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Phycocyanin 620 (PC620) is the outermost light-harvesting complex in phycobilisome of cyanobacteria, engaged in light collection and energy transfer to the core antenna, allophycocyanin. Recently, long-lived exciton–vibrational coherences have been observed in allophycocyanin, accounting for the coherent energy transfer [Zhu et al., Nat. Commun. 15, 3171 (2024)]. PC620 has a nearly identical spatial location of three α84–β84 phycocyanobilin pigment pairs to those in allophycocyanin, inferring an existence of possible coherent energy transfer pathways. However, whether PC620 undergoes coherent or incoherent energy transfer remains debated. Furthermore, accurate determination of energy transfer rates in PC620 is still necessary owing to the spectral overlap and broadening in conventional time-resolved spectroscopic measurements. In this work, the energy transfer process within PC620 was directly resolved by polarization-controlled two dimensional electronic spectroscopy (2DES) and global analysis. The results show that the energy transfer from α84 to the adjacent β84 has a lifetime constant of 400 fs, from β155 to β84 of 6–8 ps, and from β155 to α84 of 66 ps, fully conforming to the Förster resonance energy transfer mechanism. The circular dichroism spectrum also reveals that the α84–β84 pigment pair does not form excitonic dimer, and the observed oscillatory signals are confirmed to be vibrational coherence, excluding the exciton–vibrational coupling. Nodal line slope analysis of 2DES further reveals that all the vibrational modes participate in the energy dissipation of the excited states. Our results consolidate that the ultrafast energy transfer process in PC620 is incoherent, where the twisted conformation of α84 is suggested as the main cause for preventing the formation of α84–β84 excitonic dimer in contrast to allophycocyanin. [ABSTRACT FROM AUTHOR]

In the recently discovered proton-coupled energy transfer (PCEnT) mechanism, the transfer of electronic excitation energy between donor and acceptor chromophores is coupled to a proton transfer reaction. Herein, we develop a general theory for PCEnT and derive an analytical expression for the nonadiabatic PCEnT rate constant. This theory treats the transferring hydrogen nucleus quantum mechanically and describes the PCEnT process in terms of nonadiabatic transitions between reactant and product electron–proton vibronic states. The rate constant is expressed as a summation over these vibronic states, and the contribution of each pair of vibronic states depends on the square of the vibronic coupling as well as the spectral convolution integral, which can be viewed as a generalization of the Förster-type spectral overlap integral for vibronic rather than electronic states. The convolution integral also accounts for the common vibrational modes shared by the donor and acceptor chromophores for intramolecular PCEnT. We apply this theory to model systems to investigate the key features of PCEnT processes. The excited vibronic states can contribute significantly to the total PCEnT rate constant, and the common modes can either slow down or speed up the process. Because the pairs of vibronic states that contribute the most to the PCEnT rate constant may correspond to spectroscopically dark states, PCEnT could occur even when there is no apparent overlap between the donor emission and acceptor absorption spectra. This theory will assist in the interpretation of experimental data and will guide the design of additional PCEnT systems. [ABSTRACT FROM AUTHOR]

Electronic energy transfer in molecular wires is usually theoretically investigated with a harmonic bath to model the environment. The present study is a continuation of our previous work [A. Sindhu and A. Jain, Chem. Phys. Chem. 23, e2022003 (2022)] on studying the dynamics of molecular wires using surface hopping simulations. We extend our study to a 7-site model Hamiltonian and investigate the effects of an anharmonic bath on coherent energy transfer in molecular wires. We show that oscillatory and coherent population dynamics remain intact even in the presence of the anharmonic bath and further highlight the multiple channels available for energy flow in molecular wires. [ABSTRACT FROM AUTHOR]

A previously developed semiclassical theory of nonadiabatic energy transfer is used to analyze electronic excitation and quenching in three-dimensional atomic collisions. The predicted transition probabilities, cross sections, and rate coefficients are compared with the quantum scattering calculations for O + O and N + N, for the same interaction potentials and nonadiabatic coupling, and with the experimental data where available. The theory predictions are in very good agreement with quantum scattering, at the conditions when the energy transfer is dominated by a single pair of adiabatic potentials. Closed-form analytic expressions for the cross sections and rate coefficients are obtained, for both the strongly and weakly coupled cases. The results quantify and illustrate the effect of the interaction potentials and their coupling on the energy transfer. The analytic cross sections and rate coefficients are in good agreement with the numerical predictions. The same approach has been used to predict the rate coefficients of electronic excitation and quenching in collisions of N + O atoms. The fidelity of these predictions may be improved considerably if accurate potentials for the excited electronic states of N + O and their coupling are available. The applicability of the semiclassical theory for the prediction of the rates of heavy particle impact excitation in atom–molecule collisions is discussed. [ABSTRACT FROM AUTHOR]

The compound 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) is a versatile fluorophore widely used in Förster resonance energy transfer (FRET) spectroscopy studies due to its remarkable sensitivity, enabling precise donor–acceptor distance measurements, even for short peptides. Integrating time-resolved and FRET spectroscopies with molecular dynamics simulations provides a robust approach to unravel the structure and dynamics of biopolymers in a solution. This study investigates the structural behavior of three octapeptide variants: Trp-(Gly-Ser)3-Dbo, Trp-(GlyGly)3-Dbo, and Trp-(SerSer)3-Dbo, where Dbo represents the DBO-containing modified aspartic acid, using molecular dynamics simulations. Glycine- and serine-rich amino acid fragments, common in flexible protein regions, play essential roles in functional properties. Results show excellent agreement between end-to-end distances, orientational factors from simulations, and the available experimental and theoretical data, validating the reliability of the GROMOS force field model. The end-to-end distribution, modeled using three Gaussian distributions, reveals a complex shape, confirmed by cluster analysis highlighting a limited number of significant conformations dominating the peptide landscape. All peptides predominantly adopt a disordered state in the solvent, yet exhibit a compact shape, aligning with the model of disordered polypeptide chains in poor solvents. Conformations show marginal dependence on chain composition, with Ser-only chains exhibiting slightly more elongation. This study enhances our understanding of peptide behavior, providing valuable insights into their structural dynamics in solution. [ABSTRACT FROM AUTHOR]

Conical intersection (CI) leads to fast electronic energy transfer. However, Hamm and Stock [Phys. Rev. Lett. 109, 173201 (2012)] showed the existence of a vibrational CI and its role in vibrational energy relaxation. In this paper, we further investigate the vibrational energy relaxation using an isolated model Hamiltonian system of four vibrational modes with two distinctively different timescales (two fast modes and two slow modes). We show that the excitation of the slow modes plays a crucial role in the energy relaxation mechanism. We also analyze the system from a mixed quantum-classical (surface hopping method) and a completely classical point of view. Notably, surface hopping and even classical simulations also capture fast energy relaxation, which is a signature of CI's existence. [ABSTRACT FROM AUTHOR]

N-methyl-D-aspartate receptors are ionotropic glutamate receptors that mediate synaptic transmission and plasticity. Variable GluN2 subunits in diheterotetrameric receptors with identical GluN1 subunits set very different functional properties. To understand this diversity, we use single-molecule fluorescence resonance energy transfer (smFRET) to measure the conformations of the ligand binding domain and modulatory amino-terminal domain of the common GluN1 subunit in receptors with different GluN2 subunits. Our results demonstrate a strong influence of the GluN2 subunits on GluN1 rearrangements, both in non-agonized and partially agonized activation intermediates, which have been elusive to structural analysis, and in the fully liganded state. Chimeric analysis reveals structural determinants that contribute to these subtype differences. Our study provides a framework for understanding the conformational landscape that supports highly divergent levels of activity, desensitization, and agonist potency in receptors with different GluN2s and could open avenues for the development of subtype-specific modulators.

