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1.
Biomaterials ; 279: 121227, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34736151

RESUMO

Bacterial keratitis (BK) is one of the most commonly leading causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Herein, we report a cationic diphenyl luminogen with aggregation-induced emission called IQ-Cm containing isoquinolinium and coumarin units for theranostic study of BK. IQ-Cm has no obvious cytotoxicity to mammalian cells below a certain concentration, and could preferentially bind to bacteria over mammalian cells. IQ-Cm can be used as a sensitive self-reporting probe to rapidly discriminate live and dead bacteria by the visual emission colors. The intrinsic dark toxicity to bacteria and generation of reactive oxygen species under light irradiation endow IQ-Cm with excellent antibacterial activity in vitro and in BK rabbit models infected with S. aureus. The present study provides a sensitive and efficient theranostic strategy for rapid discrimination of various bacterial states and the combined treatment of BK based on the intrinsic dark antibacterial activity and photodynamic therapy effect.

2.
Adv Mater ; : e2105113, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605067

RESUMO

Microscopic control of macroscopic phenomena is one of the core subjects in materials science. Particularly, the spatio-temporal control of material behaviors through a non-contact way is of fundamental importance but is difficult to accomplish. Herein, a strategy to realize remote spatio-temporal control of luminescence behaviors is reported. A multi-arm salicylaldehyde benzoylhydrazone-based aggregation-induced emission luminogen (AIEgen)/metal-ion system, of which the fluorescence can be gated by the UV irradiation with time dependency, is developed. By changing the metal-ion species, the fluorescence emission and the intensity can also be tuned. The mechanism of the UV-mediated fluorescence change is investigated, and it is revealed that a phototriggered aggregation-induced emission (PTAIE) process contributes to the behaviors. The AIEgen is further covalently integrated into a polymeric network and the formed gel/metal-ion system can achieve laser-mediated mask-free writing enabled by the PTAIE process. Moreover, by further taking advantage of the time-dependent self-healing property of hydrazone-based dynamic covalent bond, transformable 4D soft patterns are generated. The findings and the strategy increase the ways to manipulate molecules on the supramolecule or aggregate level. They also show opportunities for the development of controllable smart materials and expand the scope of the materials in advanced optoelectronic applications.

3.
JACS Au ; 1(3): 344-353, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-34467298

RESUMO

Photoresponsive polymers have attracted extensive attention due to their tunable functionalities and advanced applications; thus, it is significant to develop facile in situ synthesis strategies, extend polymers family, and establish various applications for photoresponsive polymers. Herein, we develop a catalyst-free spontaneous polymerization of dihaloalkynes and disulfonic acids without photosensitive monomers for the in situ synthesis of photoresponsive polysulfonates at room temperature in air with 100% atom economy in high yields. The resulting polysulfonates could undergo visible photodegradation with strong photoacid generation, leading to various applications including dual-emissive or 3D photopatterning, and practical broad-spectrum antibacterial activity. The halogen-rich polysulfonates also exhibit a high and photoswitched refractive index and could undergo efficient postfunctionalizations to further expand the variety and functionality of photoresponsive heteroatom-containing polyesters.

4.
Nanoscale ; 13(32): 13610-13616, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34477635

RESUMO

Biofilm-related infections, such as dental plaque, chronic sinusitis, native valve endocarditis, and chronic airway infections in cystic fibrosis have brought serious suffering to patients and financial burden to society. Materials that can eliminate mature biofilms without developing drug resistance are promising tools to treat biofilm-related infections, and thus they are in urgent demand. Herein, we designed and readily prepared organic nanoparticles (NPs) with highly efficient photothermal conversion by harvesting energy via excited-state intramolecular motions and enlarging molar absorptivity. The photothermal NPs can sufficiently eliminate mature bacterial biofilms upon low-power near-infrared laser irradiation. NPs hold great promise for the rapid eradication of bacterial biofilms by photothermal therapy.


Assuntos
Antibacterianos , Nanopartículas , Antibacterianos/farmacologia , Biofilmes , Humanos , Terapia Fototérmica
5.
Adv Healthc Mater ; : e2101055, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418306

RESUMO

The emergence of the concept of aggregation-induced emission (AIE) has opened new opportunities in many research areas, such as biopsy analysis, biological processes monitoring, and elucidation of key physiological and pathological behaviors. As a new class of luminescent materials, AIE luminogens (AIEgens) possess many prominent advantages such as tunable molecular structures, high molar absorptivity, high brightness, large Stokes shift, excellent photostability, and good biocompatibility. The past two decades have witnessed a dramatic growth of research interest in AIE, and many AIE-based bioprobes with excellent performance have been widely explored in biomedical fields. This review summarizes some of the latest advancements of AIE molecular probes and AIE nanoparticles (NPs) with regards to biomedical and healthcare applications. According to the research areas, the review is divided into five sections, which are imaging and identification of cells and bacteria, photodynamic therapy, multimodal theranostics, deep tissue imaging, and fluorescence-guided surgery. The challenges and future opportunities of AIE materials in the advanced biomedical fields are briefly discussed. In perspective, the AIE-based bioprobes play vital roles in the exploration of advanced bioapplications for the ultimate goal of addressing more healthcare issues by integrating various cutting-edge modalities and techniques.

