Differences of anticholinergic drug burden between older hospitalized patients with and without delirium: a systematic review and meta-analysis based on prospective cohort studies.

OBJECTIVES: This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification. RESULTS: Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6-83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13-0.28). In subgroup analysis, the age subgroup was split into < 75 and ≥ 75 according to the median age of the older people. There were significant differences in ADB scores between older people with delirium and those without delirium in various subgroups: surgical (SMD = 0.20, 95%CI 0.12-0.28), internal medicine (SMD = 0.64, 95%CI 0.25-1.02), age < 75 (SMD = 0.17, 95%CI 0.08-0.26), age ≥ 75 (SMD = 0.27, 95%CI 0.15-0.39), ADS scale (SMD = 0.13, 95%CI 0.13-0.40), ARS scale (SMD = 0.15, 95%CI 0.03-0.26), ACB scale (SMD = 0.13, 95%CI 0.01-0.25), pre-admission ADB (SMD = 0.24, 95%CI 0.05-0.43) and ADB during hospitalization (SMD = 0.20, 95%CI 0.12-0.27). CONCLUSIONS: We found a quantitative relationship between ADB and delirium in older patients admitted for internal medicine and surgery. And this relationship remained significant in different age, ADB scale type and ADB classification subgroups. However, the actual difference in ADB scores between patients with delirium and without delirium was small. More high-quality observational studies should be conducted to explore the impact of ADB on delirium and subsyndromal delirium. CLINICAL TRIAL REGISTRATION: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42022353649].

Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease.

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that represent the interface between blood cells on one side and hepatocytes on the other side. LSECs not only form a barrier within the hepatic sinus, but also play important physiological functions such as regulating hepatic vascular pressure, anti-inflammatory and anti-fibrotic. Pathologically, pathogenic factors can induce LSECs capillarization, that is, loss of fenestra and dysfunction, which are conducive to early steatosis, lay the foundation for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), and accelerate metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The unique localization, phenotype, and function of LSECs make them potential candidates for reducing liver injury, inflammation, and preventing or reversing fibrosis in the future.

A Novel tsRNA, m7G-3' tiRNA LysTTT, Promotes Bladder Cancer Malignancy Via Regulating ANXA2 Phosphorylation.

Emerging evidence indicates that transfer RNA (tRNA)-derived small RNAs (tsRNAs), originated from tRNA with high abundance RNA modifications, play an important role in many complex physiological and pathological processes. However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel m7G-modified tsRNA, m7G-3'-tiRNA LysTTT (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an m7G small RNA-modified chip. Moreover, it is found that mtiRL, catalyzed by the tRNA m7G-modifying enzyme mettl1, promotes bladder cancer (BC) malignancy in vitro and in vivo. Mechanistically, mtiRL is found to specifically bind the oncoprotein Annexin A2 (ANXA2) to promote its Tyr24 phosphorylation by enhancing the interactions between ANXA2 and Yes proto-oncogene 1 (Yes1), leading to ANXA2 activation and increased p-ANXA2-Y24 nuclear localization in BC cells. Together, these findings define a critical role for mtiRL and suggest that targeting this novel m7G-modified tsRNA can be an efficient way for to treat BC.

Efficacy of rituximab in treating steroid-resistant Graves' orbitopathy in active moderate-to-severe and sight-threatening forms: A retrospective observation from China.

Background and objectives: The efficacy of rituximab (RTX) in treating steroid-resistant Graves' orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. Methods: Data from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. Results: The median follow-up time was 22 (8-34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves' Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values < 0.05). No significant improvement was seen in terms of proptosis and eye muscle duction. Notably, a higher baseline IgG4 to IgG ratio was a predictor for RTX-induced positive EUGOGO outcomes. After RTX treatment, all 8 patients with DON demonstrated inactivation, and 4 improved in visual acuity by ≥ 1 line. No patient with DON experienced obvious deterioration. Conclusion: A single dose of 500 mg RTX seemed to be an effective and tolerable treatment for steroid-resistant GO. However, larger-scale studies with a control group are required for a more solid conclusion. The role of RTX in steroid-resistant DON management where surgery is unavailable or ineffective should be further explored.

Two-dimensional tetragonal AlOX (X = Cl, Br, or I) monolayers with promising photocatalytic performance: first-principles investigations.

