Biology subjects

Gong, Y.

Publications and source records attributed to Gong, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Interactive Effects of Biological Maturation and Relative Age Effect on Talent Identification for U16 Elite Soccer Players

This retrospective study aims to explore the interactive effects of biological maturation and relative age effect (RAE) on talent identification. 56 male elite soccer players matched for chronological age (15.08{+/-}0.41 years) were studied. Test items included anthropometry (height, body mass, sitting height, leg length, BMI and Quetelet index), physiology (power, speed, agility, speed endurance and aerobic performance), soccer-specific skills (passing, shooting and dribbling), psychology (achievement motivation, orientation and resilience) and biological maturation (APHV) tests. The test results were analyzed independent sample t-test, Pearson correlation analysis, and stratified regression. Conclusion: Biological maturation significantly influences anthropometry (height, weight and Quetelet index), lower limb explosive, and speed (single-leg jump, standing triple jump, and 30-m sprint) in U16 male elite soccer players in Shanghai. The relative age effect shows no significant impact on talent selection indicators, which is attributed to the accumulated training load effect. The mechanisms of biological maturation and RAE in youth soccer talent selection are distinct and operate independently.

developmental biology↗

bioRxiv2026

Neural cell state modulation by PARK2 and dopaminergic neuroprotection by small molecule Parkin agonism

Parkin, an E3 ubiquitin ligase encoded by PARK2, plays a key role in both hereditary and sporadic Parkinsons disease (PD), yet there are no therapies currently available that can target this important pathway. Here, we show that Parkin is critical for successful neuronal differentiation and survival, and we develop small-molecule Parkin agonists that can protect dopaminergic neurons. Upon differentiation of neural progenitor cells, loss of Parkin results in a reduced capacity to maintain neuronal cell state, dopaminergic neuronal phenotypes, and stress resistance. Moreover, Parkin loss disrupted cell morphology and the stability of neurites. Transcriptional and single-cell analyses reveal that Parkin controls critical pathways regulating stem-like cell transitions and is needed for stable neuronal maturation. We also examined the effects of FB231, a small molecule enhancer of Parkin E3 ligase activity, in models of PD. FB231 reduced pathological -synuclein and enhanced cell survival in human iPSC-derived dopaminergic neurons treated with -synuclein preformed fibrils. Furthermore, FB231 attenuated -synuclein pathology and dopaminergic neurodegeneration in a gut -synuclein murine model of PD. Our findings support that Parkin plays a crucial role in maintaining neuronal homeostasis and that pharmacologic activation of Parkin may be a promising strategy to attenuate neurodegeneration in PD.

neuroscience↗

bioRxiv2026

Estimating chronological and brain age using risk-taking behavior under uncertainty

Risky decision-making under uncertainty reflects complex cognitive processes supported by distributed brain networks that are vulnerable to aging. However, it remains unclear whether risk-taking behavior can serve as a behavioral marker of brain aging. In the present study, we combined behavioral tasks, computational modeling, and structural magnetic resonance imaging to investigate the relationship between risky decision-making, chronological age, and brain age. A total of 55 young adults and 112 healthy older adults completed the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), along with neuropsychological assessments and neuroimaging scanning. Decision processes were quantified using computational models, including the Value-Plus-Perseveration model and Exponential-Weight Mean-Variance. Brain age was estimated from gray matter volume. The results showed significant age-related alterations in parameters reflecting feedback sensitivity, learning rate, and loss aversion in both tasks. Within older adults, several decision parameters were significantly associated with both chronological age and brain age. Regression analyses further showed that computational parameters significantly predicted chronological age and brain age, whereas traditional cognitive screening measures did not show significant predictive effect. Structural brain analyses indicated that IGT-related parameters were primarily associated with the basal ganglia, while BART-related parameters were linked to a broader network including prefrontal, cingulate, and temporal regions. These findings suggest that computational markers of risk-taking behavior capture subtle age-related changes in cognitive processes and brain deterioration. Therefore, risk-taking parameters may serve as reliable functional markers of brain aging, providing critical insights into the mechanisms underlying successful aging.

