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1.
Sci Total Environ ; 782: 146833, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33845369

RESUMO

The destabilization of rock glaciers and permafrost variations is of great importance to the safety of the population and infrastructure in the Karakoram region because of their effects on land stability and river obstructions. In this study, we compiled the first complete rock glacier inventory for the Hunza Basin, western Karakoram, of 616 rock glaciers with an area of 194 km2 between 2800 and 5700 m a.s.l. We categorized the rock glaciers as intact or relict, and their distributions and destabilization were further analyzed and used along with in situ climate and elevation dataset to model the permafrost probability distribution. The modeled areas where the permafrost zonation index (PZI) is 0.5-1.00 indicate that permafrost occurs over 85% of the catchment area and lies above 3525 m a.s.l., which closely matches the zero-degree isotherm of 3800 m a.s.l. Based on the sensitivity analysis of the independent variables, elevation is the most sensitive variable, followed by net radiation, for predicting the probabilities of the presence and absence of permafrost. The model distributions are quite precise, with median posterior areas under the curve of 0.98 and 0.96 for model training and testing, respectively. We analyzed the rock glacier destabilization for 68 rock glaciers that interacted with river channels, of which 50 blocked or diverted river channels. Destabilized rock glaciers can be closely linked to the 0 °C isotherm between 3400 and 4600 m a.s.l. The significant damage caused by periodic floods from the subsequent blockage of river channels by landslides can be attributed to variations in permafrost. Which demolished infrastructure, including a hydropower plant, suspension bridge and water supply system in Hassan-abad catchment. Quantification of rock glacier dynamics and permafrost in the region can further improve policies related to the reduction in disaster risk and mitigation of associated hazards.

2.
Int Immunopharmacol ; 96: 107580, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823430

RESUMO

Corneal lymphangiogenesis induced by macrophages played a critical role in corneal allograft rejection (CGR). However, there are few Food and Drug Administration (FDA)-approved drugs that target lymphangiogenesis. The aim of our study is to evaluate the effects of dimethyl fumarate (DMF) on corneal allograft survival in rats. Penetrating corneal transplantation was performed in rats. Subconjunctival injections of dimethyl fumarate (20 µg) were administered at the end of the operation and postoperative day 3 to day 11. The clinical signs of corneal allografts were evaluated. Immunohistochemistry, quantitative real-time PCR (qPCR), flow cytometry and western blot were performed respectively. The effects and mechanism of DMF on RAW264.7 cells were determined by qPCR, enzyme-linked immunosorbent assay (ELISA), and western blot in vitro. The results showed that subconjunctival injections of DMF could significantly inhibit corneal lymphangiogenesis and CGR with decreased corneal macrophage infiltration compared with the vehicle group. Moreover, DMF could reduce the mRNA expression of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and vascular endothelial growth factor-C (VEGF-C) in the corneal grafts and RAW264.7 macrophages by inhibiting NF-κB activation. Furthermore, compared with the vehicle group, the number of dendritic cells in the ipsilateral cervical lymph nodes of the DMF-treated group was decreased significantly. Collectively, our findings showed that DMF could suppress CGR by inhibiting the macrophage-induced corneal lymphoangiogenesis.

3.
Nanomaterials (Basel) ; 11(2)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673373

RESUMO

Organic-inorganic perovskite single crystals are promising in the field of optoelectronics due to their excellent optoelectronic properties. However, the ion transport of perovskite precursor is poor in confined spaces, which results in difficulty in the preparation of perovskite single-crystal films. Herein, MAPbBr3 films consisting of square grains were fabricated by the surface-confined process using the organic molecule PEAI (phenethylammonium iodide). Under the effect of oversaturation gradient, PEA+ is combined with the surface of perovskite grain from top to side, which constrains the lateral growth of grains and induces a downward growth of perovskite, leading to the formation of square grains. With the improvement of concentration PEAI, the perovskite film exhibits a decreased side length of grains (from 0.98 to 12.96 µm) and increased grain number and coverage, as well as crystallinity. The perovskite single crystalline grain films with PEAI showed double photoluminescence (PL) emission peaks due to the existence of iodine-rich perovskite. This work may provide a practical way to fabricate high-quality perovskite films for perovskite photoelectronic devices.

