Ratiometric fluorescence(FL)probes can eliminate the background interference and provide more accurate detection results than single emission intensity-based nanoprobes.Recently,carbon dots(CDs)-based ratiometric FL p...Ratiometric fluorescence(FL)probes can eliminate the background interference and provide more accurate detection results than single emission intensity-based nanoprobes.Recently,carbon dots(CDs)-based ratiometric FL probes have received extensive research attention due to their excellent biocompatibility,water solubility,and multi-emission capabilities.In this review,we firstly summarize the construction strategies of CDs-based ratiometric FL probes,including physical mixing,nanohybrid,and dual-emitting CDs strategies.Additionally,we classify the sensing types of CDs-based ratiometric FL probes into five categories according to the difference in spectral variation caused by analytes:“single-response-ON”,“single-response-OFF”,“doubleresponses-ON”,“double-responses-OFF”,and“double-responses-Reverse”types.Finally,a thorough overview of CDs-based ratiometric FL probe applications in ions,molecules,pH,and temperature sensing is provided.We believe this review can show the latest research progress of CDs-based ratiometric FL sensing fields and provide perspectives on future developments for the construction of CDs-based ratiometric FL probes and their potential applications.展开更多
Multicomponent polymerizations(MCPs)are powerful tools to synthesize functional polymers with great structural diversity,low cost and high efficiency,which usually generate single polymer product.Herein,a robust one-p...Multicomponent polymerizations(MCPs)are powerful tools to synthesize functional polymers with great structural diversity,low cost and high efficiency,which usually generate single polymer product.Herein,a robust one-pot diamines,CS_(2)and monoisocyanide-participated catalyst-free polymerization was developed at room temperature to produce polythiourea and thioformamide simultaneously in equal equivalent,which was featured with cheap monomers,simple operation and mild condition,affording various polythioureas with high Mws of up to 4.75×10^(4)g/mol in high yields of up to 98%.Polythioureas with varied chain composition and sequence-controlled structure could be synthesized in 62 g-scale from copolymerization or multicomponent tandem polymerization,enabling facile tuning of thermal property,crystallinity,mechanical property,and fluorescence.The abundant irregular hydrogen bonds endowed the polythioureas excellent glassy state self-healing property at room temperature or below 0℃.This polymerization provided an efficient and economic approach to access functional polythioureas.展开更多
The development of new and efficient polymerization strategies for the synthesis of multisubstituted fused heterocyclic polymers with attractive properties is of great significance.Herein,a rhodium-catalyzed polyannul...The development of new and efficient polymerization strategies for the synthesis of multisubstituted fused heterocyclic polymers with attractive properties is of great significance.Herein,a rhodium-catalyzed polyannulation route is developed for the in situ generation of multisubstituted polyquinolines with efficient aggregate-state fluorescence.Based on the cascade C-H activation of isonicotinamides and their annulations with internal diynes,a series of high molecular weight polyquinolines are efficiently produced in high yields of up to 99%in a facile and atom-economical manner.Unlike conventional two-component stepwise polymerizations,these polyannulation reactions are tolerant to monomer non-stoichiometric conditions and proceed even more thoroughly in the presence of an excess amount of the isonicotinamide monomer.Benefiting from the unique multisubstituted polyquinoline structures,the obtained polymers show high thermal and morphological stability,useful aggregation-induced emission(AIE)properties,and tunable aggregated-state fluorescence behaviors.The AIE-active polyquinoline is demonstrated to be a good lysosome-specific fluorescent probe with low cytotoxicity and excellent photostability.展开更多
The development of a facile and efficient polymerization to prepare cyclopentadiene-containing polymers is of vital importance and highly desired. In this work, a metal-free multicomponent polymerization of activated ...The development of a facile and efficient polymerization to prepare cyclopentadiene-containing polymers is of vital importance and highly desired. In this work, a metal-free multicomponent polymerization of activated diyne, electrophilic styrene and isocyanide for the preparation of highly substituted poly(cyclopentadiene) was established. Soluble and thermally stable polymers with high molecular weights are obtained in high yields under mild conditions. By introducing the tetraphenylethene or triphenylamine moiety into polymer backbones, the resultant polymers show unique aggregation-induced emission(AIE)characteristics. Interestingly, AIE polymers can also be generated in situ from non-AIE monomers. Moreover, the prepared polymers can generate photopatterns to function as photoresists and can also serve as visualizing agents to selectively stain the lipid droplets in live cells. This efficient polymerization will open up enormous opportunities for preparing functional cyclopentadiene-containing polymers applicable in diverse areas.展开更多
The research on pharmacology usually focuses on the structure-activity relationships of drugs,such as antibiotics,to enhance their activity,but often ignores their optical properties.However,investigating the photophy...The research on pharmacology usually focuses on the structure-activity relationships of drugs,such as antibiotics,to enhance their activity,but often ignores their optical properties.However,investigating the photophysical properties of drugs is of great significance because they could be used to in situ visualize their positions and help us to understand their working metabolism.In this work,we identified a class of commercialized antibiotics,such as levofloxacin,norfloxacin,and moxifloxacin(MXF)hydrochloride,featuring the unique aggregation-induced emission(AIE)characteristics.By taking advantage of their AIE feature,antibiotic metabolism in cells could be in situ visualized,which clearly shows that the luminescent aggregates accumulate in the lysosomes.Moreover,after a structure-activity relationship study,we found an ideal site of MXF to be modified with a triphenylphosphonium and an antibiotic derivative MXF-P was prepared,which is able to specifically differentiate bacterial species after only 10 min of treatment.Moreover,MXF-P shows highly effective broad-spectrum antibacterial activity,excellent therapeutic effects and biosafety for S.aureus-infected wound recovery.Thus,this work not only discovers the multifunctionalities of the antibiotics but also provides a feasible strategy to make the commercialized drugs more powerful.展开更多
