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1. A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles.

作者: Daniel B Grabarczyk.;Eric J Aird.;Vanessa Reznikow.;Paul C Kirchgatterer.;Julian F Ehrmann.;Robert Kurzbauer.;Lillie E Bell.;Max J Kellner.;Ritika Aggarwal.;Alexander Schleiffer.;Victoria Faas.;Luiza Deszcz.;Anton Meinhart.;Gijs A Versteeg.;Josef M Penninger.;Lukas S Stelzl.;Moritz M Gaidt.;Ingrid Tessmer.;Jacob E Corn.;Tim Clausen.
来源: Cell. 2025年
Eukaryotic cells use a multi-layered immune response to combat intracellular pathogens. The ubiquitin ligase ZNFX1 has emerged as a crucial yet little understood player that regulates the immune response while protecting against RNA viruses. Our study unveils the molecular mechanism of ZNFX1, mediated by the joint activity of a helicase serving as a nucleic acid sensor and a non-conventional E3 module featuring a split active site. We demonstrate that single-stranded RNA stimulates E3 activity by fostering dimerization of ZNFX1 subunits that translocate along nucleic acid tracks. Juxtaposed E3 domains complement each other, leading to the ubiquitination of ZNFX1 itself and engaged RNA molecules, while clustering nucleic acids into dense nucleoprotein particles. We show that the E3 ligase activity of ZNFX1 protects cells during an immune response and propose that ubiquitin-coated particles formed by ZNFX1 represent part of an ancient mechanism to regulate both foreign and host RNA in the cell.

2. Proximity-specific ribosome profiling reveals the logic of localized mitochondrial translation.

作者: Jingchuan Luo.;Stuti Khandwala.;Jingjie Hu.;Song-Yi Lee.;Kelsey L Hickey.;Zebulon G Levine.;J Wade Harper.;Alice Y Ting.;Jonathan S Weissman.
来源: Cell. 2025年
Localized translation broadly enables spatiotemporal control of gene expression. Here, we present LOV-domain-controlled ligase for translation localization (LOCL-TL), an optogenetic approach for monitoring translation with codon resolution at any defined subcellular location under physiological conditions. Application of LOCL-TL to mitochondrially localized translation revealed that ∼20% of human nuclear-encoded mitochondrial genes are translated on the outer mitochondrial membrane (OMM). Mitochondrially translated messages form two classes distinguished by encoded protein length, recruitment mechanism, and cellular function. An evolutionarily ancient mechanism allows nascent chains to drive cotranslational recruitment of long proteins via an unanticipated bipartite targeting signal. Conversely, mRNAs of short proteins, especially eukaryotic-origin electron transport chain (ETC) components, are specifically recruited by the OMM protein A-kinase anchoring protein 1 (AKAP1) in a translation-independent manner that depends on mRNA splicing. AKAP1 loss lowers ETC levels. LOCL-TL thus reveals a hierarchical strategy that enables preferential translation of a subset of proteins on the OMM.

3. Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection.

作者: Bin Ju.;Congcong Liu.;Jingjing Zhang.;Yaning Li.;Haonan Yang.;Bing Zhou.;Baoying Huang.;Jianrong Ma.;Jiahan Lu.;Lin Cheng.;Zhe Cong.;Lin Zhu.;Tianhao Shi.;Yuehong Sun.;Na Li.;Ting Chen.;Miao Wang.;Shilong Tang.;Xiangyang Ge.;Juanjuan Zhao.;Wen-Jie Tan.;Renhong Yan.;Jing Xue.;Zheng Zhang.
来源: Cell. 2025年
The A35 protein, expressed on the enveloped virion of monkeypox (mpox) virus (MPXV), is essential for viral infection and spread within the host, making it an effective antiviral target. In this study, we demonstrated two human anti-A35 monoclonal antibodies (mAbs) displayed potential protection against MPXV in CAST/EiJ mice and rhesus macaques. Using cryo-electron microscopy, we determined two high-resolution structures of the A35 dimer in complex with the fragment of antigen binding of mAb 975 or mAb 981, revealing detailed interactions at the antigen-antibody interfaces. Structural analysis showed that these structurally conserved mAbs bind to a groove region at the interface of A35 dimer. Overall, we provided a proof of concept for a single administration of anti-A35 mAbs mitigating the pathogenic effects of MPXV infection in rhesus macaques. These human-derived mAbs could be served as antibody drug candidates, and their binding models to the A35 dimer will provide valuable insights for future vaccine design.

