To the Editor,Half a century ago,one of the most important theoretical physicists who shaped the field of condensed matter physics,Professor Philip Anderson,expressed in his landmark article“More is Different”[1]tha...To the Editor,Half a century ago,one of the most important theoretical physicists who shaped the field of condensed matter physics,Professor Philip Anderson,expressed in his landmark article“More is Different”[1]that“...the behavior of large and complex aggregates of elementary particles,it turns out,is not to be understood in terms of a simple extrapolation of the properties of a few particles.Instead,at each level of complexity entirely new properties appear...”.The concept“More is Different”emphasized the significance of emergence in complex systems,where emergent behaviors and properties that cannot be found from the individual parts.Professor Anderson’s own research in condensed matter physics also reflects the importance of emergence and complexity science.He was most concerned about how complex phenomena emerge from simple systems[2,3].展开更多
Phase separation(PS)plays a fundamental role in organizing aggregates during the viral lifecycle,providing significant opportunities for in viral disease treatment by inhibiting PS.Intrinsically disordered regions(IDR...Phase separation(PS)plays a fundamental role in organizing aggregates during the viral lifecycle,providing significant opportunities for in viral disease treatment by inhibiting PS.Intrinsically disordered regions(IDRs)have been extensively studied and found to be critical for PS.However,the discovery of small molecules that target residues within IDRs remains underexplored,particularly in the field of pesticides.Herein,we report a novel phytovirucide compound 29,which was screened from a series of vanillin derivatives designed with sulfonylpiperazine motifs.The inactivation efficacy of compound 29 against tomato spotted wilt virus(TSWV)was significantly superior to that of the control agents vanisulfane and ribavirin.Mechanistically,compound 29 binds to the TSWV nucleocapsid protein(NP)at residues Lys68(K68),Thr92(T92),and Arg94(R94),with T92 and R94 located in the IDRs of NP.Mutations at these sites impair the ability to form aggregates.Furthermore,a host factor,GTP(Guanosine Triphosphate)-binding nuclear protein Ran-like(Niben101scf08341g01001,NbRANL),which interacts with NP and promotes its aggregation,was identified.Compound 29 also suppresses the expression of NbRANL,resulting in the dual inhibition of ribonucleoprotein complexes(RNPs)formation.This unique mechanism of action provides insights into IDRs-based virucide discovery.展开更多
J.Xu,L.Cao,S.Yang,et al.,“Droplets Cas13a-RPA Measurement Delineates Potential Role for Plasma Circwdr37 in Colorectal Cancer,”Aggregate 6(2025):e663,https://doi.org/10.1002/agt2.663.In Figure 2G,the first image on ...J.Xu,L.Cao,S.Yang,et al.,“Droplets Cas13a-RPA Measurement Delineates Potential Role for Plasma Circwdr37 in Colorectal Cancer,”Aggregate 6(2025):e663,https://doi.org/10.1002/agt2.663.In Figure 2G,the first image on the right among the three control images was incorrect.It has now been replaced with the correct control image.展开更多
Electronic excited state inmolecular aggregate or exciton states continue to attract great attention due to the increasing demands for applications of molecular optoelectronics and sensing technology.The working princ...Electronic excited state inmolecular aggregate or exciton states continue to attract great attention due to the increasing demands for applications of molecular optoelectronics and sensing technology.The working principle behind the application is closely related to the excited state structure and dynamic processes inmolecular aggregate.In our previous review article(Aggregate 2021;2:e91),we focused more on the molecular mechanism for aggregation-induced emission process.Here,we are going to summarize our recent progress on theoretical investigations on the effects of excitonic coupling(J)and the intermolecular charge transfer(CT)on the excited state structure and dynamic processes.These are in general missing for molecular quantum chemistry studies.We will first present a novel definition of exciton coherence length which can present a bijective relation with the radiative decay rate and obviously we have clarified the confusion appeared in literature.Then,we will look at the CT effect for aggregate starting from a simple three-state model coupled with quantum chemical calculation for molecular dimer and we focus on the intensity borrowing,which can turn H-aggregate into emissive when the electron transfer and hole transfer integrals possessing the same sign and being large enough.We are able to propose amolecular descriptor to designmolecularmaterials possibly possessing both high photoluminescence quantum yield and carrier mobility.Finally,we introduce our work on the modified energy gap law for non-radiative decay rate in aggregates.We found there exist optimal J to minimize the non-radiative decay loss.展开更多
More than a century ago,it was known that the accumulation of ordered protein aggregates,amyloid fibrils,accompanies several serious and still largely incurable pathologies,including Alzheimer’s and Parkinson’s dise...More than a century ago,it was known that the accumulation of ordered protein aggregates,amyloid fibrils,accompanies several serious and still largely incurable pathologies,including Alzheimer’s and Parkinson’s diseases.The striking gap between decades of research identifying amyloids as one of the key drivers of neurodegeneration and the persistent lack of effective antiamyloid therapies reveals a perplexing contradiction,which we define as the“amyloid paradox.”To address this paradox,here we summarize and analyze current perspectives on the unique properties and pathogenic mechanisms of amyloids,highlighting the variability and complexity of their biological consequences and uncovering the risks and limitations encountered in combating these aggregates.We conceptualize amyloid fibril pathogenicity as a complex cascade extending well beyond direct cytotoxicity,such as that arising from disruption of membranes and other cellular organelles.This review encompasses amyloids’disruptive effects on cellular processes and ability to trigger inflammatory responses,their resistance to degradation,capacity to regenerate after apparent destruction,tendency to propagate throughout the organism,propensity to cytotoxicity-increasing transformation,and ability to sequester and pathologically modify essential biomolecules.This integrated analysis reveals why single-target therapeutic approaches often fail and suggests that effective anti-amyloid strategies must address multiple aspects of amyloid pathogenicity simultaneously.The conceptual reframing of the threats of amyloid fibrils helps explain the origins of the amyloid paradox,enhances our understanding of these complex pathogenic agents,and provides a foundation for developing more effective and safe therapeutic strategies for neurodegenerative diseases.These strategies should address the complex and interconnected nature of amyloid pathogenicity rather than its targeting isolated aspects.展开更多
