Latest publication

EMBO J. 2026 Jun 3. doi: 10.1038/s44318-026-00825-w. Online ahead of print.

ABSTRACT

Interferons (IFN) are cytokines that regulate the expression of hundreds of genes during viral infections to generate a broadly antiviral environment in the stimulated cell. Antiviral breadth is provided by the concurrent expression of many individual IFN-stimulated genes (ISG), each encoding a protein with often exquisite antiviral specificity. Here, we identify mechanistic plasticity at a single genetic locus as a novel mechanism to diversify the antiviral profile of human cells. Through alternative splicing, the OAS2 gene encodes two antiviral molecules with distinct target specificities. The shorter OAS2 p69 isoform restricts seasonal human coronavirus OC43 (HCoV-OC43), whereas the longer p71 isoform restricts picornavirus Cardiovirus A (EMCV). The restriction profile is determined by the variable length OAS2 C-terminal tails. Notably, these antiviral activities differ in their dependence on RNase L, suggesting that alternative splicing separates canonical restriction and virus sensing functions across two distinct OAS2 polypeptides. Together, these findings show how alternative splicing expands antiviral diversity at the human OAS2 locus.

PMID:42236548 | DOI:10.1038/s44318-026-00825-w

NPJ Vaccines. 2026 Jun 2. doi: 10.1038/s41541-026-01501-0. Online ahead of print.

ABSTRACT

Helminth parasites of the genus Schistosoma cause 290,000 deaths annually, mostly in tropical and subtropical regions. An estimated 250 million people are currently chronically infected with Schistosoma parasites, imposing a risk of new and recurrent infections in an additional 800 million people. SchistoShield® (Sm-p80 + GLA-SE) is a leading vaccine candidate for schistosomiasis that has successfully completed Phase 1 (USA) and Phase 1b (Africa) safety and immunogenicity clinical trials. Using Peripheral Blood Mononuclear Cells (PBMCs) obtained from intercontinental Phase 1 and Phase 1b trial participants, adaptive immune effector and memory responses to SchistoShield® were investigated. Functional recall responses were measured in vitro using Sm-p80 vaccine antigen. Results clearly demonstrate that the vaccine induced pronounced effector and memory T-cell responses. Upon recall with Sm-p80 antigen, cytokines including IFN-γ, TNF-α, IL-17A, IL-9, and granzyme B were produced, indicating the generation of functionally heterogeneous CD4 T-helper and cytotoxic lymphocyte responses. Consistent with T-helper responses that promote humoral immunity, Sm-p80 antigen-specific antibody-secreting plasmablasts were detected in vaccinated volunteers who were tracked longitudinally. Taken together, the SchistoShield® vaccine induced robust cell-mediated effector and memory responses, hallmarks of a potentially efficacious vaccine against schistosome/helminth parasites.

PMID:42230670 | DOI:10.1038/s41541-026-01501-0

iScience. 2026 Apr 28;29(6):115910. doi: 10.1016/j.isci.2026.115910. eCollection 2026 Jun 19.

ABSTRACT

Distinct from vaccine-first models, infection-first exposures provide a critical context for understanding SARS-CoV-2 immune imprinting in unvaccinated populations. We analyzed neutralizing antibody responses in two independent unvaccinated Nigerian cohorts sampled in early 2023. Using a BA.1 receptor-binding domain (RBD)-based assay for Omicron exposure discrimination, we identified widespread pre-Omicron and partial Omicron exposure. Despite recent Omicron infection, plasma neutralization titers against Omicron lineages remained equal or lower compared to those against ancestral Wu-1, indicating infection-derived imprinting. Depletion of Wu-1 spike-binding antibodies abrogated neutralization of both Wu-1 and Omicron pseudoviruses, confirming dominance of ancestral cross-reactive antibodies. Following Wu-1-based vaccination, neutralizing responses increased across all variants, yet Omicron titers did not exceed Wu-1 titers even after breakthrough infection. These findings demonstrate durable infection-induced immune imprinting established before vaccination and only partially mitigated by repeated Omicron exposures, underscoring the influence of infection-first exposure sequence on antibody breadth and broader global relevance for vaccine design.

