Establishment of an Animal Model of Dog Bite Injuries.

Nowadays dog bite is becoming a world public health problem. Therefore, the study aimed to develop a dog bite animal model that is helpful to solve these problems. In this study, the skull of an adult dog was scanned. The three-dimensional model of the dog maxillofacial bones and dentition was built by MIMICS. Next, the model was printed with Co-Cr alloy by using selective laser sintering technology to develop the dog bite simulation pliers. Then, to simulate dog bite to most, the maximum bite force of the pliers was measured and actions contained in dog bite process was analyzed. Afterwards, according to action analysis results, rabbits were bitten by the prepared instrument in actions that simulate dog's bite. Finally, the reproducibility and controllability of this animal model of dog bite injuries was validated in an in vivo study. The results showed a reliable animal model of dog bite injuries has been developed in this study. The sites and severities of the injuries could be adjusted as the operator wishes and the animal model of dog bite injuries was highly repeatable. This study also indicates the feasibility of using digital technology in establishing animal bite models.

Association of Retinal Neurovascular Impairment with Disease Severity in Patients with Major Depressive Disorder: An Optical Coherence Tomography Angiography Study.

Background: Identifying the fundus objective biomarkers for the major depressive disorders (MDD) may help promote mental health. The aim of this study was to evaluate retinal neurovascular changes and further investigate their association with disease severity in MDD. Methods: This cross-sectional study conducted in the hospital enrolled patients with MDD and healthy controls.The retinal neurovascular parameters for all subjects, including vessel density (VD), thickness of ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL), and optic nerve head (ONH) eg are automatically calculated by the software in optical coherence tomography angiography (OCTA). The severity of MDD including depressive symptoms, anxiety, cognition, and insomnia was assessed by Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), and Insomnia Severity Index (ISI) respectively. Results: This study included 74 MDD patients (n=74 eyes) and 60 healthy controls (HCs) (n=60 eyes). MDD patients showed significantly decreased VD of superficial and deep capillary plexus, thickness of GCC and RNFL, and volume of ONH (all p<0.05) and increased vertical cup-to-disc ratio and global loss volume (GLV) (all p<0.05) compared to HCs. Positive associations were found between HAMD scores and cup area (r=0.30, p=0.035), cup volume (r=0.31, p=0.029), and disc area (r=0.33, p=0.020) as well as ISI scores and RNFL thickness (r=0.34, p=0.047). Conclusion: We found the retinal neurovascular impairment and its association with disease severity in MDD patients. OCTA showed promise as a potential complementary assessment tool for MDD.

Synthesis of Calix[4]arene-Based Porous Organic Cages and Their Gas Adsorption.

Two crystalline large-sized porous organic cages (POCs) based on conical calix[4]arene (C4A) were designed and synthesized. The four-jaw C4A unit tends to follow the face-directed self-assembly law with the planar triangular building blocks such as tris(4-aminophenyl)amine (TAPA) or 1,3,5-tris(4-aminophenyl)benzene (TAPB) to generate a predictable cage with a stoichiometry of [6+8]. The formation of the large cages is confirmed through their relative molecular mass measured using MALDI-TOF/TOF spectra. The protonated molecular ion peaks of C4A-TAPA and C4A-TAPB were observed at m/z 5109.0 (calculated for C336H240O24N32: m/z 5109.7) and m/z 5594.2 (calculated for C384H264O24N24: m/z 5598.4). C4A-POCs exhibit I-type N2 adsorption-desorption isotherms with the BET surface areas of 1444.9 m2×g-1 and 1014.6 m2×g-1. The CO2 uptakes at 273 K are 62.1 cm3×g-1 and 52.4 cm3×g-1 at a pressure of 100 KPa. The saturated iodine vapor static uptakes at 348 K are 3.9 g∙g-1 and 3.5 g∙g-1. The adsorption capacity of C4A-TAPA for SO2 reaches to 124.4 cm3×g-1 at 298 K and 1.3 bar. Additionally, the adsorption capacities of C4A-TAPA for C2H2, C2H4, and C2H6 were evaluated.

