Recent Publications

Nat Cell Biol. 2026 Mar 6. doi: 10.1038/s41556-026-01886-z. Online ahead of print.

ABSTRACT

Pattern recognition receptor (PRR)-induced interferon (IFN) is critical for effective immunity. The PRRs Toll-like receptor (TLR) 3, TLR4 and cyclic GMP-AMP synthase (cGAS), together with the stimulator of IFN genes (STING), signal through TANK-binding kinase 1 (TBK1), which activates the type-I/III IFN-inducing transcription factor interferon-response factor 3 (IRF3). The mechanism by which these PRRs activate TBK1 remains unresolved. Here we show that lysine-11 (K11)-linked ubiquitination drives TBK1 activation by these PRRs. The E3 ligase ANKIB1 attaches K11-linked ubiquitin chains to components of the TLR3- and cGAS-STING-induced signalosomes. This facilitates Optineurin recruitment to these complexes, in turn enabling recruitment and activation of TBK1 and IRF3, defining an uncharacterized signalling axis. In mice, ANKIB1 deficiency dampens IFN induction via TLR3 and cGAS-STING, reducing interferonopathy and compromising protection against HSV-1, respectively. Together, our results demonstrate an unanticipated and critical role for ANKIB1-generated K11-linked ubiquitination in the immune response activated by cGAS-STING, TLR3 and TLR4.

PMID:41792265 | DOI:10.1038/s41556-026-01886-z

Front Immunol. 2026 Feb 17;17:1745692. doi: 10.3389/fimmu.2026.1745692. eCollection 2026.

ABSTRACT

INTRODUCTION: New biomarkers are needed for better stratification and personalized treatment of Systemic Lupus Erythematosus (SLE). Phosphoinositide 3-kinase δ (PI3Kδ) has been implicated in SLE pathogenesis. Here, we investigated whether a subset of SLE patients has increased PI3Kδ activity after T cell activation.

METHODS: T cells were isolated from frozen PBMCs of 108 SLE patients, 19 healthy controls, and one patient with Activated PI3K Delta syndrome (APDS), which provided a benchmark of increased PI3Kδ activity. After 90-minute anti-CD3/CD28 stimulation, phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 4,5-bisphosphate (PIP2) were measured using high-performance liquid chromatography-mass spectrometry.

RESULTS: Higher levels of PIP3 (measured as the ratio of PIP3/PIP2) in stimulated T cells distinguished APDS patient from other subjects providing a useful biomarker of increased PI3Kδ activity. We observed no significant difference in T-cell PIP3 levels between SLE patients and healthy controls. However, a subset of SLE patients (n = 4) exhibited strong upregulation of PIP3 following T-cell stimulation, comparable to that observed in the APDS patient. PIP3 levels in stimulated T cells positively correlated with the frequency of CD4+ T cells and negatively correlated with the frequencies of CD8+, EMRA CD4+, and EMRA CD8+ T cells.

CONCLUSIONS: We describe the range of variation of PI3Kδ activity in T cells from a large cohort of patients with SLE and from healthy subjects. Our findings suggest that increased PI3Kδ activity is not associated with SLE in general, although some SLE patients exhibit a particularly strong upregulation of PIP3 levels after T-cell stimulation. This subgroup of SLE patients warrants further investigation given the promising effect of PI3Kδ inhibitors in restoring normal immune regulation.

PMID:41782874 | PMC:PMC12953358 | DOI:10.3389/fimmu.2026.1745692

Sci Rep. 2026 Mar 4. doi: 10.1038/s41598-026-42003-2. Online ahead of print.