4. Human monoclonal antibodies targeting A35 protect from death caused by mpox.

作者: Raianna F Fantin.;Meng Yuan.;Seok-Chan Park.;Bailey Bozarth.;Hallie Cohn.;Maxinne Ignacio.;Patricia Earl.;Alesandro Civljak.;Gabriel Laghlali.;Ding Zhang.;Xueyong Zhu.;Jameson Crandell.;Valter Monteiro.;Jordan J Clark.;Catherine Cotter.;Martin Burkhardt.;Gagandeep Singh.;Prajakta Warang.;Juan García-Bernalt Diego.;Komal Srivastava.;Luz A Lugo.;Lauren Pischel.; .;Inci Yildirim.;Saad B Omer.;Daniel da Silva.;Florian Krammer.;Goran Bajic.;Viviana Simon.;Michael Schotsaert.;Carolina Lucas.;Ian A Wilson.;Bernard Moss.;Camila H Coelho.
来源: Cell. 2025年
The 2022 mpox outbreak highlighted the serious threat of monkeypox virus (MPXV), yet effective treatments are lacking. From an mpox-convalescent individual, we identified three high-affinity human monoclonal antibodies (mAbs) (named EV35-2, EV35-6, and EV35-7) that target the A35 protein in MPXV. These antibodies block viral spread in vitro and protect mice against lethal MPXV and vaccinia virus infection via both Fc-dependent and independent mechanisms. Levels of serum antibodies targeting the same epitopes are increased in mpox-convalescent humans, and higher levels of these antibodies in the sera are linked to shorter symptom duration and no hospitalization. Systems-level multivariate analysis indicated that mpox-convalescent serum antibodies targeting the same epitopic region as these three mAbs may function cooperatively, with additive associations to clinical protection. Two of the antibodies use a conserved IGHD2-21-encoded CxGGDCx motif in their CDRH3 region to bind a highly conserved poxvirus epitope. These findings establish A35 as a critical therapeutic target and highlight A35-specific mAbs as promising candidates for next-generation orthopoxvirus treatments.

5. Extensive cross-species transmission of pathogens and antibiotic resistance genes in mammals neglected by public health surveillance.

作者: Yuqi Shi.;Yuxing Li.;Haipeng Li.;Ayidana Haerheng.;Vanessa R Marcelino.;Meng Lu.;Philippe Lemey.;Jia Tang.;Yuhai Bi.;John H-O Pettersson.;Jon Bohlin.;Joon Klaps.;Zuowei Wu.;Wenbo Wan.;Bowen Sun.;Mei Kang.;Edward C Holmes.;Na He.;Shuo Su.
来源: Cell. 2025年
Non-traditional farmed and wild mammals are often neglected in pathogen surveillance. Through metagenomic and metatranscriptomic sequencing of fecal and tissue samples from 973 asymptomatic mammals, we identified 128 viruses (30 novel), including a new coronavirus genus, 10,255 bacterial species (over 7,000 undescribed), 201 fungi, and 7 parasites. Farmed and wild mammals shared 13.3% of virus species, including canine coronavirus in Asiatic black bears and Getah virus in rabbits, while the 2.3.4.4b clade of H5N1 avian influenza virus was found in a wild leopard cat. We identified potential bacterial pathogen transmission between farmed and wild mammals and bacterial strains with high genetic similarity to those found in humans. We observed 157 clinically prioritized antibiotic resistance genes (ARGs) in mammalian microbiomes with greater than 99% identity to ARGs from human microbiomes, often co-occurring with mobile genetic elements. Overall, this work highlights cross-species risks at the human-animal interface.

