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In traditional cemented carbides, Co is mainly used as a binder. Recently, replacing Co with medium- to high-entropy alloys has shown significant improvements in hardness, fracture toughness, high-temperature oxidation resistance, and corrosion resistance, making it a research focus globally. Both the typical grain refiner Cr3C2 and medium- to high-entropy alloy binders affect the WC grain size in cemented carbides. This study investigates the synergistic grain refinement mechanism of Cr3C2 and medium- to high-entropy alloy binders on WC grains and their impact on the microstructure and mechanical properties of cemented carbides. The results show that increasing the Cr3C2 addition refined WC grains in the WC-CoNiFe alloy, increased coercivity, and enhanced hardness, with transverse rupture strength first increasing and then decreasing. The alloy achieved optimal performance at 0.6 wt.%Cr3C2, with a hardness of 91.25 HRA and transverse rupture strength of 3883.2 MPa. [ABSTRACT FROM AUTHOR]

Ovarian cancer remains the most common gynecologic malignancy, because of its chemotherapy resistance and relapse. Anlotinib, a new oral multi-targeted tyrosine kinase inhibitor, has shown encouraging antitumor activity in several preclinical and clinical trials, while its effect on ovarian cancer has not been reported. In this study, we investigated the antitumor activity and underlying mechanism of anlotinib in ovarian cancer. Cell viability was analyzed by Cell Counting Kit-8 assay. Migration was measured by wound-healing assay. The cell cycle distribution and cell apoptosis rate were detected by flow cytometry. In vivo antitumor effect was analyzed in mouse ovarian carcinoma peritoneal metastasis model. We found that anlotinib inhibited the proliferation of ovarian cancer cells in a dose- and time- dependent manner by inducing G2/M phase arrest and apoptosis. Moreover, anlotinib upregulated the the phosphorylation of Histone H3, and expression of p21 protein in vitro. In addition, anlotinib inhibited the migration of ovarian cancer cells in vitro. Furthermore, anlotinib inhibited tumor growth by inhibiting cell proliferation and suppressing ovarian cancer angiogenesis in vivo. This study demonstrated the extraordinary anti-ovarian cancer effect of anlotinib, which may provide a promising therapeutic strategy for ovarian cancer. [ABSTRACT FROM AUTHOR]

Rationale: Neoadjuvant chemotherapy (NAC) has been recognized as an indispensable strategy for advanced malignancies. Nevertheless, the enhancement of overall patient survival in NAC recipients has encountered challenges due to the limited sustainability of its efficacy and the inability to prevent postoperative tumor recurrence and metastasis. Methods: We devise a hierarchically unlocking nanoSTING stimulant liposome (AUG) as a neoadjuvant chemoimmunotherapy agent in the debulking of tumors prior to surgery and prevention of postoperative tumor recurrence and metastasis by simultaneously activating innate and adaptive antitumor immune responses. In the weakly acidic tumor microenvironment, the hydrazone bond within AUG is initially cleaved, leading to the release of a cyclic seven-membered ring containing tertiary amine that serve to activate the stimulator of interferon genes (STING) pathway. Following this, AUG undergoes degradation within lysosomes, facilitating the release of doxorubicin and ultimately inducing immunogenic cell death along with leakage of double-stranded DNA into the cytoplasm. Results: The hierarchically acidity-unlocking pattern enables cascaded STING activation, achieving over 90% tumor growth inhibition in subcutaneous xenograft model and preventing 75% of mice from postsurgical metastasis or recurrence when combined with immune checkpoint inhibitors. Conclusion: Our strategy highlights the potency of AUG as a neoadjuvant paradigm for presurgical tumor debulking and as a preventive measure against postoperative tumor recurrence and metastasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)