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In this paper, a novel improved whale optimization algorithm (IWOA), based on the integrated approach, is presented for solving the flexible job shop scheduling problem (FJSP) with the objective of minimizing makespan. First of all, to make the whale optimization algorithm (WOA) adaptive to the FJSP, the conversion method between the whale individual position vector and the scheduling solution is firstly proposed. Secondly, a resultful initialization scheme with certain quality is obtained using chaotic reverse learning (CRL) strategies. Thirdly, a nonlinear convergence factor (NFC) and an adaptive weight (AW) are introduced to balance the abilities of exploitation and exploration of the algorithm. Furthermore, a variable neighborhood search (VNS) operation is performed on the current optimal individual to enhance the accuracy and effectiveness of the local exploration. Experimental results on various benchmark instances show that the proposed IWOA can obtain competitive results compared to the existing algorithms in a short time.

Wnt/β-catenin signaling is a conserved pathway crucially governing development, tissue homeostasis and oncogenesis in metazoan. Through screening, we identified a deubiquitinase (DUB) USP10 as a novel modulator of Wnt/β-catenin signaling. Mechanistically, USP10 binds to Axin1 via conserved motifs and stabilizes Axin1 through K48-linked deubiquitination. And in parallel, USP10 tethers Axin1 and β-catenin physically, via stabilizing the phase separation of Axin1 through its intrinsically-disordered regions, which is regardless of its enzymatic activity. Functionally, we show USP10 prominently regulates zebrafish embryonic development and murine intestinal homeostasis by antagonizing Wnt/β-catenin signaling. Additionally in human colorectal cancer, USP10 substantially represses cancer growth and correlates with Wnt/β-catenin magnitude clinically. Collectively, we discovered USP10 functioning in multiple biological processes through repressing Wnt/β-catenin signaling and unearthed a novel DUB-dependent and -independent dual-regulating mechanism by which USP10 utilizes in Wnt regulation context-dependently. Our study also suggested the potential of USP10 inhibitor in treating Wnt-related diseases.

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