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Liang, L.

Publications and source records attributed to Liang, L..

At least 55 records · Page 3Linked to original sources
bioRxiv2025

SpIC3D imaging: Spinal In-situ Contrast 3D imaging

High-definition visualization techniques are critical for understanding the neuroanatomy of the spinal cord, an essential structure for sensorimotor and autonomic functions, in both healthy and pathological conditions. Magnetic resonance imaging (MRI) is a common method for visualizing neural structures in 3D. However, techniques for spinal cord MRI have historically achieved limited visualization of rootlets and nerves, especially at lower spinal levels, due to their highly complex and compact organization. Here we developed a spinal in-situ contrast 3D imaging (SpIC3D) method that allows visualization of spinal compartments in fixed animal and human specimens with ultra-high resolution at various spinal levels. Using SpIC3D, we achieved quantification of neuronal cell density in dorsal root ganglia, multi-segment identification of individual rootlets and roots, and volumetric reconstruction of multiple spinal structures for computational modeling. SpIC3D provides a basis for accelerated spinal pathology characterization and personalized spinal cord stimulation treatments.

neuroscience↗
bioRxiv2025

Chromosome-Level Genomics Unravels Trichiurus 300-Year Taxonomic Enigma: Cryptic Speciation and Glacial Adaptations in Northwest Pacific Coast

The Trichiuridae family, comprising ecologically and commercially important hairtails, has faced persistent taxonomic uncertainties due to historical misclassifications and conflicting morphological criteria. While molecular approaches have advanced understanding, mitochondrial-based phylogenies and misapplied nomenclature have obscured species boundaries and population dynamics. Here, we integrate a chromosome-level genome assembly of Trichiurus japonicus with whole-genome resequencing of congeneric species to resolve three centuries of taxonomic ambiguity. Combining phylogenomic, demographic, and selective sweep analyses, we resolve taxonomic uncertainties by redefining species boundaries, reconstructing population dynamics, and identifying genomic adaptations underpinning environmental resilience. We confirm T. japonicus and T. nanhaiensis as distinct species. Crucially, we identify a cryptic Indian Ocean-derived lineage, misclassified as T. lepturus in previous studies, as the novel species Trichiurus sp., underscoring the impact of commercial trade on taxonomic confusion. Population genomics reveals panmixia in T. japonicus across the Northwest Pacific, supporting unified stock management. Selective sweeps in T. japonicus pinpoint cold-resilient genes (metabolic, anti-apoptotic, visual), consistent with its demographic stability during Pleistocene glaciations. This study provides a genomic roadmap for disentangling taxonomic conflicts in morphologically cryptic taxa and advances strategies for sustainable fisheries management under climate change.

evolutionary biology↗
bioRxiv2025

Single-cell multiomics of neuronal activation reveals context-dependent genetic control of brain disorders

Most causal variants for neuropsychiatric disorders (NPD) remain unknown. A major hurdle is that disease variants may act in specific contexts, such as during neuronal activation, which is difficult to study in vivo at the population level. We profiled single-nucleus neuron-activation multiomics in human induced pluripotent stem cell (iPSC)-derived neurons from 100 donors, revealing the NPD-relevant transcriptomic/epigenomic landscape of neuronal activation. We identified abundant genetic variants associated with activity-dependent gene expression (eQTL) and chromatin accessibility (caQTL), the latter explaining larger proportions of NPD heritability. Integrating multiomic data with genome-wide association studies (GWAS) further revealed NPD risk variants and genes with effects detected only upon stimulation, such as activity-dependent cholesterol metabolism. Our work highlights the power of cell stimulation to reveal context-specific "hidden" genetic effects.

neuroscience↗
bioRxiv2025

Cholecystokinin input from the anterior cingulate cortex to the lateral periaqueductal gray mediates nocebo pain behavior in mice

