Biology subjects

Yang, J.

Publications and source records attributed to Yang, J..

At least 55 records · Page 3Linked to original sources

bioRxiv2026

Emerging Haemagglutinin Mutations in Bovine-origin H5N1 Influenza Viruses from Humans and Cattle Retain Avian Receptor Binding with Increased Stability

The current H5N1 panzootic has seen an unprecedented host range expansion, including sustained circulation in US dairy cattle, detected in March 2024. By July 2026, infections had been reported on more than 1,150 dairy farms across 19 states. Although the outbreak initially centred in Texas, California has emerged as the principal focus of transmission and accounts for most human infections associated with exposure to infected dairy cattle. Continued transmission in cattle and repeated spillover into humans increase opportunities for acquisition of mammalian-adaptive mutations that could elevate zoonotic and pandemic risk. The haemagglutinin (HA) protein plays a central role in modulating virus receptor binding and airborne transmission. Here, we characterised the receptor-binding and stability phenotypes of HA mutations identified in viruses circulating in Californian dairy cattle. Receptor-binding specificity was assessed using bio-layer interferometry and pseudotype virus entry assays. All tested HA variants maintained a preference for avian-type 2,3-linked sialic acid receptors. We evaluated HA stability using fusion and thermostability assays. All mutants exhibited fusion pH values >5.5, outside the range associated with efficient airborne transmission in humans (pH 5.0-5.5). However, mutations D88G and S94N increased pH stability, with fusion pH values of 5.6 and 5.7, respectively, compared with 5.9 for wild-type HA. Viruses harbouring both mutations displayed increased thermostability. These findings demonstrate that cattle-origin H5N1 viruses retain avian-like receptor specificity despite acquiring mutations that modestly enhance HA stability. Evolution of H5N1 viruses in dairy cattle underscores the importance of genomic and phenotypic surveillance to identify mutations that may increase zoonotic risk.

microbiology↗

bioRxiv2026

Within-Subject Optogenetic Model Reveals Spatiotemporal Cortical Reorganization in Artificial Vision

Visual prostheses can elicit simple percepts such as letter forms through dynamically patterned stimulation, yet naturalistic dynamic vision remains out of reach despite hardware fully capable of high-resolution temporal control. This persistent gap suggests the bottleneck lies in how artificial input is represented by the cortex itself. A fundamental question remains unresolved: when artificial vision bypasses natural retinal encoding, what is lost in cortical representation? We address this question in this paper using a retinal optogenetic mouse model that isolates the consequence of bypassing retinal encoding while preserving downstream pathways. Using within-subject V1 cortex electrophysiology and CNN-based decoding under identical dynamic stimuli, we reveal dissociable, dimension-specific gaps. Temporally, artificial vision bypassed the frequency-dependent compression imposed by natural vision, extending stimulus-locked entrainment bandwidth. Spatially, direction-selective representations underwent systematic remapping, with disrupted phase organization and reduced encoding regularity. These findings show that bypassing natural retinal encoding reorganizes cortical representation along dissociable spatiotemporal dimensions, establishing a within-subject framework that renders such structural divergences easy to locate and quantifiable.

bioengineering↗

bioRxiv2026

Constrained Laser-Induced Cavitation for Miniaturized Treatment of Deep Vein Thrombosis

Chronic, mechanically resilient thrombi remain difficult to remove rapidly and safely using existing therapies, which are limited by slow treatment speeds, reduced efficacy against aged clots and risks associated with embolic debris. Here we introduce Constrained Laser-Induced Cavitation (CLIC), a novel approach that confines laser-induced cavitation bubble generation and collapse within a miniaturized waveguide to enhance thrombolysis. Optimized CLIC removed retracted clots at a mass-loss rate of 393.5 mg/min, [~]40-fold higher than reported state-of-the-art sonothrombolysis under similar conditions. Systematic variation of channel length and laser parameters showed that CLIC efficacy depends strongly on treatment geometry and cavitation dynamics. Post-treatment analysis revealed cylindrical channels consistent with clot removal dominated by fluid jetting and suction-driven evacuation, with cavitation shockwaves likely contributing a secondary role. Debris fragment measurements remained predominantly below a 1 mm embolic-risk threshold, consistent with a promising embolic safety profile. These findings establish CLIC as a viable strategy for rapid thrombolysis of chronic, mechanically resistant thrombi.