4.
Nat Commun ; 12(1): 1928, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772009

RESUMO

The development of organic thin-film transistors (OTFTs) with low power consumption and high gain will advance many flexible electronics. Here, by combining solution-processed monolayer organic crystal, ferroelectric HfZrOx gating and van der Waals fabrication, we realize flexible OTFTs that simultaneously deliver high transconductance and sub-60 mV/dec switching, under one-volt operating voltage. The overall optimization of transconductance, subthreshold swing and output resistance leads to transistor intrinsic gain and amplifier voltage gain over 5.3 × 104 and 1.1 × 104, respectively, which outperform existing technologies using organics, oxides and low-dimensional nanomaterials. We further demonstrate battery-powered, integrated wearable electrocardiogram (ECG) and pulse sensors that can amplify human physiological signal by 900 times with high fidelity. The sensors are capable of detecting weak ECG waves (undetectable even by clinical equipment) and diagnosing arrhythmia and atrial fibrillation. Our sub-thermionic OTFT is promising for battery/wireless powered yet performance demanding applications such as electronic skins and radio-frequency identification tags, among many others.

5.
Anal Chem ; 93(10): 4657-4665, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33651605

RESUMO

Rapid component separation and reliable surface-enhanced Raman scattering (SERS) detection of organochlorine pesticide (OCP) residues in real water samples remain major challenges because of sample complexity, trace content, and low molecular affinity for a metal surface. Here, we report a novel strategy of simultaneous in situ extraction and fabrication of plasmonic colloidal gold superparticles (AuSPs) to perform rapid SERS detection of OCPs in environmental water. In this protocol, multiple components of OCPs in complex water were facilely diffused into dichloromethane (DCM) microdroplets and specifically bound to octadecylamine-modified gold nanoparticles (Au-ODAs), affording the SERS substrate through self-assembly of the OCP-trapped Au-ODA into AuSPs with the evaporation of DCM. SERS signals of the specifically prepared Au-ODA could be used as an internal standard to calibrate the absolute signal of OCPs, and multiplex detection could be achieved depending on their molecularly narrow Raman peaks. As for simultaneously sensing four kinds of OCPs (4,4'-DDT, α-endosulfan, tetradifon, and chlordane) in water, the established method showed strong anti-interference ability and comparable quantification ranges with a low limit of detection (LOD). The recoveries ranged from 90.20 to 109.4% for OCPs in farmland, river, and fishpond water, indicating that the established AuSP-based platform is reliable and applicable to the detection of OCPs in real water samples.

7.
J Nutr ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33693698

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) has quickly spread across the world. However, the nutritional status of COVID-19 patients has not yet been extensively examined. OBJECTIVES: The aim of this study was to evaluate the nutritional status of COVID-19 patients and to identify factors independently associated with malnutrition risk. METHODS: In this single-center, cross-sectional study, we analyzed data from 760 hospitalized COVID-19 patients between 29 January 2020 and 15 March 2020. Based on the Nutrition Risk Screening (NRS) 2002 score, we divided patients into the normal nutrition group (NRS score <3) and the malnutrition risk group (NRS score ≥3). The associations of age, gender, symptoms, comorbidities, BMI, serum albumin and prealbumin concentrations, disease severity, activities of daily living (ADL) score, and clinical outcomes with malnutrition risk were analyzed. Multivariable logistic regression analysis was used to identify independent factors associated with malnutrition risk. RESULTS: Of patients with COVID-19, 82.6% were at risk of malnutrition. There were statistical differences in the age, incidence of fever, BMI, serum albumin and prealbumin concentrations, ADL score, and disease severity between the 2 groups. Multivariable logistic regression analysis revealed that age ≥65 y (vs. <65 y; OR: 5.40; P < 0.001), serum albumin <35 g/L (vs. ≥35 g/L; OR: 3.61; P < 0.001), serum prealbumin <150 mg/L (vs. ≥150 mg/L; OR: 2.88; P = 0.042), critical cases (vs. moderate cases; OR: 4.46; P < 0.001), ADL score 41-60 (vs. ADL score 100; OR: 4.50; P = 0.012), and ADL score ≤40 (vs. ADL score 100; OR: 9.49; P < 0.001) were significantly associated with the risk of malnutrition in COVID-19 patients. CONCLUSIONS: This study showed that prevalence of malnutrition risk was high in COVID-19 patients. Older age, low serum albumin and prealbumin concentrations, ADL score <60, and disease severity were independent factors associated with malnutrition risk.