The nocebo effect, the evil twin of the better-known placebo effect, in which anticipation of harm worsens pain and other symptoms, is increasingly thought to be responsible for poor clinical outcomes. In humans, nocebo hyperalgesia (i.e., increased pain sensitivity) is blocked by proglumide, a cholecystokinin (CCK) receptor antagonist. Yet, the neural circuitry underlying nocebo hyperalgesia remains unidentified, largely due to a lack of appropriate animal models. Independently, our two laboratories developed unique animal models of CCK-dependent nocebo hyperalgesia in which the expectation of pain was elicited by environmental or social cues. We find that both nocebo paradigms share a neural circuit involving CCK release from neurons projecting from the anterior cingulate cortex to the lateral periaqueductal gray. This previously unrecognized pathway could represent a promising target for therapeutic interventions in pain-related disorders. One-Sentence SummaryPain expectations, whether environmentally conditioned or socially transmitted, are mediated by a shared neural circuit involving cholecystokinin (CCK) projections from the anterior cingulate cortex (ACC) to the lateral periaqueductal gray (PAG).

neuroscience↗
bioRxiv2025

Coordination of distinct sources of excitatory inputs enhances motion selectivity in the mouse visual thalamus

Multiple sources innervate the visual thalamus to influence image-forming vision prior to the cortex, yet it remains unclear how non-retinal and retinal input coordinate to shape thalamic visual selectivity. Using dual-color two-photon calcium imaging in the thalamus of awake mice, we observed similar coarse-scale retinotopic organization between axons of superior colliculus neurons and retinal ganglion cells, both providing strong converging excitatory input to thalamic neurons. At a fine scale of [~]10 {micro}m, collicular boutons often shared visual feature preferences with nearby retinal boutons. Inhibiting collicular input significantly suppressed visual responses in thalamic neurons and specifically reduced motion selectivity in neurons preferring nasal-to-temporal motion. The reduction in motion selectivity could be the result of silencing sharply tuned direction-selective colliculogeniculate input. These findings suggest that the thalamus is not merely a relay but selectively integrates inputs from multiple regions to build stimulus selectivity and shape the information transmitted to the cortex. HIGHLIGHTSChronic dual-color calcium imaging reveals diverse visual tuning of collicular axonal boutons. Nearby collicular and retinal boutons often share feature preferences at [~]10 {micro}m scale Silencing of collicular input suppresses visual responses in the majority of thalamic neurons. Silencing of collicular input reduces motion selectivity in thalamic neurons.

neuroscience↗
bioRxiv2025

Mesoscale landscaping of the TRIM protein family reveals a novel human condensatopathy

The mesoscale organization of cells is central to cellular physiology and pathology. Cellular condensates often form via biomolecular phase separation, mediated by intrinsically disordered regions (IDRs) and represent a key mechanism for mesoscale organization. The TRI-partite Motif (TRIM) family of ubiquitin ligases is implicated in diverse cellular functions and disease, yet the role of biomolecular condensation in TRIM family organization remains understudied. Here, we systematically investigate the mesoscale localization of 72 TRIM proteins, revealing that a majority form condensates in distinct cellular compartments. IDR content correlates with dynamic condensate formation, suggesting a critical role in mesoscale organization. Focusing on TRIM8, associated with a neuro-renal disorder, we demonstrate that disease-causing truncations of the TRIM8 C-terminal IDR result in a condensatopathy, characterized by disrupted condensation, proteasomal regulation, and TAK1/NF{kappa}B signaling. Functional assays in cellular and animal models link these disruptions to podocyte dysfunction and impaired response to injury. Our findings establish a framework for understanding condensatopathies and the mesoscale principles governing TRIM family organization and function.

