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1.
Talanta ; 236: 122872, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635253

RESUMO

A conjugated microporous organic polymer (TPA-Bp) comprised of triphenylamine (TPA) and 2,2'-bipyridine-5,5'-diformaldehyde (Bp) was prepared via the Schiff-base reaction under ambient conditions. TPA-Bp is an amorphous and microporous spherical nanoparticle with very high stability. TPA-Bp suspension in DMF displayed strong fluorescence emission and selective fluorescence quenching response towards Fe3+ and Fe2+ ions. The fluorescence intensity of TPA-Bp at 331 nm presents linear relationship with the concentrations of both Fe3+ and Fe2+ with low detection limits of 1.02 × 10-5 M for Fe3+ and 5.37 × 10-6 M for Fe2+. The results of X-ray photoelectron spectroscopy (XPS) and Fourier Transform infrared spectroscopy (FTIR) confirm the selective coordination of N atoms of pyridine unit with Fe ions. The fluorescence quenching of TPA-Bp upon the addition of Fe3+/Fe2+ ions can be attributed to the absorption competition quenching (ACQ) mechanism and the energy transfer between TPA-Bp and Fe3+/Fe2+ ions. This work demonstrates that the conjugated microporous polymers are promising candidates as luminescent sensor for detection of the special analytes in practical applications.

2.
Invest New Drugs ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633577

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. According to reports, leukotriene B4 receptor 2 (LTB4R2, also known as BLT2), a chemokine receptor, is upregulated in different tumors. However, the correlation between BLT2 expression and its prognostic value in ccRCC remains to be explored. METHODS: This study used the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to evaluate the association between BLT2 expression and the clinical outcome of ccRCC. Based on TIMER2.0, the correlation between BLT2 expression in ccRCC and tumor immune characteristics was evaluated. RESULTS: The expression of BLT2 in ccRCC was higher than that in normal tissues. Kaplan-Meier survival analysis indicated that high BLT2 expression was significantly correlated with poor overall survival (HR = 1.75, p < 0.001) and disease-specific survival (HR = 1.60, p = 0.014) for patients with ccRCC. In addition, our findings revealed that there was no significant correlation between the M1 marker genes and the expression of BLT2 in ccRCC, while moderate correlations were observed between the BLT2 expression and the M2 marker genes. Tregs and T cell exhaustion marker genes were positively correlated with BLT2 expression in ccRCC (p < 0.001). CONCLUSION: BLT2 may serve as a novel prognostic biomarker and is related to the shaping of tumor immune microenvironment in ccRCC. The expression of BLT2 potentially contributes to the regulation of TAMs, T cell exhaustion, and Tregs activation in ccRCC, providing new approaches to promote the development of new immunotherapeutic strategies for ccRCC.

3.
Phys Med Biol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34619675

RESUMO

Background and objective Optical Coherence Tomography (OCT) is one of the most used retinal imaging modalities in the clinic as it can provide high-resolution anatomical images. The huge number of OCT images has significantly advanced the development of deep learning methods for automatic lesion detection to ease the doctor's workload. However, it has been frequently revealed that the deep neural network (DNN) model has difficulty handling the domain discrepancies, which widely exist in medical images captured from different devices. Many works have been proposed to solve the domain shift issue in deep learning tasks such as disease classification and lesion segmentation, but few works focused on lesion detection, especially for OCT images. Methods In this work, we proposed a faster-RCNN based, unsupervised domain adaptation model to address the lesion detection task in cross-device retinal OCT images. The domain shift is minimized by reducing the image-level shift and instance-level shift at the same time. We combined a domain classifier with a Wasserstein distance (WD) critic to align the shifts at each level. Results The model was tested on two sets of OCT image data captured from different devices, obtained an average accuracy improvement of more than 8% over the method without domain adaptation, and outperformed other comparable domain adaptation methods. Conclusion The results demonstrate the proposed model is more effective in reducing the domain shift than advanced methods.

