Biology subjects

ZHU, J.

Publications and source records attributed to ZHU, J..

4 recordsLinked to original sources

bioRxiv2026

Systematic toxicological study of PFOS/PFOA co-exposure driving prostate cancer: Core target identification, TME immune remodeling, and combination drug prediction

BackgroundPer- and polyfluoroalkyl substances (PFAS), particularly perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are persistent organic pollutants ubiquitous in the environment. Epidemiological evidence has closely linked them to an elevated risk of prostate cancer (PCa). However, the precise molecular mechanisms by which combined PFOS/PFOA exposure promotes prostate cancer and their dynamic effects on the tumor microenvironment remain unclear. MethodsThis study constructed a multi-module analytical framework integrating network pharmacology and computational biology: (1) Through ADMET toxicity prediction, multi-database target collection (three-way Venn analysis), panoramic GO/KEGG enrichment, focused androgen receptor (AR) axis analysis, GWAS genetic association validation, protein-protein interaction (PPI) network construction, machine learning-based independent screening, and a relaxed intersection strategy, we systematically identified PFOS/PFOA-prostate cancer core targets. (2) Subsequently, a PFAS-PTS score weighted purely by Cox coefficients was employed to drive gene set variation analysis (GSVA)-based pathway enrichment, tumor microenvironment (TME) deconvolution, ordinary differential equation (ODE)-based kinetic modeling, and drug intervention prediction. ResultsTarget collection identified 100 shared PFOS/PFOA-prostate cancer targets, from which 18 core targets were determined after multi-module screening. These targets were significantly enriched in the AR signaling axis, the PI3K-AKT pathway, and cell cycle regulation. Molecular docking confirmed strong binding affinities of PFOS/PFOA with AR (-9.49/-8.56 kcal/mol), AKT1 (-7.56/-6.93 kcal/mol), and PTEN (-6.36/-6.08 kcal/mol). GSVA revealed that the G2M checkpoint and E2F target gene pathways were significantly upregulated in the high-risk group (padj < 0.001), whereas the androgen response pathway was downregulated (padj = 4.8e-4). TME deconvolution (GSE141445, NNLS) revealed a significantly increased proportion of tumor cells (PCa) (p = 2.4e-4) and markedly reduced CD8+ T cell infiltration (p = 5.7e-4) in the high-risk group, indicating immunosuppressive microenvironment remodeling. ODE-based kinetic modeling confirmed that PFAS promoted tumor cell proliferation and suppressed immune surveillance in a dose-dependent manner. Drug intervention simulation demonstrated that the combination of enzalutamide and Alpelisib achieved optimal tumor cell inhibition (33.9% predicted by the ODE model). ConclusionPFOS/PFOA promote prostate cancer progression primarily through multi-target synergy involving AR axis disruption, PI3K-AKT pathway activation, and cell cycle dysregulation, while reshaping an immunosuppressive tumor microenvironment. The integrative computational framework established in this study provides systematic computational evidence for risk assessment and therapeutic intervention in PFAS-associated prostate cancer.

pharmacology and toxicology↗

bioRxiv2025

A bibliometric analysis of research on the mitochondrial roles in prostate cancer and the virtual design of LONP1 - specific antibodies using the GeoBiologics platform

