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Abstract Reversible protein phosphorylation, regulated by protein phosphatases, fine-tunes target protein function and plays a vital role in biological processes. Dysregulation of this process leads to aberrant post-translational modifications (PTMs) and contributes to disease development. Despite the widespread use of artificial catalysts as enzyme mimetics, their direct modulation of proteins remains largely unexplored. To address this gap and enable the reversal of aberrant PTMs for disease therapy, we present the development of artificial protein modulators (APROMs). Through atomic-level engineering of heterogeneous catalysts with asymmetric catalytic centers, these modulators bear structural similarities to protein phosphatases and exhibit remarkable ability to destabilize the bridging μ3-hydroxide. This activation of catalytic centers enables spontaneous hydrolysis of phospho-substrates, providing precise control over PTMs. Notably, APROMs, with protein phosphatase-like characteristics, catalytically reprogram the biological function of α-synuclein by directly hydrolyzing hyperphosphorylated α-synuclein. Consequently, synaptic function is reinforced in Parkinson’s disease. Our findings offer a promising avenue for reprogramming protein function through de novo PTMs strategy.

Joining C/C composites to Ni-based single crystal alloy DD3 can significantly broaden their industrial application. The currently used active brazing method (ABM) may cause harmful reactions with Ni-based alloys, generating brittle compounds and deteriorating joint performance. In this work, a two-step method involving chromium carbide (Cr–C) surface modification and brazing using pure Cu filler is first developed to explore avoiding brittle compounds in joints. Surprisingly, the brazed seam of joints is mainly composed of (Cu, Ni) solid solution (s, s) without generating brittle compounds. At the DD3 interface, only (Ni, Cu) (s, s) and (Cu, Ni) (s, s) layers are formed. Besides, (W, Mo) (s, s) particles are precipitated nearby the DD3 substrate. For the C/C interface, the Cu filler is tightly joined to the Cr–C layer without forming new phases. The joint microstructure has no significant change with the variation of the Cr–C layer thickness. As increased the Cr–C layer thickness, the joint strength first increases and then decreases. The maximum shear strength of ∼32 MPa is obtained when the Cr–C layer thickness is ∼4.6 μm. The joint shear strength decreases with increased testing temperatures, which can still be maintained at ∼28 MPa at 600 °C. The surface modification and brazing strategy in this work can be further applied to the joining of other carbon materials and ceramics with poor wettability.