6.
Annu Rev Anal Chem (Palo Alto Calif) ; 14(1): 413-435, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314222

RESUMO

Physiological dynamics in living cells and tissues are crucial for maintenance and regulation of their normal activities and functionalities. Tiny fluctuations in physiological microenvironments can leverage significant influences on cell growth, metabolism, differentiation, and apoptosis as well as disease evolution. Fluorescence imaging based on aggregation-induced emission luminogens (AIEgens) exhibits superior advantages in real-time sensing and monitoring of the physiological dynamics in living systems, including its unique properties such as high sensitivity and rapid response, flexible molecular design, and versatile nano- to mesostructural fabrication. The introduction of canonic AIEgens with long-wavelength, near-infrared, or microwave emission, persistent luminescence, and diversified excitation source (e.g., chemo- or bioluminescence) offers researchers a tool to evaluate the resulting molecules with excellent performance in response to subtle fluctuations in bioactivities with broader dimensionalities and deeper hierarchies.


Assuntos
Corantes Fluorescentes , Luminescência
7.
Adv Mater ; 33(36): e2102258, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34309084

RESUMO

Solar-driven interfacial steam generation (SISG) has been recognized as a promising strategy to solve water shortages in an eco-friendly and low-cost way. However, the practical application of SISG is vitally restricted by some inherent limits, especially for finite evaporation rate and insufficient working life of evaporator. Herein, a novel SISG system involving an all-fiber porous cylinder-like foam 3D evaporator, side area-assisted evaporation protocol, and aggregation-induced-emission-active solar absorber with "one stone two birds" function is explored. The solar absorber exhibits efficient photothermal conversion, endowing the side area-assisted evaporator with as high as 3.6 kg m-2 h-1 of solar evaporation rate, which is highly desirable for SISG under 1 sun of irradiation. Moreover, the solar absorber is capable of powerfully producing reactive oxygen species upon sunlight irradiation, which results in extraordinary photodynamic killing of bacteria nearby the fiber to prevent biofouling, consequently improving the working life of evaporator.

8.
J Am Chem Soc ; 143(30): 11820-11827, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34292706

RESUMO

Molecular motions are essential natures of matter and play important roles in their structures and properties. However, owing to the diversity and complexity of structures and behaviors, the study of motion-structure-property relationships remains a challenge, especially at all levels of structural hierarchy from molecules to macro-objects. Herein, luminogens showing aggregation-induced emission (AIE), namely, 9-(pyrimidin-2-yl)-carbazole (PyCz) and 9-(5-R-pyrimidin-2-yl)-carbazole [R = Cl (ClPyCz), Br (BrPyCz), and CN (CyPyCz)], were designed and synthesized, to decipher the dependence of materials' structures and properties on molecular motions at the molecule and aggregate levels. Experimental and theoretical analysis demonstrated that the active intramolecular motions in the excited state of all molecules at the single-molecule level endowed them with more twisted structural conformations and weak emission. However, owing to the restriction of intramolecular motions in the nano/macroaggregate state, all the molecules assumed less twisted conformations with bright emission. Unexpectedly, intermolecular motions could be activated in the macrocrystals of ClPyCz, BrPyCz, and CyPyCz through the introduction of external perturbations, and synergic strong and weak intermolecular interactions allowed their crystals to undergo reversible deformation, which effectively solved the problem of the brittleness of organic crystals, while endowing them with excellent elastic performance. Thus, the present study provided insights on the motion-structure-property relationship at each level of structural hierarchy and offered a paradigm to rationally design multifunctional AIE-based materials.

