A longitudinal study on the effect of PM2.5 components on blood pressure in the hypertensive patients from 2011 to 2019.

Extensive research has established the link between PM2.5 exposure and blood pressure (BP) levels among normal individuals. However, the association between PM2.5 components and BP levels in hypertensive patients has not been fully explored. In this study, 12 971 hypertensive cases from Jinchang cohort (in Jinchang City, China) with nearly 9 years of follow-up were enrolled. Based on the linear mixed-effect model, the effects of fine particulate matter (PM2.5) and five major components [sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), black carbon (BC) and organic matter (OM)]on BP [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP)]were evaluated by single-component model, component-joint model and component-residual model, respectively. A positive correlation was found between PM2.5 as well as its components (SO42-, NO3-, NH4+, BC and OM) exposure and BP levels. The effects of SO42-, BC and OM on BP were observed to be the most robust among the three models. Based on the results of interaction effects and stratified analysis, the effect of BC exposure on SBP, and the effect of PM2.5 and its five components on PP were greater in female than in males. Compared with elderly hypertensive patients, OM had more significant effects on SBP, DBP and MAP in young and (or) middle-aged hypertensive patients. During the heating season, the effect of PM2.5 and its components on BP was grater compared to the non-heating season. Meanwhile, PM2.5 and its components have a greater influence on BP in patients with hypertension combined with diabetes. Therefore, the findings suggested that both PM2.5 exposure and its components had a significant effect on BP in patients with hypertension. Women and young and middle-aged hypertensive patient were the sensitive population. The implementation of source control and reduction of PM2.5 emission (mainly for SO42-, BC and OM) may be of great significance to control BP level and could reduce the risk of cardiovascular disease in patients with hypertension.

[Prediction of color simulation prescription for traditional Chinese medicine placebo solution based on whale algorithm-optimized back propagation neural network].

Traditional Chinese medicine(TCM) placebos are simulated preparations for specific objects and the color simulation in the development of TCM placebos is both crucial and challenging. Traditionally, the prescription screening and pattern exploration process involves extensive experimentation, which is both time-consuming and labor-intensive. Therefore, accurate prediction of color simulation prescriptions holds the key to the development of TCM placebos. In this study, we efficiently and precisely predict the color simulation prescriptions of placebos using an image-based approach combined with Matlab software. Firstly, images of TCM placebo solutions are captured, and 13 chromaticity space values such as the L* a* b*, RGB, HSV, and CMYK values are extracted using Photoshop software. Correlation analysis and normalization are then performed on these extracted values to construct a 13×9×3 back propagation(BP) neural network model. Subsequently, the whale optimization algorithm(WOA) is employed to optimize the initial weights and thresholds of the BP neural network. Finally, the optimized WOA-BP neural network is validated using three representative instances. The training and prediction results indicate that, compared to the BP neural network, the WOA-BP neural network demonstrates superior performance in predicting the pigment ratios of placebos. The correlation coefficients for training, validation,testing, and the overall dataset are 0. 95, 0. 87, 0. 95, and 0. 95, respectively, approaching unity. Furthermore, all error values are reduced, with the maximum reduction reaching 99. 83%. The color difference(ΔE) values for the three validation instances are all less than 3, further confirming the accuracy and practicality of the WOA-BP neural network approach.

Orthostatic hypotension and cerebral small vessel disease: A systematic review.