Despite extensive investigations into photophysics at the molecular level,the complex interplays between intermolecular interactions,hierarchical assembly,and photoluminescence properties remain a fundamental challeng...Despite extensive investigations into photophysics at the molecular level,the complex interplays between intermolecular interactions,hierarchical assembly,and photoluminescence properties remain a fundamental challenge in materials science,particularly concerning emergent phenomena in molecular aggregates.Herein,we construct different dimeric structures in both solution and aggregate states through cycloreversion upon photoirradiation from a series of nonemissive phenanthrene cycloadducts,exhibiting state-dependent photoactivatable luminescence.Specifically,the excimer in solution is nonemissive due to its antiparallel cofacial structure.In contrast,the dimer in the crystal exhibits nonclassical excimer emission according to its cross-stacked stacking within the restriction of the crystal lattice.Prominently,the luminescent behavior in aggregate is uniquely accessible through photocycloreversion and cannot be achieved through spontaneous crystallization of their parent phenanthrene molecules.Moreover,the photoactivatable nature of these materials is successfully demonstrated in thin films,showcasing their potential applications in information encryption.This work expands the possibilities for constructing new functional aggregate materials by photochemistry and deepens our understanding of dimer-luminescence relationships in different states.展开更多
Combining high mobility and high-efficiency luminescence in one material is challenging because of their contradictory design principles.Here,under the three-state exciton model,a molecular descriptor O=(|t_(h)+t_(e)|...Combining high mobility and high-efficiency luminescence in one material is challenging because of their contradictory design principles.Here,under the three-state exciton model,a molecular descriptor O=(|t_(h)+t_(e)|−|t_(h)-t_(e)|)∕2Jis proposed to quantitatively design materials with balanced luminescence and mobility in aggregated states,where a large𝑂would promise high crystalline photoluminescence quantum yield(PLQY)with small J(excitonic coupling)and significant t_(h) and t_(e)(hole and electron transfer integrals)would indicate high mobility.Through theoretical calculation and experimental validation,it is found that the asymmetric anthracene derivatives are quite effective in simultaneously achieving high mobility and high PLQY.Following the asymmetric guideline,the newly developed compounds,2-phenyl vinyl anthracene(2-PhVA)and 6-(2-(anthracene-2-yl)vinyl)benzo[b]thiophene(6-BTVA)demonstrate high O values alongside excellent performance:2-PhVA exhibits a PLQY of 81.5%and a maximum hole mobility of 10.0 cm^(2) V^(−1) s^(−1),and 6-BTVA shows a PLQY of 30.9%with a maximum mobility of 9.3 cm^(2) V^(−1) s^(−1).The above results demonstrate the validation of the descriptor and the asymmetric strategy in further developing high-mobility light-emitting aggregated materials.展开更多
Modifications to the alkyl side chains of Y6-type nonfullerene acceptors(NFAs)continuously break through the organic solar cells(OSCs)efficiency by enhancing electron mobility.However,the role of side chains in molecu...Modifications to the alkyl side chains of Y6-type nonfullerene acceptors(NFAs)continuously break through the organic solar cells(OSCs)efficiency by enhancing electron mobility.However,the role of side chains in molecular aggregation and charge transport across different aggregates remains unclear.By employing a multiscale approach in combination with density functional theory(DFT),molecular dynamics(MD)simulations,and kinetic Monte Carlo(KMC),we addressed the issue of how side chains impact molecular aggregation,energy disorder,and the formation of near-macroscopic(∼0.3μm)conductive network,which are critical for boosting electron mobility.Specifically,the side-chain structure greatly influences the un-conjugated enveloping effect on backbones within aggregates.The effect diminishes with longer linear side chains and is further minimized by using branched side chains.Though static energy disorder increased,the improved connectivity of the conductive network led to a notable increase in electron mobility(from 2.4×10^(−4)to 3.9×10^(−4)cm^(2)⋅V^(−1)⋅s^(−1)).The findings offer insight into controlling molecular aggregation via alkyl side chains,which helps to further unlock the potential of Y6-type NFAs.展开更多
Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization under solvothermal conditions in the presence of FeCl_(3)·6H_(2)O,yielding a heterocyclic aggregate,namely 1,2,3-tris(benzo[d]thiazol-2-yl)-2,9-d...Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization under solvothermal conditions in the presence of FeCl_(3)·6H_(2)O,yielding a heterocyclic aggregate,namely 1,2,3-tris(benzo[d]thiazol-2-yl)-2,9-dihydrobenzo[b]cyclopenta[e][1,4]thiazine.Single-crystal X-ray diffraction analysis was conducted on four distinct compounds isolated during the reaction,and electrospray ionization mass spectrometry(ESI-MS)of both solid products and intermediate reaction solutions enabled the identification of 15 consecutive reaction steps,where Fe(Ⅲ)was directly involved in eight steps.These transformations comprise nine intermolecular C─C coupling events and six intramolecular ring expansion processes.The heteroatoms(N,O,and S)play distinct mechanistic roles according to their positions within the heterocyclic framework:(1)nitrogen and oxygen coordinate with Fe(Ⅲ),facilitating activation of the reaction site;(2)homolytic cleavage of the C─O bond promotes C─C coupling reactions;and(3)C─S migration induces intramolecular ring expansion.Notably,theoretical calculations indicate a decrease in Gibbs free energy along the intramolecular reaction pathways,substantiating the proposed mechanism and activation mode,which underscores the essential role of Fe(Ⅲ)in enabling the reaction progression.Furthermore,an investigation of the photophysical properties revealed that the resulting heterocyclic aggregates exhibit strong luminescence within the 535–610 nm wavelength range,approaching the near-infrared region.These findings highlight the significance of this reaction pathway in the controlled synthesis of functional oligomers and polymers from monomeric precursors,particularly through catalysis by cost-effective metal ions.展开更多
Photodynamic therapy(PDT)and photothermal therapy(PTT)have emerged promising applications in both fundamental research and clinical trials.However,it remains challenging to develop ideal photosensitizers(PSs)that conc...Photodynamic therapy(PDT)and photothermal therapy(PTT)have emerged promising applications in both fundamental research and clinical trials.However,it remains challenging to develop ideal photosensitizers(PSs)that concurrently integrate high photostability,large near-infrared absorptivity,and efficient therapeutic capabilities.Herein,we reported a sample engineering strategy to afford a benzene-fused Cy5 dimer(Cy-D-5)for synergistically boosting PDT/PTT applications.Intriguingly,Cy-D-5 exhibits a tendency to form both J-aggregates and H-aggregates in phosphate-buffered saline,which show a long-wavelength absorption band bathochromically shifted to 810 nm and a short-wavelength absorption band hypsochromically shifted to 745 nm,respectively,when compared to its behavior in ethanol(778 nm).Density-functional theory calculations combined with time-resolved transient optical spectroscopy analysis reveal that the fused dimer Cy-D-5 exhibits a lowΔEST(0.51 eV)and efficient non-radiative transition rates(12.6 times greater than that of the clinically approved PS-indocyanine green[PS-ICG]).Furthermore,the Cy-D-5 demonstrates a higher photosensitizing ability to produce 1O2,stronger photothermal conversion efficiency(η=64.4%),and higher photostability compared with ICG.These combined properties enable Cy-D-5 to achieve complete tumor ablation upon 808 nm laser irradiation,highlighting its potential as a powerful and dual-function phototherapeutic agent.This work may offer a practical strategy for engineering other existing dyes to a red-shifted spectral range for various phototherapy applications.展开更多