Lipid droplets(LDs)participate in many physiological processes,the abnormality of which will cause chronic diseases and pathologies such as diabetes and obesity.It is crucial to monitor the distribution of LDs at high...Lipid droplets(LDs)participate in many physiological processes,the abnormality of which will cause chronic diseases and pathologies such as diabetes and obesity.It is crucial to monitor the distribution of LDs at high spatial resolution and large depth.Herein,we carried three-photon imaging of LDs in fat liver.Owing to the large three-photon absorption cross-section of the luminogen named NAP-CF_(3)(1:67×10^(-79) cm^(6) s^(2)),three-photon fluorescence fat liver imaging reached the largest depth of 80μm.Fat liver diagnosis was successfully carried out with excellent performance,providing great potential for LDs-associated pathologies research.展开更多
Organic light-emitting materials have attracted considerable attention because of their promising applications in diverse areas.Most fluorophores emit brightly in either dilute solutions or aggregate states;the former...Organic light-emitting materials have attracted considerable attention because of their promising applications in diverse areas.Most fluorophores emit brightly in either dilute solutions or aggregate states;the former generally suffer from aggregation-caused quenching problem,and the latter encounter intensity loss at low concentrations.Herein,we propose a new strategy to overcome these dilemmas by balancing the planar and distorted structures of terphenyl-based luminogens and obtain three luminogens,2PB-AC,2Me2PB-AC,and 2T2PB-AC,with bright emission in both solution and aggregate states.Among them,2PB-AC shows absolute photoluminescence quantum yields(ФPL)higher than 90%in both tetrahydrofuran solution(90.2%)and aggregate states(92.7%for powder and 95.3%for crystal).Thus,2PB-AC could be an efficient probe to realize dual-channel explosive detection in both solution and aggregate states.Moreover,it could be used to image live-cell lipid droplets at a wide range of concentrations.In addition,benefiting from its thermodynamically favorable intersystem crossing process,2Me2PB-AC could be doped in polymethyl methacrylate matrix to provide efficient room-temperature phosphorescence.Thus,this work provides a feasible strategy for the design of luminogens with highly efficient emission in both solution and aggregate states,greatly facilitating and broadening their practical applications.展开更多
DNase-catalyzed hydrolysis of extracellular DNA(eDNA)has been widely employed to eradicate intractable biofilms.Although aggregation-induced emission(AIE)has become the ideal tool for killing planktonic bacteria,AIE l...DNase-catalyzed hydrolysis of extracellular DNA(eDNA)has been widely employed to eradicate intractable biofilms.Although aggregation-induced emission(AIE)has become the ideal tool for killing planktonic bacteria,AIE luminogens(AIEgens)often lack DNase-mimetic activity,so as to suffer from poor anti-biofilm capacity.Here,an“AIEzyme”,a kind of AIE nanomaterial with enzyme-like activity,is designed and synthesized,where the AIEgens are used as the ligands of Zr-based coordination polymer nanoparticles.Not only does AIEzyme have enduring DNasemimetic activity with low activation energy,but also structural rigidity-stabilized fluorescence.Due to the long-acting hydrolysis for eDNA in biofilm,AIEzyme can efficiently disorganize the established biofilms with good penetrability and realize the healing of superbug-infected wounds under only one dose of AIEzyme.This work provides a strategy to endow ordinary AIEgens with DNase-like and antibiofilm activities.Moreover,AIEzymes can be observed by virtue of their own AIE character,facilitating the study on self-positioning and residual amount of AIEzymes in wounds.The concept“AIEzyme”would hopefully stimulate the tremendous expansion for the tool kits and the application of AIEgens and artificial enzymes.展开更多
Cationic amphiphile aggregates exhibit superior antibacterial activity than monomers.However,the antimicrobial mechanism of aggregates has not been well understood because it is difficult to distinguish and monitor ag...Cationic amphiphile aggregates exhibit superior antibacterial activity than monomers.However,the antimicrobial mechanism of aggregates has not been well understood because it is difficult to distinguish and monitor aggregate and monomer in antimicrobial process.Herein,three bola-type cationic amphiphiles with aggregation-induced emission property have been developed to show distinguishable fluorescence in their monomer and aggregate.The hydrophilicity of monomer and the stability of aggregate are finely tuned by tailoring the linkers between two quaternary ammonium end groups and tetraphenylethylene skeleton.The sensitive fluorescence switching of monomer and aggregate achieves the quantitative monitoring of dynamic interaction of three amphiphiles with bacteria.The aggregates with cationic charges first attach to bacterial surface,and the monomers subsequently dissociate from aggregates to penetrate bacterial membrane.Further,our results reveal the vital role of stability of aggregates during antimicrobial process,shedding light on the rational design of high-efficient antimicrobials.展开更多
