Clinical Value of CD24 Expression in Retinoblastoma

Background. The expression of CD24 has been detected in a wide variety of human malignancies. Downregulation of CD24 inhibits proliferation and induces apoptosis in tumor cells, whereas its upregulation increases tumor growth and metastasis. However, no data on CD24 protein levels in retinoblastoma are available, and the mechanism of CD24 involvement in retinoblastoma progress has not been elucidated. The aim of this study was to explore the expression profile of CD24 in the retinoblastoma tumor samples and to correlate with clinicopathological parameters. Methods. Immunohistochemistry was performed for CD24 on the archival paraffin sections of retinoblastoma and correlated with clinicopathological features. Western blotting was performed to confirm immunoreactivity results. Results. CD24 immunoreactivity was observed in 72.0% (36/50) of the retinoblastoma specimens. Among the 35 low-risk tumors, CD24 was expressed in 62.9% (22/35) tumors and among the 15 high-risk tumors, CD24 was expressed in 93.3% (14/15) tumors. High-risk tumors showed significantly increased expression of CD24 compared to tumors with low-risk (P < 0.05). Conclusions. This is the first correlation between CD24 expression and histopathology in human retinoblastoma. Our study showed increased expression of CD24 in high risk tumors compared to low risk tumors. Further functional studies are required to explore the role of CD24 in retinoblastoma

TIDE: Test Time Few Shot Object Detection

Few-shot object detection (FSOD) aims to extract semantic knowledge from limited object instances of novel categories within a target domain. Recent advances in FSOD focus on fine-tuning the base model based on a few objects via meta-learning or data augmentation. Despite their success, the majority of them are grounded with parametric readjustment to generalize on novel objects, which face considerable challenges in Industry 5.0, such as (i) a certain amount of fine-tuning time is required, and (ii) the parameters of the constructed model being unavailable due to the privilege protection, making the fine-tuning fail. Such constraints naturally limit its application in scenarios with real-time configuration requirements or within black-box settings. To tackle the challenges mentioned above, we formalize a novel FSOD task, referred to as Test TIme Few Shot DEtection (TIDE), where the model is un-tuned in the configuration procedure. To that end, we introduce an asymmetric architecture for learning a support-instance-guided dynamic category classifier. Further, a cross-attention module and a multi-scale resizer are provided to enhance the model performance. Experimental results on multiple few-shot object detection platforms reveal that the proposed TIDE significantly outperforms existing contemporary methods. The implementation codes are available at https://github.com/deku-0621/TID

Influence of the Process Parameters on the Microhardness and the Wear Resistance of Friction Stir Processed H65 Copper Alloy

Friction stir processing (FSP) was used to modify a larger-size surface of H65 copper alloy. The influence of the traverse speed and the rotation speed on the microstructure, the microhardness and the wear resistance of the modified surface were analyzed. The wear mechanism of the modified H65 copper alloy was revealed. The results indicate that the grain size was greatly refined after FSP compared with the parent metal and that the grain size increased with the increment of the rotation speed. The average microhardness of the modified surface was higher than that of the parent metal. The average microhardness had a highest value of 174.13 HV when the traverse speed was 200 mm/min and the rotation speed was 200 rpm, i.e., 21% higher than that of the parent metal. The average microhardness decreased with the increase of the rotation speed. When the traverse speed was 200 mm/min and the rotation speed was 600 rpm, the average friction coefficient of the modified surface was the smallest (0.3213), which was lower than that of the parent metal (0.3810). The wear mechanism of the H65 copper alloy modified by FSP was mainly adhesive wear accompanied by local abrasive wear

Influence of the Process Parameters on the Microhardness and the Wear Resistance of Friction Stir Processed H65 Copper Alloy

Friction stir processing (FSP) was used to modify a larger-size surface of H65 copper alloy. The influence of the traverse speed and the rotation speed on the microstructure, the microhardness and the wear resistance of the modified surface were analyzed. The wear mechanism of the modified H65 copper alloy was revealed. The results indicate that the grain size was greatly refined after FSP compared with the parent metal and that the grain size increased with the increment of the rotation speed. The average microhardness of the modified surface was higher than that of the parent metal. The average microhardness had a highest value of 174.13 HV when the traverse speed was 200 mm/min and the rotation speed was 200 rpm, i.e., 21% higher than that of the parent metal. The average microhardness decreased with the increase of the rotation speed. When the traverse speed was 200 mm/min and the rotation speed was 600 rpm, the average friction coefficient of the modified surface was the smallest (0.3213), which was lower than that of the parent metal (0.3810). The wear mechanism of the H65 copper alloy modified by FSP was mainly adhesive wear accompanied by local abrasive wear