Adipose-derived stem cells derived decellularized extracellular matrix enabled skin regeneration and remodeling.

The tissues or organs derived decellularized extracellular matrix carry immunogenicity and the risk of pathogen transmission, resulting in limited therapeutic effects. The cell derived dECM cultured in vitro can address these potential risks, but its impact on wound remodeling is still unclear. This study aimed to explore the role of decellularized extracellular matrix (dECM) extracted from adipose derived stem cells (ADSCs) in skin regeneration. Methods: ADSCs were extracted from human adipose tissue. Then we cultivated adipose-derived stem cell cells and decellularized ADSC-dECM for freeze-drying. Western blot (WB), enzyme-linked immunosorbent assay (ELISA) and mass spectrometry (MS) were conducted to analyzed the main protein components in ADSC-dECM. The cell counting assay (CCK-8) and scratch assay were used to explore the effects of different concentrations of ADSC-dECM on the proliferation and migration of human keratinocytes cells (HaCaT), human umbilical vein endothelia cells (HUVEC) and human fibroblasts (HFB), respectively. Moreover, we designed a novel ADSC-dECM-CMC patch which used carboxymethylcellulose (CMC) to load with ADSC-dECM; and we further investigated its effect on a mouse full thickness skin wound model. Results: ADSC-dECM was obtained after decellularization of in vitro cultured human ADSCs. Western blot, ELISA and mass spectrometry results showed that ADSC-dECM contained various bioactive molecules, including collagen, elastin, laminin, and various growth factors. CCK-8 and scratch assay showed that ADSC-dECM treatment could significantly promote the proliferation and migration of HaCaT, human umbilical vein endothelia cells, and human fibroblasts, respectively. To evaluate the therapeutic effect on wound healing in vivo, we developed a novel ADSC-dECM-CMC patch and transplanted it into a mouse full-thickness skin wound model. And we found that ADSC-dECM-CMC patch treatment significantly accelerated the wound closure with time. Further histology and immunohistochemistry indicated that ADSC-dECM-CMC patch could promote tissue regeneration, as confirmed via enhanced angiogenesis and high cell proliferative activity. Conclusion: In this study, we developed a novel ADSC-dECM-CMC patch containing multiple bioactive molecules and exhibiting good biocompatibility for skin reconstruction and regeneration. This patch provides a new approach for the use of adipose stem cells in skin tissue engineering.

Sustained free chlorine-releasing polydimethylsiloxane/Ca(ClO)2 materials with long-lasting disinfection efficacy.

A novel sustained chlorine-releasing polydimethylsiloxane/Ca(ClO)2 (PDMS/Ca(ClO)2) material was fabricated by encapsulating Ca(ClO)2 in a PDMS matrix due to its high hydrophobicity and high chemical stability, which showed immediate-responsive and long-lasting antibacterial capabilities in aqueous conditions. Free chlorine could be released from the PDMS/Ca(ClO)2 after immersion in water for 2 min and could also be sustainedly released for 2 weeks, while the released concentration is negatively related to the duration time and positively with the initial Ca(ClO)2 contents. Additionally, Ca(ClO)2 powder as a filler significantly affects the crosslinking and pore size of PDMS. The PDMS/Ca(ClO)2 materials exhibited enduring antibacterial performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in both planktonic and multispecies-biofilm status. It is expected that this PDMS/Ca(ClO)2 material and its similar composite would be promising candidates for wide sustainable disinfection applications in biomedical and industrial fields.

Corrigendum: The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level.

[This corrects the article DOI: 10.3389/fendo.2023.1196293.].

Multimodal brain-controlled system for rehabilitation training: Combining asynchronous online brain-computer interface and exoskeleton.

