Biology subjects

Pan, J.

Publications and source records attributed to Pan, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

O-GlcNAcase promotes dendritic spine morphogenesis while downregulating their GluA2-containing AMPA receptors

Dendritic spines are essential for synaptic transmission, neural circuit organization, and cognitive function. Their morphology and density influence synaptic plasticity, learning, and memory. Many proteins in dendritic spines are modified with O-GlcNAc, a monosaccharide that can be attached and removed from serines and threonines. O-GlcNAc has been implicated in multiple brain disorders, yet the role of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc modification from proteins, in dendritic spine regulation remains unclear. This study examines the role of OGA in spine and synapse morphogenesis. Immunohistochemical and biochemical analyses reveal OGA present in dendritic spines. Functional assays show that OGA promotes spine maturation, increases spine density, and alters synapse size. Additionally, OGA modulates the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), down-regulating GluA2-containing receptors in developing and mature neurons. These findings highlight OGA as a key regulator of excitatory synaptic remodeling and a therapeutic target for synapse-related pathologies such as Alzheimers disease and autism.

neuroscience↗

bioRxiv2025

Distinguishing cortical indexes of arousal and awareness in sleeping patients with unresponsive wakefulness syndrome

Consciousness is assumed to be defined by two components: awareness and arousal. However, compared with awareness, the cortical index for arousal remains lacking in clues. Since patients with unresponsive wakefulness syndrome (UWS) are supposed to have no awareness but arousal, sleep-wake cycle in patients with UWS may reflect pure arousal fluctuations, and then could highlight the cortical indexes for arousal. This study recorded nighttime polysomnography in patients with UWS, patients with minimally conscious state and healthy controls. The EEG signal showed that spectral slope could index arousal, fluctuating among sleep stages in all three groups. Both spectral entropy and Lempel-Ziv complexity indexed awareness, showing a significant difference between conscious and unconscious states. These findings provide fundamental evidence for the two-component hypothesis of consciousness.

neuroscience↗

bioRxiv2025

The DDIT4L-TOM40-ATP5A pathway suppresses glioblastoma oncogenesis

The characteristics of glioblastoma (GBM), including resistance to cell death and aberrant energy metabolism, are associated with the function of mitochondria. To date, the inherent suppressors that couple mitochondrial function with cell death remain unclear. DNA damage-inducible transcript 4-like (DDIT4L) expression in human gliomas and its association with patient survival was determined by public databases, western-blot and immunostaining. The role of DDIT4L in regulating tumor growth was analyzed using lentivirus and PDX model. The mechanism of DDIT4L on GBM mitochondrial function was determined by different assays. Here, we show that DDIT4L is an endogenous inhibitor of GBM via suppressing mitochondrial function. DDIT4L was expressed at high levels in GBM and transported into mitochondria via single import channel TOM40 other than the import receptors TOM22, TOM20 or TOM70. Then, DDIT4L interacted with the subunit of ATP synthase, inhibited mitochondrial function and induced tumor cell apoptosis. Furthermore, the synthetic peptide DDIT4LV125-P132 suppressed GBM oncogenesis. Based on these results, DDIT4L suppresses GBM oncogenesis through both TOM40- and ATP5A-dependent mechanisms to curb mitochondrial dynamics and induce cell apoptosis, and the DDIT4LV125-P132 peptide is a potential therapy for GBM.

cancer biology↗

bioRxiv2025

AlphaGenome: advancing regulatory variant effect prediction with a unified DNA sequence model

Deep learning models that predict functional genomic measurements from DNA sequence are powerful tools for deciphering the genetic regulatory code. Existing methods trade off between input sequence length and prediction resolution, thereby limiting their modality scope and performance. We present AlphaGenome, which takes as input 1 megabase of DNA sequence and predicts thousands of functional genomic tracks up to single base pair resolution across diverse modalities - including gene expression, transcription initiation, chromatin accessibility, histone modifications, transcription factor binding, chro- matin contact maps, splice site usage, and splice junction coordinates and strength. Trained on human and mouse genomes, AlphaGenome matches or exceeds the strongest respective available external models on 24 out of 26 evaluations on variant effect prediction. AlphaGenomes ability to simultaneously score variant effects across all modalities accurately recapitulates the mechanisms of clinically-relevant variants near the TAL1 oncogene. To facilitate broader use, we provide tools for making genome track and variant effect predictions from sequence.