This paper reports the first universal and versatile database on aggregate materials for the field of aggregate science research.At the current stage,the database(http://119.91.135.188:8080/)contains over 1000 entries...This paper reports the first universal and versatile database on aggregate materials for the field of aggregate science research.At the current stage,the database(http://119.91.135.188:8080/)contains over 1000 entries of organic aggregate material systems(mainly luminescent systems at the current stage)with a unique data structure which is designed particularly for aggregate materials and containing the photophysics and physicochemical properties of the compounds in different statuses of aggregation,including dilute solution form,pristine solid-state,stable crystalline,and nanoaggregates formed in solvents.The web-based interface of the database provided functions to index,search,manipulate,fetch and deposit data entries.In addition,a background calculation service optimizes the chemical structure of new entries on different levels of accuracies.The database also provided background API for interactive developments of prediction or regression models based on machine-learning algorithms.展开更多
Nanotechnology hailed as a revolutionary new technology of the 21st century, has ignited a wave of innovation across diverse fields spanning chemistry, physics, materials science,medicine, engineering, and electronics...Nanotechnology hailed as a revolutionary new technology of the 21st century, has ignited a wave of innovation across diverse fields spanning chemistry, physics, materials science,medicine, engineering, and electronics. In 2016, Nature published an article titled “The nanolight revolution is coming”, underscoring that “virus-sized particles that emit light in every color could transform applications ranging from television displays to cancer treatment”.展开更多
The dual emission(DE)feature in materials holds great potential to revolutionize the development of one-component system white organic lightemitting diodes(WOLEDs).However,the reported DE materials remain scarce owing...The dual emission(DE)feature in materials holds great potential to revolutionize the development of one-component system white organic lightemitting diodes(WOLEDs).However,the reported DE materials remain scarce owing to the formidable challenge of breaking Kasha’s rule and managing the intricate energy/charge transfer processes.Herein,we have introduced a groundbreaking DE AIEgen,2CzAn-TPE,which possesses a simple structure and undergoes Z-to-E isomerization and exhibits yellow and red fluorescence powders for pre-and post-sublimation,respectively.With relatively lower potential energy,Z-conformation((Z)-1,2-diphenyl-1,2-bis(4-(10-(9-phenyl-9H-carbazol-3-yl)anthracen-9-yl)phenyl)ethene)of 2CzAn-TPE can be readily transformed into E-conformation((E)-1,2-diphenyl-1,2-bis(4-(10-(9-phenyl-9Hcarbazol-3-yl)anthracen-9-yl)phenyl)ethene)via vacuum sublimation.The utilization of X-ray diffraction and grazing-incidence-wide-angle X-ray scattering techniques confirms the structural transformation,while the crystallographic analysis reveals the establishment of numerous intermolecular CH⋅⋅⋅πinteractions between the tetraphenylethene(TPE)moiety and both the anthracene and carbazole units.This allows a densely packed molecular arrangement,thereby offering propitious conditions for excimer generation in the E-conformation aggregated state.By utilizing the sublimated 2CzAn-TPE as an emitter,a nondoped one-component WOLED was prepared,exhibiting an exceptionally high external quantum efficiency(EQE)of 5.0%,which represents one of the highest performances among all one-componentWOLEDs.This research introduces a novel,simple,and efficient approach to realize highly efficient one-molecule WOLEDs.展开更多
Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a p...Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)laser.Unfortunately,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor treatment.In this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion luminescence.The theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting glioma.Under the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ.These results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.展开更多
In the traditionalWestern culture,the first anniversary of marriage was referred to as a paper anniversary:paper is the top gift for the first-anniversary celebration.Time flies and it is now the time to celebrate the...In the traditionalWestern culture,the first anniversary of marriage was referred to as a paper anniversary:paper is the top gift for the first-anniversary celebration.Time flies and it is now the time to celebrate the first-year birthday of Aggregate.The spotlight of this anniversary celebration is also papers,not the commodity papers sold in the markets but the research papers published in Aggregate.Since the first batch of research papers published in its inauguration issue at the end of last year,Aggregate has witnessed a challenging,thrilling yet fruitful year.Overcoming the negative impact of the coronavirus pandemic on scientific research,Aggregate has made an exotic journey and reached a magnificent milestone.展开更多
Aggregate science has led to the existence of functional properties at the aggregate level that significantly differs from those of corresponding single-molecule species,leading to a number of novel conceptual materia...Aggregate science has led to the existence of functional properties at the aggregate level that significantly differs from those of corresponding single-molecule species,leading to a number of novel conceptual materials with state-dependent functionality.For developing such materials,new molecular scaffolds that allow modulating the structural and functional properties of aggregates in a controlled manner could be extremely helpful.In this study,we report a class of spiro-fused bicyclo[3,2,2]octatriene triptycene derivatives with a unique 3 D molecular scaffolding structure that displays aggregation-induced emission(AIE)activity with bright solid-state blue luminescence.The core scaffold features a Y-shaped bicyclo[3,2,2]octatriene backbone and a vertical crossover arrangement of adjacent spiro-conjugated rings.Unlike classic bicyclo[2,2,2]octatrienes with high rigidity,this stereoscopic bicyclo[3,2,2]octatriene containing a seven-membered ring allows retaining certain flexibility in the molecular scaffold,which results in a weak fluorescence in dilute solutions(Φ_(F)<10%).However,the corresponding molecular aggregates emit intense fluorescence(Φ_(F)=50%-75%)and show prominent AIE activity because of the restriction of intramolecular scaffold motions.Moreover,in principle,these stereoscopic scaffold constructions with partially restricted flexibility facilitate the assembly of multiple different crystalline packing structures in both porous and nonporous forms depending on the growth conditions of crystalline aggregates.The obtained crystals with regular voids(12.85×6.89Aeach)show reversible luminescence in response to the adsorption/desorption of iodine vapor.These materials based on an unusual 3 D scaffold exhibit a high degree of structural modulation at the aggregate level and demonstrate potential applications in chemical sensing and flexible optoelectronics,which may open up the exploration of highly stereoscopic molecular building blocks for developing functional aggregates.展开更多
Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach i...Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.展开更多
The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of brig...The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of bright organic luminogens with typical electron-donating(D)and electron-accepting(A)structures(abbreviated as LDs-BDM,LDs-BTM,and LDs-BHM)was synthesized through a simple single-step reaction.They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70%(e.g.,83.7%for LDs-BTM).Their light-emission properties could be tuned by the modulation ofπ-conjugation effect with methoxy groups at different substituent positions.Their resulting fluorescent nanoparticles(NPs)were demonstrated as specific lipid droplets(LDs)targeting probes with high brightness,good biocompatibility,and satisfactory photostability.LDs-BTM NPs with a large two-photon absorption cross section(σ2=249 GM)were further utilized as ultrabright two-photon fluorescence(2PF)nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration(0.5μmol/L).Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated.This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique.These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.展开更多
The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of du...The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of dual-activated alkyne and pyridines was developed to construct novel N-heterocyclic poly(quinolizine)s. This polymerization can proceed smoothly under catalystfree conditions with 100% atom utilization to furnish poly(quinolizine)s with high molecular weights(up to 34,100) and welldefined structures in acceptable yields. The resulting polymers show good solubility, high thermal stability and strong red emission. Moreover, the prepared poly(quinolizine)s exhibit low cytotoxicity and can selectively label lysosomes in live cells.Considering the remarkable advantages of readily available raw materials, mild polymerization conditions, atom economy, and excellent product performance, this new and efficient polymerization tool will open up enormous opportunities for preparing functional N-heterocyclic polymers.展开更多
Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several ...Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several types of cancers,and ferroptosis inducers can be used to promote ferroptosis in tumor cells and play an anti-tumor role.However,the specificity and efficacy of ferroptosis inducers remain unsatisfactory.Here,a new mitochondria-targeted photosensitizer(PS)with aggregation-induced emission(AIE)characteristic named TCSVP was designed,which efficiently generates ROS in mitochondria after light exposure.TCSVP administration significantly sensitizes tumor cells to ferroptosis inducer(RSL3)-mediated cell death by specifically and light-dependently triggering a moderate ROS generation in vitro and in vivo.Mechanically,the expression levels of ferroptosis related proteins Acyl-CoA synthetase long-chain family member 4(FACL4/ACSL4)and cyclooxygenase-2(COX2)were increased in TCSVP/RSL3-treated cells after light exposure,coupled with decreased Glutathione peroxidase 4(GPX4)activity and excessive malondialdehyde(MDA)accumulation.This study declared that light-induced moderate ROS generation within mitochondria in cancer cells by AIE-PS can be used to enhance the specificity and efficacy of ferroptosis inducers,bringing a new synergistic strategy for tumor intervention.展开更多
Polymers are everywhere.The living kingdom is full of natural polymers or biological macromolecules(e.g.,polysaccharides,polynucleotides and proteins),while the modern society is alive with synthetic polymers or manma...Polymers are everywhere.The living kingdom is full of natural polymers or biological macromolecules(e.g.,polysaccharides,polynucleotides and proteins),while the modern society is alive with synthetic polymers or manmade macromolecules(e.g.,plastics,fibers and rubbers).展开更多
基金The authors appreciate financial support from the National Natural Science Foundation of China(Nos.21788102,21974046,22176058,and 21977031)the Science and Technology Commission of Shanghai Municipality(Nos.19391901700,19520744000,and 19ZR1472300)the Fundamental Research Funds for the Central Universities.
文摘Ratiometric fluorescence(FL)probes can eliminate the background interference and provide more accurate detection results than single emission intensity-based nanoprobes.Recently,carbon dots(CDs)-based ratiometric FL probes have received extensive research attention due to their excellent biocompatibility,water solubility,and multi-emission capabilities.In this review,we firstly summarize the construction strategies of CDs-based ratiometric FL probes,including physical mixing,nanohybrid,and dual-emitting CDs strategies.Additionally,we classify the sensing types of CDs-based ratiometric FL probes into five categories according to the difference in spectral variation caused by analytes:“single-response-ON”,“single-response-OFF”,“doubleresponses-ON”,“double-responses-OFF”,and“double-responses-Reverse”types.Finally,a thorough overview of CDs-based ratiometric FL probe applications in ions,molecules,pH,and temperature sensing is provided.We believe this review can show the latest research progress of CDs-based ratiometric FL sensing fields and provide perspectives on future developments for the construction of CDs-based ratiometric FL probes and their potential applications.
基金supported by the National Natural Science Foundation of China(Nos.52173005,21788102 and 21822102)the Ministry of Science and Technology of China(No.2021YFA1501600)+1 种基金the Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates(No.2019B030301003)the Fundamental Research Funds for the Central Universities.