The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase-AMP complex and the ligase-AMP-DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase-AMP complex that persist in the ligase-AMP-DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments.

BackgroundChronic sympathetic stimulation drives desensitization and downregulation of β1 adrenergic receptor (β1AR) in heart failure. We aim to explore the differential downregulation subcellular pools of β1AR signaling in the heart.Methods and resultsWe applied chronic infusion of isoproterenol to induced cardiomyopathy in male C57BL/6J mice. We applied confocal and proximity ligation assay to examine β1AR association with L-type calcium channel, ryanodine receptor 2, and SERCA2a ((Sarco)endoplasmic reticulum calcium ATPase 2a) and Förster resonance energy transfer-based biosensors to probe subcellular β1AR-PKA (protein kinase A) signaling in ventricular myocytes. Chronic infusion of isoproterenol led to reduced β1AR protein levels, receptor association with L-type calcium channel and ryanodine receptor 2 measured by proximity ligation (puncta/cell, 29.65 saline versus 14.17 isoproterenol, P

Exciton transport in extended molecular systems and how to manipulate such transport in a complex environment are essential to many energy and optical-related applications. We investigate the mechanism of plasmon-coupled exciton transport by using the Pauli master equation approach, combined with kinetic rates derived from macroscopic quantum electrodynamics. Through our theoretical framework, we demonstrate that the presence of a silver nanorod induces significant frequency dependence in the ability of transporting exciton through a molecule chain, indicated by the exciton diffusion coefficient, due to the dispersive nature of the silver dielectric response. Compared with the same system in vacuum, great enhancement (up to a factor of 103) in the diffusion coefficient can be achieved by coupling the resonance energy transfer process to localized surface plasmon polariton modes of the nanorod. Furthermore, our analysis reveals that the diffusion coefficients with the nearest-neighbor coupling approximation are ∼10 times smaller than the results obtained beyond this approximation, emphasizing the significance of long-range coupling in exciton transport influenced by plasmonic nanostructures. This study not only paves the way for exploring practical approaches to study plasmon-coupled exciton transport but also provides crucial insights for the design of innovative plasmon-assisted photovoltaic applications. [ABSTRACT FROM AUTHOR]

Integrin mechanosensing plays an instrumental role in cell behavior, phenotype, and fate by transmitting mechanical signals that trigger downstream molecular and cellular changes. For instance, force transfer along key amino acid residues can mediate cell adhesion. Disrupting key binding sites within α 5 β 1 integrin's binding partner, fibronectin (FN) diminishes adhesive strength. While past studies have shown the importance of these residues in cell adhesion, the relationship between the dynamics of these residues and how integrin distributes force across the cell surface remains less explored. Here, we present a multiscale mechanical model to investigate the mechanical coupling between integrin nanoscale dynamics and whole-cell adhesion mechanics. Our framework leverages molecular dynamics simulations to investigate residues within α 5 β 1 -FN during stretching and the finite element method to visualize the whole-cell adhesion mechanics. The forces per integrin across the cell surface of the whole-cell model were consistent with past atomic force microscopy and Förster resonance energy transfer measurements from the literature. The molecular dynamics simulations also confirmed past studies that implicate two key sites within FN that maintain cell adhesion: the synergy site and arginine-glycine-aspartic acid (RGD) motif. Our study contributed to our understanding of molecular mechanisms by which these sites collaborate to mediate whole-cell integrin adhesion dynamics. Specifically, we showed how FN unfolding, residue binding/unbinding, and molecular structure contribute to α 5 β 1 -FN's nonlinear force–extension behavior during stretching. Our computational framework could be used to explain how the dynamics of key residues influence cell differentiation or how uniquely designed protein structures could dynamically limit the spread of metastatic cells. [ABSTRACT FROM AUTHOR]

Calmodulin transduces [Ca2+] information regulating the rhythmic Ca2+ cycling between the sarcoplasmic reticulum and cytoplasm during contraction and relaxation in cardiac and skeletal muscle. However, the structural dynamics by which calmodulin modulates the sarcoplasmic reticulum Ca2+ release channel, the ryanodine receptor, at physiologically relevant [Ca2+] is unknown. Using fluorescence lifetime FRET, we resolve different structural states of calmodulin and Ca2+-driven shifts in the conformation of calmodulin bound to ryanodine receptor. Skeletal and cardiac ryanodine receptor isoforms show different calmodulin-ryanodine receptor conformations, as well as binding and structural kinetics with 0.2-ms resolution, which reflect different functional roles of calmodulin. These FRET methods provide insight into the physiological calmodulin-ryanodine receptor structural states, revealing additional distinct structural states that complement cryo-EM models that are based on less physiological conditions. This technology will drive future studies on pathological calmodulin-ryanodine receptor interactions and dynamics with other important ryanodine receptor bound modulators.

In this work, a novel Y-NaBi(MoO 4) 2 @NaYF 4 :Yb, Tm composite was successfully synthesized for the first time by hydrothermal method. The lamellar Y-NaBi(MoO 4) 2 was dispersed on the surface of the hexagonal prism NaYF 4 :Yb, Tm without aggregation. The composite achieved a broad spectral response. The NaYF 4 :Yb, Tm absorbed near-infrared light and emitted ultraviolet and visible light by the energy transfer upconversion process. The emitted light was reabsorbed by Y-NaBi(MoO 4) 2 through the fluorescence resonance energy transfer process. Moreover, the doping of Y3+ ions enhanced the light response capability of the composite. The experimental results revealed that the photocatalytic degradation efficiency of ciprofloxacin (CIP) reached 96.2 % after 180 min of illumination under simulated sunlight. Meanwhile, the degradation pathways and attack sites of CIP were intensively investigated by liquid chromatography-mass spectrometry analysis and density functional theory theoretical calculations. The upconversion process, the separation of photogenerated carriers and rare earth metal ion doping all contributed to the high effective photodegradation. This work provided a new strategy for effective utilization of solar energy for the degradation of emerging pollutants to mitigate environmental pollution. [ABSTRACT FROM AUTHOR]

We report the luminescence-based detection of Group-1 carcinogen formaldehyde (FA) and Cr(VI)-oxoanions with a mesoporous Mn(II)-MOF (1), featuring a uninodal 4-c net topology and linear 1D square channels forming a polymeric 2D network. The Mn-MOF i.e., [Mn(phen)(hia)(H2O)]∞ was solvothermally constructed using π-conjugated, chelating phenanthroline (phen) and µ3–η2:η1 binding 5-hydroxyisophthalic acid (hia) ligands. The 2D rod-like crystallites of 1 demonstrated excellent phase purity, high thermal and photostability, and robustness under harsh conditions. The SCXRD and XPS studies established the structural framework and elemental composition, while the Hirshfeld surface analysis and NCI-RDG plot confirmed the presence of π–π stacking and weak interactions in 1. We explored the bright-blue emission of 1 for recyclable and fast-responsive (∼70 s) 'turn-off' detection of FA, with a low limit of detection (LOD) of 8.49 µM. Based on this, a 04-input-03-output molecular logic gate was proposed, which can be useful as a molecular switch for future applications. Furthermore, a unique experimental setup using the MOF film demonstrated ∼57% quenching upon exposure to FA vapor (an indoor VOC). Additionally, 1 exemplified itself as an efficient probe towards Cr(VI)-oxyanions, depicting LODs of 79 and 170 ppb, Stern–Volmer constants (KSV) of 16.13 × 104 and 12.73 × 104 M−1, and response times of ∼48 and ∼40 s for CrO42− and Cr2O72−, respectively. DFT calculations and specific wet-chemical investigations elucidated the FA detection to be triggered by photo-induced electron transfer (PET), while the Cr(VI)-sensing involved a combination of PET, the inner-filter effect (IFE), resonance energy transfer (RET), and electrostatic H-bonding interactions. The FA detection was validated using food samples (fish and meat) and wastewater specimens, achieving excellent recovery rates of ∼92–95%. Furthermore, the MOF's efficacy in recognizing the Cr(VI)-species in complex matrices (coal mine wastewater, sewage, and tap water) was investigated to yield high KSV values (3.10–5.17 × 104 and 2.16–7.03 × 104 M−1 for CrO42− and Cr2O72−), which demonstrated the probe's consistency and reliability. [ABSTRACT FROM AUTHOR]

