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1.
Small ; : e2405759, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221523

RESUMEN

The stability of supported nano-metal catalysts holds significant importance in both scientific and economic practice, beyond the long pursuit of enhanced activity. While previous efforts have concentrated on augmenting the interaction between nano-metals and carriers, in the thermodynamic macro-perspective, to achieve optimized repression upon particle migration coalescence and Ostwald ripening, nevertheless, the microscale kinetics of migrating catalyst particles driven by the reaction remains unknown. In this work, the migration of nano-copper particles is investigated during hydrogen oxidation reaction by utilizing high spatiotemporal resolution of environmental transmission electron microscopy. It is shown that there exists a delicate correlation between the migration dynamics of nano-copper particles and the evolution of asymmetrically distributed Cu and Cu2O phases over the particle surface. It is found that the interplay of reduction and oxidation near the surface areas filled with Cu and Cu2O phases can facilitate the pressure gradient, which drives the migration of nano-particles. A driving force model is therefore established which is capable of qualitatively explaining the influences of reaction conditions such as temperature and hydrogen-to-oxygen ratio on the reaction-driven particle migration. This work adds a potential yet critical perspective to understanding particle migration and thus the nano-metal catalyst particle sintering in heterogeneous catalysis.

3.
Health Informatics J ; 30(3): 14604582241272771, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39115432

RESUMEN

Purpose: To identify the main variables affecting the academic adaptability of hospital nursing interns and key areas for improvement in preparing for future unpredictable epidemics. Methods: The importance of academic resilience-related variables for all nursing interns was analyzed using the random forest method, and key variables were further identified. An importance-performance analysis was used to identify the key improvement gaps regarding the academic resilience of nursing interns in the case hospital. Results: The random forest showed that five items related to cooperation, motivation, confidence, communication, and difficulty with coping were the main variables impacting the academic resilience of nursing interns. Moreover, the importance-performance analysis revealed that three items regarding options examination, communication, and confidence were the key improvement areas for participating nursing interns in the case hospital. Conclusions: For the prevention and control of future unpredictable pandemics, hospital nursing departments can strengthen the link between interns, nurses, and physicians and promote their cooperation and communication during clinical practice. At the same time, an application can be created considering the results of this study and combined with machine learning methods for more in-depth research. These will improve the academic resilience of nursing interns during the routine management of pandemics within hospitals.


Asunto(s)
Resiliencia Psicológica , Humanos , Internado y Residencia/métodos , Masculino , Femenino , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos
4.
JMIR Med Inform ; 12: e53427, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39113391

RESUMEN

Background: Recently, the growing demand for pediatric sedation services outside the operating room has imposed a heavy burden on pediatric centers in China. There is an urgent need to develop a novel system for improved sedation services. Objective: This study aimed to develop and implement a computerized system, the Pediatric Sedation Assessment and Management System (PSAMS), to streamline pediatric sedation services at a major children's hospital in Southwest China. Methods: PSAMS was designed to reflect the actual workflow of pediatric sedation. It consists of 3 main components: server-hosted software; client applications on tablets and computers; and specialized devices like gun-type scanners, desktop label printers, and pulse oximeters. With the participation of a multidisciplinary team, PSAMS was developed and refined during its application in the sedation process. This study analyzed data from the first 2 years after the system's deployment. Unlabelled: From January 2020 to December 2021, a total of 127,325 sedations were performed on 85,281 patients using the PSAMS database. Besides basic variables imported from Hospital Information Systems (HIS), the PSAMS database currently contains 33 additional variables that capture comprehensive information from presedation assessment to postprocedural recovery. The recorded data from PSAMS indicates a one-time sedation success rate of 97.1% (50,752/52,282) in 2020 and 97.5% (73,184/75,043) in 2021. The observed adverse events rate was 3.5% (95% CI 3.4%-3.7%) in 2020 and 2.8% (95% CI 2.7%-2.9%) in 2021. Conclusions: PSAMS streamlined the entire sedation workflow, reduced the burden of data collection, and laid a foundation for future cooperation of multiple pediatric health care centers.

