Biology subjects

Han, J.

Publications and source records attributed to Han, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Diagnostic Performance of Fluorescence-Based Rapid On-Site Specimen Evaluation for Helicobacter pylori Antimicrobial Susceptibility Testing Before and After Algorithm Optimization: A Two-Round Comparative Study

ObjectiveThis study was designed to evaluate the diagnostic performance of fluorescence-based rapid on-site specimen evaluation (F-ROSE) for antimicrobial susceptibility testing of Helicobacter pylori (H. pylori) and to compare test performance before and after iterative optimization of fluorescence image acquisition and of the artificial intelligence (AI) recognition algorithm, using two consecutive rounds of paired testing, so as to provide trial data supporting clinical implementation of rapid susceptibility testing. MethodsForty patients with a urea breath test (UBT) or rapid urease test (RUT) positive for H. pylori within the preceding 2 weeks, together with strongly positive endoscopic findings, were prospectively enrolled. In order of enrollment they were allocated to two rounds in which F-ROSE was compared with culture-based susceptibility testing. Twenty patients were tested in round 1 on an automated fluorescence immunoassay scanner running the original algorithm; a further 20 were tested in round 2 with the optimized algorithm. With in vitro culture and E-test as the reference standard, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of F-ROSE were calculated for each round for amoxicillin, levofloxacin hydrochloride and clarithromycin, and agreement between methods was assessed with Cohens kappa. Receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff of the fluorescence residual rate (FRR) and to determine how far threshold adjustment improved performance. ResultsCulture succeeded in 15 patients in round 1 and in 14 patients in round 2, leaving 29 evaluable samples. Overall diagnostic performance after algorithm optimization was clearly better than before. Pooled across the three antibiotics, sensitivity was 92.9%, specificity 71.0% and accuracy 77.8% before optimization; after optimization sensitivity rose to 100.0%, specificity increased slightly to 74.2% and accuracy to 81.0%. NPV reached 100.0% for all three agents after optimization, and no resistant isolate was missed. The gain was largest for clarithromycin, for which sensitivity rose from 85.7% to 100.0%, accuracy from 66.7% to 78.6% and kappa from 0.348 to 0.571, indicating a clear improvement in agreement between the two methods. ROC analysis showed that drug-specific optimal cutoffs derived from the Youden index improved specificity appreciably compared with the uniform 50% FRR threshold currently applied, the gain being most evident for levofloxacin hydrochloride. ConclusionsWith sharper fluorescence images and an improved AI recognition algorithm, F-ROSE performs better in H. pylori susceptibility testing, and the reduction in missed resistant strains is particularly noteworthy; the assay is therefore a plausible option for rapid susceptibility screening in clinical practice. Multicenter studies with larger samples are still required to confirm the stability of the technique.

microbiology↗

bioRxiv2026

Targeting cellular senescence alleviates bone marrow aging

Aging of the hematopoietic system impairs hematopoietic stem cell (HSC) function and alters bone marrow niche behavior, increasing susceptibility to anemia, infections, and hematologic malignancies. Here, pharmacologic clearance of senescent cells with the PROTAC compound 753b simultaneously targeting BCL-xL and BCL-2 reverses key secretory, transcriptional, and functional hallmarks of hematopoietic aging with low toxicity, restoring balanced lineage output. Single-cell RNA sequencing further demonstrates that 753b treatment attenuates aging-associated transcriptional signatures in HSCs, while selectively eliminating senescent, pro-survival niche cells without grossly perturbing niche composition. Functionally, 753b suppresses pro-inflammatory cues from both niche and hematopoietic cells including those emanating from neutrophil progenitors, rebalancing global bone marrow secretory ecosystem across stromal and hematopoietic compartments. Collectively, we identify 753b-induced senescent cell clearance as a powerful strategy to rejuvenate aged hematopoiesis and re-establish homeostatic communication between HSCs and their microenvironment, with implications for mitigating age-related hematologic dysfunction and improving hematologic health in older individuals.

cell biology↗

bioRxiv2026

Myeloid-Specific Pck1 Deficiency Does Not Alter Aortic Root Atherosclerosis in Mice