A functionalized Hf(IV)-based metal–organic framework (MOF) was synthesized, characterized, and successfully employed as a highly sensitive and selective fluorometric sensor for (1,1-diamino-2,2-dinitroethylene) FOX-7, which is a significant nitro explosive. The fluorescent sensor (MOF), denoted as CSMCRI-KNC′, exhibited a turn-off fluorescence signal towards FOX-7 in a water medium even in the presence of other potentially competitive explosives. The limit of detection (LOD) value for the detection of FOX-7 is fairly low (189 nM), and the response time is extremely rapid (<20 s). The sensing mechanism was investigated in detail and found to be based on non-covalent interactions, fluorescence resonance energy transfer (FRET), and photo-induced electron transfer (PET) processes. The sensing medium (water), detection time, sensitivity, and selectivity demonstrate the great potential of CSMCRI-KNC′ in the fluorescence-based sensor field. Additionally, the MOF was utilized as an efficient, recyclable, and heterogeneous catalyst for Knoevenagel condensation between barbituric acid and aromatic aldehydes in the presence of ethanol in an eco-friendly reaction medium. The present catalytic methodology has several attractive features, including mild reaction conditions, a short reaction time, high atom economy, and tolerance of various functional moieties. The catalyst could be recovered and reused successively without any remarkable loss in its catalytic activity. Moreover, the "hot filtration method (Sheldon's test)" has also been established to ensure the heterogeneity of the catalyst. Furthermore, the plausible mechanism of the catalysis is well presented. [ABSTRACT FROM AUTHOR]

[Display omitted] Since the chiral emission of excited states is observed on carbon dots (CDs), exploration towards the design and synthesis of chiral CDs nanomaterials with circularly polarized luminescence (CPL) properties has been at a brisk pace. In this regard, the "host and guest" co-assembly strategy based on the combination of CDs and chiral templates has been of unique interest recently for its convenient operation, multicolor tunable CPL, and wide application of prepared CDs-composited materials in optoelectronic devices and information encryption. However, the existing chiral templates that match perfectly with chiral CDs exhibiting optical activity both in ground and excited states are rather scarce. In this work, we synthesize the chiral CDs that could induce the spontaneous supramolecular self-assembly of N-(9-fluorenylmethox-ycarbonyl) (Fmoc)-protected glutamic acid to form chiral hydrogels with helical nanostructure. The co-assembled hydrogels show powerful chiral template function, which not only enable chiral CDs with a luminescence dissymmetry factor (g lum) up to 10-2, but also have universal chiral transfer to inserted dye molecules, realizing full-color CPL and Förster resonance energy transfer (FRET) CPL as well as the distinction between left and right circularly polarized light. This CPL-active template based on chiral CDs enriches the design scenario of chiral functionalized nanomaterials. [ABSTRACT FROM AUTHOR]

The small GTPase Rho family are the major factors in mediating actin cytoskeleton dynamics. Rho-specific guanine nucleotide dissociation inhibitors (RhoGDIs) serve as important negative regulators by complexing with inactive Rho into the cytoplasm. However, how these two molecules interact still needs experimental verification. Based on fluorescence resonance energy transfer (FRET) measurements, we would demonstrate crucial sites in RhoGDI and RhoA for this regulatory role. Cotransfection of RhoGDI markedly reduced RhoA or Cdc42 activity in airway smooth muscle (ASM) cells, while D185R-RhoGDI mutant reversed this decrease, indicating that RhoGDI Asp185 residue is essential for the molecular interaction. R68D-RhoA (mutation in the switch II region) resulted in a deficiency in RhoGDI regulation, while TV37/38NG-RhoA (in the switch I region) displayed low RhoA activity. Hence, the Arg68 site in RhoA is indispensable for regulation by RhoGDI, and Thr37Val38 site is important for maintaining RhoA activity. Additionally, microtubule but not actin cytoskeleton showed inhibitory role in RhoA activity, while the dissolution of either cytoskeleton did not change the regulatory role of RhoGDI. In checking the downstream effect, reduction of RhoA activity induced by PDGF stimulation or RhoGDI decreased cellular stress fibers. In this study, FRET visualization was applied to have experimentally demonstrated the interaction sites and crucial role of RhoGDI in regulating RhoA activity. Highlights: • This study used FRET visualization to demonstrate the interaction sites and crucial role of RhoGDI in negatively regulating RhoA activity; • The Asp185 residue in RhoGDI is essential for molecular interaction between RhoGDI and RhoA; • The Arg68 site in RhoA is indispensable for regulation by RhoGDI, while Thr37Val38 site important for normal RhoA activity; • Microtubule showed inhibitory role in RhoA, and decreased RhoA activity induced by PDGF stimulation or RhoGDI reduced cellular stress fibers. [ABSTRACT FROM AUTHOR]

β-Cyclodextrin (β-CD)—functionalized carbon quantum dots (CDs) loaded with curcumin (CCM) were used for ClO– sensing with high sensitivity and selectivity. This fluorescence resonance energy transfer (FRET)-based sensor was created through attaching CCM to the CDs via β-CD linker. CCM could get into the interior of β-CD triggering the FRET from CDs to CCM, providing an 'off' state of the CDs. However, the effect of FRET was weakened by the ClO–, because the o-methoxyphenol structure from CCM was oxidized to be benzoquinone. The fluorescence intensity of CDs@β-CD@CCM at 440 nm can be heightened and 520 nm from CCM can decrease along with the increased ClO–. Therefore, a ratiometric fluorescence probe for ClO– sensing is successfully constructed. It conforms to a polynomial curve equation which is I440/I520 = −0.0268 + 0.0315 CClO–+ 0.0055[CClO–]2 (R 2 = 0.9958) between 0 and 18.4 μ M ClO–. Furthermore, we also obtain excellent results using this spectrophotometric method for ClO–-sensing in pure water and commercial disinfectants, which afford potential in the environment monitoring area. We expect this sensing platform could be helpful in other analogous probes in relevant fields. [ABSTRACT FROM AUTHOR]

MotY homologs are present in a variety of monotrichous bacterial strains and are thought to form an additional structural T ring in flagellar motors. While MotY potentially plays an important role in motor torque generation, its impact on motor output dynamics remains poorly understood. In this study, we investigate the role of MotY in P. aeruginosa, elucidating its interactions with the two sets of stator units (MotAB and MotCD) using Förster resonance energy transfer (FRET) assays. Employing a newly developed bead assay, we characterize the dynamic behavior of flagellar motors in motY mutants, identifying MotY as the key functional protein to affect the clockwise bias of naturally unbiased motors in P. aeruginosa. Our findings reveal that MotY enhances stator assembly efficiency without affecting the overall assembly of the flagellar structure. Additionally, we demonstrate that MotY is essential for maintaining motor torque and regulating switching rates. Our study highlights the physiological significance of MotY in fine-tuning flagellar motor function in complex environments. [ABSTRACT FROM AUTHOR]

