Science Translational Medicine最新文献

{"title":"A complete Sigmodon hispidus genome and dynamic single-cell transcriptomics reveal evolutionarily conserved responses to RSV infection","authors":"Shijie Qin,&nbsp;Xiao Qu,&nbsp;Chao Lv,&nbsp;Yali Hou,&nbsp;Xiaoyan Li,&nbsp;Fei Ma,&nbsp;Shuguang Tan,&nbsp;Kefang Liu,&nbsp;Ye Yin,&nbsp;Yi Jing,&nbsp;Xuancheng Lu,&nbsp;Xin Zhao,&nbsp;Xiaopeng Ma,&nbsp;George Fu Gao","doi":"10.1126/scitranslmed.adw7535","DOIUrl":"10.1126/scitranslmed.adw7535","url":null,"abstract":"<div >The cotton rat (<i>Sigmodon hispidus</i>) has emerged as a preclinical model for human respiratory syncytial virus (RSV) research because of its ability to support effective viral replication and recapitulate disease; however, the mechanisms supporting this evolutionarily conserved phenotype remain unclear. Here, we report both the chromosomal genome and respiratory single-cell transcriptomic atlas of the cotton rat throughout the course of RSV infection. Phylogenetic analysis showed that cotton rats are in different evolutionary branches from common mouse and rat models and exhibit substantial conservation of tissue profiles with humans. The respiratory cell atlas, alveolar cell trajectory, and distribution of potential viral receptors are also similar to those of humans, explaining the superiority of cotton rats as an RSV infection model. The target cells of RSV, including club cells, secretory2 cells, mesothelial cells, and nerve-associated astrocytes, were expanded after infection. We also identified differential transcriptional regulators, specific antiviral proteins, and cytokines that could be translated into potential clinical markers in humans. Candidate host factors were also identified, which will enable the exploration of host-RSV interactions and offer a source of therapeutic targets.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 816","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in HIV-1 reservoir cell selection are linked to altered innate immune profiles","authors":"Toong Seng Tan,&nbsp;Ce Gao,&nbsp;Alexander S. Hochroth,&nbsp;Liliana Vela,&nbsp;Leah Carrere,&nbsp;Sruthi Kalavacherla,&nbsp;Seohyun Hong,&nbsp;Melanie Lancien,&nbsp;Chloe M. Naasz,&nbsp;Aischa Niesar,&nbsp;Samantha K. Marzi,&nbsp;Isabelle C. Roseto,&nbsp;Benjamin Bone,&nbsp;Xiaodong Lian,&nbsp;Yuko Yuki,&nbsp;Mathias Viard,&nbsp;Rebecca Hoh,&nbsp;Deborah K. McMahon,&nbsp;Ronald J. Bosch,&nbsp;Seble G. Kassaye,&nbsp;Rajesh T. Gandhi,&nbsp;Mary Carrington,&nbsp;Steven G. Deeks,&nbsp;Phyllis C. Tien,&nbsp;Michael J. Peluso,&nbsp;Jeffrey M. Jacobson,&nbsp;Mathias Lichterfeld,&nbsp;Xu G. Yu","doi":"10.1126/scitranslmed.adu7154","DOIUrl":"10.1126/scitranslmed.adu7154","url":null,"abstract":"<div >HIV-1 persistence despite suppressive antiretroviral therapy (ART) is primarily because of infected memory CD4 T cells, so-called viral reservoir cells, that harbor chromosomally integrated viral DNA as a “provirus” and resist clearance by the human immune system. Biological sex affects host immune responses and may influence selection and evolution of HIV-1 reservoir cells during long-term ART for HIV infection. We assessed more than 4073 individual proviruses through single-molecule amplification from 30 females and 35 males living with HIV-1 and treated with ART for a median of 20 years. We observed that the HIV-1 reservoir profile in females was characterized by lower proviral phylogenetic complexity, an increased proportion of clonally expanded intact proviruses, and a higher proportion of intact proviruses integrated into repressive heterochromatin locations of the human genome. The evolution of this distinct viral reservoir profile in females was associated with an improved signature of innate immune responses, specifically those of NK cells. On the contrary, signs of viral sequence adaptation to adaptive T cell immune responses were more pronounced in intact HIV-1 proviruses from males. Collectively, these data suggest a stronger ability of the female immune system to drive immune selection of HIV-1 reservoir cells during ART, putatively because of improved innate immune function.