ABSTRACT

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), remains a pressing global health challenge, with a high burden in West Africa, including The Gambia. Understanding the genetic diversity of circulating MTBC strains is essential for improving diagnosis, surveillance and treatment strategies. In this study, we characterise the population structure and drug resistance landscape of MTBC strains circulating in The Gambia over nearly two decades (2002-2021). We analysed whole-genome sequencing (WGS) data from 1,803 TB isolates. Lineage 4 (L4) was predominant (67.2%), followed by the West Africa-restricted lineage 6 (L6, 26.6%), with L4 exhibiting greater genetic diversification over time. Drug susceptibility profiling of these isolates revealed that 78% (1421/1803) were drug-susceptible, while 6.5% (119/1803) harboured resistance to first-line drugs, primarily to isoniazid, rifampicin, or both. Notably, 15.5% (282/1803) isolates carried mutations classified as having uncertain significance according to the WHO resistance catalogue. Comparative analyses revealed a lineage 6-specific ethambutol-associated mutation of uncertain significance (embC Ala307Thr) occurring at a higher frequency in Gambian isolates than in the broader West Africa region or globally. Structural modelling demonstrated that many first-line drug resistance mutations are located in highly conserved, solvent-inaccessible regions of target proteins, often impacting protein stability, suggesting a trade-off between drug resistance, bacterial fitness, and evolutionary adaptation. Together, these findings highlight the coexistence of globally widespread and regionally restricted MTBC lineages in The Gambia and reveal a substantial burden of resistance-associated mutations of uncertain significance in the WHO catalogue. Sustained genomic surveillance and region-specific interpretation of resistance mutations are essential to support End TB strategies in high-burden settings.

PMID:41781593 | DOI:10.1038/s41598-026-42003-2

J Gen Virol. 2026 Mar;107(3):002237. doi: 10.1099/jgv.0.002237.

ABSTRACT

Herpes simplex virus (HSV)-1 infection of cortical neurones is a leading cause of encephalitis. Whilst we have substantial knowledge about the molecular virology of HSV-1 lytic infection in cells of the periphery, like keratinocytes or fibroblasts, we know much less about infection of human neurones owing to the challenges of working with neuronal cell-based models. Here, we demonstrate the use of a human induced pluripotent stem cell-derived cortical neurone model (i3Neurones) for HSV-1 infection. i3Neurones are highly scalable and can be rapidly and efficiently differentiated into an isogenic population of cortical glutamatergic neurones. We show that i3Neurones support the full HSV-1 lytic replication cycle. We present an optimized protocol for the infection of i3Neurones with HSV-1 that allows their synchronous infection at near-100% efficiency and optimized fixation methods that preserve organelle and neurite structure for immunocytochemistry analysis. Our study highlights i3Neurones as a robust, scalable platform for microscopy and biochemical studies of HSV-1 and other neurotropic pathogens.

PMID:41770591 | PMC:PMC12952538 | DOI:10.1099/jgv.0.002237

Health Place. 2026 Feb 23;98:103635. doi: 10.1016/j.healthplace.2026.103635. Online ahead of print.

ABSTRACT

This study describes the provision of calorie labelling in the digital out-of-home food sector after the implementation of mandatory calorie labelling for large businesses in England in April 2022. Using online menu data from two major food delivery services between June 2022 and October 2023, the number of restaurants available for delivery and the share of restaurants displaying calories was determined for every neighbourhood (Lower layer Super Output Area/Data Zone) in Great Britain. Among restaurants that display calories, we determined the share of labelled menu items and these items' calorie content. We assessed differences by area deprivation and restaurant type. Online food delivery was available in ∼89% of Great Britain, with more restaurants available in more deprived neighbourhoods. The share of restaurants that display calories was overall low and decreasing over time (median 14% in June 2022 to 12% in October 2023), and was lowest in most deprived (9%) compared with 14% in the least deprived neighbourhoods in October 2023. Among restaurants displaying calories, the share of labelled items was high (79%-76%), while calorie content decreased slightly (by 14 kcal/food item and 5 kcal/drink item). Changes by deprivation were limited and heterogenous by restaurant type. The observed, small reduction in median calorie content may suggest positive, structural change and warrants further investigation. However, the coverage of calorie labelling is limited, and the lower provision in more deprived neighbourhoods may widen dietary health inequalities.

PMID:41734677 | DOI:10.1016/j.healthplace.2026.103635

iScience. 2026 Jan 20;29(2):114759. doi: 10.1016/j.isci.2026.114759. eCollection 2026 Feb 20.

ABSTRACT

Breast cancer immune response is important to patient outcome, but the prognostic interaction between tissue-infiltrating immune cell (TIIC) types is not well-characterized. We evaluated the associations between CD8+, FOXP3+, CD20+, and CD163+ TIICs and breast cancer-specific survival (BCSS). We developed an AI in Halo to score TIIC percentage by compartment (overall, stromal, or intra-tumoral) in 99,051 microarray images from 12,285 female breast cancers. The associations between log-transformed TIIC scores and BCSS were assessed using Cox regression. CD8+ and FOXP3+ TIICs were associated with better BCSS in ER-negative disease; CD8+ and CD20+ TIICs were associated with a better prognosis in ER-positive disease; and CD163+ TIICs were associated with a poorer prognosis in ER-positive disease in multi-marker models. These results may have implications for breast cancer immunotherapy.

