Differentiating Definite and Probable Ménière Disease: A Comprehensive Evaluation of Audio-Vestibular Function Testing Combined with Inner Ear MRI.

OBJECTIVES: To evaluate the differences between audio-vestibular function testing and inner ear gadolinium magnetic resonance imaging (MRI) in distinguishing definite Ménière disease (DMD) and probable Ménière disease (PMD), and to provide a reference for early clinical diagnosis and intervention. METHODS: A total of 116 patients diagnosed with DMD (n = 80) and PMD (n = 36) were enrolled. The differences in the results of pure tone audiometry, caloric test, and tympanic injection of gadolinium for contrast-enhanced MRI between the two groups were compared and analyzed. Parameters that could differentiate between the two conditions were identified, and the sensitivity and specificity and the area under the curve (AUC) of individual and combined indices in the differential diagnosis of DMD and PMD were evaluated. RESULTS: The hearing threshold and hearing asymmetry rate of the DMD group were significantly higher than those of the PMD group (p < 0.001), 98.8% and 30.6%, respectively. The abnormal rates of canal paresis (CP) and severity of endolymphatic hydrops in the DMD group were higher than those in the PMD group (p < 0.05). When combined with high-frequency hearing thresholds, hearing asymmetry, hearing curve type, endolymphatic hydrops, and abnormal CP, the diagnostic accuracy of DMD was improved compared to using high-frequency alone (p < 0.05). CONCLUSION: This study showed that PMD and DMD may represent two different stages in the development of MD disease. The comprehensive assessment of audio-vestibular function testing and inner ear MRI proves beneficial for early diagnosis, potentially contributing to the preservation of inner ear function.

Revisiting X-linked congenital ichthyosis.

X-linked recessive ichthyosis (XLI) is a hereditary skin disease characterized by generalized dryness and scaling of the skin, with frequent extracutaneous manifestations. It is the second most common type of ichthyosis, with a prevalence of 1/6,000 to 1/2,000 in males and without any racial or geographical differences. The causative gene for XLI is the steroid sulfatase gene (STS), located on Xp22.3. STS deficiency causes an abnormal cholesterol sulfate (CS) accumulation in the stratum corneum (SC). Excess CS induces epidermal permeability barrier dysfunction and scaling abnormalities. This review summarizes XLI's genetic, clinical, and pathological features, pathogenesis, diagnosis and differential diagnoses, and therapeutic perspectives. Further understanding the role of the STS gene pathogenic variants in XLI may contribute to a more accurate and efficient clinical diagnosis of XLI and provide novel strategies for its treatment and prenatal diagnosis.

Development of best evidence-based practice protocols for central venous catheter placement and maintenance to reduce CLABSI.

Although evidence-based interventions can reduce the incidence of central line-associated bloodstream infection (CLABSI), there is a large gap between evidence-based interventions and the actual practice of central venous catheter (CVC) care. Evidence-based interventions are needed to reduce the incidence of CLABSI in intensive care units (ICU) in China. Professional association, guidelines, and database websites were searched for data relevant to CLABSI in the adult ICUs from inception to February 2020. Checklists were developed for both CVC placement and maintenance. Based on the Integrated Promoting Action on Research Implementation in Health Services framework, a questionnaire collected the cognition and practice of ICU nursing and medical staff on the CLABSI evidence-based prevention guidelines. From January 2018 to December 2021, ICU CLABSI rates were collected monthly. Ten clinical guidelines were included after the screening and evaluation process and used to develop the best evidence-based protocols for CVC placement and maintenance. The CLABSI rates in 2018, 2019, and 2020 were 2.98‰ (9/3021), 1.83‰ (6/3276), and 1.69‰ (4/2364), respectively. Notably, the CLABSI rate in 2021 was 0.38‰ (1/2607). In other words, the ICU CLABSI rate decreased from 1.69‰ to 0.38‰ after implementation of the new protocols. Additionally, our data suggested that the use of ultrasound-guidance for catheter insertion, chlorhexidine body wash, and the use of a checklist for CVC placement and maintenance were important measures for reducing the CLABSI rate. The evidence-based processes developed for CVC placement and maintenance were effective at reducing the CLABSI rate in the ICU.

Recent progress on DNAzyme-based biosensors for pathogen detection.