neuroscience↗

bioRxiv2026

ATG5 regulates autophagy-apoptosis-ER stress dysregulation in steroid-induced osteonecrosis of the femoral head (SONFH) pathogenesis

The aim is to investigate how ATG5 regulates autophagy, endoplasmic reticulum stress (ERS), and apoptosis in steroid-induced osteonecrosis of the femoral head (SONFH), and to evaluate ATG5-targeted inhibition as a SONFH intervention. Differentially expressed genes in SONFH were screened using GEO dataset GSE74089. Autophagy/apoptosis/ERS pathway activities were analyzed via GSEA, GO/KEGG enrichment, and GSVA. Rat bone marrow mesenchymal stem cells (BMSCs) were isolated for osteoblast modeling. Groups included: control (A), steroid-treated (B, methylprednisolone), and intervention (C, steroid + ATG5-siRNA). Autophagosome formation, apoptosis rate, and ATG5/PERK/LC3 expression were assessed by electron microscopy, flow cytometry, qPCR, and western blotting. Sixty SD rats were divided into three groups (as above). The SONFH model was established via intramuscular methylprednisolone injection, with intervention group receiving ATG5-siRNA. Bone pathology, cell death, and pathway regulation were evaluated using HE/TUNEL staining, electron microscopy, and molecular detection. Transcriptome analysis revealed synergistic activation of autophagy (ATG5/BECN1), apoptosis (CASP3/9/12), and ERS (PERK) pathways in SONFH, with ATG5 strongly correlating with all three. Steroids upregulated ATG5 to overactivate autophagy, triggering PERK-mediated ERS and ERS-specific apoptosis. ATG5-siRNA intervention inhibited autophagosome formation, reduced apoptosis, downregulated PERK, and alleviated trabecular fractures and empty lacunae. ATG5 deficiency blocked PERK signaling, suppressing both autophagic death and ERS-dependent apoptosis.ATG5 drives autophagy overactivation and ERS-apoptosis cascades via PERK pathway activation, constituting a core SONFH mechanism. Targeted ATG5 silencing effectively blocks this pathology, offering novel preventive/therapeutic strategies.

molecular biology↗

bioRxiv2026

Transcranial direct current stimulation combined cognitive training modulates risk-taking behavior in older adults

Risk-taking behavior is a complex cognitive function that often declines with aging, contributing to impaired decision-making and reduced quality of life. While transcranial direct current stimulation (tDCS) has shown promising effects in modulating cognitive function, its influence on ecologically valid, complex behaviors like risky decision-making in older adults remains poorly understood. We investigated whether a single-session stimulation over the medial orbitofrontal cortex (MOFC) combined with cognitive training could enhance decision-making in healthy older adults. In a randomized, sham-controlled study, bilateral MOFC stimulation (left/anode, right/cathode) was applied during a training task based on the Iowa Gambling Task. Pre- and post-intervention assessments utilized conventional behavioral measures and the Values-Plus-Perseveration computational model, alongside task-related fMRI to examine MOFC network changes. Compared to sham, tDCS significantly enhanced the ability to distinguish advantageous from disadvantageous options. Modeling analysis revealed stimulation-induced changes in multiple latent components, such as learning rate, loss aversion, and perseveration decay. Generalized Psychophysiological Interaction analysis showed that tDCS reconfigured the MOFC network by reducing fronto-frontal hyper-connectivity and enhancing fronto-striatal connectivity. These behavioral improvements were specifically associated with the left MOFC network targeted by anodal stimulation. Our results provide causal evidence that tDCS can mitigate age-related impairments in risk-taking by reconfiguring MOFC-related networks. These findings advance the mechanistic understanding of tDCS in aging and highlight its potential as an intervention to prevent age-related decline in decision making.

neuroscience↗

bioRxiv2026

Cigarette smoke induces colon cancer by regulating the gut microbiota and related metabolites

