_2D_PH for PH and Kasp_6D_HD for HD, were developed and validated in another 162 spring wheat accessions. Our study uncovered the genetic basis of adaptive traits and provided the associated SNPs and varieties with more favorable alleles for wheat MAS breeding.
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BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) fibrosis is a reversible stage of liver disease accompanied by inflammatory cell infiltration. Neutrophils extrude a meshwork of chromatin fibers to establish neutrophil extracellular traps (NETs), which play important roles in inflammatory response regulation. Our previous work demonstrated that NETs promote HCC in MASH. However, it is still unknown if NETs play a role in the molecular mechanisms of liver fibrosis. APPROACH AND RESULTS: Following 12 weeks of Western diet/carbon tetrachloride, MASH fibrosis was identified in C57BL/6 mice with increased NET formation. However, NET depletion using DNase I treatment or mice knocked out for peptidyl arginine deaminase type IV significantly attenuated the development of MASH fibrosis. NETs were demonstrated to induce HSCs activation, proliferation, and migration through augmented mitochondrial and aerobic glycolysis to provide additional bioenergetic and biosynthetic supplies. Metabolomic analysis revealed markedly an altered metabolic profile upon NET stimulation of HSCs that were dependent on arachidonic acid metabolism. Mechanistically, NET stimulation of toll-like receptor 3 induced cyclooxygenase-2 activation and prostaglandin E2 production with subsequent HSC activation and liver fibrosis. Inhibiting cyclooxygenase-2 with celecoxib reduced fibrosis in our MASH model. CONCLUSIONS: Our findings implicate NETs playing a critical role in the development of MASH hepatic fibrosis by inducing metabolic reprogramming of HSCs through the toll-like receptor 3/cyclooxygenase-2/cyclooxygenase-2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.
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INTRODUCTION: Patients with bilateral vocal fold paralysis (BVFP) experience airway obstruction because of loss of abductor function of posterior cricoarytenoid (PCA) muscles. We previously reported that implantation of autologous muscle progenitor (stem) cells into thyroarytenoid muscles during reinnervation resulted in improved adductor function. In this study, that same approach was applied to treating PCA muscles in a canine model of BVFP. DESIGN: Animal study. METHODS: Two canines underwent baseline measures of glottal resistance (GR), then complete transection and suture repair of both recurrent laryngeal nerves. Muscle stem cells were isolated from skeletal muscle and cultured. Two months later, GR was measured, and then 107 stem cells were implanted into one PCA muscle of each animal. After four more months, GR and glottal opening force (GOF) were measured and the muscles were harvested for histologic study. One control dog underwent the same procedures without stem cell implantation, for comparison. RESULTS: GR increased by 21%-25% over baseline at 2 months, but after stem cell implantation, improved to 10%-14% over baseline at 6 months. PCA muscle strength, as determined by GOF, was 61%-65% on control sides (no stem cells), and 78%-83% on treated sides (with stem cells). Histology confirmed survival of stem cells and a 50% higher rate of innervation of motor endplates in the stem cell treated sides. CONCLUSION: Autologous muscle progenitor (stem) cells show promise as a potential new therapy for patients with bilateral vocal fold paralysis. Additional studies are needed to determine the optimal number of cells, timing of implantation, and other variables before launching a clinical trial. LEVEL OF EVIDENCE: NA (animal study) Laryngoscope, 134:324-328, 2024.
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Paralisia das Pregas Vocais , Prega Vocal , Animais , Cães , Eletromiografia , Músculos Laríngeos/inervação , Músculos , Nervo Laríngeo Recorrente/cirurgia , Células-Tronco , Paralisia das Pregas Vocais/cirurgia , Prega Vocal/cirurgiaRESUMO
Nonalcoholic fatty liver disease (NAFLD) is an expanding worldwide health concern, and the underlying mechanisms contributing to its progression still need further exploration. Neutrophil extracellular traps (NETs) are intricate formations comprised of nuclear constituents and diverse antimicrobial granules that are released into the extracellular milieu by activated neutrophils upon various triggers, which play a pivotal part in the onset and advancement of NAFLD. NETs actively participate in the genesis of NAFLD by fostering oxidative stress and inflammation, ultimately resulting in hepatic fat accumulation and the escalation of liver injury. Recent insights into the interaction with other hepatic immune populations and mediators, such as macrophages and T regulatory cells, have revealed several important mechanisms that can trigger further liver injury. In conclusion, the formation of NETs emerged as an important factor in the development of NAFLD, offering a promising target for innovative therapeutic approaches against this debilitating condition. This comprehensive review seeks to compile existing studies exploring the involvement of NETs in the genesis of NAFLD and their influence on the immune response throughout the progression of NAFLD.