cell biology↗
bioRxiv2024

Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate

Inorganic phosphate (Pi) is fundamental to life, and its intracellular concentration must be tightly regulated to prevent toxicity. XPR1, the only known phosphate exporter, plays a crucial role in maintaining this delicate balance. However, the mechanisms underlying the function and regulation of XPR1 remain elusive until now. Here we present cryo-electron microscopy structures of the human XPR1-KIDINS220 complex in both substrate-free closed states and substrate-bound outward-open states, as well as the structure of an XPR1 mutant alone in a substrate-bound inward-facing state. In the presence of inositol hexaphosphate (InsP6) and phosphate, the XPR1-KIDINS220 complex adopts an outward-open conformation. InsP6 binds both the SPX domain and the peripheral juxtamembrane regions of XPR1, indicative of an active phosphate-export state. Conversely, in the absence of either phosphate or InsP6, the complex assumes a closed state, where the extracellular half of transmembrane 9 occupies the outward cavity, and a C-terminal plug-in loop blocks the intracellular cavity. Notably, XPR1 without KIDINS220 adopts a closed state despite the presence of phosphate and InsP6. The functional mutagenesis experiments further demonstrate that InsP6, whose concentrations fluctuate in response to Pi availability, functions synergistically with KIDINS220 to regulate the phosphate export activity of XPR1. These findings not only elucidate the intricate mechanisms of cellular phosphate regulation but also hold promise for the development of targeted therapies for ovarian cancer, where XPR1 plays a significant role.

biophysics↗
bioRxiv2024

Involvement of Hepatitis B Core-Related Antigen in Viral Genome Integration in Patients With Prior Hepatitis B Virus Infection

BackgroundThe incidence of non-B non-C hepatocellular carcinoma (NBNC-HCC), which is negative for hepatitis B surface antigen and hepatitis C virus antibodies, is on the rise. Relatively high numbers of NBNC-HCC patients are hepatitis B core antibody (HBcAb) positive, suggesting that previous HBV infection may play a role in NBNC-HCC development, though the exact mechanisms are unclear. This study aimed to investigate whether HBV genomes are integrated into the host genome of HBcAb-positive NBNC-HCC cases and how these integrations may contribute to cancer development and progression. MethodsHBV detection PCR using HBV-specific primers on DNA extracted from HBcAb-positive NBNC-HCC tissue samples was performed. Positive samples were further examined for HBV integration sites using viral DNA-capture sequencing. Additionally, hepatitis B core-related antigen (HBcrAg) serum levels were measured to assess whether they could be predictive for HBV detection PCR results. ResultsAmong 90 HBcAb-positive NBNC-HCC samples, HBV genome amplification was detected in 18 samples, and elevated HBcrAg levels were associated with the HBV detection PCR results. Seventeen of these samples exhibited HBV integration. The HBV genome was integrated near the TERT gene in 7 samples, resulting in significantly increased TERT mRNA levels; in the KMT2B gene (2 samples); and downstream of LOC441666 (2 samples). ConclusionThe integration sites we identified in our samples have been previously reported in HBV-related HCC, suggesting that HBV integration may also contribute to hepatocarcinogenesis in HBcAb-positive NBNC-HCC. Furthermore, HBcrAg could serve as a potential, noninvasive marker for detecting HBV integration in these cases.

microbiology↗
bioRxiv2024

Structural insights into cholesterol sensing by the LYCHOS-mTORC1 pathway

The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cellular metabolism and growth by coordinating nutrient resources, including cholesterol, and its aberrant activation is linked to various age-related diseases. LYCHOS is a cholesterol sensor on the lysosome and bound to the GATOR1 complex, a GTPase-activating protein for the Rag GTPase, at high cholesterol concentrations, thereby activating the protein kinase mTORC1. However, how LYCHOS senses cholesterol and transduces signal to GATOR1 remain largely unknown. Here we report six cryo-electron microscopy structures of human LYCHOS, depicting five distinct states. These are categorized into a contracted state when complexed with a sufficient amount of the cholesterol analogue cholesteryl hemisuccinate (CHS), and an expanded state when CHS is deficient. The structure forms a homodimer, within each monomer the transmembrane region is divided into a permease-like domain (PLD) and a GPCR-like domain (GLD) with two clearly defined adjacent cholesterol binding sites between them. The PLD shares a conserved Na+/H+ antiporter (NhaA) fold, which much resembles plant auxin transporter PINs. Cholesterol locates between PLD and GLD and cholesterol binding induces a translation of GLD towards PLD and exposes the cytosolic extension of transmembrane 15, which mediates the interaction between LYCHOS and GATOR1. Strikingly, structure-guided mutations of Gly702 in GLD of LYCHOS increase its affinity for cholesterol, leading to sustained mTORC1 activation in cells. This indicates that LYCHOSs moderate affinity for cholesterol is crucial as a cholesterol sensor. Our results not only showed a solute carrier mechanistically coordinates a GPCR domain, elucidating the structural mechanism of cholesterol sensing by the mTORC1 pathway on the lysosome; but also provides a structural basis for developing inhibitors that selectively target to mTORC1 pathway to treat age-related diseases by blocking LYCHOS in its expanded state.