bioengineering↗

bioRxiv2026

CryoForge: A Self-Correcting Agent for Cryo-EM Model Building That Learns When to Act and When to Stop

Automated atomic model building has accelerated cryo-EM structure determination, but different builders leave distinct residual error profiles requiring expert inspection. The post-building challenge is to decide which local interpretations are sufficiently supported by experimental evidence to be retained, corrected or rejected. Here we introduce CryoForge, an evidence-gated post-builder agent that separates repair proposal from repair acceptance. Rule and learning-based components identify candidate regions and prioritize legal actions, whereas an independent evidence gate evaluates each edit using map and half-map support, stereochemistry, connectivity and local structural context. Supported edits are retained; unsupported or conflicting modifications are rejected, rolled back, stopped or escalated for expert review. Across a resolution-stratified benchmark, 84.9% of 26,153 released trajectories yielded standard validated improvements and 3.7% yielded low-confidence partial improvements, with no quality-degrading edit retained in the final promoted models. Relative to rule-only control, learned prioritization reduced non-improving candidates and harmful actions while preserving global structural stability. External evaluations using an alternative initializer, same-team automated/manual-assisted challenge submissions and three recently released complex assemblies showed that CryoForge adapts to distinct residual error phenotypes and performs bounded, evidence-supported correction without uncontrolled remodeling. CryoForge provides a builder-independent, scalable and auditable correction layer between automated model generation and expert structural interpretation.

bioinformatics↗

bioRxiv2026

PASTRI: Resolving Stage-Specific Cell-State Dynamics from Annotated Cell Lineage Trees

Cellular transitions between phenotypic states are fundamental to development and disease, yet quantitative analysis of their dynamics remains challenging. Here we present PASTRI (Phylogenetic Adjacency-based State Transition Rate Inference), a computational framework that infers transition rates from cell lineages/phylogenies annotated with terminal phenotypic states, such as single-cell transcriptomes. We validate PASTRI using simulated lineages and the Caenorhabditis elegans embryonic lineage. Importantly, by leveraging cell pairs at varying phylogenetic distances, PASTRI accurately resolves stage-specific transition rates, circumventing the issue of developmental changes in dynamics. Applied to three cell phylogeny datasets from our lineage-tracing experiments spanning diverse developmental/disease models and tracing systems, PASTRI uncovers rate-limiting steps in the activation of hepatic stellate cells and the differentiation of primordial lung progenitors, as well as attractor states that support cancer cell proliferation. PASTRI thus opens up a venue for dissecting cell state transition dynamics from annotated cell lineage/phylogeny.

bioinformatics↗

bioRxiv2026

Suppression of RIPK3 by EZH2 contributes to cigarette smoking-induced chemoresistance in lung cancer

Lung cancer remains the leading cause of cancer-related mortality worldwide, with cigarette smoking (CS) representing its primary risk factor. In addition to promoting tumorigenesis, chronic CS exposure contributes to chemotherapy resistance, although the underlying mechanisms remain poorly understood. Here, we established a long-term CS exposure model by repeatedly treating Lewis lung carcinoma (LLC) cells with cigarette smoke extract (CSE). After 4 months of exposure, CSE-treated cells exhibited enhanced proliferation, migration, and resistance to chemotherapy-induced cell death. Mechanistically, chronic CSE exposure suppressed receptor-interacting protein kinase 3 (RIPK3) expression by upregulating the epigenetic regulator enhancer of zeste homolog 2 (EZH2), which promoted repressive histone methylation at the RIPK3 promoter. Loss of RIPK3 impaired chemotherapy-induced cell death primarily by inhibiting ferroptosis rather than necroptosis. Importantly, genetic depletion or pharmacological inhibition of EZH2 restored RIPK3 expression and sensitized lung cancer cells to gemcitabine treatment both in vitro and in vivo. Furthermore, analysis of human lung cancer datasets revealed an inverse correlation between EZH2 and RIPK3 expression, with RIPK3 levels progressively decreasing with smoking history. Collectively, these findings identify the EZH2/RIPK3 axis as a critical mediator of smoking-associated chemoresistance and uncover a previously unrecognized role for RIPK3 in ferroptosis regulation. Targeting EZH2-mediated RIPK3 suppression may represent a promising therapeutic strategy to overcome chemoresistance in lung cancer patients with a history of smoking.