9.
ACS Nano ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34181408

RESUMO

The development of effective antifungal agents remains a big challenge in view of the close evolutionary relationship between mammalian cells and fungi. Moreover, rapid mutations of fungal receptors at the molecular level result in the emergence of drug resistance. Here, with low tendency to develop drug-resistance, the subcellular organelle mitochondrion is exploited as an alternative target for efficient fungal killing by photodynamic therapy (PDT) of mitochondrial-targeting luminogens with aggregation-induced emission characteristics (AIEgens). With cationic isoquinolinium (IQ) moiety and proper hydrophobicity, three AIEgens, namely, IQ-TPE-2O, IQ-Cm, and IQ-TPA, can preferentially accumulate at the mitochondria of fungi over the mammalian cells. Upon white light irradiation, these AIEgens efficiently generate reactive 1O2, which causes irreversible damage to fungal mitochondria and further triggers the fungal death. Among them, IQ-TPA shows the highest PDT efficiency against fungi and negligible toxicity to mammalian cells, achieving the selective and highly efficient killing of fungi. Furthermore, we tested the clinical utility of this PDT strategy by treating fungal keratitis on a fungus-infected rabbit model. It was demonstrated that IQ-TPA presents obviously better therapeutic effects as compared with the clinically used rose bengal, suggesting the success of this PDT strategy and its great potential for clinical treatment of fungal infections.

10.
Angew Chem Int Ed Engl ; 60(35): 19222-19231, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-33991002

RESUMO

We reported an efficient multicomponent polyannulation for in situ generation of heteroaromatic hyperbranched polyelectrolytes by using readily accessible internal diynes and low-cost, commercially available arylnitriles, NaSbF6 , and H2 O/AcOH. The polymers were obtained in excellent yields (up to 99 %) with extraordinary high molecular weights (Mw up to 1.011×106 ) and low polydispersity indices. The resulting polymers showed good processibility and high quantum yields with tunable emission in the solid state, making them ideal materials for highly ordered fluorescent photopatterning. These hyperbranched polyelectrolytes also possessed strong ability to generate reactive oxygen species, which allowed their applications in efficient bacterial killing and customizable photodynamic patterning of living organisms in a simple and cost-effective way.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Hidrocarbonetos Aromáticos/farmacologia , Polieletrólitos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Bactérias/metabolismo , Compostos Heterocíclicos/química , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Peso Molecular , Polieletrólitos/síntese química , Polieletrólitos/química , Espécies Reativas de Oxigênio/metabolismo
11.
Adv Sci (Weinh) ; 8(9): 2001750, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33977040

RESUMO

Bacteria infected cells acting as "Trojan horses" not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden internalized bacteria, especially multidrug-resistant (MDR) bacteria. Herein, aggregation-induced emission luminogens (AIEgens) such as N,N-diphenyl-4-(7-(pyridin-4-yl) benzo [c] [1,2,5] thiadiazol-4-yl) aniline functionalized with 1-bromoethane (TBP-1) and (3-bromopropyl) trimethylammonium bromide (TBP-2) (TBPs) show potent broad-spectrum bactericidal activity against both extracellular and internalized Gram-positive pathogens. TBPs trigger reactive oxygen species (ROS)-mediated membrane damage to kill bacteria, regardless of light irradiation. TBPs effectively kill bacteria without the development of resistance. Additionally, such AIEgens activate mitochondria dependent autophagy to eliminate internalized bacteria in host cells. Compared to the routinely used vancomycin in clinic, TBPs demonstrate comparable efficacy against methicillin-resistant Staphylococcus aureus (MRSA) in vivo. The studies suggest that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.

12.
ACS Nano ; 15(5): 9176-9185, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33939413

RESUMO

Gold complexes have been recognized as potential anticancer agents against various kinds of diseases due to their inherent suppressions of antioxidant thioredoxin reductase (TrxR) activity. Herein, a powerful aggregation-induced emission luminogen (AIEgen), TBP-Au, was designed and synthesized by integrating an anticancer Au(I) moiety with an AIE-active photosensitizer (TBP), in which both the production and consumption routes of reactive oxygen species (ROS) were elaborately considered simultaneously to boost the anticancer efficacy. It has been demonstrated that TBP-Au could realize superior two-photon fluorescence imaging in tumor tissues with high resolution and deep penetration as well as long-term imaging in live animals due to its AIE property. In addition, the introduction of a special Au(I) moiety could tune the organelle specificity and efficiently facilitate the ROS-determined photodynamic therapy (PDT). More impressively, TBP-Au could efficiently eliminate cancer cells under light irradiation through the preconceived synergetic approaches from the PDT and the effective suppression of TrxR, demonstrating that TBP-Au holds great potential for precise cancer theranostics.