5.
Int J Biol Macromol ; 279(Pt 1): 134625, 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39163962

RESUMEN

The wound healing process was often accompanied by bacterial infection and inflammation. The combination of electrically conductive nanomaterials and wound dressings could accelerate cell proliferation through endogenous electrical signaling, effectively promoting wound healing. In this study, polypyrrole was modified with dopamine hydrochloride by an in situ polymerization to form dopamine-polypyrrole (DA-Ppy) conductive nanofibers which successfully enhanced the water dispersibility and biocompatibility of polypyrrole. The DA-Ppy nanofibers were dispersed in an aqueous solution for >48 h and still maintained good stability. In addition, the DA-Ppy nanofibers showed good photothermal properties, and the temperature could reach 59.7 °C by 1.5 W/cm2 near-infrared light irradiation (NIR) for 10 min. DA-Ppy conductive nanofibres could be well dispersed in 3,4-dihydroxyphenylpropionic acid modified chitosan-carboxymethylated ß-cyclodextrin modified gelatin (CG) hydrogel due to the presence of DA, which endowed CG/DA-Ppy hydrogel with good adhesion properties, and the hydrogel adhered to the pigskin would not be dislodged by washing with running water. Under NIR, the CG/DA-Ppy hydrogel showed significant antimicrobial properties. Moreover, the CG/DA-Ppy hydrogel had excellent biocompatibility. In addition, CG/DA-Ppy hydrogel was effective in scavenging ROS, inducing macrophage polarization towards the M2 phenotype, and modulating the level of wound inflammation in vitro. Finally, it was confirmed in rat-infected wounds that the tissue regeneration effect and collagen deposition in the CG/DA-Ppy + NIR group were significantly better than the other groups in the repair of infected wounds, indicating better repair of infected wounds. The results suggested that the photothermal, antioxidant DA-Ppy conductive nanofiber had great potential for application in infected wound healing.

6.
Nano Lett ; 24(30): 9296-9301, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39037306

RESUMEN

The two-dimensional (2D) honeycomb lattice has attracted intensive research interest due to the appearance of Dirac-type band structures as the consequence of two sublattices in the honeycomb structure. Introducing strong spin-orbit coupling (SOC) leads to a gap opening at the Dirac point, transforming the honeycomb lattice into a 2D topological insulator as a platform for the quantum spin Hall effect (QSHE). In this work, we realize a 2D honeycomb-structured film with tellurium, the heaviest nonradioactive element in Group VI, namely, tellurene, via molecular beam epitaxy. We revealed the gap opening of 160 meV at the Dirac point due to the strong SOC in the honeycomb-structured tellurene by angle-resolved photoemission spectroscopy. The topological edge states of tellurene are detected via scanning tunneling microscopy/spectroscopy. These results demonstrate that tellurene is a novel 2D honeycomb lattice with strong SOC, and they unambiguously prove that tellurene is a promising candidate for a room-temperature QSHE system.

7.
Cell ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39043179

RESUMEN

Neurons produce and release neuropeptides to communicate with one another. Despite their importance in brain function, circuit-based mechanisms of peptidergic transmission are poorly understood, primarily due to the lack of tools for monitoring and manipulating neuropeptide release in vivo. Here, we report the development of two genetically encoded tools for investigating peptidergic transmission in behaving mice: a genetically encoded large dense core vesicle (LDCV) sensor that detects presynaptic neuropeptide release and a genetically encoded silencer that specifically degrades neuropeptides inside LDCVs. Using these tools, we show that neuropeptides, not glutamate, encode the unconditioned stimulus in the parabrachial-to-amygdalar threat pathway during Pavlovian threat learning. We also show that neuropeptides play important roles in encoding positive valence and suppressing conditioned threat response in the amygdala-to-parabrachial endogenous opioidergic circuit. These results show that our sensor and silencer for presynaptic peptidergic transmission are reliable tools to investigate neuropeptidergic systems in awake, behaving animals.

