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1.
IEEE Trans Cybern ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32386173

RESUMO

Influenced by many complex factors, it is very difficult to obtain high-performance industrial power load forecasting. The industrial power load forecasting is deeply studied by fusing some machine-learning methods for industrial enterprise power consumers. As a result, a novel power load forecasting method is proposed by taking into account the variation of load characteristics in different regions, industries, and production patterns. First, through the improved K-means clustering analysis, the historical load data are classified as the production patterns to which they belong. Then, the prediction algorithm combining reinforcement learning with particle swarm optimization and the least-squares support vector machine is proposed. Finally, the improved algorithm in this article is used for short-term load forecasting separately by the load data in different patterns after the above processing. The forecasting method in this article is based on data driven with real datasets. The results of the simulation experiment show that the improved prediction algorithm can distinguish the changes in different production patterns and identify the load characteristics of different regions and industries with high prediction accuracy, which has practical application value.

2.
Curr Neuropharmacol ; 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359338

RESUMO

Melatonin is a hormone produced in and secreted by the pineal gland. Besides its role in regulating circadian rhythms, melatonin has a wide range of protective functions in central nervous system (CNS) disorders. The mechanisms underlying this protective function are associated with the regulatory effects of melatonin on related genes and proteins. In addition to messenger ribonucleic acid (RNA) that can be translated into protein, an increasing number of non-coding RNAs in the human body are proven to participate in many diseases. This review discusses the current progress of research on the effects of melatonin modulation of non-coding RNAs (ncRNAs) including microRNA, long ncRNA, and circular RNA. The role of melatonin in regulating common pathological mechanisms through these ncRNAs are also summarized. Furthermore, the ncRNAs currently shown to be involved in melatonin signaling in CNS diseases are discussed. The information compiled in this review will open new avenues for future research into melatonin mechanisms and provide a further understanding of ncRNAs in the CNS.

3.
Chem Asian J ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286007

RESUMO

As an energy-storage system, rechargeable potassium-ion batteries (PIBs) have aroused widespread attention in recent years due to their earth abundance, low standard redox potential, and high ionic conductivity. The development of high-performance electrode materials is key to optimize the battery performance and useful to improve the feasibility of PIB technology. In this sense, a minireview on alloying-type anode materials for advanced PIBs is provided, covering the potassium storage properties, reaction mechanisms, theoretical analysis, electrochemical performance, and suitable binders and electrolytes.

4.
Paediatr Anaesth ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32323398

RESUMO

BACKGROUND: The use of lung-protective ventilation strategies with low tidal volumes may reduce the occurrence of postoperative pulmonary complications. However, evidence of the association of intraoperative tidal volume settings with pulmonary complications in pediatric patients undergoing major spinal surgery is insufficient. AIMS: This study examined whether postoperative pulmonary complications were related to tidal volume in this population and, if so, what factors affected the association. METHODS: In this retrospective cohort study, data from pediatric patients (<18 years old) who underwent posterior spinal fusion between 2016 and 2018 were collected from the hospital electronic medical record. The associations between tidal volume and the clinical outcomes were examined by multivariate logistic regression and stratified analysis. RESULTS: Postoperative pulmonary complications occurred in 41 (16.1%) of 254 patients who met the inclusion criteria. For the entire cohort, tidal volume was associated with an elevated risk of pulmonary complications (adjusted odds ratio [OR] per 1 mL/kg ideal body weight [IBW] increase in tidal volume, 1.28; 95% confidence interval [CI], 1.01-1.63, P = .038). In subgroup analysis, tidal volume was associated with an increased risk of pulmonary complications in patients older than 3 years (adjusted OR per 1 mL/kg IBW increase in tidal volume, 1.43, 95% CI: 1.12-1.84), but not in patients aged 3 years or younger (adjusted OR, 0.78, 95% CI: 0.46-1.35), indicating a significant age interaction (P = .035). CONCLUSION: In pediatric patients undergoing major spinal surgery, high tidal volume was associated with an elevated risk of postoperative pulmonary complications. However, the effect of tidal volume on pulmonary outcomes in the young subgroup (≤3 years) differed from that in the old (>3 years). Such information may help to optimize ventilation strategy for children of different ages.