bioinformatics↗

bioRxiv2025

Common Gene Networks Orchestrate Organelle Architecture and Inter-Organelle Metabolic Flows for Mucin Production in High Endothelial and Goblet Cells

High endothelial cells (HECs) are specialized vascular gatekeepers that control lymphocyte entry into lymph nodes, a process essential for immune surveillance and adaptive responses. However, how HECs coordinate their high biosynthetic demands with the secretory apparatus to support immune function remains unclear. Using multi-omic approaches, we identify IRE1-XBP1-centered transcriptional networks that, together with CREB3L2-associated gene programs, coordinate inter-organelle metabolic and secretory pathways required for glycosylation and assembly of peripheral node addressin (PNAd), a sulfated sialomucin critical for lymphocyte homing. Genetic or pharmacological perturbation of these pathways disrupts HEC morphology and lymphocyte recruitment during homeostasis and impairs HEC induction during inflammation. Parallel transcriptional programs operate in mucin-producing intestinal goblet cells, suggesting common regulatory pathways linking metabolism and sulfated mucin specialization with the associated expansion of secretory organelles across immune and barrier tissues. Thus, our findings identify transcriptional programs that coordinately scale metabolic pathways and secretory organelles to support the biosynthetic infrastructure underlying the morphology and immune trafficking functions of HEVs. Key pointsXBP1-centered transcriptional networks coordinate metabolic and secretory programs for PNAd biosynthesis. IRE1 or S1P inhibition flattens HEVs, prevents ectopic HEV formation and, reduces lymphocyte recruitment Endothelial XBP1 deletion disrupts HEV morphology and lymphocyte trafficking. Goblet cells share secretory transcriptional programs and regulatory logic with HEV.

immunology↗

bioRxiv2025

Dendritic computation for rule-based flexible categorization

A hallmark of intelligent behavior is the ability to flexibly respond to external sensory inputs based on dynamically changing rules. A central question is how neurons in the brain implement computations underlying intelligent behaviors. The neocortical pyramidal neurons use their elaborated dendritic arbors to segregate a plethora of inputs and dynamically integrate them--a process known as dendritic computation--which may play important roles in rule-dependent sensory processing. However, evidence directly linking dendritic computation with intelligent cognitive behaviors has been absent. Here we combine two-photon imaging and a rule-switching flexible categorization task in mice to show that a projectome-defined extratelencephalic (ET) cortical layer 5 (L5) neurons in the auditory cortex integrate dendritic rule information and somatic sensory input to enable rule-dependent flexible categorization. The apical dendrite and soma within the same ET neurons exhibit distinct compartmental representations for sensory and rule information, with the soma predominantly encoding sensory information and the dendrites representing inferred task rule. Simultaneous optogenetic dendritic inhibition and two-photon imaging revealed that dendritic rule coding is essential for somatic output of flexible categorization. Our findings indicate that nonlinear dendritic integration of rule and sensory information constitutes a neuronal computational mechanism underlying rule-switching flexible decision-making.

neuroscience↗

bioRxiv2025

Peptides alleviate cognitive impairment by inhibiting and disassembling amyloid-beta aggregates in Alzheimer disease

Alzheimers disease (AD) is a devasting neurodegenerative disorder characterized by {beta}-amyloid formation, further exacerbated by RIPK1/RIPK3 necrosome-induced programmed necrosis (necroptosis). We previously showed that the RIPK1/RIPK3 necrosome forms a functional amyloid complex using its RIP homotypic interaction motifs (RHIMs). Here, we discovered that the core RIPK1/RIPK3 necrosome shares strikingly structural similarity to the C-terminal region of {beta}-amyloid (A{beta}42), and the RHIM-derived tetrapeptides (IQIG or VQVG) directly inhibit A{beta} aggregation, disassemble preformed A{beta} fibrils (PFFs), and reduce RIPK1 polymerization. Also, the peptides exhibit effective membrane permeability and could reduce A{beta}40 or A{beta}42-induced neural death and TNF-induced necroptosis in SH-SY5Y cells. IQIG and VQVG injected by ICV increase learning and memory abilities by reducing A{beta} plaques and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 double-transgenic mice. Mechanistically, the peptides directly interact with A{beta} to block A{beta} aggregation and alleviate microglia-mediated neuroinflammation. Strikingly, single-cell RNA sequencing revealed that the peptides-treated AD transgenic mice restored neuronal homeostasis with increased GABAergic neurons and decreased glutamatergic neurons. Furthermore, total cell-cell interaction strength increased while the AD risk gene Apoe expression decreased in the specific oligodendrocyte subtype of peptides-treated AD mice. Thus, our findings revealed that the peptides could improve cognition and memory capabilities and serve as promising structural templates for potential drugs against AD.