biochemistry↗
bioRxiv2024

A 3D Image Segmentation Study of U-Net on CT Images of the Human Aorta with Morphologically Diverse Anatomy

For the machine learning -assisted diagnosis of cardiac diseases, such as thoracic aortic aneurysm, the geometries of the heart and blood vessels need to be reconstructed from medical images, which is usually done by image segmentation followed by meshing. In this study, we applied U-Net (2D and 3D versions), a deep neural network with a U-shaped architecture, to segment human aorta from CT images. From our experiments, we have the following observations: (1) 2D U-Net, which segments each of the 2D slices of a 3D CT image independently, produced erroneous fragments (e.g., missing part of the aorta) and boundaries (i.e., aortic walls) in 3D; (2) 3D U-Net, which does segmentation in 3D regions of a 3D CT image, performed much better than 2D U-Net. We also observe the major weakness of the 3D U-Net: the reconstructed geometries of the aortic wall had large errors (measured by HD95) for some cases. The 3D U-Net in this study serves as a baseline for developing more advanced architectures of deep neural networks for more accurate geometry reconstruction of human aorta.

bioengineering↗
bioRxiv2024

NanoLAS 2.0: A Comprehensive Update on a Nanobody-Focused Platform with Advanced Visualization and Docking Simulation Features

SummaryNanobodies, a unique subclass of antibodies initially discovered in camelids, characterized by the absence of light chains and consisting solely of a heavy chain variable region. This distinctive structure endows nanobodies with inherent advantages in the realms of disease treatment and biopharmaceutical applications. Presently, research and applications concerning nanobodies are experiencing rapid growth. However, existing databases suffer from non-uniform data sources and a lack of data standardization. To address these issues, we developed the NanoLAS database in 2023. Despite the progress in data integration made by NanoLAS, there was room for improvement in search functionality, three-dimensional structural display, and other areas. Building upon this foundation, we introduce the comprehensively updated NanoLAS 2.0. This version offers updates to data sources, precise 3D structural presentation, and molecular docking simulation capabilities, refines the multi-condition search mechanism, and incorporates a brand-new sequence viewer as well as epitope prediction functionality. Additionally, to cater to the needs of researchers, we have designed a user-friendly and intuitive interface. In summary, we anticipate that NanoLAS 2.0 will serve as a powerful and easy-to-use research tool, facilitating researchers in their exploration of nanobodies and propelling advancements in the field of nanobody research and application. AvailabilityNanoLAS 2.0 is available at https://www.nanolas2.online Contactbingdinghuang@sztu.edu.cn and wangxin@sztu.edu.cn

bioinformatics↗
bioRxiv2024

Evaluation of Deep Neural Network Models for Instance Segmentation of Lumbar Spine MRI

Intervertebral disc disease, a prevalent ailment, frequently leads to intermittent or persistent low back pain, and diagnosing and assessing of this disease rely on accurate measurement of vertebral bone and intervertebral disc geometries from lumbar MR images. Deep neural network (DNN) models may assist clinicians with more efficient image segmentation of individual instances (discs and vertebrae) of the lumbar spine in an automated way, which is termed as instance image segmentation. In this work, we evaluated 15 existing DNN models for lumbar spine MR image segmentation. We introduced a new data augmentation technique to create synthetic yet realistic MR image dataset, named SSMSpine, which is made publicly available. The 15 image segmentation models are evaluated on our private in-house dataset and the public SSMSpine dataset, using two metrics, Dice Similarity Coefficient and 95% Hausdorff Distance. The SSMSpine dataset are available at https://github.com/jiasongchen/SSMSpine.

