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1.
Adv Mater ; : e2404787, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39126131

RESUMEN

The stability and catalytic activity of acidic oxygen evolution reaction (OER) are strongly determined by the coordination states and spatial symmetry among metal sites at catalysts. Herein, an ultrafast oxygen evaporation technology to rapidly soften the intrinsic covalent bonds using ultrahigh electrical pulses is suggested, in which prospective charged excited states at this extreme avalanche condition can generate a strong electron-phonon coupling to rapidly evaporate some coordinated oxygen (O) atoms, finally leading to a controllable half-metallization feature. Simultaneously, the relative metal (M) site arrays can be orderly locked to delineate some intriguing atom-fingerprints at pyrochlore catalysts, where the coexistence of metallic bonds (M─M) and covalent bonds (M─O) at this symmetry-breaking configuration can partially restrain crystal field effect to generate a particular high-spin occupied state. This half-metallization catalyst can effectively optimize the spin-related reaction kinetics in acidic OER, giving rise to 10.3 times (at 188 mV overpotential) reactive activity than pristine pyrochlores. This work provides a new understanding of half-metallization atom-fingerprints at catalyst surfaces to accelerate acidic water oxidation.

2.
Front Psychol ; 15: 1385746, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962234

RESUMEN

Interoception is the perception of the body's internal signals in response to various external and internal stimuli. The present study uses a novel method adapted from the CARdiac Elevation Detection Task to examine cardiac interoception objectively and subjectively in a unique context-in the presence of art. Self-report questionnaires were used to measure subjective interoceptive awareness, subjective interoceptive accuracy, and aesthetic appreciation. For objective interoceptive accuracy and sensibility, a wearable device (Shimmer) measured heart rate (HR) and connected to a mobile application to prompt two questions: "Is your heart beating faster than usual?" and "How confident are you in your previous response?" Participants explored an art gallery for 40 minutes while the Shimmer measured their HR and randomly prompted them to answer the questions. Using a Generalized Estimating Equation model, interoceptive sensibility was not found to predict the odds of submitting a correct response. It was also found that art does not improve participants' perceptions of their HR. Finally, there was no relation between aesthetic appreciation and subjective or objective cardiac interoception. Despite lack of statistical significance, the current study's method presents an improved method by examining interoceptive accuracy in the moment under ecological conditions. To date, findings and methods used in interoception are inconsistent or flawed; the value in the current study lies in the development and demonstration of a method to examine how the environment influences the body and self-awareness across a wide variety of contexts, thereby offering a possible standardized measure of interoception for investigators to adopt.

3.
Adv Mater ; : e2404418, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38973652

RESUMEN

Osmotic energy, often referred to as "blue energy", is the energy generated from the mixing of solutions with different salt concentrations, offering a vast, renewable, and environmentally friendly energy resource. The efficacy of osmotic power production considerably relies on the performance of the transmembrane process, which depends on ionic conductivity and the capability to differentiate between positive and negative ions. Recent advancements have led to the development of membrane materials featuring precisely tailored ion transport nanochannels, enabling high-efficiency osmotic energy harvesting. In this review, ion diffusion in confined nanochannels and the rational design and optimization of membrane architecture are explored. Furthermore, structural optimization of the membrane to mitigate transport resistance and the concentration polarization effect for enhancing osmotic energy harvesting is highlighted. Finally, an outlook on the challenges that lie ahead is provided, and the potential applications of osmotic energy conversion are outlined. This review offers a comprehensive viewpoint on the evolving prospects of osmotic energy conversion.

4.
Childs Nerv Syst ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012355

RESUMEN

Rosai-Dorfman disease (RDD) with craniocervical junction involvement is a rare clinical entity. We present herein a case of a pediatric patient with craniocervical junction RDD which was surgically treated. A 10-year-old female with a history of B-cell acute lymphoblastic leukemia (B-ALL) in remission and RDD presented with frontal migraine headaches. She previously had a right posterior chest wall lesion which was biopsy-proven RDD. She was found on imaging to have a dural-based right craniocervical junction lesion. Given her history of B-ALL, after a multidisciplinary discussion, the decision was made to proceed with resection with possible initiation of cobimetinib or clofarabine. The patient underwent a suboccipital craniotomy, C1 laminectomy, and resection of the dural-based lesion. Gross total resection was achieved, and histopathology confirmed the diagnosis of RDD. She was discharged home on postoperative day 4. No recurrence was seen on follow-up imaging at 3 months. We conducted a systematic literature review examining all cases of pediatric intracranial RDD and all cases of craniocervical junction RDD. This represents, to the best of our knowledge, only the second case of pediatric craniocervical junction RDD. Although RDD is often self-limiting, medical treatment is often considered for intracranial disease, but tissue confirmation is necessary. Surgical resection provides histopathologic diagnosis and can sometimes serve as definitive treatment for a particular lesion.