8.
Org Lett ; 23(7): 2538-2542, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33739847

RESUMO

Compounds bearing fluorinated moieties are pervasive in a wide range of pharmaceuticals and agrochemicals. The installation of fluorinated units is a persistently vital task in synthetic chemistry, where facile and manipulable assays are highly demanding. Herein, we establish a general and programmable fluorination strategy for the modular assembly of mono- and difluoromethylarenes through the controllable deprotonation and fluorination of phosphonium ylides. Moreover, the rational combination of the reaction sequence allows the rapid construction of diversified fluorine-containing arenes.

9.
J Tradit Chin Med ; 41(1): 117-124, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33522204

RESUMO

OBJECTIVE: To evaluate the efficacy of Huanglian root decoction (, HLD) on kidney injury in rat's model of metabolic syndrome (MetS), and investigate the possible mechanism. METHODS: A fructose-induced MetS rat model and human renal tubular epithelial cell-line model were used to compare the efficacy of HLD with that of berberine and tauroursodeoxycholic acid (TUDCA). Blood pressure, biochemical parameters, histopathological changes and the expression levels of oxidative stress markers were evaluated in the animal model at the end of an 8-week treatment regimen. Oxidative stress markers and molecules of the signal pathway of endoplasmic reticulum (ER) stress were evaluated in the human cell-line model. RESULTS: Levels of fasting insulin, systolic blood pressure and diastolic blood pressure were significantly decreased in rats in the Huanglian group compared to those in the MetS group (P < 0.05). Rats treated with HLD and TUDCA exhibited a significant reduction in blood levels of malondialdehyde compared to those in rats in the MetS group (P < 0.05). Significant increases in glutathione peroxidase in human tubular epithelial cells was found in the Huanglian group compared to that in the MetS group (14.02 vs 18.31, P < 0.05). The mRNA expression of protein kinase RNA-like endoplasmic reticulum kinase and eukaryotic translation initiation factor 2 α decreased significantly in Huanglian groups compared with that in the MetS group. CONCLUSION: HLD has therapeutic efficacy on kidney injury in the MetS rat's model, and is non-inferior to berberine and TUDCA.

10.
Chem Commun (Camb) ; 57(19): 2392-2395, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33543206

RESUMO

A series of functional IRMOF-3 frameworks with solid-state luminescence and tuneable light emission (from 490 to 608 nm) have been synthesized by per-functionalizing AIE-active Schiff-bases with zinc. These precursor AIE-active ligands endowed the functional frameworks with boosted fluorescence emission efficiencies (from 0.16% to 1.03%). IRMOF-3-h revealed a flower-like morphology attributed to the formation of J-aggregates, and could be used as a fluorescent probe for sensitive detection of copper(ii) (135 pM) and thiols (subnanomole).