The causal relationship between smoking and colorectal cancer (CRC) remains unclear. In this study, a cigarette smoke-exposed mouse model demonstrated that smoking significantly increased CRC incidence by inducing gut microbiota dysbiosis and altering related metabolites. Smoke exposure reduced beneficial bacteria (e.g., Lactobacillus), increased harmful bacteria (e.g., Firmicutes and Clostridium), elevated metabolites such as histamine, and suppressed the tumor suppressor genes PARG, CPT2, and ALDH1A1, thereby promoting tumor development. Functional assays in CRC cell lines further confirmed that CPT2 knockdown enhanced malignant phenotypes, including proliferation, migration, and invasion. Clinical analysis showed that these genes were markedly downregulated in smoking-related CRC patients, with strong diagnostic value (AUC > 0.8). ConclusionSmoking promotes CRC by inducing gut microbiota dysbiosis, metabolic reprogramming, and suppression of tumor suppressor genes, particularly CPT2. These findings highlight the importance of smoking cessation in CRC prevention and provide potential biomarkers for early diagnosis and therapeutic intervention.

bioinformatics↗

bioRxiv2025

Rapid evolution of synteny associated with multiple origins of dioecy and XY sex determination

Chromosomal rearrangements are a major driver of evolutionary innovation, shaping processes including local adaptation, speciation, and sex chromosome evolution. Multispecies synteny datasets are rich in information on the drivers of genomic rearrangement, but statistical approaches that enable insights to be obtained from this information are still in their infancy. Here, we present a novel framework for the application of phylogenetic comparative methods to multispecies synteny datasets. We apply this approach to Rumex, a clade of flowering plants that exhibits rapid karyotypic evolution, including multiple origins of XY sex determination from hermaphroditic ancestors. Leveraging new genome assemblies, we find evidence for accelerated syntenic evolution associated with evolutionary transitions to dioecy, highlighting how explicit phylogenetic hypothesis testing can generate new insights into adaptive hypotheses for rearrangements.

evolutionary biology↗

bioRxiv2025

Post-weaning social isolation impairs the orbitofrontal cortical circuit subserving contagious pain and prosocial behaviors

Empathic behaviors are sensitive to environmental factors like post-weaning social isolation (SI), yet the mechanisms by which SI affects empathy remain unclear. Here, we show that mice subjected to SI exhibit marked impairments in contagious pain and prosocial behaviors, including allo-grooming and allo-licking toward cagemates experiencing inflammatory pain. Mechanistically, we identify the glutamatergic projection from the ventromedial thalamic nucleus (VM) to the orbitofrontal cortex (OFC) as critical for these empathy-like responses. SI induces hypoexcitability of OFC glutamatergic neurons and attenuates excitatory synaptic transmission within the VM[->]OFC pathway. Remarkably, chemogenetic activation of OFC neurons or the VM[->]OFC projection restores empathic behaviors in SI mice. Furthermore, we uncover a molecular basis for SI-induced OFC hypoexcitability: the downregulation of Grik3, encoding a kainate-type glutamate receptor subunit. These findings reveal a previously uncharacterized thalamocortical mechanism through which early-life social deprivation disrupts empathic behaviors, offering insights into the underpinnings of social-affective dysfunction.

neuroscience↗

bioRxiv2025

Noninvasive enrichment of circulating tumor biomarkers in a mouse model of diffuse midline glioma using focused ultrasound