BackgroundWe previously performed a strain intercross between atherosclerosis resistant AKR Apoe-/-mice and atherosclerosis sensitive DBA/2 Apoe-/- mice and identified the Ath28 quantitative trait locus (QTL) on the distal end of chromosome 2. Congenic strain fine mapping identified the Ath28.1 QTL atherosclerosis modifying subregion, encompassing 217 Kb, containing for only three protein-coding genes, Zbp1, Pck1, and Pmepa1, encoding respectively, Z-DNA binding protein 1, phosphoenolpyruvate carboxykinase 1, and prostate transmembrane protein androgen induced 1. MethodsThe effect of macrophage-specific knockout of Pck1 (KO) was tested using the AAV2 transduced proprotein convertase subtilisin kexin type 9 (PCSK9) overexpression mouse model of hyperlipidemia and atherosclerosis. ResultsUnexpectedly, macrophage Pck1 deficiency lowered body weight, liver weight, and HDL-cholesterol levels in both sexes, while total and non-HDL cholesterol levels were only decreased in male mice. Aortic root lesion area and necrotic lesion area were unchanged in KO mice of both sexes. ConclusionPck1 was not confirmed as an atherosclerosis modifier gene.

genetics↗

bioRxiv2026

Injectable Electrospun Hydrogel with Antimicrobial, pH Sensing Nanoparticles for Local Infection Control and Monitoring

Most antimicrobial drug candidates currently in development are derivatives of established antibiotic classes. In contrast, antimicrobial heteroatom-doped carbon quantum dot (COD) nanoparticles vastly differ from their chemical antibiotic counterparts and exhibit potent antibacterial activity and favourable biocompatibility, representing a promising alternative strategy, particularly for topical applications. Here, we report the incorporation of cobalt-doped carbon quantum dots (Co-CODs) into injectable, biocompatible hydrogels capable of both sensing pH and eliminating bacteria. Ultrasmall Co-CODs demonstrated broad-spectrum activity against gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (PAO1), mediated by membrane hyperpolarisation and reactive oxygen species (ROS) induced membrane damage. The particles showed negligible effect on primary fibroblast and endothelial cell viability at concentrations that were bactericidal to MRSA. Polymeric hydrogels were fabricated via electrospinning of chitosan, polyvinylpyrrolidone (PVP), and polyvinyl alcohol (PVA) polymer blends incorporating Co-COD and pH-responsive HPTS particles. This approach provided accurate measurement of environmental pH within the physiological range observed across healthy and chronic wounds. In vivo, the injectable hydrogels exhibited robust antimicrobial efficacy against MRSA without impairing wound closure relative to untreated controls, while also reducing inflammatory immune responses in infected tissues. Collectively, these findings demonstrate the potential of ultrasmall metal-doped CODs for infection control and their integration into 3D matrices as multifunctional theragnostic platforms. ToC (<60 words describe the main results)Ultrasmall antimicrobial carbon nanoparticles were incorporated into polymeric hydrogels containing a pH-responsive probe. This platform enabled detection across a physiologically relevant pH range of 5.0-6.5, spanning conditions associated with both healthy healing and chronically infected wounds. The hydrogel demonstrated strong antibacterial activity by generating damaging reactive oxygen species, and, in mice, effectively controlled infection while reducing pro-inflammatory immune responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/736887v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1a52b32org.highwire.dtl.DTLVardef@b6eed2org.highwire.dtl.DTLVardef@1f94143org.highwire.dtl.DTLVardef@12b9ff3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOScheme 1:C_FLOATNO Antimicrobial nanoparticle-doped hydrogel glows in alkaline wound conditions which are representative of chronic infections. Once in the wound bed, the hydrogel removes all MRSA infection, reducing inflammatory macrophage (iNOS) and neutrophil (MPO) populations, and restores healthy wound collagen deposition. C_FIG

bioengineering↗

bioRxiv2026

Culture-Free Rapid Phenotypic Antimicrobial Susceptibility Testing for Helicobacter pylori Based on Fluorescence Rapid On-Site Evaluation Technology: A Preliminary Study

