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Steel-concrete composite beam has been increasingly applied to large span cable-stayed bridges. It takes full advantage of the material properties of steel and concrete. However, the concrete deck bears tension in the negative moment zone, such as zero block, which is disadvantageous to structures. Aiming at this problem, a finite element model of the zero block in the negative moment zone of a semi-floating cable-stayed bridge is built, and the local mechanical performance of the bridge deck under completed status is studied. Based on the analysis results, three improvement measures have been proposed. The improvement effect of each method and composed of three methods has been studied. The numerical results show that the whole zero block zone is in the compressed state under the combined action of the bending moment and axial force of the stay cable. However, the local negative moment effect in the zero block zone is very prominent under the support of the diaphragm plate. Removing parts of the diaphragm plate at the bearing position can significantly improve local mechanical behavior in the concrete deck, which transfers the local support to the adjacent two diaphragm plates. The composed improvement effect is prominent when the three measures are adopted simultaneously.

Abstract Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions.

Abstract This study focuses on the application of deep learning for transforming semantic point clouds into semantic Building Information Models (BIM) to create a Heritage Digital Twin, centering on Taoping Village, a site of historical and cultural significance in Sichuan, China. Utilizing advanced technologies such as unmanned aerial vehicles and terrestrial laser scanning, we capture detailed point cloud data of the village. A pivotal element of our methodology is the KP-SG neural network, which exhibits outstanding overall performance, particularly excelling in accurately identifying 11 categories. Among those categories, buildings and vegetation, achieves recognition rates of 81% and 83% respectively, and a 2.53% improvement in mIoU compared to KP-FCNN. This accuracy is critical for constructing detailed and accurate semantic BIM models of Taoping Village, facilitating comprehensive architecture and landscape analysis. Additionally, the KP-SG’s superior segmentation capability contributes to the creation of high-fidelity 3D models, enriching virtual reality experiences. We also introduce a digital twin platform that integrates diverse datasets, their semantic information, and visualization tools. This platform is designed to support process automation and decision-making and provide immersive experiences for tourists. Our approach, integrating semantic BIM models and a digital twin platform, marks a significant advancement in preserving and understanding traditional villages like Taoping and demonstrates the transformative potential of deep learning in cultural heritage conservation.

Background: The eighth‐leading cause of cancer‐related mortality and the seventh‐most prevalent malignancy in women globally is ovarian cancer (OV). However, 5‐year survival expectancy after conventional treatment is not good. Therefore, there is an urgent need for novel signatures to guide the designation of therapeutic schemes for OV patients. Methods: We used univariate Cox analysis to screen hormone secretion regulation axis‐related microRNAs (miRNAs), least absolute shrinkage and selection operator analysis to select candidate miRNAs and multivariate Cox analysis to build the risk model. To evaluate possible route and functional differences, enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the differentially expressed genes (DEGs) across various risk groups. We compared Tumor Immune Dysfunction and Exclusion (TIDE) scores across risk categories by analyzing immune cell infiltration, immune checkpoint gene expression, immunological function and TIDE scores. In the end, we determined the half maximal inhibitory concentration (IC50) of chemotherapy and targeted medicines for individual patients. Cell assays were determined to test the migration of the miRNA‐target genes and western blotting was used to test the correlation of the miRNA‐target genes and the pathways. Results: We finally identified hormone secretion regulation axis‐related 13 microRNAs to build a risk model. The validation of observed and anticipated values revealed a fair level of agreement. To evaluate the molecular pathways between various groups in accordance with the GO and KEGG analyses, we then discovered 173 DEGs between distinct risk groups. The risk score was shown to be inversely related to the number of immune cells, including myeloid dendritic, granulocytes, M1 and M2 macrophages, B cells, t‐lymphocytes, and CD4+ and CD8+ cells, suggesting that immune cells are more frequent in the low‐risk group. Immune cell infiltration investigation yielded these results. Finally, we recognized 11 chemotherapeutic drugs and 30 novels targeted drugs on the basis of IC50 between the different risk groups. GJB5 was determined to be the mir‐219 target gene and was identified as promoting the cell cycle process. In addition, hormone secretion regulation axis related miRNAs were reported to affects the heterogeneity of endocrine microenvironment and anti‐tumor immune pattern. Conclusions: In conclusion, a 13‐miRNA prognostic model was constructed to know the immune status, prognosis, immunotherapeutic response and anti‐tumor drug sensitivity for OV, which provides theoretical guidance for the effective and individualized treatment of OV patients. [ABSTRACT FROM AUTHOR]