bioengineering↗
bioRxiv2024

Mechanical confinement induces ferroptosis through mitochondrial dysfunction

Cells exist in highly crowded environments where they are exposed to fluctuating mechanical forces arising from surrounding cells and the extracellular matrix microenvironment. In these settings, external forces are transmitted to intracellular organelles including the nucleus. While cells can survive confinement, extended duration of confinement or confinement in settings where cells are unable to escape, can result in cell death. How cells sense and respond to prolonged confinement to trigger cell death remains unclear. Here, we demonstrate that nuclear deformation generated by axial confinement triggers the programmed cell death pathway - ferroptosis. We show that axial confinement results in Drp1-dependent mitochondrial fragmentation and cPLA2 translocation to mitochondria, where Drp1 undergoes acute phase separation. Ensuing mitochondrial ROS accumulation and arachidonic acid production concertedly leads to lipid peroxidation evoking ferroptosis. Finally, of clinical relevance, we find that in human osteoarthritis tissue cPLA2 exhibits mitochondrial localization and high ROS levels. Together, our findings unveil a pivotal role for Drp1 and cPLA2 in linking mechanical confinement with mitochondrial dysfunction resulting in ferroptosis, which sheds new light on a mechanical mechanism of pathophysiology in osteoarthritis.

cell biology↗
bioRxiv2024

An open-source MRI compatible frame for multimodal presurgical mapping in macaque and capuchin monkeys

HighlightsO_LIWe present a compact MRI-compatible stereotaxic frame for large nonhuman primates. C_LIO_LIThe design is 3D printable, inexpensive, and matches size of an adult human head. C_LIO_LIEnabled real-time, accurate, MRI-guided deep-brain viral vector injection. C_LIO_LIFacilitated multimodal alignment for deep-brain electrophysiology planning. C_LIO_LIAll computer-aided-design files are modularized and publicly available and editable. C_LI BackgroundHigh-precision neurosurgical targeting in nonhuman primates (NHPs) often requires presurgical anatomy mapping with noninvasive neuroimaging techniques (MRI, CT, PET), allowing for translation of individual anatomical coordinates to surgical stereotaxic apparatus. Given the varied tissue contrasts that these imaging techniques produce, precise alignment of imaging-based coordinates to surgical apparatus can be cumbersome. MRI-compatible stereotaxis with radiopaque fiducial markers offer a straight-forward and reliable solution, but existing commercial options do not fit in conformal head coils that maximize imaging quality. New methodWe developed a compact MRI-compatible stereotaxis suitable for a variety of NHP species (Macaca mulatta, Macaca fascicularis, and Cebus apella) that allows multimodal alignment through technique-specific fiducial markers. Comparison with existing methodsWith the express purpose of compatibility with clinically available MRI, CT, and PET systems, the frame is no larger than a human head, while allowing for imaging NHPs in the supinated position. This design requires no marker implantation, special software, or additional knowledge other than the operation of a common large animal stereotaxis. ResultsWe demonstrated the applicability of this 3D-printable apparatus across a diverse set of experiments requiring presurgical planning: 1) We demonstrate the accuracy of the fiducial system through a within-MRI cannula insertion and subcortical injection of viral vectors. 2) We also demonstrated accuracy of multimodal (MRI and CT) alignment and coordinate transfer to guide a surgical robot electrode implantation for deep-brain electrophysiology. ConclusionsThe computer-aided design files and engineering drawings are publicly available, with the modular design allowing for low cost and manageable manufacturing.