PMID:42221816 | PMC:PMC13218260 | DOI:10.1016/j.isci.2026.115910

Cell Rep. 2026 May 28;45(6):117460. doi: 10.1016/j.celrep.2026.117460. Online ahead of print.

ABSTRACT

Prolonged infections in immunocompromized individuals are associated with accumulation of unexpected combinations of mutations, as exemplified by the Omicron variant. Here, we show that intra-host evolution during a chronic SARS-CoV-2 infection in the pre-Omicron era was associated with mutations that modulate antibody evasion, cell entry efficiency, spike processing, and fusogenicity. Single spike N-terminal mutations S13I and W64G exerted deleterious impacts on S1/S2 cleavage, syncytia formation, and cell entry but combined through an inferred recombination event with P330S to restore function. The single mutants were never detected individually in respiratory samples, but mediated temperature-dependent evasion from neutralizing antibodies and altered reliance on TMPRSS2-mediated membrane fusion, possibly explaining their transient selection. Molecular dynamics simulations revealed that W64G induces local N-terminal domain destabilization with distal effects at the S1/S2 cleavage loop, linking structural perturbation to functional defects and immune evasion. Together, these findings demonstrate how intra-host recombination contributes to viral adaptation.

PMID:42213788 | DOI:10.1016/j.celrep.2026.117460

Clin Microbiol Infect. 2026 May 21:S1198-743X(26)00265-X. doi: 10.1016/j.cmi.2026.05.023. Online ahead of print.

NO ABSTRACT

PMID:42173193 | DOI:10.1016/j.cmi.2026.05.023

Vaccine. 2026 May 16;85:128691. doi: 10.1016/j.vaccine.2026.128691. Online ahead of print.

ABSTRACT

BACKGROUND: Typhoid fever incidence estimates are central to policy decisions on vaccine introduction and investments in non-vaccine prevention and control but are often unavailable. We explored whether prevalence metrics from sentinel studies of community-onset bloodstream infections could accurately predict local Salmonella enterica serovar Typhi (Salmonella Typhi) incidence.

METHODS: Using a previous systematic review (January 2018-December 2024), we identified studies reporting both typhoid incidence and prevalence of community-onset bloodstream infections from sentinel sites. From authors, we requested data on blood culture isolates and analysed four metrics: (i) Salmonella Typhi prevalence among probable pathogens, (ii) Salmonella Typhi rank order, (iii) Salmonella Typhi to Escherichia coli ratio, and (iv) Salmonella Typhi to 'stably endemic' organisms ratio. Typhoid incidence was categorized as low (<10), medium (10-100) or high (>100) per 100,000 person-years. We used univariate ordinal regression to assess the association between each metric and typhoid incidence level. The model performance was evaluated by the c-statistic, sensitivity, and specificity.

RESULTS: Analysis of 29 study sites (20 Africa, 9 Asia) yielded 4625 probable pathogens. The median (IQR) typhoid incidence was 140 (28-319) per 100,000 person-years. All metrics were associated with increased typhoid incidence level: for each 1% increase in Salmonella Typhi prevalence OR 1.07 (95%CI 1.02-1.15); for each unit increase in rank order OR 0.25 (95%CI 0.06-0.64); for each unit increase in the log Salmonella Typhi to E. coli ratio OR 2.88 (95%CI 1.48-7.39) for each unit increase in the log Salmonella Typhi to 'stably endemic' organisms ratio OR 3.74 (95%CI 1.80-10.7). A parsimonious model using Salmonella Typhi prevalence alone achieved c-statistics of 0.87 (0.58-0.97), 0.76 (0.51-0.91), and 0.88 (0.69-0.96) for low, medium, and high incidence, respectively.

CONCLUSION: Sentinel prevalence metrics from bloodstream infections, particularly Salmonella Typhi prevalence among probable pathogens, could be useful for inferring local typhoid fever incidence where direct data are unavailable.