6.
J Craniofac Surg ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32282479

RESUMO

OBJECTIVE: This study aimed to investigate the clinical outcomes of endoscopic transnasal optic canal decompression (ETOCD) for patients with indirect traumatic optic neuropathy (TON) and identify the relevant prognostic factors. METHODS: Seventy-two indirect TON patients who underwent ETOCD surgery from August 2017 to May 2019 were analyzed retrospectively. The paired t-test was used to compare the visual acuity (VA) before and after ETOCD, and multiple linear regression analysis was used to distinguish the potential prognostic factors. RESULTS: Among the patients analyzed, postoperative VA (-2.87 ±â€Š0.19) was significantly higher than the preoperative VA (-3.92 ±â€Š0.13) (P < 0.05). Multiple linear regression analysis models showed that poor initial VA and longer time to surgery were independent risk factors for VA prognosis (P < 0.05), but surgical time alone was significantly associated with the improvement degree of visual acuity (IDVA) (P < 0.05). Optic canal fracture, orbital fracture, and hemorrhage within the ethmoid and/or sphenoid sinus were not significantly correlated with IDVA and VA prognosis (P > 0.05). CONCLUSIONS: ETOCD surgery could salvage VA impairment in patients with indirect TON. A better initial VA indicates better final VA outcomes after surgery. Additionally, shorter time to surgery implies better VA prognosis and higher IDVA.

7.
Cell Commun Signal ; 18(1): 62, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293472

RESUMO

Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. Despite its high prevalence, effective treatment strategies for TBI are limited. Traumatic brain injury induces structural and functional alterations of astrocytes, the most abundant cell type in the brain. As a way of coping with the trauma, astrocytes respond in diverse mechanisms that result in reactive astrogliosis. Astrocytes are involved in the physiopathologic mechanisms of TBI in an extensive and sophisticated manner. Notably, astrocytes have dual roles in TBI, and some astrocyte-derived factors have double and opposite properties. Thus, the suppression or promotion of reactive astrogliosis does not have a substantial curative effect. In contrast, selective stimulation of the beneficial astrocyte-derived molecules and simultaneous attenuation of the deleterious factors based on the spatiotemporal-environment can provide a promising astrocyte-targeting therapeutic strategy. In the current review, we describe for the first time the specific dual roles of astrocytes in neuronal plasticity and reconstruction, including neurogenesis, synaptogenesis, angiogenesis, repair of the blood-brain barrier, and glial scar formation after TBI. We have also classified astrocyte-derived factors depending on their neuroprotective and neurotoxic roles to design more appropriate targeted therapies. Video Abstract.

8.
Microorganisms ; 8(3)2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32245148

RESUMO

Salmonella is an important cause of foodborne diseases. This study was undertaken to investigate the prevalence, serotype distribution, antimicrobial resistance, virulence genes, and genetic diversity of Salmonella isolates recovered from fresh duck meat obtained from retail markets in Southern China. In total, 365 samples of fresh duck meat were collected from retail markets in six different cities of Guangdong Province between May 2017 and April 2019. High levels of Salmonella contamination were detected in duck meat (151/365, 41.4%). Twenty-six different Salmonella serotypes were identified: S. Corvallis (n = 25, 16.6%), S. Kentucky (n = 22, 14.6%) and S. Agona (n = 20, 13.3%) were the most prevalent serotypes. All isolates were resistant to at least one antibiotic and 133 (88.1%) isolates exhibited multidrug resistance (MDR). Most (86.1%) Salmonella isolates carried seven classes of virulence-associated genes. This study showed the diversity of Salmonella serotypes and genotypes and the high prevalence of MDR isolates carrying multiple virulence-associated genes among isolates from duck meat obtained from retail markets in Southern China. Isolates from different districts had similar pulsed-field gel electrophoresis (PFGE) patterns indicating that circulating foodborne Salmonella constitutes a potential public health issue across different districts.