11.
Parasitol Res ; 120(4): 1281-1289, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33615408

RESUMO

Cryptosporidium is a genus of single-celled protozoa, infecting a wide range of animals and humans. Although Cryptosporidium infections of cattle have been reported in some provinces in China, there is no available information on the prevalence and predominant species of Cryptosporidium in cattle in Jiangxi province. To investigate the prevalence of Cryptosporidium in cattle in Jiangxi province of China, 556 fecal samples were collected from eight farms in four cities and the SSU rRNA locus of Cryptosporidium was amplified from the DNA of each fecal sample by PCR. The overall prevalence of Cryptosporidium was 12.8% (71/556) in cattle in Jiangxi province, with 24.3% (54/222) in Nanchang city, 7.8% (13/166) in Gao'an city, 3.7% (4/108) in Xinyu city, and 0.0% (0/60) in Ji'an city. The differences of the prevalence rates by region, breed, and age groups were statistically significant. All positive PCR products of Cryptosporidium were successfully sequenced and identified as three Cryptosporidium species, namely Cryptosporidium bovis (1/556, 0.18%), Cryptosporidium ryanae (7/556, 1.3%), and Cryptosporidium andersoni (63/556, 11.3%). Furthermore, 36 C. andersoni isolates were successfully classified into three MLST (multilocus sequence typing) subtypes based on four genetic loci (MS1, MS2, MS3, and MS16). The predominant MLST subtype was A4, A4, A4, A1 (n = 30). These findings not only revealed the prevalence and predominant species of Cryptosporidium in cattle in Jiangxi province, but also provided a baseline for studying the genetic structure of C. andersoni, offering a novel resource for better understanding of the epidemiology of Cryptosporidium infection in cattle in Jiangxi province, southeastern China.

12.
Org Lett ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33587645

RESUMO

Reported herein is the design and synthesis of new O-perhalopyridin-4-yl hydroxylamines as shelf-stable and versatile amidyl-radical precursors. The novel amination reagents can be easily prepared via a single synthetic step from inexpensive commercially available starting materials using monoprotected HONH2 as amino source. The synthetic potency of the developed reagents was well demonstrated by direct amination of a series of quinoxalin-2(1H)-ones and their analogues under photocatalytic conditions, even without any additive and photocatalysts.

13.
Int Immunopharmacol ; 93: 107430, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33581500

RESUMO

BACKGROUND: Anti-tumor necrosis factor-alpha was regarded as an option in treatment of non-infectious uveitis. However, few studies in the far easter region have concentrated on this therapy and current studies have not emphasized the elimination of retinal vasculitis. To compare the effectiveness of adalimumab (ADA) plus conventional therapy (CT) versus CT alone in treating patients with retinal vasculitis (RV) due to refractory Behçet's uveitis (BU). DESIGN: Retrospective cohort study. METHODS: Clinical records of BU patients with previously treated but poorly controlled RV were analyzed. Patients were allocated into two groups depending on ADA use. Each group was treated for no less than 6 months between February 2015 and September 2020. The primary outcome parameter was the RV score. Best-corrected visual acuity (BCVA), number of relapses, macular thickness and ocular complications were considered concomitantly. RESULTS: Forty-two patients (72 eyes) were included; 21 patients were in CT group, and 21 patients were in ADA group. Inflammatory parameters improved in both groups. The improvement in the fluorescein angiography (FA) score and anterior chamber inflammation were significantly better in ADA group than in CT group (P < 0.05). The relapse time was significantly lower in ADA group than in CT group (P = 0.01). Daily glucocorticoid dose tapers were more evident in ADA group than in CT group (P < 0.05). Adverse events were detected in 7 patients (5 had upper respiratory tract infection and 2 had gastrointestinal discomfort) in ADA group; in CT group, upper respiratory infection and recurrent gum swelling were observed in 1 patient each. CONCLUSION: Our results indicate that ADA plus CT outperforms CT alone in patients with RV due to refractory BU. More agile ADA use in these patients should be considered to achieve optimal treatment.

14.
J Environ Manage ; 286: 112230, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33636622

RESUMO

Debris flow alluvial fans (DFAFs) are vulnerable, although they can be used as a natural resource. The relationships between different factors related to DFAF systems and between these factors and systems are important both for identifying the risks and opportunities presented by DFAFs and for tracking system status. In this regard, resilience may be used to characterize the status of a DFAF. This study aimed to explore the processes and mechanisms of interactions among the social, economic, and ecological factors related to DFAF with respect to resilience, and to discuss potential problems in a representative DFAF. Based on the site condition and characteristics of the Awang DFAF (China) in the period 1996-2017, we formed a comprehensive indicator evaluation framework by analyzing disturbance, function, and feedback. We also established a model for evaluating resilience by integrating the analytic hierarchy process (AHP) - an entropy evaluation method (EEM) and set pair analysis (SPA). The results showed that the system of the studied DFAF was dynamically stable. The domination of the ecological system was subsequently superseded by social and economic resilience. While disturbance had direct and immediate effects, coping ability was cumulative and characterized by hysteresis at a particular response time. Overall, resilience fluctuated within an acceptable range rather than linearly increasing or decreasing. This analysis illuminated the dynamic processes of DFAFs and contributed to the understanding and planning of system trade-offs and degraded-land utilization.


