Siyu Zhu

The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This differentiation process plays a crucial role in bone formation and homeostasis and is regulated by two intricate processes: cell signal transduction and transcriptional gene expression. Various essential cell signaling pathways, including Wnt, BMP, TGF-β, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, and Piezo1/2, play a critical role in facilitating osteoblast differentiation, bone formation, and bone homeostasis. Key transcriptional factors in this differentiation process include Runx2, Cbfβ, Runx1, Osterix, ATF4, SATB2, and TAZ/YAP. Furthermore, a diverse array of epigenetic factors also plays critical roles in osteoblast differentiation, bone formation, and homeostasis at the transcriptional level. This review provides an overview of the latest developments and current comprehension concerning the pathways of cell signaling, regulation of hormones, and transcriptional regulation of genes involved in the commitment and differentiation of osteoblast lineage, as well as in bone formation and maintenance of homeostasis. The paper also reviews epigenetic regulation of osteoblast differentiation via mechanisms, such as histone and DNA modifications. Additionally, we summarize the latest developments in osteoblast biology spurred by recent advancements in various modern technologies and bioinformatics. By synthesizing these insights into a comprehensive understanding of osteoblast differentiation, this review provides further clarification of the mechanisms underlying osteoblast lineage commitment, differentiation, and bone formation, and highlights potential new therapeutic applications for the treatment of bone diseases.

One emerging and exciting topic in robotics research is the design of micro-/nanoscale robots for biomedical operations. Unlike industrial robots that are developed primarily to automate routine and dangerous tasks, biomedical nanorobots are designed for complex, physiologically relevant environments, and tasks that involve unanticipated biological events. Here, a biologically interfaced nanorobot is reported, made of magnetic helical nanomotors cloaked with the plasma membrane of human platelets. The resulting biomimetic nanorobots possess a biological membrane coating consisting of diverse functional proteins associated with human platelets. Compared to uncoated nanomotors which experience severe biofouling effects and hence hindered propulsion in whole blood, the platelet-membrane-cloaked nanomotors disguise as human platelets and display efficient propulsion in blood over long time periods. The biointerfaced nanorobots display platelet-mimicking properties, including adhesion and binding to toxins and platelet-adhering pathogens, such as Shiga toxin and Staphylococcus aureus bacteria. The locomotion capacity and platelet-mimicking biological function of the biomimetic nanomotors offer efficient binding and isolation of these biological threats. The dynamic biointerfacing platform enabled by platelet-membrane cloaked nanorobots thus holds considerable promise for diverse biomedical and biodefense applications.

The growth plate (GP) comprising sequentially differentiated cell layers is a critical structure for bone elongation and regeneration. Although several key regulators in GP development have been identified using genetic perturbation, systematic understanding is still limited. Here, we used single-cell RNA-sequencing (RNA-seq) to determine the gene expression profiles of 217 single cells from GPs and developed a bioinformatics pipeline named Sinova to de novo reconstruct physiological GP development in both temporal and spatial high resolution. Our unsupervised model not only confirmed prior knowledge, but also enabled the systematic discovery of genes, potential signal pathways, and surface markers CD9/CD200 to precisely depict development. Sinova further identified the effective combination of transcriptional factors (TFs) that regulates GP maturation, and the result was validated using an in vitro EGFP-Col10a screening system. Our case systematically reconstructed molecular cascades in GP development through single-cell profiling, and the bioinformatics pipeline is applicable to other developmental processes. VIDEO ABSTRACT.

Illumina is the leading sequencing platform in the next-generation sequencing (NGS) market globally. In recent years, MGI Tech has presented a series of new sequencers, including DNBSEQ-T7, MGISEQ-2000 and MGISEQ-200. As a complex application of NGS, cancer-detecting panels pose increasing demands for the high accuracy and sensitivity of sequencing and data analysis. In this study, we used the same capture DNA libraries constructed based on the Illumina protocol to evaluate the performance of the Illumina Nextseq500 and MGISEQ-2000 sequencing platforms. We found that the two platforms had high consistency in the results of hotspot mutation analysis; more importantly, we found that there was a significant loss of fragments in the 101-133 bp size range on the MGISEQ-2000 sequencing platform for Illumina libraries, but not for the capture DNA libraries prepared based on the MGISEQ protocol. This phenomenon may indicate fragment selection or low fragment ligation efficiency during the DNA circularization step, which is a unique step of the MGISEQ-2000 sequence platform. In conclusion, these different sequencing libraries and corresponding sequencing platforms are compatible with each other, but protocol and platform selection need to be carefully evaluated in combination with research purpose.

Preservatives are essential components in cosmetic products, but their safety issues have attracted widespread attention. There is an urgent need for safe and effective alternatives. Antimicrobial peptides (AMPs) are part of the innate immune system and have potent antimicrobial properties. Using machine learning-assisted rational design, we obtained a novel antibacterial peptide, IK-16-1, with significant antibacterial activity and maintaining safety based on β-defensins. IK-16-1 has broad-spectrum antimicrobial properties against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, and has no haemolytic activity. The use of IK-16-1 holds promise in the cosmetics industry, since it can serve as a preservative synergist to reduce the amount of other preservatives in cosmetics. This study verified the feasibility of combining computational design with artificial intelligence prediction to design AMPs, achieving rapid screening and reducing development costs.