BackgroundPhenotypic antibiotic susceptibility testing (AST) for Helicobacter pylori (H. pylori) has relied on bacterial culture for three decades, requiring 5-7 days to yield results. Genotypic rapid tests can only detect known resistance mutations and fail to reliably identify amoxicillin resistance. To our knowledge, no culture-free rapid phenotypic AST method for H. pylori has been previously reported. MethodsWe developed a phenotypic AST method based on fluorescence rapid on-site evaluation (ROSE) technology that completely bypasses bacterial culture. Gastric mucosal biopsy specimens from 40 H. pylori-positive patients were homogenized and co-incubated with an acridine orange/ethidium bromide (AO/EB)-based viability staining reagent and three first-line antibiotics--amoxicillin, clarithromycin, and levofloxacin--at concentrations corresponding to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for H. pylori, at 37 {degrees}C for 1 hour. Fluorescence intensity was measured using a microplate reader. A reduction in fluorescence relative to an antibiotic-free control indicated susceptibility, whereas no significant reduction indicated resistance. Conventional culture-based AST (E-test) served as the reference method. The overall concordance rate, sensitivity, specificity, and Cohens kappa coefficient were calculated. ResultsFourteen of the 40 samples had unsuccessful culture and were excluded, leaving 26 samples for statistical analysis of each antibiotic. The overall concordance rates between the ROSE method and culture-based AST were 84.6% (22/26) for amoxicillin, 76.9% (20/26) for levofloxacin, and 69.2% (18/26) for clarithromycin. Cohens kappa coefficients indicated moderate agreement for all three antibiotics ({kappa} = 0.523, 0.539, and 0.412, respectively). Unlike genotypic methods, the ROSE method successfully assessed amoxicillin susceptibility in all 40 patients--a critical first-line antibiotic for which no reliable genetic resistance marker currently exists. The turnaround time was approximately 1 hour (55-65 minutes), compared with 5-7 days for culture-based methods; preliminary estimates indicated a cost reduction of approximately 3,000-5,000 Chinese yuan (CNY) per patient, mainly attributable to the elimination of culture media, prolonged incubation, and repeat clinic visits. ConclusionsThis study reports, for the first time, a culture-free 1-hour phenotypic AST for H. pylori. The method enables same-day, susceptibility-guided treatment decisions, addressing an unmet clinical need spanning three decades. Algorithm optimization and a prospective randomized controlled trial are currently underway to further improve diagnostic accuracy and validate clinical utility.

microbiology↗

bioRxiv2026

Multimodal Human Scalp Atlas Defines Cell Landscape and Lineage Architecture In Situ

Human scalp hair has an extraordinary ability to grow continuously for years while maintaining structural and functional integrity. However, the cell states and lineage organization that enable this capacity and how they are disrupted in inflammatory hair loss disorders remain poorly defined in humans. Here we establish a high-resolution, multimodal atlas of human scalp by integrating deep-coverage spatial transcriptomics with single-cell RNA-seq and multiomics data. This reference resolves spatially organized epithelial and mesenchymal states and links in situ transcriptional programs to chromatin accessibility dynamics and lineage trajectories at single-cell resolution, revealing human-specific principles of tissue organization and previously unrecognized features of hair follicle architecture and lineage progression. We validate key aspects of matrix cell organization and cell activities using live imaging, connecting molecularly defined cell states to dynamic cell behaviors and lineage progression in the matrix. Leveraging the atlas as a spatial reference, we project patient scRNA-seq profiles from alopecia areata and lichen planopilaris onto defined cell compartments, resolving disease-specific perturbations in fibroblasts, epithelial and immune populations. This comparison delineates distinct cellular programs associated with non-scarring versus scarring hair loss and highlights compartment- and state-specific pathways with diagnostic and therapeutic potential. Together, this work provides a foundational resource for human hair biology and establishes a generalizable framework for spatially resolved, multimodal interrogation of tissue organization and disease in complex human tissues.