9.
Microsyst Nanoeng ; 10: 101, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035364

RESUMEN

The emergence of biomagnetism imaging has led to the development of ultrasensitive and compact spin-exchange relaxation-free (SERF) atomic magnetometers that promise high-resolution magnetocardiography (MCG) and magnetoencephalography (MEG). However, conventional optical components are not compatible with nanofabrication processes that enable the integration of atomic magnetometers on chips, especially for elliptically polarized laser-pumped SERF magnetometers with bulky optical systems. In this study, an elliptical-polarization pumping beam (at 795 nm) is achieved through a single-piece metasurface, which results in an SERF magnetometer with a high sensitivity reaching 10.61 fT/Hz1/2 by utilizing a 87Rb vapor cell with a 3 mm inner diameter. To achieve the optimum theoretical polarization, our design combines a computer-assisted optimization algorithm with an emerging metasurface design process. The metasurface is fabricated with 550 nm thick silicon-rich silicon nitride on a 2 × 2 cm 2 SiO2 substrate and features a 22.17° ellipticity angle (a deviation from the target polarization of less than 2%) and more than 80% transmittance. This study provides a feasible approach for on-chip polarization control of future all-integrated atomic magnetometers, which will further pave the way for high-resolution biomagnetism imaging and portable atomic sensing applications.

10.
J Environ Manage ; 366: 121694, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38971066

RESUMEN

The total organic carbon (OC) from plant litter in riparian zones is an important nutrient source for aquatic organisms and plays a crucial role in the nutrient cycling of river ecosystems. Nevertheless, the total amount of OC in dammed rivers gradually decreases, and the restoration methods are rarely researched. A hypothesis was proposed that the periodic inundation altered the process of OC release from plant litter. To explore the impact of periodic inundation on OC release from litter in the riparian zone, litter bags in situ tests were conducted in the Yalong River. Three inundation treatments were conducted for the test samples, which were NS (never submerged by water), PIS (periodic submerged), and PMS (permanent submerged). Results indicated that the amount of OC released from litters in PIS treatment was about 1.1 times that in PMS treatment, and about 2.1 times that in NS treatment. The average release rate coefficient k of PIS treatment (at mean water level) was the highest (12.8 × 10-4 d-1), followed by PMS treatment (11.0 × 10-4 d-1), and NS treatment (5.6 × 10-4 d-1), which demonstrated that the periodic inundation was critical for OC release. The mean water level was a demarcation line where there was a significant difference in the release of OC in the riparian zone (p < 0.05). Flow velocity alone could account for 84% of the variation in OC release rate, while the flow velocity and inundation duration together could achieve an explanatory degree of 86%. This research can provide a valuable scientific basis for the protection and restoration of river ecosystems, especially for the recovery of OC concentration in dammed rivers.


Asunto(s)
Carbono , Ríos , Ríos/química , Plantas , Ecosistema
11.
BMC Genomics ; 25(1): 634, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918701

RESUMEN

BACKGROUND: Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. RESULTS: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. CONCLUSIONS: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.


Asunto(s)
Adenosina , Adipogénesis , Desmetilasa de ARN, Homólogo 5 de AlkB , Pollos , Fosfatidilcolina-Esterol O-Aciltransferasa , Estabilidad del ARN , Animales , Adipogénesis/genética , Pollos/genética , Pollos/metabolismo , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Fosfatidilcolina-Esterol O-Aciltransferasa/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Femenino , Adenosina/análogos & derivados , Adenosina/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Metilación
12.
Plants (Basel) ; 13(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38891375

RESUMEN

In this study, we selected four grassland plots in Altai forest area and used the field survey method of "two-valued occurrence" to obtain the occurrence data of each plant species in the plots so as to calculate the species diversity index value of the community as a whole and the species diversity index value of each plant species not present in the community and to make use of the difference between these two diversity indices to determine the role of each plant species in the overall species diversity of the community. The difference between these two diversity indices was used to investigate the role of each plant species in the overall species diversity of the community. The results show the following: (1) In the grassland of the Altai forest area in Xinjiang, Asteraceae, Poaceae, Fabaceae, Polygonaceae, and Rosaceae are the dominant families, among which the genera Puccinellia Parl, Taraxacum, Pharbitis, Lactuca, Geranium, and Alchemilla are the dominant genera. (2) The plant species with the greatest contribution to species diversity in the four grassland samples was not the first dominant species of the community, but rather the plant species whose dominance was in the second to sixth position. (3) The first dominant species was overwhelmingly dominant in the four sample plots, and it served to increase the overall diversity of the community. (4) The overall trend in the size of the role of species in diversity is unimodal, i.e., logarithmically increasing to a maximum as species dominance decreases and then exponentially or linearly decreasing and eventually converging to zero. The synthesis showed that it was not the first dominant species that played the largest role in species diversity in the different grassland communities and that the overwhelmingly dominant species reduced the species diversity of the community.