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 816","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1–targeted cis-delivery of an IL-2 variant induces a multifaceted antitumoral T cell response in human lung cancer","authors":"Irene Fusi,&nbsp;Clara Serger,&nbsp;Petra Herzig,&nbsp;Markus Germann,&nbsp;Michael T. Sandholzer1,&nbsp;Nicole Oelgarth1,&nbsp;Petra C. Schwalie,&nbsp;Leyla Don,&nbsp;Viola K. Vetter,&nbsp;Viktor H. Koelzer,&nbsp;Didier Lardinois,&nbsp;Henry Kao,&nbsp;Laura Codarri Deak,&nbsp;Pablo Umaña,&nbsp;Christian Klein,&nbsp;Aljaz Hojski,&nbsp;Marina Natoli,&nbsp;Alfred Zippelius","doi":"10.1126/scitranslmed.adr3718","DOIUrl":"10.1126/scitranslmed.adr3718","url":null,"abstract":"<div >Antibody-cytokine fusion proteins are being developed as next-generation cancer immunotherapies, aiming to deliver activation signals to targeted immune populations. Among these, PD1-IL2v—an engineered interleukin-2 variant (IL-2v) lacking CD25 binding, fused to a high-affinity programmed cell death protein 1 (PD-1) blocking antibody—has shown promising results in murine tumor models. Here, using human model systems, we show that PD1-IL2v elicits a multifaceted antitumor T cell response by targeting both CD8⁺ and conventional CD4⁺ T (T_conv) cells. Single-cell RNA sequencing (scRNAseq) on a lung cancer patient–derived tumor fragment (PDTF) platform revealed that PD1-IL2v drives the expansion of proliferative, cytotoxic CD8⁺ T cells exhibiting features of tumor reactivity. This was accompanied by up-regulation of CXCR6, enhancing their migratory capacity. In T_conv cells, PD1-IL2v up-regulated CXCL13 expression and promoted a T follicular helper/T helper 1 (T_FH/T_H1)–like transcriptional program associated with anti-PD1 responsiveness. Our findings provide mechanistic insights into the effects of IL-2v–targeted delivery to PD-1⁺ cells within human tumors, supporting the clinical development of next-generation immunocytokines.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 816","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal antibody titers measured after COVID-19 mRNA vaccination can identify individuals at risk for subsequent infection","authors":"Hyeongki Park,&nbsp;Naotoshi Nakamura,&nbsp;Sho Miyamoto,&nbsp;Yoshitaka Sato,&nbsp;Kwang Su Kim,&nbsp;Kosaku Kitagawa,&nbsp;Yurie Kobashi,&nbsp;Yuta Tani,&nbsp;Yuzo Shimazu,&nbsp;Tianchen Zhao,&nbsp;Yoshitaka Nishikawa,&nbsp;Fumiya Omata,&nbsp;Moe Kawashima,&nbsp;Toshiki Abe,&nbsp;Yoshika Saito,&nbsp;Saori Nonaka,&nbsp;Morihito Takita,&nbsp;Chika Yamamoto,&nbsp;Hiroshi Morioka,&nbsp;Katsuhiro Kato,&nbsp;Ken Sagou,&nbsp;Tetsuya Yagi,&nbsp;Takeshi Kawamura,&nbsp;Akira Sugiyama,&nbsp;Aya Nakayama,&nbsp;Yudai Kaneko,&nbsp;Risa Yokokawa Shibata,&nbsp;Kazuyuki Aihara,&nbsp;Tatsuhiko Kodama,&nbsp;Akifumi Kamiyama,&nbsp;Tomokazu Tamura,&nbsp;Takasuke Fukuhara,&nbsp;Kenji Shibuya,&nbsp;Tadaki Suzuki,&nbsp;Shingo Iwami,&nbsp;Masaharu Tsubokura","doi":"10.1126/scitranslmed.adv4214","DOIUrl":"10.1126/scitranslmed.adv4214","url":null,"abstract":"<div >A key issue in the post–COVID-19 pandemic era is the ongoing administration of COVID-19 vaccines. Repeated vaccination is essential for preparing against currently circulating and newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, optimizing vaccination strategies is crucial to efficiently manage medical resources and establish an effective vaccination framework. Therefore, a strategy to identify poor responders with lower sustained antibody titers would be beneficial because these individuals should be considered high priority for revaccination. We investigated longitudinal antibody titer data in a cohort of 2526 people in Fukushima, Japan, collected between April 2021 and November 2022. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers after two primary doses and one booster dose of COVID-19 messenger RNA vaccines. We identified three populations, which we refer to as the durable, the vulnerable, and the rapid-decliner populations, and approximately half of the participants remained in the same population after the booster dose. The rapid-decliner population experienced earlier infections than the others. Furthermore, when comparing spike protein–specific immunoglobulin G (IgG) titers, spike protein–specific IgA titers, and SARS-CoV-2–specific T cell responses between participants who experienced subsequent infections after booster vaccination and those who did not, we found that spike protein–specific IgA titers were lower during the early stage after booster vaccination in participants who went on to become infected with SARS-CoV-2. This approach could be used to inform policy decisions on vaccine distribution to maximize population-level immunity both in future pandemics and in the post–COVID-19 pandemic era.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 816","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/scitranslmed.adv4214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal spreading depolarization as a driver of postictal ambulation","authors":"Bence Mitlasóczki,&nbsp;Adrián Gutiérrez Gómez,&nbsp;Midia Kamali,&nbsp;Natalia Babushkina,&nbsp;Mayan Baues,&nbsp;Laura Kück,&nbsp;André Nathan Haubrich,&nbsp;Theodoros Tamiolakis,&nbsp;Annika Breuer,&nbsp;Simon Granak,&nbsp;Merlin Schwering-Sohnrey,&nbsp;Ingo Gerhauser,&nbsp;Wolfgang Baumgärtner,&nbsp;Martin Karl Schwarz,&nbsp;Laura Ewell,&nbsp;Thoralf Opitz,&nbsp;Julika Pitsch,&nbsp;Simon Musall,&nbsp;Rainer Surges,&nbsp;Florian Mormann,&nbsp;Heinz Beck,&nbsp;Michael Wenzel","doi":"10.1126/scitranslmed.adv3260","DOIUrl":"10.1126/scitranslmed.adv3260","url":null,"abstract":"<div >Postseizure (postictal) symptoms are regularly encountered in epilepsy and can be life threatening, yet their neurobiological underpinnings remain understudied. Using two-photon or widefield imaging, field potential and unit recordings, optogenetics, and basic behavioral assessment under healthy conditions or viral encephalitis, we studied seizures and postictal symptoms in mice. We show a propensity of the hippocampus for seizure-associated spreading depolarization (sSD). Through optogenetic stimulation, we provide evidence that induced isolated hippocampal SD is sufficient to elicit postictal ambulation (PIA), whereas induced isolated seizure-like episodes are not. Furthermore, PIA occurred in the absence of SD progression to the neocortex. In addition, we analyzed Behnke-Fried depth-electrode recordings in four patients with focal epilepsy. Of 13 recorded seizures, we observed five slow shifts at seizure termination in the regionwise analysis that could reflect putative sSD. In support of our experiments in mice, we also found an increased vulnerability of the human temporomesial system (hippocampus and amygdala) for this phenomenon and longer recovery times of affected as compared with nonaffected brain regions. This work suggests sSD as a previously underrecognized pathoclinical entity underlying distinct postictal symptoms in epilepsy.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 816","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Export by a quorum sensing–controlled drug exporter underlies rifampicin’s strong activity against staphylococcal biofilms","authors":"Yao Liu,&nbsp;Lei He,&nbsp;Ryan Liu,&nbsp;Dylan J. Burgin,&nbsp;Min Li,&nbsp;Michael Otto","doi":"10.1126/scitranslmed.adq8328","DOIUrl":"10.1126/scitranslmed.adq8328","url":null,"abstract":"<div >Biofilm infections on indwelling medical devices are a major cause of health care–associated infection and mortality. Most of these infections are caused by staphylococci. Biofilm formation presents a continued clinical challenge because of the association with dramatically increased nonspecific antimicrobial resistance. Unlike most antibiotics, rifampicin is active against staphylococcal biofilm infections; however, the mechanism is unknown. Using in vitro assays and mouse models of biofilm infection, we show here that rifampicin is more effective than other antibiotics against staphylococcal <i>agr</i> mutants, which are linked to serious biofilm infections because they produce extended biofilms. We found that this superiority results from an Agr-controlled rifampicin efflux system, which makes <i>agr</i> mutant biofilms less resistant to rifampicin, rather than more resistant, than they are to other antibiotics. Our study provides a scientific rationale supporting the use of rifampicin in staphylococcal biofilm infections and emphasizes the importance of understanding genetic adaptations during infection for the use and development of biofilm therapeutics.