4.
Exp Cell Res ; : 112864, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626586

RESUMO

Dental implant surgery is currently a routine therapy for the repair of missing dentition or dentition defects. Both clinical and basic research have elucidated that oxidative stress caused by the accumulation of reactive oxygen species (ROS) for various reasons impairs the process of osteointegration after dental implantation. Therefore, the osteogenic micro-environment must be ameliorated to decrease the damage caused by oxidative stress. Selenomethionine (SEMET) has been reported to play an important role in alleviating oxidative stress and accelerating cell viability and growth. However, it remains unclear whether it exerts protective effects on bone-marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress. In this study, we explored the influence of selenomethionine on the viability and osteogenic differentiation of BMSCs under oxidative stress and the underlying mechanisms. Results showed that 1 µM selenomethionine was the optimum concentration for BMSCs under H2O2 stimulation. H2O2-induced oxidative stress suppressed the viability and osteogenic differentiation of BMSCs, manifested by the increases in ROS production and cell apoptosis rates, and by the decrease of osteogenic differentiation-related markers. Notably, the aforementioned oxidative damage and osteogenic dysfunction induced by H2O2 were rescued by selenomethionine. Furthermore, we found that the PTEN expression level was suppressed and its downstream PI3K/AKT pathway was activated by selenomethionine. However, when PTEN was stimulated, the PI3K/AKT pathway was down-regulated, and the protective effects of selenomethionine on BMSC osteogenic differentiation diminished, while the inhibition of PTEN up-regulated the protective effects of selenomethionine. Together, these results revealed that selenomethionine could attenuate H2O2-induced BMSC dysfunction through an antioxidant effect, modulated via the PTEN/PI3K/AKT pathway, suggesting that selenomethionine is a promising antioxidant candidate for reducing oxidative stress during the process of dental implant osteointegration.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34607429

RESUMO

A novel integrated bioinspired surface is fabricated by using an innovative capillarity-induced selective oxidation method, to achieve the combination of the fog-collecting characteristics of a variety of creatures, i.e., the micronanostructures of spider silk, the wettable patterns of desert beetle, the conical structure of cactus spine, and the hierarchical microchannel of Sarracenia trichome. The fog is captured effectively via multistructures on the cone tips, and captured droplet is collected and confined in the microchannel to realize rapid transport via the formation of wettable pattern on the surface and the introduction of wettable gradient in the microchannel. Consequently, the fog harvest efficiency reaches 2.48 g/h, increasing to nearly 320% compared to the normal surface. More interestingly, similar to Sarracenia trichome, the surface also presents two transport modes, namely, Mode I (water transport along dry microchannel) and Mode II (succeeding water slippage on the water film). In Mode II, the velocity of 34.10 mm/s is about three times faster than that on the Sarracenia trichome. Such a design of integrated bioinspired surface may present potential applications in high-efficiency water collection systems, microfluidic devices, and others.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34599442

RESUMO

Previous studies have found that non-optimal temperature influences the development of gout, but the results have been inconsistent. The present study aimed to explore the effects of high temperature and high temperature variation on hospitalizations for gout in Anqing, China. We collected daily data on air pollutants, meteorological factors, and hospitalizations for gout between 1January 2016 and 31 December 2020 in Anqing City, China. We used Poisson generalized linear regression model and a distributed lag non-linear model (DLNM) to explore the relationship of high temperature, diurnal temperature range (DTR), and temperature change between neighboring days (TCN) with hospitalizations for gout. Stratified analysis by gender (male, female) and age (<65 years, ≥65 years) was conducted. Hospitalizations for gout attributed to high temperature, high DTR, and high TCN were also quantified. A total of 8675 hospitalized patients with gout were reported during the study period. We observed that exposure to high temperature was linked with an increased risk of hospitalizations for gout (lag 0, RR: 1.081, 95% confidence interval (CI): 1.011, 1.155). Exposure to high DTR was also associated with increased risk of hospitalizations for gout (lag9, RR: 1.017, 95% CI: 1.001,1.035). A large drop in temperature between neighboring days was associated an increased risk of hospitalizations for gout (lag 0-2 days, RR: 1.234, 95% CI: 1.017, 1.493). Stratified analysis results revealed that older adults and men were more sensitive to high-level DTR exposure than their counterparts. Nearly 15% of hospitalizations for gout could be attributable to high temperature (attributable fraction: 14.93%, 95% CI: 5.99%, 22.11%). This study suggests that high temperature and high temperature variation may trigger hospitalizations for gout, indicating that patients with gout need to take proactive actions in the face of days with non-optimal temperature.