5.
Cureus ; 16(6): e62645, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39036104

RESUMEN

Sickle cell disease (SCD) is an autosomal recessive genetic disorder characterized by the abnormal formation of sickle hemoglobin (HbS). Under conditions of deoxygenation, HbS undergoes polymerization, resulting in microvascular occlusion, tissue hypoxia, and infarction. The elevated mortality rate associated with SCD is primarily attributed to complications such as sepsis, acute chest syndrome, stroke, acute multiorgan failure, and pulmonary hypertension. Despite advancements in awareness and treatments, preventing mortality in young individuals with SCD remains a formidable challenge. In an effort to shed light on these challenges, we present a case of unexpected death associated with SCD to emphasize the pressing need for continued research and intervention strategies to improve patient outcomes.

6.
Hum Cell ; 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004663

RESUMEN

The prevalence of autoimmune diseases ranks as the third most common disease category globally, following cancer and heart disease. Numerous studies indicate that long non-coding RNA (lncRNA) plays a pivotal role in regulating human growth, development, and the pathogenesis of various diseases. It is more than 200 nucleotides in length and is mostly involve in the regulation of gene expression. Furthermore, lncRNAs are crucial in the development and activation of immune cells, with an expanding body of research exploring their association with autoimmune disorders in humans. LncRNA Ifng antisense RNA 1 (IFNG-AS1), a key regulatory factor in the immune system, also named NeST or TMEVPG1, is proximally located to IFNG and participates in the regulation of it. The dysregulation of IFNG-AS1 is implicated in the pathogenesis of several autoimmune diseases. This study examines the role and mechanism of IFNG-AS1 in various autoimmune diseases and considers its potential as a therapeutic target.

7.
Small ; : e2401674, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39077956

RESUMEN

Electrochemical growth of metal nanocrystals is pivotal for material synthesis, processing, and resource recovery. Understanding the heterogeneous interface between electrolyte and electrode is crucial for nanocrystal nucleation, but the influence of this interaction is still poorly understood. This study employs advanced in situ measurements to investigate the heterogeneous nucleation of metals on solid surfaces. By observing the copper nanocrystal electrodeposition, an interphase interaction-induced nucleation mechanism highly dependent on substrate surface energy is uncovered. It shows that a high-energy (HE) electrode tended to form a polycrystalline structure, while a low-energy (LE) electrode induced a monocrystalline structure. Raman and electrochemical characterizations confirmed that HE interface enhances the interphase interaction, reducing the nucleation barrier for the sturdy nanostructures. This leads to a 30.92-52.21% reduction in the crystal layer thickness and a 19.18-31.78% increase in the charge transfer capability, promoting the formation of a uniform and compact film. The structural compactness of the early nucleated crystals enhances the deposit stability for long-duration electrodeposition. This research not only inspires comprehension of physicochemical processes correlated with heterogeneous nucleation, but also paves a new avenue for high-quality synthesis and efficient recovery of metallic nanomaterials.

8.
J Mol Neurosci ; 74(3): 71, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031207

RESUMEN

Acupuncture is a traditional Chinese therapy with treating potential against cognitive dysfunction. MicroRNA-21-3p (miR-21-3p) is well characterized for its benefits on neural tissues. The current study hypothesizes that the acupuncture aiming "Du" channel could attenuate IS-induced neural disorders by modulating the function of REST/miR-21-3p axis. Complications associated with IS are induced by a middle cerebral artery occlusion (MCAO) model in vivo. The disorders are then handled with the acupuncture with nimodipine as the positive control. It is found that the acupuncture improved cognitive function, reduced brain apoptosis, and increased the viable neuron number of model rats. Additionally, the production of cytokines is also suppressed by the acupuncture. At the molecular level, the level of miR-21-3p was up-regulated, while the level of REST was down-regulated by the acupuncture. The changes in miR-REST/21-3p contributed to the inhibition of PDCD4. Collectively, the findings in the current study highlight that miR-21-3p is associated with the anti-IS function of the acupuncture, which is mediated by the inhibition of REST.