Pathogens endanger food safety, agricultural productivity, and human health. Those pathogens are spread through direct/indirect contact, airborne transmission and food/waterborne transmission, and some cause severe health consequences. As the population grows and global connections intensify, the transmission of infectious diseases expands. Traditional detection methods for pathogens still have some shortcomings, such as time-consuming procedures and high operational costs. To fulfil the demands for simple and effective detection, numerous biosensors have been developed. DNAzyme, a unique DNA structure with catalytic activity, is gradually being applied in the field of pathogen detection owing to its ease of preparation and use. In this review, we concentrated on the two main types of DNAzyme, hemin/G-quadruplex DNAzyme (HGD) and RNA-cleaving DNAzyme (RCD), explaining their research progress in pathogen detection. Furthermore, we introduced two additional novel DNAzymes, CLICK 17 DNAzyme and Supernova DNAzyme, which showed promising potential in pathogen detection. Finally, we summarize the strengths and weaknesses of these four DNAzymes and offer feasible recommendations for the development of biosensors.

[Effects of Straw Addition on N2O and CO2 Emissions from Red Soil Subjected to Different Long-Term Fertilization].

Straw return, as an important measure for soil fertility improvement in farmland, significantly affects the emissions of greenhouse gases N2O and CO2. Thus, the collected soil samples from five long-term (30-year) fertilization treatments (no fertilization, CK; recommended chemical fertilizer, F; 200 % of recommended chemical fertilizer, 2F; pig manure, M; and chemical fertilizer combined with pig manure, FM) were amended with and without straw and incubated under constant temperature and humidity conditions (25 ℃ and 65 % maximum field water holding capacity) for 20 days so as to investigate the key factors influencing N2O and CO2 emissions in response to straw addition in long-term fertilization treatments. The results showed that fertilization significantly increased N2O emissions. Compared to those under the unfertilized treatment[(22.05 ±2.09) µg·kg-1, calculated as nitrogen, the same as below], cumulative N2O emissions from the chemical fertilizer treatments significantly increased by 119 %-195 %[(48.38 ±20.81) µg·kg-1 and (65.13 ±12.55) µg·kg-1 from the F and 2F treatments, respectively], and those from the manure treatments increased by 275 %-399 %[(82.72 ±12.73) µg·kg-1 and (1 101.99 ±425.71) µg·kg-1 from the M and FM treatments, respectively]. Soil NO3--N, DOC, and DTN were the main factors influencing N2O emissions from fertilized treatments in the absence of straw addition. Straw addition significantly increased cumulative N2O emissions by 345 % and 247 % in the 2F and M treatments, respectively, compared to those in the corresponding fertilized treatments without straw addition, with no significant effect on N2O emissions in the CK, F, and FM treatments. Straw addition increased DOC content and microbial activity and decreased soil NO3--N and DTN contents, thereby increasing N2O emissions. Fertilization also significantly increased CO2 emissions. Compared to those from the unfertilized treatment, cumulative CO2 emissions from the manure treatments significantly increased by 120 %-130 %[(122.11 ±4.3) mg·kg-1 (calculated as carbon, the same as below) and (116.47 ±4.55) mg·kg-1 from the M and FM treatments, respectively], and those in the 2F treatment increased by 28 %[(65.13 ±12.55) mg·kg-1]. In the absence of straw addition, soil MBC, DOC, and DTN were the main factors influencing CO2 emissions. Compared to those in the treatments without straw addition, straw addition significantly increased cumulative CO2 emissions by 660 %-1132 % among fertilization treatments, due to increased DOC and MBC contents and enhanced microbial activity. In conclusion, straw addition significantly increased N2O and CO2 emissions through increased soil DTN consumption and DOC content among fertilization treatments. In soils treated with manure amendment, straw return should be rationally considered for the purpose of balancing the comprehensive trade-offs between fertility improvement and greenhouse gas emissions.

Immunoglobulin G4 (IgG4) Positive Associated Liver Disease.