7.
Zhongguo Zhen Jiu ; 41(10): 1161-5, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628751

RESUMO

Based on literature research and Delphi expert consensus method, the important acupoints for cancer pain was summarized to provide evidence basis for the formulation of Clinical Practice Guide of Acupuncture in the Treatment of Cancer Pain. Through systematic search of Chinese and English databases, 28 clinical studies regarding acupuncture for cancer pain were included. The acupoint selection methods and high-frequency acupoints were summarized and analyzed. Based on this, a Delphi questionnaire was designed and two rounds of questionnaire survey on 30 experts in acupuncture and tumor related fields in China and abroad were conducted. As a result, it was suggested that the individualized acupoint selection should be adopted for acupuncture treatment of cancer pain, with Zusanli (ST 36), Hegu (LI 4), Taichong (LR 3), Sanyinjiao (SP 6), Yanglingquan (GB 34) and ashi points as the main acupoints. Combined with clinical research evidence and expert consensus, the important acupoints for cancer pain were identified. However, clinical acupoint selection still needed further research and refinement.


Assuntos
Terapia por Acupuntura , Dor do Câncer , Meridianos , Neoplasias , Pontos de Acupuntura , Dor do Câncer/terapia , Humanos , Neoplasias/complicações , Neoplasias/terapia , Publicações
8.
Neoplasma ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34641697

RESUMO

We conducted a prospective study to evaluate the efficacy and safety of cladribine, cytarabine, mitoxantrone, and granulocyte colony-stimulating factor (CLAG-M) regimen combined with busulfan and cyclophosphamide (Bucy) as new intensive conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML). 24 patients were enrolled. The median follow-up was 15.2 months (range 1.9-67.0 months). Except for one patient who died before graft infusion, the evaluable 23 patients (96%) achieved complete remission (CR). The two-year overall survival (OS) rate and leukemia-free survival (LFS) rate were 61.4% and 59.4%, respectively. The non-relapse mortality (NRM) was 9.1%. Univariate analysis revealed that the myeloid blast phase of chronic myelomonocytic leukemia (CMML), an EVI1 mutated, blood blasts ≥ 20% at transplant and extramedullary disease were risk factors for LFS.

9.
Food Funct ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585194

RESUMO

The aim of this study was to investigate the anti-fatigue activity of Chinese Yam polysaccharides (CYPs). The structural characterization of CYPs was conducted using Fourier transform-infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography-light scattering-refractive index, and ion chromatography. The weight-loaded swimming capability, behavior performance, tumor growth, content of adenosine triphosphate (ATP), and biochemical markers of CYP in a cancer-related fatigue mouse model were tested. The results showed that CYP is a mixture with an average Mw of 75.57 kDa and is mainly composed of rhamnose, glucuronic acid, glucose, galactose, and arabinose with a molar ratio of 0.01 : 0.06 : 1.00 : 0.17 : 0.01. CYP increased the exhausting swimming time, which was decreased in the cisplatin (DDP) control group and the model group. CYP also increased the content of ATP in musculus gastrocnemius, which was down-regulated by DDP; the DDP had significantly enhanced the contents of interleukin-1ß (IL-lß), malondialdehyde (MDA), blood urea nitrogen (BUN) and lactic dehydrogenase (LDH) and inhibited the activity of superoxide dismutase (SOD) in the muscle. Administration of CYP decreased the levels of IL-lß, MDA, BUN and LDH, and up-regulated the SOD activity. The DDP + CYP group presented a decreased tumor volume and a lower tumor weight as compared with the model group. Moreover, the mice in the CYP or DDP + CYP groups had heavier body weights than the mice in the model group and DDP group. These results suggest that CYP should improve cancer-related fatigue via the regulation of inflammatory responses, oxidative stress and increase in energy supplementation.

10.
Commun Biol ; 4(1): 1042, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493786

RESUMO

High mortality of prostate cancer patients is primarily due to metastasis. Understanding the mechanisms controlling metastatic processes remains essential to develop novel therapies designed to prevent the progression from localized disease to metastasis. CdGAP plays important roles in the control of cell adhesion, migration, and proliferation, which are central to cancer progression. Here we show that elevated CdGAP expression is associated with early biochemical recurrence and bone metastasis in prostate cancer patients. Knockdown of CdGAP in metastatic castration-resistant prostate cancer (CRPC) PC-3 and 22Rv1 cells reduces cell motility, invasion, and proliferation while inducing apoptosis in CdGAP-depleted PC-3 cells. Conversely, overexpression of CdGAP in DU-145, 22Rv1, and LNCaP cells increases cell migration and invasion. Using global gene expression approaches, we found that CdGAP regulates the expression of genes involved in epithelial-to-mesenchymal transition, apoptosis and cell cycle progression. Subcutaneous injection of CdGAP-depleted PC-3 cells into mice shows a delayed tumor initiation and attenuated tumor growth. Orthotopic injection of CdGAP-depleted PC-3 cells reduces distant metastasic burden. Collectively, these findings support a pro-oncogenic role of CdGAP in prostate tumorigenesis and unveil CdGAP as a potential biomarker and target for prostate cancer treatments.

