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Abstract Directed evolution generates novel biomolecules with desired functions by iteratively diversifying the genetic sequence of wildtype biomolecules, relaying the genetic information to the molecule with function, and selecting the variants that progresses towards the properties of interest. While traditional directed evolution consumes significant labor and time for each step, continuous evolution seeks to automate all steps so directed evolution can proceed with minimum human intervention and dramatically shortened time. A major application of continuous evolution is the generation of novel enzymes, which catalyze reactions under conditions that are not favorable to their wildtype counterparts, or on altered substrates. The challenge to continuously evolve enzymes lies in automating sufficient, unbiased gene diversification, providing selection for a wide array of reaction types, and linking the genetic information to the phenotypic function. Over years of development, continuous evolution has accumulated versatile strategies to address these challenges, enabling its use as a general tool for enzyme engineering. As the capability of continuous evolution continues to expand, its impact will increase across various industries. In this review, we summarize the working mechanisms of recently developed continuous evolution strategies, discuss examples of their applications focusing on enzyme evolution, and point out their limitations and future directions. 

Zwitterionic hydrogels, as highly hydrated and soft materials, have been considered as promising materials for wound dressing, due to their unique antifouling and mechanical properties. While the viscoelasticity and softness of zwitterionic hydrogels are hypothetically essential for creating adaptive cellular niches, the underlying mechanically regulated wound healing mechanism still remains elusive. To test this hypothesis, we fabricated zwitterionic poly(sulfobetaine methacrylate) (polySBMA) hydrogels with different elastic moduli prepared at different crosslinker contents, and then applied the hydrogels to full-thickness cutaneous wounds in mice. In vivo wound healing studies compared the mechanical cue-induced effects of soft and stiff polySBMA hydrogels on wound closure rates, granulation tissue formation and collagen deposition. Collective results showed that the softer and more viscoelastic hydrogels facilitated cell proliferation, granulation formation, collagen aggregation, and chondrogenic ECM deposition. Such high wound healing efficiency by the softer hydrogels is likely attributed to stress dissipation by expanding the cell proliferation, the up-regulation of blood vessel formation, and the enhanced polarization of M2/M1 macrophages, both of which would provide more oxygen and nutrients for cell proliferation and migration, leading to enhanced wound repair. This work not only reveals a mechanical property–wound healing relationship of zwitterionic polySBMA hydrogels, but also provides a promising candidate and strategy for the next-generation of wound dressings. 

ABSTRACT Measurements of large-scale structure are interpreted using theoretical predictions for the matter distribution, including potential impacts of baryonic physics. We constrain the feedback strength of baryons jointly with cosmology using weak lensing and galaxy clustering observables (3 × 2pt) of Dark Energy Survey (DES) Year 1 data in combination with external information from baryon acoustic oscillations (BAO) and Planck cosmic microwave background polarization. Our baryon modelling is informed by a set of hydrodynamical simulations that span a variety of baryon scenarios; we span this space via a Principal Component (PC) analysis of the summary statistics extracted from these simulations. We show that at the level of DES Y1 constraining power, one PC is sufficient to describe the variation of baryonic effects in the observables, and the first PC amplitude (Q1) generally reflects the strength of baryon feedback. With the upper limit of Q1 prior being bound by the Illustris feedback scenarios, we reach $$\sim 20{{\ \rm per\ cent}}$$ improvement in the constraint of $$S_8=\sigma _8(\Omega _{\rm m}/0.3)^{0.5}=0.788^{+0.018}_{-0.021}$$ compared to the original DES 3 × 2pt analysis. This gain is driven by the inclusion of small-scale cosmic shear information down to 2.5 arcmin, which was excluded in previous DES analyses that did not model baryonic physics. We obtain $$S_8=0.781^{+0.014}_{-0.015}$$ for the combined DES Y1+Planck EE+BAO analysis with a non-informative Q1 prior. In terms of the baryon constraints, we measure $$Q_1=1.14^{+2.20}_{-2.80}$$ for DES Y1 only and $$Q_1=1.42^{+1.63}_{-1.48}$$ for DESY1+Planck EE+BAO, allowing us to exclude one of the most extreme AGN feedback hydrodynamical scenario at more than 2σ.