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5-formylcytidine (f5C) is a unique post-transcriptional RNA modification found in mRNA and tRNA at the wobble site, playing a crucial role in mitochondrial protein synthesis and potentially contributing to the regulation of translation. Recent studies have unveiled that the f5C modifications may drive mitochondrial mRNA translation to power cancer metastasis. Accurate identification of f5C sites is essential for further unraveling their molecular functions and regulatory mechanisms, but there are currently no computational methods available for predicting their locations. In this study, we introduce an innovative ensemble approach, successfully enabling the computational recognition of Saccharomyces cerevisiae f5C. We conducted a comprehensive model selection process that involved multiple basic machine learning and deep learning algorithms such as recurrent neural networks, convolutional neural networks and Transformer-based models. Initially trained only on sequence information, these individual models achieved an AUROC ranging from 0.7104 to 0.7492. Through the integration of 32 novel domain-derived genomic features, the performance of individual models has significantly improved to an AUROC between 0.7309 and 0.8076. To further enhance accuracy and robustness, we then constructed the ensembles of these individual models with different combinations. The best performance attained by our ensemble models reached an AUROC of 0.8391. Shapley additive explanations were conducted to explain the significant contributions of genomic features, providing insights into the putative distribution of f5C across various topological regions and potentially paving the way for revealing their functional relevance within distinct genomic contexts. A freely accessible web server that allows real-time analysis of user-uploaded sites can be accessed at: www.rnamd.org/Resf5C-Pred.

Abstract Some cases of chronic rhinosinusitis (CRS) require surgical treatment and postoperative nasal packing, but bleeding and adhesion are common complications after nasal surgery. Biodegradable drug-loaded implants hold great therapeutic options for the treatment of CRS, but little data are available regarding the safety and efficacy of a novel drug-loaded haemostatic sponge (DLHS) in the sinus. The aim of this study was to investigate the safety and efficacy of DLHS in the sinus. We conducted a prospective, randomized, controlled, double-blind clinical trial. In this clinical trial, 49 patients were enrolled and randomly divided into 2 groups: group A (n = 25) had the DLHS containing 1 mg budesonide and 0.67 mg sodium hyaluronate placed into the sinus, and group B (n = 24) had the Nasopore placed after ESS. Endoscopic follow-up was performed for 12 weeks, and the findings were classified using the discharge, inflammation, polyps/oedema (DIP) endoscopic appearance scores. All patients completed questionnaires to evaluate their sinonasal symptoms by using the sinonasal outcome test-22 (SNOT-22) Chinese version and visual analogue scale (VAS). Serum cortisol concentration in group A was measured prior to surgery and at days 1, 3, 7, and 14 after nasal surgery. Comparing group A and group B, at 2 weeks, no significant differences were observed in either objective or subjective parameters. The mean value of VAS for rhinorrhoea and DIP for oedema and the mean value of nasal adhesion were significantly lower in Group A than in Group B at 6 and 12 weeks, but a significant difference did not occur in SNOT-22 and VAS for dysosmia between the two groups at 6 and 12 weeks. The mean serum cortisol concentrations in group A at the follow-up were within normal limits without remarkable fluctuations. This study demonstrates the safety and efficacy of a novel biodegradable DLHS with the possibility of being used in CRS patients, and this sponge may reduce inflammation and minimize adhesions via controlled local drug delivery without measurable systemic exposure.

For the development of new energy automobile industry and the trend of automobile lightweight have put forward a huge demand for high-strength lightweight materials, so developing high strength aluminum alloys is particularly momentous. As the most widely used aluminum alloy, 6000 series aluminum alloys (Al–Mg–Si alloys) have the advantages such as better mechanical properties, outstanding welding properties, excellent formability and fine processing capability, and therefore have obtained great attention as the structural materials. In addition, the Al–Mg–Si alloys with low density and corrosion resistance not only reduce the total weight of the car, but also extend the service life when subjected to chemical corrosion, which effectively achieve energy saving and emission reduction. This paper summarizes the research progress of 6000 series aluminum alloys, in particular, and reviews the methods of microalloying and particle strengthening, and their effects on the microstructure and properties of the alloy, thus providing a reference for the subsequent development of high-performance aluminum alloys in automobile and aerospace industries.