cancer biology↗

bioRxiv2026

RNA m6A demethylase ALKBH4 governs whitefly development

N6-methyladenosine (m6A) modification is the most predominant and ubiquitous internal modification of RNA in eukaryotes, serving as a key post-transcriptional regulator of gene expression that is dynamically modulated by methyltransferases (writers) and demethylases (erasers). However, while the functions of m6A methylases have been partially elucidated in insects, the identity of m6A erasers in arthropods and their chemical catalytic mechanisms, as well as biological functions, remains largely enigmatic. Here, we uncovered 2499 putative methylase genes and 1148 putative demethylase genes in 266 insect genomes, and demonstrated that ALKBH4 functions as an m6A demethylase in the whitefly, Bemisia tabaci, catalyzing the oxidative reversal of mRNA m6A modifications both in vitro and in vivo. Furthermore, we established that ALKBH4, in coordination with other core components of the m6A pathway, fulfills an essential function in regulating the transcript stability of Imaginal Disk Growth Factor 1 (IDGF1) during whitefly development. Collectively, our findings expand the evolutionary scope of the eukaryotic m6A modification system, and reveal a conserved yet insect-specific epitranscriptomic regulatory mechanism governing fundamental physiological processes and adaptive phenotypes. Significance statementThe addition of a methyl group to the N6-position of adenosine (m6A) is a highly abundant chemical modification of RNA. However, the functional role of m6A in insects and the key enzymes that regulate its levels remains poorly understood. In this study, we explored putative methylase genes and demethylase genes in hundreds insect genomes, and identified an m6A RNA demethylase, ALKBH4, in the whitefly, Bemisia tabaci. We demonstrate that ALKBH4 oxidatively reverses mRNA methylation in vivo and in vitro, in combination with other components of the m6A pathway, plays an important role in whitefly development. These findings provide new insight into m6A methylation system of insect.

zoology↗

bioRxiv2026

A longevity-associated ubiquitin E3 ligase UBE3C governs lamin B1 homeostasis through selective autophagy and delay senescence

Nuclear lamina integrity is fundamental to cellular homeostasis across the lifespan 1, and its progressive deterioration is closely linked to human aging 2. Yet, the regulatory mechanism that govern this decline and how they might be counteracted in long-lived individuals remain poorly defined. Here, by combining whole-exome sequencing of Ashkenazi Jewish centenarians with GTEx transcriptomes, we identify ubiquitin E3 ligase UBE3C strongly associated with exceptional longevity and progressively declines with age across human tissues. UBE3C knockdown triggers premature senescence and destabilizes key nuclear lamina components Lamin B1 (LMNB1) and Lamin B receptor (LBR), while the longevity-associated UBE3C variant delays senescence and preserves LMNB1/LBR expression. Mechanistically, UBE3C interacts directly with LMNB1/LBR and modulates their abundance via selective autophagy. Notably, we uncover the ER- resident autophagy trigger CKAP4 3 bridges UBE3C and LMNB1. UBE3C loss enhances LMNB1-CKAP4 binding, linking nuclear lamina turnover to autophagy. Together, our findings establish UBE3C as a central guardian of nuclear lamina maintenance during senescence and offering novel insights into interventions against age-related nuclear lamina deterioration.

cell biology↗

bioRxiv2026

A benchmarking framework for single-cell genome-scale metabolic model construction

Single-cell genome-scale metabolic models (scGEMs) enable characterization of metabolic heterogeneity underlying cellular states and phenotypes. However, methodological choices during scGEM construction can substantially alter model structure and predictions, challenging the reliability and comparability of resulting analyses. Here, we established a systematic benchmark to assess three key construction factors: data preprocessing method, model extraction method (MEM) and gene expression threshold. We evaluated 26 strategies representing different combinations of these factors across nine scRNA-seq datasets in three dimensions: accuracy, sensitivity to expression perturbation and computational feasibility. We found that MEM had the greatest influence on most accuracy metrics, data preprocessing strongly influenced the discrimination of cellular identities, and expression threshold balanced model completeness and cellular specificity. These findings indicate that strategy performance varies across evaluation criteria. Our benchmark provides practical guidance for strategy selection and an empirical basis for standardized evaluation and future scGEM method development.