PMID:42142522 | DOI:10.1016/j.vaccine.2026.128691

Int J Infect Dis. 2026 May 7:108759. doi: 10.1016/j.ijid.2026.108759. Online ahead of print.

ABSTRACT

BACKGROUND: Young women aged 15-24 bear a disproportionate burden of new HIV infections in sub-Saharan Africa. Age-disparate relationships with older men have been proposed as a major contributor to this pattern.

METHODS: We conducted whole-genome sequencing of HIV in large cohort of individuals in KwaZulu-Natal, South Africa, (the Vukuzazi cohort). Samples with viral loads >50 copies/ml were sequenced. Genomes passing quality control were grouped into clusters using maximum-likelihood phylogenetic analysis. Potential transmission pairs were analysed alongside participant age and sex data. A Bayesian random-effects model estimated transmission rates between demographic groups while accounting for population age-sex structure.

FINDINGS: Among 18,025 participants enrolled 2018-2020, 6,096 were HIV-positive. Sequencing yielded 1,097 genomes, identifying 89 clusters containing 205 individuals and 73 likely male-female linked phylogenetic pairs. Across pairs, men were a median of 5 years older than women (IQR -1, 12). Women <30 years paired with men a median of 7 years older, whereas among women ≥30 years men were typically younger. After accounting for population structure, the strongest signal for transmission was between women aged 25-29 and men up to four years older.

CONCLUSIONS: Relative transmission rates were greatest with moderate age differences. Large intergenerational age gaps were not dominant.

PMID:42106143 | DOI:10.1016/j.ijid.2026.108759

PLoS Genet. 2026 May 8;22(5):e1012141. doi: 10.1371/journal.pgen.1012141. Online ahead of print.

ABSTRACT

Colocalisation analysis integrates GWAS and molecular QTL datasets to identify candidate effector genes. Even with a wide range of molecular QTLs, 40% or more of GWAS loci remain unexplained, leaving a "colocalisation gap". We systematically characterised two large-scale eQTL colocalisation studies, to describe the determinants of this gap and ultimately inform the selection and design of eQTL studies to close the gap. We analyse over 1.3 million colocalisation tests from Open Targets Genetics (OTG) and perform and analyse colocalisations from 14 immune-mediated disease (IMD) GWAS and 12 diverse immune cell eQTL studies, selected to cover a range of cellular granularities and sample sizes. We find that 50% of GWAS peaks in OTG and 34% in IMDs colocalised and were more likely to colocalise if they were located nearer to genes and had a more common lead variant. Colocalisation was also more likely to occur in disease relevant tissues. The lowest granularity immune cell eQTL studies had the largest sample sizes, the greatest eQTL discovery and produced the largest number of colocalisations, particularly for lower-frequency variants. However, while higher resolution eQTL studies detected fewer eQTLs, each of those eQTLs was more likely to colocalise with a GWAS peak, emphasising the importance of cell specific eQTLs. Indeed, over 50% of colocalisations were found in only one cell type. Overall, our results suggest that a diverse set of cells in different contexts, and large, high granularity studies will be needed to identify remaining colocalisations. In addition, we observed that 47% of GWAS peaks colocalised with multiple genes in OTG and 37% in IMDs. Through simulations, sensitivity analyses, and integration of enhancer-promoter capture data we find that multiple colocalisations likely represent coregulation. While disentangling causality from horizontal pleiotropy will ultimately require experimental perturbation, triangulation using different sources of observational data is likely to be necessary for gene prioritisation.

PMID:42102166 | DOI:10.1371/journal.pgen.1012141

J Virol. 2026 May 7:e0019526. doi: 10.1128/jvi.00195-26. Online ahead of print.