文摘Multicomponent polymerizations(MCPs)are powerful tools to synthesize functional polymers with great structural diversity,low cost and high efficiency,which usually generate single polymer product.Herein,a robust one-pot diamines,CS_(2)and monoisocyanide-participated catalyst-free polymerization was developed at room temperature to produce polythiourea and thioformamide simultaneously in equal equivalent,which was featured with cheap monomers,simple operation and mild condition,affording various polythioureas with high Mws of up to 4.75×10^(4)g/mol in high yields of up to 98%.Polythioureas with varied chain composition and sequence-controlled structure could be synthesized in 62 g-scale from copolymerization or multicomponent tandem polymerization,enabling facile tuning of thermal property,crystallinity,mechanical property,and fluorescence.The abundant irregular hydrogen bonds endowed the polythioureas excellent glassy state self-healing property at room temperature or below 0℃.This polymerization provided an efficient and economic approach to access functional polythioureas.
基金supported by the National Natural Science Foundation of China(22271197,21905176)the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province(2020B1515020011)+1 种基金the Science and Technology Plan of Shenzhen(JCYJ20190808142403590,JCYJ20190808153415062)the Instrumental Analysis Center of Shenzhen University。
文摘The development of new and efficient polymerization strategies for the synthesis of multisubstituted fused heterocyclic polymers with attractive properties is of great significance.Herein,a rhodium-catalyzed polyannulation route is developed for the in situ generation of multisubstituted polyquinolines with efficient aggregate-state fluorescence.Based on the cascade C-H activation of isonicotinamides and their annulations with internal diynes,a series of high molecular weight polyquinolines are efficiently produced in high yields of up to 99%in a facile and atom-economical manner.Unlike conventional two-component stepwise polymerizations,these polyannulation reactions are tolerant to monomer non-stoichiometric conditions and proceed even more thoroughly in the presence of an excess amount of the isonicotinamide monomer.Benefiting from the unique multisubstituted polyquinoline structures,the obtained polymers show high thermal and morphological stability,useful aggregation-induced emission(AIE)properties,and tunable aggregated-state fluorescence behaviors.The AIE-active polyquinoline is demonstrated to be a good lysosome-specific fluorescent probe with low cytotoxicity and excellent photostability.
基金supported by the National Natural Science Foundation of China(21788102,22101028)the Research Grants Council of Hong Kong(16304819,16305320,C6014-20W)+3 种基金the Innovation and Technology Commission(ITC-CNERC14SC01)the Natural Science Foundation of Guangdong Province(2019B121205002)Shenzhen Key laboratory of Functional Aggregate Materials(ZDSYS20212021222400001)the Nissan Chemical Industries,Ltd.
文摘The development of a facile and efficient polymerization to prepare cyclopentadiene-containing polymers is of vital importance and highly desired. In this work, a metal-free multicomponent polymerization of activated diyne, electrophilic styrene and isocyanide for the preparation of highly substituted poly(cyclopentadiene) was established. Soluble and thermally stable polymers with high molecular weights are obtained in high yields under mild conditions. By introducing the tetraphenylethene or triphenylamine moiety into polymer backbones, the resultant polymers show unique aggregation-induced emission(AIE)characteristics. Interestingly, AIE polymers can also be generated in situ from non-AIE monomers. Moreover, the prepared polymers can generate photopatterns to function as photoresists and can also serve as visualizing agents to selectively stain the lipid droplets in live cells. This efficient polymerization will open up enormous opportunities for preparing functional cyclopentadiene-containing polymers applicable in diverse areas.
基金Animal experiment protocols were reviewed and approved by South China Agricultural University and complied with all relevant ethical regulations.(Approval number:2021c075).
文摘The research on pharmacology usually focuses on the structure-activity relationships of drugs,such as antibiotics,to enhance their activity,but often ignores their optical properties.However,investigating the photophysical properties of drugs is of great significance because they could be used to in situ visualize their positions and help us to understand their working metabolism.In this work,we identified a class of commercialized antibiotics,such as levofloxacin,norfloxacin,and moxifloxacin(MXF)hydrochloride,featuring the unique aggregation-induced emission(AIE)characteristics.By taking advantage of their AIE feature,antibiotic metabolism in cells could be in situ visualized,which clearly shows that the luminescent aggregates accumulate in the lysosomes.Moreover,after a structure-activity relationship study,we found an ideal site of MXF to be modified with a triphenylphosphonium and an antibiotic derivative MXF-P was prepared,which is able to specifically differentiate bacterial species after only 10 min of treatment.Moreover,MXF-P shows highly effective broad-spectrum antibacterial activity,excellent therapeutic effects and biosafety for S.aureus-infected wound recovery.Thus,this work not only discovers the multifunctionalities of the antibiotics but also provides a feasible strategy to make the commercialized drugs more powerful.
基金supported by National Natural Science Foundation of China (61975172,82001874,62105184)the Guangdong Basic and Applied Basic Research Foundation (2020A1515110578).
文摘Lipid droplets(LDs)participate in many physiological processes,the abnormality of which will cause chronic diseases and pathologies such as diabetes and obesity.It is crucial to monitor the distribution of LDs at high spatial resolution and large depth.Herein,we carried three-photon imaging of LDs in fat liver.Owing to the large three-photon absorption cross-section of the luminogen named NAP-CF_(3)(1:67×10^(-79) cm^(6) s^(2)),three-photon fluorescence fat liver imaging reached the largest depth of 80μm.Fat liver diagnosis was successfully carried out with excellent performance,providing great potential for LDs-associated pathologies research.
基金This work was financially supported by the National Natural Science Foundation of China(grant no.21788102)the Natural Science Foundation of Guangdong Province(grant nos.2019B030301003 and 2016A030312002)the Innovation and Technology Commission of Hong Kong(grant no.ITC-CNERC14S01).
