High serum mannose in colorectal cancer: a novel biomarker of lymph node metastasis and poor prognosis

BackgroundLymph node status is an important prognostic indicator and it significantly influences treatment decisions for colorectal cancer (CRC). The objective of this study was to evaluate the ability of serum monosaccharides in predicting lymph node metastasis (LNM) and prognosis.MethodsHigh performance anion exchange chromatography coupled with pulsed amperometric detector (HPAEC-PAD) was used to quantify serum monosaccharides from 252 CRC patients. Receiver operating characteristic (ROC) curves were used to evaluate predictive performance of parameters. Predictors of LNM were evaluated by univariate and multivariate analyses. The prognostic role of the factors was evaluated by survival analysis.ResultsThe levels of serum mannose (Man) and galactose (Gal) were significantly increased in patients with LNM (p <0.0001, p =0.0017, respectively). The area under the curves (AUCs) of Man was 0.8140, which was higher than carcinoembryonic antigen (CEA) (AUC =0.6523). Univariate and multivariate analyses demonstrated histologic grade (G3) (odds ratio [OR] =2.60, p =0.043), histologic grade (mucin-producing subtype) (odds ratio [OR] =3.38, p =0.032), lymphovascular invasion (LVI) (OR =2.42, p <0.01), CEA (>5ng/ml) (OR =1.85, p =0.042) and high Man (OR =2.65, p =0.006) to be independent risk factors of LNM. The survival analysis showed that the high serum Man was independent risk factor for poor prognosis in CRC patients (HR=1.75, p =0.004).ConclusionsThe Man is superior to CEA in prediction of LNM for CRC patients. Man is expected to be a predictor for LNM in CRC. High serum Man is associated with poor prognosis of CRC patients

What's Behind the Mask: Understanding Masked Graph Modeling for Graph Autoencoders

The last years have witnessed the emergence of a promising self-supervised learning strategy, referred to as masked autoencoding. However, there is a lack of theoretical understanding of how masking matters on graph autoencoders (GAEs). In this work, we present masked graph autoencoder (MaskGAE), a self-supervised learning framework for graph-structured data. Different from standard GAEs, MaskGAE adopts masked graph modeling (MGM) as a principled pretext task - masking a portion of edges and attempting to reconstruct the missing part with partially visible, unmasked graph structure. To understand whether MGM can help GAEs learn better representations, we provide both theoretical and empirical evidence to comprehensively justify the benefits of this pretext task. Theoretically, we establish close connections between GAEs and contrastive learning, showing that MGM significantly improves the self-supervised learning scheme of GAEs. Empirically, we conduct extensive experiments on a variety of graph benchmarks, demonstrating the superiority of MaskGAE over several state-of-the-arts on both link prediction and node classification tasks.Comment: KDD 2023 research track. Code available at https://github.com/EdisonLeeeee/MaskGA

Language Agents for Detecting Implicit Stereotypes in Text-to-image Models at Scale

The recent surge in the research of diffusion models has accelerated the adoption of text-to-image models in various Artificial Intelligence Generated Content (AIGC) commercial products. While these exceptional AIGC products are gaining increasing recognition and sparking enthusiasm among consumers, the questions regarding whether, when, and how these models might unintentionally reinforce existing societal stereotypes remain largely unaddressed. Motivated by recent advancements in language agents, here we introduce a novel agent architecture tailored for stereotype detection in text-to-image models. This versatile agent architecture is capable of accommodating free-form detection tasks and can autonomously invoke various tools to facilitate the entire process, from generating corresponding instructions and images, to detecting stereotypes. We build the stereotype-relevant benchmark based on multiple open-text datasets, and apply this architecture to commercial products and popular open source text-to-image models. We find that these models often display serious stereotypes when it comes to certain prompts about personal characteristics, social cultural context and crime-related aspects. In summary, these empirical findings underscore the pervasive existence of stereotypes across social dimensions, including gender, race, and religion, which not only validate the effectiveness of our proposed approach, but also emphasize the critical necessity of addressing potential ethical risks in the burgeoning realm of AIGC. As AIGC continues its rapid expansion trajectory, with new models and plugins emerging daily in staggering numbers, the challenge lies in the timely detection and mitigation of potential biases within these models

