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Esophageal squamous cell carcinoma (ESCC), a malignancy of the digestive system, is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective therapeutic targets. Dysregulated ribonucleotide reductase (RNR) expression has been confirmed to be causally linked to tumorigenesis. This study demonstrated that ribonucleotide reductase small subunit M2 (RRM2) is significantly upregulated in ESCC tissue and that its expression is negatively correlated with clinical outcomes. Mechanistically, HuR promotes RRM2 mRNA stabilization by binding to the adenine/uridine (AU)-rich elements (AREs) within the 3′UTR, resulting in persistent overexpression of RRM2. Furthermore, bifonazole is identified as an inhibitor of HuR via computational screening and molecular docking analysis. Bifonazole disrupts HuR-ARE interactions by competitively binding to HuR at F65, R97, I103, and R153 residues, resulting in reduced RRM2 expression. Furthermore, bifonazole exhibited antitumor effects on ESCC patient-derived xenograft (PDX) models by decreasing RRM2 expression and the dNTP pool. In summary, this study reveals the interaction network among HuR, RRM2, and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.

Abstract Precast Concrete Sandwich Panel (PCSP) is composed of concrete load-bearing panels, thermal insulation panels, and decorative panels, which are assembled through connectors, integrating load-bearing, thermal insulation, and decorative functions. The connector bears the main shear force between the wall panels, and the shear resistance and insulation performance of the connector largely determine the mechanical stability and insulation effect of the wall panels, which is a key component in PCSPs. The current common practice is to cross assemble stainless steel insulation (SSI) connectors and Glass-Fiber-Reinforced Plastic (GFRP) connectors into PCSPs, which can reduce building energy consumption and save resources while meeting strength and insulation requirements. A large-scale pull-out test on a PCSP with intersecting SSI-GFRP connectors was conducted in this paper. The damage process and damage pattern of PCSP were observed and the shear performance of SSI-GFRP connectors was analyzed. Secondly, a numerical analysis model of the test PCSP was built using ABAQUS finite element software and its validity was verified through the test data. In addition, parameters such as connector diameter, connector number ratio and concrete strength were analyzed for their effect on the shear performance of SSI-GFRP connectors and it was found that connector diameter and connector number ratio had a significant effect. Finally, it is found that there are some differences between the classical theory for calculating the shear performance of SSI-GFRP connectors and the actual results. A theoretical correction factor (ζ) is given to improve the accuracy of the calculation of the classical theory, and its influencing factors and changing rules are investigated.

BackgroundA definite diagnosis goes undiscovered for a percentage of children with undiagnosed disorders, with significant medical, psychological, and social effects. Other than specialized clinical centers, exceptional molecular studies, common procedures, and devoted activities at the national and international levels, children with complex undiagnosed disorders require innovative approaches.MethodsIn March 2016, Children’s hospital of Fudan university represented the Children’s Undiagnosed Diseases Program (UDP). The purpose of this study is to describe the project findings and underline the critical significance of multidisciplinary teamwork in China’s undiagnosed rare illnesses program. We investigated the 758 cases in our UDP system retrospectively. Demographic information, laboratory test results, and genetic information were gathered.ResultsBetween January 2017 and December 2021, 758 cases were examined. Males made up 436 (57.5%) of the total. Over half of the patients were children under the age of five. The average patient course time preceding admission to UDP was 6.0 months (95% CI 10.512.6). These patients visited an average of 1.8 clinics during their diagnostic journey. Except for 69 individuals (90.9%), all had more than one presenting symptom in various organs: 460 (60.7%) had neurology difficulties, 151 (19.9%) had endocrine problems, and 141 (18.6%) had immunology problems. UDP has a diagnosis rate of 61.3%. Genetic testing was performed on 469 of the 758 patients, for a genetic diagnosis rate of 15.8%. The UDP method has a sensitivity of 94.5%, a specificity of 86.4%, a positive predictive value of 92.8%, and an negative predictive value of 89.5%.ConclusionOur UDP targets an unmet need, namely the diagnosis of patients with complicated, multisystem illnesses. Using a multidisciplinary team model approach, this UDP pilot study achieved a reasonable diagnosis success rate, increasing the possibility of more diagnoses and new scientific discoveries of difficult and rare diseases.

This review aims to explore the current application of Cranial Ultrasound Screening (CUS) in the diagnosis and treatment of brain diseases in extremely preterm infants. It also discusses the potential role of emerging ultrasound-derived technologies such as Super Microvascular Structure Imaging (SMI), Shear Wave Elastography (SWE), Ultrafast Doppler Ultrasound (UfD), and 3D ventricular volume assessment and automated segmentation techniques in clinical practice. A systematic search of medical databases was conducted using the keywords ''(preterm OR extremely preterm OR extremely low birth weight) AND (ultrasound OR ultrasound imaging) AND (neurodevelopment OR brain development OR brain diseases OR brain injury OR neuro*)'' to identify relevant literature. The titles, abstracts, and full texts of the identified articles were carefully reviewed to determine their relevance to the research topic. CUS offers unique advantages in early screening and monitoring of brain diseases in extremely preterm infants, as it can be performed at the bedside without the need for anesthesia or special monitoring. This technique facilitates early detection and intervention of conditions such as intraventricular hemorrhage, white matter injury, hydrocephalus, and hypoxic-ischemic injury in critically ill preterm infants. Continuous refinement of the screening and follow-up processes provides reliable clinical decision-making support for healthcare professionals and parents. Emerging ultrasound technologies, such as SWE, SMI, and UfD, are being explored to provide more accurate and in-depth understanding of brain diseases in extremely preterm infants. SWE has demonstrated its effectiveness in assessing the elasticity of neonatal brain tissue, aiding in the localization and quantification of potential brain injuries. SMI can successfully identify microvascular structures in the brain, offering a new perspective on neurologic diseases. UfD provides a high-sensitivity and quantitative imaging method for the prevention and treatment of neonatal brain diseases by detecting subtle changes in red blood cell movement and accurately assessing the status and progression of brain diseases. CUS and its emerging technologies have significant applications in the diagnosis and treatment of brain diseases in extremely preterm infants. Future research aims to address current technical challenges, optimize and enhance the clinical decision-making capabilities related to brain development, and improve the prevention and treatment outcomes of brain diseases in extremely preterm infants.

As an emerging method in engineering construction, concrete 3D printing has experienced rapid development in recent years due to its advantages in terms of automation, digitization, and intelligence. In order to comprehensively understand the research progress of concrete 3D printing technology, the literature on concrete 3D printing technology published in the Web of Science core database from 2014 to 2023 is used as a data source, and the visualization tool CiteSpace is utilized to research and analyze these results from the following aspects: number of publications, collaboration networks, research hotspots, and evolutionary trends. The results show that the number of publications in the field of concrete 3D printing technology has been increasing from year to year, with a gradually accelerating growth rate. The top three journals in terms of publication volume are Construction and Building Materials, Cement and Concrete Composites, and Materials. Research in the field of concrete 3D printing technology is mainly conducted through collaborations among research groups or institutions, while there are relatively fewer interactions among researchers from different institutions, regions, and countries. The current research direction mainly focuses on 3D printing materials, process parameters, and technology. The research content has progressed from initial explorations of concrete 3D printing technology to detailed studies of 3D printing materials and their performance. Overall, the research in this field continues to add further details to our knowledge of concrete 3D printing technology, and its application in engineering is gradually increasing. The automated, digitized, and intelligent construction methods of concrete 3D printing technology serve as a powerful driving force for the transformation and upgrading of the field of architecture.