PMID:41732488 | PMC:PMC12925133 | DOI:10.1016/j.isci.2026.114759

Popul Stud (Camb). 2026 Feb 16:1-15. doi: 10.1080/00324728.2026.2620692. Online ahead of print.

ABSTRACT

This paper uses population smallpox mortality rates in eighteenth-century Sweden and the death toll from the 1707-09 smallpox epidemic in Iceland to estimate plausible ranges for the case fatality rate (CFR) of smallpox (Variola major). We find that smallpox CFRs could be extremely high (43-55 per cent) when smallpox attacked a population where both children and adults were susceptible, as in Iceland. However, where smallpox was endemic and therefore a disease of childhood, as in Sweden, the estimated CFR is only 8-10 per cent: far lower than the consensus CFR of 20-30 per cent. We argue that social factors explain these differences. Where both adults and children were susceptible, smallpox epidemics fundamentally disrupted basic household tasks and nursing of the sick, dramatically increasing the CFR. Thus, when historians and epidemiologists give CFRs for smallpox, they should consider the population and context rather than relying on an implausible intrinsic CFR of 20-30 per cent.

PMID:41693525 | DOI:10.1080/00324728.2026.2620692

Nat Commun. 2026 Feb 14. doi: 10.1038/s41467-026-69336-w. Online ahead of print.

ABSTRACT

Designing synthetic biomolecular condensates, or membraneless organelles, offers insights into the functions of their natural counterparts and is equally valuable for cellular and metabolic engineering. Choosing E. coli for its biotechnological relevance, we deploy RNA nanotechnology to design and express non-natural membraneless organelles in vivo. The designer condensates assemble co-transcriptionally from branched RNA motifs interacting via base-pairing. Exploiting binding selectivity, we express orthogonal, non-mixing condensates, and by embedding a protein-binding aptamer, we achieve selective protein recruitment. Condensates can be made to dissolve and reassemble upon thermal cycling, thereby reversibly releasing and re-capturing protein clients. The synthetic organelles are expressed robustly across the cell population and remain stable despite enzymatic RNA processing. Compared with existing solutions based on peptide building blocks or repetitive RNA sequences, these nanostructured RNA motifs enable algorithmic control over interactions, affinity for clients, and condensate microstructure, opening further directions in synthetic biology and biotechnology.

PMID:41688461 | DOI:10.1038/s41467-026-69336-w

Influenza Other Respir Viruses. 2026 Feb;20(2):e70230. doi: 10.1111/irv.70230.

ABSTRACT

BACKGROUND: Genomic surveillance of human seasonal influenza viruses is an essential component of the Global Influenza Surveillance and Response system (GISRS) and informs the recommendations for the seasonal influenza vaccine composition. Phylogenetic analysis of viral genome sequences is used to identify groups of viruses sharing potential antigenic change, and computational models are used to predict which viral variants are likely to circulate at high levels in upcoming seasons. To facilitate discussion and reporting of genetic diversity, as well as to communicate antigen recommendations, up-to-date and sufficiently granular definitions of genetic clades are important.

METHODS: We implemented a nomenclature system for Segments 4 (haemagglutinin) and 6 (neuraminidase) of human Influenza A(H3N2), A(H1N1)pdm09, and Influenza B that dynamically adapts to the diversity of circulating viruses. New subclades were proposed by a clade suggestion algorithm based on criteria including (i) the number of sequences in the group, (ii) the distance from the direct parent clade, and (iii) the weighted number of amino acid substitutions on the branch leading to the common ancestor of the subclade.

RESULTS: Algorithmic clade proposals were reviewed and assigned a systematic hierarchical label consisting of a leading letter, followed by numbers (e.g., G.1.3). Names are kept short by aliasing that is collapsing prefixes into unique letters. Subclade definitions are shared openly to promote adoption and tool development. Nextclade is supporting this new nomenclature, and it is being used routinely by the GISRS network.

CONCLUSIONS: With increasing genomic surveillance, the need for up-to-date classification schemes is growing and we hope that the current dynamic proposal will adapt to growing data volumes and aid in simplifying the interpretation of these data.