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Armadilhas Extracelulares , Hepatopatia Gordurosa não Alcoólica , Humanos , Inflamação , NeutrófilosRESUMO
The accurate identification of highly similar sheet metal parts remains a challenging issue in sheet metal production. To solve this problem, this paper proposes an effective mean square differences (EMSD) algorithm that can effectively distinguish highly similar parts with high accuracy. First, multi-level downsampling and rotation searching are adopted to construct an image pyramid. Then, non-maximum suppression is utilised to determine the optimal rotation for each layer. In the matching, by re-evaluating the contribution of the difference between the corresponding pixels, the matching weight is determined according to the correlation between the grey value information of the matching pixels, and then the effective matching coefficient is determined. Finally, the proposed effective matching coefficient is adopted to obtain the final matching result. The results illustrate that this algorithm exhibits a strong discriminative ability for highly similar parts, with an accuracy of 97.1%, which is 11.5% higher than that of the traditional methods. It has excellent potential for application and can significantly improve sheet metal production efficiency.
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Here we provide a novel method for fabricating a pH- and thermal-responsive triple-shape memory hydrogel based on a single reversible switch phase. A high-density quadruple hydrogen-bonding ureido-pyrimidinone (UPy) system was introduced into the hydrogel network, which can occur to varied degrees of dissociation under different pH and temperature conditions. Different degrees of dissociation and reassociation can be viewed as different subsets of memory elements to freeze and unfreeze the temporary shapes. Although this class of hydrogels contains only a single transition phase, they feature a large dissociative differential in response to varied external stimuli to provide multiple windows for programming different temporary shapes.
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Environmental-friendly biochar (BC) with low cost was obtained by simple pyrolysis of corn stalk core, which was employed as an adsorbent for efficiently removing organic pollutants in water. The physicochemical properties of BCs were characterized by various techniques, including X-ray diffractometer (XRD), Fourier transforms infrared (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectrometer (XPS), Raman, Thermogravimetric (TGA), N2 adsorption-desorption and zeta potential tests. The influence of pyrolysis temperature on the structure and adsorption efficiency of the adsorbent was emphasized. The graphitization degree and sp2 carbon content of BCs were enhanced by increasing the pyrolysis temperature, which was favorable for the enhancement of the adsorption efficiency. The adsorption results showed that corn stalk core calcined at 900 °C (BC-900) displayed exceptional adsorption efficiency toward bisphenol A (BPA) in wide pH (1-13) and temperature (0-90 °C) ranges. Moreover, adsorbent BC-900 could adsorb various pollutants from water, including antibiotics, organic dyes, and phenol (50 mg·L-1). The adsorption process of BPA over BC-900 matched well with the Langmuir isotherm and pseudo-second-order kinetic model. Mechanism investigation suggested that large specific surface area and pore filling acted the foremost role in the adsorption process. Adsorbent BC-900 has the potential application in wastewater treatment due to its simple preparation, low cost, and excellent adsorption efficiency.
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Poluentes Químicos da Água , Zea mays , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise , Carvão Vegetal/química , Fenóis , Adsorção , Cinética , ÁguaRESUMO
Chemotherapy remains the mainstay of treatment for patients with advanced liposarcoma (LPS), but response rates are only 25% and the overall survival at 5 years is dismal at 20-34%. Translation of other therapies have not been successful and there has been no significant improvement in prognosis for nearly 20 years. The aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in the aggressive clinical behavior LPS and in resistance to chemotherapy, but the precise mechanism remains elusive and efforts to target AKT clinically have failed. Here we show that the AKT-mediated phosphorylation of the transcription elongation factor IWS1, promotes the maintenance of cancer stem cells in both cell and xenograft models of LPS. In addition, phosphorylation of IWS1 by AKT contributes to a "metastable" cell phenotype, characterized by mesenchymal/epithelial plasticity. The expression of phosphorylated IWS1 also promotes anchorage-dependent and independent growth, cell migration, invasion, and tumor metastasis. In patients with LPS, IWS1 expression is associated with reduced overall survival, increased frequency of recurrence, and shorter time to relapse after resection. These findings indicate that IWS1-mediated transcription elongation is an important regulator of human LPS pathobiology in an AKT-dependent manner and implicate IWS1 as an important molecular target to treat LPS.