ABSTRACT

The most recently acquired and transcriptionally active family of human endogenous retroviruses (HERVs) is HERV-K. Of the approximately 100 copies of HERV-K in our genome, many retain the potential to proliferate by retrotransposition, express viral proteins, and form functional virus particles. Aberrant expression of the HERV-K envelope glycoprotein (Env) has been associated with cancer and neurodegeneration. Autoantibodies against HERV-K Env have been found in patients with various autoimmune diseases. Here, we report the crystal structure of the Env surface subunit (SU) from HERV-K HML-2, determined at 2.25-Å resolution. The overall fold is somewhat similar to Syncytin-2 SU and distantly related to HIV-1 gp120. The structure contains five disulfides, four N-linked glycans, and two sulfate ions bound to a basic surface groove. Two extended loops form a surface for potential interactions with cell-surface receptors or other cellular factors. The structure also contains three steroid molecules bound to hydrophobic surface patches. This crystal structure provides a platform for future studies to map autoantigenic epitopes, identify small molecules that interfere with HERV-K activity, and extend our mechanistic understanding of retroviruses.IMPORTANCEEight percent to 15% of the human genome consists of endogenous retroviruses and other virus-derived elements inherited from ancestral viral infections. Many endogenous retroviruses from the HERV-K family retain the ability to proliferate across the genome and produce virus-like particles. Aberrant expression of the HERV-K envelope glycoprotein is associated with cancer, neurodegeneration, and autoimmune disease. Here, we report the crystal structure of the HERV-K envelope glycoprotein surface subunit. The structure provides an atomic-level view of the molecular components in HERV-K most likely to trigger autoimmune responses and identifies potential binding sites for drug-like molecules and cell-surface polysaccharides.

PMID:42095673 | DOI:10.1128/jvi.00195-26

Lancet Reg Health Southeast Asia. 2026 Apr 22;48:100769. doi: 10.1016/j.lansea.2026.100769. eCollection 2026 May.

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection (ARI) in young children, but evidence on burden from low- and middle-income countries has largely been derived from hospital-based studies. This prospective, community-based study estimated the burden of RSV-associated ARI among children younger than two years of age in rural Bangladesh.

METHODS: This observational study was conducted in two unions of the Mirzapur sub-district, Tangail District, Bangladesh between August 2021 and June 2023. Village healthcare workers visited each household in the selected area weekly to identify ARI episodes among children younger than two years using the WHO definition. Following parental written consent, nurses collected nasopharyngeal swabs for RSV testing by RT-qPCR from children who were experiencing ARI episodes. RSV incidence and incidence rate ratios were estimated using Poisson regression.

FINDINGS: Overall, 3667 children contributed to 3008 child-years of follow-up. Out of 5907 ARI episodes recorded, 4586 specimens were collected and tested. 7.1% of the samples (324/4586) tested positive for RSV. RSV infections showed a peak in August-September 2021 and October 2022-February 2023 with 37.6% and 16.1% of samples testing positive, respectively, and near-zero detection during the remaining months. The overall RSV-ARI incidence was 107.7 per 1000 child-years (95% CI: 96.6-120.1). The incidence was highest during the first six months of life (164.5 per 1000 child-years), which was 2.2 times higher (incidence rate ratio [IRR] 2.2; 95% CI: 1.6-3.0) than in the second year of life. Preterm infants had a 50% higher risk of RSV-ARI (IRR 1.5; 95% CI: 1.2-2.0) than term infants. Cough was present in 95.7% and chest indrawing was observed in 9.8% of RSV infections.

INTERPRETATION: RSV-ARI imposes a substantial community burden among rural Bangladeshi children, especially in infancy. These findings support consideration of RSV-specific interventions, such as maternal immunisation or monoclonal antibodies for infants to address the disease burden.

FUNDING: The Robert Koch Institute, Germany; and the International Vaccine Institute (IVI), South Korea.

PMID:42058847 | PMC:PMC13123609 | DOI:10.1016/j.lansea.2026.100769

Adv Sci (Weinh). 2026 Apr 28:e75319. doi: 10.1002/advs.75319. Online ahead of print.