BACKGROUND: The goal was to explore the cognition of diagnosis and treatment level of IgG4-related diseases mainly involving lymph nodes. METHODS: The clinical manifestations, laboratory indicators, histopathology, and therapeutic effects of a patient with IgG4-RD suspected of lymphoma were analyzed and the relevant literature was reviewed. RESULTS: Lymph node biopsy showed reactive hyperplasia of lymph node tissue. The liver biochemical indexes were abnormal and the bone marrow smear showed atypical lymphocytes. Lymph node section: IgG4+ cells > 100/HPF (IgG4/IgG > 40%). The serum IgG4 level was 17,200 mg/L, and the diagnosis was IgG4-RD. Oral glucocorticoids took effect after 2 weeks, and no significant enlargement of lymph nodes was observed. CONCLUSIONS: For the diagnosis of IgG4-RD, at present, histopathology is still the gold standard, but a single result cannot diagnose the disease. Comprehensive judgment should be made by combining clinical symptoms, serum IgG4 level and imaging results to prevent misdiagnosis and missed diagnosis, and to avoid over-diagnosis. Short-term hormonal diagnostic therapy may be used in highly suspected patients who cannot be diagnosed. Once diagnosed, standardized medication, adhere to follow-up, regular review, to prevent recurrence and adverse drug reactions.

Outcomes of ankle arthrodesis in adult patients with ankle osteoarthritis in Kashin-Beck disease.

PURPOSE: We retrospectively evaluated the characteristics of these patients and the effectiveness of ankle arthrodesis in the treatment of ankle arthritis caused by Kashin-Beck disease (KBD). METHODS: A retrospective study of KBD patients with ankle osteoarthritis who underwent ankle arthrodesis between December 2012 and January 2022 was performed. A total of 46 patients were included. The general characteristics, clinical manifestations and imaging features of the patients were recorded and summarized. measured using the VAS score, and ankle function was assessed by the AOFAS ankle-hindfoot score. RESULTS: Multiple subchondral cystic changes were found in 42(91.3%) patients. The VAS scores for both resting and weight-bearing conditions were 6.28 ± 1.30 vs. 2.09 ± 1.12 (P < .001) and 6.87 ± 1.01 vs. 2.17 ± 0.98 (P < .001), respectively. The AOFAS scores were 59.17 ± 5.50 and 88.39 ± 1.42, respectively (P < .001). CONCLUSIONS: The subchondral multiple cystic transformation of the ankle KBD has a certain suggestive role.Arthrodesis is an effective method to reduce ankle pain and improve ankle function in KBD patients with ankle osteoarthritis.

Toripalimab Plus Bevacizumab as First-line Treatment for Advanced Hepatocellular Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Trial.

PURPOSE: This phase II, multicenter, prospective, single-arm study aimed to evaluate the efficacy and safety of toripalimab plus bevacizumab for treating advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Treatment-naïve patients with advanced HCC received toripalimab 240 mg plus bevacizumab 15 mg/kg every 3 weeks. The primary endpoints included safety and tolerability and objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: Fifty-four patients were enrolled between April 17, 2020, and December 11, 2020. As assessed by the investigator according to RECIST v1.1, the ORR was 31.5% [95% confidence interval (CI), 19.5-45.6] and the lower bound of the 95% CI was above the prespecified boundary of 10%. The independent review committee (IRC) assessed ORR according to the modified RECIST (mRECIST), which was 46.3% (95% CI, 32.6-60.4). The median progression-free survival was 8.5 (95% CI, 5.5-11.0) and 9.8 months (95% CI, 5.6 to not evaluable) as assessed by the investigator according to RECIST v1.1 and IRC according to mRECIST criteria, respectively. The median overall survival (OS) was not reached, and the 12- and 24-month OS rates were 77.3% and 63.5%, respectively. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 27 patients (50.0%). The most common TEAEs were proteinuria (59.3%), hypertension (38.9%), increased aspartate aminotransferase (33.3%), increased amylase (29.6%), decreased platelet count (27.8%), and increased bilirubin levels (27.8%). CONCLUSIONS: Toripalimab plus bevacizumab showed a favorable efficacy and safety profile, supporting further studies on this combination regimen as a first-line treatment for advanced HCC.

Dissipative control for nonlinear singularly perturbed systems with dynamic quantization and actuator failure.

