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1.
Hortic Res ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35039835

RESUMO

MYB transcription factors play important roles in plant responses to cold stress, but the associated underlying mechanisms remain unclear. In this study, a cold-induced MYB transcription factor, DgMYB2, was isolated from chrysanthemum (Chrysanthemum morifolium Ramat). DgMYB2 was localized to the nucleus and exhibited transactivational activity. Overexpression of DgMYB2 improved cold tolerance in chrysanthemum, while cold tolerance in the antisense suppression lines decreased compared to that of the wild type. Additionally, electrophoretic mobility shift assays, chromatin immunoprecipitation, luciferase complementary imaging analysis, and dual-luciferase reporter gene detection experiments confirmed that DgMYB2 directly targets DgGPX1 and increases the activity of glutathione peroxidase to reduce the accumulation of reactive oxygen species, thereby improving cold resistance in chrysanthemum.

3.
Bioconjug Chem ; 33(1): 248-259, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34936326

RESUMO

Nanozymes are nanomaterials with enzyme-like activities, which have been developed for inflammatory disease therapy by reactive oxygen species (ROS) scavenging. The application of nanozymes in ulcerative colitis (UC) treatment not only inherits the merits of small molecular antioxidants (e.g., 5-aminosalicylic acid) to scavenge ROS but also achieves catalytic recycle instead of stoichiometric consumption. However, current therapies usually ignore the repair of mucosa, the first line of defense, whose damage increases the risk of infections. Herein, a multifunctional nanozyme hydrogel is designed and verified both as an ROS scavenger and a mucosal healing enhancer for UC therapy. The chitosan-coated CeO2 nanozyme (CCNZ) not only possesses excellent ROS-scavenging ability but also exhibits satisfactory antibacterial capacity. After gelation with alginate, the optimized CCNZ1:Alg1.5 nanozyme hydrogel exhibits multiple functions, including inflamed site targeting, supporting cell growth, ROS scavenging, and antibacterial activity, which alleviates UC better than a clinical medication 5-aminosalicylic acid by even a single-dose treatment. This study reveals that a nanozyme providing mucosal healing is promising for UC therapy with excellent potential for clinical application and enriches the nanozyme research of treatment for diseases.

4.
ACS Synth Biol ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878784

RESUMO

CRISPR/Cas has recently emerged as the most reliable system for genome engineering in various species. However, concerns about risks associated with the CRISPR/Cas technology are increasing on potential unintended DNA changes that might accidentally arise from CRISPR gene editing. Developing a system that can detect and report the presence of active CRISPR/Cas tools in biological systems is therefore very necessary. Here, we developed four real-time detection systems that can spontaneously indicate the presence of active CRISPR-Cas tools for genome editing and gene regulation including CRISPR/Cas9 nuclease, base editing, prime editing, and CRISPRa in plants. Using the fluorescence-based molecular biosensors, we demonstrated that the activities of CRISPR/Cas9 nuclease, base editing, prime editing, and CRISPRa can be effectively detected in transient expression via protoplast transformation and leaf infiltration (in Arabidopsis, poplar, and tobacco) and stable transformation in Arabidopsis.