BACKGROUND: Traditional therapist-based rehabilitation training for patients with movement impairment is laborious and expensive. In order to reduce the cost and improve the treatment effect of rehabilitation, many methods based on human-computer interaction (HCI) technology have been proposed, such as robot-assisted therapy and functional electrical stimulation (FES). However, due to the lack of active participation of brain, these methods have limited effects on the promotion of damaged nerve remodeling. NEW METHOD: Based on the neurofeedback training provided by the combination of brain-computer interface (BCI) and exoskeleton, this paper proposes a multimodal brain-controlled active rehabilitation system to help improve limb function. The joint control mode of steady-state visual evoked potential (SSVEP) and motor imagery (MI) is adopted to achieve self-paced control and thus maximize the degree of brain involvement, and a requirement selection function based on SSVEP design is added to facilitate communication with aphasia patients. COMPARISON WITH EXISTING METHODS: In addition, the Transformer is introduced as the MI decoder in the asynchronous online BCI to improve the global perception of electroencephalogram (EEG) signals and maintain the sensitivity and efficiency of the system. RESULTS: In two multi-task online experiments for left hand, right hand, foot and idle states, subject achieves 91.25% and 92.50% best accuracy, respectively. CONCLUSION: Compared with previous studies, this paper aims to establish a high-performance and low-latency brain-controlled rehabilitation system, and provide an independent and autonomous control mode of the brain, so as to improve the effect of neural remodeling. The performance of the proposed method is evaluated through offline and online experiments.

Is postmastectomy radiotherapy necessary for breast cancer patients with clinically node-positive downstaging to ypN0 after neoadjuvant chemotherapy?

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.

Development and comprehensive validation of a predictive prognosis model for very early HCC recurrence within one year after curative resection: a multicenter cohort study.

BACKGROUND: The high incidence of early recurrence after liver resection for hepatocellular carcinoma (HCC) is the main obstacle in achieving good long-term survival outcomes. The aim of the present study is to develop a prognostic model in predicting the risk of very early (1-year) recurrence. MATERIAL AND METHODS: Consecutive patients who underwent liver resection for HCC with curative intent at multi-centers in China were enrolled in this study. The VERM-pre (the Preoperative Very Early Recurrence Model of HCC) with good performance was derived and validated by internal and external cohorts retrospectively and by another two-center cohort prospectively. RESULTS: 7401 patients were enrolled and divided randomly into 3 cohorts. Eight variables (tumor diameter, tumor number, macrovascular invasion, satellite nodule, alpha-fetoprotein, level of HBV-DNA, γ-GT and prothrombin time) were identified as independent risk factors for recurrence-free survival on uni- and multi-variate analyses. The VERM-pre model was developed which showed a high capacity of discrimination (C-index: 0.722; AUROC at 1 year: 0.722)) and was validated comprehensively by the internal, external and prospective cohorts, retrospectively. Calibration plots showed satisfactory fitting of probability of early HCC recurrence in the cohorts. Three risk strata were derived to have significantly different recurrence free survival rates (low-risk: 80.4%-85.4%; intermediate-risk: 59.7%-64.8%; high-risk: 32.6%-42.6%). In the prospective validation cohort, the swimming plot illustrated consistent outcomes with the beginning predictive score. CONCLUSION: The VERM-pre model accurately predicted the 1-year recurrence rates of HCC after liver resection with curative intent. The model was retrospectively and prospectively validated and then developed as the online tool.

Reniformin A suppresses non-small cell lung cancer progression by inducing TLR4/NLRP3/caspase-1/GSDMD-dependent pyroptosis.