6. Mitochondrial activity tunes nociceptor resilience to excitotoxicity.

作者: Lin Yuan.;Navdeep S Chandel.;David Julius.
来源: Cell. 2025年
The capsaicin receptor, TRPV1, mediates the detection of noxious chemical and thermal stimuli by nociceptors, primary sensory neurons of the pain pathway. Overactivation of TRPV1 leads to cellular damage or death through calcium entry and excitotoxicity. We have exploited this phenomenon to conduct a systematic analysis of excitotoxicity through a genome-wide CRISPRi screen, thereby revealing a comprehensive network of regulatory pathways. We show that decreased expression of mitochondrial electron transport chain (ETC) components protects against capsaicin-induced toxicity and other challenges by mitigating both calcium imbalance and the generation of mitochondrial reactive oxygen species via distinct pathways. Moreover, we confirm the regulatory roles of the ETC in sensory neurons through gain-of-function and loss-of-function experiments. Interestingly, TRPV1+ sensory neurons maintain lower expression of ETC components and can better tolerate excitotoxicity and oxidative stress compared with other sensory neuron subtypes, implicating ETC tuning as an intrinsic cellular strategy that protects nociceptors against excitotoxicity.

7. Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers.

作者: Emily Grist.;Peter Dutey-Magni.;Marina A Parry.;Larissa Mendes.;Ashwin Sachdeva.;James A Proudfoot.;Anis A Hamid.;Mazlina Ismail.;Sarah Howlett.;Stefanie Friedrich.;Lia DePaula Oliveira.;Laura Murphy.;Christopher Brawley.;Oluwademilade Dairo.;Sharanpreet Lall.;Yang Liu.;Daniel Wetterskog.;Anna Wingate.;Karolina Nowakowska.;Leila Zakka.;Claire L Amos.;Nafisah B Atako.;Victoria Wang.;Hannah L Rush.;Robert J Jones.;Hing Leung.;William R Cross.;Silke Gillessen.;Chris C Parker.;Teresa Marafioti.;Alfonso Urbanucci.;Matthew Fittall.;Edward M Schaeffer.;Daniel E Spratt.;David Waugh.;Thomas Powles.;Matthew R Sydes.;Felix Y Feng.;Daniel M Berney.;Mahesh K B Parmar.;Noel W Clarke.;Elai Davicioni.;Tamara L Lotan.;Christopher J Sweeney.;Louise C Brown.;Nicholas D James.;Gerhardt Attard.
来源: Cell. 2025年
Advanced prostate cancers respond to hormone therapy but outcomes vary and no predictive tests exist for informed treatment selection. To identify novel biomarker-treatment pairings, we examined associations between biological pathways and 14-year survival outcomes of patients randomized in practice-changing phase 3 trials (testing docetaxel or abiraterone). We included transcriptome-wide expression signatures and immunohistochemistry markers (Ki-67 and PTEN) on prostate tumors from 1,523 patients (832 metastatic). Tumor androgen receptor signaling is associated with longer survival, whereas increased proliferation predicted shorter survival. In a pre-specified analysis, the previously identified decipher RNA signature was both prognostic and predicted survival benefit from docetaxel for metastatic cancers (biomarker-docetaxel interaction p = 0.039). Additionally, transcriptome-based classification of PTEN inactivation identified tumors more likely to have PTEN protein loss (p = 4 × 10-37) and metabolically perturbed metastatic cancers that had shorter survival with hormone therapies (p < 0.001) but exhibited docetaxel sensitivity (biomarker-docetaxel interaction p = 0.002). Transcriptome classifiers predict docetaxel benefit and could be clinically implemented for improved patient management.

