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Li, C. J.

Publications and source records attributed to Li, C. J..

4 recordsLinked to original sources
bioRxiv2025

Functional Activity of HIV-1 bNAbs Across Diverse Strains is Driven by Binding Site and Can be Enhanced Through Fc Engineering

Broadly neutralizing antibodies (bNAbs) are promising tools for HIV-1 treatment and prevention, due to their ability to mediate both Fab-dependent neutralization and Fc-dependent effector functions. While antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) have been implicated in antiviral activity, the extent to which these functions vary across bNAb epitopes, viral strains, and Fc region remains unclear. Here, we systematically evaluated twenty bNAbs targeting five distinct Env epitopes against a diverse panel of nine HIV-1 strains. We found that epitope specificity and Env sequence both critically influenced bNAb effector functions. CD4 binding site (CD4bs)- and V3 glycan-targeting bNAbs mediated the broadest and most potent ADCC and ADCP, while V1/V2 apex-directed bNAbs preferentially induced ADCP. In contrast, MPER-targeting bNAbs triggered ADCC more selectively, and gp120/gp41 interface-targeting bNAbs showed limited activity. Irrespective of binding epitope, different strains exhibited a broad range of effector function sensitivities. To investigate the impact of Fc modifications on this variability, we subclass-switched and introduced previously identified Fc mutations known to change Fc{gamma} receptor affinity. Some of these mutations significantly boosted ADCC, while IgG3 subclass switching dramatically enhanced ADCP, even against highly resistant strains. Collectively, these results demonstrate that effector function is shaped by both antibody specificity and viral Env context and that rational Fc modification has the potential to improve antibody-based therapeutics against HIV. One Sentence SummaryThis study systematically evaluates the impact of bNAb epitope specificity, Env sequence, and Fc engineering on antibody-mediated effector functions.

immunology↗
bioRxiv2025

Sex Based Differences in Active Avoidance and Approach Strategy in the Platform Mediated Avoidance Task

Sex differences have been documented in threat conditioning, but research into potential sex differences in avoidance paradigms, particularly active avoidance, remains limited. This research gap is particularly concerning given that women are disproportionately affected by stress- and anxiety-related disorders, characterized by maladaptive avoidance. Yet, preclinical research has historically focused on male subjects, limiting our understanding of the neurobiological mechanisms underlying sex differences in threat responses. To address this, we investigated sex-specific strategies in adult Long Evans rats (10 female, 9 male) using a modified platform-mediated avoidance (PMA) task that created a high-conflict choice between reward-seeking and safety. Behavior was tracked over 25 days, with analyses focusing on a stable performance phase (days 20-25) objectively defined using change point analysis. The study design included an initial cohort and a replication cohort to ensure the findings robustness. Females consistently prioritized safety, spending significantly more time foregoing reward to avoid foot shock, while males engaged in more persistent reward-seeking despite the risk of shock. This difference was not driven by differential reward motivation. Furthermore, female strategies were not significantly modulated by the estrous cycle. Thus, male and female rats employ fundamentally different strategies to resolve approach-avoidance conflict: females adopt a robust, safety-first strategy, while males demonstrate a risk-prone, reward-oriented approach. These findings highlight the importance of considering biological factors underlying threat responses, suggesting that characterizing these neural mechanisms may guide more targeted interventions for anxiety and trauma-related disorders.

animal behavior and cognition↗
bioRxiv2021

Mechanical stimulation promotes enthesis injury repair by mobilizing Prx1+ cells via ciliary TGF-β signaling

Proper mechanical stimulation can improve rotator cuff enthsis injury repair. However, the underlying mechanism of mechanical stimulation promoting injury repair is still unknown. In this study, we found that Prx1+ cell was essential for murine rotator cuff enthesis development identified by single-cell RNA sequence and involved in the injury repair. Proper mechanical stimulation could promote the migration of Prx1+ cells to enhance enthesis injury repair. Meantime, TGF-{beta} signaling and primary cilia played an essential role in mediating mechanical stimulation signaling transmission. Proper mechanical stimulation enhanced the release of active TGF-{beta}1 to promote migration of Prx1+ cells. Inhibition of TGF-{beta} signaling eliminated the stimulatory effect of mechanical stimulation on Prx1+ cell migration and enthesis injury repair. In addition, knockdown of Pallidin to inhibit TGF-{beta}R2 translocation to the primary cilia or deletion of IFT88 in Prx1+ cells also restrained the mechanics-induced Prx1+ cells migration. These findings suggested that mechanical stimulation could increase the release of active TGF-{beta}1 and enhance the mobilization of Prx1+ cells to promote enthesis injury repair via ciliary TGF-{beta} signaling.

cell biology↗