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Abstract This study investigates the role of RNF4-mediated ubiquitination and degradation of PDHA1 in colorectal cancer (CRC) metabolism and metastasis. Integrating (The Cancer Genome Atlas) TCGA and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, proteomic, clinical, and metabolomic analyses were performed, revealing PDHA1 as a prognostic marker in CRC. Immunohistochemical staining confirmed lower PDHA1 expression in metastatic CRC tissues. In vitro experiments demonstrated that PDHA1 overexpression inhibited CRC cell proliferation, migration, and invasion. RNF4 was identified as a key mediator in the ubiquitination degradation of PDHA1, influencing glycolytic pathways in CRC cells. Metabolomic analysis of serum samples from metastatic CRC patients further supported these findings. In vivo experiments, including xenograft and metastasis models, validated that RNF4 knockdown stabilized PDHA1, inhibiting tumor formation and metastasis. This study highlights the critical role of RNF4-mediated PDHA1 ubiquitination in promoting glycolytic metabolism, proliferation, and metastasis in CRC.

Abstract The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance’s core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

In recent years, the service life of building materials has become the focus of attention. Among them, the service life of concrete and steel bars is particularly affected by the corrosion of external ions (such as Cl−) in the environment. To solve this problem, a new type of composite nanocolloid was prepared through a controllable preparation method. The composite nanocolloid is prepared from aluminum chloride sol and silica sol as raw materials. The prepared colloidal particles have a particle size distribution between 10.5 and 17.5 nm, exhibiting excellent stability and dispersibility. In order to verify the improvement effect of the composite nanocolloid on the properties of building materials, the influence of it on the porosity of concrete and the anti-corrosion performance of steel bars was experimentally studied. The results indicate that the moisture absorption and dehumidification speed of concrete treated with composite nano colloids is slower, and the pore size distribution is mainly concentrated in 100–1,000 nm, indicating that the colloids can effectively optimize the pore structure of concrete. In addition, the processed steel plate samples showed high AC impedance values and low corrosion current logarithmic values in electrochemical testing, indicating that composite nanocolloids have a significant protective effect on the corrosion of steel bars, which can effectively improve the performance of building materials and extend their service life.

Soybean soluble dietary fiber (SSDF) was extracted from soy sauce residue and soybean meal. The influence of SSDF on the physicochemical stability and digestive characteristics of soybean oil body (SOB) lotion was investigated by taking the absolute value of Zeta potential, average particle size, peroxide value (POV value), thiobarbituric acid value (TBARS value) and fatty acid release rate (FFA) as characteristic parameters. The results showed that certain concentration of SSDF could effectively reduce the Zeta potential, average particle size, POV value, TBARS value of SOB lotion system, and significantly improve the physical and chemical stability of SOB lotion. In addition, in vitro simulated digestion experiments further showed that the introduction of SSDF can significantly reduce the FFA release rate of SOB emulsion, which effectively delayed the digestion process of lipids in the gastrointestinal tract. This study can provide theoretical basis and reference for the high-value utilization of soybean processing by- products such as soy sauce oil residue and soybean meal, which could improve the processing applicability of SOB, and develop new low-fat health foods containing SOB and SSDF.

Degos disease also known as malignant atrophic papulosis (MAP), is an autoinflammatory disease that mainly affects small- to medium-sized arteries. Gastrointestinal and nervous system are most commonly affected systems. Herein, we reported a case of Degos disease with disease onset during infantile and had severe neurological involvement.

Abstract Limited endoscopic sphincterotomy (EST) combined with endoscopic papillary balloon dilation (EPBD) is widely used. However, the optimal duration of small balloon dilation in choledocholithiasis remains controversial. We aimed to determine the optimal duration for 10 mm diameter balloon dilation after limited EST in choledocholithiasis. In this randomized controlled clinical trial, 320 patients were randomly assigned to receive small balloon dilation (10 mm in diameter) for 1 min (n = 160) or 3 min (n = 160) after deep bile duct cannulation. No significant difference in success rate of stone extraction between the two groups was observed. The incidence of post-ERCP pancreatitis (PEP) was higher in the 1 min group (10.6%) than in the 3 min group (4.4%) (P = 0.034). The logistic regression analysis showed that guidewire into the pancreatic duct, cannulation time > 5 min and 1 min balloon dilation were independent risk factors for PEP. There were no significant differences in other post-ERCP adverse events such as acute cholangitis, bleeding, perforation, etc. between the two groups. In conclusion, 3 min in duration was determined to be the optimal dilation condition for the removal of common bile duct stones.