PMID:41688063 | PMC:PMC12904685 | DOI:10.1111/irv.70230

PLoS Pathog. 2026 Feb 9;22(2):e1013967. doi: 10.1371/journal.ppat.1013967. eCollection 2026 Feb.

ABSTRACT

Enteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and the main polyprotein. In some enteroviruses, in addition to the canonical upstream AUG (uAUG), there is another AUG that may represent an alternative upstream initiation site. An analysis of enterovirus sequences containing additional upstream AUGs identified several clusters, including strains of pathogenic Enterovirus alphacoxsackie and E. coxsackiepol. Using ribosome profiling on coxsackievirus CVA13 (E. coxsackiepol), we demonstrate that both upstream AUG codons can be used for translation initiation in infected cells. Moreover, we confirm translation from both upstream AUGs using a reporter system. Mutating the additional upstream AUG in the context of CVA13 did not result in phenotypic changes in immortalized cell lines. However, the wild-type virus outcompeted this mutant in human intestinal organoids and differentiated neuronal systems, representing an advantage in physiologically relevant infection sites. Mutation of the stop codon of the shorter upstream ORF led to dysregulated translation of the other ORFs in the reporter system, suggesting a potential role for the additional uORF in modulating the expression level of the other ORFs. Additionally, we demonstrate regulation of uORF translation in response to stress. These findings reveal the remarkable plasticity of enterovirus IRES-mediated initiation and the competitive advantage of double-upstream-AUG-containing viruses in terminally differentiated intestinal organoids and neuronal systems.

PMID:41662385 | PMC:PMC12904569 | DOI:10.1371/journal.ppat.1013967

bioRxiv [Preprint]. 2026 Jan 30:2026.01.28.702248. doi: 10.64898/2026.01.28.702248.

ABSTRACT

Phagocytosis is a fundamental process of the innate immune system, yet the physical determinants that govern the engulfment of soft, deformable targets remain poorly understood. Existing theoretical models typically approximate targets as rigid particles, overlooking the fact that both immune cells and many biological targets undergo significant membrane deformation during contact. Here, we develop a Monte Carlo-based membrane simulation framework to model the interactions of multiple vesicles, enabling us to explore phagocytosis-like processes in systems where both the phagocyte and the target possess flexible, thermally fluctuating membranes. We first validate our approach against established observations for the engulfment of rigid objects. We then investigate how the mechanical properties of a soft target-specifically membrane bending rigidity govern the outcome of phagocytic interactions. Our simulations reveal three distinct mechanical regimes: (i) biting or trogocytosis, in which the phagocyte extracts a portion of the target vesicle; (ii) pushing, where the target is displaced rather than engulfed; and (iii) full engulfment, in which the target is completely internalized. Increasing membrane tension via internal pressure produces analogous transitions, demonstrating a unified mechanical origin for these behaviours. Qualitative comparison with experiments involving Giant Unilamellar Vesicles (GUVs, deformable microparticles) and lymphoma cells supports the relevance of these regimes to biological phagocytosis. Together, these results highlight how target deformability fundamentally shapes phagocytic success and suggest that immune cells may exploit mechanical cues to recognize among different classes of soft targets.

PMID:41659410 | PMC:PMC12873970 | DOI:10.64898/2026.01.28.702248

Front Vet Sci. 2026 Jan 21;12:1690335. doi: 10.3389/fvets.2025.1690335. eCollection 2025.

ABSTRACT

Positive deviant (PD) farmers can be differentiated from the wider farming community by their inherent capacity to leverage farming innovations and technologies in addressing challenges faced in engaging in agricultural production. There is currently a limited body of literature on how positive deviance and entrepreneurial behavior allow some dairy farmers to develop strategies that enable them to cope better with and creatively overcome challenges faced by their peers. This study employed a positive deviance approach to identify innovative dairy farmers in urban and peri-urban areas of the Addis Ababa and Oromia administrative regions of Ethiopia. PD farmers were identified and selected through a descriptive study design, utilizing a purposive and snowball sampling approach based on the number of technologies adopted in a previous survey study and referrals from other farmers. Data were collected through key informant interviews and participant observation on selected farms. We observed that PD dairy farmers had adopted and/or modified a variety of technologies to overcome context-specific challenges faced, such as seasonal feed shortages exacerbated by climate change, reduced land size and availability of land for grazing and waste disposal, and restrictions on farming resulting from the development of urban areas. These technologies enabled farmers to improve feed production, manure disposal, breeding practices, the quality of livestock housing, and animal welfare and enabled them to control diseases and add value to milk production. This study underscores the important role that PD dairy farmers could play as social referents, not only for their peers in urban and peri-urban areas but also for policymakers, extension workers and academics who are interested in working with dairy farmers in co-identifying and co-developing solutions to challenges currently undermining the sustainability of the dairy sector in Ethiopia and beyond.