BACKGROUND: The development of tissues and organs in the body is a precise and autonomously regulated process, and the function of biomechanical factors at this macroscale is a basic scientific question worth exploring. OBJECTIVE: To investigate the roles of cell mechanics in morphogenesis of the lobular organoid of 3D Madin-Darby canine kidney (MDCK). METHODS: The formation of MDCK lobular organoid was visualized by fluorescence resonance energy transfer technology, and the influence of different cellular mechanical signals and extracellular matrix environment on lobular organoid formation and corresponding changes in extracellular regulated protein kinases (ERK) activity were examined. RESULTS AND CONCLUSION: (1) Inhibition of ERK signaling pathway can inhibit the growth of MDCK lobular organoid. (2) Inhibition of cell contractile force signals such as ROCK pathway and Myosin II activity, reduced ERK activity and lobular organoid size. (3) Selective inhibition of calcium channels in plasma membrane and endoplasmic reticulum led to reduced ERK activity and lobular organoid growth. (4) By inhibiting the mechanically-sensitive receptor Piezo ion channel or integrin signal on the cell membrane, the lobular organoid became smaller or MDCK cells could not generate tissue morphology. (5) Extracellular matrix compositions affected the morphogenesis of lobular organoid. The addition of type I collagen in Matrigel changed the lobular organoid to elongated shape. (6) The results of this study preliminarily show that mechanical signals in the cells and extracellular matrix environment play an important role in culturing MDCK lobular organoid, and provides certain molecular mechanisms. [ABSTRACT FROM AUTHOR]

Replicating the microstructural basis and the near 100% excitation energy transfer efficiency in naturally occurring light‐harvesting complexes (LHCs) remains challenging in synthetic energy‐harvesting devices. Biological photosynthesis regulates active ensembles of light‐absorbing and funneling chlorophylls in proteins in response to fluctuating sunlight. Here, use of long‐range liquid crystal (LC) ordering to tailor chain orientation and packing structure in liquid crystalline conjugated polymer (LCCP) layers for bio‐mimicry of certain structural basis and light‐harvesting properties of LHCs is reported. It is found that long‐range orientational ordering in an LC phase of poly(9,9‐dioctylfluorene‐co‐benzothiadiazole) (F8BT) copolymer stabilizes a small fraction of randomly‐oriented F8BT nanocrystals dispersed in an amorphous matrix of F8BT chains, resembling a self‐doped host–guest system whereby excitation energy funneling and photoluminescence quantum efficiencies are enhanced significantly by triggering 3D donor‐to‐acceptor Förster resonance energy transfer (FRET) and dominant intrachain emission in the nano‐crystal acceptor. Further, photoalignment of nematic F8BT layers is combined with LC orientational ordering to fabricate large‐area‐extended monodomains exhibiting >60% crystallinity and ≈20 nm‐long interchain packing order. Remarkably, these monodomains demonstrate strong linearly polarized emission, whilst also promoting a new band‐edge absorption species and an extra emissive interchain excited state as compared to the non‐aligned films. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs), crucial for diverse physiological responses, have traditionally been investigated in their monomeric form. However, some GPCRs can form heteromers, revealing complexity in their functional characteristics such as ligand binding properties, downstream signaling pathways, and trafficking. Understanding GPCR heteromers is crucial in both physiological contexts and drug development. Here, we review the methodologies for investigating physical interactions in GPCR heteromers, including co-immunoprecipitation, proximity ligation assays, interfering peptide approaches, and live cell imaging techniques based on resonance energy transfer and bimolecular fluorescence complementation. In addition, we discuss recent advances in live cell imaging techniques for exploring functional features of GPCR heteromers, for example, circularly permuted fluorescent protein-based GPCR biosensors, TRUPATH, and nanobody-based GPCR biosensors. These advanced biosensors and live cell imaging technologies promise a deeper understanding of GPCR heteromers, urging a reassessment of their physiological importance and pharmacological relevance. Highlights: The discovery of G protein-coupled receptor (GPCR) heteromers has revealed a new level of complexity in their functional characteristics. This review explores a variety of methodologies and live cell imaging technologies for the investigation of physical interactions in GPCR heteromers and their functional alterations. Live cell imaging technologies such as fluorescent protein-based biosensors promise a deeper understanding of GPCR heteromers, urging a reassessment of their physiological importance and pharmacological relevance. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron entry involves spike (S) glycoprotein-mediated fusion of viral and late endosomal membranes. Here, using single-molecule Förster resonance energy transfer (sm-FRET) imaging and biochemical measurements, we directly visualized conformational changes of individual spike trimers on the surface of SARS-CoV-2 Omicron pseudovirions during fusion activation. We observed that the S2 domain of the Omicron spike is a dynamic fusion machine. S2 reversibly interchanges between the pre-fusion conformation and two previously undescribed intermediate conformations. Acidic pH shifts the conformational equilibrium of S2 toward an intermediate conformation and promotes the membrane hemi-fusion reaction. Moreover, we captured conformational reversibility in the S2 domain, which suggests that spike can protect itself from pre-triggering. Furthermore, we determined that Ca2+ directly promotes the S2 conformational change from an intermediate conformation to post-fusion conformation. In the presence of a target membrane, low pH and Ca2+ stimulate the irreversible transition to S2 post-fusion state and promote membrane fusion. [Display omitted] • Omicron spike fusion domain S2 shows dynamic plasticity • S2 spontaneously samples two functional intermediate conformations to fusion pathway • Low pH promotes formation of fusion competent intermediate conformations • Ca2+ catalyzes an S2 conformational change to a stable post fusion conformation at low pH Dey et al. used single molecule FRET for a real-time visualization of SARS-CoV-2 spike conformational dynamics on the virion surface during fusion triggered by low pH and Ca2+. The intermediates identified during dynamic S protein mediated fusion provide mechanistic insights for Omicron entry that may guide CoV inhibitor design. [ABSTRACT FROM AUTHOR]

White afterglow is very appealing both in scenario‐specific luminescence and background‐free bio‐imaging, while it is challenging to obtain stable white afterglow due to the difficulty in matching the emission lifetimes of complementary colors. It is reported here that assisted partial phosphorescence resonance energy transfer (ap‐PRET) can be a very efficient way toward this goal. When a blue afterglow of energy donor with long lifetime is obtained in a polymeric network displaying phosphorescent clusterization‐triggered emission (CTE), the network assisted partial phosphorescence resonance energy transfer (ap‐PRET) between it and a yellow fluorescent acceptor would yields orange afterglow. Owing to the energy supply of the CTE network, the lifetime of the donors blue afterglow can be tuned close to that of the acceptors orange afterglow through ap‐PRET in a wide donor to accepter ratios, and emissions ranging from the cold to warm white afterglows can be obtained. Amazingly, these white afterglows are along the blackbody radiation line in the CIE plot, disclosing the powerful ability of ap‐PRET in generating desired white afterglows for applications in diversified luminescent scenarios. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) stands out as a highly promising modality for tumor treatment, yet previous works have primarily centered around either boosting the production of reactive oxygen species (ROS) in tumor tissues or restricting it in normal tissues. The current challenge lies in the urgent need to achieve precise modulation of ROS production by simultaneously controlling both aspects. To achieve this goal, a precise PDT platform through a “locking‐unlocking‐boosting” ROS production strategy is presented, in which the generation of ROS is modulated by bidirectionally regulating the upconversion luminescence (UCL) of lanthanide‐doped nanoparticles (LnNPs), thus ROS production is “locked” in normal tissues but “boosted” in tumor tissues. In detail, by introducing an energy acceptor BHQ3, the UCL is initially quenched to prevent Chlorin e6 (Ce6) from generating ROS. However, under the tumor microenvironment with overexpressed miR‐21, LnNPs are sequestered from BHQ3 to “unlock” ROS generation and then assembled with QDs@B2, which functions as an antenna to sensitize LnNPs luminescence, to further “boost” ROS generation. With the assistance of spherical nucleic acids, this therapeutic agent effectively traverses the blood‐brain barrier (BBB), enabling efficient PDT for glioblastoma. [ABSTRACT FROM AUTHOR]