5.
Chemosphere ; : 133046, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883130

RESUMO

In order to overcome the sluggish kinetics of the redox conversion between Fe3+ and Fe2+ in Fenton process, we established a novel electro-Fenton system based on GO-Fe3O4 cathode and tannic acid (TA) for the efficient degradation of p-nitrophenol (PNP). Under the optimal degradation parameters (including the initial PNP concentration of 20 mg L-1, pH = 5, current density of 30 mA cm-2 and feeding ratio of PNP: TA = 1:2), the TA reinforced GO-Fe3O4 electro-Fenton system exhibited the removal rate of PNP over 90.1 ±â€¯0.2%, the COD removal rate of 69.5 ±â€¯0.84% and satisfactory reusability (with the removal rate of ∼80% after 5 recycles). The excellent degradation performance of the proposed TA reinforced GO-Fe3O4 electro-Fenton system was partly attributed to the optimized morphology (with the particle size of Fe3O4 reduced to tens of nanometers, pore size decreased by ∼80% and pore volume increased by 24.3 times) and larger specific surface area (increased by 72.7 times) after compositing GO with Fe3O4, which exposed more active sites. In return, the electron transfer process, the two-electron oxygen reduction reaction (ORR) and the degradation efficiency were promoted in the cooperation of GO and Fe3O4. Moreover, the incorporated TA would form a TA-Fe(III) complex to promote the reduction reaction from Fe3+ to Fe2+, which strengthened the self-circulation of Fe2+ and Fe3+ and indirectly enhanced the conversion of H2O2 to ROS to decompose PNP into smaller organic fragments or mineralize into CO2, H2O, NO2- or NO3-, etc. Obviously, the incorporation of TA provided a promising strategy to improve the electro-Fenton efficiency and realize the efficient removal of PNP in wastewater.

6.
Retina ; 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34954775

RESUMO

PURPOSE: The study aimed to evaluate fixation stability and position changes after epiretinal membrane (ERM) surgery. METHODS: This is a retrospective study that included 60 consecutive eyes with idiopathic ERM. All patients received comprehensive ophthalmic examinations preoperatively and 1, 4, 10 months postoperatively. Main outcome measures included fixation stability and position, bivariate contour ellipse area (BCEA), and preferred retinal locus (PRL). RESULTS: The number of patients with stable fixation as well as predominantly central fixation was increased significantly after ERM surgery (61.7% vs. 73.3%, P=0.001; 41.7% vs. 71.7%, P=0.037). The correlation analysis showed that the preoperative factors associated with improved postoperative fixation stability were a larger BCEA value (P<0.001), poorer visual acuity (P=0.002), advanced stage (P=0.002), thicker CFT (P=0.015), and a longer PRL-foveal distant (P=0.0025). As for improved fixation location, the associated preoperative factors were age (P=0.003), CFT (P=0.044) and PRL-foveal distant (P<0.001). CONCLUSION: Our observations point to the changes of fixation parameters in patients after ERM surgery. We found that patients with preoperative unstable, eccentric fixation and poor BCVA can significantly benefit from the surgery. This result indicates that even in patients with severe macular damage, the ERM surgery still has great benefits in recovering visual function.

7.
3 Biotech ; 11(11): 486, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34790510

RESUMO

Tumor genome methylation is closely related to tumor immunosuppression. In the present study, we evaluated the fluctuations in DNA methylation levels, and the numbers of infiltrating T cells and their cytokines in different-grade cervical lesions. A total of 154 human cervical specimens that included LSIL (43 cases), HSIL (48 cases), and cervical squamous cancer (63 cases) were used for this study. Immunohistochemistry for 5-hydroxymethylcytosine (5hmC) and T-cell-attracting chemokines was performed, and multiplex immunofluorescence labeling was used to identify different T-cell subtypes. We found that the proportions of samples that immunostained weakly or negatively for 5hmC were increased commensurately with elevations in the severity of cervical lesions. The expression of T-cell-attracting chemokines-including CXCL9, CXCL10, and CXCL11-was positively associated with 5hmC levels, and CXCL9 was the cytokine that was most pronounced. With the progression of cervical lesions, the numbers of total T cells, CTL, and NK cells in the cervical tissues all gradually decreased. During the occurrence and development of cervical squamous carcinoma, 5hmC was gradually lost, and immunosuppression occurred in precancerous cervical lesions.