neuroscience↗

bioRxiv2025

An aphid-resistant plant metabolite as a candidate aphicide: Insight into the bioactivity and action mode of betulin against aphids

Pest-resistant plants usually utilize secondary metabolites to cope with insect infestation. Betulin, a key bioactive compound in aphid-resistant wild peach, possesses promising applications in crop protection. Here, betulin, in both greenhouse and field experiments, displayed excellent control efficacy against Myzus persicae. RNA-seq, qRT-PCR, and western blotting revealed that betulin significantly inhibited the expression of MpGABR (encoding a GABAA receptor). Besides, RNAi-mediated silencing of MpGABR markedly increased aphid sensitivity to betulin. Furthermore, MST (microscale thermophoresis) and voltage-clamp assays indicated that betulin bound to MpGABR (Kd = 2.24 {micro}M) and acted as an inhibitor of MpGABR. Molecular docking, mutagenesis and genome editing suggested that THR228 is a critical and highly conserved site in MpGABR that betulin binds to specifically, causing aphid death. Overall, the activity of betulin depends on specific targeting and inhibition of MpGABR. Elucidating the mechanism of action of this peach-derived insecticide may offer a sustainable green strategy for aphid control.

molecular biology↗

bioRxiv2025

MALER: a web server to build, evaluate, and apply machine learning models for numerical biomedical data analysis

The explosive growth of numerical biomedical data poses a challenge in uncovering meaningful insights within from vast omics and clinical data. In recent years, machine learning has emerged as a powerful tool for processing and dissecting numerical biomedical data, making it a popular choice for addressing analytical challenges in biomedical research. Nevertheless, the intricate algorithms and complex optimization processes of machine learning model frameworks have deterred numerous non-machine learning experts. To address the need for comprehensive signatures exploration in biomedical field, we have developed Maler (http://www.inbirg.com/maler/home), a platform designed to facilitate the effortless and efficient application of machine learning models to high-dimensional biomedical data for bioscientists. Maler primarily offers four machine learning modes and a variety of machine learning algorithms to accommodate diverse analysis requirements. Simultaneously, it employs multiple feature selection methods to acquire relevant features and selects the optimal combinations of features based on machine learning models to achieve the best predictive outcomes. Maler is expected to provide a user-friendly and efficient platform for marker discovery, catering to the needs of biologists and clinical experts.

bioinformatics↗

bioRxiv2025

An embryonic artery-forming niche reactivates in pulmonary arterial hypertension

Developmental programs that orchestrate cell fate and tissue architecture during organogenesis can cause disease when reactivated in adults. Here we identify a population of endothelial cells (ECs) defined by the pioneer factor early B cell factor 1 (EBF1) that controls both pulmonary artery (PA) morphogenesis and pulmonary arterial hypertension (PAH). During embryonic development, the PA emerges from an endothelial niche harbored within the vascular plexus, where Aplnr+ endothelial progenitors give rise to both arterial ECs and EBF1+ ECs. Rather than directly incorporating into the PA intima, EBF1+ ECs control the branching and maturation of the PA tree through paracrine vasculotrophic signals that direct plexus expansion, arterialization, and mural cell recruitment. Although essential for development, most EBF1+ ECs disappear upon completion of PA morphogenesis. In adult PAH, vascular injury reactivates this developmental program: normally quiescent general capillary ECs re-enter the cell cycle and differentiate into arterial ECs and EBF1+ ECs, reconstituting this artery-forming niche in a maladaptive reprise. Unlike their transient embryonic counterparts, EBF1+ ECs persist within neointimal lesions and express vasculotrophic signals associated with pathological PA remodeling. Capillary-restricted Ebf1 induction combined with endothelial injury recapitulates this program, driving neo-arterialization, neointimal formation, and severe PAH. Conversely, endothelial-targeted AAV-mediated Ebf1 knockdown achieves complete protection in a preclinical model of disease, demonstrating that endothelial EBF1 is necessary for PAH pathogenesis. These findings demonstrate that reactivation and persistence of a transient embryonic artery-forming niche in adulthood can promote pathological vascular remodeling and PAH.