Assuntos
Ouro , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Animais , Antioxidantes , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
13.
Nat Commun ; 12(1): 960, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574252

RESUMO

Nitric oxide (NO) is an important signaling molecule overexpressed in many diseases, thus the development of NO-activatable probes is of vital significance for monitoring related diseases. However, sensitive photoacoustic (PA) probes for detecting NO-associated complicated diseases (e.g., encephalitis), have yet to be developed. Herein, we report a NO-activated PA probe for in vivo detection of encephalitis by tuning the molecular geometry and energy transformation processes. A strong donor-acceptor structure with increased conjugation can be obtained after NO treatment, along with the active intramolecular motion, significantly boosting "turn-on" near-infrared PA property. The molecular probe exhibits high specificity and sensitivity towards NO over interfering reactive species. The probe is capable of detecting and differentiating encephalitis in different severities with high spatiotemporal resolution. This work will inspire more insights into the development of high-performing activatable PA probes for advanced diagnosis by making full use of intramolecular motion and energy transformation processes.


Assuntos
Técnicas Biossensoriais/métodos , Encefalite/diagnóstico , Encefalite/metabolismo , Óxido Nítrico/isolamento & purificação , Técnicas Fotoacústicas/métodos , Animais , Técnicas Biossensoriais/instrumentação , Modelos Animais de Doenças , Encefalite/patologia , Masculino , Camundongos , Imagem Molecular/métodos , Sondas Moleculares/química , Técnicas Fotoacústicas/instrumentação
14.
Biomaterials ; 268: 120598, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33321291

RESUMO

Pathogenic microbes can cause infections or diseases in hosts and they pose ongoing threats to human health. Antibiotics have been taken an active role in treating a wide variety of infections or diseases since they were first introduced in the 1940s. However, the emergence of antibiotic-resistant microbes makes these previously effective drugs invalid regrettably. So it is urgently needed to accelerate research and development for new antimicrobial systems and strategies. Recently, luminogens with aggregation-induced emission characteristics (AIEgens) have emerged as powerful fluorescent tools for microbial detection and antimicrobial therapy. In this review, we highlighted the latest advancements of AIEgen-based biofunctional materials and systems in this research field. AIE fluorescent probes have the advantages of excellent sensitivity and rapid response, which make them useful for ultrafast bacterial imaging, bacteria classification, and pathogen discrimination. Early microbial detection and identification could help us study the mechanism of antibiotic resistance more scientifically. Moreover, the AIEgens-based photosensitizers (AIE-PSs) with strong photosensitization show good performance on the efficient elimination of multidrug-resistant bacteria and intracellular bacteria. At the end of the review, a short perspective on aggregate science is concluded.


Assuntos
Anti-Infecciosos , Fármacos Fotossensibilizantes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana Múltipla , Corantes Fluorescentes , Humanos , Fármacos Fotossensibilizantes/farmacologia
15.
Chem Commun (Camb) ; 56(93): 14613-14616, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33150877

RESUMO

A new ratiometric fluorescent probe, namely TPE-RNS, has been developed for detecting intracellular HClO/ClO- in living cells and discriminating cancer cells from normal cells. Based on the ratiometric fluorescence properties conferred by the AIE and DTBET effects, this probe has excellent sensitivity and specificity for the HCIO response.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/química , Animais , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , Humanos , Camundongos , Microscopia de Fluorescência , Células RAW 264.7
16.
ACS Nano ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33197171

RESUMO

Photodynamic therapy (PDT), a noninvasive therapeutic strategy for cancer treatment, which always suffers from the low reactive oxygen species (ROS) yield of traditional organic dyes. Herein, we present lipid-encapsulated aggregation-induced emission nanoparticles (AIE NPs) that have a high quantum yield (23%) and a maximum two-photon absorption (TPA) cross-section of 560 GM irradiated by near-infrared light (800 nm). The AIE NPs can serve as imaging agents for spatiotemporal imaging of tumor tissues with a penetration depth up to 505 µm on mice melanoma model. Importantly, the AIE NPs can simultaneously generate singlet oxygen (1O2) and highly toxic hydroxyl radicals (•OH) upon irradiation with 800 nm irradiation for photodynamic tumor ablation. In addition, the AIE NPs can be effectively cleared from the mouse body after the imaging and therapy. This study provides a strategy to develop theranostic agents for cancer image-guided PDT with high brightness, superior photostability, and high biosafety.