8.
Hortic Res ; 8(1): 234, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719678

RESUMO

Green fluorescent protein (GFP) has been widely used for monitoring gene expression and protein localization in diverse organisms. However, highly sensitive imaging equipment, like fluorescence microscope, is usually required for the visualization of GFP, limitings its application to fixed locations in samples. A reporter that can be visualized in real-time regardless the shape, size and location of the target samples will increase the flexibility and efficiency of research work. Here, we report the application of a GFP-like protein, called eYGFPuv, in both transient expression and stable transformation, in two herbaceous plant species (Arabidopsis and tobacco) and two woody plant species (poplar and citrus). We observed bright fluorescence under UV light in all of the four plant species without any effects on plant growth or development. eYGFPuv was shown to be effective for imaging transient expression in leaf and root tissues. With a focus on in vitro transformation, we demonstrated that the transgenic events expressing 1x eYGFPuv could be easily identified visually during the callus stage and the shoot stage, enabling early and efficient selection of transformants. Furthermore, whole-plant level visualization of eYGFPuv revealed its ubiquitous stability in transgenic plants. In addition, our transformation experiments showed that eYGFPuv can also be used to select transgenic plants without antibiotics. This work demonstrates the feasibility of utilizing 1x eYGFPuv in studies of gene expression and plant transformation in diverse plants.

9.
Signal Transduct Target Ther ; 6(1): 375, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34728602

RESUMO

The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.

10.
Ann Work Expo Health ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34608940

RESUMO

OBJECTIVES: The present study aimed to investigate the distribution of lymphocyte subsets and cytokines expression in the peripheral blood of bitumen fumes-exposed workers. METHODS: In this study, 129 workers from molding and roasting workshops were recruited as the exposed group and 99 office and quality inspection staff were chosen as the control. The polycyclic aromatic hydrocarbons (PAHs) levels of bitumen fumes in individual and fixed-point air samples and the urinary levels of 1-hydroxypyrene (1-OH-P), 1-hydroxynaphthols (1-OH-N) and 2-hydroxynaphthols (2-OH-N) in workers were measured using High Performance Liquid Chromatography. The lymphocyte subsets and serum cytokines concentrations were analyzed by flow cytometry and cytometric bead array, respectively. RESULTS: The median values of PAHs were 0.08 mg/m3 for permissible concentration-time weighted average and 0.12 mg/m3 for permissible concentration-short term exposure (PC-STEL) in molding and roasting workshops, which were higher than that in the control area (< 0.01 mg/m3). Multivariate linear regression models were used to adjust for influential covariates, including age, gender, work age, smoking status, and alcohol consumptions. After adjusting for these covariates, we compared levels of urinary PAHs metabolites, the percentages of lymphocyte subsets, and serum cytokines concentrations between the two groups. The 1-OH-P, 1-OH-N, and 2-OH-N levels in the urine of bitumen fumes exposed workers were significantly higher than that in the controls (P < 0.05). Compared with the control group, the percentage of the natural killer (NK) cell (CD56+ cell) was significantly increased in the exposed group (P < 0.001). There was a significant decrease in the percentages of CD3+ T cell, CD4+ T cell, and CD8+ T cell in the exposed group compared to the control (P < 0.001). The serum levels of interleukin-1ß (IL-1ß) and IL-6 in bitumen fumes exposed workers were significantly higher than that of the controls (P < 0.05). Moreover, positive correlations were observed between the serum levels of IL-1ß, IL-6, and urinary 1-OH-P levels in bitumen fumes-exposed workers, respectively (P < 0.05). There were no significant differences in the serum levels of IL-8, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1ß (MIP-1ß) and monocyte chemotactic protein-1 (MCP-1) between the exposed group and the control group (P > 0.05). CONCLUSION: Our study suggested that low dose of bitumen fumes exposure could decrease the percentage of T cell, increase the percentage of NK cell and stimulate the release of serum IL-1ß and IL-6 in the peripheral blood of exposed workers. The serum levels of IL-1ß and IL-6 were positive correlated with the urinary 1-OH-P levels in bitumen fumes exposed workers. These results may inform the search for potential effective biomarkers and provide evidences for early health monitoring in workers occupationally exposed to bitumen fumes.