LasTGL: An Industrial Framework for Large-Scale Temporal Graph Learning

Over the past few years, graph neural networks (GNNs) have become powerful and practical tools for learning on (static) graph-structure data. However, many real-world applications, such as social networks and e-commerce, involve temporal graphs where nodes and edges are dynamically evolving. Temporal graph neural networks (TGNNs) have progressively emerged as an extension of GNNs to address time-evolving graphs and have gradually become a trending research topic in both academics and industry. Advancing research and application in such an emerging field necessitates the development of new tools to compose TGNN models and unify their different schemes for dealing with temporal graphs. In this work, we introduce LasTGL, an industrial framework that integrates unified and extensible implementations of common temporal graph learning algorithms for various advanced tasks. The purpose of LasTGL is to provide the essential building blocks for solving temporal graph learning tasks, focusing on the guiding principles of user-friendliness and quick prototyping on which PyTorch is based. In particular, LasTGL provides comprehensive temporal graph datasets, TGNN models and utilities along with well-documented tutorials, making it suitable for both absolute beginners and expert deep learning practitioners alike.Comment: Preprint; Work in progres

Isolation and Characterization of a Chinese Hamster Ovary Heparan Sulfate Cell Mutant Defective in Both Met Receptor Binding and Hepatocyte Growth Factor NK1/Met Signaling

Background/Aims: The up-regulation of hepatocyte growth factor/receptor, HGF/Met, signal transduction is observed in most of human cancers. Specific heparan sulfate structures enhance the HGF/Met signaling at both cell and animal-based model systems. Biochemical studies indicate that heparan sulfate interacts with HGF and a natural occurring splicing variant NK1 of HGF with similar affinity. However, it is currently unknown if cell surface heparan sulfate binds to Met at physiological conditions and if specific cell surface heparan sulfate structures are required for effective HGF/Met or NK1/Met signaling. Methods: An established flow sorting strategy was used to isolate a soluble Met recombinant protein-binding positive or negative CHO cell clones different only in specific heparan sulfate structures. The cell surface bindings were imaged by confocal microscopy and flow cytometry analysis. Glucosamine vs. galactosamine contents from media-, cell surface-, and cell association glycosaminoglycans were quantified by HPLC. 35S-sulfate labeled glycosaminoglycans were characterized by anion exchange and size-exclusion HPLC. Heparan sulfate disaccharide compositions were determined by HPLC-MS analysis. Western blot analyses of MAPK-p42/44 were used to monitor HGF- and NK1-facillated Met signaling. Results: CHO-Positive but not CHO-Negative cell surface heparan sulfate bound to Met recombinant protein and HGF/NK1 further promoted the binding. Overall glycosaminoglycan analysis results indicated that the CHO-Negative cells had reduced amount of heparan sulfate, shorter chain length, and less 6-O-sulfated disaccharides compared to that of CHO-Positive cells. Moreover, CHO-Negative cells were defective in NK1/Met but not HGF/Met signaling. Conclusions: This study demonstrated that soluble Met recombinant protein bound to cell surface HS at physiological conditions and a Met /HGF or NK1/HS ternary signaling complex might be involved in Met signaling. Shorter HS chains and reduced 6-O-sulfation might be responsible for reduced Met binding and the diminished NK1-initiated signaling in the CHO-Negative cells. The unique CHO-Positive and CHO-Negative cell clones established in current study should be effective tools for studying the role of specific glycosaminoglycan structures in regulating Met signaling. Such knowledge should be useful in developing glycosaminoglycan-based compounds that target HGF/Met signaling

A Pilot Study: Changes of Gut Microbiota in Post-surgery Colorectal Cancer Patients

