Direct detection of acetylcholinesterase by Fe(HCOO)2.6(OH)0.3. H2O nanosheets with oxidase-like activity on a smartphone platform.

Monitoring acetylcholinesterase (AChE) is crucial in clinical diagnosis and drug screening. Traditional methods for detecting AChE usually require the addition of intermediates like acetylthiocholine, which complicates the detection process and introduces interference risks. Herein, we develop a direct colorimetric assay based on alkaline iron formate nanosheets (Fe(HCOO)2.6(OH)0.3·H2O NSs, Fef NSs) for the detection of AChE without any intermediates. The as-prepared Fef NSs exhibit oxidase-like activity, catalyzing the generation of O2·-, 1O2 and ·OH, which leads to a color change from colorless to blue when exposed to 3,3',5,5'-tetramethylbenzidine. AChE directly inhibits the oxidase-like activity of Fef NSs, resulting in a hindered color reaction, enabling the detection of AChE. The biosensor has a linear detection range of 0.1-30 mU/mL, with a minimum detection limit of 0.0083 mU/mL (S/N = 3), representing a 100-fold improvement in detection sensitivity over the traditional Ellman's method. Satisfactory results were obtained when analyzing real AChE samples. Attractively, a method for the quantitative detection of AChE by a smartphone is established based on the Fef NSs. This method enables instant acquisition of AChE concentrations, achieving real-time visualized detection.

Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy.

Proteolysis targeting chimeras (PROTACs) have emerged as revolutionary anticancer therapeutics that degrade disease-causing proteins. However, the anticancer performance of PROTACs is often impaired by their insufficient bioavailability, unsatisfactory tumor specificity and ability to induce acquired drug resistance. Herein, we propose a polymer-conjugated PROTAC prodrug platform for the tumor-targeted delivery of the most prevalent von Hippel-Lindau (VHL)- and cereblon (CRBN)-based PROTACs, as well as for the precise codelivery of a degrader and conventional small-molecule drugs. The self-assembling PROTAC prodrug nanoparticles (NPs) can specifically target and be activated inside tumor cells to release the free PROTAC for precise protein degradation. The PROTAC prodrug NPs caused more efficient regression of MDA-MB-231 breast tumors in a mouse model by degrading bromodomain-containing protein 4 (BRD4) or cyclin-dependent kinase 9 (CDK9) with decreased systemic toxicity. In addition, we demonstrated that the PROTAC prodrug NPs can serve as a versatile platform for the codelivery of a PROTAC and chemotherapeutics for enhanced anticancer efficiency and combination benefits. This study paves the way for utilizing tumor-targeted protein degradation for precise anticancer therapy and the effective combination treatment of complex diseases.

Laparoscopic-assisted retrieval of inferior vena cava filter: A case report and literature review.

BACKGROUND: The retrieval of inferior vena cava filters beyond the retrieval window poses challenges, requiring alternative techniques. OBJECTIVES: To discuss the laparoscopy-assisted retrieval approach for difficult inferior vena cava filters. RESEARCH DESIGN: Case report. SUBJECTS: A 57-year-old male with a retrievable inferior vena cava filter placed 8 months prior. MEASURES: Laparoscopy-assisted retrieval technique utilized after unsuccessful interventional attempts. RESULTS: Successful retrieval of the filter despite thickened intimal tissue involvement, with no postoperative complications. CONCLUSIONS: Laparoscopy-assisted retrieval offers a direct visual approach for challenging filter removal, proving minimally invasive, safe, and effective.

The downregulation of Tapasin in dendritic cell regulates CD8+ T cell autophagy to hamper hepatitis B viral clearance in the induced pluripotent stem cell-derived hepatocyte organoid.

Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.

Prevalence of Neutralizing Autoantibodies Against Type I Interferon in a Multicenter Cohort of Severe or Critical COVID-19 Cases in Shanghai.

OBJECTIVE: We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2. METHODS: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted. RESULTS: In this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts. CONCLUSION: The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population.