BackgroundDiagnosing diffuse midline glioma (DMG) through invasive tissue biopsies is challenging due to the tumors eloquent location at the pons. Liquid biopsies offer a promising noninvasive alternative; however, their limited detection sensitivity and lack of information on the source of biomarkers pose great challenges. This study aimed to evaluate the feasibility and safety of using focused ultrasound (FUS) with microbubbles to enrich circulating DMG tumor biomarkers in blood and cerebrospinal fluid (CSF) using a mouse model. MethodsMurine DMG cells, transfected with enhanced green fluorescent protein (EGFP) and firefly luciferase (Fluc) genes, were orthotopically injected into the mouse brain. Magnetic resonance imaging was used to guide FUS targeting of the DMG tumor. Droplet digital PCR assays were developed to detect circulating tumor DNA (ctDNA) and RNA (ctRNA) of EGFP and Fluc in blood and CSF samples collected after FUS. ResultsFUS enhanced the plasma levels of EGFP ctRNA by 5.4-fold (p=0.0112), compared with liquid biopsy without FUS. CSF EGFP ctDNA was increased by 2.5-fold (p=0.0253), and Fluc ctDNA was increased by 2.6-fold (p=0.0253) with FUS. No brain tissue damage was associated with FUS sonication. ConclusionsThis study demonstrated the feasibility and safety of FUS in enriching tumor biomarkers in blood and CSF in a mouse model of DMG. The enrichment ratio for circulating biomarkers depends on the source (plasma vs. CSF), analyte type (ctDNA vs. ctRNA), and individual marker (EGFP vs. Fluc). These findings support the potential future application of FUS to advance the diagnosis of DMG through liquid biopsy. Key pointsO_LIddPCR assays were developed to detect plasma and CSF ctDNA and ctRNA in a mouse model of DMG C_LIO_LIFUS with microbubbles enriched ctDNA and ctRNA in the blood and CSF of a mouse model of DMG C_LIO_LIThe enrichment ratio on circulating biomarkers is dependent on the source (plasma vs. CSF), analyte type (ctDNA vs. ctRNA), and individual marker (EGFP vs. Fluc) C_LI Importance of the studyLiquid biopsy via detecting circulating tumor biomarkers holds enormous clinical value in the diagnosis of diffuse midline glioma (DMG), where the eloquent location of the tumor poses significant risks to invasive surgical tissue biopsies. However, the effectiveness of liquid biopsy is hindered by its low sensitivity and the lack of information about the source of biomarkers. This study demonstrated that noninvasive and spatially targeted FUS treatment can release tumor-derived DNA and RNA into the blood and CSF in a mouse model of DMG. This study also found that the enrichment effect of FUS on circulating biomarkers depends on the source (plasma vs. CSF), analyte type (ctDNA vs. ctRNA), and individual marker (EGFP vs. Fluc). This study opens new avenues for advancing noninvasive DMG diagnosis through FUS-enhanced liquid biopsy (sonobiopsy).

bioengineering↗

bioRxiv2025

Widespread loss of Y expression in the absence of transcriptional dosage compensation in Rumex hastatulus

There is growing interest in the potential role of gene regulatory evolution in the expansion and degeneration of Y chromosomes. Evolutionarily young sex chromosomes, such as those found in the flowering plant Rumex hastatulus, can provide insights into the early stages of this process. Using a new high-quality genome assembly with a well-assembled Y chromosome and a highly replicated transcriptome dataset, we found widespread underexpression of Y genes compared to their homologous counterparts on the X chromosome. We also found evidence for increased expression differences for more distantly diverged gametologs, suggestive of progressive loss of expression of Y linked genes over time. Genes with greater expression loss on the Y chromosome also showed elevated rates of protein evolution, as expected if silencing alleles mask the effects of deleterious mutations on the Y and/or if selective interference drives early degeneration in regulatory sequences. However, in contrast with the predictions of recent models of sex chromosome expansion and degeneration by regulatory evolution, there was no evidence of early dosage compensation. Overall, we conclude that in Rumex Hill-Robertson interference alone may be the main driver of Y chromosome degeneration, although further understanding of the temporal order of regulatory changes could help further untangle cause and effect.

genomics↗

bioRxiv2025

PIWIL3-piRNA Pathway Is Essential for Rabbit Oogenesis and Embryogenesis via Broad Regulation of the Transcriptome and Proteome