Asunto(s)
Terapia por Acupuntura , Proteínas Reguladoras de la Apoptosis , Infarto de la Arteria Cerebral Media , MicroARNs , Transducción de Señal , Animales , Masculino , Ratas , Terapia por Acupuntura/métodos , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Encéfalo/metabolismo , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/genética , MicroARNs/genética , MicroARNs/metabolismo , Ratas Sprague-Dawley , Proteínas Represoras , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética
9.
Rev Cardiovasc Med ; 25(4): 113, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39076537

RESUMEN

In recent years, the interaction of intracellular organelles such as mitochondria and lysosomal functions has attracted increasing attention. Recent evidence suggests that mitochondrion-lysosomal contact plays a key role in regulating lysosomal biogenesis and maintaining cellular homeostasis. Myocardial ischemia and reperfusion will lead to corresponding changes in the autophagy flux in cardiomyocytes, and lysosomes are a key link in the process of autophagy, and the fusion of lysosomes and autophagosomes is an essential link in the occurrence of autophagy. Therefore, the function and homeostasis of lysosomes also undergo different changes during myocardial ischemia and reperfusion. Lysosomal-related biological factors and membrane proteins also play different roles. This article will review the mechanism of lysosomes in myocardial ischemia-reperfusion injury and the research progress of lysosomal-related proteins.

10.
Cardiovasc Toxicol ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026038

RESUMEN

Cardiovascular disease remains the leading cause of death worldwide, with acute myocardial infarction and anticancer drug-induced cardiotoxicity being the significant factors. The most effective treatment for acute myocardial infarction is rapid restoration of coronary blood flow by thrombolytic therapy or percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury (MI/RI) after reperfusion therapy is common in acute myocardial infarction, thus affecting the prognosis of patients with acute myocardial infarction. There is no effective treatment for MI/RI. Anthracyclines such as Doxorubicin (DOX) have limited clinical use due to their cardiotoxicity, and the mechanism of DOX-induced cardiac injury is complex and not yet fully understood. N6-methyladenosine (m6A) plays a crucial role in many biological processes. Emerging evidence suggests that m6A methylation plays a critical regulatory role in MI/RI and DOX-induced cardiotoxicity (DIC), suggesting that m6A may serve as a novel biomarker and therapeutic target for MI/RI and DIC. M6A methylation may mediate the pathophysiological processes of MI/RI and DIC by regulating cellular autophagy, apoptosis, oxidative stress, and inflammatory response. In this paper, we first focus on the relationship between m6A methylation and MI/RI, then further elucidate that m6A methylation may mediate the pathophysiological process of MI/RI through the regulation of cellular autophagy, apoptosis, oxidative stress, and inflammatory response. Finally, briefly outline the roles played by m6A in DIC, which will provide a new methodology and direction for the research and treatment of MI/RI and DIC.

11.
Ecology ; : e4380, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39031002

RESUMEN

Mutualistic symbioses between ants and plants are widespread in nature. Ants can deter unwanted pests and provide protection for plants in return for food or housing rewards. Using a long-term demographic dataset in a tropical seasonal rain forest in Southwest China, we found that associations with ants positively influenced seedling survival and adult growth, and also, species with extrafloral nectaries experienced weaker conspecific negative density dependence compared with species without extrafloral nectaries. Furthermore, we found strong evidence suggesting that species in our forest experienced conspecific density dependence, which we interpreted as heavy pest pressure that may drive the development of anti-pest symbioses such as the plant-ant relationship. Our findings suggest that ants and conspecific neighbors play important but inverse roles on plant survival and growth and that ants can buffer tree neighborhood interactions in this tropical forest.

12.
Sci Rep ; 14(1): 17249, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39060459

RESUMEN

At present, many trackers exhibit commendable performance in well-illuminated scenarios but overlook target tracking in low-light environments. As night falls, the tracker's accuracy drops dramatically. Challenges such as high image resolution, intricate backgrounds, uneven illumination, and the resemblance between targets and backgrounds in Hawk-Eye surveillance videos make tracking small objects in low-light and wide-field scenarios exceedingly difficult for previous trackers. To address these challenges, this paper introduces an innovative approach by integrating the difference constraint method into the CF (correlation filters) tracker, which generates a change-aware mask using inter-frame difference information. In addition, a dual regression model and inter-frame difference constraint term are introduced to restrict each other for dual filter learning. In this paper, we construct a new benchmark comprising 41 night surveillance sequences captured by Hawk-Eye cameras. Exhaustive experiments are conducted on this benchmark. The results show that the proposed method maintains superior accuracy, surpasses state-of-the-art trackers in this dataset, and achieves a real-time performance of 27 fps on a single CPU, substantially advancing tiny object tracking on Hawk-Eye surveillance videos in low light and in night scenes.