Orthostatic hypotension(OH) is highly prevalent in ageing populations and may contribute to cognitive decline through cerebral small vessel disease(CSVD). Research on the association between OH and CSVD is fragmented and inconsistent. We systematically reviewed the literature for studies assessing the association between OH and CSVD, published until December 1st 2023 in MEDLINE, PubMed or Web of Science. We included studies with populations aged ≥60, that assessed OH in relation to CSVD including white matter hyperintensities(WMH), lacunes and cerebral microbleeds. Modified JBI checklist was used to assess risk of bias. A narrative synthesis of the results was presented. Of 3180 identified studies, eighteen were included. Fifteen studies reported on WMH, four on lacunes, seven on microbleeds. Six of fifteen studies on WMH found that OH was related to an increased burden of WMH, neither longitudinal studies found associations with WMH progression. Findings were inconsistent across studies concerning lacunes and microbleeds. Across outcomes, adequate adjustment for systolic blood pressure tended to coincide with smaller effect estimates. Current evidence on the OH-CSVD association originates mostly from cross-sectional studies, providing inconsistent and inconclusive results. Longitudinal studies using standardized and fine-grained assessment of OH and CSVD and adequate adjustment for supine blood pressure are warranted.

GA-BP-Based Low-Noise FBG Hydroacoustic Monitoring System with Reference Sensor.

To address the issue of harsh marine background noise impacting the monitoring signal of fiber-optic hydrophones, we propose a low-noise fiber Bragg grating (FBG) hydroacoustic monitoring system with a reference sensor based on genetic algorithm backpropagation (GA-BP). Through theoretical analysis, we deduce the noise suppression steps of the GA-BP algorithm based on the reference sensor and construct train and test sets based on the data from the reference sensor and monitoring sensor at different times, optimizing the GA-BP algorithm to find the best fitting results and thereby obtaining the low-noise monitoring signal. Experimental results from the anechoic tank show that the proposed method can suppress background noise interference on effective signals and that the suppression effect improves as the background noise increases. The sound pressure sensitivity ranges from -173.76 dB to -171.33 dB at frequencies of 8 kHz to 12 kHz, with a response flatness of less than 2.43 dB. The noise suppression effect is obvious under the condition of poor signal-to-noise ratio (SNR), which can reach more than 18.3 dB. The advantages of the proposed algorithm in array signal processing are further demonstrated by the directivity experiment, which proves that the algorithm has a great potential for engineering applications in harsh marine environment.

Evaluation of the Predictive Character of the Expiratory Inferior Vena Cava/Abdominal Aorta (eIVC/Ao) Index for Minimum Blood Pressure Following Spinal Anesthesia With 0.5% Hyperbaric Bupivacaine.

Spinal anesthesia has many side effects, one of them being a drop in blood pressure (BP). Identifying predictive factors for this drop is a clear matter of concern. In this regard, the expiratory inferior vena cava/abdominal aorta (eIVC/Ao) index has already been spotted as such for doses of 0.5% hyperbaric bupivacaine greater than 12mg. Departing from the demonstrated correlation between this index and hypotension post-spinal anesthesia, our study aimed to (1) evaluate whether an eIVC/Ao index greater than 0.7, thus defining non-hypovolemic patients, can also predict minimal BP for doses inferior to 12mg and (2) identify other predictive factors for minimal BP post-spinal anesthesia. Lastly, we verified whether preoperative fasting induces hypovolemia.  This single-center prospective observational pilot study included 20 patients. The baseline measurements of BP, eIVC/Ao index, and fasting time were recorded at time T0'. Then spinal anesthesia was administered with 0.5% hyperbaric bupivacaine in doses inferior to 12 mg. The patients' systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and metameric levels were each recorded at times T5', T10', T15', and T20'.  The results indicated that baseline DBP was predictive of low DBP and minimum MAP, which reflect myocardial perfusion and systemic pressures, respectively. Therefore, it should trigger prophylaxis (spinal-lateralized, continuous, or lower dose) in patients with a low DBP baseline. Additionally, baseline SBP was predictive of minimum SBP, an independent risk factor for post-anesthetic hypotension if its baseline is less than 120 mmHg. Although female gender was linked to minimum SBP, other confounding factors (size, dose administered, and type of surgery related to gender) must also be considered. Moreover, a correlation was established between height and MAP in parturients. Hypotension was not recorded at local anesthetic (LA) doses between 8 and 12 mg and the doses administered were sufficient to achieve the metameric levels required for surgery (ether tests). Since 8 mg of 0.5% hyperbaric bupivacaine achieved the same level as 12 mg, lower doses of LA might prevent a significant drop in BP and its deleterious effects. Therefore, in the current cohort, the eIVC/Ao index was not predictive of minimum BP during spinal anesthesia with doses less than 12 mg of 0.5% hyperbaric bupivacaine. However, predictive factors for minimum BP included gender and baseline SBP (for minimum SBP), height and baseline DBP (for minimum MAP), and baseline DBP (for minimum DBP). Lastly, preoperative fasting did not cause hypovolemia.