YAP1-induced RBM24 promotes the tumorigenesis of triple-negative breast cancer through the ß-catenin pathway.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and refractory to current treatments. RBM24 is an RNA-binding protein and shows the ability to regulate tumor progression in multiple cancer types. However, its role in TNBC is still unclear. In this study, we analyzed publicly available profiling data from TNBC tissues and cells. Loss- and gain-of-function experiments were performed to determine the function of RBM24 in TNBC cells. The mechanism for RBM24 action in TNBC was investigated. RBM24 was deregulated in TNBC tissues and TNBC cells with depletion of SIPA1, YAP1, or ARID1A, three key regulators of TNBC. Compared to MCF10A breast epithelial cells, TNBC cells had higher levels of RBM24. Knockdown of RBM24 inhibited TNBC cell proliferation, colony formation, and tumorigenesis, while overexpression of RBM24 promoted aggressive phenotype in TNBC cells. YAP1 overexpression induced the expression of RBM24 and the RBM24 promoter-driven luciferase reporter. YAP1 was enriched at the promoter region of RBM24. Overexpression of RBM24 increased ß-catenin-dependent transcriptional activity. Most importantly, knockdown of CTNNB1 rescued RBM24 aggressive phenotype in TNBC cells. Collectively, the YAP1/RBM24/ß-catenin axis plays a critical role in driving TNBC progression. RBM24 may represent a novel therapeutic target for TNBC treatment.

A Wash-Free Spheres-on-Sphere Strategy for On-Site and Multiplexed Biosensing.

Respiratory infections and food contaminants pose severe challenges to global health and the economy. A rapid on-site platform for the simultaneous detection of multiple pathogens is crucial for accurate diagnosis, appropriate treatment, and a reduced healthcare burden. Herein, we present a spheres-on-sphere (SOS) platform for multiplexed detection using a portable Coulter counter, which employs millimeter- and micron-sized spheres coupled with antibodies as multitarget probes. The assay allows for quantitative detection of multiple analytes within 20 min by simple mixing, enabling on-site detection. The platform shows high accuracy in identifying three respiratory viruses (SARS-CoV-2, influenza A virus, and parainfluenza virus) from throat swab samples, with LOD of 50.7, 32.4, and 49.1 pg/mL. It also demonstrates excellent performance in quantifying three mycotoxins (aflatoxin B1, deoxynivalenol, and ochratoxin A) from food samples. The SOS platform offers a rapid on-site approach with high sensitivity and specificity for applications in resource-limited settings.

Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study.

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34-7.62; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32; P = 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82-1.66; P = 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6-8 compared to baseline was a risk factor for 28-day mortality (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6-8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.IMPORTANCEThis prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.Registered at ClinicalTrials.gov (NCT05190861).

Proline-rich protein PRPL1 enhances Panax notoginseng defence against Fusarium solani by regulating reactive oxygen species balance and strengthening the cell wall barrier.

The root rot mainly caused by Fusarium solani is a bottleneck in the cultivation of Panax notoginseng. In this study, we reported a gene encoding a plant cell wall structural protein, P. notoginseng proline-rich protein (PnPRPL1), whose transcription was upregulated by F. solani and induced by some hormone signals. The PnPRPL1 recombinant protein significantly inhibited the growth and conidial germination of the root rot pathogens. Downregulation of PnPRPL1 by RNA interference (RNAi) in P. notoginseng leaves increased the susceptibility to F. solani, whereas overexpression of PnPRPL1 in tobacco (Nicotiana tabacum) enhanced the resistance to F. solani. Compared with wild-type tobacco, the PnPRPL1-overexpressing transgenic tobacco had higher reactive oxygen species (ROS)-scavenging enzyme activities, lower ROS levels, and more lignin and callose deposition. The opposite results were obtained for the P. notoginseng expressing PnPRPL1 RNAi fragments. Furthermore, the PnPRPL1 promoter transcription activity was induced by several plant hormones and multiple stress stimuli. In addition, the transcription factor PnWRKY27 activated the expression of PnPRPL1 by directly binding to the promoter region. Thus, PnPRPL1, which is positively regulated by a WRKY transcription factor, encodes an antimicrobial protein that also mediates ROS homoeostasis and callose/lignin deposition during the response to F. solani infection.

Spatiotemporal and direct capturing global substrates of lysine-modifying enzymes in living cells.