11.
Plant Biotechnol J ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510693

RESUMO

Recent advances in plant genomics are scaling up gene expression profiling from the individual level to the population level, making transcriptomics a more powerful tool while deciphering the genome function. This study developed an efficient 3'RNA-seq method, Simplified Poly(A) Anchored Sequencing (SiPAS), to perform large-scale experiments of gene expression quantification. Aside from being cost-effective, by conducting a comprehensive performance assessment of SiPAS in hexaploid wheat, we demonstrated that SiPAS is highly sensitive, accurate, and reproducible while quantifying gene expression. Our method is anticipated to boost studies of population transcriptomics in plants and improve our understanding of genome biology.

12.
Cells ; 10(9)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34571864

RESUMO

The circadian clock drives time-specific gene expression, enabling biological processes to be temporally controlled. Plants that conduct crassulacean acid metabolism (CAM) photosynthesis represent an interesting case of circadian regulation of gene expression as stomatal movement is temporally inverted relative to stomatal movement in C3 plants. The mechanisms behind how the circadian clock enabled physiological differences at the molecular level is not well understood. Recently, the rescheduling of gene expression was reported as a mechanism to explain how CAM evolved from C3. Therefore, we investigated whether core circadian clock genes in CAM plants were re-phased during evolution, or whether networks of phase-specific genes were simply re-wired to different core clock genes. We identified candidate core clock genes based on gene expression features and then applied the Local Edge Machine (LEM) algorithm to infer regulatory relationships between this new set of core candidates and known core clock genes in Kalanchoë fedtschenkoi. We further inferred stomata-related gene targets for known and candidate core clock genes and constructed a gene regulatory network for core clock and stomata-related genes. Our results provide new insight into the mechanism of circadian control of CAM-related genes in K. fedtschenkoi, facilitating the engineering of CAM machinery into non-CAM plants for sustainable crop production in water-limited environments.


Assuntos
Metabolismo Ácido das Crassuláceas/genética , Redes Reguladoras de Genes/genética , Kalanchoe/genética , Relógios Circadianos , Regulação da Expressão Gênica de Plantas/genética , Fotossíntese/genética , Proteínas de Plantas/genética
13.
Proteomics ; 21(20): e2100127, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34482644

RESUMO

Populus spp. are dedicated woody biomass feedstocks for advanced biofuels and bioproducts. Proper growth and fitness of poplar as a sustainable feedstock depends on timely perception and response to environmental signals (e.g., light, temperature, water). Poplar leaves, like other C3 photosynthesis plants, have evolved oscillating or circadian rhythms that play important roles in synchronizing biological processes with external cues. To characterize this phenomenon at a molecular level, we employed bottom-up proteomics using high-resolution mass spectrometry and de novo-assisted database searching to identify abundance changes in proteins and post-translational modifications in poplar leaf tissue sampled across a 12/12-hour light/dark diurnal period.


Assuntos
Populus , Ritmo Circadiano , Fotossíntese , Folhas de Planta , Processamento de Proteína Pós-Traducional
14.
Trends Plant Sci ; 26(11): 1133-1152, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34340931

RESUMO

CRISPR construct design is a key step in the practice of genome editing, which includes identification of appropriate Cas proteins, design and selection of guide RNAs (gRNAs), and selection of regulatory elements to express gRNAs and Cas proteins. Here, we review the choices of CRISPR-based genome editors suited for different needs in plant genome editing applications. We consider the technical aspects of gRNA design and the associated computational tools. We also discuss strategies for the design of multiplex CRISPR constructs for high-throughput manipulation of complex biological processes or polygenic traits. We provide recommendations for different elements of CRISPR constructs and discuss the remaining challenges of CRISPR construct optimization in plant genome editing.

