Efficient Prediction of Peptide Self-assembly through Sequential and Graphical Encoding

In recent years, there has been an explosion of research on the application of deep learning to the prediction of various peptide properties, due to the significant development and market potential of peptides. Molecular dynamics has enabled the efficient collection of large peptide datasets, providing reliable training data for deep learning. However, the lack of systematic analysis of the peptide encoding, which is essential for AI-assisted peptide-related tasks, makes it an urgent problem to be solved for the improvement of prediction accuracy. To address this issue, we first collect a high-quality, colossal simulation dataset of peptide self-assembly containing over 62,000 samples generated by coarse-grained molecular dynamics (CGMD). Then, we systematically investigate the effect of peptide encoding of amino acids into sequences and molecular graphs using state-of-the-art sequential (i.e., RNN, LSTM, and Transformer) and structural deep learning models (i.e., GCN, GAT, and GraphSAGE), on the accuracy of peptide self-assembly prediction, an essential physiochemical process prior to any peptide-related applications. Extensive benchmarking studies have proven Transformer to be the most powerful sequence-encoding-based deep learning model, pushing the limit of peptide self-assembly prediction to decapeptides. In summary, this work provides a comprehensive benchmark analysis of peptide encoding with advanced deep learning models, serving as a guide for a wide range of peptide-related predictions such as isoelectric points, hydration free energy, etc

Hub gene associated with prognosis in bladder cancer is a novel therapeutic target

Objective Bladder cancer is a clinical and social conundrum due to its high incidence and recurrence rate. It is urgent to find new targets for the diagnosis and treatment of bladder cancer and improve the prognosis and survival rate of bladder cancer patients. We sought a prognosis-related gene, built related models of evaluated bladder cancer and identified the function of the hub gene in bladder cancer. Methods We downloaded the data of bladder cancer patients from the TCGA database, and used differentially expressed genes (DEGs), copy number variation (CNV) and survival analysis to scan the hub genes associated with prognosis in bladder cancer. Then, multi-factor cox regression was used to obtain the bladder cancer prognosis correlation model. Then, we analyzed the relationship between the expression of hub gene and immune microenvironment of bladder cancer. The relationship between the expression of hub gene and prognosis in bladder cancer patients was verified by immunohistochemistry. Cell proliferation assay and drug sensitivity test in vivo were used to verify the inhibition of bladder cancer by targeted inhibitors. Results In bladder cancer, we screened seven hub genes (ACLY, CNP, NKIRAS2, P3H4, PDIA6, VPS25 and XPO1) associated with survival. Moreover, the multifactor regression model constructed with hub gene can well distinguish the prognosis of bladder cancer. Hub gene is mostly associated with immune microenvironment. Immunohistochemical results basically confirmed the importance of XPO1 in bladder cancer. Selinexor (an inhibitor of XPO1) could effectively inhibit the proliferation of bladder cancer in the cell proliferation experiments by CCK-8 assays and it could suppress the growth of bladder cancer in mouse bladder cancer model. Conclusions In this study, a prognostic model with seven hub genes has provided great help for the prognosis prediction of bladder cancer patients. And XPO1 is an important target affecting the prognosis of bladder cancer, and inhibition of XPO1 can effectively inhibit bladder cancer proliferation and growth

Simple Cholecystectomy Is Adequate for Patients With T1b Gallbladder Adenocarcinoma < 1 cm in Diameter