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In recent years, marine oil spill accidents have been occurring frequently during extraction and transportation, and seriously damage the ecological balance. Accurate monitoring of oil spills plays a vital role in estimating oil spill volume, determination of liability, and clean-up. The oil that leaks into natural environments is not a single type of oil, but a mixture of various oil products, and the oil film thickness on the sea surface is uneven under the influence of wind and waves. Increasing the mixed oil film thickness dimension and the mix proportion dimension has been proposed to weaken the effect of the detection environment on the fluorescence measurement results. To preserve the relationships between the data of oil films with different thicknesses and the relationships between the data of oil films with different mixing proportions, the three-dimensional fluorescence spectral data of mixed oil films on a seawater surface were measured in the laboratory, producing a thickness-fluorescence matrix and a proportion-fluorescence matrix. The nonlinear variation of the fluorescence spectra was investigated according to the fluorescence lidar equation. This work pre-processes the data by sum normalization and two-dimensional principal component analysis (2DPCA) and uses the dimensionality reduction results as two feature-point views. Then, semi-supervised classification of collaborative training (co-training) with K-nearest neighbors (KNN) and a decision tree (DT) is used to identify the samples. The results show that the average overall accuracy of this coupling model can reach 100%, which is 20.49% higher than that of the thickness-only view. Using unlabeled data can reduce the cost of data acquisition, improve the classification accuracy and generalization ability, and provide theoretical significance and application prospects for discrimination of spectrally similar oil species in natural marine environments.
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In this study, a unidirectional and plain weave carbon fiber/epoxy prepreg was used as the raw material, and the prepreg tape winding process was used to prepare carbon fiber/epoxy prepreg composites with 65% and 75% carbon fiber volume content, respectively. Based on traditional damage experiments and mechanical measurements, electrical measurements are introduced to study the damage to carbon fiber prepreg composites. The damage behavior of the carbon fiber prepreg composite under a high-speed impact load was monitored using the resistance method. By arranging electrodes on the sample and tracking the change in resistance during the entire process of high-speed impact of the material, the relationship between the damage and the change in resistance parameters of the carbon fiber prepreg composite winding products under high-speed impact was determined. The stress-strain curve and the final failure mode of the sample and the microstructure mechanics of carbon fiber prepreg winding products under different strain rates were analyzed. These results indicate that, as the change in resistance over time was almost stable from 0 to 200 µs. From 200 to 250 µs, the resistance decreases sharply; from 250 to 400 µs, the resistance approximates a plateau. From 400 to 500 µs, the resistance value increases again; at this time, the resistance value decreases to 3.2% of the initial resistance value.
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To date, poly(vinyl alcohol) (PVA) gels attract tremendous attention because of their potential applications in a wide variety of fields. Here, a novel monocarboxylic acid induction strategy was developed to fabricate tough and thermo-reversible PVA physical gels by introducing monocarboxylic acids into the PVA/dimethyl sulfoxide (DMSO) system. The obtained PVA gels exhibited appropriate crystalline architectures, leading to superior mechanical properties and high transparency. Furthermore, the role of monocarboxylic acids in the formation of PVA physical gels and the effects of alkyl chain length, concentration, and the induction time of monocarboxylic acids on the properties of PVA physical gels were also investigated.
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The solar X-ray and Extreme Ultraviolet Imager (X-EUVI), developed by the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), is the first space-based solar X-ray and Extreme ultraviolet (EUV) imager of China loaded on the Fengyun-3E (FY-3E) satellite supported by the China Meteorological Administration (CMA) for solar observation. Since started work on July 11, 2021, X-EUVI has obtained many solar images. The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun, which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region. X-EUVI has a field of view of 42', an angular resolution of 2.5â³ per pixel in the EUV band and an angular resolution of 4.1â³ per pixel in the X-ray band. The instrument also includes an X-ray and EUV irradiance sensor (X-EUVS) with the same bands as its imaging optics, which measures the solar irradiance and regularly calibrates the solar images. The radiometric calibration of X-EUVS on the ground has been completed, with a calibration accuracy of 12%. X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate. Flat-field calibration is conducted by utilizing successive rotation solar images. The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.