Uterine corpus endometrial carcinoma (UCEC) is a prevalent form of cancer in women, affecting the inner lining of the uterus. Inflammation plays a crucial role in the progression and prognosis of cancer, making it important to identify inflammatory response‐related subtypes in UCEC for targeted therapy and personalized medicine. This study discovered significant variation in immune response within UCEC tumors based on molecular subtypes of inflammatory response‐related genes. Subtype A showed a more favorable prognosis and better response to immunotherapies like anti‐CTLA4 and anti‐PDCD1 therapy. Functional analysis revealed subtype‐specific differences in immune response, with subtype A exhibiting higher expression of genes related to cytokine signaling pathways, NK cell‐mediated cytotoxicity pathways and inflammatory processes. Subtype A also showed increased sensitivity to three chemotherapeutic agents. A 12‐gene inflammatory response‐related signature was found to have prognostic value for 1, 2 and 3 year survival in UCEC patients. Additionally, a validated machine learning‐based signature demonstrated significant differences in clinical traits between low‐risk and high‐risk cohorts. Elevated risk scores were associated with higher pathological grading, older age, advanced stage and immune subtype C2. Low‐risk groups had higher infiltration of immune cell types such as CD8 + T cells and activated CD4 + cells. However, the abundance of cytotoxic immune cells decreased with increasing risk scores. Finally, PCR was applied to test the different expression in P2PX4. P2RX4 knockdown inhibited the proliferation and proliferation of the endometrial carcinoma Ishikawa cell line. In conclusion, this developed signature can serve as a clinical prediction index and reveal distinct immune expression patterns. Ultimately, this study has the potential to enhance targeted therapy and personalized medicine for UCEC patients. [ABSTRACT FROM AUTHOR]

The challenge of delivering therapeutics to the central nervous system due to the restrictive nature of the blood-brain barrier (BBB) is a substantial hurdle in neuropharmacology. Our research introduces a breakthrough approach using microtubule-dependent transcytosis facilitated by novel aqueous compounds. We synthesized a series of red-emitting pyran nitrile derivatives. The molecular structure of compounds, photophysical properties, and water solubility were characterized. BBB permeability of BN1 was assessed in an in vitro BBB model. The transmembrane transport mechanism was next analyzed. The derivative was injected in the wild-type mouse for evaluation of brain penetration and biodistribution in the brain. We further investigated the potential of BN1-functionalized BBB-nonpenetrated silica nanoparticles for brain targeting. This compound demonstrated an ability to form endosomes within the phospholipid layer, thus enabling efficient penetration of the BBB via microtubule-mediated transcytosis, as evidenced in vitro model. This was further confirmed by in vivo experiments that BN1 displays the excellent BBB penetration and retained in brain parenchyma. Furthermore, BBB-impermeable mesoporous silica nanoparticle codelivery system markedly enhanced the transport efficiency to the brain in vivo by BN1-functionalized. These findings indicate that our designed aqueous molecules not only are capable of traversing the BBB but also serve as a viable new strategy for central-nervous-system-targeted drug delivery., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Mingzhu Zhang et al.)

Objective: Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease, but cervical spine surgery may affect sagittal alignment parameters and induce adjacent segment degeneration (ASD). This study aimed to determine the risk factors for developing ASD following anterior cervical plate and cage (ACPC) compared with the use of zero-profile anchored spacer (ROI-C)., Methods: A retrospective contrastive study included 105 patients who underwent ACPC or ROI-C between January 2014 and October 2019 at our treatment centre. There were 50 cases in the ROI-C group and 55 patients in the ACPC group. Clinical and radiological results and the incidence of ASD were assessed after surgery. All patients were further divided into the ASD and non-ASD groups for subgroup analysis., Results: At each follow-up time, there was no statistically significant in radiographic parameters between the two groups. The overall ASD rate was higher in the ACPC group than in the ROI-C group (65.5% vs. 44.0%, p = 0.027). The low preoperative Cobb angle, low preoperative segment angle (SA), and loss of Cobb (ΔCobb) were significantly correlated with ASD. However, clinical outcomes were not associated with ASD at any postoperative follow-up visit., Conclusion: Equally good therapeutic effects were achieved with both the ROI-C and ACPC. The occurrence of ASD was considerably higher in the ACPC group than in the ROI-C group. The preoperative Cobb angle, preoperative SA, and ΔCobb were the most associated with an increase in the risk of ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Wang, Zhou, Xiang, Li, Yang and Chu.)