Developmental Biology↗

bioRxiv2026

Conversion of a Viral Glycan Shield into a Binding Anchor via Causal-Driven Antibody Optimization

Therapeutic antibodies are challenged by rapidly evolving pathogens that exploit glycosylation to shield epitopes. SARS-CoV-2 JN.1 exemplifies this, escaping antibodies through the N354-linked glycan. However, targeting glycosylated epitopes remains vacant, as scarce and heterogeneous glycan structures render existing approaches ineffective. Here, we introduce the Antibody Evolution Nexus with Causal-Driven Simulation (AENCS), integrating molecular simulation with causal inference. Applying AENCS to restore S309 efficacy against JN.1, we identified ACC01, exhibiting [~]24-fold improved neutralization. With limited prior knowledge of the N354 glycosylation site, ACC01 stabilized this glycan conformation, facilitating the determination of its cryo-EM structure. Causal dissection revealed how this glycan shield is functionally inverted into a binding anchor through multi-layered interactions. This mechanistic conversion, combined with the conservation of N354 glycosylation, enabled ACC01 to maintain potent activity against the latest variant NB.1.8.1. Collectively, AENCS demonstrates causal-driven antibody engineering can illuminate cryptic glycosylated epitopes, providing viable paradigms for exploring this vacant frontier.

bioengineering↗

bioRxiv2026

SEMFA: A General Framework for Inferring Statistical Significance of Mahalanobis Similarity between Multi-Omics Profiled Samples Built on Multiple Factor Analysis

MotivationWith rapid advances in sequencing technologies, many heterogeneous omics datasets have been generated, as seen in the Encyclopedia of DNA Elements (ENCODE) and many single-cell multi-omics sequencing projects, bringing substantial challenges to existing integrative methods. In this article, we report a novel multi-omics fusion and analysis software SEMFA which performs general parametric tests for the Mahalanobis Similarity of samples based on the factor scores generated by an Extended version of conventional Multiple Factor Analysis. ResultsOur developed method is effective and robust under both Gaussian and non-Gaussian assumptions. The mean F1 scores are over 0.8 when the column similarity level is 0.9 and the noise level ranges between 0.1 and 0.2, using simulation studies based on ENCODE count data. It was also efficient and effective at handling large-scale single-cell multi-omics data, as demonstrated in colon cancer cases as it unveiled signature network organization patterns of cells for stages III and IV.

bioinformatics↗

bioRxiv2026

Catalytic rewiring of RuvC-II catalytic site activates trans-cleavage in Fanzor2

Fanzors are eukaryotic RNA-guided endonucleases that mediate programmable cis-cleavage in eukaryotic cells, but their potential target-induced collateral (trans) cleavage activity remains largely unexplored. Here, we show that catalytic rewiring of the RuvC-II catalytic site activates robust trans-cleavage activity in Acanthamoeba polyphaga mimivirus Fanzor2 (ApmFz2). The representative variant ApmFz2-EP displayed DNA- and RNA-triggered trans-cleavage, attenuated cis-cleavage, minimal TAM dependence, and activation by as few as seven nucleotides of guide-target complementarity. Mechanistic analyses indicate that relieving steric constraints surrounding the conserved alternative glutamate within the RuvC-II activates trans-cleavage and reshapes target-recognition specificity. Coupling ApmFz2-EP with nucleic acid amplification enabled FINDER, a Fanzor-based diagnostic platform for sensitive pathogen detection and broad detection across genetically diverse target subtypes. In addition, the mismatch-sensitive ApmFz2-EA variant enabled specific single-nucleotide variant (SNV) genotyping. Together, this work expands the functional scope of Fanzors and identifies catalytic-center engineering as a strategy for developing compact, programmable nucleic acid diagnostics.

bioengineering↗

bioRxiv2026

Dawn of segmented bilaterians unveiled by soft-bodied fossils in microbial pseudomorphs from the Basal Cambrian