developmental biology↗

bioRxiv2025

Molecular organization of the distal tip of vertebrate motile cilia

The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. But while the structure and function of basal bodies and axonemes have received significant attention recently, the distal tips of MCC cilia remain relatively poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, characterizing two distinct domains occupied by distinct protein constituents. Using frog, mouse, and human MCCs, we find that two largely uncharacterized proteins, Ccdc78 and Ccdc33 occupy a previously undefined region at the extreme distal tip, and these are required for the normal organization of all other known tip proteins. Ccdc78 and Ccdc33 each display robust microtubule-bundling activity both in vivo and in vitro, yet each is independently required for normal length regulation of MCC cilia. Moreover, loss of each protein elicits a distinct pattern of defective cilia beating and resultant fluid flow. Thus, two previously undefined proteins form a key module essential for organizing and stabilizing the distal tip of motile cilia in vertebrate MCCs. We propose that these ill-defined proteins represent potential disease loci for motile ciliopathies.

cell biology↗

bioRxiv2025

Influence of the ATP-dependent DNA ligase, Lig E, on Neisseria gonorrhoeae microcolony and biofilm formation

BackgroundNeisseria gonorrhoeae, the causative agent of the sexually transmitted infection, gonorrhoea, is known to form biofilms rich in extracellular DNA on human cervical cells. Biofilm formation is conducive to increased antimicrobial resistance and evasion of the host immune system, potentially causing asymptomatic infections. Using plate-based assays we have previously shown that disruption of a potential extracellular DNA ligase, Lig E, in N. gonorrhoeae (Ngo-Lig E) impacts biofilm formation. In this research, we further explored this phenotype using confocal and scanning electron microscopy to directly visualise the morphology of microcolony and biofilm formation. Biofilm growth on artificial surfaces and on 3-dimensional human vaginal epithelial tissue was evaluated for strains where ngo-lig E was either disrupted or overexpressed. ResultsResults demonstrated that Ngo-Lig E was important for the formation of robust, compact N. gonorrhoeae microcolonies, as well as extensive biofilms on artificial surfaces. The ngo-lig E deletion strain also had the highest tendency to be retained on the surface of epithelial tissues, with decreased invasion and damage to host cell layers. ConclusionsThese findings support a role for Ngo-Lig E to be secreted from N. gonorrhoeae cells for the purpose of inter-cell adhesion and biofilm formation. We suggest that Ngo-Lig E strengthens the extracellular matrix and hence microcolony and biofilm formation of N. gonorrhoeae by ligation of extracellular DNA.

microbiology↗

bioRxiv2025

The membrane skeleton density of red blood cells in MYH9-related disease patients is decreased

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9 gene, which encodes the heavy chain of nonmuscle myosin IIA. Nearly all MYH9-RD patients present with macrothrombocytopenia, characterized by decreased platelet count and increased platelet size. In this study, we collected blood samples from three MYH9-RD patients (R702S, D1424N, and R1464C) and unexpectedly found that the actin levels in the red blood cells (RBCs) from all three MYH9-RD patients are substantially lower than the healthy controls. We further revealed that the levels of two RBC membrane skeleton proteins, -spectrin and tropomodulin, are also reduced in MYH9-RD RBCs. We showed that the membrane skeleton of MYH9-RD RBCs was more porous and that MYH9-RD RBCs produced more severe deformation under hyperosmotic pressure compared to healthy controls. We conclude that MYH9-RD mutations reduce the RBC membrane skeleton density and impair its mechanical properties, and propose that defects in the membrane skeleton network in RBCs may be a common symptom in MYH9-RD. Key pointsThe levels of membrane skeleton proteins and the density of membrane skeleton network in RBCs of MYH9-RD patients are reduced. MYH9-RD RBCs produce greater deformation under hypertonic conditions compared to healthy controls.