11.
ACS Biomater Sci Eng ; 7(10): 4933-4945, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34583510

RESUMO

Titanium and its alloys have been widely used as bone implants, but for reduced treatment span, improvements are urgently needed to achieve faster and better osteointegration. In this study, we found that miR-132-3p inhibited bone-marrow-derived stem cell (BMSC) osteogenic differentiation via targeting BMP2, and that inhibiting miR-132-3p could significantly improve the osteogenic capability of BMSCs. Moreover, we fabricated a biocompatible selenomethionine (SEMET)-modified polyethylene glycol (PEG)/polyethylenimine (PEI) nanoparticle (SeNP) cross-linked with 0.2% gelatin solutions and delivered miR-132-3p inhibitor to biofunctionalize alkali heat-treated titanium implants, resulting in the development of a novel coating for reverse transfection. The biological performances of PEG/PEI/miR-132-3p inhibitor and SeNP/miR-132-3p inhibitor-biofunctionalized titanium were compared. The biological effects, including cell viability, cytotoxicity, adhesion, cellular uptake, and osteogenic capacity of SeNP/miR-132-3p inhibitor-biofunctionalized titanium implants, were then assessed. Results showed that SeNPs presented appropriate morphology, diameter, and positive zeta potential for efficient gene delivery. The transfection efficiency of the SeNP/miR-132-3p inhibitor was comparable to that of the PEG/PEI/miR-132-3p inhibitor, but the former induced less reactive oxygen species (ROS) production and lower apoptosis rates. Confocal laser scanning microscopy (CLSM) demonstrated that SeNP/miR-132-3p inhibitor nanoparticles released from the titanium surfaces and were taken up by adherent BMSCs. In addition, the release profile showed that transfection could obtain a long-lasting silencing effect for more than 2 weeks. The cell viability, cytotoxicity, and cell spreading of SeNP/miRNA-132-3p inhibitor-biofunctionalized titanium were comparable with those of untreated titanium and the SeNP/miRNA-132-3p inhibitor negative control (NC)-biofunctionalized titanium but resulted in higher ALP activity and osteogenic gene expression levels. In vivo animal studies further certified that SeNP/miRNA-132-3p inhibitor nanoparticles from titanium surfaces promoted osteointegration, which was revealed by microcomputed tomography (micro-CT) and histological observations. Taken together, these findings suggested that selenomethionine-modified PEI-based nanoparticles could achieve better biocompatibility. Moreover, titanium implants biofunctionalized by SeNP/miRNA-132-3p inhibitor nanoparticles might have significant clinical potential for more effective osteointegration.

12.
Chem Commun (Camb) ; 57(80): 10371-10374, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34541598

RESUMO

A transformative concept of solid electrochemical corrosion has been put forward, in which solid-state electrolyte LiPON has been applied to replace the liquid one to prelithiate graphite with Li-metal. Thus, high prelithiation efficiency and low polarization of the treated anode can be obtained, with a unique mosaic structure left at the surface.

14.
Environ Technol ; : 1-29, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498542

RESUMO

Jiaxing is a medium-sized city in the Yangtze River Delta (YRD), which showed complex local and surrounding pollution sources. To study the COVID-19 impact on the ambient PM2.5 in Jiaxing, we collected the PM2.5 samples from January 2 to April 25, 2020 and analyzed their chemical compositions (including carbon components, water-soluble ions (WSIs), and inorganic elements). The concentration of PM2.5 was 83.13 ± 30.93 µg/m3 before COVID-19 pandemic, and then remarkably decreased with COVID-19 outbreak due to the suspension of mobility and industrial activities. Meanwhile, the concentrations of main chemical species (carbon components, water-soluble ions and inorganic elements) of PM2.5 all decreased from period A (January 2 to 20, 2020) to period B (January 23 to February 10, 2020). Moreover, Trajectory clustering analysis showed that close-range transport was one of the dominant factors throughout all the period, except for period D (April 1 to 25, 2020). In addition, PSCF model indicated that the COVID-19 outbreak resulted in a significant decrease of WPSCF value. This study highlighted the differences in chemical compositions and sources of PM2.5 since COVID-19 pandemic were reported and provide a better understanding of the impact of COVID-19 outbreak on PM2.5.