8. Molecular impact of antisense oligonucleotide therapy in C9orf72-associated ALS.

作者: Zachary T McEachin.;Mingee Chung.;Sabrina A Stratton.;Changhee Han.;Woo Jae Kim.;Udit Sheth.;Eleanor V Thomas.;Ethan Issenberg.;Tanvi Kamra.;Paola Merino.;Yona Levites.;Nisha Raj.;Eric B Dammer.;Duc M Duong.;Lingyan Ping.;Anantharaman Shantaraman.;Adam N Trautwig.;Joshna Gadhavi.;Ezana Assefa.;Marla Gearing.;Kaylor M Kelly.;Shanu F Roemer.;Michael DeTure.;Seneshaw Asress.;Thomas Kukar.;Christina Fournier.;Dennis W Dickson.;Leonard Petrucelli.;Todd E Golde.;Björn Oskarsson.;Tania F Gendron.;Nicholas T Seyfried.;Jonathan D Glass.
来源: Cell. 2025年
C9orf72-associated amyotrophic lateral sclerosis (c9ALS) is caused by an intronic G4C2 repeat expansion that leads to toxic RNA transcripts and dipeptide repeat proteins (DPRs). A clinical trial using the antisense oligonucleotide (ASO) BIIB078 to target these transcripts was discontinued after failing to provide clinical benefit. Here, we determine the extent of target engagement in the central nervous system (CNS) and elucidate pharmacodynamic cerebrospinal fluid (CSF) biomarkers following treatment. CSF from BIIB078-treated cases showed reduced DPRs and sustained increases in inflammatory biomarkers, including C-C motif chemokine ligand 26 (CCL26). BIIB078 was widely distributed in postmortem CNS tissue; however, DPRs and phosphorylated TDP-43 remained abundant. Proteomic signatures in c9ALS spinal cord were not altered with treatment, although a distinct increase in RNase T2 abundance that correlated with BIIB078 concentration was observed. Thus, despite widespread distribution, BIIB078 did not significantly impact key CNS pathologies, emphasizing the need to identify pharmacodynamic biomarkers that reflect disease-relevant neuropathological changes in response to ASO therapies.

9. Uncovering phenotypic inheritance from single cells with Microcolony-seq.

作者: Raya Faigenbaum-Romm.;Noam Yedidi.;Orit Gefen.;Naama Katsowich-Nagar.;Lior Aroeti.;Irine Ronin.;Maskit Bar-Meir.;Ilan Rosenshine.;Nathalie Q Balaban.
来源: Cell. 2025年
Uncovering phenotypic heterogeneity is fundamental to understanding processes such as development and stress responses. Due to the low mRNA abundance in single bacteria, determining biologically relevant heterogeneity remains a challenge. Using Microcolony-seq, a methodology that captures inherited heterogeneity by analyzing microcolonies originating from single bacterial cells, we uncover the ubiquitous ability of bacteria to maintain long-term inheritance of the host environment. Notably, we observe that growth to stationary phase erases the epigenetic inheritance. By leveraging this memory within each microcolony, Microcolony-seq combines bulk RNA sequencing (RNA-seq) with whole-genome sequencing and phenotypic assays to detect the distinct subpopulations and their fitness advantages. Applying this directly to infected human samples enables us to uncover a wealth of diverse inherited phenotypes. Our observations suggest that bacterial memory may be a widespread phenomenon in both Gram-negative and Gram-positive bacteria. Microcolony-seq provides potential targets for the rational design of therapies with the power to simultaneously target the coexisting subpopulations.