Rapid growth in industrial sectors such as automotive and shipbuilding has highlighted the significance of strip casting technology to produce lightweight alloys, particularly aluminum alloys widely used in both industrial production and daily life. Twin-roll casting (TRC), as an economically and environmentally friendly method for slab/strip production and processing, has attracted significant interest from researchers. However, the development of TRC aluminum alloys faces many challenges due to limited understanding of microstructural characteristics and control mechanisms. To further enhance comprehension of TRC aluminum alloys, this article reviews the influencing parameters, control methods, and existing issues related to TRC sub-rapid solidification (SRS) microstructure. It firstly summarizes TRC equipment types and their solidification characteristics, followed by a detailed analysis on key parameters affecting the evolution of TRC microstructure including rolling speed, roll separation force (RSF), and heat transfer coefficient (HTC). Finally, solutions to TRC defects are summarized and evaluated alongside their underlying mechanisms. This article provides a comprehensive review of the characteristics and control mechanisms of TRC microstructure while offering valuable insights for the future production of high-quality TRC aluminum strips.

Abstract Background Idiopathic ventricular arrhythmias (IVAs) arising from different portions of the communicating vein of the left ventricular summit (summit-CV) are not a rare phenomenon. Whereas its electrocardiographic (ECG) and electrophysiological characteristics are not fully investigated. Objective This study aimed to identify distinct ECG and electrophysiological features of IVAs originating from different portions of summit-CV. Methods Nineteen patients confirmed arising from summit-CV were included in this study. Results The 19 patients were divided into proximal and distal portion groups based on their target sites in summit-CV. In the proximal portion group, 100% (11/11) VAs showed dominant negative (rs or QS) waves in lead I, while in the distal portion group, 87.5% (7/8) showed dominant positive waves (R, Rs or r) (p 4mV, SI3.5mV, RI/SI>0.83, and RV1/SV1< 2.6 indicated a distal portion of summit-CV with the predictive value of 0.909, 1.000, 0.653, 0.972, 0.903, 0.966, respectively. A more positive wave in lead I and a more negative wave in lead V1 indicated more distal origin in summit-CV. Target sites in proximal and distal summit-CV groups showed similar electrophysiological characteristics during mapping. Conclusions There were significant differences in ECG characteristics of VAs at different portions of summit-CV, which could aid pre-procedure planning and facilitate radiofrequency catheter ablation (RFCA) procedures.

In the global pursuit of energy conservation, reduction in consumption and emissions, as well as lightweighting, 5xxx-series aluminum alloys have emerged as a promising lightweight and high-strength material with a wide range of applications in aerospace, transportation, building structures, medical devices, and more. However, it is worth noting that 5XXX-series aluminum alloys belong to a category of non-heat-treatable reinforced aluminum alloys with limited means of enhancing their properties through heat treatment. Consequently, the development of high-performance 5XXX-series aluminum alloys poses a significant challenge. This paper provides an overview of the research progress on 5xxx-series aluminum alloys while discussing the current state of research regarding the influence of microalloying elements on their microstructure and properties. Furthermore, it elucidates the emerging trends in synergistic regulation between deformation processes and heat treatment processes for enhancing organizational refinement and improving alloy properties. Additionally, this study analyzes the reinforcement mechanism responsible for the exceptional properties exhibited by 5xxx-series aluminum alloys. Lastly, it discusses the exceptional properties exhibited by 5xxx-series alloys along with their primary areas of application. The findings presented herein can serve as a valuable reference for future advancements in advanced high-performance 5xxx-series aluminum alloys.

Cancer is a complex and multifaceted group of diseases characterized by uncontrolled cell growth that leads to the formation of malignant tumors. Recent studies suggest that N6-methyladenosine (m6A) RNA methylation plays pivotal roles in cancer pathology by influencing various cellular processes. However, the degree to which these mechanisms are shared across different cancer types remains unclear. In this study, we analyze an expansive array of 167 m6A epitranscriptome profiles covering 12 distinct cancer types and their originating normal tissues. We trained 12 distinct, cancer type-specific interpretable deep cross network models, which successfully distinguish between specific pairs of normal and cancer m6A contexts using integrated information from both the sequences and curated genomic knowledge. Interestingly, cross-cancer type testing indicated the existence of shared genomic patterns across various cancers at the epitranscriptome level. A pan-cancer model was subsequently developed to identify these shared patterns that could not be observed in a single cancer type. Our analysis uncovered, for the first time, a common epitranscriptome signature shared across multiple cancer types, particularly associated with RNA hybridization process and aberrant splicing. This highlights the importance of a comprehensive understanding of the pan-cancer epitranscriptome and holding potential implications in the development of RNA methylation-based therapeutics for various cancers.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment modality, offering promising outcomes for various malignancies. However, the efficacy of ICIs varies among patients, highlighting the essential need of accurate predictive biomarkers. This review synthesizes the current understanding of biomarkers for ICI therapy, and discusses the clinical utility and limitations of these biomarkers in predicting treatment outcomes. It discusses three US Food and Drug Administration (FDA)-approved biomarkers, programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and microsatellite instability (MSI), and explores other potential biomarkers, including tumor immune microenvironment (TIME)-related signatures, human leukocyte antigen (HLA) diversity, non-invasive biomarkers such as circulating tumor DNA (ctDNA), and combination biomarker strategies. The review also addresses multivariable predictive models integrating multiple features of patients, tumors, and TIME, which could be a promising approach to enhance predictive accuracy. The existing challenges are also pointed out, such as the tumor heterogeneity, the inconstant nature of TIME, nonuniformed thresholds and standardization approaches. The review concludes by emphasizing the importance of biomarker research in realizing the potential of personalized immunotherapy, with the goal of improving patient selection, treatment strategies, and overall outcomes in cancer treatment.