Assuntos
Conservação dos Recursos Naturais , Utensílios Domésticos , China , Ecossistema
15.
Exp Cell Res ; 401(1): 112521, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33609534

RESUMO

Oxygen therapy is a common treatment in neonatal intensive care units, but long-term continuous hyperoxia ventilation may induce acute lung injury (ALI). Gasdermin D (GSDMD)-mediated pyroptosis participates in various diseases including ALI, but the role of GSDMD in hyperoxia-induced ALI is yet understood. Here, we showed a significant increase in GSDMD after exposure to high oxygen. To elucidate the molecular mechanisms involved in GSDMD regulation, we identified the core promoter of GSDMD, -98 ~ -12 bp relative to the transcriptional start site (TSS). The results of mutational analysis, overexpression or siRNA interference, EMSA and ChIP demonstrated that E2F4 and TFAP2A positively regulate the transcriptional activity of the GSDMD by binding to its promoter. However, only TFAP2A showed a regulatory effect on the expression of GSDMD. Moreover, TFAP2A was increased in the lung tissues of rats exposed to hyperoxia and showed a strong linear correlation with GSDMD. Our results indicated that TFAP2A positively regulates the GSDMD expression via binding to the promoter region of GSDMD.

16.
Dalton Trans ; 50(7): 2436-2447, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33507196

RESUMO

In this work, a novel NiFe layered double hydroxide-derived sulfide (NiFeSx)-modified g-C3N4 nanosheet photocatalyst (NiFeSx/g-C3N4) was synthesized, and its morphology, structure and visible light absorption capacity were simultaneously characterized by XRD, SEM, TEM, FT-IR, XPS, UV-Vis DRS, PL techniques and EIS Nyquist plots. Furthermore, it was discovered that at an optimum mass ratio of 3% (NiFeSx to g-C3N4), 3% NiFeSx/g-C3N4 composites exhibited the best degradation efficiency toward tetracycline hydrochloride refractory pollutants. The degradation rate of tetracycline hydrochloride by 3% NiFeSx/g-C3N4 composites was 92.54% under 70 min of visible light illumination, which was about 2.61 times higher than that of pure g-C3N4. The improved degradation activity may be attributed to the synergistic effect between the two constituents of as-synthesized composites, and the formed heterojunction reduced the efficiency of photogenerated carriers. More importantly, this work also gives some inspiration to synthesize some similar photocatalysts for a targeted environmental remediation.

17.
Org Lett ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33481615

RESUMO

An organocatalyzed enantiodivergent synthesis of a multifunctionalized spirooxindole-norcamphor scaffold via a [4 + 2]-annulation between cyclicα, ß-unsaturated ketone and methylene indolinones has been established. The presence of CaCl2 in DMF could reverse the enantioselectivity to facilely deliver the enantiomers of the corresponding spirooxindoles. Both enantiomers of the corresponding spirooxindoles were obtained in excellent yield and diastereo-/enantioselectivity by employing one single prolinosulfonamide catalyst.