It is estimated that the evolution of segmented bilaterians occurred during the Ediacaran, whereas most of their unambiguous body fossils did not appear until Cambrian Stage 3. This fossil gap hampers our understanding of the early history of body segmentation, which is a crucial evolutionary innovation for bilaterians. Trace fossils from the late Ediacaran and basal Cambrian suggest this gap is likely to represent a taphonomic bias, implying that the progenitors of segmented bilaterians that existed within this temporal span were hardly preserved. Here, we report a variety of segmented bilaterians from the lowermost Cambrian of South China. These fossils are preserved as microbial pseudomorphs, rather than as ordinary phosphatization. These findings demonstrate that microbial pseudomorphs represent a major pathway for the preservation of segmented bilaterians during this period, as well as an effective mechanism for overcoming the taphonomic bias that affects micro-animals with delicate, non-biomineralized bodies. Moreover, the newly described animals, among the earliest segmented bilaterians, reveal a high diversity of segmented bilaterians during Ediacaran-Cambrian transition, shedding new light on the evolution of body segmentation.

paleontology↗

bioRxiv2026

Hyperalignment Reveals Shared Information in Macaques' Idiosyncratic Fine-Grained Movie fMRI Patterns

Response hyperalignment (RHA) of fMRI patterns acquired during movie-viewing in 12 rhesus monkeys revealed shared representational spaces despite idiosyncratic functional topographies. RHA greatly improved inter-subject correlation of movie response time-series in occipital, temporal, and prefrontal cortices and afforded highly accurate between-subject decoding of movie time-points and estimation of idiosyncratic functional topographies. These results demonstrate that nonhuman primates share high-dimensional, high-capacity representational spaces encoded in idiosyncratic fine-grained functional topographies.

neuroscience↗

bioRxiv2026

Hepatic Acetate is an Essential Fuel for the Heart during Energy-Deprived States

Energy supply is fundamental to cardiac performance, yet the mechanisms by which the heart adapts to nutrient scarcity remain incompletely understood. Here, we identify acetate as a pivotal metabolic substrate that sustains cardiac contractile function during fasting-induced energy deficiency. Fasted mice reveal significant elevation of circulating acetate derived from hepatic fatty acid catabolism. Physiological concentrations of acetate alone can maintain ex vivo beating and electrical stability in Langendorff-perfused hearts. Primary mouse cardiomyocytes preferentially utilize acetate under energy-restricted conditions, which is abolished by knockdown of mitochondrial Acss1, the enzyme responsible for converting acetate to acetyl-CoA. Isotopic tracing with 13C-acetate demonstrated selective cardiac uptake during fasting. In vivo, acetate supplementation preserved heart rate and systolic function in fasted wild-type mice but not in Acss1-deficient hearts. These findings reveal an Acss1-dependent metabolic pathway enabling the heart to harness hepatic acetate as an endogenous fuel, representing a nutrient stress-responsive adaptation based on inter-organ crosstalk and implying therapeutic potential of acetate to energy-deficient heart diseases.

biochemistry↗

bioRxiv2026

Intron 13 retention expands the ADAR1 isoform repertoire to rewire PKR signaling and promote tumorigenesis

For decades, the biology of ADAR1 has been framed around two major isoforms: the nuclear-enriched p110 and the predominantly cytoplasmic p150. Here, we reveal an unexpected repertoire expansion of ADAR1 isoforms that is driven by intron retention. Specifically, intron 13 (I13) can be retained in ADAR1 transcripts, conferred by an evolutionarily conserved weaker 5SS. In addition, we found that the I13 retention (I13R) is negatively autoregulated by ADAR1 through antagonizing the binding of hnRNPA1 to I13 in an editing-independent manner. Despite being sensitive to nonsense-mediated decay, I13R generates two previously uncharacterized truncated isoforms - p90 and p130, that both lack the C-terminal portion of the deaminase domain. Intriguingly, ADAR1p90 - a derivative of the canonical nuclear-enriched p110 isoform - is predominantly cytoplasmic, that effectively represses PKR and eIF2 activation through the sequestration of immunogenic double-stranded RNA (dsRNA) substrates. Furthermore, in a colorectal cancer (CRC) cohort, p90 levels are increased in most tumors relative to matched normal tissues that positively correlates with hnRNPA1 expression. Functionally, xenografts expressing ADAR1p90 grow significantly faster and larger than those expressing ADAR1p110, indicating enhanced tumorigenic potential. These findings revise the canonical view of ADAR1 isoforms, demonstrating that intron retention can generate alternative isoforms with augmented functions that tumors readily exploit. One Sentence SummaryThe conserved retention of I13 in ADAR1 transcripts gives rise to previously uncharacterized C-terminal truncated cytoplasmic ADAR1 isoforms, p90 and p130, which, although devoid of catalytic activity, sequester immunogenic dsRNA substrates, thereby preventing PKR binding and downstream activation of eIF2.