文摘Organic light-emitting materials have attracted considerable attention because of their promising applications in diverse areas.Most fluorophores emit brightly in either dilute solutions or aggregate states;the former generally suffer from aggregation-caused quenching problem,and the latter encounter intensity loss at low concentrations.Herein,we propose a new strategy to overcome these dilemmas by balancing the planar and distorted structures of terphenyl-based luminogens and obtain three luminogens,2PB-AC,2Me2PB-AC,and 2T2PB-AC,with bright emission in both solution and aggregate states.Among them,2PB-AC shows absolute photoluminescence quantum yields(ФPL)higher than 90%in both tetrahydrofuran solution(90.2%)and aggregate states(92.7%for powder and 95.3%for crystal).Thus,2PB-AC could be an efficient probe to realize dual-channel explosive detection in both solution and aggregate states.Moreover,it could be used to image live-cell lipid droplets at a wide range of concentrations.In addition,benefiting from its thermodynamically favorable intersystem crossing process,2Me2PB-AC could be doped in polymethyl methacrylate matrix to provide efficient room-temperature phosphorescence.Thus,this work provides a feasible strategy for the design of luminogens with highly efficient emission in both solution and aggregate states,greatly facilitating and broadening their practical applications.
基金Youth Innovation Team Project for Talent Introduction and Cultivation in Universities of Shandong Province,Grant/Award Number:096-1622002Research Foundation for Distinguished Scholars of Qingdao Agricultural University,Grant/Award Number:663-1117015。
文摘DNase-catalyzed hydrolysis of extracellular DNA(eDNA)has been widely employed to eradicate intractable biofilms.Although aggregation-induced emission(AIE)has become the ideal tool for killing planktonic bacteria,AIE luminogens(AIEgens)often lack DNase-mimetic activity,so as to suffer from poor anti-biofilm capacity.Here,an“AIEzyme”,a kind of AIE nanomaterial with enzyme-like activity,is designed and synthesized,where the AIEgens are used as the ligands of Zr-based coordination polymer nanoparticles.Not only does AIEzyme have enduring DNasemimetic activity with low activation energy,but also structural rigidity-stabilized fluorescence.Due to the long-acting hydrolysis for eDNA in biofilm,AIEzyme can efficiently disorganize the established biofilms with good penetrability and realize the healing of superbug-infected wounds under only one dose of AIEzyme.This work provides a strategy to endow ordinary AIEgens with DNase-like and antibiofilm activities.Moreover,AIEzymes can be observed by virtue of their own AIE character,facilitating the study on self-positioning and residual amount of AIEzymes in wounds.The concept“AIEzyme”would hopefully stimulate the tremendous expansion for the tool kits and the application of AIEgens and artificial enzymes.
基金National Natural Science Foundation of China,Grant/Award Number:22002137Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20200920+1 种基金Beijing Natural Science Foundation,Grant/Award Number:2212013Shenzhen Key Laboratory of Functional Aggregate Materials,Grant/Award Number:ZDSYS20211021111400001。
文摘Cationic amphiphile aggregates exhibit superior antibacterial activity than monomers.However,the antimicrobial mechanism of aggregates has not been well understood because it is difficult to distinguish and monitor aggregate and monomer in antimicrobial process.Herein,three bola-type cationic amphiphiles with aggregation-induced emission property have been developed to show distinguishable fluorescence in their monomer and aggregate.The hydrophilicity of monomer and the stability of aggregate are finely tuned by tailoring the linkers between two quaternary ammonium end groups and tetraphenylethylene skeleton.The sensitive fluorescence switching of monomer and aggregate achieves the quantitative monitoring of dynamic interaction of three amphiphiles with bacteria.The aggregates with cationic charges first attach to bacterial surface,and the monomers subsequently dissociate from aggregates to penetrate bacterial membrane.Further,our results reveal the vital role of stability of aggregates during antimicrobial process,shedding light on the rational design of high-efficient antimicrobials.
基金the National Science Foundation of China,Grant/Award Numbers:21975077,52003228,21788102Shenzhen Key Laboratory of Functional Aggregate Materials,Grant/Award Number:ZDSYS20211021111400001+1 种基金the Science and Technology Plan of Shenzhen,Grant/Award Number:JCYJ2021324134613038Open Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates,Grant/Award Number:2019B030301003。
文摘This paper reports the first universal and versatile database on aggregate materials for the field of aggregate science research.At the current stage,the database(http://119.91.135.188:8080/)contains over 1000 entries of organic aggregate material systems(mainly luminescent systems at the current stage)with a unique data structure which is designed particularly for aggregate materials and containing the photophysics and physicochemical properties of the compounds in different statuses of aggregation,including dilute solution form,pristine solid-state,stable crystalline,and nanoaggregates formed in solvents.The web-based interface of the database provided functions to index,search,manipulate,fetch and deposit data entries.In addition,a background calculation service optimizes the chemical structure of new entries on different levels of accuracies.The database also provided background API for interactive developments of prediction or regression models based on machine-learning algorithms.
文摘Nanotechnology hailed as a revolutionary new technology of the 21st century, has ignited a wave of innovation across diverse fields spanning chemistry, physics, materials science,medicine, engineering, and electronics. In 2016, Nature published an article titled “The nanolight revolution is coming”, underscoring that “virus-sized particles that emit light in every color could transform applications ranging from television displays to cancer treatment”.