PMID:41647432 | PMC:PMC12870667 | DOI:10.3389/fvets.2025.1690335

ArXiv [Preprint]. 2026 Jan 28:arXiv:2601.20719v1.

ABSTRACT

Phagocytosis is a fundamental process of the innate immune system, yet the physical determinants that govern the engulfment of soft, deformable targets remain poorly understood. Existing theoretical models typically approximate targets as rigid particles, overlooking the fact that both immune cells and many biological targets undergo significant membrane deformation during contact. Here, we develop a Monte Carlo-based membrane simulation framework to model the interactions of multiple vesicles, enabling us to explore phagocytosis-like processes in systems where both the phagocyte and the target possess flexible, thermally fluctuating membranes. We first validate our approach against established observations for the engulfment of rigid objects. We then investigate how the mechanical properties of a soft target-specifically membrane bending rigidity govern the outcome of phagocytic interactions. Our simulations reveal three distinct mechanical regimes: (i) biting or trogocytosis, in which the phagocyte extracts a portion of the target vesicle; (ii) pushing, where the target is displaced rather than engulfed; and (iii) full engulfment, in which the target is completely internalized. Increasing membrane tension via internal pressure produces analogous transitions, demonstrating a unified mechanical origin for these behaviours. Qualitative comparison with experiments involving Giant Unilamellar Vesicles (GUVs, deformable microparticles) and lymphoma cells supports the relevance of these regimes to biological phagocytosis. Together, these results highlight how target deformability fundamentally shapes phagocytic success and suggest that immune cells may exploit mechanical cues to recognize among different classes of soft targets.

PMID:41647196 | PMC:PMC12869388

Front Public Health. 2026 Jan 20;13:1731706. doi: 10.3389/fpubh.2025.1731706. eCollection 2025.

ABSTRACT

OBJECTIVE: To identify ways of improving antimicrobial stewardship at Kakamega County Teaching and Referral Hospital (KCTRH) in western Kenya.

METHODS: A knowledge and awareness test was conducted among surgical ward healthcare workers to assess their understanding of how to counter antimicrobial resistance. In parallel, the global Point Prevalence Survey (PPS) was used to understand antibiotic prescription practices at the referral facility. Patient records from the adult surgical and pediatric surgical wards were examined for information on antibiotic prescription and usage. A total of 47 healthcare workers and 106 patient records were examined.

RESULTS: Healthcare workers showed the highest competence when tested on the appropriate use of antimicrobials, with a mean score of 78.7%. However, their understanding of surveillance and monitoring was lower, with a mean score of 60.2%, followed by awareness and education (which achieved a mean score of 64.5%). The majority of prescriptions (62.3%) were for empiric treatment, with a lack of laboratory data to support targeted therapies. Prolonged antibiotic courses were noted for surgical prophylaxes with over 83% of patients being administered antibiotics for more than 1 day. The survey also revealed over-prescription of broad-spectrum agents such as ceftriaxone at 36.7%.

CONCLUSION: There is a high use of antibiotics, but a weakness in AMR monitoring at KCTRH. Better use of laboratory testing (AMR profiles for infecting bacteria, etc) is recommended as the best way to improve patient management and deployment of antibiotics.

PMID:41641045 | PMC:PMC12864384 | DOI:10.3389/fpubh.2025.1731706

J Pept Sci. 2026 Mar;32(3):e70071. doi: 10.1002/psc.70071.