Protein-modifying enzymes regulate the dynamics of myriad post-translational modification (PTM) substrates. Precise characterization of enzyme-substrate associations is essential for the molecular basis of cellular function and phenotype. Methods for direct capturing global substrates of protein-modifying enzymes in living cells are with many challenges, and yet largely unexplored. Here, we report a strategy to directly capture substrates of lysine-modifying enzymes via PTM-acceptor residue crosslinking in living cells, enabling global profiling of substrates of PTM-enzymes and validation of PTM-sites in a straightforward manner. By integrating enzymatic PTM-mechanisms, and genetically encoding residue-selective photo-crosslinker into PTM-enzymes, our strategy expands the substrate profiles of both bacterial and mammalian lysine acylation enzymes, including bacterial lysine acylases PatZ, YiaC, LplA, TmcA, and YjaB, as well as mammalian acyltransferases GCN5 and Tip60, leading to discovery of distinct yet functionally important substrates and acylation sites. The concept of direct capturing substrates of PTM-enzymes via residue crosslinking may extend to the other types of amino acid residues beyond lysine, which has the potential to facilitate the investigation of diverse types of PTMs and substrate-enzyme interactive proteomics.

Efficacy and Safety of Nirmatrelvir/Ritonavir in Severe Hospitalized Patients with COVID-19 and in Patients at High Risk for Progression to Critical Illness: A Real-World Study.

Background: Nirmatrelvir/Ritonavir is an orally administered anti-SARS-Cov-2 drug used in mild-to-moderate COVID-19 patients. Our retrospective cohort study aims to evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in severe hospitalized patients with Omicron infection, as well as in patients at high risk for progression to critical illness in real-world settings. Methods: A total of 350 patients received Nirmatrelvir/Ritonavir while 350 matched controls did not. Patients with confirmed COVID-19 were administered Nirmatrelvir 300 mg and Ritonavir 100 mg orally twice a day for 5 days, with the medication initiated on the first day after admission. The primary endpoint of the study was a composite outcome of hospitalization or death from any cause within 28 days. Secondary endpoints included the occurrence of adverse events and the evaluation of serum levels of IL-6 and viral load. Results: We documented the mortality risk from any cause within 28 days, viral load, serum IL-6 levels, and adverse events. Nirmatrelvir/Ritonavir reduced the 28-day risk of all-cause mortality by 86% (P = .011, hazard ratio (HR) = 0.14, 95% confidence interval (CI) = 0.03, 0.64). At baseline, the serum level of IL-6 was significantly higher in the antiviral treatment group compared to the control group (P < .001), but no significant difference (P = .990) was found between the two groups at discharge. In CKD patients undergoing hemodialysis, no significant worsening of renal function was observed in the Nirmatrelvir/Ritonavir treatment group compared to the control group. Conclusion: Nirmatrelvir/Ritonavir may reduce the 28-day risk of all-cause mortality in critically ill patients with COVID-19 and in patients at high risk for critical disease progression.

Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells.

Dysregulation of anti-apoptotic and pro-apoptotic protein isoforms arising from aberrant splicing is a crucial hallmark of cancers and may contribute to therapeutic resistance. Thus, targeting RNA splicing to redirect isoform expression of apoptosis-related genes could lead to promising anti-cancer phenotypes. Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. In this study, through RT-PCR and Western Blot analysis, we found that BCLX pre-mRNA is aberrantly spliced in GBM cells with a favored splicing of anti-apoptotic Bcl-xL. Modulation of BCLX pre-mRNA splicing using splice-switching oligonucleotides (SSOs) efficiently elevated the pro-apoptotic isoform Bcl-xS at the expense of the anti-apoptotic Bcl-xL. Induction of Bcl-xS by SSOs activated apoptosis and autophagy in GBM cells. In addition, we found that ionizing radiation could also modulate the alternative splicing of BCLX. In contrast to heavy (carbon) ion irradiation, low energy X-ray radiation-induced an increased ratio of Bcl-xL/Bcl-xS. Inhibiting Bcl-xL through splicing regulation can significantly enhance the radiation sensitivity of 2D and 3D GBM cells. These results suggested that manipulation of BCLX pre-mRNA alternative splicing by splice-switching oligonucleotides is a novel approach to inhibit glioblastoma tumorigenesis alone or in combination with radiotherapy.