It is of great significance to search for new two-dimensional materials with excellent photocatalytic water splitting properties. Here, the AlOX (X = Cl, Br, or I) monolayers were constructed to explore their electronic and optical properties as a potential photocatalyst and mechanism of high photocatalytic activity by first principles calculations, for the first time. The results show that the AlOX (X = Cl, Br, or I) monolayers are all dynamically and thermodynamically stable. It is found that the AlOI monolayer exhibits visible optical absorption with a 538 nm absorption band edge, due to its direct band gap of 2.22 eV. Moreover, an appropriate band edge potential ensures its excellent reduction-oxidation (redox) ability. The asymmetry of crystals along different directions results in a noncoplanar HOMO and LUMO as well as an anisotropy effective mass and favors the separation of photogenerated carriers. These findings present the potential of the AlOX (X = Cl, Br, or I) monolayers as photocatalysts.

Ionic Current Saturation Enabled by Cation Gating Effect in Metal-Organic-Framework Membranes.

Ion transport through nanoporous two-dimensional (2D) membranes is predicted to be tunable by controlling the charging status of the membranes' planar surfaces, the behavior of which though remains to be assessed experimentally. Here we investigate ion transport through intrinsically porous membranes made of 2D metal-organic-framework layers. In the presence of certain cations, we observe a linear-to-nonlinear transition of the ionic current in response to the applied electric field, the behavior of which is analogous to the cation gating effect in the biological ion channels. Specifically, the ionic currents saturate at transmembrane voltages exceeding a few hundreds of millivolts, depending on the concentration of the gating cations. This is attributed to the binding of cations at the membranes' surfaces, tuning the charging states there and affecting the entry/exit process of translocating ions. Our work also provides 2D membranes as candidates for building nanofluidic devices with tunable transport properties.

Higher dietary live microbe intake is associated with a lower risk of sarcopenia.

OBJECTIVE: This study aimed to investigate the potential association between dietary live microbe intake and sarcopenia. METHODS: Data from 5368 participants were gathered from the National Health and Nutrition Examination Survey (NHANES). Dietary information was assessed using a self-report questionnaire. The participants were categorized into low, medium, and high dietary live microbe groups. Sarcopenia was defined according to the National Institutes of Health (NIH) definition (appendicular skeletal muscle mass/body mass index <0.789 for men and <0.512 for women). Multivariate regression analysis and stratified analyses were performed. RESULTS: After adjusting for potential confounding factors, individuals in the high dietary live microbe group exhibited a lower prevalence of sarcopenia compared to those in the low dietary live microbe group. The adjusted odds ratio (with 95% confidence intervals) was 0.63 (0.44-0.89) (p for trend <0.05). Subgroup analyses indicated a potential difference in the impact of dietary live microbe intake on sarcopenia between individuals with and without diabetes (p for interaction = 0.094). CONCLUSION: Higher dietary live microbe intake was associated with a lower risk of sarcopenia.

Experimental and Thermal Stress Field Numerical Simulation Study on Laser Metal Deposition of Ti-48Al-2Cr-2Nb Alloy.

The experimental and numerical simulation analysis of a TiAl alloy by laser metal deposition technology is presented in this paper. The research examines the macroscopic morphology, microstructure, and mechanical properties of samples as laser power varies. It also delves into how the temperature field and residual stress evolve under different laser powers. The results reveal that the microstructure of samples is mainly composed of α2-Ti3Al phase and a γ-TiAl phase and that the details of the microstructure are significantly affected by laser power. As laser power increases, coarse lamellar structure content increases, corresponding to a decrease in α2 phase content. The deposited layer hardness ranges from 550 HV to 600 HV, and the average deposition layer hardness decreases with increased laser power. Simulation results predict the molten pool's size, temperature, and residual stresses. A significant increase in the molten pool size is observed when the laser power exceeds 1000 W, and the measured molten pool depths correspond closely to simulation predictions. However, significant tensile stresses are generated in the deposition layer due to high cooling rates, mainly in the x direction. Cracks are observed on the surface of the deposition layer at all laser powers.

Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

Pharmacokinetics, Safety, and Tolerability of Tenapanor in Healthy Chinese and Caucasian Volunteers: A Randomized, Open-Label, Single-Center, Placebo-Controlled Phase 1 Study.

Background: Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods: This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results: 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion: Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.

Dual-energy computed tomography in the early evaluation of acute radiation pneumonia.