Female infertility represents a significant challenge in reproductive medicine. Although it is known to be primarily due to oogenic and early embryonic failures, the molecular mechanisms underlying these failures remain elusive. The Piwi-piRNA pathway is crucial for gametogenesis in diverse organisms. Yet, its role in mammalian female fertility is unclear. This is partly because most studies are done in mice, which contain only PIWIL1, PIWIL2, and PIWIL4 that are essential for spermatogenesis but not for oogenesis. PIWIL3 emerges in higher mammals and is highly expressed in human oocytes. Interestingly, female PIWIL3-knockout golden hamsters exhibit only reduced fertility without detectable defects in oogenesis. This has left the function of PIWIL3 in higher mammals, including humans, unexplored. Here, we discovered that PIWIL3 in the rabbit (Oryctolagus cuniculus) shares high homology with human PIWIL3. It is the predominant PIWI protein in oocytes in both species. Using CRISPR-cas9-mediated knockout, we demonstrated that rabbit PIWIL3 is essential for female fertility. Its loss leads to severe defects in oogenesis. Moreover, embryos lacking maternal PIWIL3 arrest developmentally at the 8-cell stage. Mechanistically, rabbit PIWIL3 binds [~]18-nucleotide piRNAs, mirroring the behavior of human PIWIL3, and is critical for piRNA biogenesis. Moreover, it regulates transcriptomic and proteomic landscapes and silences a broad array of transposons during late oogenesis yet activates another set of transposons during early embryogenesis. These findings establish PIWIL3 as a pivotal dual regulator of gene expression and transposon activity, which is essential for oogenesis and early embryogenesis in non-rodent mammals, potentially including humans.

developmental biology↗

bioRxiv2025

Biomimetic Cues Enable Predictive Mechanisms in Simulatedand Physical Robot-Human Object Handovers

Object handovers - while representing one of the simplest forms of physical interaction between two agents - involve a complex interplay of predictive and reactive control mechanisms in both agents. As human-human pairs have unrivaled skills in physical collaboration tasks, we take the approach of understanding and applying biomimetic concepts to human-robot interaction. Here, we apply the concept of passer movement cues, that is, slower movement for heavy objects and faster movements for lighter objects, to robot-human handovers. We first show that when a simulated passing agents movement is scaled with object mass, participants as receivers adapt their anticipatory grip forces according to mass in a virtual environment. We then apply the same concept to a physical robot-human handover and show that our approach generalizes to the real-world. The predictive scaling of grip forces is learned iteratively upon repeated presentations of trajectory-mass pairings, whether the masses are presented in a random or blocked order. Overall we demonstrate that the presentation of robotic kinematic cues can provide intuitive and naturalistic human predictive control in object handover. This extends the use of non-verbal cues in robot-human handover tasks and facilitates more legible and efficient physical robot-human interactions.

neuroscience↗

bioRxiv2025

De Novo Design of Anti-Aging Peptides

Aging, a universal biological process in complex organisms, is increasingly recognized to be driven by progressive loss of epigenetic information, as proposed in the Information Theory of Aging (ITOA). However, research on anti-aging peptides remains scarce, with most existing efforts confined to derivatives of natural proteins, while systematic design attempts are virtually absent. This limitation not only restricts discovery within the evolutionary sequence space but also hampers the identification of candidates with novel mechanisms and improved efficacy. Here, we present ElixirSeeker2, the first computational framework for de novo design of anti-aging peptides. By integrating modeling of known anti-aging peptides, activity scoring from the IC50 database, and penalty constraints from toxic peptides, ElixirSeeker2 enables large-scale virtual screening and identification of novel peptide candidates. Several lead peptides demonstrated significant effects in delaying cellular senescence, restoring cellular functions in vitro and in enhancing locomotor activity of aged Caenorhabditis elegans. This study not only validates the feasibility of de novo design in anti-aging interventions but also establishes a strategy for the development of next-generation biologics.

bioinformatics↗

bioRxiv2025

scRNA + TCR + BCR-seq Reveals the proportion and characteristics of dual TCR T cells and dual BCR B cells in mice infected with Echinococcus granulosus

