Chemical Research in Toxicology最新文献

{"title":"An ultrasensitive flexible force sensor with nature-inspired minimalistic architecture to achieve a detection resolution and threshold of 1 mN for underwater applications","authors":"Peilin Cao ,&nbsp;Cong Wang ,&nbsp;Shichao Niu ,&nbsp;Zhiwu Han ,&nbsp;Linpeng Liu ,&nbsp;Ji’an Duan","doi":"10.1016/j.mser.2024.100862","DOIUrl":"10.1016/j.mser.2024.100862","url":null,"abstract":"<div><div>Highly sensitive flexible force sensors enable precise detection of underwater signals for monitoring biological activity, environmental conditions, and vehicle movement. Multilayer stack assembly and micro/nano structure array are often seen in most force/pressure sensors which are toughly hard to control the interlayer spacing and micro/nano structures alignment precisely, resulting in poor consistency and stability. Herein, we first reported a new force sensor with a nature-inspired minimalistic architecture, addressing such issues in an elegant and surprising approach by using a single-layer arched functional membrane with one microgroove. Inspired by the scorpions’ slit sensilla and mantis’ campaniform sensilla, a highly sensitive and waterproof flexible force sensor was fabricated. It is demonstrated that the force sensor has a sensitivity of 27.6 N⁻¹, a high force resolution (1 mN), a fast response time of 70 ms, excellent stability over 5000 cycles and linearity (0.996), and a small force detection limit (≤ 1 mN), showing great potential in underwater environment sensing and motion monitoring of vehicles. This novel but minimalistic architecture provides a new direction in the development of sensors with advanced performance.</div></div>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"161 ","pages":"Article 100862"},"PeriodicalIF":31.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context transcription factors establish cooperative environments and mediate enhancer communication","authors":"Judith F. Kribelbauer-Swietek,&nbsp;Olga Pushkarev,&nbsp;Vincent Gardeux,&nbsp;Katerina Faltejskova,&nbsp;Julie Russeil,&nbsp;Guido van Mierlo,&nbsp;Bart Deplancke","doi":"10.1038/s41588-024-01892-7","DOIUrl":"10.1038/s41588-024-01892-7","url":null,"abstract":"Many enhancers control gene expression by assembling regulatory factor clusters, also referred to as condensates. This process is vital for facilitating enhancer communication and establishing cellular identity. However, how DNA sequence and transcription factor (TF) binding instruct the formation of high regulatory factor environments remains poorly understood. Here we developed a new approach leveraging enhancer-centric chromatin accessibility quantitative trait loci (caQTLs) to nominate regulatory factor clusters genome-wide. By analyzing TF-binding signatures within the context of caQTLs and comparing episomal versus endogenous enhancer activities, we discovered a class of regulators, ‘context-only’ TFs, that amplify the activity of cell type-specific caQTL-binding TFs, that is, ‘context-initiator’ TFs. Similar to super-enhancers, enhancers enriched for context-only TF-binding sites display high coactivator binding and sensitivity to bromodomain-inhibiting molecules. We further show that binding sites for context-only and context-initiator TFs underlie enhancer coordination, providing a mechanistic rationale for how a loose TF syntax confers regulatory specificity. This study identifies context-only transcription factors (TFs), a TF class that enhances DNA accessibility initiated by cell type-specific TFs and establishes cooperative environments. Enhancers enriched with motifs of both TF classes show high coactivator binding, enhanced coordination and sensitivity to bromodomain inhibitors.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"56 10","pages":"2199-2212"},"PeriodicalIF":31.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01892-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-African analysis identifies genetic differences in prostate cancer risk","authors":"","doi":"10.1038/s41588-024-01932-2","DOIUrl":"10.1038/s41588-024-01932-2","url":null,"abstract":"To understand the genetic basis of disease, it is essential to study diverse populations. We conducted the largest study to date of African men to evaluate the evolutionary genetics and causes of prostate cancer. Our findings reveal novel genetic associations, including those that were not observed in studies of non-African populations.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"56 10","pages":"2006-2007"},"PeriodicalIF":31.