Purpose: Consensus-based clinical guidelines recommend that simple cholecystectomy (SC) is adequate for T1a gallbladder adenocarcinoma (GBA), but extended cholecystectomy (EC), SC plus lymphatic dissection, should be considered for T1b and more advanced GBA. Whether lymphatic dissection is necessary for the treatment of T1b GBA remains controversial. This study attempts to better define the current criteria for local treatment of T1b GBA, by examining the relationship between lymph node (LN) metastasis and tumor size in such patients.Patients and methods: Clinical data from patients with T1b GBA receiving curative surgical treatment between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Baseline characteristics for the entire cohort were described, and overall survival (OS) and cancer-specific survival (CSS) were analyzed with the Kaplan–Meier method.Results: In total, 277 patients were enrolled for further analysis; 127 underwent lymphadenectomy. Among them, 23 patients had tumors &lt;1 cm in diameter, none of which had LN metastasis; 104 patients had tumors ≥1 cm, 15 of which had positive LNs. In the group with tumor size &lt;1 cm, there was no significant survival difference between treatment with SC or EC (P = 0.694). A clinical benefit was observed in T1b GBA patients with a tumor size ≥1 cm receiving EC vs. those receiving SC (P = 0.012).Conclusion: SC was adequate for treatment of T1b GBA &lt; 1 cm in diameter. This evidence may be included as part of current guidelines

Highly CO2-permeable membranes derived from a midblock-sulfonated multiblock polymer after submersion in water

To mitigate the effect of atmospheric CO2 on global climate change, gas separation materials that simultaneously exhibit high CO2 permeability and selectivity in gas mixtures must be developed. In this study, CO2 transport through midblock-sulfonated block polymer membranes prepared from four different solvents is investigated. The results presented here establish that membrane morphology and accompanying gas transport properties are sensitive to casting solvent and relative humidity. We likewise report an intriguing observation: submersion of these thermoplastic elastomeric membranes in liquid water, followed by drying prior to analysis, promotes not only a substantial change in membrane morphology, but also a significant improvement in both CO2 permeability and CO2/N2 selectivity. Measured CO2 permeability and CO2/N2 selectivity values of 482 Barrer and 57, respectively, surpass the Robeson upper bound, indicating that these nanostructured membranes constitute promising candidates for gas separation technologies aimed at CO2 capturepublishedVersio

Contezolid, a novel oxazolidinone antibiotic, may improve drug-related thrombocytopenia in clinical antibacterial treatment

One of the major limitations in the clinical use of existing oxazolidinone antibiotics is their characteristic adverse reactions, in particular thrombocytopenia. In anti-infective treatment, if patients are suspected of having drug-induced thrombocytopenia, the first step is to immediately discontinue the offending drug. Even in patients with severe infections, the antibacterial drug may need to be changed or the antibacterial treatment may need to be discontinued because thrombocytopenia may have a more serious clinical prognosis. In addition, if the patient needs to continue antibacterial treatment after discharge, the lack of conditions for monitoring platelet levels may also pose hidden dangers to the patient. Contezolid is an orally administered oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021. We found that contezolid may have an improved safety profile with a significantly reduced potential for myelosuppression based on the results of our observational clinical study. In this article, we review the advantages of contezolid as a new oxazolidinone antibiotic and describe three typical clinical cases of patients who experienced drug-induced thrombocytopenia after using linezolid. The platelet levels of these different patients were all significantly improved to varying degrees after initiation of contezolid treatment

Screening and Expression Analysis of Key Regulator Genes Associated with (Z)-3-Hexenal and (E)-2-Hexenal Transformation during Manufacturing Process of Oolong Tea

In this study, the contents of (Z)-3-hexenal and (E)-2-hexenal during oolong tea processing were measured and four (3Z):(2E)-hexenal isomerase (HI) genes were selected based on transcriptomic data. Meanwhile, the correlation between the changes of (Z)-3-hexenal and (E)-2-hexenal contents and related gene expression was analyzed. The results indicated that during oolong tea processing, one of the two compounds fell, while the other rose. Mechanical damage caused by tossing increased and reduced the contents of (Z)-3-hexenal and (E)-2-hexenal, respectively. Subsequent spreading contributed to the transformation of (Z)-3-hexenal into (E)-2-hexenal, resulting in an increase in the content of (E)-2-hexenal. The four selected genes all responded to mechanical stress and water deficit stress. The constructed phylogenetic tree indicated that CsHI was closely related to many germin-like proteins in plants such as tea (Camellia sinensis) and carrot (Daucus carota). This study provides a reference for clarifying the formation and transformation mechanism of volatile substances during oolong tea processing and improving the quality of oolong tea