基金National Science Fund for Distinguished Young Scholars,Grant/Award Number:21925506National Natural Science Foundation of China,Grant/Award Numbers:U21A20331,51773212,81903743,52003088Ningbo Key Scientific and Technological Project,Grant/Award Numbers:2022Z124,2022Z119。
文摘The dual emission(DE)feature in materials holds great potential to revolutionize the development of one-component system white organic lightemitting diodes(WOLEDs).However,the reported DE materials remain scarce owing to the formidable challenge of breaking Kasha’s rule and managing the intricate energy/charge transfer processes.Herein,we have introduced a groundbreaking DE AIEgen,2CzAn-TPE,which possesses a simple structure and undergoes Z-to-E isomerization and exhibits yellow and red fluorescence powders for pre-and post-sublimation,respectively.With relatively lower potential energy,Z-conformation((Z)-1,2-diphenyl-1,2-bis(4-(10-(9-phenyl-9H-carbazol-3-yl)anthracen-9-yl)phenyl)ethene)of 2CzAn-TPE can be readily transformed into E-conformation((E)-1,2-diphenyl-1,2-bis(4-(10-(9-phenyl-9Hcarbazol-3-yl)anthracen-9-yl)phenyl)ethene)via vacuum sublimation.The utilization of X-ray diffraction and grazing-incidence-wide-angle X-ray scattering techniques confirms the structural transformation,while the crystallographic analysis reveals the establishment of numerous intermolecular CH⋅⋅⋅πinteractions between the tetraphenylethene(TPE)moiety and both the anthracene and carbazole units.This allows a densely packed molecular arrangement,thereby offering propitious conditions for excimer generation in the E-conformation aggregated state.By utilizing the sublimated 2CzAn-TPE as an emitter,a nondoped one-component WOLED was prepared,exhibiting an exceptionally high external quantum efficiency(EQE)of 5.0%,which represents one of the highest performances among all one-componentWOLEDs.This research introduces a novel,simple,and efficient approach to realize highly efficient one-molecule WOLEDs.
基金Natural Science Foundation of China,Grant/Award Numbers:T2222021,32011530115,32025021National Key R&D Programs,Grant/Award Number:2019YFE0198700+2 种基金Science and Technology Bureau of Ningbo City,Grant/Award Numbers:2020Z094,2021Z072Excellent Member of Youth Innovation Promotion Association Foundation of CAS,Grant/Award Number:Y2021079Innovation and Technology Commission,Grant/Award Number:MHP/047/19。
文摘Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)laser.Unfortunately,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor treatment.In this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion luminescence.The theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting glioma.Under the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ.These results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.
文摘In the traditionalWestern culture,the first anniversary of marriage was referred to as a paper anniversary:paper is the top gift for the first-anniversary celebration.Time flies and it is now the time to celebrate the first-year birthday of Aggregate.The spotlight of this anniversary celebration is also papers,not the commodity papers sold in the markets but the research papers published in Aggregate.Since the first batch of research papers published in its inauguration issue at the end of last year,Aggregate has witnessed a challenging,thrilling yet fruitful year.Overcoming the negative impact of the coronavirus pandemic on scientific research,Aggregate has made an exotic journey and reached a magnificent milestone.
基金supported by the National Key Research and Development Program of China(2020YFC1807302)the National Natural Science Foundation of China(51922039)+4 种基金the Science and Technology Innovation Program of Hunan Province(2020RC5033)the Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates(2019B03031003)Hunan Provincial Grant for Innovative Province Construction(2019RS2023)Shenzhen Science and Technology Program(RCJC20200714114434015)the Natural Science Foundation of Hunan Province(2020JJ3003)。
文摘Aggregate science has led to the existence of functional properties at the aggregate level that significantly differs from those of corresponding single-molecule species,leading to a number of novel conceptual materials with state-dependent functionality.For developing such materials,new molecular scaffolds that allow modulating the structural and functional properties of aggregates in a controlled manner could be extremely helpful.In this study,we report a class of spiro-fused bicyclo[3,2,2]octatriene triptycene derivatives with a unique 3 D molecular scaffolding structure that displays aggregation-induced emission(AIE)activity with bright solid-state blue luminescence.The core scaffold features a Y-shaped bicyclo[3,2,2]octatriene backbone and a vertical crossover arrangement of adjacent spiro-conjugated rings.Unlike classic bicyclo[2,2,2]octatrienes with high rigidity,this stereoscopic bicyclo[3,2,2]octatriene containing a seven-membered ring allows retaining certain flexibility in the molecular scaffold,which results in a weak fluorescence in dilute solutions(Φ_(F)<10%).However,the corresponding molecular aggregates emit intense fluorescence(Φ_(F)=50%-75%)and show prominent AIE activity because of the restriction of intramolecular scaffold motions.Moreover,in principle,these stereoscopic scaffold constructions with partially restricted flexibility facilitate the assembly of multiple different crystalline packing structures in both porous and nonporous forms depending on the growth conditions of crystalline aggregates.The obtained crystals with regular voids(12.85×6.89Aeach)show reversible luminescence in response to the adsorption/desorption of iodine vapor.These materials based on an unusual 3 D scaffold exhibit a high degree of structural modulation at the aggregate level and demonstrate potential applications in chemical sensing and flexible optoelectronics,which may open up the exploration of highly stereoscopic molecular building blocks for developing functional aggregates.