Extracellular vesicles(EVs)are essential for host–pathogen interactions,mediating processes such as immune modulation and pathogen survival.Pathogen-derived EVs hold significant diagnostic potential because of their ...Extracellular vesicles(EVs)are essential for host–pathogen interactions,mediating processes such as immune modulation and pathogen survival.Pathogen-derived EVs hold significant diagnostic potential because of their unique cargo,offering a wealth of potential biomarkers.In this review,we first discuss the roles of EVs derived from various pathogens in host–pathogen interactions and summarize the latest advancements in pathogen detection based on EVs.Then,we highlight innovative strategies,including novel aggregate materials and machine learning approaches,for enhancing EV detection and analysis.Finally,we discuss challenges in the field and future directions for advancing EV-based diagnostics,aiming to translate these insights into clinical applications.展开更多
The increasing prevalence of methicillin-resistant Staphylococcus aureus(MRSA)due to antibiotic misuse necessitates novel therapeutic strategies to counter multidrug-resistant infections.Here,we introduce a self-assem...The increasing prevalence of methicillin-resistant Staphylococcus aureus(MRSA)due to antibiotic misuse necessitates novel therapeutic strategies to counter multidrug-resistant infections.Here,we introduce a self-assembling,aggregation-enhanced tetrahedralDNAnanostructure(tFNA)platform that achieves targeted drug delivery through controlled aggregation and sustained release,effectively restoring MRSA susceptibility toβ-lactam antibiotics.These tetrahedral frameworks,termed tFNAs-ASOsceftriaxone sodium(TACs),serve as a dual-functional system that co-encapsulates antisense oligonucleotides(ASOs)targeting the mecA gene and the β-lactam antibiotic ceftriaxone sodium(Cef).Aggregation of TACs plays a pivotal role in maximizing drug retention and stability,prolonging the localized release of both ASOs and antibiotics while maintaining high bioavailability at the infection site.Characterization studies,including size distribution,zeta potential,and fluorescence quenching assays,confirm their robust aggregation stability and encapsulation efficiency,ensuring controlled drug kinetics and prolonged therapeutic effects.Upon interaction with bacterial cells,the locally concentrated TACs facilitate efficient ASO-mediated mecA silencing,thereby disrupting PBP2a expression and re-sensitizing MRSA to β-lactams.Simultaneously,the aggregated ceftriaxone sodium reservoir ensures sustained inhibition of bacterial cell wall synthesis,leading to effective bacterial clearance.In addition,TACs display potent antibiofilm activity by penetrating the biofilm matrix and delivering therapeutics directly to the embedded bacterial population,thereby overcoming the diffusion barriers.In vivo,TACs exhibit superior therapeutic efficacy in an MRSA-induced pneumonia mouse model,significantly improving survival rates,reducing bacterial burden,and mitigating lung tissue damage.These findings highlight the transformative potential of tFNAs as an intelligent drug aggregation and release system,offering a novel paradigm for optimizing antibiotic therapy against multidrug-resistant pathogens.展开更多
Designing starch-based foods with controlled digestibility is critical for addressing global health challenges like diabetes,yet the molecular mechanisms underlying starch–protein interactions remain poorly quantifie...Designing starch-based foods with controlled digestibility is critical for addressing global health challenges like diabetes,yet the molecular mechanisms underlying starch–protein interactions remain poorly quantified.Here,we investigate how wheat starch(WS)interacts with distinct protein fractions—wheat globulin(Glo),gliadin(Gli),and glutelin(Glu)—to form molecular aggregates that modulate digestion.By integrating experimental analyses(FTIR,XRD,rheology)with molecular dynamics(MD)simulations,we demonstrate that Gli and Glu exhibit stronger non-covalent binding to starch than Glo,driven by hydrophobic forces and hydrogen bonding.These interactions disrupt starch chain entanglement,reduce short-and long-range structural order,and inhibitα-amylase activity.At a 50:9 starch-to-protein ratio,Gli and Glu increased resistant starch content by 6.74%and 6.91%,respectively,outperforming Glo(2.96%).MD simulations quantified binding free energies(−107.67 kcal/mol for Gli,−99.50 kcal/mol for Glu),revealing electrostatic contributions from Glu’s lysine/arginine residues and hydrophobic interactions in Gli.Notably,Glo and Glu synergistically inhibit amylase via mixed competitive/non-competitive mechanisms.This work establishes a predictive framework for starch–protein aggregate design,bridging molecular interactions to functional outcomes.By elucidating how protein composition dictates digestibility,we advance strategies for engineering low-glycemic-index foods,offering transformative potential for nutrition and food science.展开更多
Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super-resolution is highly demanded yet quite challenging.Herein,a ratiometric HClO probe AHOH is designed an...Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super-resolution is highly demanded yet quite challenging.Herein,a ratiometric HClO probe AHOH is designed and synthesized which is capable of simultaneously staining lysosomes and mitochondria with red and green colour,respectively.AHOH could be selectivity oxidized by HClO,leading to a large emission blue shift(90 nm)and an over 1300-fold enhancement of the emission ratio of Fl547nm/Fl637nm.We apply AHOH in super-resolution microscopy and clearly visualize the dynamics of mitochondria-lysosomes interactions and the oxidative stress states upon different stimuli.Mitochondria dysfunction triggered by different drugs and genetic defect lead to elevated oxidative stress and higher levels of mitophagy.Moreover,AHOH could serve as a reliable tool for evaluating the efficacy of drugs regulating mitochondria dysfunction.This work provides a powerful dual-colour super-resolution imaging agent for real-time monitoring the dynamics of organelle interactions and oxidative stress.展开更多
Unveiling the dependence of stability and luminescence properties on the size of organic aggregates is crucial for biomedical and optoelectronic applications.Taking the helical hexaphenylsilole(HPS)and planar 3-(2-cya...Unveiling the dependence of stability and luminescence properties on the size of organic aggregates is crucial for biomedical and optoelectronic applications.Taking the helical hexaphenylsilole(HPS)and planar 3-(2-cyano-2-phenylethenyl-Z)-NH-indole(CPEI)aggregates of different sizes as examples,their stability and luminescent properties are investigated using multiscale modeling and thermal vibration correlation function approach.The size of stable aggregates formed depends on the molecular shape,with the critical aggregate sizes of 2.62 nm(2 molecules)and 2.87 nm(10 molecules)for helical HPS and planar CPEI,respectively.Their critical sizes for luminescence are 2.99 nm(6 molecules)and 2.87 nm(10 molecules),respectively.For HPS aggregates,as the size increases the luminescence is blue-shifted and enhanced owing to denser molecular packing until the size is large enough(4.66 nm,20 molecules)the luminescence tends to remain unchanged;and thermal annealing makes these changesmore pronounced.In contrast,the luminescent properties of CPEI aggregates are insensitive to aggregate size and thermal annealing treatment.These findings provide dynamic insights into the AIE mechanism and invaluable guidance for optimizing the size of AIE-based nanoparticles in practical applications.展开更多