The paper discusses the dissipative control problem of nonlinear singularly perturbed systems (SPSs) with dynamic quantization and actuator failure. The nonlinear singularly perturbed plant is described by Takagi-Sugeno (T-S) fuzzy model. The dynamic quantizer is considered to realize the effective utilization of the limited network channel bandwidth resources, and the possible transmission failure between the controller and the actuator is also considered. Based on linear matrix inequalities, sufficient design conditions for the ϵ-independent state feedback controller are given such that the constructed quantized closed-loop system is asymptotically stable and satisfies a predefined dissipative performance. Furthermore, a short search algorithm is given to search the maximum stability bound ϵ̄. Finally, two examples are provided in order to prove the feasibility and effectiveness of the proposed method.

Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1.

Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis. And overexpression of SPNS1 exhibited opposite functions. Furthermore, ESCC cells became more sensitive to 5-fluorouracil (5-FU) when SPNS1 was knocked down. Transcriptome sequencing revealed that NEU1 was one significant DEG affected by SPNS1 and positively correlated with SPNS1 expression. Oseltamivir phosphate (OP), one NEU1 inhibitor, markedly reversed 5-FU resistance, migration, and proliferation induced by high expression of SPNS1 both in vivo and in vitro. Our findings indicated that SPNS1 might promote the progression of ESCC by upregulating NEU1 expression and influencing chemotherapy sensitivity. These results provide new perceptions into potential therapeutic targets for ESCC treatment. The present study aimed to investigate the role and underlying mechanism of SPNS1 in ESCC.

Comprehensive Analyses of PANoptosome with Potential Implications in Cancer Prognosis and Immunotherapy.

Cell death resistance significantly contributes to poor therapeutic outcomes in various cancers. PANoptosis, a unique inflammatory programmed cell death (PCD) pathway activated by specific triggers and regulated by the PANoptosome, possesses key features of apoptosis, pyroptosis, and necroptosis, but these cannot be accounted for by any of the three PCD pathways alone. While existing studies on PANoptosis have predominantly centered on infectious and inflammatory diseases, its role in cancer malignancy has been understudied. In this comprehensive investigation, we conducted pan-cancer analyses of PANoptosome component genes across 33 cancer types. We characterized the genetic, epigenetic, and transcriptomic landscapes, and introduced a PANoptosome-related potential index (PANo-RPI) for evaluating the intrinsic PANoptosome assembly potential in cancers. Our findings unveil PANo-RPI as a prognostic factor in numerous cancers, including KIRC, LGG, and PAAD. Crucially, we established a significant correlation between PANo-RPI and tumor immune responses, as well as the infiltration of diverse lymphoid and myeloid cell subsets across nearly all cancer types. Moreover, a high PANo-RPI was consistently associated with improved immunotherapy response and efficacy, as evidenced by re-analysis of multiple immunotherapy cohorts. In conclusion, our study suggests that targeting PANoptosome components and modulating PANoptosis may hold tremendous therapeutic potential in the context of cancer.

Optimizing electrochemical performance of Na0.67Ni0.17Co0.17Mn0.66O2 with P2 structure via preparing concentration-gradient particles for sodium-ion batteries.

P2-type layered oxides for rechargeable sodium-ion batteries have drawn a lot of attention because of their excellent electrochemical performance. However, these types of cathodes usually suffer from poor cyclic stability. To overcome this disadvantage, in this work, novel ball-shaped concentration-gradient oxide Na0.67Ni0.17Co0.17Mn0.66O2 with P2 structure modified by Mn-rich surface is successfully prepared using co-precipitation method. The concentration of Mn increased from the inner core to the surface, endowing the material with an excellent cyclic stability. The cathode exhibits enhanced electrochemical properties than that of the sample synthesized by solid-state method and concentration-constant material. It shows 143.2 mAh/g initial discharge capacity and retains 131 mAh/g between 2 V and 4.5 V after 100 rounds. The significant improvement in the electrochemical properties of the sample benefits from the unique concentration-gradient structure, and the Mn-rich surface that effectively stabilizes the basic P2 structure. The relatively higher Ni content in the core leads to a slight improvement in the discharge capacity of the sample. This strategy may provide new insights for preparing layered cathodes for sodium-ion batteries with high electrochemical performance.

Single image super-resolution with denoising diffusion GANS.