OBJECTIVE: To investigate the value of dual-energy dual-source computed tomography (DSCT) in evaluating pulmonary perfusion changes before and after radiotherapy for esophageal cancer, and its clinical use in the early diagnosis of acute radiation pneumonia (ARP). METHODS: We selected 45 patients with pathologically confirmed esophageal cancer who received radiotherapy (total irradiation dose of 60 Gy). Dual-energy DSCT scans were performed before and after radiotherapy and the normalized iodine concentrations (NIC) in the lung fields of the areas irradiated with doses of > 20 Gy, 10-20 Gy, 5-10 Gy, and < 5 Gy were measured. We also checked for the occurrence of ARP in the patients, and the differences in NIC values and NIC reduction rates before and after radiotherapy were calculated and statistically analyzed. RESULTS: A total of 16 of the 45 patients developed ARP. The NIC values in the lung fields of all patients decreased at different degrees after radiotherapy, and the NIC values in the area where ARP developed, decreased significantly. The rate of NIC reduction and incidence rate of ARP increased gradually with the increasing irradiation dose, and the inter-group difference in NIC reduction rate was statistically significant (P < 0.05). Based on the receiver operating characteristic (ROC) curve analysis, the areas under the curves of NIC reduction rate versus ARP occurrence in the V5-10 Gy, V10-20 Gy, and V> 20 Gy groups were 0.780, 0.808, and 0.772, respectively. Sensitivity of diagnosis was 81.3%, 75.0%, and 68.8% and the specificity was 65.5%, 82.8%, and 79.3%, when taking 12.50%, 16.50%, and 26.0% as the diagnostic thresholds, respectively. The difference in NIC values in the lung fields of V<5 Gy before and after radiotherapy was not statistically significant (P > 0.05). CONCLUSION: The dual-energy DSCT could effectively evaluate pulmonary perfusion changes after radiotherapy for esophageal cancer, and the NIC reduction rate was useful as a reference index to predict ARP and provide further reference for decisions in clinical practice.

TRIB2-Mediated Modulation of AMPK Promotes Hepatic Insulin Resistance.

Insulin resistance and its linked health complications are increasing in prevalence. Recent work has caused the role of Tribbles2 (TRIB2) in metabolism and cellular signaling to be increasingly appreciated, but its role in the progression of insulin resistance has not been elucidated. Here, we explore the functions of TRIB2 in modulating insulin resistance and the mechanism involved in insulin-resistant mice and palmitic acid-treated HepG2 cells. We demonstrate that whole-body knockout and hepatic-specific TRIB2 deficiency protect against diet-induced insulin resistance, inflammation, and endoplasmic reticulum stress. Accordingly, upregulation of TRIB2 in the liver aggravates these metabolic disturbances in high-fat diet-induced mice and ob/ob mice. Mechanistically, TRIB2 directly binds to the αγ-SBS domain of PRKAB through its pseudokinase domain, subsequently inhibiting the formation and activity of the AMPK complex. Moreover, the results of intervention against AMPK suggest that the effects of TRIB2 depend on AMPK. Our findings reveal that TRIB2 is a novel target for the treatment of insulin resistance and its associated metabolic complications and clarify the function of TRIB2 as a regulatory component of AMPK activity.

CNN-based diagnosis model of children's bladder compliance using a single intravesical pressure signal.

Bladder compliance assessment is crucial for diagnosing bladder functional disorders, with urodynamic study (UDS) being the principal evaluation method. However, the application of UDS is intricate and time-consuming in children. So it'S necessary to develop an efficient bladder compliance screen approach before UDS. In this study, We constructed a dataset based on UDS and designed a 1D-CNN model to optimize and train the network. Then applied the trained model to a dataset obtained solely through a proposed perfusion experiment. Our model outperformed other algorithms. The results demonstrate the potential of our model to alert abnormal bladder compliance accurately and efficiently.

Referral to hepatologists or a second-line examination requirement is common in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: To estimate the number of patients who required a referral to hepatologists following the 2016 EASL-EASD-EASO guideline and a second-line vibration controlled transient elastography (VCTE) examination following the 2021 EASL guideline according to obesity, glycated hemoglobin (HbA1c), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) control status in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A total of 2515 T2DM patients who were hospitalized were cross-sectionally assessed. When we applied the 2016 EASL-EASD-EASO guideline, 26.8 %-46.4 % (depending on the scores used for diagnosing fibrosis) of T2DM patients needed a referral to hepatologists. When we applied the 2021 EASL guideline, a VCTE examination was required in 10.9 %-35 % (depending on the scores used for diagnosing fibrosis) of T2DM patients. The referral rates and the VCTE requirement were even higher in patients who were obese and/or had poor HbA1c, BP, and/or LDL-C control. CONCLUSIONS: Application of the screening guidelines would lead to a referral to hepatologists or a second-line VCTE examination requirement for a substantial number of T2DM patients, regardless of obesity and metabolic goal attainment status.