Current radiotherapy(RT)lacks the ability to accurately discriminate between tumor and healthy tissues,resulting in significant radiation-induced damage for patients.Therefore,there is an urgent need for precise RT te...Current radiotherapy(RT)lacks the ability to accurately discriminate between tumor and healthy tissues,resulting in significant radiation-induced damage for patients.Therefore,there is an urgent need for precise RT techniques that can optimize tumor control while minimizing adverse effects on surrounding healthy tissues.In this study,we developed a nanodrug(AuNR@Peptide)composed of furin-responsive RVRR peptide-conjugated AuNRs,which integrates an activatable probe and a radiosensitizer into a single system for accurate tumor localization,enabling imageguided precision RT.Upon reaching the tumor site after intravenous administration,proteolytic cleavage of RVRR substrates on AuNR@Peptide by biomarker triggers aggregation of gold nanorods(AuNRs)into larger aggregates,leading to activation of near-infrared(NIR)-II photoacoustic(PA)signals to precisely localize the tumor and enhance tumor retention by preventing migration and backflow of AuNRs.This significantly amplifies radiosensitivity efficiency.The peak time point at which the NIR-II PA signal was observed at the tumor site after injection serves as a reference for initiating RT,demonstrating substantial improvement in tumor RT through investigations related to radiosensitization mechanisms.The integration of imaging and therapy in this study offers a promising image-guided therapeutic modality for tumors.展开更多
Lysosomes are essential organelles for cells that act as the“recycling center”for decomposing biomolecules and clearing out damaged organelles.The status of lysosomes is tightly regulated by cells to maintain normal...Lysosomes are essential organelles for cells that act as the“recycling center”for decomposing biomolecules and clearing out damaged organelles.The status of lysosomes is tightly regulated by cells to maintain normal homeostasis.To monitor subcellular lysosomal status,super-resolution imaging has emerged as a promising technology that surpasses conventional imaging limitations,offering extraordinary visualization capability.However,existing fluorescent probes for super-resolution imaging still suffer from significant drawbacks,such as complex synthesis,poor intracellular stability,and the lack of near-infrared(NIR)imaging capability.Besides,to quantitatively analyze fluorescence images,traditional human-driven image interpretation is time-consuming and prone to information loss and human error.To tackle these challenges,we first developed a quinoliniumbased fluorescent probe,PA-2,for NIR super-resolution imaging of lysosomes with low cytotoxicity and stable fluorescence.Harnessing PA-2’s strong resistance to photobleaching,the lysosomal dynamic statuses,encompassing autophagy,mitochondrialysosome contacts,and mitophagy,were successfully visualized.Building on this,we next demonstrate a novel approach leveraging a large multimodal model(LMM),an advanced artificial intelligence(AI)tool,for automated analysis of super-resolution images.The LMM accurately interprets images of PA-2 and predicts lysosomal status under various drug treatments with remarkable speed,precision,and explainability,significantly outperforming human experts in image analysis.To sum up,this work highlights the strong potential of combining advanced fluorescent probe design with AI-assisted image interpretation to drive revolutionary innovation in bioimaging and beyond.展开更多
This year marks the fifth anniversary of Aggregate—a significant milestone for the journal.Since its launch in December 2020,we have embarked on a concerted journey to advance aggregate science,a field dedicated to t...This year marks the fifth anniversary of Aggregate—a significant milestone for the journal.Since its launch in December 2020,we have embarked on a concerted journey to advance aggregate science,a field dedicated to the science of systems beyond isolated molecules.Over the past 5 years,we have been gratified towitness the journal’s growing academic recognition.On this occasion,we reflect on our progress and chart the course forward by reviewing the journal’s development from its inception toward a promising future.展开更多
Ultrahigh signal-to-noise ratio(SNR)labeling enables precise visualization of biological structures in vivo.We boosted fluorogenicity in group-14-rhodamines by comprehensively manipulating their dynamics in physical(a...Ultrahigh signal-to-noise ratio(SNR)labeling enables precise visualization of biological structures in vivo.We boosted fluorogenicity in group-14-rhodamines by comprehensively manipulating their dynamics in physical(aggregate/monomer,K_(A/M))and chemical(closed/open spirolactone,K_(C/O))states.Fluorogenic rhodamines were designed by group 14(C,Si,Ge)substituted bridging regions in xanthene with tuned dialkylation.We quantified the impact of alkylation with the hydrophobicity(logP)over a wide range and confirmed that SNR can be sharply improved,owing to the promoted nano-aggregation(K_(A/M))with high logP.Integrating K_(A/M) with K_(C/O) mechanisms,unparalleled fluorogenicity was observed in group-14-rhodamines:HaloTag probe with dipentylsilyl exhibits remarkable fluorogenicity(>2000)in vitro,enabling no-wash and multicolor super-resolution stimulated emission depletion imaging of high SNR(>300)in vivo.Overexpression ofα_(v)β_(3) was sensitively tracked in vivo by RGDyK-based fluorogenic SiR probe through tuned K_(A/M).Our proposed strategy has significantly promoted the fluorogenicity of group 14 rhodamines as a general mechanism.展开更多
Organic luminescent radicals are promising for optoelectronic applications,yet their practical implementation remains hindered by aggregation-caused quenching(ACQ)in aggregated states.In this study,we present a molecu...Organic luminescent radicals are promising for optoelectronic applications,yet their practical implementation remains hindered by aggregation-caused quenching(ACQ)in aggregated states.In this study,we present a molecular design strategy that enables unprecedented intrinsic luminescence from pure radicals across multiple aggregated states,including crystalline states,powders,and amorphous films,through the incorporation of sterically demanding TPP(2,4,6-triisopropylphenyl)groups.Comprehensive photophysical characterization coupled with structural analysis reveals that the TPP moieties effectively suppress detrimental intermolecular interactions,particularly exchange coupling andπ–πstacking between radical centers.The luminescent properties were analyzed via systematic theoretical calculations.The universality of this design principle is further demonstrated through its successful application to diradical systems,including Chichibabin’s and Muller’s hydrocarbons,which exhibit significantly enhanced emission in aggregated states.This work establishes a generalizable strategy for designing stable and efficient luminescent radicals in aggregated states,opening new avenues for radical-based optoelectronic devices.展开更多
文摘To the Editor,Half a century ago,one of the most important theoretical physicists who shaped the field of condensed matter physics,Professor Philip Anderson,expressed in his landmark article“More is Different”[1]that“...the behavior of large and complex aggregates of elementary particles,it turns out,is not to be understood in terms of a simple extrapolation of the properties of a few particles.Instead,at each level of complexity entirely new properties appear...”.The concept“More is Different”emphasized the significance of emergence in complex systems,where emergent behaviors and properties that cannot be found from the individual parts.Professor Anderson’s own research in condensed matter physics also reflects the importance of emergence and complexity science.He was most concerned about how complex phenomena emerge from simple systems[2,3].