Cardiac troponin I (cTnI) is the most resorted biomarker for the detection of cardiovascular disease (CVD). The means of rapid quantification of cTnI levels in the blood can substantially minimize the risk of acute myocardial infarction and heart failure. A sensor for the non‐enzymatic evaluation of cardiac troponin‐I has been developed using fluorescent iron nanoclusters via a one‐pot synthesis employing (BSA) as the template and reducing agent, and hydrogen peroxide as the additive. The fluorescence of Iron Nanocluster is quenched with graphene oxide (GO) via fluorescence resonance energy transfer (FRET) between conjugate iron nanoclusters and graphene oxide. The sensor shows a low detection limit of 0.011 ng/mL. The benefits of utilizing a non‐enzymatic probe for detecting cardiac troponin I is that it avoids the need for enzymes and hence is economical, stable, and less impacted by environmental conditions such as temperature and pH. Non‐enzymatic probes are more useful for clinical use since they are more stable and have a longer shelf life. The developed non‐enzymatic probes are also highly selective and sensitive to the target analyte, making them suitable for the direct detection of cardiac troponin I in actual biological samples. [ABSTRACT FROM AUTHOR]

Noninvasive control over the reversible generation of singlet oxygen (1O2) has found the enormous practical implications in the field of biomedical science. However, metal‐free pure organic emitters, connected with a photoswitch, capable of generating "on‐demand" 1O2via triplet harvesting remain exceedingly rare; therefore, the utilization of these organic materials for the reversible control of singlet oxygen production remains at its infancy. Herein, an ambient triplet mediated emission in quinoline‐dithienylethene (DTE)‐core‐substituted naphthalene diimide (cNDI) derivative is unveiled via delayed fluorescence. The quinoline‐DTE‐cNDI triad displayed enhanced photoswitching efficiency via double FRET mechanism. It was found to have direct utilization in controlled photosensitized organic transformations via efficient generation of singlet oxygen (yield ΦΔ~0.55 in DCM and 0.73 in methanol). The designed molecule exhibits a long‐lived emission (τ∼1.1 μs) and very small singlet‐triplet splitting (ΔEST) of 0.13 eV empowering it to display delayed fluorescence. Comprehensive steady state and time‐resolved emission spectroscopy (TRES) analyses along with DFT calculations offer detailed understandings into the excited‐state manifolds of organic compound and energy transfer (ET) pathways involved in 1O2 generation. [ABSTRACT FROM AUTHOR]

Significant advances are made in understanding the structure‐property relationship in room‐temperature phosphorescence (RTP) materials. For example, intramolecular charge transfer (ICT) structural molecules based on electron donors(D) and electron acceptors(A) are an efficient method to achieve RTP. However, the ability to precisely regulate the singlet‐triplet energy gap (ΔEST) through molecular design to control RTP emissions remains constrained. Herein, a group of 4BN‐NP and 5BN‐NP isomers is reported with D and A position isomerization, where 4BN‐NP exhibits a photo‐induced orange afterglow phenomenon in PMMA. Calculations show that the spin‐orbit coupling (SOC) value of 4BN‐NP is greater compared to 5BN‐NP and the intersystem crossing (ISC) channel is more efficient, resulting in a smaller ΔEST value for 4BN‐NP. This indicates that the short ICT channel is more conducive to inducing phosphorescence emission. In addition, compound 4BN‐NP co‐doped with red fluorescent dyes (RhB, Rh6G, and RBNN) in PMMA produces phosphorescence resonance energy transfer (PRET), inducing red afterglow emission. Surprisingly, light‐activated yellow RTP can be obtained by attaching 4BN‐NP with polymethyl methacrylate (PMMA) to nylon filaments, and its phosphorescence intensity does not diminish even when it is immersed in water containing detergent solution, thus expanding the prospects of its application in textile encryption. [ABSTRACT FROM AUTHOR]

Key points Volume‐regulated anion channels (VRACs) formed by leucin‐rich repeat containing 8 (LRRC8) proteins play a pivotal role in regulatory volume decrease by mediating the release of chloride and organic osmolytes. Apart from the regulation of cell volume, LRRC8/VRAC function underlies numerous physiological processes in vertebrate cells including membrane potential regulation, glutamate release and apoptosis. LRRC8/VRACs are also permeable to antibiotics and anti‐cancer drugs, representing therefore important therapeutic targets. The activation mechanisms for LRRC8/VRACs are still unclear. Besides through osmotic cell swelling, LRRC8/VRACs can be activated by various stimuli under isovolumetric conditions. Sphingosine‐1‐phosphate (S1P), an important signalling lipid, which signals through a family of G protein‐coupled receptors (GPCRs), has been reported to activate LRRC8/VRACs in several cell lines. Here, we measured inter‐subunit Förster resonance energy transfer (FRET) and used whole‐cell patch clamp electrophysiology to investigate S1P‐induced LRRC8/VRAC activation. We systematically assessed the involvement of GPCRs and G protein‐mediated signal transduction in channel activation. We found that S1P‐induced channel activation is mediated by S1PR1 in HeLa cells. Following the downstream signalling pathway of S1PR1 and using toxin‐mediated inhibition of the associated G proteins, we showed that Gβγ dimers rather than Gαi or Gαq play a critical role in S1P‐induced VRAC activation. We could also show that S1P causes protein kinase D (PKD) phosphorylation, suggesting that Gβγ recruits phospholipase Cβ (PLCβ) with the consequent PKD activation by diacylglycerol. Notably, S1P did not activate LRRC8/VRAC in HEK293 cells, but overexpression of Gβγ‐responsive PLCβ isoform could facilitate S1P‐induced LRRC8/VRAC currents. We thus identified S1PR1‐mediated Gβγ‐PLCβ signalling as a key mechanism underlying isosmotic LRRC8/VRAC activation. Leucin‐rich repeat containing 8 (LRRC8) anion/osmolyte channels are involved in multiple physiological processes where they can be activated as volume‐regulated anion channels (VRACs) by osmotic cell swelling or isovolumetric stimuli such as sphingosine‐1‐phosphate (S1P). In the present study, using pharmacological modulation and gene‐depleted cells in patch clamp recording and optical monitoring of LRRC8 activity, we find that LRRC8/VRAC activation by S1P is mediated by the G protein‐coupled receptor S1PR1 coupled to G proteins of the Gi family. The signal transduction to LRRC8/VRAC activation specifically involves phospholipase Cβ activation by βγ subunits of pertussis toxin‐insensitive heteromeric Gi proteins. S1P‐mediated and hypotonicity‐induced LRRC8/VRAC activation pathways converge in protein kinase D activation. [ABSTRACT FROM AUTHOR]