Based on the improved fuzzy analytic hierarchy and the TSE-MLR model energy consumption prediction of university: A case study.

The accurate prediction of building energy consumption on university campuses is a significant research area. Current studies often focus on predicting the energy consumption of specific building areas or individual equipment, and typically consider only one factor, limiting the accuracy and applicability of the predictions. This study introduces the Time Segmented Energy-Multiple Linear Regression (TSE-MLR) prediction model, which integrates the improved fuzzy analytic hierarchy and the multiple linear regression algorithm. The model is compared with traditional (MLR, BP) and advanced (RNN) models, and their various indexes are discussed and analyzed. By collecting meteorological and energy consumption data from the study site over the past 12 years, the key factors affecting energy consumption on the university campus were identified using the improved fuzzy analytic hierarchy. Subsequently, the TSE-MLR model was trained using energy consumption data from 2010 to 2016 and validated using data from 2017 to 2019. The prediction results of the TSE-MLR model were compared with those obtained through Multiple linear regression, BP neural networks, and RNN. The results demonstrated that the TSE-MLR model significantly reduced the prediction error by 13.8 % and exhibited higher accuracy compared to the other models. Therefore, the TSE-MLR model introduced in this study offers a new and effective approach to predicting university energy consumption and supporting energy management using existing data from university building operations across different periods.

N6-methyladenosine enhances the expression of TGF-ß-SMAD signaling family to inhibit cell growth and promote cell metastasis.

TGF-ß-SMAD signaling pathway plays an important role in the progression of various cancers. However, posttranscriptional regulation such as N6-methyladenosine (m6A) of TGF-ß-SMAD signaling axis remains incompletely understood. Here, we reveal that insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) is low expression as well as associated with poor prognosis in clear cell renal cell carcinoma (ccRCC) patients and inhibits proliferation as well as promotes metastasis of ccRCC cells. Mechanistically, IGF2BP2 systematically regulates TGF-ß-SMAD signaling family, including TGF-ß1/2, TGF-ßR1/2 and SMAD2/3/4, through mediating their mRNA stability in an m6A-dependent manner. Furthermore, the functional effects of IGF2BP2 on ccRCC cells is mediated by TGF-ß-SMAD signaling downstream effector SMAD4, which is identified three m6A sites in 5'UTR and CDS. Our study establishes IGF2BP2-TGF-ß-SMAD axis as a new regulatory effector in ccRCC, providing new insights for developing novel therapeutic strategies.

Knockdown of IGF2BP3 Down-Regulates PDCD4 Levels to Attenuate Hypoxic-Ischemic Brain Damage.