9.
J Autoimmun ; 109: 102432, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32115259

RESUMO

The pathogenesis of rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor (TCR) repertoires of different CD4+ T-cell subsets could help understand RA pathogenesis. Here, peripheral CD4+ T cells from treatment-naïve RA patients and healthy controls were sorted into seven subsets including naïve, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor ß chain repertoires were then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells of RA patients, with highly similar TCR repertoires. Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Notably, we showed that TCR diversity and abundance of differentiated T cells of Th17 were significantly correlated with RA disease activity. Based on these observations, we propose that abnormal differentiation from EMT to Th17 and expansion of Th17 play pivotal role in RA pathogenesis.

10.
J Phys Condens Matter ; 32(32): 325001, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32209744

RESUMO

Thin films with stable half-metallic (HM) character and 100% spin-polarization (SP) are required to be used in spintronic devices. The HM character has been predicted theoretically in many Heusler alloys thin films and confirmed by experiments. Full-Heusler alloy Ti2FeSn has been studied extensively. It has been reported that their (001)-oriented thin films with TiFe or TiSn terminations preserve 100% SP, but the HM character is unstable because the edge of the bandgap is closed to the Fermi level E F. Therefore, we investigate the effects of the Co-doping on the structural, electronic and magnetic properties of the bulk full-Heusler alloys Ti2Fe1-x Co x Sn (x = 0.00, 0.25, 0.50, 0.75 or 1.00) and their (001)-oriented thin films. The bulk Ti2Fe1-x Co x Sn (x = 0.00, 0.25, 0.50, 0.75 or 1.00) alloys are all HM ferromagnets. We investigate twelve possible terminations and show that five of them preserve HM character with 100% SP at the Fermi level E F, while in the remaining seven, surface states emerge in the spin-down channel at the Fermi level E F, significantly reducing their SP. The Co-doping significantly increases the stability of the TiSn slab, also increases its spin-down bandgap [Formula: see text] and HM gap [Formula: see text] at x = 0.50. The stable HM character makes it is a slab of maximum benefit in the applications of spintronic devices, especially in magnetic tunnel junctions.

11.
Front Immunol ; 11: 294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174916

RESUMO

Ischemic stroke, which accounts for 75-80% of all strokes, is the predominant cause of morbidity and mortality worldwide. The post-stroke immune response has recently emerged as a new breakthrough target in the treatment strategy for ischemic stroke. Glial cells, including microglia, astrocytes, and oligodendrocytes, are the primary components of the peri-infarct environment in the central nervous system (CNS) and have been implicated in post-stroke immune regulation. However, increasing evidence suggests that glial cells exert beneficial and detrimental effects during ischemic stroke. Microglia, which survey CNS homeostasis and regulate innate immune responses, are rapidly activated after ischemic stroke. Activated microglia release inflammatory cytokines that induce neuronal tissue injury. By contrast, anti-inflammatory cytokines and neurotrophic factors secreted by alternatively activated microglia are beneficial for recovery after ischemic stroke. Astrocyte activation and reactive gliosis in ischemic stroke contribute to limiting brain injury and re-establishing CNS homeostasis. However, glial scarring hinders neuronal reconnection and extension. Neuroinflammation affects the demyelination and remyelination of oligodendrocytes. Myelin-associated antigens released from oligodendrocytes activate peripheral T cells, thereby resulting in the autoimmune response. Oligodendrocyte precursor cells, which can differentiate into oligodendrocytes, follow an ischemic stroke and may result in functional recovery. Herein, we discuss the mechanisms of post-stroke immune regulation mediated by glial cells and the interaction between glial cells and neurons. In addition, we describe the potential roles of various glial cells at different stages of ischemic stroke and discuss future intervention targets.