基金support from the National Natural Science Foundation of China(Nos.32330087 and 32302388)the Key Technologies R&D Program of Guizhou Province in China(No.2017-5788-1)the Scientific Research Innovation Team of Guizhou University(No.202403).
文摘Phase separation(PS)plays a fundamental role in organizing aggregates during the viral lifecycle,providing significant opportunities for in viral disease treatment by inhibiting PS.Intrinsically disordered regions(IDRs)have been extensively studied and found to be critical for PS.However,the discovery of small molecules that target residues within IDRs remains underexplored,particularly in the field of pesticides.Herein,we report a novel phytovirucide compound 29,which was screened from a series of vanillin derivatives designed with sulfonylpiperazine motifs.The inactivation efficacy of compound 29 against tomato spotted wilt virus(TSWV)was significantly superior to that of the control agents vanisulfane and ribavirin.Mechanistically,compound 29 binds to the TSWV nucleocapsid protein(NP)at residues Lys68(K68),Thr92(T92),and Arg94(R94),with T92 and R94 located in the IDRs of NP.Mutations at these sites impair the ability to form aggregates.Furthermore,a host factor,GTP(Guanosine Triphosphate)-binding nuclear protein Ran-like(Niben101scf08341g01001,NbRANL),which interacts with NP and promotes its aggregation,was identified.Compound 29 also suppresses the expression of NbRANL,resulting in the dual inhibition of ribonucleoprotein complexes(RNPs)formation.This unique mechanism of action provides insights into IDRs-based virucide discovery.
文摘J.Xu,L.Cao,S.Yang,et al.,“Droplets Cas13a-RPA Measurement Delineates Potential Role for Plasma Circwdr37 in Colorectal Cancer,”Aggregate 6(2025):e663,https://doi.org/10.1002/agt2.663.In Figure 2G,the first image on the right among the three control images was incorrect.It has now been replaced with the correct control image.
基金supported by the National Natural Science Foundation of China(grant nos.T2350009 and 22433007)the Guangdong Provincial Natural Science Foundation(grant no.2024A1515011185)+1 种基金the Shenzhen City Pengcheng Peacock Talent Program,and Shenzhen Science and Technology Program(no.KQTD20240729102028011)supported by the National Natural Science Foundation of China(grant nos.22273005 and 22422301).
文摘Electronic excited state inmolecular aggregate or exciton states continue to attract great attention due to the increasing demands for applications of molecular optoelectronics and sensing technology.The working principle behind the application is closely related to the excited state structure and dynamic processes inmolecular aggregate.In our previous review article(Aggregate 2021;2:e91),we focused more on the molecular mechanism for aggregation-induced emission process.Here,we are going to summarize our recent progress on theoretical investigations on the effects of excitonic coupling(J)and the intermolecular charge transfer(CT)on the excited state structure and dynamic processes.These are in general missing for molecular quantum chemistry studies.We will first present a novel definition of exciton coherence length which can present a bijective relation with the radiative decay rate and obviously we have clarified the confusion appeared in literature.Then,we will look at the CT effect for aggregate starting from a simple three-state model coupled with quantum chemical calculation for molecular dimer and we focus on the intensity borrowing,which can turn H-aggregate into emissive when the electron transfer and hole transfer integrals possessing the same sign and being large enough.We are able to propose amolecular descriptor to designmolecularmaterials possibly possessing both high photoluminescence quantum yield and carrier mobility.Finally,we introduce our work on the modified energy gap law for non-radiative decay rate in aggregates.We found there exist optimal J to minimize the non-radiative decay loss.
基金funded by the Russian Science Foundation(Grant No.23-74-10092).
文摘More than a century ago,it was known that the accumulation of ordered protein aggregates,amyloid fibrils,accompanies several serious and still largely incurable pathologies,including Alzheimer’s and Parkinson’s diseases.The striking gap between decades of research identifying amyloids as one of the key drivers of neurodegeneration and the persistent lack of effective antiamyloid therapies reveals a perplexing contradiction,which we define as the“amyloid paradox.”To address this paradox,here we summarize and analyze current perspectives on the unique properties and pathogenic mechanisms of amyloids,highlighting the variability and complexity of their biological consequences and uncovering the risks and limitations encountered in combating these aggregates.We conceptualize amyloid fibril pathogenicity as a complex cascade extending well beyond direct cytotoxicity,such as that arising from disruption of membranes and other cellular organelles.This review encompasses amyloids’disruptive effects on cellular processes and ability to trigger inflammatory responses,their resistance to degradation,capacity to regenerate after apparent destruction,tendency to propagate throughout the organism,propensity to cytotoxicity-increasing transformation,and ability to sequester and pathologically modify essential biomolecules.This integrated analysis reveals why single-target therapeutic approaches often fail and suggests that effective anti-amyloid strategies must address multiple aspects of amyloid pathogenicity simultaneously.The conceptual reframing of the threats of amyloid fibrils helps explain the origins of the amyloid paradox,enhances our understanding of these complex pathogenic agents,and provides a foundation for developing more effective and safe therapeutic strategies for neurodegenerative diseases.These strategies should address the complex and interconnected nature of amyloid pathogenicity rather than its targeting isolated aspects.
基金supported by the National Natural Science Foundation of China(52303382,52333007)Shenzhen Key Laboratory of Functional Aggregate Materials(ZDSYS20211021111400001)+2 种基金the Science Technology Innovation Commission of Shenzhen Municipality(KQTD20210811090142053,JCYJ20220530143805012)Shenzhen Science and Technology Program(grant no.2024SC0019)the 2022 Joint Fund Project between the Second Affiliated Hospital and the Chinese University of Hong Kong,Shenzhen(Special project of AIE Center).
文摘Despite extensive investigations into photophysics at the molecular level,the complex interplays between intermolecular interactions,hierarchical assembly,and photoluminescence properties remain a fundamental challenge in materials science,particularly concerning emergent phenomena in molecular aggregates.Herein,we construct different dimeric structures in both solution and aggregate states through cycloreversion upon photoirradiation from a series of nonemissive phenanthrene cycloadducts,exhibiting state-dependent photoactivatable luminescence.Specifically,the excimer in solution is nonemissive due to its antiparallel cofacial structure.In contrast,the dimer in the crystal exhibits nonclassical excimer emission according to its cross-stacked stacking within the restriction of the crystal lattice.Prominently,the luminescent behavior in aggregate is uniquely accessible through photocycloreversion and cannot be achieved through spontaneous crystallization of their parent phenanthrene molecules.Moreover,the photoactivatable nature of these materials is successfully demonstrated in thin films,showcasing their potential applications in information encryption.This work expands the possibilities for constructing new functional aggregate materials by photochemistry and deepens our understanding of dimer-luminescence relationships in different states.
基金supported by the National Natural Science Foundation of China(T2225028,22475219,12204167,22325305,T2350009,52203210,and 22003030)the Chinese Academy of Sciences(Hundred Talents Plan,Youth Innovation Promotion Association,the Strategic Priority Research Program of Sciences[XDB0520200]and Young Scientists in Basic Research[YSBR-053])the Guangdong Provincial Natural Science Foundation(2024A1515011185).