Characteristics and formation mechanism of Land use conflicts in northern Anhui: A Case study of Funan county.

The rapid development of global urbanization and industrialization not only promotes a significant improvement in the level of socio-economic development, but also exacerbates the complexity and vulnerability of regional land resource utilization, resulting in frequent land use conflicts and seriously constraining the sustainable development of regional socio-economic and ecological environment. Taking Funan County as an example, based on interpretation data of Landsat TM/ETM remote sensing image data from 1980 to 2020, this paper analyses the temporal and spatial evolution characteristics of land use conflict in Funan County from 1980 to 2020 using the ArcGIS spatial analysis method, land use conflict measurement model, geographically weighted regression and geographical detector and then deeply analyses the main factors affecting land use conflict in Funan County and its driving mechanisms. In descending order, land use types undergoing the most change include cultivated land, urban and rural construction land, grassland, forestland and water area. The results of land use change are mainly the occupation of cultivated land by construction land, water area and forestland. Overall land use conflict in Funan County is serious with approximately 80 % of land use in the county in conflict, the severe land use conflict is mostly concentrated in urban and township built-up areas, and there is an increase trend year by year. Land use conflict is the result of multiple factors. Policy, economic development, and the social population and natural environment are the key driving factors behind land use conflict, which have a significant impact on the direction, location, scale and rate of land use transfer.Accurately identifying regional land use changes and conflicts and exploring the driving mechanism behind land use conflicts are of great significance for achieving the sustainable development of regional social economies and ecological environments.

Carrier systems of radiopharmaceuticals and the application in cancer therapy.

Radiopharmaceuticals play a vital role in cancer therapy. The carrier of radiopharmaceuticals can precisely locate and guide radionuclides to the target, where radionuclides kill surrounding tumor cells. Effective application of radiopharmaceuticals depends on the selection of an appropriate carrier. Herein, different types of carriers of radiopharmaceuticals and the characteristics are briefly described. Subsequently, we review radiolabeled monoclonal antibodies (mAbs) and their derivatives, and novel strategies of radiolabeled mAbs and their derivatives in the treatment of lymphoma and colorectal cancer. Furthermore, this review outlines radiolabeled peptides, and novel strategies of radiolabeled peptides in the treatment of neuroendocrine neoplasms, prostate cancer, and gliomas. The emphasis is given to heterodimers, bicyclic peptides, and peptide-modified nanoparticles. Last, the latest developments and applications of radiolabeled nucleic acids and small molecules in cancer therapy are discussed. Thus, this review will contribute to a better understanding of the carrier of radiopharmaceuticals and the application in cancer therapy.

Protective effects of chlorogenic acid against cyclophosphamide induced liver injury in mice.

We investigated possible protective effects of chlorogenic acid (CGA) against cyclophosphamide (CP) induced hepatic injury in mice. We measured aminotransferase alanine transaminase (ALT) and aspartate transaminase (AST) levels in the serum. We assayed catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hepatic tissue. We assessed expression of nuclear transcription factor 2 (Nrf2) and Kelch sample related protein-1 (keap1) proteins in hepatic tissues using immunohistochemistry. The relative mRNA expression levels of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Hematoxylin & eosin staining was used to assess liver histopathology. We found that administration of CGA prior to induction of injury by CP decreased serum ALT, AST and MDA expressions in hepatic tissue, while CAT, SOD, GSH and GSH-Px concentrations were increased. We found that hepatocytes of animals administered CGA gradually returned to normal morphology. CGA increased the protein expression of Nrf2 in murine hepatic tissue. Administration of CGA up-regulated mRNA expression levels of HO-1, NQO1, TNF-α and IL-6 in hepatic tissue. CGA exhibited a marked protective effect on CP induced liver injury in mice.

A narrative review of acute pancreatitis-induced splanchnic vein thrombosis: from pathogenesis to clinical management.