systems biology↗

bioRxiv2026

Introns encode a vast class of Kink-loop RNAs that autoregulate pre-mRNA splicing

Introns occupy nearly one-third of the human genome, yet whether they encode widespread regulatory functions remains unclear. Here, we identify a vast new class of intron-derived Kink-loop RNAs (klRNAs) that autoregulate host pre-mRNA splicing. We developed orthogonal sequencing methods to systematically uncover approximately 15,200 and 3,500 previously unannotated klRNAs in humans and mice, respectively. Bound by the conserved RNA-binding protein 15.5K, klRNAs are compact orphan RNAs characterized by stereotypically positioned terminal C/D motifs that form K-loop structures. Depletion of 15.5K broadly disrupts klRNA biogenesis. Functional and genetic perturbations establish that klRNAs suppress host intron excision through a K-loop-dependent mechanism. Together, our findings establish klRNA-mediated autoregulation as a widespread principle governing intron fate and reveal a previously unrecognized regulatory layer encoded within mammalian introns.

molecular biology↗

bioRxiv2026

A pyramidal silicon nanopore for single misfolded Tau protein characterisation

Solid-state nanopores offer a versatile platform for single-molecule sensing owing to their mechanical robustness, tuneable geometry, and compatibility with scalable fabrication. Here, we present a pyramidal silicon nanopore with a 40 nm sensing aperture for label-free characterisation of protein molecules by resistive pulse sensing. The nanopore operates stably over transmembrane voltages ranging from -2 to +2 V and across a broad range of electrolyte concentrations, enabling analysis under diverse experimental conditions. As molecules traverse the confined sensing region, transient ionic current modulations are generated that reflect their excluded volume and molecular geometry. Using this approach, we characterise unlabelled Tau species spanning monomeric proteins, intermediate aggregates, and mature fibrillar assemblies. Analysis of the resulting current signatures, together with simplified geometrical models, enables reconstruction of molecular dimensions and discrimination of distinct Tau populations based on their electrical fingerprints. These results demonstrate that pyramidal silicon nanopores provide a sensitive and scalable platform for label-free monitoring of structurally heterogeneous protein aggregation and establish a framework for investigating protein aggregation using solid-state nanopore sensing.

bioengineering↗

bioRxiv2026

Diet-derived peptides mediate the effects of dietary protein source on gastrointestinal health

Plant-based diets support gastrointestinal (GI) health while animal-based diets can disrupt gut homeostasis. Although multiple aspects of these diet types are believed to confer their respective effects, the role of their protein component is less well understood. Here, we conducted a randomized crossover-controlled feeding trial wherein healthy subjects consumed 70% of their daily protein intake in the form of pea protein (PP) or egg white protein (EWP) isolate (NCT05619939). Individuals who consumed EWP reported increased GI symptoms and exhibited elevated intestinal permeability. In contrast, these endpoints did not change following PP consumption. Fecal analysis showed increased diet-derived peptides only following EWP consumption, which was associated with resistance of EWP isolate to degradation by digestive enzymes in vitro. Metagenomic, metaproteomic and metabolomic analyses of stool after the EWP-based diet showed reduced abundance of multiple gut-protective bacterial species and increased bacterial amino acid utilization compared to samples following the PP-based diet. Dietary peptides in the gut luminal content of EWP-fed subjects reduced metabolic function of intestinal epithelial cell in culture. Providing an amino acid-based diet mimicking EWP composition to mice prevented colonic accumulation of diet-derived proteins and GI dysfunction associated with EWP diet consumption. Collectively, these findings demonstrate that dietary protein source is a key mediator of GI function, revealing a modifiable lifestyle factor that impacts human health.