ABSTRACT

Sensitive and multiplexed RNA analysis at the single-molecule level remains a key challenge in molecular diagnostics. Conventional fluorescence microarrays provide high throughput but lack molecular resolution, whereas single-molecule sensors such as nanopores offer exquisite precision but limited scalability. Here, we present a DNA carrier-based nanoarray that integrates programmable nucleic acid hybridization with solid-state nanopore readout for direct, multiplexed RNA detection. Each modular DNA carrier is pre-assembled with spatially defined probe sites that sequence-specifically capture RNA targets of varying lengths and conformations, in which poly(dT) sequences both structurally facilitate target binding and enhance signal strength without the need for fluorescent or protein labeling. Upon nanopore translocation, hybridized carrier-target complexes generate binary ionic current signatures, allowing single-molecule identification of target occupancy at each sensing site. Using a ternary coordinate encoding system, we constructed a nanoarray comprising 27 carriers with 81 addressable sensing sites, enabling simultaneous detection of multiple bacterial and viral RNA targets within a single assay directly from total RNA extracts without target-specific isolation, amplification, or enrichment. By combining the multiplexing capability of traditional microarrays with the single-molecule precision of nanopore sensing, this carrier-based nanoarray establishes a scalable, programmable, and universally adaptable framework for high-throughput molecular diagnostics in complex biological backgrounds.

PMID:42047202 | DOI:10.1002/advs.75319

Nature. 2026 Apr 15. doi: 10.1038/s41586-026-10391-0. Online ahead of print.

ABSTRACT

A number of currently untreatable diseases, including neurodegenerative disorders, optic nerve atrophy and heart failure, are associated with mitochondrial dysfunction. Transplantation of healthy mitochondria has been proposed as a potential therapeutic strategy1-3. However, the lack of methods to target donor mitochondria to disease-affected cell types limits treatment specificity and efficacy. Here we developed MitoCatch as a system to deliver mitochondria to specific cell types using different types of protein binders. Donor mitochondria are captured by target cells by cell-surface-displayed monospecific binders, mitochondrion-displayed monospecific binders or bispecific binders linking mitochondria to target cells. Using MitoCatch, we show that donor mitochondria are efficiently internalized, exposed to the cytosol, move, and undergo fusion and fission inside target cells. By engineering binders with different affinities, we tune the efficiency of mitochondrial delivery. We demonstrate targeted mitochondrial transplantation to retinal cell types, neurons and cardiac, endothelial and immune cells in humans and mice. Transplanted mitochondria promoted the survival of damaged neurons from an individual with optic nerve atrophy in vitro and after neuronal injury in mice in vivo. MitoCatch is a potential strategy to target disease-affected cell types with mitochondria in organs affected by diseases associated with mitochondrial dysfunction.

PMID:41986718 | DOI:10.1038/s41586-026-10391-0

QJM. 2026 Apr 8:hcag090. doi: 10.1093/qjmed/hcag090. Online ahead of print.

ABSTRACT

Iron is essential for the survival of both humans and pathogens, creating intense competition for the metal during infection. Whilst hosts seek to restrict access to iron via nutritional immunity, microbes including bacteria, viruses, and fungi have adapted unique mechanisms to acquire it. The lungs function as a key battleground in this contest, with local iron homeostasis mediated by tissue-resident alveolar macrophages. Systemic iron status-either overload or deficiency-also dictates the efficacy of innate and adaptive immunity, thus directly influencing the outcomes of respiratory disease. This review will examine our current understanding of the host-iron-pathogen axis in the lung, as well as consider how it could be exploited to improve health outcomes in respiratory infection.

PMID:41965073 | DOI:10.1093/qjmed/hcag090

Nucleic Acids Res. 2026 Mar 19;54(6):gkag274. doi: 10.1093/nar/gkag274.