10. Structural basis of poxvirus fusion regulation and anti-A16/G9 antibody-mediated neutralization and protection.

作者: Annalisa Meola.;Riccardo Vernuccio.;Leandro Battini.;Guillermo Albericio.;Pilar Delgado.;Rebecca Bamford.;Laura Pokorny.;Manon Broutin.;Alejandro Martínez León.;Sébastien Gallien.;María Gil.;María A Noriega.;Florence Guivel-Benhassine.;Françoise Porrot.;Jeanne Postal.;Julian Buchrieser.;Mathieu Hubert.;Ahmed Haouz.;Pierre Lafaye.;Mariano Esteban.;Jochen S Hub.;Matthieu Mahévas.;Pascal Chappert.;Jason Mercer.;Juan Garcia-Arriaza.;Olivier Schwartz.;Pablo Guardado-Calvo.
来源: Cell. 2025年
Monkeypox virus (MPXV) is a poxvirus endemic to Central and West Africa with high epidemic potential. Poxviruses enter host cells via a conserved entry-fusion complex (EFC), which mediates viral fusion to the cell membrane. The EFC is a promising therapeutic target, but the absence of structural data has limited the development of fusion-inhibiting treatments. Here, we investigated A16/G9, a subcomplex of the EFC that controls fusion timing. Using cryo-electron microscopy, we showed how A16/G9 interacts with A56/K2, a viral fusion suppressor that prevents superinfection. Immunization with A16/G9 elicited a protective immune response in mice. Using X-ray crystallography, we characterized two neutralizing antibodies and engineered a chimeric antibody that cross-neutralizes several poxviruses more efficiently than 7D11, the most potent antibody targeting the EFC described to date. These findings highlight the potential of A16/G9 as a candidate for subunit vaccines and identify regions of the EFC as targets for antiviral development.

11. Transient gene melting governs the timing of oligodendrocyte maturation.

作者: Kevin C Allan.;Jesse J Zhan.;Andrew R Morton.;Erin F Cohn.;Marissa A Scavuzzo.;Anushka Nikhil.;Matthew S Elitt.;Benjamin L L Clayton.;Lucille R Hu.;H Elizabeth Shick.;Jost K Vrabic.;Hannah E Olsen.;Daniel C Factor.;Jonathan E Henninger.;Gemma Bachmann.;Berit E Powers.;Richard A Young.;Charles Y Lin.;Peter C Scacheri.;Tyler E Miller.;Paul J Tesar.
来源: Cell. 2025年
Cellular maturation is a crucial step for tissue formation and function, distinct from the initial steps of differentiation and cell fate specification. In the central nervous system, failure of oligodendrocyte maturation is linked to diseases such as multiple sclerosis. Here, we report a transcriptional mechanism that governs the timing of oligodendrocyte maturation. After progenitor cells differentiate into immature oligodendrocytes, the transcription factor SOX6 redistributes from super-enhancers to cluster across specific gene bodies. These sites exhibit extensive chromatin decondensation and transcription, which abruptly turn off upon maturation. Suppression of SOX6 deactivates these immaturity loci, accelerating the transition to mature, myelinating oligodendrocytes. Notably, cells harboring this immature SOX6 gene signature are enriched in multiple sclerosis patient brains and antisense oligonucleotide-mediated Sox6 knockdown drives oligodendrocyte maturation in mice. Our findings establish SOX6 as a key regulator of oligodendrocyte maturation and highlight its potential as a therapeutic target to promote myelination in disease.

12. Interferons in health and disease.

作者: Daniel Boehmer.;Ivan Zanoni.
来源: Cell. 2025年188卷17期4480-4504页
Interferons (IFNs) are signaling proteins that play fundamental roles during health and disease. Although types I, II, and III IFNs are structurally and functionally different, all IFNs signal via an intricate network of Janus kinases, named after the Roman god of time and duality. IFNs are characterized by activities that vary over time and can lead to opposing outcomes. IFNs have protective roles during bacterial, viral, and fungal infections but can also drive numerous inflammatory and autoimmune diseases. In this review, we provide an overview of the cellular and molecular mechanisms governing IFN induction and responses, emphasizing their roles in infections, tumorigenesis, and inflammatory, autoimmune, and genetic diseases, with particular attention to mucosal tissues. Overall, we spotlight how the balanced production of distinct members of the IFN families over time is necessary to exert their protective functions and the detrimental consequences for the host when this balance is lost.

