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Fluorescent proteins (FPs) are noninvasive genetically encodable probes that have revolutionized bioimaging and health fields with vivid images and an ever-growing repertoire from jellyfish to sea anemones and corals. Inside the protein matrix, chromophore nonplanarity and flexibility have long been argued to govern the fluorescence efficiency of FPs, yet their fundamental roles and relative importance have been elusive which hinder the rational design of versatile FPs and biosensors. Herein, we tackle this central question by investigating two recently engineered FP-based turn-on chloride (Cl^–) sensors, ChlorON1 and 3, using an ultrafast electronic and vibrational spectroscopic toolset together with advanced multireference simulations for both structure and spectrum. We elucidate that fluorescence enhancement of the chloride-bound ChlorON3 stems from a substantially more twisted chromophore than ChlorON1 via comprehensive simulations starting from the available crystal structure of parent protein (mNeonGreen), also featuring an enhanced radiative pathway due to an adjacent leucine residue in the emissive population. This finding indicates that the commonly stated chromophore planarity is not, but conformational rigidity is, the decisive factor for high fluorescence efficiency. Such mechanistic insights into FPs are generalizable to chromoproteins and other photosensitive biomolecules, which can facilitate the targeted design of brighter and/or tunable biosensors. 

Photoconvertible fluorescent proteins (pcFPs) have enabled exquisite images of cellular structures due to their genetic encodability and red-shifted emission with high brightness, hence receiving increased traction in the field. However, the red form of Kaede-like pcFPs after photoconversion remains underexplored. We implemented ultrafast electronic and vibrational spectroscopies on the red Kaede chromophore in solution vs the protein pocket of the least-evolved ancestor (LEA, a Kaede-like green-to-red pcFP) to gain crucial insights into the photophysical processes of the chromophore. The measured fluorescence quantum yield (FQY) values were correlated with ultrafast dynamics to reveal that hydrogen-bonding interactions with the solvent can quench the excited-state Kaede in solution. A viscosity-dependent sub-ps decay indicates nonradiative relaxation involving swift chromophore conformational motions. Femtosecond transient absorption and stimulated Raman spectroscopy (FSRS) reveal an additional ∼1 ps decay of the photoconverted red form of LEA that is absent in green LEA before photoconversion. Transient structural dynamics from FSRS elucidate this decay to involve the phenolate and imidazolinone ring twists that are implicated during cis → trans isomerization and on → off photoswitching in phototransformable fluorescent proteins (FPs). Compared to green-emitting species, the FQY of red LEA (∼0.58) and many other red FPs are often reduced, limiting their applications in modern bioimaging techniques. By shining more light on the often overlooked photoconverted form of pcFPs with ultrafast spectroscopies, we envision such essential mechanistic insights to enable a bottom-up approach for rationally improving the brightness of red-emitting LEA and many other controllable bioprobes, including FPs. 

The Front Cover illustrates ultrafast spectroscopic insights into the photoexcited energy relaxation pathways of St. John's wort-derived fluorescent photosensitizer hypericin in solution. The bidirectional excited-state intramolecular proton transfer (ESIPT) gains prominence after UV excitation with enhanced photoprotection in a “proton pachinko”, whereas visible excitation results in more phototoxicity. More information can be found in the Research Article by C. Fang and co-workers (DOI: 10.1002/chem.202500639). Cover design by S. Johnson and C. Fang. 

The PEG addition into aqueous electrolytes has an opposite effect on an Fe metal anode compared to a Zn metal anode. 

Abstract Here, four MOFs, namely Sc-TBAPy, Al-TBAPy, Y-TBAPy, and Fe-TBAPy (TBAPy: 1,3,6,8-tetrakis(p-benzoic acid)pyrene), were characterized and evaluated for their ability to remediate glyphosate (GP) from water. Among these materials, Sc-TBAPy demonstrates superior performance in both the adsorption and degradation of GP. Upon light irradiation for 5 min, Sc-TBAPy completely degrades 100% of GP in a 1.5 mM aqueous solution. Femtosecond transient absorption spectroscopy reveals that Sc-TBAPy exhibits enhanced charge transfer character compared to the other MOFs, as well as suppressed formation of emissive excimers that could impede photocatalysis. This finding was further supported by hydrogen evolution half-reaction (HER) experiments, which demonstrated Sc-TBAPy’s superior catalytic activity for water splitting. In addition to its faster adsorption and more efficient photodegradation of GP, Sc-TBAPy also followed a selective pathway towards the oxidation of GP, avoiding the formation of toxic aminomethylphosphonic acid observed with the other M³⁺-TBAPy MOFs. To investigate the selectivity observed with Sc-TBAPy, electron spin resonance, depleted oxygen conditions, and solvent exchange with D₂O were employed to elucidate the role of different reactive oxygen species on GP photodegradation. The findings indicate that singlet oxygen (¹O₂) plays a critical role in the selective photodegradation pathway achieved by Sc-TBAPy. 

In the present study, we demonstrated that the introduction of a 1,4-diethyl-1,2,3,4-tetrahydroquinoxalin moiety into the arylidene part of GFP chromophore-derived compounds results in the formation of environment-sensitive fluorogens. The rationally designed and synthesized compounds exhibit remarkable solvent- and pH-dependence in fluorescence intensity. The solvent-dependent variation in fluorescence quantum yield makes it possible to use some of the proposed compounds as polarity sensors suitable for selective endoplasmic reticulum fluorescent labeling in living cells. Moreover, the pH-dependent emission intensity variation of other fluorogens makes them selective fluorescent labels for the lysosomes in living cells. 

Vector databases have recently gained significant attention due to the emergence of large language models that produce vector embeddings for text. Existing vector databases can be broadly categorized into two types: specialized and generalized. Specialized vector databases are explicitly designed and optimized for managing vector data, while generalized ones support vector data management within a general purpose database. While specialized vector databases are interesting, there is a substantial customer base interested in generalized vector databases for various reasons, e.g., a reluctance to move data out of relational databases to reduce data silos and costs, the desire to use SQL, and the need for more sophisticated query processing of vector and non-vector data. However, generalized vector databases face two main challenges: performance and interoperability of vector search with SQL, such as combining vector search with filters, joins, or even fulltext search. In this paper, we present SingleStore-V, a full-fledged generalized vector database integrated into SingleStore, a modern distributed relational database optimized for both OLAP and OLTP workloads. SingleStore-V achieves high performance and interoperability via a suite of optimizations. Experiments on standard vector benchmarks show that SingleStore-V performs comparably to Milvus, a highly-optimized specialized vector database, and significantly outperforms pgvector, a popular generalized vector database in PostgreSQL. We believe this paper will shed light on integrating vector search into relational databases in general, as many design concepts and optimizations apply to other databases.