15.
Front Plant Sci ; 12: 704905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305991

RESUMO

A continuous increase in ambient temperature caused by global warming has been considered a worldwide threat. As sessile organisms, plants have evolved sophisticated heat shock response (HSR) to respond to elevated temperatures and other abiotic stresses, thereby minimizing damage and ensuring the protection of cellular homeostasis. In particular, for perennial trees, HSR is crucial for their long life cycle and development. HSR is a cell stress response that increases the number of chaperones including heat shock proteins (HSPs) to counter the negative effects on proteins caused by heat and other stresses. There are a large number of HSPs in plants, and their expression is directly regulated by a series of heat shock transcription factors (HSFs). Therefore, understanding the detailed molecular mechanisms of woody plants in response to extreme temperature is critical for exploring how woody species will be affected by climate changes. In this review article, we summarize the latest findings of the role of HSFs and HSPs in the HSR of woody species and discuss their regulatory networks and cross talk in HSR. In addition, strategies and programs for future research studies on the functions of HSFs and HSPs in the HSR of woody species are also proposed.

16.
Front Public Health ; 9: 695931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307288

RESUMO

Unlike past health crises that were more localized, the highly contagious coronavirus disease 2019 (COVID-19) crisis is impacting the world to an unprecedented extent. This is the first study examining how and whether the COVID-19 pandemic affects herding behavior in the Eastern European stock markets. Using samples from the stock markets of Russia, Poland, the Czech Republic, Hungary, Croatia, and Slovenia from January 1, 2010 to March 10, 2021, we demonstrate that the COVID-19 pandemic has increased herding behavior in all the sample stock markets. Our results show that the COVID-19 crisis reinforces the impact of global market returns on herding behavior in these specific stock markets. We find that COVID-19 strengthens the spillover effect of regional herding on herding behavior. Thus, financial authorities should monitor investors in the stock market to avoid the increase in herding behavior as well as the reinforcement of the global market returns and regional return dispersion on herding during the period of pandemic.


Assuntos
COVID-19 , Pandemias , Comércio , Croácia , República Tcheca , Humanos , Hungria , Investimentos em Saúde , Polônia , Federação Russa , SARS-CoV-2 , Eslovênia
17.
Ann Transl Med ; 9(9): 764, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34268377

RESUMO

Background: Andrographolide (Andro), a diterpenoid extracted from Andrographis paniculata, has been shown to attenuate pulmonary fibrosis in rodents; however, the potential mechanisms remain largely unclear. This study investigated whether and how Andro alleviates bleomycin (BLM)-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and epithelial-mesenchymal transition (EMT) in the lung epithelial cells. Methods: The in vivo effects of Andro were evaluated in a rat model of BLM-induced pulmonary fibrosis. The roles of Andro in BLM-induced NLRP3 inflammasome activation, EMT and AKT/mTOR signaling were investigated using human alveolar epithelial A549 cells. Results: We found that Andro significantly alleviated pulmonary edema and histopathological changes, decreased weight loss, and reduced collagen deposition. Andro downregulated the levels of NLRP3, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in the lungs of BLM-treated rats, suggesting the inhibitory effect of Andro on NLRP3 inflammasome activation in vivo. Additionally, the symptoms of BLM-mediated EMT phenotype in the lung were also attenuated after Andro administration. In vitro, Andro also markedly inhibited BLM-induced NLRP3 inflammasome activation and EMT in A549 cells. Moreover, Andro inhibited BLM-induced phosphorylation of AKT and mTOR in A549 cells, suggesting that AKT/mTOR inactivation mediates Andro-induced effects on BLM-induced NLRP3 inflammasome activation and EMT. Conclusions: These data indicate that Andro can reduce BLM-induced pulmonary fibrosis through suppressing NLRP3 inflammasome activation and EMT in lung epithelial cells via AKT/mTOR signaling pathway.