pathology↗

bioRxiv2025

Local nucleolar surveillance mechanisms maintain rDNA stability

The nucleoli are subdomains of the nucleus that form around actively transcribed ribosomal RNA (rRNA) genes. The highly repetitive and transcribed nature of the rRNA genes (rDNA) by RNA polymerase I (Pol I) poses a challenge for DNA repair and replication machineries. Here, we profile the nucleolar proteome and the chromatin landscape of stalled replication sites upon rDNA damage to characterize the early steps of nucleolar DNA damage response (nDDR). We observed early dynamics in nucleolar-nucleoplasmic proteome localization and identified nucleolar replication stress signatures involving chromatin remodeling networks, transcription-replication conflicts and DNA repair. Our findings define localized surveillance mechanisms that activate the nDDR. Further, we identified that upon rDNA damage, nucleolar RNA Polymerase (Pol) II binds to intergenic rDNA sequences and generates R-loops (DNA:RNA hybrid structures) that are essential for recruiting nDDR factors. Using a boutique CRISPR-Cas9 synthetic lethal screen of DNA repair factors with inhibitors of RNA Pol I transcription, we identified an unexpected protective role for the DNA translocase RAD54L in nDDR. Loss of Rad54L increases nucleolar R-loops and rDNA damage leading to defects in nucleolar structure and enhanced sensitivity to PARP and RNA Pol I inhibitors. Altogether, our study uncovers localized surveillance networks within the nucleolus that respond to rDNA damage. These insights expand our understanding of the molecular mechanisms governing nDDR and opens new avenues for developing nDDR-targeting therapies.

molecular biology↗

bioRxiv2025

The membrane topology problem inherent in ciliogenesis is solved by ciliary recruitment of a phospholipid flippase

The cilium is a slender cellular projection whose membrane transduces signals essential in development and homeostasis. Although assembly of the axonemal core of the organelle is well-studied, the mechanisms that underlie formation of the [~]250 nm diameter ciliary membrane from oppositely curved 50-100 nm diameter pre-ciliary vesicles remain poorly understood. Here we report that during ciliogenesis in the bi-ciliated alga, Chlamydomonas reinhardtii, aminophospholipid flippase 2 (ALA2) is recruited laterally from a reservoir on the plasma membrane onto the nascent ciliary membrane where it transfers conically shaped phosphatidyl ethanolamine (PE) from the outer to the inner leaflet. In cells lacking ALA2, initiation of cilia regeneration after experimentally induced de-ciliation is delayed, PE flipping is impaired, the ciliary membrane becomes distorted, and cilia that do form are shorter than wild type. Our results uncover a membrane topology problem inherent in ciliogenesis and demonstrate that it is resolved by a phospholipid flippase. HighlightsO_LIMembranes of pre-ciliary vesicles reverse curvature to become the ciliary membrane C_LIO_LIUpon initiation of ciliogenesis, plasma membrane ALA2 transits laterally to cilia C_LIO_LIThe ciliary membranes of ala2 mutants fail to conform to axonemal shape C_LIO_LIALA2 flips PE to establish ciliary membrane curvature C_LI

cell biology↗

bioRxiv2024

High-resolution mastigoneme structure reveals 5',5'-phosphodiesters stabilized glycan folding

Glycans play a crucial role in structure organization, energy metabolism, and signal transduction in living organisms. Compared with proteins and nucleic acids, glycans exhibit remarkable molecular heterogeneity, extensive conformational flexibility, and diverse linkages. These properties pose significant challenges for obtaining high-resolution structure of glycans. Here, we report a cryo-EM structure of the heavily glycosylated Chlamydomonas mastigoneme at 2.3-2.5 [A] resolutions. In addition to enabling analysis of accurate interactions for glycosyl packing, the high resolution map reveals an unprecedented 5,5-phosphodiester bond that links adjacent glycan chains attached to hydroxyproline (Hyp) residues n and n+3. Structural analysis reveals a secondary structural element for glycoconjugates, which we name the poly-Hyp (pHP) glycohelix. Our work represents an important advancement in deciphering glycan folding.

