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  1. Order is one of the most important concepts to interpret various phenomena such as the emergence of turbulence and the life-evolution process. The generation of laser can also be treated as an ordering process in which the interaction between the laser beam and the gain medium leads to the correlation between photons in the output optical field. Here, we demonstrate experimentally in a hybrid Raman-laser-optomechanical system that an ordered Raman laser can be generated from an entropy-absorption process by a chaotic optomechanical resonator. When the optomechanical resonator is chaotic or disordered enough, the Raman-laser field is in an ordered lasing mode. This can be interpreted by the entropy transfer from the Raman-laser mode to the chaotic motion mediated by optomechanics. Different order parameters, such as the box-counting dimension, the maximal Lyapunov exponent, and the Kolmogorov entropy, are introduced to quantitatively analyze this entropy transfer process, by which we can observe the order transfer between the Raman-laser mode and the optomechanical resonator. Our study presents a new mechanism of laser generation and opens up new dimensions of research such as the modulation of laser by optomechanics.

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  2. The incorporation of noncanonical amino acids (ncAAs) into fluorescent proteins is promising for red-shifting their fluorescence and benefiting tissue imaging with deep penetration and low phototoxicity. However, ncAA-based red fluorescent proteins (RFPs) have been rare. The 3-aminotyrosine modified superfolder green fluorescent protein (aY-sfGFP) represents a recent advance, yet the molecular mechanism for its red-shifted fluorescence remains elusive while its dim fluorescence hinders applications. Herein, we implement femtosecond stimulated Raman spectroscopy to obtain structural fingerprints in the electronic ground state and reveal that aY-sfGFP possesses a GFP-like instead of RFP-like chromophore. Red color of aY-sfGFP intrinsically arises from a unique “double-donor” chromophore structure that raises ground-state energy and enhances charge transfer, notably differing from the conventional conjugation mechanism. We further developed two aY-sfGFP mutants (E222H and T203H) with significantly improved (∼12-fold higher) brightness by rationally restraining the chromophore's nonradiative decay through electronic and steric effects, aided by solvatochromic and fluorogenic studies of the model chromophore in solution. This study thus provides functional mechanisms and generalizable insights into ncAA-RFPs with an efficient route for engineering redder and brighter fluorescent proteins. 
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    Free, publicly-accessible full text available June 15, 2024
  3. Free, publicly-accessible full text available May 1, 2024
  4. Recent advances in protein structure prediction have generated accurate structures of previously uncharacterized human proteins. Identifying domains in these predicted structures and classifying them into an evolutionary hierarchy can reveal biological insights. Here, we describe the detection and classification of domains from the human proteome. Our classification indicates that only 62% of residues are located in globular domains. We further classify these globular domains and observe that the majority (65%) can be classified among known folds by sequence, with a smaller fraction (33%) requiring structural data to refine the domain boundaries and/or to support their homology. A relatively small number (966 domains) cannot be confidently assigned using our automatic pipelines, thus demanding manual inspection. We classify 47,576 domains, of which only 23% have been included in experimental structures. A portion (6.3%) of these classified globular domains lack sequence-based annotation in InterPro. A quarter (23%) have not been structurally modeled by homology, and they contain 2,540 known disease-causing single amino acid variations whose pathogenesis can now be inferred using AF models. A comparison of classified domains from a series of model organisms revealed expansions of several immune response-related domains in humans and a depletion of olfactory receptors. Finally, we use this classification to expand well-known protein families of biological significance. These classifications are presented on the ECOD website ( ). 
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    Free, publicly-accessible full text available March 21, 2024
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  7. A far-red fluorescent protein-based indicator allowed the imaging of synaptic Zn 2+ in brain slices and awake mice. 
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    Free, publicly-accessible full text available March 1, 2024
  8. DIRECT-NET identifies cis-regulatory elements and constructs regulatory networks from single-cell multiomics data. 
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