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardizing variant naming in literature with VariantValidator to increase diagnostic rates","authors":"Peter J. Freeman,&nbsp;John F. Wagstaff,&nbsp;Ivo F. A. C. Fokkema,&nbsp;Garry R. Cutting,&nbsp;Heidi L. Rehm,&nbsp;Angela C. Davies,&nbsp;Johan T. den Dunnen,&nbsp;Liam J. Gretton,&nbsp;Raymond Dalgleish","doi":"10.1038/s41588-024-01938-w","DOIUrl":"10.1038/s41588-024-01938-w","url":null,"abstract":"Accurate naming of genetic variants is essential to identify clinical data that interpret the consequences of such variants. In partnership with the Human Genome Organization, we advocate for integration of VariantValidator in publishing of journals and databases, to improve the quality of shared genetic data and ultimately patient outcomes.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"56 11","pages":"2284-2286"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bio-heterointerface charging through ultrasound-boosted extracellular and intracellular electron transfer for rapid bacterial killing","authors":"Jun Li ,&nbsp;Xiangmei Liu ,&nbsp;Chaofeng Wang ,&nbsp;Yufeng Zheng ,&nbsp;Zhenduo Cui ,&nbsp;Zhaoyang Li ,&nbsp;Shengli Zhu ,&nbsp;Hui Jiang ,&nbsp;Yu Zhang ,&nbsp;Paul K. Chu ,&nbsp;Shuilin Wu","doi":"10.1016/j.mser.2024.100861","DOIUrl":"10.1016/j.mser.2024.100861","url":null,"abstract":"<div><div>The deep-seated drug-resistant bacterial infection is one of the most noticeable public-health threat owing to poor drug therapeutic effect, high recurrence, and devastating complication. Herein, we propose a bactericidal strategy of bio-heterointerface charging through ultrasound-boosted bacterial extracellular and intracellular electron transfer for eradicating implant-related drug-resistant bacterial infection, where a TiO₂-modified porphyrin-based two-dimensional metal-organic framework (2DMOF-TiO₂) is selected as a sonosensitizer. The ultrasound-boosted extracellular and intracellular electron transfer between methicillin-resistant <em>Staphylococcus aureus</em> and 2DMOF-TiO₂ induces rapid reactive oxygen species (ROS) burst surrounding bacterial outer and inner, contributing to intracellular oxidation, membrane potential decrease (∼5 mV), membrane disruption, and pyrimidine metabolism disorder, thus causing bacterial death. The in vivo results of 2DMOF-TiO₂ implant exhibit rapid sonocatalytic anti-infection and enhanced osseointegration at bone-implant interface. This platform may inspire the universal thinking about ultrasound-boosted extracellular and intracellular electron-transfer-induced ROS and provide a superior therapeutic candidate for various deep-seated infectious diseases.</div></div>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"161 ","pages":"Article 100861"},"PeriodicalIF":31.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution","authors":"Clare Puttick,&nbsp;Thomas P. Jones,&nbsp;Michelle M. Leung,&nbsp;Felipe Galvez-Cancino,&nbsp;Jiali Liu,&nbsp;Manuel Varas-Godoy,&nbsp;Andrew Rowan,&nbsp;Oriol Pich,&nbsp;Carlos Martinez-Ruiz,&nbsp;Robert Bentham,&nbsp;Krijn K. Dijkstra,&nbsp;James R. M. Black,&nbsp;Rachel Rosenthal,&nbsp;Nnennaya Kanu,&nbsp;Kevin Litchfield,&nbsp;Roberto Salgado,&nbsp;David A. Moore,&nbsp;Peter Van Loo,&nbsp;Mariam Jamal-Hanjani,&nbsp;Sergio A. Quezada,&nbsp;TRACERx Consortium,&nbsp;Charles Swanton,&nbsp;Nicholas McGranahan","doi":"10.1038/s41588-024-01883-8","DOIUrl":"10.1038/s41588-024-01883-8","url":null,"abstract":"Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution. Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"56 10","pages":"2121-2131"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01883-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa","authors":"Rohini Janivara,&nbsp;Wenlong C. Chen,&nbsp;Ujani Hazra,&nbsp;Shakuntala Baichoo,&nbsp;Ilir Agalliu,&nbsp;Paidamoyo Kachambwa,&nbsp;Corrine N. Simonti,&nbsp;Lyda M. Brown,&nbsp;Saanika P. Tambe,&nbsp;Michelle S. Kim,&nbsp;Maxine Harlemon,&nbsp;Mohamed Jalloh,&nbsp;Dillon Muzondiwa,&nbsp;Daphne Naidoo,&nbsp;Olabode O. Ajayi,&nbsp;Nana Yaa Snyper,&nbsp;Lamine Niang,&nbsp;Halimatou Diop,&nbsp;Medina Ndoye,&nbsp;James E. Mensah,&nbsp;Afua O. D. Abrahams,&nbsp;Richard Biritwum,&nbsp;Andrew A. Adjei,&nbsp;Akindele O. Adebiyi,&nbsp;Olayiwola Shittu,&nbsp;Olufemi Ogunbiyi,&nbsp;Sikiru Adebayo,&nbsp;Maxwell M. Nwegbu,&nbsp;Hafees O. Ajibola,&nbsp;Olabode P. Oluwole,&nbsp;Mustapha A. Jamda,&nbsp;Audrey Pentz,&nbsp;Christopher A. Haiman,&nbsp;Petrus V. Spies,&nbsp;André van der Merwe,&nbsp;Michael B. Cook,&nbsp;Stephen J. Chanock,&nbsp;Sonja I. Berndt,&nbsp;Stephen Watya,&nbsp;Alexander Lubwama,&nbsp;Mazvita Muchengeti,&nbsp;Sean Doherty,&nbsp;Natalie Smyth,&nbsp;David Lounsbury,&nbsp;Brian Fortier,&nbsp;Thomas E. Rohan,&nbsp;Judith S. Jacobson,&nbsp;Alfred I. Neugut,&nbsp;Ann W. Hsing,&nbsp;Alexander Gusev,&nbsp;Oseremen I. Aisuodionoe-Shadrach,&nbsp;Maureen Joffe,&nbsp;Ben Adusei,&nbsp;Serigne M. Gueye,&nbsp;Pedro W. Fernandez,&nbsp;Jo McBride,&nbsp;Caroline Andrews,&nbsp;Lindsay N. Petersen,&nbsp;Joseph Lachance,&nbsp;Timothy R. Rebbeck","doi":"10.1038/s41588-024-01931-3","DOIUrl":"10.1038/s41588-024-01931-3","url":null,"abstract":"Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations. Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"56 10","pages":"2093-2103"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aneuploidy as a driver of human cancer","authors":"Eran Sdeor,&nbsp;Hajime Okada,&nbsp;Ron Saad,&nbsp;Tal Ben-Yishay,&nbsp;Uri Ben-David","doi":"10.1038/s41588-024-01916-2","DOIUrl":"10.1038/s41588-024-01916-2","url":null,"abstract":"Aneuploidy, an abnormal chromosome composition, is a major contributor to cancer development and progression and an important determinant of cancer therapeutic responses and clinical outcomes. Despite being recognized as a hallmark of human cancer, the exact role of aneuploidy as a ‘driver’ of cancer is still largely unknown. Identifying the specific genetic elements that underlie the recurrence of common aneuploidies remains a major challenge of cancer genetics. In this Review, we discuss recurrent aneuploidies and their function as drivers of tumor development. We then delve into the context-dependent identification and functional characterization of the driver genes underlying driver aneuploidies and examine emerging strategies to uncover these driver genes using cancer genomics data and cancer models. Lastly, we explore opportunities for targeting driver aneuploidies in cancer by leveraging the functional consequences of these common genetic alterations. This Review discusses recurrent aneuploidies driving human cancer, methods to identify them and strategies to uncover underlying driver genes. It highlights genomic and experimental approaches to study and ultimately target driver aneuploidies.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"56 10","pages":"2014-2026"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and non-genetic HLA disruption is widespread in lung and breast tumors","authors":"","doi":"10.1038/s41588-024-01886-5","DOIUrl":"10.1038/s41588-024-01886-5","url":null,"abstract":"Immune recognition of cancers can be inhibited if the molecules that present cancer cell-specific antigens are disrupted. We have developed a tool that can detect four different types of disruption. Overall, we find that both genetic and non-genetic disruption of these molecules is common in lung and breast tumors.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"56 10","pages":"2008-2009"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the integration of covalent-organic-framework with organic, inorganic, and polymeric materials for light-assisted green H2 generation: A review of emerging trends","authors":"Dong-Eun Lee ,&nbsp;Asim Ali ,&nbsp;Kyeong Tae Kang ,&nbsp;Mohtaram Danish ,&nbsp;Wan-Kuen Jo","doi":"10.1016/j.mser.2024.100858","DOIUrl":"10.1016/j.mser.2024.100858","url":null,"abstract":"<div><div>The growing demand for sustainable energy has driven significant advancements in covalent organic frameworks (COFs) for photocatalytic H₂ production. In this context, this review comprehensively examines the integration of COFs with various organic, inorganic, and polymeric materials to enhance light-assisted H₂ generation. We explore key synthesis approaches, including solvothermal, mechanochemical, sonochemical, interfacial, and post-synthetic modifications. Additionally, innovative methods such as photochemical synthesis, microwave-assisted solvothermal techniques, plasma-induced synthesis, and electron-beam-induced synthesis are discussed, highlighting their potential to optimize the structural and photocatalytic properties of COF-based heterojunction systems. Furthermore, extensive research has been conducted on the development of various composite materials, such as MOF-COF, metal oxide-COF, metal sulfide-COF, MXene-COF, g-C₃N₄-COF, and graphitic oxide-COF composites, to investigate their combined effects in improving photocatalytic efficiency. Particular attention is given to heterojunction systems and their structural features, which are critical for enhancing the photophysical and chemical properties required for efficient H₂ generation. Lastly, our findings reveal that the highest photocatalytic H₂ generation rate reported to date has been achieved using specific heterojunction systems. Successively, by synthesizing recent advancements and emerging trends, this review underscores the potential of COF-based composites to revolutionize sustainable energy solutions and provides valuable insights into future research directions aimed at significantly enhancing H₂ production efficiency under light irradiation.</div></div>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"161 ","pages":"Article 100858"},"PeriodicalIF":31.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}