Interactions between gold metallic nanoparticles and molecular dyes have been well described by the nanometal surface energy transfer (NSET) mechanism. However, the expansion and testing of this model for nanoparticles of different metal composition is needed to develop a greater variety of nanosensors for medical and commercial applications. In this study, the NSET formula was slightly modified in the size-dependent dampening constant and skin depth terms to allow for modeling of different metals as well as testing the quenching effects created by variously sized gold, silver, copper, and platinum nanoparticles. Overall, the metal nanoparticles followed more closely the NSET prediction than for Förster resonance energy transfer, though scattering effects began to occur at 20 nm in the nanoparticle diameter. To further improve the NSET theoretical equation, an attempt was made to set a best-fit line of the NSET theoretical equation curve onto the Au and Ag data points. An exhaustive grid search optimizer was applied in the ranges for two variables, 0.1 ≤ C ≤ 2.0 and 0 ≤ α ≤ 4 , representing the metal dampening constant and the orientation of donor to the metal surface, respectively. Three different grid searches, starting from coarse (entire range) to finer (narrower range), resulted in more than one million total calculations with values C = 2.0 and α = 0.0736 . The results improved the calculation, but further analysis needed to be conducted in order to find any additional missing physics. With that motivation, two artificial intelligence/machine learning (AI/ML) algorithms, multilayer perception and least absolute shrinkage and selection operator regression, gave a correlation coefficient, R 2 , greater than 0.97 , indicating that the small dataset was not overfitting and was method-independent. This analysis indicates that an investigation is warranted to focus on deeper physics informed machine learning for the NSET equations. [ABSTRACT FROM AUTHOR]

Different classes of Imidazopyridine i.e., Imidazo[1,2-a]pyridine, Imidazo[1,5-a] pyridine, Imidazo[4,5-b]pyridine, have shown versatile applications in various fields. In this review, we have concisely presented the usefulness of the fluorescent property of imidazopyridine in different fields such as imaging tools, optoelectronics, metal ion detection, etc. Fluorescence mechanisms such as excited state intramolecular proton transfer, photoinduced electron transfer, fluorescence resonance energy transfer, intramolecular charge transfer, etc. are incorporated in the designed fluorophore to make it for fluorescent applications. It has been widely employed for metal ion detection, where selective metal ion detection is possible with triazole-attached imidazopyridine, β-carboline imidazopyridine hybrid, quinoline conjugated imidazopyridine, and many more. Also, other popular applications involve organic light emitting diodes and cell imaging. This review shed a light on recent development in this area especially focusing on the optical properties of the molecules with their usage which would be helpful in designing application-based new imidazopyridine derivatives. [ABSTRACT FROM AUTHOR]

Supramolecules are considered a promising approach for molecular logic gates due to their inherent dynamic responsiveness driven by non‐covalent forces. However, the lack of input sequence dependence in these logic gates may lead to misinterpretation of outputs, compromising their reliability. This study proposes an efficient universal supramolecular Förster resonance energy transfer (FRET) platform for logic gates with self‐locking features. Specifically, well‐designed naphthalene‐based monomers serve as energy donors, while dyes such as eosin Y (EY), rhodamine B (RhB), and sulforhodamine 101 (SR101), spanning from yellow to red, are employed as energy acceptors. Leveraging large exciton migration rates (1.21 × 1014 to 1.36 × 1014 L mol−1 s−1) between donor and acceptors, FRET processes are effectively facilitated. Building upon this framework, supramolecular logic gates with self‐locking features are successfully constructed. Notably, in these logic gates, even with the correct truth table, any deviation in the order of inputs can lead to alterations in the original outputs. [ABSTRACT FROM AUTHOR]

In the endeavor to mimic natural light‐harvesting systems (LHSs), a persistent challenge has been the tendency of synthetic materials to adopt spherical architectures rather than the desired multitubular structures found in nature. In this study, a novel carboxylbetaine‐type zwitterionic surfactant with aggregation‐induced emission (AIE) properties is designed. By coassembling with anionic surfactants, multiwalled tubules comprising bilayer membranes ≈5 nm thick are successfully constructed. With AIE fluorophores densely packed at the center, their AIE properties are triggered to serve as an efficient antenna for light harvesting and energy transfer. This facilitated high antenna effects via energy transfer from cyan fluorescent donor to yellow fluorescent acceptor and then to red fluorescent acceptor. Additionally, the emission color can be adjusted from blue to red by manipulating the donor/acceptor/acceptor ratio, with pure white‐light emission achievable at specific ratios. This achievement not only realizes the construction of efficient sequential LHSs but also offers inspiration for the future design of artificial multitubular systems. [ABSTRACT FROM AUTHOR]

Transmembrane serine protease 2 (TMPRSS2) is a membrane-bound protease belonging to the type II transmembrane serine protease (TTSP) family. It is a multidomain protein, including a serine protease domain responsible for its self-activation. The protein has been implicated as an oncogenic transcription factor and for its ability to cleave (prime) the SARS-CoV-2 spike protein. In order to characterize the TMPRSS2 biochemical properties, we expressed the serine protease domain (rTMPRSS2_SP) in Komagataella phaffii using the pPICZαA vector and purified it using immobilized metal affinity (Ni Sepharose™ excel) and size exclusion (Superdex 75) chromatography. We explored operational fluorescence resonance energy transfer FRET peptides as substrates. We chose the peptide Abz-QARK-(Dnp)-NH2 (Abz = ortho-aminobenzoic acid, the fluorescence donor, and Dnp = 2,4-dinitrophenyl, the quencher group) as a substrate to find the optimal conditions for maximum enzymatic activity. We found that metallic ions such as Ca2+ and Na+ increased enzymatic activity, but ionic surfactants and reducing agents decreased catalytic capacity. Finally, we determined the rTMPRSS2_SP stability for long-term storage. Altogether, our results represent the first comprehensive characterization of TMPRSS2's biochemical properties, providing valuable insights into its serine protease domain. [ABSTRACT FROM AUTHOR]

Achieving full‐color emission with just two emitters presents a significant challenge. Two N‐heterocyclic carbene metallacycles (NHC‐M; M ═ Ag, Au) featuring a tetraphenylethene core, combining covalent and coordination bonds are synthesized to restrict rotation within the NHC‐M‐BC (BC = bicyclic) metallacycles and greatly enhanced their quantum yields. The enhancement is accomplished by adjusting the CH3CN/H2O solvent mixture, allowing emission tuning from blue to green for NHC‐Ag‐BC. Further diversification of the emission spectrum, including access to high‐quality white light (CIE coordinates 0.33, 0.34), is facilitated through the addition of sulforhodamine B via fluorescence resonance energy transfer (FRET). The compatibility of NHC‐Ag‐BC with agarose gel extends its applicability to UV‐LEDs chromic coatings, as well as information encryption and anti‐counterfeiting materials. The results underscore the viability of dual‐fluorophore systems for achieving full‐color emission and highlight the potential for developing versatile, multi‐colored functional materials. [ABSTRACT FROM AUTHOR]

Summary: Vitamin A (VA) is a fat‐soluble compound that is essential for physiological functions including vision, fetal growth, immune response, cell differentiation and proliferation. However, its susceptibility to environmental conditions leading to poor stability limits its application in food. This study investigated the interaction between egg white protein (EWP) and VA by spectroscopy and molecular docking. The results indicated one EWP could bind 16.00 ± 0.89 VA molecules and the binding constant is (2.59 ± 0.71) × 105 m−1. What's more, there was a fluorescence resonance energy transfer between EWP and VA, and the Förster radius is 5.28 nm. In addition, VA enhanced the hydrophobic interactions with the EWP, resulting in protein aggregation, larger average particle size and more uniform particle size distribution. Finally, the combination of VA with EWP could significantly improve the photothermal stability and storage stability of VA. These studies indicate that EWP nanocomplexes can be used as ideal delivery carriers for bioactive substances. [ABSTRACT FROM AUTHOR]