Single image super-resolution (SISR) refers to the reconstruction from the corresponding low-resolution (LR) image input to a high-resolution (HR) image. However, since a single low-resolution image corresponds to multiple high-resolution images, this is an ill-posed problem. In recent years, generative model-based SISR methods have outperformed conventional SISR methods in performance. However, the SISR methods based on GAN, VAE, and Flow have the problems of unstable training, low sampling quality, and expensive computational cost. These models also struggle to achieve the trifecta of diverse, high-quality, and fast sampling. In particular, denoising diffusion probabilistic models have shown impressive variety and high quality of samples, but their expensive sampling cost prevents them from being well applied in the real world. In this paper, we investigate the fundamental reason for the slow sampling speed of the SISR method based on the diffusion model lies in the Gaussian assumption used in the previous diffusion model, which is only applicable for small step sizes. We propose a new Single Image Super-Resolution with Denoising Diffusion GANS (SRDDGAN) to achieve large-step denoising, sample diversity, and training stability. Our approach combines denoising diffusion models with GANs to generate images conditionally, using a multimodal conditional GAN to model each denoising step. SRDDGAN outperforms existing diffusion model-based methods regarding PSNR and perceptual quality metrics, while the added latent variable Z solution explores the diversity of likely HR spatial domain. Notably, the SRDDGAN model infers nearly 11 times faster than diffusion-based SR3, making it a more practical solution for real-world applications.

Differentiating Meniere's Disease and Vestibular Migraine: Insights from Gadolinium-Enhanced Magnetic Resonance Imaging and Clinical Features.

OBJECTIVE: To explore the predictive factors between Meniere's disease (MD) and vestibular migraine (VM) by Gadolinium-enhanced Magnetic resonance imaging (MRI) of the inner ear and Clinical Features. METHODS: Eighty-seven patients (50 MD and 37 VM) underwent intratympanic injection of gadolinium and MRI was performed 24 h later. All patients underwent pure tone audiometry and caloric tests. RESULTS: In the MD group, 46 (92%) of 50 patients developed endolymphatic hydrops, although only 2 (5.4%) in the vestibular migraine (VM) group had positive results groups (p < 0.001). The incidence of migraine was 14% in the MD group and 67.7% in the VM group (p < 0.001). Multivariate logistic regression of the two groups of patients indicated that the greater the sum of the maximum slow phase velocity (SPV) of the ipsilateral ear, the higher the risk of VM occurrence (p = 0.009). The incidence of carsickness was positively correlated with the incidence of VM (p < 0.001) and asymmetric hearing loss (AHL) was negatively correlated with the diagnosis of VM (p = 0.045). CONCLUSION: Gadolinium-enhanced MRI of the inner ear is helpful for the differential diagnosis of VM and MD. Carsickness, decreased AHL, and increased Sum of the maximum SPV in the ipsilateral side (SSPVI) may act as diagnostic predictors of VM. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:426-432, 2024.

The value of gadolinium-enhanced MRI in predicting the development of sudden hearing loss into Ménière's disease.

OBJECTIVE: To compare the clinical features of sudden hearing loss (SHL) in patients with and without endolymphatic hydrops (EH), and to investigate the association between SHL with EH and Ménière's disease (MD). METHODS: The clinical data of 63 SHL patients with first symptoms were evaluated retrospectively. Patients were separated into two groups based on the results of gadolinium-enhanced magnetic resonance imaging: EH and non-EH groups. Independent sample t-test and U-test were used to compare groups for continuous variables, and the chi-squared test, corrected chi-squared test and Bonferroni correction test were used to compare groups for binary and ordinal variables. The binary logistic regression model was utilised for univariate and multivariate analysis of follow-up patient prognosis. RESULTS: The EH and non-EH groups contained 32 and 31 patients, respectively. The EH group had a higher prevalence of low-tone descending hearing loss. Fifty-one patients were followed for more than 2 years. In the EH group, 11 and 15 patients were diagnosed with sudden sensorineural hearing loss (SSNHL) and MD, respectively, while in the non-EH group, 24 patients were diagnosed with SSNHL and only one with MD. EH, low-tone descending hearing loss and vertigo were risk factors for the diagnosis of MD in a subgroup univariate regression analysis of patients experiencing SHL. EH was found to be a risk factor for the progression of SHL into MD in a multifactor regression analysis. CONCLUSIONS: Patients with SHL who have EH are more likely to present with low-tone descending hearing loss. EH is a risk factor for the subsequent development of MD.