13.
Nanomicro Lett ; 16(1): 245, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995472

RESUMEN

Broadband electromagnetic (EM) wave absorption materials play an important role in military stealth and health protection. Herein, metal-organic frameworks (MOFs)-derived magnetic-carbon CoNiM@C (M = Cu, Zn, Fe, Mn) microspheres are fabricated, which exhibit flower-like nano-microstructure with tunable EM response capacity. Based on the MOFs-derived CoNi@C microsphere, the adjacent third element is introduced into magnetic CoNi alloy to enhance EM wave absorption performance. In term of broadband absorption, the order of efficient absorption bandwidth (EAB) value is Mn > Fe = Zn > Cu in the CoNiM@C microspheres. Therefore, MOFs-derived flower-like CoNiMn@C microspheres hold outstanding broadband absorption and the EAB can reach up to 5.8 GHz (covering 12.2-18 GHz at 2.0 mm thickness). Besides, off-axis electron holography and computational simulations are applied to elucidate the inherent dielectric dissipation and magnetic loss. Rich heterointerfaces in CoNiMn@C promote the aggregation of the negative/positive charges at the contacting region, forming interfacial polarization. The graphitized carbon layer catalyzed by the magnetic CoNiMn core offered the electron mobility path, boosting the conductive loss. Equally importantly, magnetic coupling is observed in the CoNiMn@C to strengthen the magnetic responding behaviors. This study provides a new guide to build broadband EM absorption by regulating the ternary magnetic alloy.

14.
J Am Chem Soc ; 146(31): 21922-21931, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39052980

RESUMEN

Donor-acceptor (D-A) conjugated systems have been extensively investigated and play important roles in organic electronics. Incorporating D-A structures into (hetero)cycloarenes endows them tunable electronic properties, while the well-defined cavity remains. However, the synthetic complexity of introducing electron-acceptor moieties into (hetero)cycloarenes limits their development and applications. In this paper, the first family of electronically tunable D-A heterocycloarenes (DAHCn, n = 1-5) based on pyrazine derivatives was facilely synthesized through cyclocondensation reaction from a tetraketone-functionalized heterocycloarene precursor prepared using the ketal-protection strategy. The effect of expanded conjugation and the inserted electron-withdrawing group on the electronic structures of the D-A heterocycloarenes was studied systematically by X-ray crystallographic analysis, various spectroscopic measurements, and theoretical calculations. Interestingly, the presence of an electron-withdrawing group polarizes the inner C(sp2)-H and significantly increases the binding affinities of D-A heterocycloarenes to the iodide anion. Meanwhile, the anion affinity can be further modulated by the type of attached substituents and the distance of polarization. More importantly, the dicyanopyrazine derivative DAHC3 shows the highest binding strength to the iodide ion as a 2:1 sandwich complex (log ß2 = 12.3 and ΔG = -69.1 kJ mol-1), which is the strongest iodide receptor using C(sp2)-H hydrogen bonding interactions reported to date. Our finding provides a new strategy to design and synthesize D-A heterocycloarenes and strong anion receptors.

15.
Neurotoxicology ; 103: 310-319, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39004286

RESUMEN

Isoflurane is one of the most commonly used anaesthetic agents in surgery procedures. During the past decades, isoflurane has been found to cause impairment in neurological capabilities in new-borns and elderly patients. Luteolin is a flavonoid that has been documented to possess a neuroprotective effect. Here we investigated the putative neuroprotective effects of luteolin on isoflurane-induced neurotoxicity in mouse hippocampal neuronal HT22 cells and explored the potential mechanisms. We demonstrated that luteolin improved mitochondrial dysfunction and reduced oxidative stress and apoptosis in isoflurane-treated HT22 cells, and thus inhibiting the isoflurane-induced neuronal injury. Further investigations showed that isoflurane exposure caused miR-214 downregulation, which could be mitigated by treatment with luteolin. Knockdown of miR-214 attenuated the neuroprotection of luteolin on isoflurane-induced neuronal injury. More importantly, luteolin inhibited isoflurane-caused regulation of the PTEN/Akt pathway, while miR-214 knockdown altered the regulatory effect of luteolin on the PTEN/Akt pathway. Furthermore, the effects of miR-214 knockdown on the neuroprotection of luteolin could also be prevented by knockdown of PTEN, implying that the neuroprotective effect of luteolin was mediated by miR-214/PTEN/Akt signaling pathway. These findings provided evidence for the potential application of luteolin in preventing isoflurane-induced neurotoxicity.