This paper systematically reviews 150 (VR/AR)-supporting language learning articles from 2008 to 2019 and summarizes the development trends. The definition of VR/AR is given firstly, and then the model of VR/AR supporting learning is proposed. This model's language types, research participants, learning devices, learning goals, research issues, research methods, research domains and learning strategies act as a coding scheme here. Meanwhile, through review and analysis, empirical study has been proven to be in its peak period; the VR/AR is increasingly applied, and larger numbers of immersive devices are being used. Under such circumstances, higher education is the principal of research, and speaking/expressing and words are still the most significant learning goals. As for research issues, the first period (2008-2013), which focuses more on learners' opinions, learning behaviours, learning attitudes and learning performance, is still the main scheme even though the second period (2014-2019) has more research issues and wider research scale. Right now, research about teaching and learning has already drawn the most attention, and task-based learning, situated learning, and game-based learning are the most commonly used learning strategies. Finally, this paper analyses VR/AR used in language learning through SWOT analysis to provide more profound suggestions and further discussion.

5G technology is the foundation for achieving intelligent mining construction. In response to the problem of difficult interoperability between mining 5G intelligent terminals and control platforms among different manufacturers, it is necessary to unify and standardize the data exchange and sharing process in the 5G system. The deployment architecture of '5G+intelligent mining' is proposed. The mining 5G intelligent terminals can interact and share data with servers containing control platforms through 5G base stations, switches, and 5G core networks in coal mines. This paper introduces the message types, message transmission formats, message composition, and message connection methods transmitted in the mining 5G system. For specific application scenarios in the mining field, the data in the mining 5G system is divided into voice data, video data, sensor data, and control data. The data types transmitted by the mining 5G intelligent terminal in different application scenarios are provided. This paper analyzes the basic transmission capabilities that mining 5G intelligent terminals and control platforms should have to meet data interaction. It is pointed out that the process of data interaction between mining 5G intelligent terminals and control platforms includes device information query and reporting, device upgrade, log collection, alarm issuance and processing, and platform configuration issuance and processing. It proposes the participating entities, security levels, and processes for data sharing of mining 5G intelligent terminals (including data aggregation, application, authorization, provision, and feedback). By implementing standardized processes, while ensuring communication reliability, the data exchange and sharing process under the '5G+intelligent mine' system architecture has been simplified to accelerate the intelligent construction of mines.

Soft scale insects (Hemiptera, Coccidae) are important pests of various agricultural and horticultural crops and ornamental plants. They have negative impacts on agriculture and forestry. The tribe Coccini represents one of the most ancient evolutionary lineages of soft scale insects. However, no complete Coccini mitochondrial genome (mitogenome) is available in public databases. Here, we described the complete mitogenome of Coccus hesperidum L., 1758. The 15,566 bp mitogenome of C. hesperidum had a high A+T content (83.4%) and contained a typical set of 37 genes, with 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs) and two ribosomal RNA genes (rRNAs). Only seven tRNAs had the typical clover-leaf secondary structure and the remaining tRNAs lacked the DHU arm, TψC arm or both. Moreover, a comparative analysis of all reported scale insect mitogenomes from GenBank database was performed. The mitogenomes of scale insects showed high similarities in base composition and A+T content. Additionally, our phylogenetic analysis confirmed the monophyly of Coccomorpha and revealed that the archaeococcoids were the most basal lineage within Coccomorpha, while Ericerus pela and Didesmococcus koreanus, belonging to Coccidae, were often mixed with Aclerdidae, making Coccidae a paraphyletic group. These findings expand the mitogenome database of scale insects and provide new insights on mitogenome evolution for future studies across different insect groups.