13. A conserved mechanism for the retrieval of polyubiquitinated proteins from cilia.

作者: Sven M Lange.;Jeremy A Bennett.;Robyn J Eisert.;Alan Brown.
来源: Cell. 2025年
The temporospatial distribution of proteins within cilia is regulated by intraflagellar transport (IFT), wherein molecular trains shuttle between the cell body and cilium. Defects in this process impair various signal-transduction pathways and cause ciliopathies. Although K63-linked ubiquitination appears to trigger protein export from cilia, the mechanisms coupling polyubiquitinated proteins to IFT remain unclear. Using a multidisciplinary approach, we demonstrate that a complex of CFAP36, a conserved ciliary protein of previously unknown function, and ARL3, a GTPase involved in ciliary import, binds polyubiquitinated proteins and links them to retrograde IFT trains. CFAP36 uses a coincidence detection mechanism to simultaneously bind two IFT subunits accessible only in retrograde trains. Depleting CFAP36 accumulates K63-linked ubiquitin in cilia and disrupts hedgehog signaling, a pathway reliant on the retrieval of ubiquitinated receptors. These findings advance our understanding of ubiquitin-mediated protein transport and ciliary homeostasis and demonstrate how structural changes in IFT trains achieve cargo selectivity.

14. Shank3 oligomerization governs material properties of the postsynaptic density condensate and synaptic plasticity.

作者: Bowen Jia.;Zeyu Shen.;Shihan Zhu.;Jingguo Huang.;Zhitao Liao.;Shuaizhu Zhao.;Hao Li.;Shiwen Chen.;Yang Xu.;Yu Wang.;Haitang Peng.;Guanhua Bai.;Youming Lu.;Penger Tong.;Wucheng Tao.;Mingjie Zhang.
来源: Cell. 2025年
Cells contain numerous types of membraneless organelles or biological condensates formed via phase separation. Cellular biological condensates have broad material properties ranging from Newtonian fluids to elastic solids. How the material property of a biological condensate is regulated for cellular functions is poorly understood. Here, we discovered that, like native postsynaptic densities (PSDs), the reconstituted PSD condensate forms a soft glass material without signs of irreversible amyloid structure formation. Such glass-like PSD condensate formation is based on percolation of the PSD protein network via specific and multivalent interactions among scaffold proteins. Disruption of Shank3 SAM domain-mediated oligomerization, one type of SHANK3 mutation observed in Phelan-McDermid syndrome patients, softened the PSD condensate by weakening its network percolation, impaired synaptic transmission and plasticity, and caused autistic-like behavior in mice. Thus, our study suggests that the material properties of the PSD condensate are critical for learning and memory mediated by neuronal synapses.

15. Bacteriophages inhibit and evade cGAS-like immune function in bacteria.

作者: Erin Huiting.;Xueli Cao.;Jie Ren.;Januka S Athukoralage.;Zhaorong Luo.;Sukrit Silas.;Na An.;Héloïse Carion.;Yu Zhou.;James S Fraser.;Yue Feng.;Joseph Bondy-Denomy.
来源: Cell. 2025年

16. A receptor antagonist counterbalances multiple systemin phytocytokines in tomato.

作者: Lei Wang.;Louis-Philippe Maier.;Nga Pham.;Yan L Wang.;Xu Wang.;Andreas Schaller.;Judith Fliegmann.;Matthias Erb.;Thomas Boller.;Georg Felix.
来源: Cell. 2025年
Tight regulation of immune activation is crucial for plant health. How plants control the actions of their immunostimulatory phytocytokines is largely unknown. Here, we identify antiSYS as a natural inhibitor of the tomato cytokine systemin. AntiSYS is a systemin-like peptide encoded in a gene cluster with four additional paralogs, three of which comprise newly identified agonistic systemins. AntiSYS is a potent and specific antagonist of the systemin receptor. Tomato mutants lacking antiSYS show aberrant growth and reduced reproductive fitness. These symptoms of antiSYS deficiency are not observed in plants lacking functional systemin receptors, suggesting a role of antiSYS in counterbalancing agonistic systemins. Thus, reminiscent of antagonistic interleukins controlling immune homeostasis in animals, antiSYS serves a crucial role in the regulation of phytocytokine activity in tomato plants.