SIRT1-mediated downregulation of p27(Kip1) is essential for overcoming contact inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Despite intensive studies in the last two decades, the mechanism of KSHV-induced cellular transformation and tumorigenesis remains unclear. In this study, we found that the expression of SIRT1, a metabolic sensor, was upregulated in a variety of KSHV-infected cells. In a model of KSHV-induced cellular transformation, SIRT1 knockdown with shRNAs or knockout by CRISPR/Cas9 gene editing dramatically suppressed cell proliferation and colony formation in soft agar of KSHV-transformed cells by inducing cell cycle arrest and contact inhibition. SIRT1 knockdown or knockout induced the expression of cyclin-dependent kinase inhibitor 1B (p27(Kip1)). Consequently, p27 knockdown rescued the inhibitory effect of SIRT1 knockdown or knockout on cell proliferation and colony formation. Furthermore, treatment of KSHV-transformed cells with a SIRT1 inhibitor, nicotinamide (NAM), had the same effect as SIRT1 knockdown and knockout. NAM significantly inhibited cell proliferation in culture and colony formation in soft agar, and induced cell cycle arrest. Significantly, NAM inhibited the progression of tumors and extended the survival of mice in a KSHV-induced tumor model. Collectively, these results demonstrate that SIRT1 suppression of p27 is required for KSHV-induced tumorigenesis and identify a potential therapeutic target for KS.

Fc fragment of IgG binding protein is correlated with immune infiltration levels in hepatocellular carcinoma

The Fc fragment of IgG binding protein (FCGBP) has been confirmed to play an important role in various cancers. However, the specific role of FCGBP in hepatocellular carcinoma (HCC) remains undefined. Thus, in this study, the enrichment analyses (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis) of FCGBP in HCC and extensive bioinformatic analyses using data of clinicopathologic characteristics, genetic expression and alterations, and immune cell infiltration were perfomed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of FCGBP in both HCC tissues and cell lines. The subsequent results confirmed thatFCGBP overexpression positively correlated with poor prognosis in patients with HCC. Additionally, FCGBP expression could effectively distinguish tumor tissues from normal tissues, which was verified by qRT-PCR. The result was further confirmed by using HCC cell lines. The time-dependent survival receiver operator characteristic curve exhibited the strong ability of FCGBP to predict survival in patients with HCC. Additionally, we revealed the strong relationship between FCGBP expression and a number of classic regulatory targets and classical oncogenic signaling pathways of tumors. Finally, FCGBP was involved in the regulation of immune infiltration in HCC. Therefore, FCGBP has potential value in the diagnosis, treatment, and prognosis of HCC and may be a potential biomarker or therapeutic target

SIRT1 Activation by a c-MYC Oncogenic Network Promotes the Maintenance and Drug Resistance of Human FLT3-ITD Acute Myeloid Leukemia Stem Cells

SummaryThe FLT3-ITD mutation is frequently observed in acute myeloid leukemia (AML) and is associated with poor prognosis. In such patients, FLT3 tyrosine kinase inhibitors (TKIs) are only partially effective and do not eliminate the leukemia stem cells (LSCs) that are assumed to be the source of treatment failure. Here, we show that the NAD-dependent SIRT1 deacetylase is selectively overexpressed in primary human FLT3-ITD AML LSCs. This SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability. Inhibition of SIRT1 expression or activity reduced the growth of FLT3-ITD AML LSCs and significantly enhanced TKI-mediated killing of the cells. Therefore, these results identify a c-MYC-related network that enhances SIRT1 protein expression in human FLT3-ITD AML LSCs and contributes to their maintenance. Inhibition of this oncogenic network could be an attractive approach for targeting FLT3-ITD AML LSCs to improve treatment outcomes

A Fast Radio Burst Discovered in FAST Drift Scan Survey

We report the discovery of a highly dispersed fast radio burst (FRB), FRB 181123, from an analysis of ~1500 hr of drift scan survey data taken using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). The pulse has three distinct emission components, which vary with frequency across our 1.0–1.5 GHz observing band. We measure the peak flux density to be... (See full abstract in article)

SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate

共济失调是一类以运动协调性紊乱为主要特征的神经系统症状，临床表现包括步态不稳、丧失平衡、吞咽困难、眼球运动异常、肌张力受损等。厦门大学医学院神经科学研究所王鑫教授团队首次从轴突线粒体运输这一全新视角揭示了一类遗传性共济失调的发病机制，并发现抗癫痫药--丙戊酸大幅度减缓模型小鼠的疾病进程，具有较强的转化应用价值，有望为共济失调提供新的治疗手段。 该研究工作由王鑫教授指导完成，厦门大学医学院助理教授张洪峰和博士生洪育娟共同完成主要实验工作。Loss-of-function mutations in SNX14 cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggests valproate as a potential therapeutic agent.We thank Tim Huang for helpful discussion, Wei Mo for sharing mouse lines, Li Zhong for sharing reagents, Aidong Han, Luming Yao, Caiming Wu, Mingxia Zhu, Qingfeng Liu, Lin Zhu, Shuo Zhang, Haiping Zheng, and Changchuan Xie for technical assistance, and Cui Li for providing bioinformatics software. We also thank Novogene Co., Ltd. and PTM Biolab Co., Ltd. for technical assistance in the transcriptomic and proteomic analyses, respectively. 厦门大学医学院许华曦、赵颖俊、张云武、杜丹教授在研究过程中给予大力帮助和支持。本研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持