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Biology subjects

Men, X.

Publications and source records attributed to Men, X..

3 recordsLinked to original sources

SMART: An Integrated Platform Revolutionizing Cryo-Electron Microscopy Workflow from Data Acquisition to Atomic Modeling

Recent advancements in cryo-electron microscopy (cryo-EM) have revolutionized structural biology, yet persistent workflow fragmentation between data acquisition, reconstruction, and modeling limits its full potential. This paper presents SMART, the first fully integrated cryo-EM platform unifying three critical AI-driven modules: DataSmart (automated data collection), CryoSmart (3D reconstruction), and ModelSmart (end-to-end atomic modeling). The platform embeds more than 10 distinct AI algorithms across its workflow, achieving unprecedented automation levels. These advancements not only lower the expertise barrier for cryo-EM adoption but also establish a new paradigm for AI-empowered structural biology, with broad implications for high-throughput drug discovery. This protocol provides a comprehensive delineation of the operational procedures for the SMART platform. As an example, this protocol enabled the determination of the 2.1 [A] resolution structure of TRPML1, a Ca2+-permeable, nonselective, six-transmembrane tetrameric cation channel found in late endosomes and lysosomes (LELs) of mammalian cells. This integrated workflow enables users, including those with minimal cryo-EM experience, to efficiently complete the entire pipeline from data collection to atomic model building.

bioinformatics↗

ITGB4 promotes the progression of colorectal cancer by activating Wnt/β-catenin signaling pathway via targeting EZR

ObjectivesColorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Integrin beta 4 (ITGB4) has been previously identified as being overexpressed in CRC; however, its precise oncogenic mechanism remains unclear. The present study aimed to elucidate the functional role of ITGB4 in CRC progression and identify its downstream molecular effectors to provide new insights for targeted therapy. MethodsThe biological functions of ITGB4 were investigated in CRC cell lines (SW480 and HCT116) using a series of in vitro assays, including CCK-8, colony formation, Transwell migration and invasion, and flow cytometry for apoptosis following ITGB4 knockdown. An in vivo xenograft mouse model was used to evaluate the effect of ITGB4 on tumor growth. Downstream targets were screened using RNA sequencing (RNA-seq) and validated by co-immunoprecipitation and co-immunofluorescence. The underlying signaling pathway was investigated by Western blotting and functional rescue experiments. ResultsKnockdown of ITGB4 significantly suppressed CRC cell proliferation, migration, and invasion, while promoting apoptosis in vitro. Similarly, silencing ITGB4 markedly inhibited tumor growth in the in vivo xenograft model. RNA-seq analysis identified Ezrin (EZR) as a key downstream target of ITGB4, and a direct protein-protein interaction was confirmed between them. Mechanistically, ITGB4 knockdown decreased the expression of EZR at both the mRNA and protein levels. ITGB4 was demonstrated to exert its pro-tumorigenic effects through the regulation of EZR, which subsequently activated the Wnt/{beta}-catenin signaling pathway. Interestingly, EZR overexpression partially restored ITGB4 levels, suggesting a potential positive feedback loop via Wnt/{beta}-catenin signaling that further amplifies this oncogenic axis. Notably, the malignant phenotypes suppressed by ITGB4 silencing were significantly rescued by the overexpression of EZR. ConclusionThe present study identified a novel ITGB4/EZR/Wnt/{beta}-catenin signaling axis in colorectal cancer. ITGB4 promotes CRC progression by modulating EZR expression and subsequently activating the Wnt/{beta}-catenin pathway. These findings highlight ITGB4 as a potential prognostic biomarker and a promising therapeutic target for CRC.

molecular biology↗

Contact toxicity, antifeedant activity and oviposition preference of osthole against agricultural pests

Osthole, the dominant bioactive constituent in Cnidium monnieri, has been shown to exhibit acute insecticidal activities. However, its detailed toxicity, antifeedant and oviposition preference effects against agricultural pests has not been fully understood, which has greatly hindered its practical applications. This study is designed to investigate the contact toxicity, antifeedant activity and oviposition preference of osthole against three agricultural pests (T. urticae, M. persicae and B. dorsalis) to evaluate its potential agricultural applications. Our results showed that Cnidium monnieri (L.) Cusson (CMC) have a high osthole content of 11.4 mg/g. Osthole exhibited a comparable level of acute toxicity against T. urticae to four other coumarins found in CMC. Osthole demonstrated significant insecticidal activity against first instar nymphs and adults of T. urticae and M. persicae in a dose-dependent manner, but not against B. dorsalis adults. Osthole exposure reduced the fecundity and prolonged the developmental time of T. urticae and M. persicae. Leaf choice bioassays revealed potent antifeedant activity in T. urticae. Furthermore, female B. dorsalis showed a distinct preference for laying eggs in mango juice with 0.02 mg/mL osthole at 48 hours, a preference which persisted at 96 hours. These results provide valuable insights into the toxicity, repellent activity, and attractant activity of osthole, thereby contributing to its expanded use in pest control.

zoology↗