Biology subjects

Hong, L. Z.

Publications and source records attributed to Hong, L. Z..

3 recordsLinked to original sources

bioRxiv2025

Cardiac Adaptations in the Cave Nectar Bat Eonycteris spelaea: Insights into Metabolic Resilience and Stress Response

AimsBats are unique mammals with remarkable adaptations, including powered flight, which demands significant energy expenditure. While previous studies have documented basic structural characteristics of bat hearts, a comprehensive understanding of their response to physiological stress remains unexplored. This study investigates the cardiac adaptations of the cave nectar bat Eonycteris spelaea to elucidate the mechanisms underlying their unique physiological capabilities. Methods and ResultsWe performed RNA sequencing to analyse the cardiac gene expression profile of E. spelaea and 6 other bat species in comparison to mouse and human hearts, revealing enriched transcriptomic signatures related to oxidative phosphorylation and fatty acid metabolism across multiple bat species. Metabolomic profiling compared acylcarnitine metabolites and tricarboxylic acid (TCA) cycle intermediates between bat and mouse hearts, indicating a distinct acylcarnitine profile and increased levels of TCA cycle intermediates in bats, suggesting enhanced metabolic capacity. Structural adaptations were assessed through anatomical and histological analyses on cardiac tissues, showing thicker left ventricular walls and increased vascular density in bats without pathological hypertrophy. Functional characteristics were evaluated using dobutamine stress echocardiography, demonstrating superior cardiac reserve in bats with significant increases in ejection fraction, stroke volume, and cardiac output under stress conditions. Additionally, isolated cardiomyocytes were treated with Angiotensin II (Ang II) to assess stress responses. Bat cardiomyocytes displayed resistance to Ang II-induced hypertrophy and mitochondrial dysfunction compared to mice, further highlighting their resilience to stress-induced damage. ConclusionThe unique adaptations observed in bat hearts, including enhanced metabolic pathways, structural remodelling, and cellular resilience contribute to their ability to meet the high energy demands of powered flight while maintain cardiac function under stress. These insights into bat cardiac physiology provide valuable information on cardioprotective mechanisms that could be applicable to other species. Translational PerspectiveBats exhibit remarkable cardiac adaptations that sustain the high energy demands of powered flight while resisting stress-induced damage. These insights into evolutionarily conserved cardioprotective mechanisms highlight potential therapeutic pathways for preventing heart failure, including resistance to hypertrophy and mitochondrial dysfunction under stress. Studying non-model organisms like bats may offer innovative approaches to enhance metabolic and stress resilience in human hearts, paving the way for translational research in cardiovascular disease management and treatment.

systems biology↗

bioRxiv2020

STUB1 is an intracellular checkpoint for interferon gamma sensing

Immune checkpoint blockade (ICB) leads to durable and complete tumour regression in some patients but in others gives temporary, partial or no response. Accordingly, significant efforts are underway to identify tumour-intrinsic mechanisms underlying ICB resistance. Results from a published CRISPR screen in a mouse model suggested that targeting STUB1, an E3 ligase involved in protein homeostasis, may overcome ICB resistance but the molecular basis of this effect remains unclear. Herein, we report an under-appreciated role of STUB1 to dampen the interferon gamma (IFN{gamma}) response. Genetic deletion of STUB1 increased IFNGR1 abundance on the cell surface and thus enhanced the downstream IFN{gamma} response as showed by multiple approaches including Western blotting, flow cytometry, qPCR, phospho-STAT1 assay, immunopeptidomics, proteomics, and gene expression profiling. Human prostate and breast cancer cells with STUB1 deletion were also susceptible to cytokine-induced growth inhibition. Furthermore, blockade of STUB1 protein function recapitulated the STUB1-null phenotypes. Despite these encouraging in vitro data and positive implications from clinical datasets, we did not observe in vivo benefits of inactivating Stub1 in mouse syngeneic tumour models - with or without combination with anti-PD-1 therapy. However, our findings elucidate STUB1 as a barrier to IFN{gamma} sensing, prompting further investigations to assess if broader inactivation of human STUB1 in both tumors and immune cells could overcome ICB resistance.

cancer biology↗

bioRxiv2017

Single-Virion Sequencing Of Lamivudine Treated HBV Populations Reveal Population Evolution Dynamics And Demographic History

Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. We obtained 248-8,796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were also able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently on PacBio and Illumina sequencers. Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance, differentiating between soft or hard selective sweeps, and the reconstruction of intra-host viral population demographic history.

evolutionary biology↗