Biology subjects

Zhou, y.

Publications and source records attributed to Zhou, y..

3 recordsLinked to original sources

bioRxiv2026

Construction of a GnRH mRNA Immunocastration Vaccine and Evaluation of Its Immunogenicity and Safety in Mice and Cats

Immunocastration has emerged as an alternative to surgical and chemical castration for managing reproductive function in animals, yet the development of safe and effective vaccines remains challenging. This study aimed to develop a gonadotropin-releasing hormone (GnRH)-based messenger RNA (mRNA) vaccine and systematically evaluate its immunogenicity, reproductive suppression efficacy, long-term durability, and biosafety in mice and cats. GnRH epitopes were fused to three carrier proteins, Fc, Foldon, and lumazine synthase nanoparticles (pLS) via a flexible linker. After identifying pLS as the optimal scaffold, three mRNA vaccine candidates (GnRH-3, GnRH-4, and GnRH-5) were generated with one, five, or ten tandem GnRH repeats, encapsulated in lipid nanoparticles (LNPs), and assessed in rodent and feline models. Immunogenicity was determined by enzyme-linked immunosorbent assay, gonadal histopathology, hormone measurements, transcriptomic analysis, and mating trials. Among the fusion partners, the pLS-based vaccine (GnRH-3) induced the strongest antibody responses and most pronounced reproductive suppression. Further optimization showed that GnRH-4, containing five tandem GnRH repeats, elicited the highest antibody titers, induced severe gonadal atrophy, and reduced litter size by 93.8% in mice. Transcriptomic analysis revealed that differentially expressed genes in males were enriched in spermatogenesis and motility pathways, whereas those in females were associated with RNA splicing and immune responses. In cats, the optimal regimen was a twoLdose schedule with 50Lg per dose and a 21Lday interval, which induced robust antibody responses lasting at least 12 Lmonths and sustained reproductive suppression. HighLdose (500Lg) administration showed no clinical toxicity or histopathological abnormalities, confirming favorable biosafety. This study successfully developed a pLSLbased GnRH mRNA vaccine (GnRH-4) with five tandem GnRH epitopes that demonstrates strong immunogenicity, longLlasting contraceptive effects, and excellent safety in both rodent and feline models, supporting its potential for clinical application in immunocastration.

immunology↗

bioRxiv2024

Osterix Facilitates Osteocytic Communication by Targeting Connexin43

Osteocytes, terminal-differentiated cells in bone, are now considered as more pivotal regulators of mature bone homeostasis than other bone cells, since they constitute 90- 95% of the bone cell population. Given their non-migratory nature within the mineralized matrix, their unique dendrites are crucial for cell-to-cell communication in response to both intracellular and extracellular stimuli, such as bone fracture or mechanical load. Here, we showed that Osterix (Osx), usually recognized as a specific doorkeeper for osteoblast differentiation during new bone formation marked by collagen type I 1 (Col11), was unexpectedly co-expressed with Col11 in osteocytes within the cortical bone of mice. Deleting Osx in Col11-positive osteocytes disrupted cortical bone structure and osteocytic dendrites in mice, thus impairing transcellular fluid flow and intercellular communication. Conversely, overexpression of Osx in osteocytes enhanced these processes. Furthermore, we identified Connexin43, a critical protein of gap junction channel, was a direct transcriptional target of Osx in regulating dendrites of osteocytes. Pharmacological restoration of Connexin43 levels rescued the dysfunction in Osx-deficient osteocytes both in vitro and in vivo. Taken together, this work demonstrated Osxs distinct role in osteocyte function through maintaining intercellular signaling, which broadened the current understanding of its role in Col11-positive bone cells, extending beyond osteoblasts and bone mineralization, offering new insights into bone diseases such as fracture nonunion or disuse osteoporosis.

cell biology↗

bioRxiv2018

The distribution of large floating seagrass (Zostera marina) clumps in northern temperate zones of Bohai Bay in the Bohai Sea, China

Seagrass meadows (Zostera marina) are important coastal ecosystems with high levels of productivity and biodiversity. They are subject to considerable natural and anthropogenic threats in China, such as oyster and snail aquaculture, wastewater discharge, electro-fishing, shellfish collection, typhoons and floods. When seagrass communities are disturbed, they can become removed from the sediment and converted into floating clumps, which then serve as marine hot spots attracting a variety of marine organisms that then inhabit them. They are important nursery habitats for many economic fish such as red drum (Sciaenops ocellatus), Atlantic cod (Gadus morhua), queen conch (Strombus gigas), and blue crab (Callinectes sapidus). Thus, it is necessary to study the distribution and biological characteristics of these floating seagrass clumps. In September 2016 we observed large scale floating Z. marina clumps in the northernmost area of Bohai Bay (38{degrees}571.14\"-39{degrees} 041.28\" N, 118{degrees}4523.22\"-118{degrees}476.96\" E), in the Bohai Sea, China. We observed characteristics that precluded their origination from the nearby Caofeidian seagrass meadows. Two research cruises were undertaken, during which we did not observe other marine organisms accompanying these floating Z. marina clumps. The dominant frond lengths were 40-50 cm, with less than 5% of the total number of fronds found in larger size categories (80-90 and 90-100 cm). We aim to pursue future research into the breakdown and dislodgement characteristics of Z. marina clumps and the processes whereby they sink and integrate with the sediment.

ecology↗