ABSTRACT

Long double-stranded RNA (dsRNA) in the cytosol acts as a potent inflammatory molecule recognized by the receptor MDA5, triggering the innate immune response. Mutations affecting MDA5 ATPase activity lead to severe pathological conditions. MDA5 nucleoprotein filament assembly-disassembly dynamics are proposed to regulate dsRNA recognition, though the exact mechanism remains unclear. Here, we employed magnetic tweezers to monitor the assembly and manipulate MDA5 filaments at the single dsRNA level. Following a slow nucleation event, MDA5 assembles cooperatively and directionally into (partial) filaments and utilizes ATP hydrolysis to compact dsRNA through unwinding into single-stranded RNA (ssRNA), even against a significant opposing force. This compacted state is further stabilized by oligomerization of the caspase recruitment domain of MDA5 and requires high force to be disrupted. ssRNA gaps impaired compaction, suggesting a new mechanism for dsRNA recognition. We propose that MDA5-mediated dsRNA compaction captures viral dsRNA, preventing further usage for viral replication.

PMID:41914501 | DOI:10.1093/nar/gkag274

Antibiotics (Basel). 2026 Mar 6;15(3):271. doi: 10.3390/antibiotics15030271.

ABSTRACT

Background: Antimicrobial resistance (AMR), particularly due to extended-spectrum beta-lactamases (ESBL), is a growing threat to public health in sub-Saharan Africa. This study investigates the prevalence, epidemiological characteristics, resistance patterns and resistance dynamic over time of ESBL-producing non-typhoidal Salmonella (NTS) bacteremia in Kisantu, Democratic Republic of Congo (DRC), from 2019 to 2022. Methods: A retrospective observational study used routine bloodstream infection data from the AMR network at Saint Luc Hospital in Kisantu. Blood cultures from suspected bacteremia cases were processed using standard microbiological techniques. Bacterial identification relied on biochemical reactions. Antibiotic susceptibility testing and ESBL-producing NTS detection were performed by disk diffusion following Clinical and Laboratory Standards Institute guidelines. Associations between ESBL production and patient characteristics (age, sex) were assessed using Pearson's Chi-square test, and annual temporal trends in ESBL-producing NTS from 2019 to 2022 were analyzed by logistic regression using 2019 as the reference year. Results: Of the 19,430 blood cultures, 1681 NTS isolates were identified, and 1568 of these were screened for ESBL. ESBL prevalence was significantly associated with age (p = 0.007), peaking in children under 2 years, but not with sex (p = 0.570). Compared with 2019, the likelihood of isolating ESBL-producing NTS increased markedly through 2022, with adjusted probabilities rising from 58% to 87%, reflecting a strong upward temporal trend. High levels of extensively drug-resistant (94.1%) were observed. No carbapenem resistance was detected. Conclusions: ESBL-producing NTS bacteremia is rising in Kisantu, DRC, mainly affecting children under 2 years. Rising resistance to key antibiotics limits treatment options and highlights the need for strengthened AMR surveillance, optimized antibiotic use, and vaccination strategies.

PMID:41892433 | DOI:10.3390/antibiotics15030271

J Cell Biol. 2026 May 4;225(5):e202506111. doi: 10.1083/jcb.202506111. Epub 2026 Mar 18.

ABSTRACT

Secreted proteins are essential for processes like immune responses, cellular communication, and extracellular matrix remodeling. Once synthesized and processed at the Golgi, some of these proteins are packaged for delivery to the plasma membrane. While this transport and sorting rely on complex molecular machinery, the precise mechanisms remain unclear. In this study, we affinity-isolated and analyzed post-Golgi carriers by mass spectrometry. Candidate machinery was subsequently assessed in a pooled CRISPR-KO screen. This led to the identification of a rich set of new genes functionally important for Golgi-to-plasma membrane delivery including PTPN23, a component of the endosomal sorting complex required for transport (ESCRT) complex. Depletion of PTPN23, as well as the ESCRT subunits CHMP1 and VPS4, disrupts tubule fission from the trans-Golgi, impairing cargo delivery to the surface. Furthermore, the loss of PTPN23 also prevents the constitutive secretion of soluble cargoes, and of endogenous hormones and antibodies in specialized cells. We propose that PTPN23 is essential for secretion from the trans-Golgi.

PMID:41848521 | DOI:10.1083/jcb.202506111

Nat Commun. 2026 Mar 12. doi: 10.1038/s41467-026-70517-w. Online ahead of print.