biochemistry↗

bioRxiv2024

White Spot Syndrome Virus Immediate-Early Protein (wsv100) Antagonizes the NF-kappaB Pathway to Inhibit Innate Immune Response in shrimp

Viruses have evolved sophisticated strategies to evade host immune defenses, often targeting conserved signaling pathways. In shrimp, the NF-{kappa}B signaling pathway is crucial for antiviral immunity, yet its regulation during White Spot Syndrome Virus (WSSV) infection remains poorly understood. Here, we identify and characterize wsv100, an immediate-early (IE) protein of WSSV, as a key antagonist of the NF-{kappa}B pathway. wsv100 interacts directly with the transcription factor Dorsal and the adaptor protein IMD, preventing Dorsal phosphorylation by Pelle kinase. This inhibition suppresses Dorsals nuclear translocation and downstream expression of antimicrobial peptides (AMPs), essential for antiviral defense. Knockdown of wsv100 reduced WSSV replication, increased Dorsal phosphorylation, and enhanced AMP expression, leading to higher survival rates in infected shrimp. Conversely, wsv100 overexpression promoted WSSV replication and AMPs suppression. These findings reveal a novel immune evasion mechanism by which WSSV subverts the NF-{kappa}B pathway and highlight the evolutionary arms race between hosts and viruses. This study enhances our understanding of host-virus interactions and offers potential targets for antiviral strategies in shrimp aquaculture. Author SummaryThe innate immune system is the first line of defense against viral infections in invertebrates, with the NF-{kappa}B signaling pathway playing a central role in orchestrating antiviral responses. In this study, we uncover a novel immune evasion mechanism employed by White Spot Syndrome Virus (WSSV), a devastating pathogen in shrimp aquaculture. The WSSV immediate-early protein wsv100 directly targets the transcription factor Dorsal and prevents its phosphorylation by Pelle kinase, a critical step in NF-{kappa}B activation. This interaction suppresses Dorsals nuclear translocation and downstream expression of antimicrobial peptides (AMPs), thereby impairing the shrimps ability to mount an effective immune response. Knockdown of wsv100 significantly reduced WSSV replication and enhanced shrimp survival, while wsv100 overexpression had the opposite effect. These findings not only elucidate how WSSV exploits the NF-{kappa}B pathway but also underscore its central role in shrimp antiviral immunity. This work advances our understanding of host-virus co-evolution and provides a foundation for developing novel antiviral strategies to mitigate the economic losses caused by WSSV in shrimp aquaculture.

microbiology↗

bioRxiv2024

A Novel Bispecific Antibody CVL006 Superior to AK112 for Dual Targeting of PD-L1 and VEGF in Cancer Therapy

Both preclinical and clinical studies have shown that combining anti-VEGF/VEGFR drugs with immune checkpoint inhibitors (ICIs) significantly enhances anticancer efficacy. Currently, PDL-1/ VEGF bispecific antibodies demonstrate superior antitumor activity compared to monotherapy or even the combination of PD-L1 inhibitors with anti-VEGF antibodies. This enhanced efficacy results from the simultaneous blockade of the PD-1/PD-L1 pathway and the inhibition of VEGF-driven angiogenesis. In this study, we developed a novel bispecific antibody, CVL006, by fusing an anti-PDL1 VHH domain with a humanized IgG1 anti-VEGF monoclonal antibody while retaining antibody-dependent cellular cytotoxicity (ADCC) functionality. CVL006 demonstrated high affinity and specificity for both human PD-L1 and VEGF, effectively blocking both the VEGF/VEGFR signaling pathway and the PD-L1/PD-1 axis. This dual blockade not only suppressed VEGF-induced angiogenesis but also reactivated T cells, increasing the secretion of cytokines essential for immune response. In vivo studies further indicated that CVL006 achieved superior antitumor efficacy compared to the PD-L1 inhibitor atezolizumab in mouse models, with greater tumor growth inhibition and reduced angiogenesis. To compare with approved bispecific antibody PD-1/VEGF AK112 (ivonescimab), CVL006 showed superior antitumor efficacy in vivo. These findings underscore the therapeutic potential of CVL006, which integrates immune checkpoint inhibition with disruption of tumor vascularization, offering a robust and comprehensive anticancer strategy.

pharmacology and toxicology↗