12.
Biomed Res Int ; 2020: 9707238, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190693

RESUMO

Numerous grading scales have been proposed to predict the outcome of aneurysmal subarachnoid hemorrhage (SAH); however, these have not been validated in angiogram-negative SAH patients. In this study, we aim to validate and compare the aneurysmal SAH grading scales in angiogram-negative SAH patients. There were 190 angiogram-negative SAH patients analyzed from January 2014 to December 2015. The outcomes were measured by delayed cerebral ischemia (DCI) and poor outcome (defined as modified Rankin Scale (mRS) 3-6 or 4-6). The predictive performance of the grading scales was assessed via evaluation of distribution, trend, association, and discrimination. In regard to the distribution, none of the patients were categorized as HAIR 8 and SAH score 8. Both grading scales indicated a significant trend between scores and outcome (P < 0.05), and association with the outcome (OR > 1). The modified Fisher Scale (mFS), World Federation of Neurosurgical Societies scale (WFNS), and combined scores VASOGRADE and HAIR showed good predictive accuracy (area under the curve (AUC) > 0.750) for DCI. The predictive accuracy in each scale performed well in predicting poor outcome, with the exception of mFS and the Subarachnoid hemorrhage Early Brain Edema Score (SEBES). However, the mFS performed with increased accuracy when predicting mRS 4-6. The VASOGRADE, HAIR, and WFNS may be valuable prognostic tools for predicting both DCI and poor outcome. The mFS can be applicable for predicting DCI and mRS 4-6. The SAH score and the Hunt-Hess were also optimal for predicting poor outcome. The predictive performance of SEBES was relatively poor compared to the other scales.

13.
J Cell Mol Med ; 24(7): 3901-3916, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32091665

RESUMO

Using molecular signatures, previous studies have defined glioblastoma (GBM) subtypes with different phenotypes, such as the proneural (PN), neural (NL), mesenchymal (MES) and classical (CL) subtypes. However, the gene programmes underlying the phenotypes of these subtypes were less known. We applied weighted gene co-expression network analysis to establish gene modules corresponding to various subtypes. RNA-seq and immunohistochemical data were used to validate the expression of identified genes. We identified seven molecular subtype-specific modules and several candidate signature genes for different subtypes. Next, we revealed, for the first time, that radioresistant/chemoresistant gene signatures exist only in the PN subtype, as described by Verhaak et al, but do not exist in the PN subtype described by Phillips et al PN subtype. Moreover, we revealed that the tumour cells in the MES subtype GBMs are under ER stress and that angiogenesis and the immune inflammatory response are both significantly elevated in this subtype. The molecular basis of these biological processes was also uncovered. Genes associated with alternative RNA splicing are up-regulated in the CL subtype GBMs, and genes pertaining to energy synthesis are elevated in the NL subtype GBMs. In addition, we identified several survival-associated genes that positively correlated with glioma grades. The identified intrinsic characteristics of different GBM subtypes can offer a potential clue to the pathogenesis and possible therapeutic targets for various subtypes.

14.
Phys Chem Chem Phys ; 22(7): 3867-3874, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32026893

RESUMO

Using first-principles calculations based on density functional theory, we systematically investigated the electronic properties and charge transfer of topological insulator Bi2Te3-xSex thin films under an external electric field. As the selenium content in Bi2Te3-xSex thin films increases, the band gap is gradually opened, with changes in the charge distribution. In addition, the experimentally stable Bi2Te2Se and Bi2Se2Te thin films are extremely robust under vertical electric fields up to 0.2 V Å-1. The electronic structures of Bi2Te2Se and Bi2Se2Te thin films are insensitive to the electric fields and exhibit only a Rashba-like splitting pattern near the Fermi level. Remarkably, the charge transfer in Bi2Te2Se and Bi2Se2Te thin films under an external electric field is suppressed. We found that the robustness characteristic is inextricably linked to the strong covalent bonding of tellurium and bismuth atoms. These results indicated that Bi2Te2Se and Bi2Se2Te thin films are robust to the internal electrical field during growth on the substrate, which is beneficial for experimental studies as well as for the potential applications of spintronic devices.