Pyroptosis is an inflammatory form of programmed cell death that plays an important role in regulating tumor progression. Reniformin A (RA) is a natural compound isolated from the medicinal herb Isodon excisoides that has been applied as folk medicine in the treatment of esophageal cancer. However, whether RA has an individual function in cancer and the molecular mechanisms remain unclear. Here, we show that in non-small-cell lung cancer (NSCLC), RA inhibits tumor growth by functioning as a pyroptosis inducer to promote TLR4/NLRP3/caspase-1/GSDMD axis. Specially, RA treatment increased Toll-like receptor 4 (TLR4) protein expression level by enhancing the TLR4 stability. Based on the molecular docking, we identified that RA directly bound to TLR4 to activate the NLRP3 inflammasome and promote pyroptosis in A549 cells. Moreover, TLR4 is essential for RA-induced pyroptosis, and loss of TLR4 abolished RA-induced pyroptosis and further reduced the inhibitory effect of RA on NSCLC. In vivo experiments confirmed that RA inhibited the growth of lung tumors in mice by affecting pyroptosis in a dose-dependent manner. Furthermore, TLR4 knockdown abolished RA-induced pyroptosis and inhibited the effect of RA chemotherapy in vivo. In conclusion, we propose that RA has a significant anticancer effect in NSCLC by inducing TLR4/NLRP3/caspase-1/GSDMD-mediated pyroptosis, which may provide a potential strategy for the treatment of NSCLC.

Characteristics of Atherosclerotic Plaques and Stroke Mechanism in Patients with Border-Zone Infarcts: A High-resolution Magnetic Resonance Imaging Study.

BACKGROUND: Relatively little is known about the plaque characteristics of border-zone infarcts and how they differ between cortical border-zone (CBZ) and internal border-zone (IBZ) infarcts. METHODS: We conducted a retrospective observational cohort study of patients with intracranial atherosclerotic disease who underwent high-resolution magnetic resonance imaging (HR-MRI) examination. Individuals with border-zone infarcts in the middle cerebral artery (MCA) territory, detected by diffusion-weighted imaging, were enrolled. Plaque morphological and compositional parameters of both IBZ and CBZ groups were compared. Independent predictors were identified using a binary logistic regression model, and the sensitivity and specificity of the model were assessed using a receiver operating characteristic curve. Kaplan-Meier survival analysis further explored differences in stroke recurrence between BZ patients with mono or dual antiplatelet therapy. RESULTS: We reviewed 101 symptomatic patients with border-zone infarcts (BZ) within the MCA territory in the study. Out of the patients meeting the imaging eligibility criteria, we detected 34 cases with isolated IBZ, 23 cases with isolated CBZ, and six cases with both IBZ and CBZ infarcts. Those with IBZ infarcts had a higher plaque burden than those without (p < 0.001), and those with CBZ infarcts exhibited a complicated plaque less frequently than those without (37.9% vs 67.6%, p = 0.018). In those with isolated IBZ or CBZ infarcts, plaque burden was independently associated with isolated IBZ infarcts (odd ratio=1.08; 95% CI, 1.02-1.15; p = 0.023). During the median follow-up period of 37 (27, 50) months, 13.8% of patients receiving early dual antiplatelet treatment and 30.4% of those on single antiplatelet therapy experienced stroke recurrence (p = 0.182). CONCLUSION: Intracranial atherosclerotic plaque morphology and composition differ between patients with IBZ and those with CBZ infarcts. Higher plaque burden is more associated with IBZ infarcts.

Protective effect of chlorogenic acid on liver injury in heat-stressed meat rabbits.