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of VHL, and uncover that loss of Core Binding Factor β (CBF-β) causes cell death in VHL-null ccRCC cell lines and impairs tumour establishment and growth in vivo. This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in VHL-null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-β. Mechanistically, CBF-β loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-β at the STING locus controlling Interferon Stimulated Gene expression. Targeting CBF-β in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.

PMID:41820368 | DOI:10.1038/s41467-026-70517-w

Nat Rev Urol. 2026 Feb 26. doi: 10.1038/s41585-026-01130-1. Online ahead of print.

ABSTRACT

Bacterial urinary tract infections (UTIs) are prevalent in childhood and adolescence. Paediatric UTIs present unique challenges with respect to diagnosis, prevention and management, and the potential for adverse sequelae. Uropathogenic Escherichia coli (UPEC) accounts for the majority of UTIs and is the best studied uropathogen. Novel discoveries have advanced our understanding of host-pathogen interactions, cellular and molecular mechanisms of host defence, and risk factors for UTI recurrence. Emerging evidence also highlights an association of the gut, vaginal and urinary microbiota in influencing UTI risk and recurrence. Yet, key knowledge gaps persist regarding UTI pathogenesis, host susceptibility, optimal diagnostic and management strategies and prevention of UTI recurrence and sequelae, especially in paediatric populations. The development of standardized clinical pathways offers an opportunity to improve care consistency and outcomes by integrating evidence-based practices into routine management. As technologies evolve and understanding deepens, future efforts must integrate host, microbial and clinical insights to optimize UTI prevention and treatment in paediatric populations.

PMID:41748741 | DOI:10.1038/s41585-026-01130-1

bioRxiv [Preprint]. 2026 Feb 11:2026.02.10.704860. doi: 10.64898/2026.02.10.704860.

ABSTRACT

Single-cell transcriptomic and proteomic technologies enable molecular profiling of immune cells at scale but provide limited access to cellular phenotypes shaped by spatial organisation, organelle architecture and cytoskeletal remodelling. Here we present TGlow, a scalable high-content imaging platform optimized for systematic single-cell phenotyping of primary human lymphocytes. TGlow integrates cyclic immunofluorescence, deep z-stack confocal imaging, and open-source data processing pipelines, including both classical and self-supervised vision transformer-based feature extraction, to jointly quantify cellular morphology, organelle organization, and immune activation states. Applied across over 400,000 primary human T cells spanning CD4+ activation time courses, drug perturbations, CRISPR knockouts and CD8+ T-cell exhaustion, TGlow resolves distinct and reproducible phenotypic states. We uncover dose-dependent and mechanism-specific drug phenotypes, such as defective endoplasmic reticulum polarisation under mycophenolic acid and tofacitinib. We show that mitochondrial clustering reveals activation- and cell-cycle-linked remodelling programs, CRISPR perturbations map gene-specific phenotypes that reposition cells along activation trajectories, and we identify a previously unrecognised collapse of cytoskeletal architecture in exhausted CD8+ T cells. TGlow provides a scalable framework for high-dimensional phenotyping of lymphocyte states advancing functional genomics, perturbation screening and population-level immune profiling by resolving the morphological and functional heterogeneity of lymphocytes and enabling systematic linkage of genetic and pharmacological perturbations to cellular function.

PMID:41726991 | PMC:PMC12918823 | DOI:10.64898/2026.02.10.704860

Pediatr Nephrol. 2026 Feb 20. doi: 10.1007/s00467-026-07166-0. Online ahead of print.

ABSTRACT

The imminent availability of multiple therapeutic complement inhibitors, which target different complement pathway components, could revolutionise treatment for a broad range of kidney diseases. However, the complexity of complement activity within and between kidney diseases, for which IgA nephropathy is an illustrative example, and the possible adverse effects of complement inhibition mean robust patient selection and stratification to appropriately targeted inhibitors will be needed to maximise this therapeutic opportunity. Despite promising candidates, novel biomarkers that stratify patients to targeted complement inhibition have not yet been validated for clinical practice.

PMID:41714421 | DOI:10.1007/s00467-026-07166-0