physiology↗

bioRxiv2026

Hidden genetic diversity in 320 nearly-complete East Asian genome assemblies

East Asian populations, representing over 20% of the global population, remain critically underrepresented in human genomic studies, limiting our understanding of population-stratified genetic variation and its implications for health and disease. Here we present the first phase of the Asian Pan-Genome project (APG), comprising 320 nearly complete, fully phased haploid genome assemblies from 160 East Asian individuals. These assemblies achieve unprecedented quality, with an average contig N50 of 144.3 megabase pairs and an average quality value of 64.5. Leveraging these superior assemblies, we reveal previously uncharacterized diversity in human repeatome, including population-stratified patterns in centromere satellites and rDNA arrays. Compared to existing global human genome assemblies, the newly generated genomes supplement 152 million base pairs of novel sequences, 355 gene gains, 18,300 structural variation loci and 26 large euchromatic inversions missing from current human pangenomes. We perform population stratification analyses of structural variations, and further resolve the structural haplotypes of complex genomic regions such as Major Histocompatibility Complex and Survival Motor Neuron loci across global pangenomes, exemplifying tandem-duplicate and inversion-rich complex locus architectures in the human genome, respectively. This resource provides a critical foundation for human genetic studies, especially for East Asian populations, promoting more accurate variant discovery, reducing bias, and ultimately advancing the equity and efficacy of genomic medicine.

genomics↗

bioRxiv2026

Mutations in severe human H5N1 cases facilitate evasion from human mucus and antivirals

In late 2024, two individuals in Canada and the United States were treated in intensive care for acute respiratory distress caused by infection with the avian Influenza A Virus H5N1 2.3.4.4b genotype D1.1. Viral sequence data obtained from sampling these patients indicated mixed alleles at haemagglutinin (HA) positions 190 and 226. Mutations at these positions are key determinants of HA usage of 2,6-linked sialic acids (SA), the most abundant influenza receptors in human upper respiratory tracts. Thus, these mutations raised concerns about human adaptation and pandemic potential of the H5N1 virus. In this study, we investigated the impact of the mutations at residues 190 and 226 in H5 HA. We studied the receptor binding properties, cell entry phenotypes and fitness impacts of the mutations using recombinant proteins, pseudotyped lentiviruses, and in the context of influenza viruses using reverse genetics. The mutations did not confer any detectable 2,6-linked sialic acid receptor usage either alone or in combination. Rather, viruses carrying these mutations exhibit weakened binding towards 2,3-linked sialic acid receptors. This correlated with an enhanced capacity to evade human airway mucus, and a reduced susceptibility to oseltamivir and zanamivir. This research underscores that in addition to the way HA interacts with SA as entry receptors, other factors that impact the HA/NA balance might influence the evolutionary trajectory of a zoonotic virus in the human respiratory tract. This study presents a new paradigm for the evolutionary drivers of HA, where reduced sialic acid binding can serve as an advantage for escape from host barriers and antivirals.

microbiology↗

bioRxiv2026

Machine Learning-Assisted Evolution of Broadly Functional Enzyme Libraries

Biocatalysis offers sustainable solutions to pressing challenges in chemical synthesis by exploiting the remarkable efficiency and selectivity of enzymes. Importantly, enzymes are able to accommodate non-native substrates and mediate transformations outside of their natural repertoire. Enzymes can be engineered for diverse applications by harnessing these promiscuous activities and optimizing them using directed evolution (DE). The success of a DE campaign, however, depends on the availability of a protein starting point that displays detectable levels of the desired function. To find a starting point, researchers often screen libraries of protein variants for novel activities, typically with low rates of success. Here, instead, we diversified the active site of a desirable parent protein and applied machine learning to generate informed, promiscuous libraries of protein variants. Specifically, we tested 26 different carbene and nitrene transfer reactions and used active learning-assisted directed evolution (ALDE) to generate optimized protoglobin variants with high activity across multiple reactions. We observed improvements in activity and selectivity for every reaction performed by the parent enzyme in at least one member of the ALDE-predicted libraries. Moreover, variants from these libraries can catalyze 5 out of 10 reactions not catalyzed by the parent protoglobin. These results indicate that supervised machine learning can help guide the construction of high-value enzyme libraries with expanded catalytic scope. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/740427v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@fc2071org.highwire.dtl.DTLVardef@b5e787org.highwire.dtl.DTLVardef@737976org.highwire.dtl.DTLVardef@12b5e51_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

A highly penetrant LMNA R541C variant associated with dilated cardiomyopathy leads to dysregulation in metabolism and proliferation pathways in stem cell-derived cardiomyocytes