cell biology↗

bioRxiv2026

An aromatic substrate prenyltransferase involved in the chemical diversification of flavonoids in Glycyrrhiza glabra

Prenylated isoflavonoids are widely distributed specialized metabolites within the Fabaceae and contribute to various characteristic biological activities for both plants and humans. Several aromatic prenyltransferases (PTs) have been identified in Glycyrrhiza species, which are the most widely consumed crude drugs in traditional Chinese medicine. However, these enzymes do not sufficiently explain the structural diversity of prenylated flavonoids produced in the Glycyrrhiza genus. To identify additional novel PTs, we used elicited cultured Glycyrrhiza glabra roots as source material, in which elicitor treatment of cultured roots increased the accumulation of multiple prenylated flavonoids. To identify the responsible enzyme, PT candidates were screened using G. uralensis transcriptomes, currently the sole publicly available transcriptomic resource within the genus, and a homolog designated GgBSPT1 (BSPT; a broad-substrate prenyltransferase) was subsequently isolated from elicited cultured G. glabra roots. GgBSPT1 differed from previously identified Glycyrrhiza PTs in both amino acid sequence and enzymatic properties. GgBSPT1 catalyzed 3'-prenylation of isoliquiritigenin and 6-prenylation of five flavonoids, i.e., this PT displayed broad substrate acceptance across 20 distinct flavonoid structures. Overall, elicited cultured G. glabra roots enabled the identification of a previously unrecognized PT that is functionally distinct from earlier reported Glycyrrhiza PTs. This study provides a new insight into the metabolic plasticity of Glycyrrhiza species and expands the enzymatic toolkit for future metabolic engineering of prenylated phytochemicals by the unusually broad substrate specificity of GgBSPT1. Main conclusionUsing cultured Glycyrrhiza glabra roots, we identified a new prenyltransferase involved in the formation of a variety of flavonoids, thereby revealing novel prenylated isoflavonoid pathways in licorice.

molecular biology↗

bioRxiv2026

Interactomics-driven discovery of alkaloid biosynthetic pathways in kratom

Plant monoterpene indole alkaloids (MIAs) exhibit important pharmacological activities, yet understanding of their biosyntheses remains incomplete. Since protein-protein interactions (PPIs) represent a conserved regulatory mechanism in MIA-producing plants, we developed a large-scale, yeast-based screening pipeline to profile PPIs of a key enzyme, strictosidine {beta}-D-glucosidase (SGD) from Mitragyna speciosa (kratom). This screen identified six novel medium-chain dehydrogenases/reductases (MDRs) as high-confidence interaction partners of SGD. Biochemical characterization revealed that all six MsMDRs produce an MIA we named charlamine by acting directly on the reactive strictosidine aglycone intermediate, preventing its spontaneous rearrangement and establishing a functional rationale for SGD-MDR interaction. One MsMDR additionally catalyzed the reduction of vallesiachotamine, derived from the spontaneous rearrangement of strictosidine aglycone, to another previously unreported MIA, vallesiachotaminol. Parallel transcriptomics and genomics analyses uncovered a biosynthetic gene cluster containing a dihydrocorynantheine aldehyde esterase, functioning downstream of MsMDRs. Collectively, these findings demonstrate the utility of interactomics-driven plant pathway discovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/722234v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1ccc22dorg.highwire.dtl.DTLVardef@1e03f3borg.highwire.dtl.DTLVardef@15773deorg.highwire.dtl.DTLVardef@782ae0_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2026

Lithocholic acid modulates the growth of butyrate-producing bacteria and is decreased in the feces of stunted children