FBXW7 inhibits the progression of ESCC by directly inhibiting the stemness of tumor cells.

F-box and WD repeat domain containing 7 (FBXW7) is an aboriginal and high-frequency mutant gene associated with esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of FBXW7 in the development of ESCC. The clinical significance of FBXW7 was analyzed in ESCC from TCGA data. The effects of FBXW7 on proliferation, colony formation, migration and invasion, angiogenesis, and apoptosis were tested in ESCC cells. PCR-array, sphere formation assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the mechanism of FBXW7. FBXW7 was a significantly mutated gene in ESCC. It was an independent and potential predictor for survival in ESCC patients. In addition, FBXW7 overexpression significantly inhibited ESCC cell proliferation, migration, invasion, angiogenesis, and promoted cell apoptosis. PCR array revealed that FBXW7 overexpression leads to a significant change of gene expressions associated with angiogenesis, cell senescence, and DNA damage and repair. Sphere formation assay and qPCR showed FBXW7 was associated with ESCC stem cell formation. Our results suggest that FBXW7 may act as a tumor suppressor by repressing cancer stem cell formation and regulating tumor angiogenesis, cell senescence, DNA damage, and repair in ESCC.

The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.

Cholesteatoma is a chronic inflammatory ear disease with abnormal keratinized epithelium proliferation and tissue damage. However, the mechanism of keratinized epithelium hyperproliferation in cholesteatoma remains unknown. Hence, our study sought to shed light on mechanisms affecting the pathology and development of cholesteatoma, which could help develop adjunctive treatments. To investigate molecular changes in cholesteatoma pathogenesis, we analyzed clinical cholesteatoma specimens and paired ear canal skin with mass spectrometry-based proteomics and bioinformatics. From our screen, alpha-synuclein (SNCA) was overexpressed in middle ear cholesteatoma and might be a key hub protein associated with inflammation, proliferation, and autophagy in cholesteatoma. SNCA was more sensitive to lipopolysaccharide-induced inflammation, and autophagy marker increase was accompanied by autophagy activation in middle ear cholesteatoma tissues. Overexpression of SNCA activated autophagy and promoted cell proliferation and migration, especially under lipopolysaccharide inflammatory stimulation. Moreover, inhibiting autophagy impaired SNCA-mediated keratinocyte proliferation and corresponded with inhibition of the PI3K/AKT/CyclinD1 pathways. Also, 740Y-P, a PI3K activator reversed the suppression of autophagy and PI3K signaling by siATG5 in SNCA-overexpressing cells, which restored proliferative activity. Besides, knockdown of SNCA in RHEK-1 and HaCaT cells or knockdown of PI3K in RHEK-1 and HaCaT cells overexpressing SNCA both resulted in attenuated cell proliferation. Our studies indicated that SNCA overexpression in cholesteatoma might maintain the proliferative ability of cholesteatoma keratinocytes by promoting autophagy under inflammatory conditions. This suggests that dual inhibition of SNCA and autophagy may be a promising new target for treating cholesteatoma.

A programmable DNA nanodevice for colorimetric detection of DNA methyltransferase activity using functionalized hemin/G-quadruplex DNAzyme.

The measurement of DNA methyltransferase (MTase) activity and screening of DNA MTase inhibitors holds significant importance for the diagnosis and therapy of methylation-related illness. Herein, we developed a colorimetric biosensor (PER-FHGD nanodevice) to detect DNA MTase activity by integrating the primer exchange reaction (PER) amplification and functionalized hemin/G-quadruplex DNAzyme (FHGD). By replacing the native hemin cofactor into the functionalized cofactor mimics, FHGD has exhibited significantly improved catalytic efficiency, thereby enhancing the detection performance of the FHGD-based system. The proposed PER-FHGD system is capable of detecting Dam MTase with excellent sensitivity, exhibiting a limit of detection (LOD) as low as 0.3 U/mL. Additionally, this assay demonstrates remarkable selectivity and ability for Dam MTase inhibitors screening. Furthermore, using this assay, we successfully detect the Dam MTase activity both in serum and in E. coli cell extracts. Importantly, this system has the potential to serve as a universal strategy for FHGD-based diagnosis in point-of-care (POC) tests, by simply altering the recognition sequence of the substrate for other analytes.