15.
Neurosurg Rev ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32100134

RESUMO

To analyze the impact of the initial vision and surgical time for endoscopic transnasal/transethmosphenoid optic canal decompression (ETOCD) in the treatment of indirect traumatic optic neuropathy (TON). This retrospective case series analysis included 72 patients with indirect TON who underwent ETOCD from August 2017 to May 2019. Visual acuity (VA) was compared before and after surgery to estimate the improvement rate. The overall VA improvement rate of ETOCD was 54.2%. There were 83.3% and 33.3% improvement rate of patients with residual vision and blindness, respectively. VA was improved in 60.9% of patients treated within 3 days, 61.5% treated within 7 days, and 35.0% treated later than 7 days. Of the blindness patients, 50.0%, 37.5%, and 0.0% were treated within 3 days, 3-7 days, and later than 7 days, respectively. Of patients with residual vision, 85.7%, 92.3%, and 70.0% were treated within 3 days, 3-7 days, and later than 7 days, respectively. A statistically significant difference was found between patients with residual vision and those with blindness (P < 0.01), as well as between patients who received ETOCD within 7 days and those who received ETOCD later than 7 days (P = 0.043). The improvement rate of blindness patients managed within 3 days (P = 0.008) and 3-7 days (P = 0.035) was significantly higher than that for patients managed beyond 7 days. Indirect TON patients can directly benefit from ETOCD, and patients with residual vision have better improvement rates. ETOCD should be performed as soon as possible to salvage the patient's VA, especially within the first 7 days. For blindness patients, it is necessary to carry out the surgery within 7 days with increased benefit seen before 3 days.

16.
Clin Neurol Neurosurg ; 191: 105691, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31986364

RESUMO

OBJECTIVES: Current guidelines paid little attention to a unique severe disease about intracranial hematoma owing to aneurysm rupture. We attempted to explore the predictive factors for prognosis in these poor patient population. PATIENTS AND METHODS: One hundred twenty-one aneurysmal subarachnoid hemorrhage combined with intracerebral hematoma patients discharged between 2013 and 2016 were reviewed in this retrospective study. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score of 3, 4, 5, or 6 at 6 months. Multivariable logistic regression was performed to evaluate the association of unfavorable outcome with preoperative and postoperative clinical characteristics. RESULTS: Of 121 patients with intact follow-up data, 34 (28.10 %) had an unfavorable prognosis. The preoperative prognostic model included patients' age, respiratory rate, Hunt-Hess scale, red cell distribution width, and serum sodium at admission. The postoperative prognostic model included patients' age, respiratory rate, red cell distribution width, serum sodium, postoperative delayed cerebral ischemia, and pulmonary infection. Both preoperative and postoperative prognostic models had excellent discrimination with Area Under The Curve (AUC) of 0.864 (P < .001) and 0.898 (P < .001), respectively. CONCLUSION: In clinical practice, we should pay more attention to those old patients with worse admission Hunt-Hess score, presenting deep-slow respiratory and lower serum sodium. Reduction of postoperative delayed cerebral ischemia and pulmonary infection might improve outcomes after aneurysmal SAH with intracerebral hematoma.

17.
J Psychopharmacol ; 34(4): 441-451, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31913078

RESUMO

BACKGROUND: Fast-acting and cognitive-enhancing antidepressants are desperately needed. Activation of translocator protein (18 kDa, TSPO) is a novel strategy for developing potential antidepressants, but there are no data available on the onset time of TSPO ligands. This study aimed to investigate the fast-onset antidepressant actions of AC-5216, a selective TSPO ligand, in TSPO knock-out (KO) mice. METHODS: TSPO wild-type (WT) and KO mice were subjected to a six-week chronic unpredicted stress (CUS) paradigm. Then, the mice were treated with AC-5216 and tested with depressive and cognitive behaviours. RESULTS: A single dose of AC-5216 (0.3 mg/kg) exerted anxiolytic- and antidepressant-like actions in TSPO WT mice. Moreover, in chronically stressed WT mice, two to four days of AC-5216 treatment (0.3 mg/kg, once per day) produced fast-onset antidepressant-like effects in the novelty-suppressed feeding and sucrose preference tests, as well as memory-enhancing effects in the novel object recognition test. In addition, a rapid (with five days of treatment) restoration of serum corticosterone levels and prefrontal cortex (PFC) allopregnanolone levels was found. Further studies showed that in these stress-exposed WT mice, AC-5216 significantly increased the levels of mTOR signalling-related proteins (mBDNF, p-mTOR, PSD-95, synapsin-1, GluR1), as well as the total dendritic length and branching points of pyramidal neurons in the PFC. CONCLUSIONS: These results suggest that TSPO mediates the fast-onset antidepressant-like and memory-enhancing effects of AC-5216, possibly through the rapid activation of mTOR signalling and restoration of dendritic complexity in the PFC.