15.
Front Immunol ; 12: 667097, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557183

RESUMO

The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk.

16.
Ultrasonics ; 118: 106578, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34560381

RESUMO

High-order harmonics and sub-harmonics that are engendered upon interaction between surface Rayleigh waves and material flaws have been exploited intensively, for characterizing material defects on or near to waveguide surfaces. Nevertheless, theoretical interpretation on underlying physics of defect-induced nonlinear features of Rayleigh waves remains a daunting task, owing to the difficulty in analytically modeling the stress and displacement fields of a Rayleigh wave in the vicinity of defect, in an explicit and accurate manner. In this study, the Rayleigh wave scattered by a surface or a sub-surface micro-crack is scrutinized analytically, and the second harmonic triggered by the clapping and rubbing behaviors of the micro-crack is investigated, based on the elastodynamic reciprocity theorem. With a virtual wave approach, a full analytical, explicit solution to the micro-crack-induced second harmonic wavefield in the propagating Rayleigh wave is ascertained. Proof-of-concept numerical simulation is performed to verify the analytical solution. Quantitative agreement between analytical and numerical results has demonstrated the accuracy of the solution when used to depict a surface/sub-surface crack-perturbed Rayleigh wavefield and to calibrate the crack-induced wave nonlinearity. The analytical modeling and solution advance the use of Rayleigh waves for early awareness and quantitative characterization of embryonic material defects that are on or near to structural surfaces.

17.
Curr Pharm Des ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579628

RESUMO

Galectins are a highly conserved protein family that binds to ß-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. It can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies indicate that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D) and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. These information may provide a novel and promising therapeutic target for autoimmune diseases.

18.
Prenat Diagn ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486758

RESUMO

OBJECTIVE: To evaluate the utility of clinical exome sequencing (ES)-based carrier screening in Chinese consanguineous couples. METHODS: Consanguineous couples were screened for autosomal recessive (AR) disorders using the clinical ES of 5000 genes associated with human diseases. RESULTS: We recruited 14 couples who elected to have sequencing. One couple was related as first cousins and 13 as second cousins. Both partners carrying the same pathogenic variant were detected in four couples. One couple was found in which one partner carried a splice variant, and the other had a missence variant of the same gene. These five couples were identified as being at risk of having a child affected by an AR disorder. CONCLUSION: Our study demonstrates that ES-based preconception screening yields a clinical value for Chinese consanguineous couples. It enables to detect at-risk couples for rare AR diseases.

20.
Arthritis Rheumatol ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480835

RESUMO

OBJECTIVES: To determine the role of gasdermin E (GSDME)-mediated pyroptosis in the pathogenesis and progression of rheumatoid arthritis (RA), and explore the potential therapeutic targets for RA. METHODS: The expression and activation of caspase3 and GSDME in the synovium, macrophages, and monocytes of RA patients was detected by immunohistochemistry, immunofluorescence, and western blot analysis. The correlation of activated GSDME with RA disease activity was evaluated. The pyroptotic ability of monocytes from RA patients was also tested. In addition, the effect of TNF-α on caspase3/GSDME-mediated pyroptosis of monocytes and macrophages was investigated. Furthermore, mice lacking Gsdme were subjected to collagen-induced arthritis, and the incidence and severity of arthritis was assessed. RESULTS: Monocytes and synovial macrophages from RA patients showed increased expression of activated caspase3, GSDME, and GSDME-N. The expression of GSDME-N in monocytes from RA patients correlated positively with the disease activity. Monocytes from RA patients with higher GSDME levels were more susceptible to pyroptosis. Furthermore, TNF-α induced pyroptosis in monocytes and macrophages by activating the caspase3/GSDME pathway. The use of a caspase3 inhibitor and silencing of GSDME significantly blocked TNF-α-induced pyroptosis. Gsdme deficiency effectively alleviated arthritis in a collagen-induced arthritis mice model. CONCLUSIONS: These results support a pathogenic role of GSDME in RA and provide an alternative mechanism for RA pathogenesis involving TNF-α, which activates GSDME-mediated pyroptosis of monocytes and macrophages in RA. In addition, targeting GSDME might be a potential therapeutic approach for RA.

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