17. Glycan shielding enables TCR-sufficient allogeneic CAR-T therapy.

作者: Zeguang Wu.;Jinhong Shi.;Qiezhong Lamao.;Yuanyuan Qiu.;Jinxin Yang.;Yang Liu.;Feifei Liang.;Xue Sun.;Wei Tang.;Changya Chen.;Qingming Yang.;Chunmeng Wang.;Zhifang Li.;Haixia Zhang.;Zhonghan Yang.;Yunyi Zhang.;Yuting Yi.;Xufen Zheng.;Yu Sun.;Kuiying Ma.;Lingling Yu.;Huihui Yang.;Zhaoxuan Wang.;Wenjuan Zheng.;Ling Yang.;Zhixuan Zhang.;Yongjian Zhang.;Zhiqiang Wu.;Yao Wang.;Catherine C L Wong.;Ming Jin.;Pengfei Yuan.;Weidong Han.;Wensheng Wei.
来源: Cell. 2025年
Despite the success of autologous chimeric antigen receptor (CAR)-T cell therapy, achieving persistence and avoiding rejection in allogeneic settings remains challenging. We showed that signal peptide peptidase-like 3 (SPPL3) deletion enabled glycan-mediated immune evasion in primary T cells. SPPL3 deletion modified glycan profiles on T cells, restricted ligand accessibility, and reduced allogeneic immunity without compromising the functionality of anti-CD19 CAR molecules. In a phase I clinical trial, SPPL3-null, T cell receptor (TCR)-deficient anti-CD19 allogeneic CAR-T cells reached the safety primary endpoint, with grade 3 or higher cytokine release syndrome (CRS) observed in 3 out of 9 patients with relapsed/refractory B cell non-Hodgkin lymphoma (B-NHL) (ClinicalTrials.gov: NCT06014073). Reverse translational research highlighted the pivotal role of TCR in sustaining T cell persistence. We therefore evaluated the safety of SPPL3-null, TCR-sufficient CAR-T therapy on three patients with lymphoma or leukemia for compassionate care and observed no clinical signs of graft-versus-host disease. Our findings suggest glycan shielding by SPPL3 deletion is a promising direction for optimizing universal CAR-T therapies.

18. Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals.

作者: Simon Haziza.;Radosław Chrapkiewicz.;Yanping Zhang.;Vasily Kruzhilin.;Jane Li.;Jizhou Li.;Geoffroy Delamare.;Rachel Swanson.;György Buzsáki.;Madhuvanthi Kannan.;Ganesh Vasan.;Michael Z Lin.;Hongkui Zeng.;Tanya L Daigle.;Mark J Schnitzer.
来源: Cell. 2025年

19. Simplifying protein engineering with deep learning.

作者: Kevin K Yang.;Ava P Amini.
来源: Cell. 2025年188卷17期4477-4479页
When it comes to deep learning for protein engineering, there is strength in simplicity. In this issue of Cell, through thoughtful deployment of existing fixed-backbone sequence design models, Caixia Gao and colleagues engineer diverse genome editing systems with improved functionality, enabling powerful capabilities in fine-grained and large-scale genome editing as demonstrated through strong experimental validation.

20. Targeting myosin II to alter the disease course of challenging diseases.

作者: Douglas N Robinson.
来源: Cell. 2025年188卷17期4475-4477页
In this issue of Cell, Kenchappa et al. and Radnai et al. report the development of selective non-muscle myosin II inhibitors that show therapeutic potential in glioblastoma and methamphetamine use disorder, opening new avenues for targeting cell mechanobiology in challenging diseases.
共有 23199 条符合本次的查询结果, 用时 1.4556762 秒