18.
J Autoimmun ; 108: 102404, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31952907

RESUMO

The chromatin modifier enhancer of zeste homolog 2 (EZH2) methylates lysine 27 of histone H3 (H3K27) and regulates T cell differentiation. However, the potential role of EZH2 in the pathogenesis of rheumatoid arthritis (RA) remains elusive. We analyzed EZH2 expression in PBMC, CD4+ T cells, CD19+ B cell, and CD14+ monocytes from active treatment-naïve RA patients and healthy controls (HC). We also suppressed EZH2 expression using EZH2 inhibitor GSK126 and measured CD4+ T cell differentiation, proliferation and apoptosis. We further examined TGFß-SMAD and RUNX1 signaling pathways in EZH2-suppressed CD4+ T cells. Finally, we explored the regulation mechanism of EZH2 by RA synovial fluid and fibroblast-like synoviocyte (FLS) by neutralizing key proinflammatory cytokines. EZH2 expression is lower in PBMC and CD4+ T cells from RA patients than those from HC. EZH2 inhibition suppressed regulatory T cells (Tregs) differentiation and FOXP3 transcription, and downregulated RUNX1 and upregulated SMAD7 expression in CD4+ T cells. RA synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4+ T cells, which was partially neutralized by anti-IL17 antibody. Taken together, EZH2 in CD4+ T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4+ T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4+ T cells. Defective EZH2 in CD4+ T cells might contribute to Treg deficiency in RA.

19.
J Phys Chem Lett ; : 1435-1442, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31922750

RESUMO

Conversion-type anode materials for sodium ion batteries have received extensive attention because of their relatively high theoretical capacity. However, multiple challenging obstacles stand in the way of their commercial application, especially their poor cycling stability resulting from the bad reversibility of the conversion reaction. Herein, Ni-Co bimetal sulfide was selected and investigated with the goal of improving the reversibility of the conversion reaction owing to the similarity of Ni and Co. As expected, when three-dimensional hierarchical Ni@NiCo2S4 (NiCo2S4 nanowires growing on the Ni foam) was applied as the free-standing anode for sodium ion batteries, it demonstrated high capacity and excellent cycling stability (90.65%, 100 cycles) compared with those of monometallic sulfides. Various characterization [in situ X-ray diffraction (XRD), ex situ XRD, ex situ X-ray photoelectron spectroscopy, FESEM mapping, and high-resolution transmission electron microscopy] tests confirmed that the Ni-Co alloy was formed during the discharge process and effectively prevented the crystalline grain growth of conversion reaction products, improving the reaction kinetics and reversibility.

20.
J Autoimmun ; 106: 102336, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31601476

RESUMO

Excessive inflammatory cytokines play crucial roles in the pathogenesis of rheumatoid arthritis (RA), however, the underlying mechanism remains unclear. In this study, we demonstrated that pentaxin 3 (PTX3), an essential component of innate immunity, was elevated in RA and preferentially bound to CD14+ monocytes. C1q promoted the binding and resulted in increased cell proliferation, activation and caspase-1-related late apoptotic cells (7-AAD+annexin V+), as well as enhanced release of inflammatory cytokines including TNF-α, IL-1ß and IL-6. Serum from RA patients, compared with healthy controls, induced gasdermin D (GSDMD)-dependent pyroptosis in monocytes, and this ability was associated with disease activity. Moreover, PTX3 synergized with C1q to promote pyroptosis in RA-serum pre-incubated monocytes by coordinately enhancing NLRP3 inflammasome over-activation and inducing GSDMD cleavage, cell swelling with large bubbles, caspase-1-dependent cell death and inflammatory cytokine release including IL-6. On the other hand, IL-6 promoted PTX3 plus C1q-induced pyroptosis in both normal and RA serum pre-incubated monocytes. These findings collectively implicated an important role of IL-6 in driving PTX3 plus C1q-mediated pyroptosis in RA and shed lights on a potential new treatment strategy targeting pyroptosis-mediated persistent inflammatory cytokine release.

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