This study investigated the protective effects of chlorogenic acid (CGA) on production performance and liver function of rabbits under heat stress (HS) condition. A total of 120 healthy New Zealand weaned rabbits with similar initial body weight, were randomly divided into 3 treatments with 20 replicates per treatment and 2 weaned rabbits per replicate: control (CON) group (rabbits were housed at 25 ± 1°C and fed a basal diet), HS group (rabbits were housed at 35 ± 1°C and fed a basal diet), and HS + CGA group (rabbits were housed at 35 ± 1°C and fed a basal diet supplemented with 800 mg/kg CGA). The trial lasted for 28 days. The results showed that HS challenge decreased (p < 0.05) growth performance, induced oxidative stress and hepatic apoptosis, and caused liver damage in rabbits. However, dietary CGA supplementation increased (p < 0.05) body weight gain and feed efficiency, and enhanced (p < 0.05) antioxidative capacity in serum and liver in HS-challenged rabbits; attenuated HS-induced increases in urea nitrogen (p = 0.03), alanine aminotransferase (p = 0.03), aspartate aminotransferase (p = 0.01), caspase-8 (p = 0.02), and caspase-3 (p = 0.04) as well as decrease albumin (p = 0.04). Moreover, supplementation with CGA upregulated Nrf2/HO-1 pathway-related genes expressions, including Nrf2 (p = 0.009), HO-1 (p = 0.03) and SOD1 (p = 0.04) in HS-challenged rabbits. Our findings demonstrated that dietary CGA supplementation could alleviate HS-induced decline in growth performance, and protect against HS-induced liver damage partially through enhancing antioxidant capacity via acting Nrf2/HO-1 pathway and inhibiting hepatic apoptosis in rabbits.

Error Compensation Method for Pedestrian Navigation System Based on Low-Cost Inertial Sensor Array.

In the pedestrian navigation system, researchers have reduced measurement errors and improved system navigation performance by fusing measurements from multiple low-cost inertial measurement unit (IMU) arrays. Unfortunately, the current data fusion methods for inertial sensor arrays ignore the system error compensation of individual IMUs and the correction of position information in the zero-velocity interval. Therefore, these methods cannot effectively reduce errors and improve accuracy. An error compensation method for pedestrian navigation systems based on a low-cost array of IMUs is proposed in this paper. The calibration method for multiple location-free IMUs is improved by using a sliding variance detector to segment the angular velocity magnitude into stationary and motion intervals, and each IMU is calibrated independently. Compensation is then applied to the velocity residuals in the zero-velocity interval after zero-velocity update (ZUPT). The experimental results show a significant improvement in the average noise performance of the calibrated IMU array, with a 3.01-fold increase in static noise performance. In the closed-loop walking experiment, the average horizontal position error of a single calibrated IMU is reduced by 27.52% compared to the uncalibrated IMU, while the calibrated IMU array shows a 2.98-fold reduction in average horizontal position error compared to a single calibrated IMU. After compensating for residual velocity, the average horizontal position error of a single IMU is reduced by 0.73 m, while that of the IMU array is reduced by 64.52%.

Slimmable transformer with hybrid axial-attention for medical image segmentation.

The transformer architecture has achieved remarkable success in medical image analysis owing to its powerful capability for capturing long-range dependencies. However, due to the lack of intrinsic inductive bias in modeling visual structural information, the transformer generally requires a large-scale pre-training schedule, limiting the clinical applications over expensive small-scale medical data. To this end, we propose a slimmable transformer to explore intrinsic inductive bias via position information for medical image segmentation. Specifically, we empirically investigate how different position encoding strategies affect the prediction quality of the region of interest (ROI) and observe that ROIs are sensitive to different position encoding strategies. Motivated by this, we present a novel Hybrid Axial-Attention (HAA) that can be equipped with pixel-level spatial structure and relative position information as inductive bias. Moreover, we introduce a gating mechanism to achieve efficient feature selection and further improve the representation quality over small-scale datasets. Experiments on LGG and COVID-19 datasets prove the superiority of our method over the baseline and previous works. Internal workflow visualization with interpretability is conducted to validate our success better; the proposed slimmable transformer has the potential to be further developed into a visual software tool for improving computer-aided lesion diagnosis and treatment planning.

Enhancement Effect Induced by the Second Metal to Promote Ozone Catalytic Oxidation of VOCs.