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by Echinococcus granulosus, and the T and B cell responses and regulatory mechanisms in CE remain unclear. In this study, we analyzed the data of peripheral blood and spleen of mice infected with Echinococcus granulosus(EG) by scRNA+TCR+BCR-seq, and made the following novel findings: (1) Peripheral blood of Echinococcus granulosus (EG)-infected mice contained a higher proportion of dual TCR(T cell receptor) T cells with higher clonality than uninfected mice; (2) There was a bias in V gene usage between single TCR T and dual TCR T cells, as well as between single BCR(B cell receptor) B cells and dual BCR B cells in EG-infected mice; (3) Dual TCR Tregs, dual TCR effector CD8 T cells, dual BCR Bregs, and dual BCR memory/dividing B cells exhibited relatively high clonal expansion in EG-infected mice; (4) Shared CDR3 sequences and consistently highly expressed mRNA molecules exist between single receptor T/B and dual receptor T/B cells in EG-infected mice. KEGG enrichment analysis revealed that dual BCR B cells are closely related to the expression of factors associated with pathways such as "Th1/Th2 differentiation" and "antigen processing and presentation". These results suggest that dual TCR T and dual BCR B cells may be involved in the specific responses and regulation of EG-infected mice, providing a novel perspective for the adaptive immune response mechanisms and targeted therapy of parasitic infections. Author summaryEchinococcosis is a zoonotic disease currently prevalent mainly in various parts of Africa. At present, it cannot be completely cured; treatment relies solely on medication to alleviate symptoms. The immunoregulatory mechanisms underlying the disease remain unclear. Using single-cell RNA sequencing, we have identified a novel T- and B-cell subpopulation that may play a role in the immune response to the parasite. This finding opens a new avenue for researchers investigating parasitic diseases.

immunology↗

bioRxiv2025

The Amplified Burden of Depression in Drug-Resistant Epilepsy: Role of Limbic Network Dynamic Reconfiguration

ObjectivesTo explore potential associations between drug resistance and limbic network (LN) dynamic functional interactions in temporal lobe epilepsy (TLE), whether these LN alterations are associated with and potentially mediate comorbid depression severity, and their potential neurochemical and transcriptomic underpinnings. MethodsThis cross-sectional study included 49 patients in the Responsive group, 33 patients in the Resistant group, and 50 healthy controls (HCs). Using resting-state fMRI, we derived LN dynamic integration coefficients and used non-negative matrix factorization (NMF) to identify coactivation patterns. Depressive symptoms (Self-Rating Depression Scale, SDS), LN integration, and NMF pattern expression were compared across groups (ANOVA) and correlated. Mediation analysis tested if LN integration mediated the relationship between drug resistance status and SDS scores. LN integration differences were spatially correlated with neurotransmitter receptor density and Allen Human Brain Atlas transcriptomic data. ResultsPatients in the Resistant group reported significantly higher SDS scores than patients in the Responsive group (p = 0.008). LN integration with the dorsal attention network (DAN) and fronto-parietal network (FPN) was significantly lower in the Resistant group compared to the Responsive group (p = 0.001; p < 0.001). NMF analysis identified key LN-DAN (p = 0.013) and LN-FPN (p < 0.001) coactivation patterns. In TLE patients, DAN-LN integration was negatively correlated with depressive symptoms (r = -0.28, p = 0.01), and lower integration levels significantly mediated the relationship between group status (Resistant vs. Responsive) and increased symptom severity (p < 0.001). These LN integration coefficient differences (Responsive group vs. Resistant group) were associated with 5-hydroxytryptamine 1B (5-HT1B; r = 0.29, p = 0.036) and dopamine D2 (D2; r = -0.29, p = 0.034) receptor densities, and linked to gene expression pathways including telomerase activity regulation (p < 0.001). InterpretationThis study identifies dynamic LN dysregulation, supported by distinct neurochemical and transcriptomic profiles, as a core bridging mechanism potentially contributing to comorbid depression linked to drug response status in TLE patients.

neuroscience↗

bioRxiv2025

Telomere replication stress-induced DNA damage response triggers inflammatory signaling via canonical and non-canonical STING pathways