BACKGROUND: Hypoxic-ischemic brain damage (HIBD) is a prevalent brain injury with high mortality and morbidity. It results from hypoxia and ischemia of the brain due to various perinatal factors. A previous study showed that knockdown of programmed cell death factor 4 (PDCD4) could reduce infarction injury resulting from ischemia/reperfusion injury. However, exact mechanism by which PDCD4 acts in HIBD is not yet understood. Our aim in present investigation was to investigate the function and mechanism of PDCD4 in alleviating HIBD. METHODS: An HIBD model was developed using neonatal rats. After 48 h of modeling, short-term neurological function was evaluated and the brain tissue removed for assessment of cerebral infarct volume and brain water content (BWC). A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) was also constructed. Overexpression or knockdown of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) or PDCD4 was performed in pretreated cells. RESULTS: The geotaxis reflex time, cerebral infarct volume, and BWC all increased after HIBD in this neonatal rat model. Additionally, the levels of PDCD4 and of the N6-Methyladenosine (m6A) reader protein IGF2BP3 were increased in HIBD rats and OGD/R-stimulated pheochromocytoma (PC12) cells relative to controls. Moreover, OGD/R-stimulated pheochromocytoma PC12 cells showed decreased cell viability, increased apoptosis, and elevated Interleukin 6 (IL-6), Interleukin 1 ß (IL-1ß), and tumor necrosis factor-α (TNF-α) contents. These features were reversed after knocking down IGF2BP3. The interaction between IGF2BP3 protein and PDCD4 mRNA was confirmed by RNA immunoprecipitation and RNA pull-down assays. Furthermore, knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells reduced cell damage via down-regulation of PDCD4. Finally, the IGF2BP3/PDCD4 axis alleviated OGD/R-induced cell injury in primary cortical neurons (PCNs). CONCLUSIONS: PDCD4 and m6A reader protein IGF2BP3 were up-regulated in an HIBD neonatal rat model. Knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells or PCNs alleviated cell damage through reducing PDCD4.

Data-Driven Power Prediction for Proton Exchange Membrane Fuel Cell Reactor Systems.

Enhancing high-performance proton exchange membrane fuel cell (PEMFC) technology is crucial for the widespread adoption of hydrogen energy, a leading renewable resource. In this research, we introduce an innovative and cost-effective data-driven approach using the BP-AdaBoost algorithm to accurately predict the power output of hydrogen fuel cell stacks. The algorithm's effectiveness was validated with experimental data obtained from an advanced fuel cell testing platform, where the predicted power outputs closely matched the actual results. Our findings demonstrate that the BP-AdaBoost algorithm achieved lower RMSE and MAE, along with higher R2, compared to other models, such as Partial Least Squares Regression (PLS), Support Vector Machine (SVM), and back propagation (BP) neural networks, when predicting power output for electric stacks of the same type. However, the algorithm's performance decreased when applied to electric stacks with varying material compositions, highlighting the need for more sophisticated models to handle such diversity. These results underscore the potential of the BP-AdaBoost algorithm to improve PEMFC efficiency while also emphasizing the necessity for further research to develop models capable of accurately predicting power output across different types of PEMFC stacks.

Engineered FHA domains can bind to a variety of Phosphothreonine-containing peptides.

Antibodies play a crucial role in monitoring post-translational modifications, like phosphorylation, which regulates protein activity and location; however, commercial polyclonal and monoclonal antibodies have limitations in renewability and engineering compared to recombinant affinity reagents. A scaffold based on the Forkhead-associated domain (FHA) has potential as a selective affinity reagent for this post-translational modification. Engineered FHA domains, termed phosphothreonine-binding domains (pTBDs), with limited cross-reactivity were isolated from an M13 bacteriophage display library by affinity selection with phosphopeptides corresponding to human mTOR, Chk2, 53BP1, and Akt1 proteins. To determine the specificity of the representative pTBDs, we focused on binders to the pT543 phosphopeptide (536-IDEDGENpTQIEDTEP-551) of the DNA repair protein 53BP1. ELISA and western blot experiments have demonstrated the pTBDs are specific to phosphothreonine, demonstrating the potential utility of pTBDs for monitoring the phosphorylation of specific threonine residues in clinically relevant human proteins.

A retrospective study on the outcome of pulpotomy with iRoot BP plus in primary molars and its relationship with hemostasis time.