基金supported by grants from the National Key R&D Program of China(2021YFA1100600 to S.S.)the Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125,D-07 to S.S.,D-11 to X.K.)+5 种基金the Pearl River Talent Recruitment Program(2019ZT08Y485)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2018ZX10302207-001-002)the Sun Yat-sen University Young Teacher Key Cultivation Project(18ykzd05 to X.K.)the Natural Science Foundation of Guangdong(2016A030313262 to X.M.)the National Natural Science Foundation of China(82170924 to X.K.,81700928 to L.M.)the Youth Teacher Training Project of Sun Yat-sen University(17ykpy71 to L.M.).
文摘Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.
基金the National Natural Science Foundation of China(Nos.81902356,82072581,21971265 and 82272842)Programs for Medical Science and Technology Research Project of Henan Province Health Commission(Nos.2018020025,SB201901029)+2 种基金Henan Province Young and Middle-Aged Health Science and Technology Innovation Talent Project(No.YXKC2022032)Shenzhen Key Laboratory of Functional Aggregate Materials(No.ZDSYS20211021111400001)Provincial Science and Technology R&D Program Joint Fund of the Department of Science and Technology of Henan Province(superior discipline cultivation category)Key Project(No.222301420018)。
文摘The application of fluorescent probes for in vivo retinal imaging is of great importance,which could provide direct and crucial imaging evidence for a better understanding of common eye diseases.Herein,a group of bright organic luminogens with typical electron-donating(D)and electron-accepting(A)structures(abbreviated as LDs-BDM,LDs-BTM,and LDs-BHM)was synthesized through a simple single-step reaction.They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70%(e.g.,83.7%for LDs-BTM).Their light-emission properties could be tuned by the modulation ofπ-conjugation effect with methoxy groups at different substituent positions.Their resulting fluorescent nanoparticles(NPs)were demonstrated as specific lipid droplets(LDs)targeting probes with high brightness,good biocompatibility,and satisfactory photostability.LDs-BTM NPs with a large two-photon absorption cross section(σ2=249 GM)were further utilized as ultrabright two-photon fluorescence(2PF)nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration(0.5μmol/L).Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated.This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique.These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.
基金supported by the National Natural Science Foundation of China(22101028,21788102)the start-up funding from Beijing Normal University(310432102,310432103)+3 种基金the Innovation and Technology Commission(ITC-CNERC14SC01)the Science and Technology Plan of Shenzhen(JCYJ20160229205601482,JCYJ20180507183832744,JCYJ20170818113602462)the Natural Science Foundation of Guangdong Province(2019B121205002)the Research Grants Council of Hong Kong(16305618,16304819,16305320,NHKUST609/19,C6009-17G,C6014-20W/16)。
文摘The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of dual-activated alkyne and pyridines was developed to construct novel N-heterocyclic poly(quinolizine)s. This polymerization can proceed smoothly under catalystfree conditions with 100% atom utilization to furnish poly(quinolizine)s with high molecular weights(up to 34,100) and welldefined structures in acceptable yields. The resulting polymers show good solubility, high thermal stability and strong red emission. Moreover, the prepared poly(quinolizine)s exhibit low cytotoxicity and can selectively label lysosomes in live cells.Considering the remarkable advantages of readily available raw materials, mild polymerization conditions, atom economy, and excellent product performance, this new and efficient polymerization tool will open up enormous opportunities for preparing functional N-heterocyclic polymers.
基金supported by the National Natural Science Foundation of China(81790633,61922047,81830054,81902412,81903184,81988101,91859205,21788102,51620105009)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-0007-E00065,21XD1404600)+4 种基金the Research Grants Council of Hong Kong(16306620,N_HKUST609/19 and C6014-20W)the Innovation and Technology Commission(ITC-CNERC14SC01,ITCPD/17-9,MHP/047/19 and ITS/301/18FX)the support of Shanghai Key Laboratory of Hepato-biliary Tumor BiologyMilitary Key Laboratory on Signal Transductionsupported by the Innovation Program of Shanghai Municipal Education Commission。
文摘Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several types of cancers,and ferroptosis inducers can be used to promote ferroptosis in tumor cells and play an anti-tumor role.However,the specificity and efficacy of ferroptosis inducers remain unsatisfactory.Here,a new mitochondria-targeted photosensitizer(PS)with aggregation-induced emission(AIE)characteristic named TCSVP was designed,which efficiently generates ROS in mitochondria after light exposure.TCSVP administration significantly sensitizes tumor cells to ferroptosis inducer(RSL3)-mediated cell death by specifically and light-dependently triggering a moderate ROS generation in vitro and in vivo.Mechanically,the expression levels of ferroptosis related proteins Acyl-CoA synthetase long-chain family member 4(FACL4/ACSL4)and cyclooxygenase-2(COX2)were increased in TCSVP/RSL3-treated cells after light exposure,coupled with decreased Glutathione peroxidase 4(GPX4)activity and excessive malondialdehyde(MDA)accumulation.This study declared that light-induced moderate ROS generation within mitochondria in cancer cells by AIE-PS can be used to enhance the specificity and efficacy of ferroptosis inducers,bringing a new synergistic strategy for tumor intervention.
文摘Polymers are everywhere.The living kingdom is full of natural polymers or biological macromolecules(e.g.,polysaccharides,polynucleotides and proteins),while the modern society is alive with synthetic polymers or manmade macromolecules(e.g.,plastics,fibers and rubbers).