Sulfonated P-W modified nitrogen-containing carbon-based solid acid catalysts for one-pot conversion of cellulose to ethyl levulinate under water-ethanol medium.

Converting cellulose (Cel) into ethyl levulinate (EL) is one of the promising strategies for supplying liquid fuels. In this paper, the prepared sulfonated P-W-modified N-containing carbon-based solid acid catalyst (PWNCS), in which the Polyaniline (PANI) was employed as N and C precursors, successfully converted Cel into EL under the water-ethanol medium. The characterization results demonstrated that a tiny addition of P increased the Brønsted acid sites (BAS) content and defective WO3 provided the Lewis acid sites (LAS), meanwhile, the sulfonation process did not change the fundamental structure but introduced the sulfonic groups to dramatically increase the acidic content. Therefore, under optimized reaction conditions, PWNCS realized about 100% Cel conversion and 71.61% of EL yield, furthermore, the selectivity of EL reached 89.14%. In addition, the effect of water on the reaction pathway of Cel to EL over PWNCS was proposed. The addition of water generally resulted in the hydration of defective WO3 to reduce the LAS and increase BAS, which significantly inhibited the side reactions of retro-aldol condensation (RAC) and subsequent etherification reactions during Cel conversion and then improved the selectivity of EL.

A graphene/Janus B2P6 heterostructure with a controllable Schottky barrier via interlayer distance and electric field.

Lowering the Schottky barrier at the metal-semiconductor interface remains a stern challenge in the field of field-effect transistors. Herein, an in-depth investigation was conducted to explore the formation mechanism of the Schottky barrier via interlayer distance and external electric field, utilizing the first-principles approach. Attributed to the vertical asymmetric structure of B2P6, ohmic contact forms at the interface of a graphene/B2P6(001) heterostructure, and an n-type Schottky contact with a Schottky barrier of 0.51 eV forms at the interface of a graphene/B2P6(001̄) heterostructure. Furthermore, the Schottky barrier height and the contact type can be changed by adjusting the interlayer spacing or applying an electric field along the Z direction. A high carrier concentration of 4.65 × 1013 cm-2 is obtained in the graphene/B2P6(001) heterostructure when an external electric field of 0.05 V Å-1 is applied. Verifiably, alterations in the energy band structure are attributed to the redistribution of charges at the interface. The new findings indicate that GR/B2P6 heterostructures are a key candidate for next-generation Schottky field-effect transistor development.

Surface diffusion enhanced ion transport through two-dimensional nanochannels.

Fast ion permeation in nanofluidic channels has been intensively investigated in the past few decades because of their potential uses in separation technologies and osmotic energy harvesting. Mechanisms governing ion transport at this ultimately small spatial regime remain to be understood, which can only be achieved in nanochannels that are controllably fabricated. Here, we report the fabrication of two-dimensional nanochannels with their top and bottom walls consisting of atomically flat graphite and mica crystals, respectively. The distinct wall structures and properties enable us to investigate interactions between ions and interior surfaces. We find an enhanced ion transport within the channels that is orders of magnitude faster than that in the bulk solutions. The result is attributed to the highly dense packing of adsorbed cations at mica surfaces, where they diffuse in-plane. Our work provides insights into surface effects on ion transport at the nanoscale.

Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation.

OBJECTIVES: Abnormal mechanical stress is the pivotal risk factor of temporomandibular joint osteoarthritis (TMJOA). This study investigated the pathogenic mechanism by which abnormal mechanical stress induced chondrocyte senescence. MATERIALS AND METHODS: Cellular senescence was investigated in the rodent model of unilateral anterior crossbite and in the chondrocytes subjected to mechanical overloading in vitro. The effects of Yes-associated protein (YAP) in chondrocyte senescence and its correlation with methyltransferase-like 3 (METTL3) and N6 -methyladenosine (m6 A) modification were evaluated. The role of m6 A modification in chondrocyte senescence was determined. The therapeutic effects of m6 A inhibition in TMJOA were investigated. RESULTS: Senescent chondrocytes were accumulated in the mechanically induced TMJOA lesions in rats and mechanical overloading could trigger chondrocyte senescence in vitro. This mechanical stress-induced cellular senescence was revealed to be mediated by YAP deficiency that promoted METTL3-dependent m6 A modification. Moreover, inhibition of m6 A modification rescued chondrocyte senescence in vitro and in vivo, and suppressed TMJOA progression in rats. CONCLUSIONS: This study uncovered the underlying mechanism of mechanically induced senescence in TMJOA from the perspective of epitranscriptomics and revealed the therapeutic potential of m6 A inhibition in TMJOA.