bioengineering↗
bioRxiv2024

RFX6 at locus 6q22 confers metastasis and drug resistance in prostate cancer

Genetic and nonmutational epigenetic alterations are cancer hallmark characteristics. However, the role of inherited cancer predisposition alleles in co-opting lineage factor epigenetic reprogramming and contributing to tumor progression remains elusive. Here the FinnGen cohort phenome-wide analysis, along with recent multiple genome-wide association studies, has consistently identified the rs339331-RFX6/6q22 locus associated with prostate cancer (PCa) risk across diverse populations. We uncover that rs339331 resides at a reprogrammed androgen receptor (AR) binding site in PCa tumors, with the T risk allele enhancing AR chromatin occupancy under androgen signaling. We establish that RFX6 is an AR-regulated gene, intricately linked with rs339331, exhibiting synergistic prognostic value for PCa recurrence and metastasis. Through comprehensive in vitro and in vivo studies, we establish the oncogenic functions of RFX6 in promoting PCa cell proliferation and metastasis. Mechanistically, RFX6 upregulates transcription factor HOXA10 that profoundly correlates with adverse PCa outcomes and is pivotal in RFX6-mediated PCa progression, facilitating the epithelial-mesenchymal transition (EMT) process and modulating the TGF{beta}/SMAD signaling axis. Clinically, HOXA10 elevation is associated with increased EMT scores, tumor advancement and PCa recurrence. Remarkably, reducing RFX6 expression restores responsiveness of enzalutamide-resistant PCa cells and tumors to treatment. Our study highlights an interplay of disrupted genetic and epigenetic mechanisms converging on prostate lineage AR signaling, resulting in abnormal expression of RFX6 conferring PCa pathogenesis and enzalutamide resistance.

cancer biology↗
bioRxiv2024

Capturing Snapshots of Nucleosomal H2A K13/K15 Ubiquitination Mediated by the Monomeric E3 Ligase RNF168

AbstractsThe DNA damage repair regulatory protein RNF168, a monomeric RING-type E3 ligase, plays a crucial role in regulating cell fate and DNA repair by specific and efficient ubiquitination of the adjacent Lys13 and Lys15 sites at the H2A N-terminal tail. However, understanding how RNF168 coordinates with its cognate E2 enzyme UbcH5c to ubiquitinate H2AK13/15 site-specifically has long been hampered by the lack of high-resolution structures of RNF168 and UbcH5c[~]Ub in complex with nucleosomes. Here, we developed mechanism-based chemical trapping strategies and determined the cryo-EM structures of the RNF168/UbcH5c-Ub/NCP complex captured in transient H2AK13/15 monoubiquitination and adjacent dual-monoubiquitination reactions. Our structural analysis revealed that RNF168 stably binds to the nucleosomal H2A-H2B acidic patch through a basic helix with multiple interactions, which positions the UbcH5c active centre directly over the H2A N-terminus, providing a "helix-anchoring" mode for monomeric E3 ligase RNF168 on nucleosome in contrast to the "compass-binding" mode of dimeric E3 ligases. Furthermore, our chemically synthesized ubiquitinated histones have enabled the elucidation of the efficiency of Ub installation and the interplay between the initial and subsequent Ub modifications on the adjacent H2A K13 and K15 sites. Overall, our work not only provides structural snapshots of H2A K13/K15 site-specific monoubiquitination and adjacent dual-monoubiquitination, but also offers a near-atomic resolution structural framework for understanding how pathogenic mutations or physiological modifications affect the molecular function of RNF168 in H2A K13/15 ubiquitination.

biochemistry↗
bioRxiv2024

Integrated Analyses of Multi-omic Data Derived from Paired Primary Lung Cancer and Brain Metastasis Reveals the Metabolic Vulnerability as a Novel Therapeutic Target

Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Here, we performed integrated analyses of genomic, transcriptomic, proteomic and metabolomic data which were derived from a total number of 174 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. We uncovered that LC-BrMs exhibited significantly higher intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, including TTN, TP53, MUC16, LRP1B, RYR2, and EGFR. In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry and multiplexed immunofluorescence staining of patients paired tumor specimens. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids specific to LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.

cancer biology↗