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 816","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis","authors":"Hongxue Shi,&nbsp;Xiaobo Wang,&nbsp;Christopher Sloas,&nbsp;Brennan Gerlach,&nbsp;Arif Yurdagul Jr.,&nbsp;Mary P. Moore,&nbsp;Eui Jung Jung,&nbsp;Faridoddin Mirshahi,&nbsp;Luisa Ronzoni,&nbsp;Arun J. Sanyal,&nbsp;Luca Valenti,&nbsp;Chyuan-Sheng Lin,&nbsp;James Montgomery,&nbsp;Bradley Zinker,&nbsp;Michael Klichinsky,&nbsp;Ira Tabas","doi":"10.1126/scitranslmed.adv2106","DOIUrl":"10.1126/scitranslmed.adv2106","url":null,"abstract":"<div >Hepatocyte apoptosis is a key feature of metabolic dysfunction–associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene <i>Timd4</i>) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid–defined (HF-CDAA) diet. Apoptotic hepatocyte accumulation is associated with impaired efferocytosis and loss of TIM4. Administration of neutralizing anti-TIM4 antibodies or genetic deletion of <i>Timd4</i> in Kupffer cells of FPC and HF-CDAA diet–fed mice decreased efferocytosis by liver macrophages, increased profibrotic activation of collagen-producing hepatic stellate cells (HSCs), and accelerated the progression to fibrotic MASH. Genetic restoration of macrophage <i>Timd4</i> in FPC and HF-CDAA diet–fed MASH mice or cell therapy with TIM4⁺ macrophages enhanced apoptotic hepatocyte clearance and decreased HSC activation and liver fibrosis. Studies using an ex vivo macrophage HSC cross-talk model and the HF-CDAA MASH model revealed that inactivation of HSCs by efferocytosing macrophages involved macrophage reprogramming to secrete interleukin-10 (IL-10), which activated the IL-10 receptor on HSCs to dampen their profibrotic activation. These findings reveal a key process in the progression from hepatic steatosis to early MASH fibrosis and identify a mechanism-based therapeutic strategy to prevent fibrotic MASH progression.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 815","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized, double-blind, placebo-controlled phase 1 trial of the topical pan–lysyl oxidase inhibitor PXS-6302 in mature scars","authors":"Natalie Morellini,&nbsp;Peijun Gong,&nbsp;Suzanne Rea,&nbsp;Helen Douglas,&nbsp;Phuoc Hao Ho,&nbsp;Barry Cense,&nbsp;Brendan F. Kennedy,&nbsp;Wolfgang Jarolimek,&nbsp;Brett Charlton,&nbsp;Alison Findlay,&nbsp;Joanna Leadbetter,&nbsp;Fiona M. Wood,&nbsp;Mark W. Fear","doi":"10.1126/scitranslmed.adv2471","DOIUrl":"10.1126/scitranslmed.adv2471","url":null,"abstract":"<div >Skin scars remain a substantial clinical challenge because of their impact on appearance and psychological well-being. Lysyl oxidases catalyze collagen cross-linking, a key factor in scar development. Here, we report a randomized, double-blind, placebo-controlled phase 1 study to assess the safety and tolerability of PXS-6302, a topical pan–lysyl oxidase inhibitor, in treating mature scars (ACTRN12621001545853). Fifty participants were enrolled across two cohorts: Cohort 1 (open label, <i>n</i> = 8) applied PXS-6302 (2%) daily, and cohort 2 (<i>n</i> = 42) was randomized 1:1 to apply PXS-6302 (2%) or placebo three times per week to a 10-square-centimeter area of scar for 3 months. No severe adverse events (AEs) were reported. Mild to moderate localized skin reactions were the only treatment-related AEs, leading to discontinuation by six participants. Treatment with PXS-6302 three times per week reduced lysyl oxidase activity by 66% and decreased hydroxyproline (a marker for collagen) and total protein concentrations in scar biopsies compared with placebo. Optical coherence tomography showed increased microvessel density and tissue attenuation [a marker of extracellular matrix (ECM) composition] at 3 months compared with the baseline, suggesting ECM remodeling toward unscarred skin architecture. No significant differences in Patient Observer Scar Assessment Scale (POSAS) scores were observed between groups after 90 days of treatment once baseline imbalances were accounted for. Together, these data showed that topical pan–lysyl oxidase inhibition was generally well tolerated and altered some measures of the ECM in mature scars, supporting the advancement of this treatment into phase 2 trials.