BackgroundProstate cancer remains one of the most prevalent malignancies among men globally, with its incidence showing an upward trend worldwide. Mitochondria, as central regulators of cellular energy metabolism, play crucial roles in prostate cancer initiation, progression, and drug resistance mechanisms. While mitochondria-targeted therapeutic strategies have emerged as a significant focus in cancer research in recent years, comprehensive bibliometric analyses mapping the evolving landscape of this field remain scarce. This study systematically investigates research trends in mitochondrial-prostate cancer interactions through bibliometric methods, identifying LONP1 as an emerging research focus in mitochondria-related prostate cancer therapy. Building on these findings, we employed artificial intelligence to virtually design a LONP1-specific antibody, proposing novel therapeutic targeting strategies for this field. MethodsUtilizing the Web of Science Core Collection database (2015-2023), we conducted visualization analyses through CiteSpace and VOSviewer to map network relationships among countries, institutions, journals, authors, and keywords. Building on this foundation, a humanized antibody targeting LONP1 was computationally designed and screened through the GeoBiologics platform. ResultsAnalysis of 452 included publications revealed the United States and China as leading contributors in this research domain. The field has progressively transitioned from fundamental mechanistic investigations to clinical applications, particularly focusing on drug resistance mechanisms, and combination therapy. LONP1 was identified as a critical mitochondrial regulator strongly associated with prostate cancer progression. Our AI-designed antibody (Antibody_82) demonstrated superior binding affinity and stability through effective targeting of LONP1s ATP-binding site. ConclusionThis bibliometric study delineates evolving research trends in mitochondrial involvement in prostate cancer. The developed LONP1-targeting antibody shows promising therapeutic potential for castration-resistant prostate cancer (CRPC) patients, potentially offering more effective treatment alternatives.

cancer biology↗

bioRxiv2025

Ultrasound Directly Activates Sparse Neurons and Modulates Visual Circuits in Deafened Mice

Focused ultrasound neuromodulation (FUN) is widely regarded as a next-generation technology for neural modulation, with applications spanning rodents, non-human primates, and humans. While mechanistic studies are advancing, a persistent confound--auditory interference--casts doubt on whether ultrasound exerts direct mechanical effects or merely indirect auditory responses. To resolve this, we engineered a circular ultrasound transducer compatible with two-photon calcium imaging and examined its effects on the primary visual cortex (V1) of surgically deafened mice, eliminating auditory contributions. Our results reveal that ultrasound directly activates a sparse subset of ultrasound-sensitive neurons (USSN) (response rate >30%) in V1, comprising only a small fraction of the total population and exhibiting a spatially sparse distribution. The proportion of USSN scale with ultrasound pressure, confirming a direct neuromodulatory effect independent of audition. Intriguingly, despite this sparse activation, ultrasound significantly modulates V1 circuitry: it alters the dynamics of light-sensitive neurons (LSN), with subsets showing excitation, inhibition, or no change in response to visual stimuli. These findings provide the first rigorous in-vivo evidence that FUN induces direct mechanical effects on neural activity, disentangling them from auditory confounds. By demonstrating both the specificity and broader circuit-level impact of ultrasound in deafened mice, this study reframes our understanding of FUNs mechanisms and strengthens its potential as a precise neuromodulatory tool. HighlightsO_LIUltrasound directly activates sparse neurons in deafened mice, demonstrating auditory-independent effects. C_LIO_LISparse ultrasound-sensitive neurons in V1 show pressure-dependent responses. C_LIO_LIUltrasound modulates visual circuitry, with diverse excitatory and inhibitory effects. C_LI

neuroscience↗

bioRxiv2024

Functional imaging of whole mouse embryonic development in utero

Despite significant advances in structural and genetic studies, investigations of early embryonic functions, such as brain activity, have long been constrained by technical challenges. Functional ultrasound (fUS) has emerged as a breakthrough modality, enabling real-time monitoring of brain activity with exceptional spatial and temporal resolution and offering unprecedented opportunities for studying functional embryonic development. In this study, we used fUS to monitor whole-embryo activity in mice from embryonic days E8.5 to E18.5, revealing patterns of neural activity throughout embryogenesis. This approach provides new opportunities to explore brain development dynamically as it unfolds. Moreover, we observed embryo responses to external stimuli, including sound, in both mice and cynomolgus macaques, offering insights into early sensory processing and neural maturation. In summary, our study establishes fUS as a powerful tool for studying embryonic brain functional development, with significant implications for scientific research, especially in non- human primate models, and clinical applications.

developmental biology↗