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Peritoneal metastases are associated with a low response rate to immune checkpoint blockade (ICB) therapy. The numbers of peritoneal resident macrophages (PRMs) are reversely correlated with the response rate to ICB therapy. We have previously shown that TLR9 in fibroblastic reticular cells (FRCs) plays a critical role in regulating peritoneal immune cell recruitment. However, the role of TLR9 in FRCs in regulating PRMs is unclear. Here, we demonstrated that the class A TLR9 agonist, ODN1585, markedly enhanced the efficacy of anti-PD-1 therapy in mouse models of colorectal peritoneal metastases. ODN1585 injected i.p. reduced the numbers of Tim4+ PRMs and enhanced CD8+ T cell antitumor immunity. Mechanistically, treatment of ODN1585 suppressed the expression of genes required for retinoid metabolism in FRCs, and this was associated with reduced expression of the PRM lineage-defining transcription factor GATA6. Selective deletion of TLR9 in FRCs diminished the benefit of ODN1585 in anti-PD-1 therapy in reducing peritoneal metastases. The crosstalk between PRMs and FRCs may be utilized to develop new strategies to improve the efficacy of ICB therapy for peritoneal metastases.
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Neoplasias Colorretais , Neoplasias Peritoneais , Camundongos , Animais , Receptor Toll-Like 9/metabolismo , Injeções Intraperitoneais , Fator de Transcrição GATA6 , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Imunoterapia , Adjuvantes Imunológicos , Neoplasias Colorretais/tratamento farmacológico , RetinoidesRESUMO
Root system architecture (RSA) and tiller are important agronomic traits. However, the mechanisms of the IGT family genes regulate RSA and tiller development in different rice varieties remain unclear. In this study, we demonstrated that 38 rice varieties obtained from Yuanyang Hani's terraced fields with different RSA and could be classified into six groups based on the ratio of root length and width. We found a positive correlation between RSA (including root width, length, and area) and tiller number in most of rice varieties. Furthermore, the IGT family genes Deeper Rooting 1 (DRO1), LAZY1, TAC1, and qSOR1 showed different expression patterns when rice grown under irrigation and drought conditions. Moreover, the qSOR1 gene had higher levels in the roots and tillers, and accompanied with higher levels of PIN1b gene in roots when rice grown under drought environmental condition. DRO1 gene had two single nucleotide polymorphisms (SNPs) in the exon 3 sequences and showed different expression patterns in the roots and tillers of the 38 rice varieties. Overexpression of DRO1 with a deletion of exon 5 caused shorter root length, less lateral roots and lower levels of LAZY1, TAC1, and qSOR1. Further protein interaction network, microRNA targeting and co-expression analysis showed that DRO1 plays a critical role in the root and tiller development associated with auxin transport. These data suggest that the RSA and tiller development are regulated by the IGT family genes in an intricate network way, which is tightly related to rice genetic background in rice adapting to different environmental conditions.
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Identification of the gene for agronomic traits is important for the wheat marker-assisted selection (MAS) breeding. To identify the new and stable loci for agronomic traits, including flag leaf length (FLL), flag leaf width (FLW), uppermost internode length (UIL), and plant morphology (PM, including prostrate, semi-prostrate, and erect). A total of 251 spring wheat accessions collected from the Northeast of China were used to conduct genome-wide association study (GWAS) by 55K SNP arrays. A total of 30 loci for morphological traits were detected, and each explained 4.8-17.9% of the phenotypic variations. Of these, 13 loci have been reported by previous studies, and the other 17 are novel. We have identified seven genes involved in the signal transduction, cell-cycle progression, and plant development pathway as candidate genes. This study provides new insights into the genetic basis of morphological traits. The associated SNPs and accessions with more of favorable alleles identified in this study could be used to promote the wheat breeding progresses.
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Primary tumors can communicate with the liver to establish a microenvironment that favors metastatic colonization prior to dissemination, forming what is termed the "pre-metastatic niche" (PMN). Through diverse signaling mechanisms, distant malignancies can both influence hepatic cells directly as well as recruit immune cells into the PMN. The result is a set of changes within the hepatic tissue that increase susceptibility of tumor cell invasion and outgrowth upon dissemination. Thus, the PMN offers a novel step in the traditional metastatic cascade that could offer opportunities for clinical intervention. The involved signaling molecules also offer promise as biomarkers. Ultimately, while the existence of the hepatic PMN is well-established, continued research effort and use of innovative models are required to reach a functional knowledge of PMN mechanisms that can be further targeted.