文摘Combining high mobility and high-efficiency luminescence in one material is challenging because of their contradictory design principles.Here,under the three-state exciton model,a molecular descriptor O=(|t_(h)+t_(e)|−|t_(h)-t_(e)|)∕2Jis proposed to quantitatively design materials with balanced luminescence and mobility in aggregated states,where a large𝑂would promise high crystalline photoluminescence quantum yield(PLQY)with small J(excitonic coupling)and significant t_(h) and t_(e)(hole and electron transfer integrals)would indicate high mobility.Through theoretical calculation and experimental validation,it is found that the asymmetric anthracene derivatives are quite effective in simultaneously achieving high mobility and high PLQY.Following the asymmetric guideline,the newly developed compounds,2-phenyl vinyl anthracene(2-PhVA)and 6-(2-(anthracene-2-yl)vinyl)benzo[b]thiophene(6-BTVA)demonstrate high O values alongside excellent performance:2-PhVA exhibits a PLQY of 81.5%and a maximum hole mobility of 10.0 cm^(2) V^(−1) s^(−1),and 6-BTVA shows a PLQY of 30.9%with a maximum mobility of 9.3 cm^(2) V^(−1) s^(−1).The above results demonstrate the validation of the descriptor and the asymmetric strategy in further developing high-mobility light-emitting aggregated materials.
基金National Natural Science Foundation of China,Grant/Award Numbers:52073005,22033006,62034001Beijing Municipal Natural Science Foundation,Grant/Award Number:JQ23020。
文摘Modifications to the alkyl side chains of Y6-type nonfullerene acceptors(NFAs)continuously break through the organic solar cells(OSCs)efficiency by enhancing electron mobility.However,the role of side chains in molecular aggregation and charge transport across different aggregates remains unclear.By employing a multiscale approach in combination with density functional theory(DFT),molecular dynamics(MD)simulations,and kinetic Monte Carlo(KMC),we addressed the issue of how side chains impact molecular aggregation,energy disorder,and the formation of near-macroscopic(∼0.3μm)conductive network,which are critical for boosting electron mobility.Specifically,the side-chain structure greatly influences the un-conjugated enveloping effect on backbones within aggregates.The effect diminishes with longer linear side chains and is further minimized by using branched side chains.Though static energy disorder increased,the improved connectivity of the conductive network led to a notable increase in electron mobility(from 2.4×10^(−4)to 3.9×10^(−4)cm^(2)⋅V^(−1)⋅s^(−1)).The findings offer insight into controlling molecular aggregation via alkyl side chains,which helps to further unlock the potential of Y6-type NFAs.
文摘Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization under solvothermal conditions in the presence of FeCl_(3)·6H_(2)O,yielding a heterocyclic aggregate,namely 1,2,3-tris(benzo[d]thiazol-2-yl)-2,9-dihydrobenzo[b]cyclopenta[e][1,4]thiazine.Single-crystal X-ray diffraction analysis was conducted on four distinct compounds isolated during the reaction,and electrospray ionization mass spectrometry(ESI-MS)of both solid products and intermediate reaction solutions enabled the identification of 15 consecutive reaction steps,where Fe(Ⅲ)was directly involved in eight steps.These transformations comprise nine intermolecular C─C coupling events and six intramolecular ring expansion processes.The heteroatoms(N,O,and S)play distinct mechanistic roles according to their positions within the heterocyclic framework:(1)nitrogen and oxygen coordinate with Fe(Ⅲ),facilitating activation of the reaction site;(2)homolytic cleavage of the C─O bond promotes C─C coupling reactions;and(3)C─S migration induces intramolecular ring expansion.Notably,theoretical calculations indicate a decrease in Gibbs free energy along the intramolecular reaction pathways,substantiating the proposed mechanism and activation mode,which underscores the essential role of Fe(Ⅲ)in enabling the reaction progression.Furthermore,an investigation of the photophysical properties revealed that the resulting heterocyclic aggregates exhibit strong luminescence within the 535–610 nm wavelength range,approaching the near-infrared region.These findings highlight the significance of this reaction pathway in the controlled synthesis of functional oligomers and polymers from monomeric precursors,particularly through catalysis by cost-effective metal ions.
基金supported by the National Natural Science Foundation of China(Nos.22308220 and 22090011)Guangdong Basic and Applied Basic Research Foundation(No.2023B1515120001)+3 种基金Research Team Cultivation Program of Shenzhen University(No.2023QNT005)Shenzhen University 2035 Program for Excellent Research(Nos.00000208,00000225)Shenzhen University Third-Phase Project of Constructing High-Level University(No.000001032104)Marshall Laboratory of Biomedical Engineering,Shenzhen University(No.86122-000001).
文摘Photodynamic therapy(PDT)and photothermal therapy(PTT)have emerged promising applications in both fundamental research and clinical trials.However,it remains challenging to develop ideal photosensitizers(PSs)that concurrently integrate high photostability,large near-infrared absorptivity,and efficient therapeutic capabilities.Herein,we reported a sample engineering strategy to afford a benzene-fused Cy5 dimer(Cy-D-5)for synergistically boosting PDT/PTT applications.Intriguingly,Cy-D-5 exhibits a tendency to form both J-aggregates and H-aggregates in phosphate-buffered saline,which show a long-wavelength absorption band bathochromically shifted to 810 nm and a short-wavelength absorption band hypsochromically shifted to 745 nm,respectively,when compared to its behavior in ethanol(778 nm).Density-functional theory calculations combined with time-resolved transient optical spectroscopy analysis reveal that the fused dimer Cy-D-5 exhibits a lowΔEST(0.51 eV)and efficient non-radiative transition rates(12.6 times greater than that of the clinically approved PS-indocyanine green[PS-ICG]).Furthermore,the Cy-D-5 demonstrates a higher photosensitizing ability to produce 1O2,stronger photothermal conversion efficiency(η=64.4%),and higher photostability compared with ICG.These combined properties enable Cy-D-5 to achieve complete tumor ablation upon 808 nm laser irradiation,highlighting its potential as a powerful and dual-function phototherapeutic agent.This work may offer a practical strategy for engineering other existing dyes to a red-shifted spectral range for various phototherapy applications.
基金supported by National Cancer Institute grant U01CA252965Eunice Kennedy Shriver National Institute of Child Health and Human Development grants R01HD090927 and R01HD103511+1 种基金National Institute of Allergy and Infectious Diseases grants R01AI144168,R01AI175618,R01AI173021,and R01AI177986National Institute of Neurological Disorders and Stroke R21NS130542.