13.
Opt Lett ; 49(12): 3364-3367, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38875621

RESUMEN

High-performance atomic magnetometers (AMs) rely on the measurement of optical rotation, which requires a set of bulky polarization optics that limit their applications in scenarios where portability and compactness are necessary. In this study, a miniaturized AM is constructed based on a cubic 87Rb vapor cell and monolithic metalens, which provides an integrated scheme to achieve optical rotation detection induced by the circular birefringence of polarized atoms. The designed metalens achieves polarization splitting with deflection angles of ±10∘ and focusing with efficiencies of approximately 30% for orthogonal linear polarizations. The sensitivity of our compact device is ∼30 fT/Hz1/2 with a dynamic range of around ±1.45 nT. We envision that the presented approach paves the way for the chip integration of emerging atomic devices, which are in demand for applications such as biomagnetic imaging and portable atomic gyroscopes.

14.
Redox Biol ; 75: 103239, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38901102

RESUMEN

Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the down-regulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuron-specific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKCα) at the Cys78 and Cys132 sites, leading to inhibition of PKCα kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKCα S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance.


Asunto(s)
Tolerancia a Medicamentos , Morfina , Proteína Quinasa C-alfa , Animales , Ratones , Morfina/farmacología , Proteína Quinasa C-alfa/metabolismo , Proteína Quinasa C-alfa/genética , Nitrosación , Aldehído Oxidorreductasas/metabolismo , Aldehído Oxidorreductasas/genética , Masculino , Ratones Noqueados , Analgésicos Opioides/farmacología , Modelos Animales de Enfermedad , Alcohol Deshidrogenasa
15.
Artículo en Inglés | MEDLINE | ID: mdl-38700969

RESUMEN

For small-object detection, vision patterns can only provide limited support to feature learning. Most prior schemes mainly depend on a single vision pattern to learn object features, seldom considering more latent motion patterns. In the real world, humans often efficiently perceive small objects through multipattern signals. Inspired by this observation, this article attempts to address small-object detection from a new prospective of latent pattern learning. To fulfill this purpose, it regards a real-world moving object as the spatiotemporal sequences of a static object to capture latent motion patterns. In view of this, we propose a motion-inspired cross-pattern learning (MICPL) scheme to capture the motion patterns for moving small-object scenarios. This scheme mainly consists of two crucial parts: motion pattern mining (MPM) and motion-vision adaption. The former is designed to effectively mine the motion pattern from time-dependent representation space. The latter is devised to correlate between motion patterns and vision semantics. In the meanwhile, we explore their cross-pattern interactions to guide MICPL to capture motion patterns effectively. Comparison experiments verify that, cooperated by motion pattern, even a simple detector could often refresh state-of-the-art (SOTA) results on moving small-object detection. Moreover, the experiments on two small-object-related tasks further prove the adaptivity and advantages of our cross-pattern feature learning scheme. Our source codes are available at https://github.com/ UESTC-nnLab/MICPL.

16.
Nat Plants ; 10(6): 1005-1017, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38773271

RESUMEN

The nuclear pore complex (NPC) is vital for nucleocytoplasmic communication. Recent evidence emphasizes its extensive association with proteins of diverse functions, suggesting roles beyond cargo transport. Yet, our understanding of NPC's composition and functionality at this extended level remains limited. Here, through proximity-labelling proteomics, we uncover both local and global NPC-associated proteome in Arabidopsis, comprising over 500 unique proteins, predominantly associated with NPC's peripheral extension structures. Compositional analysis of these proteins revealed that the NPC concentrates chromatin remodellers, transcriptional regulators and mRNA processing machineries in the nucleoplasmic region while recruiting translation regulatory machinery on the cytoplasmic side, achieving a remarkable orchestration of the genetic information flow by coupling RNA transcription, maturation, transport and translation regulation. Further biochemical and structural modelling analyses reveal that extensive interactions with nucleoporins, along with phase separation mediated by substantial intrinsically disordered proteins, may drive the formation of the unexpectedly large nuclear pore proteome assembly.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Poro Nuclear , Poro Nuclear/metabolismo , Poro Nuclear/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteoma/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Proteómica
17.
Environ Res ; 253: 119153, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763283

