Search

Impaired tumor cell antigen presentation contributes significantly to immune evasion. This study identifies Berbamine hydrochloride (Ber), a compound derived from traditional Chinese medicine, as an effective inhibitor of autophagy that enhances antigen presentation in tumor cells. Ber increases MHC-I-mediated antigen presentation in melanoma cells, improving recognition and elimination by CD8+ T cells. Mutation of Atg4b, which blocks autophagy, also raises MHC-I levels on the cell surface, and further treatment with Ber under these conditions does not increase MHC-I, indicating Ber's role in blocking autophagy to enhance MHC-I expression. Additionally, Ber treatment leads to the accumulation of autophagosomes, with elevated levels of LC3-II and p62, suggesting a disrupted autophagic flux. Fluorescence staining and co-localization analyses reveal that Ber likely inhibits lysosomal acidification without hindering autophagosome–lysosome fusion. Importantly, Ber treatment suppresses melanoma growth in mice and enhances CD8+ T cell infiltration, supporting its therapeutic potential. Our findings demonstrate that Ber disturbs late-stage autophagic flux through abnormal lysosomal acidification, enhancing MHC-I-mediated antigen presentation and curtailing tumor immune escape. [ABSTRACT FROM AUTHOR]

Permafrost is a significant part of the cryosphere, which has gained increasing attention from scientists, policy-makers, and the general public due to global warming, environmental degradation, water shortages, and intense human activities. Although many permafrost research review articles have been published, these studies were predominantly limited to either one subject or one field, while systematic studies about permafrost based on bibliometric analysis methods remain limited. We aim to fill this gap by conducting a bibliometric analysis of 13,697 articles in the field of permafrost research from 1942 to 2021, collected from the Web of Science core collection database. The results indicate that permafrost research is a typically multi-author, multi-country, and multi-institution cooperative field, involved in many research fields. The cumulative number of publications has presented an exponential increase over the past 80 years, with an average annual growth rate of 10.40%. Since 2000, China has seen a rapid growth in the number of publications per year, surpassing the USA in 2016 and leading in the years since then. In addition, the authors from China have great contributions in publications, and there is good room for permafrost development in the future according to the authors' M-index ranking. After the analysis of authors' keywords, we found that, compared to the conventional methods, machine learning and interferometric synthetic aperture radar (InSAR) are new technological approaches introduced in recent years, and the Qinghai–Tibet Plateau has become a popular study area. The results presented here can help related researchers, scholars, and students in the field to better understand the past developments, current status, and future trends of permafrost research. Furthermore, this paper presents and expands the general process of the bibliometric method used in permafrost studies, which can provide researchers with new inspirations and improve discipline research approach. [ABSTRACT FROM AUTHOR]

The identification of intrinsically disordered proteins and their functional roles is largely dependent on the performance of computational predictors, necessitating a high standard of accuracy in these tools. In this context, we introduce a novel series of computational predictors, termed PDFll (Predictors of Disorder and Function of proteins from the Language of Life), which are designed to offer precise predictions of protein disorder and associated functional roles based on protein sequences. PDFll is developed through a two-step process. Initially, it leverages large-scale protein language models (pLMs), trained on an extensive dataset comprising billions of protein sequences. Subsequently, the embeddings derived from pLMs are integrated into streamlined, yet sophisticated, deep-learning models to generate predictions. These predictions notably surpass the performance of existing state-of-the-art predictors, particularly those that forecast disorder and function without utilizing evolutionary information.

The field of understanding the association between genes and diseases is rapidly expanding, making it challenging for researchers to keep up with the influx of new publications and genetic datasets. Fortunately, there are now several regularly updated databases available that focus on cataloging gene-disease relationships. The development of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system has revolutionized the field of gene editing, providing a highly efficient, accurate, and reliable method for exploring gene-disease associations. However, currently, there is no resource specifically dedicated to collecting and integrating the latest experimentally supported gene-disease association data derived from genome-wide CRISPR screening. To address this gap, we have developed the CRISPR-Based Gene-Disease Associations (CBGDA) database, which includes over 200 manually curated gene-disease association data derived from genome-wide CRISPR screening studies. Through CBGDA, users can explore gene-disease association data derived from genome-wide CRISPR screening, gaining insights into the expression patterns of genes in different diseases, associated chemical data, and variant information. This provides a novel perspective on understanding the associations between genes and diseases. What is more, CBGDA integrates data from several other databases and resources, enhancing its comprehensiveness and utility. In summary, CBGDA offers a fresh perspective and comprehensive insights into the research on gene-disease associations. It fills the gap by providing a dedicated resource for accessing up-to-date, experimentally supported gene-disease association data derived from genome-wide CRISPR screening. Database URL: http://cbgda.zhounan.org/main., (© The Author(s) 2024. Published by Oxford University Press.)