ABSTRACT

Bicyclic peptides are emerging as next generation therapeutics by combining the affinity and specificity of antibodies with the synthetic convenience of small molecules. Phage-encoded libraries of bicyclic peptides enable the discovery of high-affinity molecules against virtually any protein target. The generation of bicyclic peptides that advanced into clinical development involves the reaction of three cysteines in a peptide to a C3-symmetric alkylating agent. In phage display, this chemical modification transforms a pool of conformationally flexible peptides into a library of structurally unique protein mimetics that are able to bind traditionally challenging protein surfaces like those with limited structural definition. In recent years, a new class of bicyclic peptides has emerged using a single atom-bismuth-in place of C3-symmetric organic scaffolds, thus expanding into an unexplored chemical space at the intersection of inorganic chemistry and biology. This mini-review aims to reflect on the discovery, evolution and potential future applications of bismuth bicycle molecules.

PMID:41634948 | PMC:PMC12868410 | DOI:10.1002/psc.70071

Mol Biol Evol. 2026 Feb 2;43(2):msag033. doi: 10.1093/molbev/msag033.

ABSTRACT

Duffy antigen receptor for chemokines (DARC) is the primary red blood cell (RBC) receptor for invasion of human RBCs by Plasmodium vivax and Plasmodium knowlesi parasites. By contrast, Plasmodium falciparum parasites use multiple RBC receptors for invasion. Whether DARC is one of these receptors has never been systematically explored. We used flow cytometry and microscopy-based approaches to investigate whether P. falciparum parasites preferentially invade specific Duffy RBC phenotypes and explored 2 potential explanations for invasion preference-differences in RBC biophysical properties and surface protein composition. P. falciparum parasites showed a consistent preference for Duffy-positive RBCs, and some biophysical properties and surface protein expression varied between Duffy-positive and Duffy-negative RBCs. We then used our in vitro invasion data to parametrize an evolutionary-epidemiological model of the relationship between P. falciparum and the FYBES allele. Our model accounts for immunity against P. falciparum virulence, gained through exposure, and thus mutations that impede infection are not always advantageous. The inhibition of P. falciparum invasion that we observed in vitro leads to FYBES frequencies increasing at low levels of P. falciparum transmission but decreasing at high levels of transmission. The impact of P. falciparum on the prevalence of Duffy negativity may therefore be most apparent in lower transmission settings. Our findings show a link between Duffy negativity and P. falciparum and suggest that DARC may directly or indirectly be involved in P. falciparum invasion of human RBCs which could, together with P. vivax, explain the distribution of Duffy negativity in sub-Saharan Africa.

PMID:41634932 | PMC:PMC12930091 | DOI:10.1093/molbev/msag033

Parasitology. 2026 Feb 2:1-12. doi: 10.1017/S0031182026101656. Online ahead of print.

ABSTRACT

Infectious diseases result from multiple interactions among microbes and hosts, but community ecology approaches are rarely applied. Manipulation of vector populations provides a unique opportunity to test the importance of vectors in infection cycles while also observing changes in pathogen community diversity and species interactions. Yet for many vector-borne infections in wildlife, a biological vector has not been experimentally verified, and few manipulative studies have been performed. Using a captive colony of fruit bats in Ghana, we conducted the first study to experimentally test the role of bat flies as vectors of Bartonella species. We observed changes in the Bartonella bacteria community over time following the decline of bat flies and again after their subsequent restocking. Reduced transmission rates led to microbial community changes attributed to ecological drift and potential species sorting through interspecific competition mediated by host immunity. We demonstrate that forces maintaining diversity in communities of free-living macroorganisms act in similar ways in communities of symbiotic microorganisms, both within and among hosts.

PMID:41622806 | DOI:10.1017/S0031182026101656

Integr Cancer Ther. 2026 Jan-Dec;25:15347354251409081. doi: 10.1177/15347354251409081. Epub 2026 Jan 27.

ABSTRACT

BACKGROUND: The NALLC trial (NCT01441752) demonstrated that postoperative adjuvant chemotherapy combined with traditional Chinese medicine (TCM) improved the quality of life (QoL) and survival in resected stage Ib-IIIa non-small-cell lung cancer (NSCLC) patients. This report updates disease-free survival (DFS) and other key outcomes.

METHODS: Between December 2012 and August 2015, 334 patients were randomized to receive either adjuvant chemotherapy plus traditional Chinese herbal granules (n = 167) or adjuvant chemotherapy plus placebo (n = 167) across 7 centers. Patients continued herbal granules or placebo daily until chemotherapy completion. DFS updates data was conducted in the intention-to-treat (ITT) population.