BACKGROUND: Pulpotomy is a crucial method to preserve primary teeth until natural exfoliation. This study aimed to evaluate the clinical and radiographic outcomes of pulpotomy with iRoot BP Plus in primary molars and to explore the association between hemostasis time and these outcomes. METHODS: Primary molars that underwent iRoot BP Plus pulpotomy and were followed for at least 12 months were selected for this study. Clinical and radiographic data were collected, and the success rate was analyzed in relation to factors such as hemostasis time, tooth type, and arch type. The tests of significance used were the chi-square test, Fisher's exact test, or Kruskal-Wallis test. Statistical significance was set at P < 0.05. RESULTS: A total of 183 teeth in 106 patients were included in the analysis. The follow-up period fell into a range of 1-3 years, with a mean of 1.6 years. The clinical and radiographic success rates were 96.7% and 92.9%, respectively. The earliest time to observe the radiographic failures was half a year after the treatment, and the latest time was two years after the treatment. Among all the teeth, 130 were recorded with hemostasis time before the application of iRoot BP Plus. Compared to teeth with a hemostasis time of 5 min or less, teeth with a hemostasis time exceeding 5 min showed no significant differences in clinical and radiographic success (P = 1.000 and 0.879). Additionally, neither arch nor teeth type showed a relationship with the pulpotomy success rate (P > 0.05). CONCLUSIONS: Pulpotomy using iRoot BP Plus in primary molars achieved favorable results. The hemostasis time may not significantly impact the outcomes of pulpotomy using iRoot BP Plus in primary molars.

Optimization of process parameters for Trifolium pratense L. seed granulation coating using GA-BP neural network.

Regarding the issue of low granulation qualification rates during the granulation coating of red clover seeds, this study theoretically analyzed the force conditions of seeds and powder particles under the action of liquid to obtain the main factors affecting seed coating quality. During the seed granulation coating process, an intermittent powder supply method combined with continuous liquid supply was utilized to control the ratio of powder to liquid. Using the granulation qualification rate as the evaluation index, single-factor experiments were conducted to investigate the effects of coating pan fill ratio, single powder supply amount, powder supply interval, and liquid supply amount on the quality of red clover seed granulation coating. Based on the results of the single-factor experiments, orthogonal experiments were conducted, revealing that the interaction of factors would influence the experimental results. To further optimize the quality of seed granulation coating, the mechanisms of powder and liquid in the adhesion process on granulation coating were explored. Orthogonal experiments were conducted on the process parameters of the granulation coating machine, and the GA-BP model was employed for optimization and solution. The optimal process parameter combination obtained was a coating pan fill ratio of 33.78 %, a single powder supply amount of 5.17 g, a powder supply interval of 7.7 s, and a liquid supply amount of 0.42 mL/s. Under this optimal parameter combination, granulation coating experiments with red clover seeds were performed, and the seed granulation coating quality was relatively high, with a granulation qualification rate of 97.7 %. The research results can provide a reference for optimization experiments on coating irregular seeds.

The pleiotropic spectrum of proximal 16p11.2 CNVs.

Recurrent genomic rearrangements at 16p11.2 BP4-5 represent one of the most common causes of genomic disorders. Originally associated with increased risk for autism spectrum disorder, schizophrenia, and intellectual disability, as well as adiposity and head circumference, these CNVs have since been associated with a plethora of phenotypic alterations, albeit with high variability in expressivity and incomplete penetrance. Here, we comprehensively review the pleiotropy associated with 16p11.2 BP4-5 rearrangements to shine light on its full phenotypic spectrum. Illustrating this phenotypic heterogeneity, we expose many parallels between findings gathered from clinical versus population-based cohorts, which often point to the same physiological systems, and emphasize the role of the CNV beyond neuropsychiatric and anthropometric traits. Revealing the complex and variable clinical manifestations of this CNV is crucial for accurate diagnosis and personalized treatment strategies for carrier individuals. Furthermore, we discuss areas of research that will be key to identifying factors contributing to phenotypic heterogeneity and gaining mechanistic insights into the molecular pathways underlying observed associations, while demonstrating how diversity in affected individuals, cohorts, experimental models, and analytical approaches can catalyze discoveries.

Role of the RNA binding protein IGF2BP1 in cancer multidrug resistance.