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 815","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A soft robotic device for rapid and self-guided intubation","authors":"David A. Haggerty,&nbsp;James R. Cazzoli,&nbsp;Marvin A. Wayne,&nbsp;Christopher J. Winckler,&nbsp;David A. Wampler,&nbsp;Jeffrey L. Jarvis,&nbsp;Lichy Han,&nbsp;Linus Rydell,&nbsp;Aman Mahajan,&nbsp;Jose P. Zevallos,&nbsp;David R. Drover,&nbsp;Elliot W. Hawkes","doi":"10.1126/scitranslmed.ads7681","DOIUrl":"10.1126/scitranslmed.ads7681","url":null,"abstract":"<div >Endotracheal intubation is a critical medical procedure for protecting a patient’s airway. Current intubation technology requires extensive anatomical knowledge, training, technical skill, and a clear view of the glottic opening. However, all of these may be limited during emergency care for trauma and cardiac arrest outside the hospital, where first-pass failure is nearly 35%. To address this challenge, we designed a soft robotic device to autonomously guide a breathing tube into the trachea with the goal of allowing rapid, repeatable, and safe intubation without the need for extensive training, skill, anatomical knowledge, or a glottic view. During initial device testing with highly trained users in a mannequin and a cadaver, we found a 100% success rate and an average intubation duration of under 8 s. We then conducted a preliminary study comparing the device with video laryngoscopy, in which prehospital medical providers with 5 min of device training intubated cadavers. When using the device, users achieved an 87% first-pass success rate and a 96% overall success rate, requiring an average of 1.1 attempts and 21 s for successful intubation, significantly (<i>P</i> = 0.008) faster than with video laryngoscopy. When using video laryngoscopy, the users achieved a 63% first-pass success rate and a 92% overall success rate, requiring an average of 1.6 attempts and 44 s for successful intubation. This preliminary study offers directions for future clinical studies, the next step in testing a device that could address the critical needs of emergency airway management and help democratize intubation.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 815","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques","authors":"Maya Sangesland,&nbsp;Ning Li,&nbsp;Yaroslav Tsybovsky,&nbsp;Megan D. Rodgers,&nbsp;Julianna Han,&nbsp;Alesandra J. Rodriguez,&nbsp;James A. Ferguson,&nbsp;Amy R. Henry,&nbsp;Sarah C. Smith,&nbsp;Jesmine Roberts-Torres,&nbsp;Rebecca A. Gillespie,&nbsp;Cuiping Liu,&nbsp;Jonah S. Merriam,&nbsp;Tyler Stephens,&nbsp;Connor Williams,&nbsp;Emma Walker,&nbsp;Martin Corcoran,&nbsp;Michelle Ravichandran,&nbsp;Adrian Creanga,&nbsp;Sarah F. Andrews,&nbsp;Theodore C. Pierson,&nbsp;Gunilla B. Karlsson Hedestam,&nbsp;Chaim A. Schramm,&nbsp;Douglas S. Reed,&nbsp;Daniel C. Douek,&nbsp;Tongqing Zhou,&nbsp;Andrew B. Ward,&nbsp;Masaru Kanekiyo","doi":"10.1126/scitranslmed.ady3570","DOIUrl":"10.1126/scitranslmed.ady3570","url":null,"abstract":"<div >Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V_H1-138, the macaque homolog of human V_H1-69, a V_H gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs containing the canonical NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded structural motifs. These findings indicate that the macaque immunoglobulin repertoire can support humanlike public bnAb responses to influenza HA, highlighting the value of the macaque model for translational vaccinology. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans have been similarly shaped during evolution.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 815","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}