Asunto(s)
Hipocampo , Isoflurano , Luteolina , MicroARNs , Neuronas , Fármacos Neuroprotectores , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Isoflurano/toxicidad , Isoflurano/farmacología , Fosfohidrolasa PTEN/metabolismo , Luteolina/farmacología , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , MicroARNs/metabolismo , Fármacos Neuroprotectores/farmacología , Transducción de Señal/efectos de los fármacos , Línea Celular , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos
16.
Langmuir ; 40(32): 17001-17008, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39073323

RESUMEN

The solid-solid insulation interface structure is a typical interface in extra-high-voltage power equipment, in which the multilayer epoxy resin material is a key component in the insulation structure of the power equipment, and the study of its interface characteristics is the most important. In this paper, epoxy-epoxy cross-linking interface specimens were prepared through experiments, and the degree of cross-linking between the interfaces was analyzed by changing the ratio of the curing agent and adding hydroxyl-terminated liquid nitrile rubber (HTBN) particles; it can be concluded that there exists a weak cross-linking reaction between the interfaces. The electrical tree measurement and alternating current (AC) breakdown test platform were set up, and three different cases of no interface, the electric field direction parallel to the interface, and the electric field direction perpendicular to the interface were tested, through which it was concluded that the existence of the interface inhibited the development of the electrical tree. For the three different cases of AC breakdown tested, it was concluded that the presence of an interface enhances the AC breakdown strength when the electric field direction is parallel to the interface and decreases the AC breakdown strength when the electric field direction is perpendicular to the interface through the interface, affecting the charge transport.

17.
Angew Chem Int Ed Engl ; : e202411415, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990843

RESUMEN

Synthesis of fully fused π-conjugated cycloarenes embedded nonbenzenoid aromatics is challenging. In this work, the first example of four-membered ring-embedded cycloarene (MF2) was designed and synthesized in single-crystal form by macrocyclization and ring fusion strategies. For comparison, single bond-linked chiral macrocycle MS2 without two fused four-membered rings and its linear-shaped polycyclic benzenoid monomer L1 were also synthesized. The pronounced anti-aromaticity of four-membered rings significantly adjusts the electronic structures and photophysical properties of cycloarene, resulting in an enhancement of the photoluminescence quantum yield (PLQY) from 10.66% and 10.74% for L1 and MS2, respectively, to 54.05% for MF2, which is the highest PLQY among the reported cycloarenes. Notably, owing to the embedded four-membered rings that reduce structural displacements, MF2 exhibits an ultra-narrowband emission with a single-digit full-width at half-maximum (FWHM) of only 7 nm (0.038 eV), which sets a new record among all reported organic narrowband luminescent molecules, and represents the first example of ultra-narrowband emission in conventional polycyclic aromatic hydrocarbons (PAHs) devoid of heteroatoms.

18.
Clin Rheumatol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990379

RESUMEN

IgG4-related diseases (IgG-RDs) are a group of fibroinflammatory diseases that affect a variety of tissues, resulting in tumour-like effects and/or organ dysfunction. Monoclonal gammopathies (MGPs) are a group of disorders characterized by clonal proliferation of plasma cells or lymphoid cells resulting in the secretion of a monoclonal immunoglobulin. Cases of MGPs in IgG4-RDs coexisting with plasma cell dyscrasias and lymphoid neoplasms have been reported over the past few years. Therefore, the results of examinations of M protein in IgG4-RD patients should be interpreted with caution. Herein, we report the case of a 58-year-old male with a history of type 2 diabetes who presented with submandibular masses, anosmia, swollen lymph nodes, proteinuria, and renal impairment. Laboratory tests revealed hyperglobulinemia and elevated levels of IgG4 (124 g/L) and serum-free light chains (sFLCs). Serum protein electrophoresis (SPEP) revealed an M spike of 5.6 g/dL, and immunofixation electrophoresis (IPE) revealed biclonal IgG-κ and IgG-λ. The patient underwent bone marrow, lymph node, and kidney biopsy, which ruled out plasma cell disorders and lymphoma. He was finally diagnosed with an IgG4-RD comorbid with diabetic nephropathy. The findings in this case highlight that significant activation of B cells in IgG4-RD patients, especially those with multiorgan involvement can lead to significant hyperglobulinemia and high sFLC and IgG4 levels, which are more pronounced in the setting of renal impairment. Relatively high concentrations of polyclonal IgG4 can give rise to a focal band bridging the ß and γ fractions, which may mimic the appearance of a monoclonal band on SPEP and monoclonal gammaglobulinemia in IFE. The patient experienced considerable improvement in his symptoms after rituximab combined with glucocorticoid therapy, and a monoclonal immunoglobulin was not detected.