Colorectal cancer (CRC) is a growing health problem throughout the world. Strong evidences have supported that gut microbiota can influence tumorigenesis; however, little is known about what happens to gut microbiota following surgical resection. Here, we examined the changes of gut microbiota in CRC patients after the surgical resection. Using the PCoA analysis and dissimilarity tests, the microbial taxonomic compositions and diversities of gut microbiota in post-surgery CRC patients (A1) were significantly different from those in pre-surgery CRC patients (A0) and healthy individuals (H). Compared with A0 and H, the Shannon diversity and Simpson diversity were significantly decreased in A1 (P < 0.05). Based on the LEfSe analysis, the relative abundance of phylum Proteobacteria in A1 was significantly increased than that in A0 and H. The genus Klebsiella in A1 had higher proportions than that in A0 (P < 0.05). Individual variation was distinct; however, 90% of CRC patients in A1 had more abundances of Klebsiella than A0. The Klebsiella in A1 was significantly associated with infectious diseases (P < 0.05), revealed by the correlation analysis between differentiated genera and metabolic pathway. The Klebsiella (Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae) in A1 was significantly linked with lymphatic invasion (P < 0.05). Furthermore, the PCA of KEGG pathways indicated that gut microbiota with a more scattered distribution in A1 was noticeably different from that in A0 and H. The nodes, the links, and the kinds of phylum in each module in A1 were less than those in A0 and H, indicating that gut microbiota in A1 had a relatively looser ecologcial interaction network. To sum up, this pilot study identified the changes of gut microbiota in post-surgery CRC patients, and highlights future avenues in which the gut microbiota is likely to be of increasing importance in the care of surgical patients

PROTECTIVE EFFECT OF SODIUM BUTYRATE ON INTESTINAL BARRIER IN HYPERURICEMIA MOUSE MODEL

Objective To investigate the protective effect of sodium butyrate on intestinal barrier in mice with hyperuricemia. Methods Male C57BL/6 mice were randomly divided into control group, model group, and sodium butyrate group. Mice in the model group were intraperitoneally injected with potassium oxonate (250 mg/kg) every day, and fed with high yeast diet freely. Mice in the sodium butyrate group were given 200 mg/kg sodium butyrate by gavage every day on the basis of the treatment in the model group. Mice in the control group were intraperitoneally injected and intragastrically administered with the same dose of normal saline every day. The intervention lasted for 21 d. The expression levels of ZO-1 and Occludin protein and mRNA in small intestine tissues of mice in each group were measured by Western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemical staining. The pathological morphology of small intestine tissues in each group was observed by hematoxylin-eosin (HE) staining. The content of inflammatory factors in small intestine tissues was measured by enzyme-linked immunosorbent assay (ELISA). Results There was a significant difference in body mass among the three groups (F=4.70,P<0.05). The body mass of the model group was significantly lower than that of the control group (t=3.03,P<0.05), and the body mass of the sodium butyrate group was significantly higher than that of the model group (t=2.90,P<0.05). The results of Western blot, RT-qPCR, and immunohistochemical staining showed that there were significant differences in the expression of ZO-1 and Occludin protein and mRNA in the small intestine between the model group and the control group, the model group and the sodium butyrate group (t=2.55-11.04,P<0.05). The results of HE staining showed that the small intestinal villi of the mo-del group were significantly reduced and broken, and the small intestinal villi of the sodium butyrate group were relatively complete. ELISA results showed that there were significant differences in the levels of tumor necrosis factor-α and interleukin-6 in the small intestine between the model group and the control group, the model group and the sodium butyrate group (t=5.74-9.79,P<0.05). Conclusion Hyperuricemia mouse models have intestinal barrier injury, and intragastric administration of sodium butyrate can protect the intestinal barrier of hyperuricemia model mice

Protective effect of sodium butyrate on intestinal barrier damage and uric acid reduction in hyperuricemia mice

Purpose: The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA). Methods: First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg−1·d−1 NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis. Results: The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice. Conclusion: The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level

Securing Physical Assets on the Blockchain : Linking a novel Object Identification Concept with Distributed Ledgers

The use of blockchain technology to track physical assets is not new. However, the state of the art concepts are not applicable due to several limitations. One limitation is the scalability of blockchains with regard to the number of transactions that can be processed by the network. The well-established technology in tracking products is based on RFID chips that can be cloned. This paper provides insights into how objects can be protected and monitored by a varnish with a unique crack pattern, as an example of a Physical Unclonable Function. The perceptual hash of the unique pattern is used to encrypt the associated data to ensure privacy. Instead of logging each event on the blockchain individually, which is not possible due to the limited transaction throughput, OriginStamp is used to preserve data integrity on the blockchain. OriginStamp aggregates events, combines them through hashing and embeds this hash into a Bitcoin transaction. Once the Bitcoin network mines the transaction into a block and confirms it, the timestamp is considered as immutable proof of existence. With this approach, the integrity of tracking data cannot be contested. In the future, the craquelure-based tracking approach could be extended to supply chain integration to secure the origin of products, including prevention of counterfeiting, securing the place of manufacture for trademark law or state surveillance of the agricultural economy.publishe