BackgroundLMNA codes a widely expressed nuclear cytoskeletal protein (lamin A/C) with multiple important functions. Pathogenic LMNA genetic variation may lead to autosomal dominant cardiomyopathy, though the severity and rate of progression can vary with the specific nucleotide change and location. Prior studies showed that induced pluripotent stem cells (iPSC)-derived cardiomyocytes (iCMs) with LMNA R541C exhibited reduced LMNA protein abundance, increased sarcomere disorganization, and abnormal electrophysiology. MethodsWe investigated the LMNA-R541C variant that exhibits a highly penetrant and severe clinical cardiomyopathy phenotype using transcriptomic analysis of iCMs. Patient-derived iPSCs with CRISPR-corrected (clustered regularly interspersed short palindromic repeats) isogenic control cells and CRISPR knock-in LMNA-R541C heterozygous iPSCs were generated for isogenic controlled experiments. ResultsIn differential gene expression analyses we observed that LMNAR541C/WT iPSC-derived cardiomyocytes had consistent perturbations in 123 genes across CRISPR-corrected and knock-in experiments compared to controls. Pathway analysis identified that the G2M checkpoint and oxidative phosphorylation processes were consistently dysregulated and confirm these findings in previously published iPSC and murine models. DiscussionThese results implicate perturbed gene expression and pathways that may contribute to the severe phenotypes in LMNA-R541C. Informatic analysis of pathways suggests several drug classes including multiple cardiac glycosides as potential targeted therapeutic candidates to be explored.

genomics↗

bioRxiv2026

Spatial Patterning of Otic Vesicles in Human Inner Ear Organoids

During development axial patterning of the otic vesicle sets up the blueprint for the adult inner ear. While human inner ear organoids recapitulate the initial steps of ear formation, whether and how vesicles are properly regionalised remains unknown. Here, we combine re-analysis of published single-cell transcriptomic datasets with 2D and 3D imaging to assess axial patterning in human stem-cell-derived otic vesicles using a new PAX2-reporter line. We find that the transcriptional signatures of individual cells do not conform to clearly defined regional characteristics, with some cells co-expressing conflicting regional markers, while markers that should be co-expressed are not. Some vesicles establish spatially segregated molecular domains. However, patterning is incomplete, stochastic, and restricted to a subset of vesicles. Within the same aggregates, patterned axes lack consistent orientation. Together, our findings point to incomplete segregation of transcriptional programs that are mutually exclusive in vivo and to the absence of morphogen gradients that are crucial for otic vesicle patterning. >One sentence summaryIn human inner ear organoids, otic vesicles show incomplete and disorganized regionalisation pointing to fundamental limits of self-organization, while suggesting new routes to increase cell complexity in vitro.

developmental biology↗

bioRxiv2026

Chemokine-Dependent Natural Killer Cells Prevent Pulmonary Metastasis in a Newly Established Mouse Osteosarcoma Model

Rampant genomic instability of osteosarcoma (OS) and associated inter- and intratumoral heterogeneity convey a high risk of metastasis despite contemporary multimodal therapy. A mouse primary OS tumor model, originating from Myc-overexpressing Trp53-null mesenchymal progenitor cells, closely mimics cardinal genetic features and gene expression patterns of human OS samples. Subcutaneous injection of OS cells into immunocompromised NSG mice produced extensive metastases, whereas many fewer metastases occurred in T cell-deficient nude mice, suggesting a principal role for innate immunity in controlling OS dissemination. Depletion of natural killer (NK) cells in nude mice facilitated OS metastasis. OS cells released a suite of chemokines, with CCL2 the most prominent. A genome-wide CRISPR/Cas9 screen in OS cells identified 11 genes, including Ccl2, whose loss facilitated pulmonary metastasis in nude mice. Disruption of CCL2 in OS cells partially phenocopied the effects of antibody-dependent NK cell depletion, underscoring a plausible OS-NK signaling pathway that limits OS metastasis. SignificanceOsteosarcoma exhibits complex genomic instability and a propensity for pulmonary metastasis that limit chemotherapeutic response and patient survival. Despite the plethora of heterogeneous genetic alterations that connote poor prognosis, a novel preclinical in vivo model for studying metastasis highlights potentially targetable signaling between osteosarcoma cell-derived chemokines and pulmonary NK cells.

cancer biology↗