19.
Oral Dis ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937944

RESUMEN

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease characterized by a dense T-cell infiltration and the degeneration of basal keratinocytes. The potential functions of mucosal associated invariant T (MAIT) cells in OLP have been analyzed in our previous study. Keratinocytes under proinflammatory conditions have been demonstrated to activate T cells. This study was aimed to investigate how keratinocytes stimulate MAIT cells in OLP, and to explore the role of activated MAIT cells on keratinocytes. METHODS AND RESULTS: Increased MAIT cells and higher activation marker CD69 were detected in OLP lesions by flow cytometry. The enhanced expression of MHC class I-like molecule (MR1) required for MAIT cell activation in the epithelial layer of OLP lesions was determined by immunohistochemistry. Keratinocytes treated by 5-A-RU prodrug and lipopolysaccharide, respectively, exhibited higher expression of MR1 and secretion of IL-18. In direct coculture systems consisting of keratinocytes and peripheral blood mononuclear cells, both 5-A-RU prodrug-pretreated keratinocytes and lipopolysaccharide-pretreated keratinocytes activated MAIT cells to secrete granzyme B, contributing to elevated keratinocyte apoptosis. CONCLUSIONS: Keratinocytes were capable to activate MAIT cells via MR1 and cytokines in OLP, and granzyme B produced by activated MAIT cells intensified keratinocyte apoptosis, engaging in the pathogenesis of OLP.

20.
Pulm Pharmacol Ther ; 86: 102303, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38848887

RESUMEN

BACKGROUND: Interferon gene stimulator (Sting) is an indispensable adaptor protein that plays a crucial role in acute lung injury (ALI) induced by sepsis, and the PARP-1/NLRP3 signaling pathway may be an integral component of the inflammatory response mediated by Sting. However, the regulatory role of Sting in the PARP-1/NLRP3 pathway in ALI remains insufficiently elucidated. METHODS: Using lipopolysaccharide (LPS) to induce ALI in C57BL/6 mice and HUVEC cells, an in vivo and in vitro model was established. In vivo, Sting agonists and inhibitors were administered, while in vitro, Sting was knocked down using siRNA. ELISA was employed to quantify the levels of IL-1ß, IL-6, and TNF-α. TUNEL staining was conducted to assess cellular apoptosis, while co-immunoprecipitation was utilized to investigate the interaction between Sting and NLRP3. Expression levels of Sting, NLRP3, PARP-1, among others, were assessed via Western blotting and RT-qPCR. Lung HE staining and lung wet/dry ratio were evaluated in the in vivo mouse model. To validate the role of the PARP-1/NLRP3 signaling pathway, PARP-1 inhibitors were employed both in vivo and in vitro. RESULTS: In vitro experiments revealed that the Sting agonist group exacerbated LPS-induced pulmonary pathological damage, pulmonary edema, inflammatory response (increased levels of IL-6, TNF-α, and IL-1ß), and cellular injury, whereas the Sting inhibitor group significantly ameliorated the aforementioned injuries, with further improvement observed in the combination therapy of Sting inhibitor and PARP-1 inhibitor. Western blotting and RT-qPCR results demonstrated significant suppression of ICAM-1, VCAM-1, NLRP3, and PARP-1 expression in the Sting inhibitor group, with this reduction further enhanced in the Sting inhibitor + PARP-1 inhibitor treatment group, exhibiting opposite outcomes to the agonist. Furthermore, in vitro experiments using HUVEC cell lines validated these findings. CONCLUSIONS: Our study provides new insights into the roles of Sting and the PARP-1/NLRP3 signaling pathway in inflammatory responses, offering novel targets for the development of therapeutic interventions against inflammatory reactions.

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