18.
Cells ; 10(6)2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204368

RESUMO

Crassulacean acid metabolism (CAM) is an important photosynthetic pathway for plant adaptation to dry environments. CAM plants feature a coordinated interaction between mesophyll and epidermis functions that involves refined regulations of gene expression. Plant microRNAs (miRNAs) are crucial post-transcription regulators of gene expression, however, their roles underlying the CAM pathway remain poorly investigated. Here, we present a study characterizing the expression of miRNAs in an obligate CAM species Kalanchoë marnieriana. Through sequencing of transcriptome and degradome in mesophyll and epidermal tissues under the drought treatments, we identified differentially expressed miRNAs that were potentially involved in the regulation of CAM. In total, we obtained 84 miRNA genes, and eight of them were determined to be Kalanchoë-specific miRNAs. It is widely accepted that CAM pathway is regulated by circadian clock. We showed that miR530 was substantially downregulated in epidermal peels under drought conditions; miR530 targeted two tandem zinc knuckle/PLU3 domain encoding genes (TZPs) that were potentially involved in light signaling and circadian clock pathways. Our work suggests that the miR530-TZPs module might play a role of regulating CAM-related gene expression in Kalanchoë.


Assuntos
Ritmo Circadiano/fisiologia , Metabolismo Ácido das Crassuláceas/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Kalanchoe/fisiologia , MicroRNAs/fisiologia , Genes de Plantas/fisiologia , Proteínas de Plantas/fisiologia , Transcriptoma
19.
Food Environ Virol ; 13(3): 357-367, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34152535

RESUMO

Norovirus, the leading cause of non-bacterial acute gastroenteritis (AGE) worldwide, is constantly mutating. Continuous monitoring of the evolution of epidemic genotypes and emergence of novel genotypes is, therefore, necessary. This study determined the prevalence and clinical characteristics of norovirus strains in AGE in Guangzhou, China in 2019/2020 season. This study included children aged 2-60 months diagnosed with AGE in Guangzhou Women and Children Hospital, from August 2019 to January 2020. Norovirus was detected by real-time polymerase chain reaction and clinical data were obtained. Genotyping and phylogenetic analyses were performed with partial gene sequence fragments located within the open reading frames 1 and 2. During the study period, 168 children (61.3% males) were confirmed as norovirus infectious AGE. The main symptoms were diarrhoea and vomiting and 38 patients (22.6%) had seizures. Norovirus was mainly prevalent in October and November, and GII.4 Sydney[P31] was the major genotype circulating in Guangzhou. The phylogenetic tree showed that the Guangzhou strains had high homology with the strains circulating in 2017-2019 worldwide. GII.4 Sydney was the main prevalent norovirus genotype in Guangzhou from August 2019 to January 2020, which had more severe diarrhoea than those of other genotypes. These findings provide a valuable reference for the prevention, control, and treatment of norovirus in the future.

20.
Int Immunopharmacol ; 98: 107859, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34153664

RESUMO

To explore the potential role of HMGB1 on TDI-induced NLRP3 inflammasome activation, HBE cells were treated with TDI-HSA conjugate to observe the changes of HMGB1, TLR4, NF-κB, Nrf2 and NLRP3 inflammasome related proteins expressions, ROS release and MMP. NAC, TPCA-1 and Resatorvid pre-treatments were applied to explore the effects of ROS, NF-κB and TLR4 on TDI-induced NLRP3 inflammasome activation. The CRISPR/Cas9 system was used to construct HMGB1 gene knockout HBE cell line and then to explore the role of HMGB1 on TDI-HSA induced NLRP3 inflammasome activation. GL pre-treatment was applied to further confirm the role of HMGB1. Results showed that TDI increased HMGB1, TLR4, P-p65, Nrf2 proteins expressions and ROS release, decreased MMP level and activated NLRP3 inflammasome in HBE cells in a dose dependent manner. NAC, TPCA-1 and Resatorvid pre-treatments decreased the expression of P-p65 and inhibited NLRP3 inflammasome activation. Inhibition of HMGB1 decreased Nrf2 expression and ROS release, improved MMP level and reduced NLRP3 inflammasome activation. GL ameliorated NLRP3 inflammasome activation via inhibiting HMGB1 regulated ROS/NF-κB pathway. These results indicated that HMGB1 was involved in TDI-induced NLRP3 inflammasome activation as a positive regulatory mechanism. The study provided a potential target for early prevention and treatment of TDI-OA.

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