文摘Extracellular vesicles(EVs)are essential for host–pathogen interactions,mediating processes such as immune modulation and pathogen survival.Pathogen-derived EVs hold significant diagnostic potential because of their unique cargo,offering a wealth of potential biomarkers.In this review,we first discuss the roles of EVs derived from various pathogens in host–pathogen interactions and summarize the latest advancements in pathogen detection based on EVs.Then,we highlight innovative strategies,including novel aggregate materials and machine learning approaches,for enhancing EV detection and analysis.Finally,we discuss challenges in the field and future directions for advancing EV-based diagnostics,aiming to translate these insights into clinical applications.
基金supported by the National Natural Science Foundation of China(Grants 22274029 and 32371439)the Jilin Provincial Scientific and Technological Development Program(Grant 20240207010CX)+3 种基金the Science and Technology Commission of Shanghai Municipality(Grant 22ZR1412000)the State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases(Grant RCGHCRB202405)the Jilin Provincial Science and Technology Development Plan(Grant YDZJ202401113ZYTS)the Jilin Provincial Science and Technology Development Plan(Grant YDZJ202501ZYTS177).
文摘The increasing prevalence of methicillin-resistant Staphylococcus aureus(MRSA)due to antibiotic misuse necessitates novel therapeutic strategies to counter multidrug-resistant infections.Here,we introduce a self-assembling,aggregation-enhanced tetrahedralDNAnanostructure(tFNA)platform that achieves targeted drug delivery through controlled aggregation and sustained release,effectively restoring MRSA susceptibility toβ-lactam antibiotics.These tetrahedral frameworks,termed tFNAs-ASOsceftriaxone sodium(TACs),serve as a dual-functional system that co-encapsulates antisense oligonucleotides(ASOs)targeting the mecA gene and the β-lactam antibiotic ceftriaxone sodium(Cef).Aggregation of TACs plays a pivotal role in maximizing drug retention and stability,prolonging the localized release of both ASOs and antibiotics while maintaining high bioavailability at the infection site.Characterization studies,including size distribution,zeta potential,and fluorescence quenching assays,confirm their robust aggregation stability and encapsulation efficiency,ensuring controlled drug kinetics and prolonged therapeutic effects.Upon interaction with bacterial cells,the locally concentrated TACs facilitate efficient ASO-mediated mecA silencing,thereby disrupting PBP2a expression and re-sensitizing MRSA to β-lactams.Simultaneously,the aggregated ceftriaxone sodium reservoir ensures sustained inhibition of bacterial cell wall synthesis,leading to effective bacterial clearance.In addition,TACs display potent antibiofilm activity by penetrating the biofilm matrix and delivering therapeutics directly to the embedded bacterial population,thereby overcoming the diffusion barriers.In vivo,TACs exhibit superior therapeutic efficacy in an MRSA-induced pneumonia mouse model,significantly improving survival rates,reducing bacterial burden,and mitigating lung tissue damage.These findings highlight the transformative potential of tFNAs as an intelligent drug aggregation and release system,offering a novel paradigm for optimizing antibiotic therapy against multidrug-resistant pathogens.
基金supported by the National Natural Science Foundation of China(32372275)the Fundamental Research Funds for the Central Universities(SWU-KR22044).
文摘Designing starch-based foods with controlled digestibility is critical for addressing global health challenges like diabetes,yet the molecular mechanisms underlying starch–protein interactions remain poorly quantified.Here,we investigate how wheat starch(WS)interacts with distinct protein fractions—wheat globulin(Glo),gliadin(Gli),and glutelin(Glu)—to form molecular aggregates that modulate digestion.By integrating experimental analyses(FTIR,XRD,rheology)with molecular dynamics(MD)simulations,we demonstrate that Gli and Glu exhibit stronger non-covalent binding to starch than Glo,driven by hydrophobic forces and hydrogen bonding.These interactions disrupt starch chain entanglement,reduce short-and long-range structural order,and inhibitα-amylase activity.At a 50:9 starch-to-protein ratio,Gli and Glu increased resistant starch content by 6.74%and 6.91%,respectively,outperforming Glo(2.96%).MD simulations quantified binding free energies(−107.67 kcal/mol for Gli,−99.50 kcal/mol for Glu),revealing electrostatic contributions from Glu’s lysine/arginine residues and hydrophobic interactions in Gli.Notably,Glo and Glu synergistically inhibit amylase via mixed competitive/non-competitive mechanisms.This work establishes a predictive framework for starch–protein aggregate design,bridging molecular interactions to functional outcomes.By elucidating how protein composition dictates digestibility,we advance strategies for engineering low-glycemic-index foods,offering transformative potential for nutrition and food science.
基金supported from the National Natural Science Foundation of China(22122701,22293050,22293051,91953201,92153303,22377050)the Excellent Research Program of Nanjing University(ZYJH004)+4 种基金the Natural Science Foundation of Jiangsu Province(BK20232020,BK20230977)Financial support from the National Postdoctoral Program for Innovative Talents(BX2021123)the China Postdoctoral Science Foundation(2021M691505)the Jiangsu Postdoctoral Research Funding Program(2021K125B)Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(23KJB150020)were also gratefully acknowledged.
文摘Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super-resolution is highly demanded yet quite challenging.Herein,a ratiometric HClO probe AHOH is designed and synthesized which is capable of simultaneously staining lysosomes and mitochondria with red and green colour,respectively.AHOH could be selectivity oxidized by HClO,leading to a large emission blue shift(90 nm)and an over 1300-fold enhancement of the emission ratio of Fl547nm/Fl637nm.We apply AHOH in super-resolution microscopy and clearly visualize the dynamics of mitochondria-lysosomes interactions and the oxidative stress states upon different stimuli.Mitochondria dysfunction triggered by different drugs and genetic defect lead to elevated oxidative stress and higher levels of mitophagy.Moreover,AHOH could serve as a reliable tool for evaluating the efficacy of drugs regulating mitochondria dysfunction.This work provides a powerful dual-colour super-resolution imaging agent for real-time monitoring the dynamics of organelle interactions and oxidative stress.
基金supported by the National Natural Science Foundation of China(Grant Nos.22325305,22273105,21973099,22173006)the Information Plan of the Chinese Academy of Sciences(Grant No.CAS-WX2023PY-0103)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.E2E40307X2)Beijing Natural Science Foundation(Grant No.2222027).
文摘Unveiling the dependence of stability and luminescence properties on the size of organic aggregates is crucial for biomedical and optoelectronic applications.Taking the helical hexaphenylsilole(HPS)and planar 3-(2-cyano-2-phenylethenyl-Z)-NH-indole(CPEI)aggregates of different sizes as examples,their stability and luminescent properties are investigated using multiscale modeling and thermal vibration correlation function approach.The size of stable aggregates formed depends on the molecular shape,with the critical aggregate sizes of 2.62 nm(2 molecules)and 2.87 nm(10 molecules)for helical HPS and planar CPEI,respectively.Their critical sizes for luminescence are 2.99 nm(6 molecules)and 2.87 nm(10 molecules),respectively.For HPS aggregates,as the size increases the luminescence is blue-shifted and enhanced owing to denser molecular packing until the size is large enough(4.66 nm,20 molecules)the luminescence tends to remain unchanged;and thermal annealing makes these changesmore pronounced.In contrast,the luminescent properties of CPEI aggregates are insensitive to aggregate size and thermal annealing treatment.These findings provide dynamic insights into the AIE mechanism and invaluable guidance for optimizing the size of AIE-based nanoparticles in practical applications.
基金supported by the Taishan Scholar Youth Expert Program in Shandong Province(Grant Number:tsqnz20230608)grants from the Natural Science Foundation of Shandong Province(Grant Number:ZR2023QB045)+1 种基金Scientific Research of Distinguished Professor from Qingdao University,China(Grant Numbers:DC2200000953,RZ2300002607,and RZ2400001462)grant from Natural Science Foundation of Qingdao Municipality,Shandong Province,China(Grant Number:23-2-1-30-zyyd-jch).
文摘Current radiotherapy(RT)lacks the ability to accurately discriminate between tumor and healthy tissues,resulting in significant radiation-induced damage for patients.Therefore,there is an urgent need for precise RT techniques that can optimize tumor control while minimizing adverse effects on surrounding healthy tissues.In this study,we developed a nanodrug(AuNR@Peptide)composed of furin-responsive RVRR peptide-conjugated AuNRs,which integrates an activatable probe and a radiosensitizer into a single system for accurate tumor localization,enabling imageguided precision RT.Upon reaching the tumor site after intravenous administration,proteolytic cleavage of RVRR substrates on AuNR@Peptide by biomarker triggers aggregation of gold nanorods(AuNRs)into larger aggregates,leading to activation of near-infrared(NIR)-II photoacoustic(PA)signals to precisely localize the tumor and enhance tumor retention by preventing migration and backflow of AuNRs.This significantly amplifies radiosensitivity efficiency.The peak time point at which the NIR-II PA signal was observed at the tumor site after injection serves as a reference for initiating RT,demonstrating substantial improvement in tumor RT through investigations related to radiosensitization mechanisms.The integration of imaging and therapy in this study offers a promising image-guided therapeutic modality for tumors.
基金support of the US National Science Foundation(CHE-2453603)supported by the National Institutes of Health(NIH R35GM128837).
文摘Lysosomes are essential organelles for cells that act as the“recycling center”for decomposing biomolecules and clearing out damaged organelles.The status of lysosomes is tightly regulated by cells to maintain normal homeostasis.To monitor subcellular lysosomal status,super-resolution imaging has emerged as a promising technology that surpasses conventional imaging limitations,offering extraordinary visualization capability.However,existing fluorescent probes for super-resolution imaging still suffer from significant drawbacks,such as complex synthesis,poor intracellular stability,and the lack of near-infrared(NIR)imaging capability.Besides,to quantitatively analyze fluorescence images,traditional human-driven image interpretation is time-consuming and prone to information loss and human error.To tackle these challenges,we first developed a quinoliniumbased fluorescent probe,PA-2,for NIR super-resolution imaging of lysosomes with low cytotoxicity and stable fluorescence.Harnessing PA-2’s strong resistance to photobleaching,the lysosomal dynamic statuses,encompassing autophagy,mitochondrialysosome contacts,and mitophagy,were successfully visualized.Building on this,we next demonstrate a novel approach leveraging a large multimodal model(LMM),an advanced artificial intelligence(AI)tool,for automated analysis of super-resolution images.The LMM accurately interprets images of PA-2 and predicts lysosomal status under various drug treatments with remarkable speed,precision,and explainability,significantly outperforming human experts in image analysis.To sum up,this work highlights the strong potential of combining advanced fluorescent probe design with AI-assisted image interpretation to drive revolutionary innovation in bioimaging and beyond.
文摘This year marks the fifth anniversary of Aggregate—a significant milestone for the journal.Since its launch in December 2020,we have embarked on a concerted journey to advance aggregate science,a field dedicated to the science of systems beyond isolated molecules.Over the past 5 years,we have been gratified towitness the journal’s growing academic recognition.On this occasion,we reflect on our progress and chart the course forward by reviewing the journal’s development from its inception toward a promising future.
基金supported by the National Natural Science Foundation of China(Grant Nos.22374163,22274056,22178377).
文摘Ultrahigh signal-to-noise ratio(SNR)labeling enables precise visualization of biological structures in vivo.We boosted fluorogenicity in group-14-rhodamines by comprehensively manipulating their dynamics in physical(aggregate/monomer,K_(A/M))and chemical(closed/open spirolactone,K_(C/O))states.Fluorogenic rhodamines were designed by group 14(C,Si,Ge)substituted bridging regions in xanthene with tuned dialkylation.We quantified the impact of alkylation with the hydrophobicity(logP)over a wide range and confirmed that SNR can be sharply improved,owing to the promoted nano-aggregation(K_(A/M))with high logP.Integrating K_(A/M) with K_(C/O) mechanisms,unparalleled fluorogenicity was observed in group-14-rhodamines:HaloTag probe with dipentylsilyl exhibits remarkable fluorogenicity(>2000)in vitro,enabling no-wash and multicolor super-resolution stimulated emission depletion imaging of high SNR(>300)in vivo.Overexpression ofα_(v)β_(3) was sensitively tracked in vivo by RGDyK-based fluorogenic SiR probe through tuned K_(A/M).Our proposed strategy has significantly promoted the fluorogenicity of group 14 rhodamines as a general mechanism.
基金supported by the National Key Research and Development Program of China(2023YFB3608902)the National Natural Science Foundation of China(Nos.22105054,22265009,62422404,62475116,and 52103210)+2 种基金the Collaborative Innovation Center Foundation of Hainan University(No.XTCX2022XXC02)the South China Sea New Star Innovation Talent Platform Project(No.NHXXRCXM202307)the Hainan University Start-up Fund,and the Natural Science Foundation of Jilin Province(No.20230101363JC).
文摘Organic luminescent radicals are promising for optoelectronic applications,yet their practical implementation remains hindered by aggregation-caused quenching(ACQ)in aggregated states.In this study,we present a molecular design strategy that enables unprecedented intrinsic luminescence from pure radicals across multiple aggregated states,including crystalline states,powders,and amorphous films,through the incorporation of sterically demanding TPP(2,4,6-triisopropylphenyl)groups.Comprehensive photophysical characterization coupled with structural analysis reveals that the TPP moieties effectively suppress detrimental intermolecular interactions,particularly exchange coupling andπ–πstacking between radical centers.The luminescent properties were analyzed via systematic theoretical calculations.The universality of this design principle is further demonstrated through its successful application to diradical systems,including Chichibabin’s and Muller’s hydrocarbons,which exhibit significantly enhanced emission in aggregated states.This work establishes a generalizable strategy for designing stable and efficient luminescent radicals in aggregated states,opening new avenues for radical-based optoelectronic devices.
