Discovery of metal-binding proteins by thermal proteome profiling.

Metal-binding proteins (MBPs) have various and important biological roles in all living species and many human diseases are intricately linked to dysfunctional MBPs. Here, we report a chemoproteomic method named 'metal extraction-triggered agitation logged by thermal proteome profiling' (METAL-TPP) to globally profile MBPs in proteomes. The method involves the extraction of metals from MBPs using chelators and monitoring the resulting protein stability changes through thermal proteome profiling. Applying METAL-TPP to the human proteome with a broad-spectrum chelator, EDTA, revealed a group of proteins with reduced thermal stability that contained both previously known MBPs and currently unannotated MBP candidates. Biochemical characterization of one potential target, glutamine-fructose-6-phosphate transaminase 2 (GFPT2), showed that zinc bound the protein, inhibited its enzymatic activity and modulated the hexosamine biosynthesis pathway. METAL-TPP profiling with another chelator, TPEN, uncovered additional MBPs in proteomes. Collectively, this study developed a robust tool for proteomic discovery of MBPs and provides a rich resource for functional studies of metals in cell biology.

A novel artificial vertebral implant with Gyroid porous structures for reducing the subsidence and mechanical failure rate after vertebral body replacement.

BACKGROUND: Prosthesis subsidence and mechanical failure were considered significant threats after vertebral body replacement during the long-term follow-up. Therefore, improving and optimizing the structure of vertebral substitutes for exceptional performance has become a pivotal challenge in spinal reconstruction. METHODS: The study aimed to develop a novel artificial vertebral implant (AVI) with triply periodic minimal surface Gyroid porous structures to enhance the safety and stability of prostheses. The biomechanical performance of AVIs under different loading conditions was analyzed using the finite element method. These implants were fabricated using selective laser melting technology and evaluated through static compression and subsidence experiments. RESULTS: The results demonstrated that the peak stress in the Gyroid porous AVI was consistently lower than that in the traditional porous AVI under all loading conditions, with a maximum reduction of 73.4%. Additionally, it effectively reduced peak stress at the bone-implant interface of the vertebrae. Static compression experiments demonstrated that the Gyroid porous AVI was about 1.63 times to traditional porous AVI in terms of the maximum compression load, indicating that Gyroid porous AVI could meet the safety requirement. Furthermore, static subsidence experiments revealed that the subsidence tendency of Gyroid porous AVI in polyurethane foam (simulated cancellous bone) was approximately 15.7% lower than that of traditional porous AVI. CONCLUSIONS: The Gyroid porous AVI exhibited higher compressive strength and lower subsidence tendency than the strut-based traditional porous AVI, indicating it may be a promising substitute for spinal reconstruction.

Discovery of cisplatin-binding proteins by competitive cysteinome profiling.

Cisplatin is a widely used cancer metallodrug that induces cytotoxicity by targeting DNA and chelating cysteines in proteins. Here we applied a competitive activity-based protein profiling strategy to identify cisplatin-binding cysteines in cancer proteomes. A novel cisplatin target, MetAP1, was identified and functionally validated to contribute to cisplatin's cytotoxicity.

Therapeutic effect of transumbilical single-port laparoscopic surgery versus triple-port laparoscopic surgery for ovarian cyst.

OBJECTIVE: To compare the therapeutic effect of transumbilical single-port laparoscopic surgery (TSPLS) and three-port laparoscopic surgery (TPLS) on ovarian cyst. METHODS: Clinical data of 60 patients with ovarian cyst admitted to our hospital were respectively analyzed. The patients were divided into a TPLS group (n=30) and a TSPLS group (n=30) according to surgical methods. Clinical indicators, visual analogue scale (VAS), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and satisfaction regarding aesthetic appearance of the incision were compared between the two groups. RESULTS: The operation time, time to anal exhaust and hospital stay in the TSPLS group were shorter than those in the TPLS group, and lower postoperative VAS, SAS and SDS scores and higher quality-of-life score were seen in the TSPLS group (all P<0.05). The incidence of postoperative complications in the TSPLS group was lower than that in the TPLS group (P<0.05). The overall satisfaction in the TSPLS group was significantly higher than that in the TPLS group (93.33% vs. 66.67%; χ2=51.526, P=0.001). CONCLUSION: Compared with TPLS, TSPLS has better therapeutic effect on ovarian cyst. TSPLS can improve the clinical indications of patients with higher safety.