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), a member of a conserved family of single-stranded RNA-binding proteins (IGF2BP1-3), is expressed in a broad range of fetal tissues, placenta and more than sixteen cancer types but only in a limited number of normal adult tissues. IGF2BP1is required for the transport from nucleus to cytoplasm of certain mRNAs that play essential roles in embryogenesis, carcinogenesis, and multidrug resistance (MDR), by affecting their stability, translation, or localization. The purpose of this review is to gather and present information on MDR mechanisms in cancer and the significance of IGF2BP1 in this context. Within this review, we will provide an overview of IGF2BP1, including its tissue distribution, expression, molecular targets in the context of tumorigenesis and its inhibitors. Our main focus will be on elucidating the interplay between IGF2BP1 and MDR, particularly with regard to chemoresistance mediated by ABC transporters.

Prediction of high-risk prostate cancer based on the habitat features of biparametric magnetic resonance and the omics features of contrast-enhanced ultrasound.

Rationale and objectives: To predict high-risk prostate cancer (PCa) by combining the habitat features of biparametric magnetic resonance imaging (bp-MRI) with the omics features of contrast-enhanced ultrasound (CEUS). Materials and methods: This study retrospectively collected patients with PCa confirmed by histopathology from January 2020 to June 2023. All patients underwent bp-MRI and CEUS of the prostate, followed by a targeted and transrectal systematic prostate biopsy. The cases were divided into the intermediate-low-risk group (Gleason score ≤7, n = 59) and high-risk group (Gleason score ≥8, n = 33). Radiomics prediction models, namely, MRI_habitat, CEUS_intra, and MRI-CEUS models, were developed based on the habitat features of bp-MRI, the omics features of CEUS, and a merge of features of the two, respectively. Predicted probabilities, called radscores, were then obtained. Clinical-radiological indicators were screened to construct clinic models, which generated clinic scores. The omics-clinic model was constructed by combining the radscore of MRI-CEUS and the clinic score. The predictive performance of all the models was evaluated using the receiver operating characteristic curve. Results: The area under the curve (AUC) values of the MRI-CEUS model were 0.875 and 0.842 in the training set and test set, respectively, which were higher than those of the MR_habitat (training set: 0.846, test set: 0.813), CEUS_intra (training set: 0.801, test set: 0.743), and clinic models (training set: 0.722, test set: 0.611). The omics-clinic model achieved a higher AUC (train set: 0.986, test set: 0.898). Conclusions: The combination of the habitat features of bp-MRI and the omics features of CEUS can help predict high-risk PCa.

HSV-1-induced N6-methyladenosine reprogramming via ICP0-mediated suppression of METTL14 potentiates oncolytic activity in glioma.

Upon infection with herpes simplex virus 1 (HSV-1), the virus deploys multiple strategies to evade the host's innate immune response. However, the mechanisms governing this phenomenon remain elusive. Here, we find that HSV-1 leads to a decrease in overall m6A levels by selectively reducing METTL14 protein during early infection in glioma cells. Specifically, the HSV-1-encoded immediate-early protein ICP0 interacts with METTL14 within ND10 bodies and serves as an E3 ubiquitin protein ligase, targeting and ubiquitinating METTL14 at the lysine 156 and 162 sites. Subsequently, METTL14 undergoes proteasomal degradation. Furthermore, METTL14 stabilizes ISG15 mRNA mediated by IGF2BP3 to promote antiviral effects. Notably, METTL14 suppression significantly enhances the anti-tumor effect of oncolytic HSV-1 (oHSV-1) in mice bearing glioma xenografts. Collectively, these findings establish that ICP0-guided m6A modification controls the antiviral immune response and suggest that targeting METTL14/ISG15 represents a potential strategy to enhance the oncolytic activity of oHSV-1 in glioma treatment.

IGF2BP1-mediated the stability and protein translation of FGFR1 mRNA regulates myogenesis through the ERK signaling pathway.