Abstract BackgroundChildren’s lives are increasingly mediated by digital technologies, yet evidence regarding the associations between internet use and depression is far from comprehensive and remains unclear. ObjectiveThis study aimed to investigate the dose-response association between internet use, including use time and addiction behaviors, and depressive symptoms among children and adolescents in Zhejiang Province. MethodsData were collected from a school-based health survey China Common Disease and Risk Factor Surveillance Among Students, encompassing 21,336 students in Zhejiang Province. The daily internet use time, internet addiction (IA) behaviors, and depressive symptoms were assessed with questionnaires. Logistic regression models were used to explore the associations of internet use time and IA behaviors with depressive symptoms among children and adolescents. Restricted cubic spline curves were used to determine the dose-response associations. ResultsA total of 6225 (29.2%) students had depressive symptoms. Compared to those reporting no internet use, boys using the internet for >2 hours/day (odds ratio [OR] 1.53, 95% CI 1.34‐1.74) and girls using internet for 1.1‐2 hours/day (OR 1.22, 95% CI 1.06‐1.39) and >2 hours/day (OR 1.70, 95% CI 1.50‐1.93) were at higher risks of depressive symptoms. A significant J-shaped association was identified between internet use time and depressive symptoms among children and adolescents, especially in boys and primary school students (nonlinear PP ConclusionsFindings suggested that excessive internet use time and IA behaviors were significantly associated with an increased risk of depressive symptoms, highlighting the importance of interventions to regulate and educate about adequate internet use during childhood and adolescence.

ABSTRACT: Silymarin, a botanical medicine derived from milk thistle seeds and is known to improve chicken growth and gut health when added to the feed. However, its role in the prevention and treatment of chicken coccidiosis remains unclear. This study investigated the efficacy of various doses of silymarin in preventing and treating Eimeria tenella infection in chicks. A total of 180 one-day-old specific pathogen-free chicks were randomized into six groups of 30 chicks each, no treatment (NC group); E. tenella infection (CC group); diclazuril medication during d 14 to 21 and E. tenella infection (DC group); and three groups infected with E. tenella and administered low, medium, or high doses of silymarin during d 12 to 21. All groups except NC were infected with E. tenella on d 14, with indicators observed on d 21. The growth performance was higher in the silymarin treated groups than that in the CC group, and the oocyst count per gram of manure, blood stool, and cecal lesion scores decreased. The medium-dose silymarin group exhibited the best treatment effect. Additionally, the silymarin groups displayed improved histological, morphology, and intestinal barrier integrity. The amounts of proinflammatory factors and harmful bacteria in the cecum were also reduced. Additionally, the activity of serum and cecal antioxidant enzymes, as well as the abundance of beneficial gut microbiota, increased in the cecum. In conclusion, this study demonstrated that silymarin can prevent and treat E. tenella infections. These data provide a scientific and conceptual basis for the development of a botanical dietary supplement from silymarin for the treatment and control of coccidiosis in chicks.

Organophosphorus flame retardants, such as triphenyl phosphate (TPhP), exist ubiquitously in various environments owing to their widespread usage. Potential toxic effects of residual flame retardants on cultured non-fish species are not concerned commonly. TPhP-induced physiological and biochemical effects in an aquatic turtle were evaluated here by systematically investigating the changes in growth and locomotor performance, hepatic antioxidant ability and metabolite, and intestinal microbiota composition of turtle hatchlings after exposure to different TPhP concentrations. Reduced locomotor ability and antioxidant activity were only observed in the highest concentration group. Several metabolic perturbations that involved in amino acid, energy and nucleotide metabolism, in exposed turtles were revealed by metabolite profiles. No significant among-group difference in intestinal bacterial diversity was observed, but the composition was changed markedly in exposed turtles. Increased relative abundances of some bacterial genera (e.g., Staphylococcus, Vogesella and Lawsonella) probably indicated adverse outcomes of TPhP exposure. Despite having only limited impacts of exposure at environmentally relevant levels, our results revealed potential ecotoxicological risks of residual TPhP for aquatic turtles considering TPhP-induced metabolic perturbations and intestinal bacterial changes.

Abstract Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1β and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1β, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies.