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Biomedical subjects

Zihao Wang

Publications and source records attributed to Zihao Wang.

3 recordsLinked to original sources

Engineering the Vero Cell Lineage: Toward a Programmable Vaccine Manufacturing Platform.

Vero cells remain an indispensable continuous substrate for human viral vaccine manufacturing. Despite decades of empirical process optimization, intrinsic genomic instability, including segmental aneuploidy and dynamic chromatin rearrangements, continues to limit the durability of engineered phenotypes under sustained viral burden and bioreactor stress. Here, we review the expanding engineering toolkit for the Vero lineage across a three-layered functional framework: the membrane interface, cytoplasmic foundry, and nuclear blueprint, evaluating translational prospects at each level. Receptor transplantation and morphological reprogramming have broadened viral entry range and enabled suspension-adapted culture formats, while metabolic flux management and temporally controlled apoptosis modulation have addressed intracellular production bottlenecks, albeit often with trade-offs between productivity, biosafety, and long-term population stability. At the genomic level, targeted perturbations of transcriptional regulators and emerging epigenetic interventions offer more durable gains, yet expression drift, clonal heterogeneity, and karyotypic instability during extended passaging highlight the need for locus-level precision rather than constitutive trait installation. Looking forward, infection-responsive dynamic logic circuits and the systematic identification of Vero-specific genomic safe harbors could shift the paradigm toward a conditionally responsive manufacturing architecture. Collectively, these advances suggest a pathway for transitioning the Vero lineage from a passive, empirically optimized biological substrate into a conditionally responsive, genomically stable, and programmable platform for modern vaccine preparedness.

Vero cells

An integrated culturomic and genomic database and analysis platform for methanogenic archaea.

Methanogenic archaea research is challenged by limited strain resources, fragmented genomic data, inconsistent genome quality, substantial uncultured lineages, and difficulties in laboratory culturing, hindering advances in biogas production, climate mitigation, and microbial ecology. These archaea play crucial roles in global carbon cycling and anaerobic environments, yet scattered data and unculturable strains limit systematic studies and applications. To address this, we created MethArDB (Methanogenic Archaeal Genome Database), a specialized database for methanogenic archaea, compiling 3919 genomes, 87 host-associated plasmids, and 42 phages, with standardized quality classifications (complete, scaffold, draft), protein sequences, and metadata on geography, habitats, metabolism, and inheritable elements. Integrated MethArCT (Methanogenic Archaeal Culturomics Toolkit) employs a dual-threshold orthologous/paralogous protein analysis to evaluate metabolic pathway completeness, predicting cultivation parameters and suggesting candidate cultivation strategies, including potential medium formulations and conditions, to support strain isolation. Overall, MethArDB and MethArCT form an integrated platform combining genomics and culturomics to facilitate methanogenic archaea research. Database URL:  http://methardb.cn.

Genome, Archaeal

Barrier effects on the kinetics of cohesin-mediated loop extrusion.

Chromosome organization mediated by structural maintenance of chromosome complexes is crucial in many organisms. Cohesin extrudes chromatin into loops that are thought to lengthen until it is obstructed by CTCF proteins. In complex cellular environments, the loop extrusion machinery may encounter other chromatin-binding proteins. How these proteins interfere with the cohesin-meditated extrusion process is largely unexplored, but recent experiments have shown that some proteins serve as physical barriers that block cohesin translocation. Other proteins containing a cohesin-interaction motif serve as chemical barriers to induce cohesin pausing through interactions with it. Here, we develop an analytically solvable approach for the loop extrusion model incorporating barriers to investigate the effect of the barrier on the passive extrusion process. To further quantify the impact of barriers, we calculate the mean looping time it takes for cohesin to translocate to form a stable loop before dissociation. Our finding reveals that the physical barrier can accelerate the loop formation, and the degree of acceleration is closely related to the impedance strength of the physical barrier. In particular, the synergy of the cohesin loading site and the physical barrier site accelerates loop formation more significantly. The proximity of the cohesin loading site to the barrier site facilitates the rapid formation of stable loops in long genomes, which implies loop extrusion and chromatin-binding proteins might shape functional genomic organization. Conversely, chemical barriers consistently impede loop formation, with increasing impedance strength of the chemical barrier leading to longer loop formation time. Our study contributes to a more comprehensive understanding of the complexity of the loop extrusion process, providing a new perspective on the potential mechanisms of gene regulation.

Cohesins