RESUMEN

Residual heavy metals in soils will destroy microbial community stability and influence its aggregation. However, exploring microbial ecology under heavy-metal stress still requires a conjoint analysis of bacterial interspecies communication and the community diversity maintenance mechanism. In this study, soil samples were collected from a heavy-metal-contaminated site in China to investigate the ecological response of indigenous microbial communities through high-throughput sequencing. Results showed that bacterial taxa and functions generated unusual decoupling phenomena. There were no significant differences in the diversity of species with the increase in concentration of heavy metals (Hg, Se, and Cr), but the functional diversity was lost. Also, the average niche breadth of bacterial species increased from 1.70 to 2.28, but community stability declined and the species assembly was always a deterministic process (NST <0.5). After the bacterial functional assembly changed from a stochastic process to a deterministic process (NST <0.5), it was transformed into a stochastic process (NST >0.5) again under the stress of high-concentration heavy metals, indicating that the collective stress resistance of bacterial communities changed from positive mutation into passive functional propagation. The research results can provide new insight into understanding the adaptive evolution of communities and ecosystem restoration under the stress of soil heavy metals.


Asunto(s)
Bacterias , Metales Pesados , Microbiología del Suelo , Contaminantes del Suelo , Metales Pesados/toxicidad , Metales Pesados/análisis , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Bacterias/genética , Bacterias/clasificación , Bacterias/efectos de los fármacos , China , Procesos Estocásticos , Microbiota/efectos de los fármacos
18.
Int J Mol Sci ; 25(7)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38612940

RESUMEN

Cell fate is precisely modulated by complex but well-tuned molecular signaling networks, whose spatial and temporal dysregulation commonly leads to hazardous diseases. Biomolecular condensates (BCs), as a newly emerging type of biophysical assemblies, decipher the molecular codes bridging molecular behaviors, signaling axes, and clinical prognosis. Particularly, physical traits of BCs play an important role; however, a panoramic view from this perspective toward clinical practices remains lacking. In this review, we describe the most typical five physical traits of BCs, and comprehensively summarize their roles in molecular signaling axes and corresponding major determinants. Moreover, establishing the recent observed contribution of condensate physics on clinical therapeutics, we illustrate next-generation medical strategies by targeting condensate physics. Finally, the challenges and opportunities for future medical development along with the rapid scientific and technological advances are highlighted.


Asunto(s)
Condensados Biomoleculares , Transducción de Señal , Biofisica , Diferenciación Celular , Fenotipo
19.
Cell Rep ; 43(4): 114088, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38602878

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.


Asunto(s)
Antígeno 2 del Estroma de la Médula Ósea , Proteínas Ligadas a GPI , Interferón-alfa , Neoplasias Pancreáticas , Macrófagos Asociados a Tumores , Animales , Femenino , Humanos , Ratones , Antígenos CD/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Proteínas Ligadas a GPI/metabolismo , Tolerancia Inmunológica , Interferón-alfa/metabolismo , Ratones Endogámicos C57BL , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Transducción de Señal , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/patología
20.
Cell Mol Immunol ; 21(6): 561-574, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38570588

RESUMEN

Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1ß expression levels and interleukin-1ß (IL-1ß) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor-/- mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor-/- Nlrp3-/- double-knockout (DKO) mice. Mechanistically, GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14 (MAPK14) at the Cys211 residue and augments MAPK14 kinase activity, thereby promoting Nlrp3 and Il-1ß transcription and stimulating NLRP3 inflammasome activity. Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.


Asunto(s)
Colitis , Sulfato de Dextran , Inflamasomas , Interleucina-1beta , Lipopolisacáridos , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Aldehído Oxidorreductasas/metabolismo , Aldehído Oxidorreductasas/genética , Colitis/inducido químicamente , Colitis/patología , Colitis/inmunología , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Macrófagos/inmunología , Nitrosación , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Choque Séptico/metabolismo , Choque Séptico/inducido químicamente , Proteína Quinasa 14 Activada por Mitógenos/metabolismo
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