18.
Talanta ; 224: 121894, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33379102

RESUMO

Low-cost, high-throughput, broadly useful photoresponsive enantiomeric excess (ee) sensing of amino acids remains challenging to date. Herein, based on the selective oxidation reaction of amino acid oxidase (AAO) to amino acid enantiomers (D/L-AA) and the oxidation reaction of substrate (H2O2) with aromatic boronic ester, we put forward a photoresponsive strategy for the determination of D/L-AA at a certain concentration. In this scheme, the substrate H2O2 produced by the enzyme-catalyzed reaction was determined by sensitive fluorescent and colorimetric response of ethyl-3-(3-(benzothiazol-2-yl)-5-methyl-2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)-2-cyanoacrylate (HBT-PB) to reflect the enantiomeric content at a certain concentration. The photoresponsive probe HBT-PB was readily available and inexpensive with sensitive long-wavelength red fluorescence and colorimetric light response to H2O2, the detection limit (LOD) was estimated as 2.91 µM. The operation of the sensing method was simple and data collection and processing are straightforward. The practicability of the scheme was favorably confirmed by accurate and scientific analysis of methionine and Dopa samples. As a result, the scheme was not only suitable for high-throughput screening but also adaptable to low-cost and sensitive RGB colorimetric analysis platform (LOD of methionine and Dopa was calculated as 9.23 µM and 8.34 µM respectively) with modern plate readers, and possessed extremely high enantioselectivity and wide applicability which benefited from the specificity and efficiency of enzyme catalytic reaction.

19.
Carbohydr Polym ; 254: 117189, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357839

RESUMO

The incidence of ulcerative colitis (UC) is high. Despite the availability of various therapeutic agents for the treatment of UC, the routine treatment has limitations and serious side effects. Therefore, a new drug that safely and effectively treats UC is urgently needed. Polysaccharides from natural resources have recently become a hot topic of study for their therapeutic effects on UC. These effects are associated with the regulation of inflammatory cytokines, intestinal flora, and immune system and protection of the intestinal mucosa. This review focuses on the recent advances of polysaccharides from natural resources in the treatment of UC. The mechanisms and practicability of polysaccharides, including pectin, guar gum, rhamnogalacturonan, chitosan, fructan, psyllium, glycosaminoglycan, algal polysaccharides, polysaccharides from fungi and traditional Chinese medicine, and polysaccharide derivatives, are discussed in detail. The good efficacy and safety of polysaccharides make them promising drugs for treating UC.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicina Tradicional Chinesa , Polissacarídeos/uso terapêutico , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal , Humanos , Estrutura Molecular , Polissacarídeos/química , Polissacarídeos/isolamento & purificação
20.
Int Immunopharmacol ; 91: 107300, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33383445

RESUMO

IL-23/IL-23R and PGE2/EP2+EP4 have been recognized as crucial signals that promote Th17 differentiation in many autoimmune diseases, including thyroid-associated ophthalmopathy (TAO). However, the interactive role of IL-23R in IL-23/Th17 signaling and PGE2/Th17 signaling has not been clarified in TAO. Furthermore, the role of IL-38, a novel anti-inflammatory cytokine, has not been explored in TAO. Thus, we aimed to investigate the roles of IL-23R and IL-38 in the pathogenesis of TAO. Activated peripheral blood mononuclear cells (PBMCs) were cultured with or without IL-23 and PGE2. The results showed that IL-23R and IL-17A were upregulated to different degrees and reached the highest levels with both stimuli, indicating that IL-23 induced PBMCs to secrete PGE2, which further boosted the proportion of IL-23R+CD4+T cells to promote IL-17A secretion. Pretreatment with antagonists aimed at EP2/EP4 receptors diminished PGE2-induced upregulation of IL-23R and IL-17A. IL-38 in TAO patients was increased. Activated orbital fibroblasts (OFs) and PBMCs were pretreated with different concentrations of IL-38. IL-23R and IL-17A expression in circulating PBMCs and IL-6 and IL-8 in resident OFs were suppressed by IL-38 at relatively low concentrations. Our findings suggest that the feedback loop of IL-23/IL-23R/PGE2/EP2+EP4/IL-23R/IL-17A plays a significant role in the pathogenesis of TAO and that IL-23R is one of the key targets. Increased IL-38 in TAO could not only inhibit the expression of IL-23R and IL-17A in PBMCs but also suppress inflammation in OFs. Therapies targeting IL-23R may be effective, and IL-38 could be a potential therapeutic approach for TAO.

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