17.
ACS Nano ; 14(10): 14228-14239, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33001627

RESUMO

The brightness of organic fluorescence materials determines their resolution and sensitivity in fluorescence display and detection. However, strategies to effectively enhance the brightness are still scarce. Conventional planar π-conjugated molecules display excellent photophysical properties as isolated species but suffer from aggregation-caused quenching effect when aggregated owing to the cofacial π-π interactions. In contrast, twisted molecules show high photoluminescence quantum yield (ΦPL) in aggregate while at the cost of absorption due to the breakage in conjugation. Therefore, it is challenging to integrate the strong absorption and high solid-state ΦPL, which are two main indicators of brightness, into one molecule. Herein, we propose a molecular design strategy to boost the brightness through the incorporation of planar blocks into twisted skeletons. As a proof-of-concept, twisted small-molecule TT3-oCB with larger π-conjugated dithieno[3,2-b:2',3'-d]thiophene unit displays superb brightness at the NIR-IIb (1500-1700 nm) than that of TT1-oCB and TT2-oCB with smaller thiophene and thienothiophene unit, respectively. Whole-body angiography using TT3-oCB nanoparticles presents an apparent vessel width of 0.29 mm. Improved NIR-IIb image resolution is achieved for femoral vessels with an apparent width of only 0.04 mm. High-magnification through-skull microscopic NIR-IIb imaging of cerebral vasculature gives an apparent width of ∼3.3 µm. Moreover, the deeply located internal organ such as bladder is identified with high clarity. The present molecular design philosophy embodies a platform for further development of in vivo bioimaging.


Assuntos
Corantes Fluorescentes , Nanopartículas , Fluorescência , Esqueleto , Tiofenos
18.
Biomaterials ; 261: 120340, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32866841

RESUMO

Although phagocytosis serves as the front line to attack invading pathogens, its low bacterial encounter and killing rates leads to an ineffective bactericidal output. In view of this, developing multifunctional theranostic probe to effectively discriminate and ablate intracellular bacteria is highly desirable. However, the shielding effect of the host macrophages put the detection and elimination of macrophage-engulfed bacteria into a challenging task. Herein, we utilize a luminogen with aggregation-induced emission (AIE) characteristics, namely TTVP, as a simple and effective probe for simultaneous tracing and photodynamic killing of intracellular Gram-positive bacteria. With the help of the AIE property, excellent water solubility, near-infrared (NIR) emission and strong reactive oxygen species (ROS) generating ability, TTVP performed ideally to be a targeting agent to intracellular Gram-positive bacteria with high signal contrast, as well as to be a photosensitizer to effectively ablate intracellular bacteria without attacking host macrophages. This work thus provides insights for the next generation antibiosis theranostic application for potential clinical trials.


Assuntos
Bactérias Gram-Positivas , Fotoquimioterapia , Antibacterianos/farmacologia , Macrófagos , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio
19.
J Am Chem Soc ; 142(35): 15146-15156, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32786775

RESUMO

Semiconducting polymer nanoparticles (SPNs) emitting in the second near-infrared window (NIR-II, 1000-1700 nm) are promising materials for deep-tissue optical imaging in mammals, but the brightness is far from satisfactory. Herein, we developed a molecular design strategy to boost the brightness of NIR-II SPNs: structure planarization and twisting. By integration of the strong absorption coefficient inherited from planar π-conjugated units and high solid-state quantum yield (ΦPL) from twisted motifs into one polymer, a rise in brightness was obtained. The resulting pNIR-4 with both twisted and planar structure displayed improved ΦPL and absorption when compared to the planar polymer pNIR-1 and the twisted polymer pNIR-2. Given the emission tail extending into the NIR-IIa region (1300-1400 nm) of the pNIR-4 nanoparticles, NIR-IIa fluorescence imaging of blood vessels with enhanced clarity was observed. Moreover, a pH-responsive poly(ß-amino ester) made pNIR-4 specifically accumulate at tumor sites, allowing NIR-IIa fluorescence image-guided cancer precision resection. This study provides a molecular design strategy for developing highly bright fluorophores.

20.
Adv Mater ; 32(36): e2001457, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32734656

RESUMO

Molecular science entails the study of structures and properties of materials at the level of single molecules or small interacting complexes of molecules. Moving beyond single molecules and well-defined complexes, aggregates (i.e., irregular clusters of many molecules) serve as a particularly useful form of materials that often display modified or wholly new properties compared to their molecular components. Some unique structures and phenomena such as polymorphic aggregates, aggregation-induced symmetry breaking, and cluster excitons are only identified in aggregates, as a few examples of their exotic features. Here, by virtue of the flourishing research on aggregation-induced emission, the concept of "aggregate science" is put forward to fill the gaps between molecules and aggregates. Structures and properties on the aggregate scale are also systematically summarized. The structure-property relationships established for aggregates are expected to contribute to new materials and technological development. Ultimately, aggregate science may become an interdisciplinary research field and serves as a general platform for academic research.

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