Telomeres are protected by the shelterin complex, but they are also common fragile sites and are particularly susceptible to replicative stress. We found that depletion of telomeric repeat-binding factor 1 (TRF1), a key shelterin component essential for telomere replication, in mouse embryonic fibroblasts (MEFs) activated ATR- and subsequent ATM-dependent DNA damage responses. TRF1 loss increased the formation of micronuclei and cytosolic DNA, leading to ATR-dependent micronuclear rupture and activation of the cGAS/STING pathway. ATM activation enhanced STING K63 modification, thereby boosting the STING/NF{kappa}B pathway. Inhibition of ATM or cGAS reduced the expression of the pro-inflammatory cytokine IL6, with combined inhibition further suppressing IL6 levels. Depletion or inhibition of STING alone decreased production of IL6 and IFN{beta}, with no major reduction by combined ATM and/or cGAS inhibitors. These findings indicate that STING acts epistatically with ATM- and cGAS-mediated inflammatory responses. Overall, the telomere replication stress and dysfunction triggered by loss of TRF1 promotes inflammation through the ATR/cGAS/STING and ATM/STING pathways.

genomics↗

bioRxiv2025

Vascularized Bioengineered Kidney Using Decellularized Scaffold Recellularized with human Placenta-Derived Angiogenic stem Cells and Kidney Organoids

A bioengineered kidney using a decellularized kidney scaffold (DKS) offers a promising solution to the kidney shortage. However, the transplantation of bioengineered kidneys using DKS recellularized with human endothelial, renal cells or others has not yet successfully achieved the vascular and renal reconstruction in vivo. In this study, we identified another type of stem cells, designated as human placenta-derived angiogenic stem cells (hPASCs), which serve as seeding cells for the vascularization of DKS. These hPASCs encompass angiogenic subpopulations, exhibit both stem cell properties and the capacity for vascular differentiation. Human fetal kidney organoids (KIO) were established as a source of renal parenchymal cells, comprising renal, immune, and vascular cell populations. We developed a vascularized bioengineered kidney by recellularizing DKS with hPASCs and KIO using a circulation perfusion culture system. The hPASCs bioengineered kidney demonstrated enhanced angiogenesis and reconstructed renal architecture in vivo, by transplantation into rat models of renal subcapsular and partial nephrectomy. Furthermore, immunofluorescence and single-cell analyses revealed that the hPASCs revascularized bioengineered kidney regenerated both vascular and renal parenchymal cells within the host. This study offers another strategy for kidney bioengineering and regeneration.

bioengineering↗

bioRxiv2025

Features fusion or not: harnessing multiple pathological foundation models using Meta-Encoder for downstream tasks fine-tuning

The emergence of diverse pathological foundation models has empowered computational pathology tasks, including tumor classification, biomarker prediction, and RNA expression prediction. However, variations in model architecture and data sources lead to inconsistent downstream performance and complicate centralized training. Specifically, the lack of data sharing makes retraining foundation models with pooled data infeasible. Alternatively, the release of model parameters enables combining multiple models during fine-tuning. Inspired by the meta-analysis method, we propose the Meta-Encoder framework, which integrates features from multiple foundation models to generate a comprehensive representation, improving downstream fine-tuning task performance. Comparative experiments demonstrate that Meta-Encoder is more effective than individual foundation models, with its strengths more pronounced in handling complex tasks. While single models may perform sufficiently well for simple tasks, Meta-Encoder can match or even surpass the best-performing single model, alleviating concerns over model selection. Moderately challenging tasks benefit from Meta-Encoders concatenation or self-attention strategies, with the latter demonstrating superior performance in more challenging scenarios. For highly complex tasks, such as high-dimensional gene expression prediction, self-attention proves to be the most effective Meta-Encoder strategy, balancing feature integration and computational efficiency. For three patch-level spatial gene expression prediction tasks (HEST-Benchmark, CRC-inhouse, and Her2ST), the self-attention strategy improved the Pearson correlation by 38.58%, 26.06%, and 20.39%, respectively, compared to the average performance of three patch-level single models. Similarly, for the TCGA-BRCA, TCGA-NSCLC, and TCGA-CRC WSI-level bulk gene expression prediction tasks, the Pearson correlation increased by 14.36%, 9.27%, and 42.55%, respectively, compared to the average performance of two WSI-level single models. By leveraging multiple pathological foundation models using Meta-Encoder, it can further improve molecular characterization in pathology images to advance precision oncology.

bioinformatics↗