Predicting recurrence in osteosarcoma via a quantitative histological image classifier derived from tumour nuclear morphological features

Recurrence is the key factor affecting the prognosis of osteosarcoma.Currently,there is a lack of clinically useful tools to predict osteosarcoma recurrence.The application of pathological images for artificial intelligence‐assisted accurate prediction of tumour out-comes is increasing.Thus,the present study constructed a quantitative histological image classifier with tumour nuclear features to predict osteosarcoma outcomes using haema-toxylin and eosin(H&E)‐stained whole‐slide images(WSIs)from 150 osteosarcoma patients.We first segmented eight distinct tissues in osteosarcoma H&E‐stained WSIs,with an average accuracy of 90.63%on the testing set.The tumour areas were auto-matically and accurately acquired,facilitating the tumour cell nuclear feature extraction process.Based on six selected tumour nuclear features,we developed an osteosarcoma histological image classifier(OSHIC)to predict the recurrence and survival of osteo-sarcoma following standard treatment.The quantitative OSHIC derived from tumour nuclear features independently predicted the recurrence and survival of osteosarcoma patients,thereby contributing to precision oncology.Moreover,we developed a fully automated workflow to extract quantitative image features,evaluate the diagnostic values of feature sets and build classifiers to predict osteosarcoma outcomes.Thus,the present study provides a novel tool for predicting osteosarcoma outcomes,which has a broad application prospect in clinical practice.

Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

A trilogy antimicrobial strategy for multiple infections of orthopedic implants throughout their life cycle

Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles.However,ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc.As these incidents could easily introduce new microbial pathogens in/onto the implants.Herein,we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning,could effectively eradicate bacterial infection at various stages of implantation.Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating.Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating.Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo.Finally,the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc,which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating.Moreover,sustained release of Sr2+and Zn2+during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.

PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis ina Temporal Manner

Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.