Acute pancreatitis-induced splanchnic vein thrombosis (APISVT) is an important sequela complication of acute pancreatitis, which may cause poor prognosis, such as severe gastrointestinal hemorrhage, bowel ischemic necrosis and liver failure. However, its mechanism remains uncertain, and there is not a general consensus on the management. In this study, we reviewed the latest academic publications in APISVT, and discussed its pathogenesis, clinical presentation, adverse outcome and treatment, especially focused on the role of anticoagulant therapy. It was indicated that anticoagulation therapy can significantly elevate thrombus recanalization and reduce the incidence of complications and mortality with no increase of bleeding. Actually, as most of these studies were retrospective analyses and prospective studies included small samples, the conclusion remains controversial. Thus, well-designed randomized controlled trials are urged to verify the effectiveness and safety of anticoagulation therapy for APISVT.

MicroRNA-34a-5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2-induced autophagy.

Osteoarthritis (OA), a late-stage complication of developmental dysplasia of the hip (DDH), is a key factor leading to further degeneration of joint function. Studies have shown that Sestrin2 (SESN2) is a positive regulator in protecting articular cartilage from degradation. However, the regulatory effects of SESN2 on DDH-OA and its upstream regulators remain obscure. Here, we first identified that the expression of SESN2 significantly decreased in the cartilage of DDH-OA samples, with an expression trend negatively correlated with OA severity. Using RNA sequencing, we identified that the upregulation of miR-34a-5p may be an important factor for the decrease in SESN2 expression. Further exploring the regulation mechanism of miR-34a-5p/SESN2 is of great significance for understanding the mechanism of DDH occurrence and development. Mechanistically, we showed that miR-34a-5p could significantly inhibit the expression of SESN2, thereby promoting the activity of the mTOR signaling pathway. We also found that miR-34a-5p significantly inhibited SESN2-induced autophagy, thereby suppressing the proliferation and migration of chondrocytes. We further validated that knocking down miR-34a-5p in vivo resulted in a significant increase in SESN2 expression and autophagy activity in DDH-OA cartilage. Our study suggests that miR-34a-5p is a negative regulator of DDH-OA, and may provide a new target for the prevention of DDH-OA.

Low-frequency pulsed electromagnetic fields alleviate the condylar cartilage degeneration and synovitis at the early stage of temporomandibular joint osteoarthritis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is characterized by articular cartilage degeneration and progressive synovitis. How to effectively inhibit TMJOA in the early stage has been a hot topic in the biomedical field. As a non-invasive physiotherapy, pulsed electromagnetic field (PEMF) treatment has shown great potential in the treatment of osteoarthritis (OA) in extremity joints. OBJECTIVE: This study aims to investigate the biological effect of PEMF intervention on TMJ cartilage degeneration and synovium inflammation at the early stage of TMJOA. METHODS: PEMF (2.0 mT, 15 Hz, 2 h/day) treatment was given to rats in which TMJOA was induced by applying the unilateral anterior crossbite (UAC). Histological and immunohistochemical staining, TUNEL assay, real-time PCR and western blotting assay were performed to detect the changes of the morphology and the expression of pro-inflammatory and degradative factors in condylar cartilage and synovium. RESULTS: Obvious condylar cartilage degeneration, characterized by decreased cartilage thickness, degraded cartilage extracellular matrix, increased expression of pro-inflammatory and degradative factors (TNF-α, IL-1ß, MMP-13, ADAMTS-5, IL-6, MMP-3, MMP-9 and COL-X) and increased chondrocytes death, was observed in UAC group, accompanied by synovium hyperplasia and up-regulation of pro-inflammatory and degradative factors in synovium. PEMF intervention reversed the decreased cartilage thickness at 3 weeks and degraded cartilage extracellular matrix at 6 weeks. Moreover, the up-regulation of pro-inflammatory, degradative and hypertrophyic factors and chondrocytes death in condylar cartilage induced by UAC were inhibited to some extent. In addition, the synovium hyperplasia and the up-regulation of pro-inflammatory and degradative factors in synovium were inhibited at 3 weeks and 6 weeks. CONCLUSIONS: Appropriate PEMF stimulation can reverse the loss of cartilage extracellular matrix, the chondrocytes death, the increased expression of pro-inflammatory and degradative factors in cartilage, the decreased cartilage thickness and synovium inflammation induced by UAC at the early stage of TMJOA to some extent. PEMF stimulation may be a promising method in clinical TMJOA treatment.