Background and Purpose: Neurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady‐state binding affinities of various neurosteroids for specific sites on the GABAA receptor. Experimental Approach: Two methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17‐methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites. The assays were developed using ELIC‐α1GABAAR, a chimeric receptor containing transmembrane domains of the α1‐GABAA receptor. Tryptophan mutagenesis was used to identify specific interactions. Key Results: Allopregnanolone (3α‐OH neurosteroid) was shown to bind at intersubunit and intrasubunit sites with equal affinity, whereas epi‐allopregnanolone (3β‐OH neurosteroid) binds at the intrasubunit site. MQ290 formed a strong FRET pair with W246, acting as a site‐specific probe for the intersubunit site. The affinity and site‐specificity of several neurosteroid agonists and inverse agonists was measured using the MQ290 binding assay. The FRET assay distinguishes between competitive and allosteric inhibition of MQ290 binding and demonstrated an allosteric interaction between the two neurosteroid binding sites. Conclusions and Implications: The affinity and specificity of neurosteroid binding to two sites in the ELIC‐α1GABAAR were directly measured and an allosteric interaction between the sites was revealed. Adaptation of the MQ290 FRET assay to a plate‐reader format will enable screening for high affinity agonists and antagonists for neurosteroid binding sites. [ABSTRACT FROM AUTHOR]

Embedding of cell-surface receptors into a membrane defines their dynamics but also complicates experimental characterization of their signaling complexes. The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. It is also targeted by the pathogen Listeria monocytogenes, whose invasion protein, internalin B (InlB), binds to MET, forming a signaling dimer that triggers pathogen internalization. Here we use an integrative structural biology approach, combining molecular dynamics simulations and single-molecule Förster resonance energy transfer (smFRET) in cells, to investigate the early stages of MET activation. Our simulations show that InlB binding stabilizes MET in a conformation that promotes dimer formation. smFRET reveals that the in situ dimer structure closely resembles one of two previously published crystal structures, though with key differences. This study refines our understanding of MET activation and provides a methodological framework for studying other plasma membrane receptors. The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. Here the authors combine molecular dynamics simulations and smFRET in cells, to investigate the early stages of MET activation. [ABSTRACT FROM AUTHOR]

Förster resonance energy transfer (FRET) plays a critical role in organic optoelectronic materials. However, developing facile and effective strategies to achieve high‐efficiency energy harvesting of chromophores with aggregation‐caused quenching (ACQ) remains an appealing yet challenging task, that has not yet been explored. Herein, a subtly strategy, crystallization‐induced precise co‐assembly (CIPCA) involving a molecular “lightening agent,” to effectively improve FRET efficiency of ACQ chromophores is developed. Bis(phenylethynyl)anthracene (BPA) and bis(phenylethynyl)naphthacene (BPN) with significant ACQ effect are chosen as representative FRET donor and acceptor, respectively, and weakly‐fluorescent octafluoronaphthalene (OFN) acted as the “lightening agent.” Thanks to precise co‐assembly with OFN, the PLQY of solid BPA is enhanced by 107%, and the BPN powder can be unprecedentedly lighted. More importantly, through such powerful CIPCA, the monotonous and weak emission for BPA@BPN can be remarkably regulated to colorful and much brighter ones with FRET efficiency improvement of as high as 180–270%. An in‐depth understanding of FRET regulation is elucidated through a precise correlation of the supramolecular structures and properties. Such achievements allow to successfully fabricate distinct multi‐stimuli‐responsive fluorescent patterns and highly‐emissive colorful flowers with high flexibility. This research provides an efficient strategy to improve the FRET efficiency of ACQ pairs. [ABSTRACT FROM AUTHOR]

Carbon quantum dots (CQDs) have gained extensive attention due to their excellent properties and wide applications. In this study, we selected the common Chinese herb mugwort as the carbon source and employed the microwave heating method to synthesize CQDs with a quantum yield of 13.54 %. These CQDs exhibited blue fluorescence under UV light irradiation. Furthermore, we constructed a fluorescence resonance energy transfer (FRET) mechanism by combining CQDs with copper nanoparticles (CuNPs) for the detection of melamine. The detection limit for melamine was determined to be 0.83 nmol/L, with a linear range of 1–100 nmol/L. The results demonstrated the potential of this sensing system for the sensitive and selective detection of melamine. [ABSTRACT FROM AUTHOR]

Phosphatase of regenerating liver (PRL) is an oncogenic protein that promotes tumor progression by directly binding to cyclin M (CNNM) membrane proteins and inhibiting their Mg2+ efflux activity. In this study, we have developed a high-throughput screening system to detect the interactions between PRL and CNNM proteins based on homogenous time-resolved fluorescence resonance energy transfer (HTR-FRET, HTRF). We optimized the tag sequences attached to the recombinant proteins of the CNNM4 CBS domains and PRL3 lacking the carboxyl terminal CAAX motif, and successfully detected the interaction by observing the FRET signal in the mixture of the tagged proteins and fluorophore-conjugated antibodies. Moreover, we performed compound library screening using this system and discovered several compounds that could efficiently inhibit the PRL-CNNM interaction. Characterization of one candidate compound revealed that it was relatively stable compared with thienopyridone, a known inhibitor of the PRL-CNNM interaction. The candidate compound can also inhibit PRL function in cells: suppression of CNNM-dependent Mg2+ efflux, and has sufficient in vitro drug metabolism and pharmacokinetic properties. Overall, these results demonstrate the effectiveness of this screening system for identifying novel inhibitors of the PRL-CNNM interaction, which could contribute to the development of novel anti-cancer drugs. [ABSTRACT FROM AUTHOR]

Physical properties of biomolecular condensates formed via phase separation of proteins and nucleic acids are associated with cell physiology and disease. Condensate properties can be regulated by several cellular factors including post-translational modifications. Here, we introduce an application of intermolecular energy migration via homo-FRET (Förster resonance energy transfer), a nanometric proximity ruler, to study the modulation in short- and long-range protein-protein interactions leading to the changes in the physical properties of condensates of fluorescently-tagged FUS (Fused in Sarcoma) that is associated with the formation of cytoplasmic and nuclear membraneless organelles. We show that homoFRET captures modulations in condensate properties of FUS by RNA, ATP, and post-translational arginine methylation. We also extend the homoFRET methodology to study the in-situ formation of cytoplasmic stress granules in mammalian cells. Our studies highlight the broad applicability of homoFRET as a potent generic tool for studying intracellular phase transitions involved in function and disease. The properties of biomolecular condensates can be regulated by multiple factors, including intermolecular dynamics. Here, the authors use fluorescence anisotropy-based homoFRET imaging to monitor the intermolecular interactions and supramolecular packing that underlie the modulation of biomolecular condensate properties. [ABSTRACT FROM AUTHOR]

The text discusses the career and research contributions of Walther Mothes in the field of retrovirology. Mothes transitioned from studying protein secretion to investigating retroviruses, focusing on topics such as virus entry pathways, cell-to-cell transmission, and antiviral immunity. His lab developed innovative tools for live-cell imaging and single molecule studies to understand the structure and dynamics of viral proteins, such as HIV-1 Env and SARS-CoV-2 spike protein. Mothes' research also delves into the interplay between viruses and the immune system, shedding light on virus dissemination and pathogenesis. [Extracted from the article]