RESULTS: The median follow-up was 116.87 months. Median DFS was 71.83 months for the TCM group versus 43.60 months for the control (HR: .86; 95% CI: .64-1.15; P = .31). Two-year and 5-year DFS rates were 73.60% and 50.16% for TCM, compared to 67.45% and 44.08% for the control (P = .23). Median overall survival (mOS) was not reached in either group, with 75% OS at 63.40 months for TCM and 53.67 months for the control. Five-year OS rates were 76.15% for TCM and 69.81% for the control (P = .23). Subgroup analysis showed stage Ib patients benefited from TCM in both DFS (HR: .51; P = .02) and OS (HR: .34; P = .01).

CONCLUSIONS: Adjuvant chemotherapy combined with TCM showed a potential trend toward improved DFS in early-stage NSCLC patients.

TRIAL REGISTRATION: This trial was registered with Clinical.

TRIALS: gov (Number: NCT01441752, July 14, 2011).

PMID:41589575 | PMC:PMC12847656 | DOI:10.1177/15347354251409081

Nature. 2026 Jan 26. doi: 10.1038/s41586-026-10156-9. Online ahead of print.

ABSTRACT

Gene expression is dynamically controlled by gene regulatory networks comprising multiple regulatory components to mediate cellular functions1. An ideal tool for analysing these processes would track multi-component dynamics with both spatiotemporal resolution and scalability within the same cells, a capability not yet achieved. Here we present CytoTape, a genetically encoded, physiologically compatible, modular protein tape recorder for multiplexed and spatiotemporally scalable recording of gene regulation dynamics continuously for up to 3 weeks, with single-cell, up to minutes-scale resolution. CytoTape uses a flexible, thread-like, elongating intracellular protein self-assembly engineered via computationally assisted rational design, built on our earlier XRI technology2. We demonstrate its utility across multiple mammalian cell types, achieving simultaneous recording of five transcription factor activities and gene transcriptional activities. CytoTape reveals that divergent transcriptional trajectories correlate with transcriptional history and signal integration, and that distinct immediate early genes (IEGs) exhibit complex temporal correlations within single cells. We further extended CytoTape into CytoTape-vivo for scalable, spatiotemporally resolved single-cell recording in the living brain, enabling simultaneous weeks-long recording of doxycycline-dependent and IEG promoter-dependent gene expression histories across up to 14,123 neurons spanning multiple brain regions per mouse. Together, the CytoTape toolkit establishes a versatile platform for scalable and multiplexed analysis of cell physiological processes in vitro and in vivo.

PMID:41588170 | DOI:10.1038/s41586-026-10156-9

Antimicrob Agents Chemother. 2026 Mar 4;70(3):e0111825. doi: 10.1128/aac.01118-25. Epub 2026 Jan 26.

ABSTRACT

Human norovirus (HNoV) is a major cause of gastroenteritis worldwide, for which no antiviral therapies exist to date. Previously, our lab has demonstrated that both HNoV and murine norovirus (MNV1) are highly dependent on the expression of the Ras-GTPase-activating protein-binding protein 1 (G3BP1), a cellular protein mostly involved in the assembly of stress granules. We, therefore, hypothesize that targeting G3BP1 could be a promising antiviral strategy against noroviruses. Here, we designed a proof-of-concept study to test targeted protein degradation as a mechanism to induce the specific proteolysis of G3BP1 via the proteasome. To do so, we generated a cellular platform for the overexpression of G3BP1 fused to the bacterial protein Halotag (HaloG3BP1). First, we showed that MNV1 replication is restored in G3BP1-knockout (ΔG3BP1) cells complemented with HaloG3BP1. We then used a PROteolysis TArgeting Chimera (PROTAC) directed toward the Halotag (HaloPROTAC) to induce the specific degradation of HaloG3BP1. We further demonstrate that proteolysis of G3BP1 reduces MNV1 replication, leading to a lower infectious virus yield and preventing virus-induced cell death. We also confirmed that the mechanism of HaloPROTAC3 is mediated via the recruitment of Cullin2-VHL E3-ubiquitin ligase. Our findings add to the body of evidence supporting that targeting of the cellular protein G3BP1 can be used as an antiviral approach and validates the use of PROTACs for the efficient and specific degradation of cellular factors as a feasible methodology to combat viral diseases.

PMID:41586493 | PMC:PMC12959154 | DOI:10.1128/aac.01118-25