N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of RNAs and plays a key regulatory role in various biological processes. As a member of the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) family, IGF2BP1 has recently demonstrated its ability to specifically bind m6A-modified sites within mRNAs and effectively regulate their mRNA stability. However, the precise roles of IGF2BP1 in mammalian skeletal muscle development, along with its downstream mRNA targets during myogenesis, have yet to be fully elucidated. Here, we observed that IGF2BP1 expression significantly decreased during myogenic differentiation. Knockdown of IGF2BP1 significantly inhibited myoblast proliferation while promoted myogenic differentiation. In contrast, IGF2BP1 overexpression robustly stimulated myoblast proliferation but suppressed their differentiation. Combined analysis of high-throughput sequencing and RNA stability assays revealed that IGF2BP1 can enhance fibroblast growth factor receptor 1 (FGFR1) mRNA stability and promote its translation in an m6A-dependent manner, thereby regulating its expression level and the Extracellular Signal-Regulated Kinase (ERK) pathway. Additionally, knockdown of FGFR1 rescued the phenotypic changes (namely increased cell proliferation and suppressed differentiation) induced by IGF2BP1 overexpression via attenuating ERK signaling. Taken together, our findings suggest that IGF2BP1 maintains the stability and translation of FGFR1 mRNA in an m6A-dependent manner, thereby inhibiting skeletal myogenesis through activation of the ERK signaling pathway. This study further enriches the understanding of the molecular mechanisms by which RNA methylation regulates myogenesis, providing valuable insights into the role of IGF2BP1-mediated post-transcriptional regulation in muscle development.

The Role of Serology in the Diagnosis of Ocular Predominant Mucous Membrane Pemphigoid and the Search for an Ocular-Specific Autoantigen.

Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of MMP that can lead to scarring and blindness. While conjunctival biopsy for direct immunofluorescence (DIF) is considered the gold standard for diagnosis, limited sensitivity results in a false-negative rate upwards of 40%. Likewise, it remains unclear to what extent a negative biopsy, whether false-negative or true-negative, results in a different prognosis, with patients previously termed "pseudopemphigoid" demonstrating comparable disease progression. Serologic testing allows for a less invasive means to demonstrate circulating autoantibodies against known autoantigens in pemphigoid diseases. Patients with MMP, particularly oMMP, however, typically demonstrate low titers of circulating autoantibodies, limiting the diagnostic utility of these tests. The autoantigen integrin ß4 has been previously reported to be a specific marker of pure ocular MMP, while in the majority of patients with oMMP, the identified target antigens are BP180 (type XVII collagen) and laminin 332. Recent studies have, however, demonstrated inconsistent reactivity and specificity for integrin ß4 as an ocular-specific marker in MMP. Herein, we review the role of serologic testing in the diagnosis and prognosis of oMMP, as well as the current understanding of autoantigens in oMMP.Abbreviations: BMZ - basement membrane zone, DIF - direct immunofluorescence, IIF - indirect immunofluorescence, MMP - mucous membrane pemphigoid, oMMP - ocular predominant mucous membrane pemphigoid.

m6A modification enhances the stability of CDC25A promotes tumorigenicity of esophagogastric junction adenocarcinoma via cell cycle.

N6-Methyladenosine (m6A) modification and its regulators play critical roles in human cancers, but their functions and regulatory mechanisms in adenocarcinoma of the esophagogastric junction (AEG) remain unclear. Here, we identified that IGF2BP3 is the most significantly up-regulated m6A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m6A regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression in vitro and in vivo. By profiling transcriptome-wide targets of IGF2BP3 and the m6A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m6A-modified targets, including targets of the cell cycle pathway, such as CDC25A, CDK4, and E2F1, are critical for AEG progression. Mechanistically, the increased m6A modification of CDC25A accelerates the G1-S transition. Clinically, up-regulated IGF2BP3, METTL3, and CDC25A show a strong positive correlation in TCGA pan-cancer, including AEG. In conclusion, our study highlights the role of post-transcriptional regulation in modulating AEG tumor progression and elucidates the functional importance of the m6A/IGF2BP3/CDC25A axis in AEG cells.