With the aim to develop a FRET-based viscosity sensor, two dyad molecules, 4 and 5, comprising tetraarylpyrrolo[3,2-b]pyrrole (TAPP) (donor) and naked boron-dipyrromethene (BODIPY) dyes (acceptor), were designed. Dyads were synthesized via acid-catalyzed multicomponent reactions followed by Sonogashira coupling. In both dyads, the BODIPY and TAPP moieties are linked through phenylethynyl groups, which allow free rotation of the BODIPY dyes; that is, they can act as molecular rotors. This was supported by X-ray crystallographic and DFT-optimized structures. Spectroscopic studies also confirmed the presence of both TAPP and BODIPY dyes in dyads with no electronic interactions that are suitable for fluorescence resonance energy transfer (FRET). Very high energy transfer efficiency (ETE >99%) from the donor TAPP moiety to the acceptor BODIPY moiety on excitation at the TAPP part was observed. However, due to the non-fluorescent nature of naked BODIPY dyes, no fluorescence emission was observed from the BODIPY moiety in both dyads. With increasing solvent viscosities, emission from the BODIPY moieties increases due to the restricted rotation of the BODIPY moieties. Plotting the logarithms of the fluorescent intensity of dyad 5 and the viscosity of the solution showed a good linear correlation obeying a Förster-Hoffmann equation. Nonfluorescent dyad 5 in methanol became greenish-yellow fluorescent in a methanol/glycerol (1:1) solvent. Furthermore, with an increase in the temperature of the methanol/glycerol (1:1) system, as the viscosity decreases, the fluorescence also starts decreasing. Thus, dyad 5 is capable of sensing the viscosity of the medium via a FRET-based "Off-On" mechanism. This type of viscosity sensor with a very large pseudo-Stokes shift and increased sensitivity will be useful for advancing chemo-bio sensing and imaging applications. [ABSTRACT FROM AUTHOR]

The overactivated immune cells in the infectious lesion may lead to irreversible organ damages under severe infections. However, clinically used immunosuppressive anti‐inflammatory drugs will usually disturb immune homeostasis and conversely increase the risk of infections. Regulating the balance between anti‐inflammation and anti‐infection is thus critical in treating certain infectious diseases. Herein, considering that hydrogen peroxide (H2O2), myeloperoxidase (MPO), and neutrophils are upregulated in the inflammatory microenvironment and closely related to the severity of appendectomy patients, an inflammatory‐microenvironment‐responsive nanomedicine is designed by using poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles to load chlorine E6 (Ce6), a photosensitizer, and luminal (Lum), a chemiluminescent agent. The obtained Lum/Ce6@PLGA nanoparticles, being non‐toxic within normal physiological environment, can generate cytotoxic single oxygen via bioluminescence resonance energy transfer (BRET) in the inflammatory microenvironment with upregulated H2O2 and MPO, simultaneously killing pathogens and excessive inflammatory immune cells in the lesion, without disturbing immune homeostasis. As evidenced in various clinically relevant bacterial infection models and virus‐induced pneumonia, Lum/Ce6@PLGA nanoparticles appeared to be rather effective in controlling both infection and inflammation, resulting in significantly improved animal survival. Therefore, the BRET‐based nanoparticles by simultaneously controlling infections and inflammation may be promising nano‐therapeutics for treatment of severe infectious diseases. [ABSTRACT FROM AUTHOR]

Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light‐harvesting ability not only amplifies superoxide radical (O2•‐) production but also promotes heat generation upon near‐infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced. [ABSTRACT FROM AUTHOR]

Ribonuclease P (RNase P) plays a vital role in the maturation of tRNA across bacteria, archaea, and eukaryotes. However, how RNase P assembles various components to achieve specific cleavage of precursor tRNA (pre-tRNA) in different organisms remains elusive. In this study, we employed single-molecule fluorescence resonance energy transfer to probe the dynamics of RNase P from E. coli (Escherichia coli) and Mja (Methanocaldococcus jannaschii) during pre-tRNA cleavage by incorporating five Cy3-Cy5 pairs into pre-tRNA and RNase P. Our results revealed significant differences in the assembly and catalytic mechanisms of RNase P between E. coli and Mja at both the RNA and protein levels. Specifically, the RNA of E. coli RNase P (EcoRPR) can adopt an active conformation that is capable of binding and cleaving pre-tRNA with high specificity independently. The addition of the protein component of E. coli RNase P (RnpA) enhances and accelerates pre-tRNA cleavage efficiency by increasing and stabilizing the active conformation. In contrast, Mja RPR is unable to form the catalytically active conformation on its own, and at least four proteins are required to induce the correct folding of Mja RPR. Mutation experiments suggest that the functional deficiency of Mja RPR arises from the absence of the second structural layer, and proper intermolecular assembly is essential for Mja RNase P to be functional over a broad temperature range. We propose models to illustrate the distinct catalytic patterns and RNA–protein interactions of RNase P in these two organisms. [ABSTRACT FROM AUTHOR]

Dopamine transfers information to striatal neurons, and disrupted neurotransmission leads to motor deficits observed in movement disorders. Striatal dopamine converges downstream to Adenylyl Cyclase Type 5 (AC5)-mediated synthesis of cAMP, indicating the essential role of signal transduction in motor physiology. However, the relationship between dopamine decoding and AC5 regulation is unknown. Here, we utilized an unbiased global protein stability screen to identify Potassium Channel Tetramerization Domain 1 (KCTD1) as a key regulator of AC5 level that is mechanistically tied to N-linked glycosylation. We then implemented a CRISPR/SaCas9 approach to eliminate KCTD1 in striatal neurons expressing a Förster resonance energy transfer (FRET)-based cAMP biosensor. 2-photon imaging of striatal neurons in intact circuits uncovered that dopaminergic signaling was substantially compromised in the absence of KCTD1. Finally, knockdown of KCTD1 in genetically defined dorsal striatal neurons significantly altered motor behavior in mice. These results reveal that KCTD1 acts as an essential modifier of dopaminergic signaling by stabilizing striatal AC5. [ABSTRACT FROM AUTHOR]

The document published in the journal "Molecular Neurodegeneration" compares the effectiveness of different anti-tau antibodies in inhibiting tau seeding from Alzheimer's disease (AD) brain extracts. The study found that an antibody targeting acetylated lysine-280 (acK280) on the microtubule-binding region (MTBR) showed the most significant decrease in tau seeding. The research suggests that targeting acK280 in the MTBR region may be a promising approach for immunotherapy in AD treatment. The study highlights the importance of epitope selection in developing effective anti-tau antibodies for combating tau pathologies. [Extracted from the article]

Bright and fast scintillators are highly crucial for high-speed X-ray imaging in the medical diagnostic radiology including angiography and cardiac computed tomography. The CsPbBr3 nanocrystal scintillator featuring a nanosecond radioluminescence decay time is a promising candidate. However, it suffers from a substantial photon self-absorption limiting the light output, and being bright and fast simultaneously is difficult. Here we design and in-situ synthesize multi-site ZnS(Ag)-CsPbBr3 heterostructures to modulate the bright and fast features of scintillators. We find external energy from ZnS(Ag) can effectively transfer to CsPbBr3 based on the non-radiative Förster resonance energy transfer, resulting in a light yield of 40,000 photons MeV−1. By combing a radioluminescence decay time of 36 ns and a spatial resolution of 30 lp mm−1, the scintillator enables high-speed X-ray imaging at 200 frames per second. This study showcases the structure design is significant for obtaining bright and fast perovskite scintillators for the real-time X-ray imaging. Yang et al. report in-situ growth of ZnS(Ag)-CsPbBr3 heterostructures through all solid-phase synthesis for X-ray scintillators. The multiple contact sites promote light yield via efficient energy transfer from ZnS(Ag) into CsPbBr3 and enable fast decay for high-speed X-ray imaging at 200 fps. [ABSTRACT FROM AUTHOR]