It is a promising research direction to develop catalysts with high stability and ozone utilization for low-temperature ozone catalytic oxidation of VOCs. While bimetallic catalysts exhibit excellent catalytic activity compared with conventional single noble metal catalysts, limited success has been achieved in the influence of the bimetallic effect on the stability and ozone utilization of metal catalysts. Herein, it is necessary to systematically study the enhancement effect in the ozone catalytic reaction induced by the second metal. With a simple continuous impregnation method, a platinum-cerium bimetallic catalyst is prepared. Also highlighted are studies from several aspects of the contribution of the second metal (Ce) to the stability and ozone utilization of the catalysts, including the "electronic effect" and "geometric effect". The synergistic removal rate of toluene and ozone is nearly 100% at 30 °C, and it still shows positive stability after high humidity and a long reaction time. More importantly, the instructive significance, which is the in-depth knowledge of enhanced catalytic mechanism of bimetallic catalysts resulting from a second metal, is provided by this work.

The function of the ELF3 gene and its mechanism in cancers.

E74-like factor 3 (ELF3) is an important member of the E-twenty-six (ETS) transcription factor family. ELF3 is expressed in various types of cells and regulates a variety of biological behaviors, such as cell proliferation, differentiation, apoptosis, migration, and invasion, by binding to DNA to regulate the expression of other genes. In recent years, studies have shown that ELF3 plays an important role in the occurrence and development of many tumors and inflammation and immune related diseases. ELF3 has different functions and expression patterns in different tumors; it can function as a tumor suppressor gene or an oncogene, highlighting its dual effects of tumor promotion and inhibition. ELF3 also affects the levels of tumor immunity-related cytokines and is involved in the regulation and expression of multiple signaling pathways. In tumor therapy, ELF3 is a complex and multifunctional gene and has become a key focus of targeted treatment research. An in-depth study of the biological function of ELF3 can help to elucidate its role in biological processes and provide ideas and a basis for the development and clinical application of ELF3-related therapeutic methods. This review introduces the structure and physiological and cellular functions of the ELF3 gene, summarizes the mechanisms of action of ELF3 in different types of malignant tumors and its role in immune regulation, inflammation, etc., and discusses treatment methods for ELF3-related diseases, providing significant reference value for scholars studying the ELF3 gene and related diseases.

Two-Dimensional Metal Halide Perovskites Created by Binary Conjugated Organic Cations for High-Performance Perovskite Photovoltaics.

Studies indicated that two-dimensional (2D) metal halide perovskites (MHPs) embodied with three-dimensional (3D) MHPs were a facile way to realize efficient and stable perovskite solar cells (PSCs) and perovskite photodetectors (PPDs). Here, high-performance PSCs and PPDs, which are based on 2D/3D MHPs bilayer thin films, where the 2D MHPs are created by binary conjugated organic cations, are reported. Systemically studies reveal that the above novel 2D/3D MHPs bilayer thin films possess an enlarged crystal size, balanced charge transport, reduced charge carrier recombination, smaller charge-transfer resistance, and accelerated charge-extraction process compared to the 2D/3D MHPs bilayer thin films, where the 2D MHPs are created by a single conjugated organic cation. As a result, the PSCs based on the above novel 2D/3D MHPs bilayer thin film exhibit a power conversion efficiency of 22.76%. Moreover, unencapsulated PSCs possess dramatically enhanced stability compared with those based on the 2D/3D MHPs bilayer thin films, where the 2D MHPs are created by a single conjugated organic cation. In addition, the PPDs based on the above novel 2D/3D MHPs bilayer thin film exhibit a projected detectivity of 1016 cm Hz1/2/W and a linear dynamic range of 108 dB at room temperature. Our studies indicate that the development of binary conjugated organic cation-based 2D MHPs incorporated with 3D MHPs is a simple method to realize high-performance PSCs and PPDs.

Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma.

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time. MiR-125b decreased the A549/DDP proliferation, and the multiple drug resistance- and autophagy-related protein expression levels, which were all reversed by the inhibition of miR-125b. In addition, xenografts of human tumors in nude mice were suppressed by miR-125b, demonstrating that through autophagy regulation, miR-125b could reverse the DDP resistance in LUAD cells, both in vitro and in vivo. Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L, which in turn inhibited autophagy and reversed chemoresistance. Based on these findings, miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.