Bile acids modulate the intestinal microbiota and serve as key signaling molecules in host physiology. Bile acid dysregulation has been implicated in nutritional and inflammatory diseases; however, data on the pool of bile acids present in stunted children or children suffering of environmental enteric dysfunction (EED) is limited, particularly in the upper intestinal compartment where disease phenotypes are most relevant. In this study, we performed a targeted metabolomics approach on 75 bile acids and their derivatives, including gastric and duodenal aspirates and fecal samples from almost 1000 children from two Sub-Saharan cities. We found that levels of secondary bile acids, especially lithocholic acid, are significantly lower in the feces of stunted and EED children, while ursocholic acid and its derivatives are significantly higher. Levels of primary and sulfated bile acids are also increased in the feces of children with EED. Microbiota sequencing revealed that high lithocholic acid levels are positively associated with butyrate-producing bacteria, while negatively associated with oral taxa like Streptococcus and Veillonella. In vitro tests on a panel of reference strains showed that oral bacteria bioaccumulate and are inhibited by a variety of bile acids, while lithocholic and chenodeoxycholic acids modulate the growth of several butyrate-producing bacteria. This effect was even stronger with tauro- or glycol-conjugated bile acids. Exposing stool-derived in vitro communities from children in Afribiota to these bile acids confirmed their positive impact on butyrate producers and negative effect on overgrowing oral taxa. Our findings suggest that secondary bile acids, reduced in stunting and EED, modulate the growth of butyrate-producing bacteria while suppressing harmful oral taxa, highlighting their potential as tools to modulate microbiota composition.

microbiology↗

bioRxiv2026

A High-Fidelity 3D Fluid-Structure Interaction Framework for Predictive Microfluidic Design

The commercial maturation of microfluidics remains bottlenecked by empirical prototyping and an absence of predictive digital design capabilities. Because optimizing advanced technologies such as passive particle separation fundamentally hinges on the precise coupling of fluid dynamics and particle mechanics, conventional two-dimensional or decoupled fluid simulations inherently fail to capture authentic multiscale behaviors. To bridge this gap, we establish a high-fidelity three-dimensional fluid-structure interaction framework combining a high-order Arbitrary Lagrangian-Eulerian mapping-based finite element method with a localized hierarchical dynamic mesh strategy. Engineered to accurately resolve complex multiscale hydrodynamics, this architecture utilizes deterministic lateral displacement structures as a stringent test case. Validated against experimental data for rigid microspheres and tumor cells, the framework predicts transport trajectories and critical separation diameters with sub-micron precision. Crucially, the simulation explicitly resolves the M-shaped spatial fluctuation of local size thresholds alongside the dynamic vertical migration of particles. Unveiling these hidden physical mechanisms provides a deterministic explanation for highly debated phenomena such as mixed-mode transport. By enabling the rigorous in silico evaluation of complex non-periodic architectures, this framework serves as a powerful instrument for predictive structural optimization. Such capabilities establish the essential infrastructure for microfluidic digital design, accelerating the transition from empirical trial-and-error to precision simulation-driven engineering.

bioengineering↗

bioRxiv2026

Convergent antigenic drift of the influenza hemagglutinin lateral patch across time and species

The lateral patch epitope of the H1 hemagglutinin (HA) was a dominant target of antibodies following exposure to the 2009 pandemic H1N1 virus. However, the conservation and potential for antigenic drift in the lateral patch remain unresolved. Here, we used lateral patch-specific monoclonal antibodies (mAbs) to understand the antigenicity of the lateral patch of human, avian, and swine H1Nx viruses spanning from 1918 to 2022. We identified discrete mutations that evaded lateral patch-targeting mAbs in pre- and post-2009 H1N1 viruses, leading to genetic differences in lateral patch-targeting antibodies in individuals across birth years. We observed that the lateral patch remains well conserved across zoonotic sources, suggesting existing lateral patch antibodies could protect against a future H1Nx pandemic. Together, these data support that lateral patch antigenic drift has shaped the human B cell repertoire against influenza viruses and that the lateral patch remains an attractive target for pandemic preparedness.

microbiology↗