基于AIEgens增强的CRISPR/Cas12a荧光探针设计及在单核细胞增生李斯特菌快速检测中的应用

研制了一种基于聚集诱导发光染料(aggregation-induced emission fluorogens,AIEgens)增强的荧光探针,建立了基于重组酶聚合酶扩增(recombinase polymerase amplification,RPA)结合CRISPR/Cas12a高灵敏检测单核细胞增生李斯特菌(Listeria monocytogenes,LM)的新方法。利用阳离子AIEgens与双链DNA结合荧光极大增强的特性,构建了一种含双链以及单链DNA的探针。该探针5’末端携带一个荧光淬灭基团,双链DNA片段结合了多个AIEgens;利用crRNA可准确识别靶标序列并激活Cas12a反式切割活性的特点,切割荧光探针单链DNA产生荧光信号,从而实现LM高灵敏检测。将AIEgens增强型荧光探针与CRISPR/Cas12a结合,在无扩增情况下检测DNA片段的检出限为0.37 pmol·L^(-1),灵敏度较传统荧光探针高40倍。将以上检测体系与RPA反应联用,检测LM的检出限为3×10^(1) CFU·mL^(-1);该方法检测人工污染LM的牛奶以及金针菇样本,批内以及批间平均回收率介于91.14%~108.47%,变异系数小于12.71%。构建了一种基于AIEgens增强的CRISPR/Cas荧光探针,极大地提高了基于荧光信号输出的CRISPR/Cas方法检测灵敏度,实现了食源性致病菌的高灵敏检测。

基于AIEgens的现场可视化方法检测环境中新型冠状病毒污染的气溶胶

新型冠状病毒暴露场所的气溶胶现场快速检测有助于快速采取控制传染措施,保证公共环境安全。该研究基于便携式聚合酶链式反应(PCR)仪和聚集诱导发光探针(AIE luminogens,AIEgens),与大气颗粒物采样器结合,建立了新型冠状病毒污染气溶胶样品的可视化识别方法。首先对阳性质粒样品进行PCR扩增,再与AIEgens 1,1,2,2-四[4-(2-溴-乙氧基)苯基]乙烯(TTAPE)结合后发出蓝色荧光。在紫外灯下用肉眼或便携式智能手机可以清楚地观察。结果表明,阳性质粒可被肉眼或智能设备检出,而阴性样品不发光,证明了方法的特异性。研究发现阳性质粒质量浓度为5 ng/L时仍然可以实现可视化区分。将该便携式系统应用于新型冠状病毒污染气溶胶实际样品的现场筛查,结果均为阴性。

D-π-A-π-D型小分子红光材料的制备及其性能

开发新型有机红光材料对于制备高性能红光有机电致发光器件具有重要的研究意义。本文采用SUZUKI偶联反应,以芴酮为受体(A)、3,4,5-三甲氧基苯为给体(D)合成了新型D-π-A-π-D结构的有机红光材料(3MeFO)。通过1H NMR谱、13 C NMR谱和X单晶衍射确认了分子结构,该化合物展示了较强的电荷转移作用和良好的共轭结构,其晶体的发射峰达到620 nm。从单晶结构中看出甲氧基的引入有利于在分子间形成大量的氢键,有效地增强了分子间的相互作用。同时,该材料表现出良好的热稳定性能和电化学性能,使得其在OLED中展示了良好的电致发光性能。

Machine learning-based real-time visible fatigue crack growth detection

Many large-scale and complex structural components are applied in the aeronautics and automobile industries.However,the repeated alternating or cyclic loads in service tend to cause unexpected fatigue fractures.Therefore,developing real-time and visible monitoring methods for fatigue crack initiation and propagation is critically important for structural safety.This paper proposes a machine learning-based fatigue crack growth detection method that combines computer vision and machine learning.In our model,computer vision is used for data creation,and the machine learning model is used for crack detection.Then computer vision is used for marking and analyzing the crack growth path and length.We apply seven models for the crack classification and find that the decision tree is the best model in this research.The experimental results prove the effectiveness of our method,and the crack length measurement accuracy achieved is 0.6 mm.Furthermore,the slight machine learning models help us realize real-time and visible fatigue crack detection.

基于近红外聚集诱导发光分子的磁性纳米材料用于光增强杀菌

近红外光敏剂由于荧光成像具有光损伤小、穿透力强和空间分辨率高等优点,能显著提高光动力治疗效果。我们合成了近红外聚集诱导探针5,6-2(4′-(二苯氨酚)-[1,1′-联苯]-4-yl)吡嗪-2,3-二甲腈(DCDPP-2TPA)用于光增强杀菌。利用聚集态/固态下荧光增强的优势,DCDPP-2TPA与磁性Fe_(3)O_(4)纳米材料复合,产生更高活性氧(ROS)用于杀菌。利用SEM、TEM、XRD和荧光光谱研究了该复合材料的结构和性质,并用于大肠杆菌和金黄色葡萄球菌杀菌实验。结果表明,在光照下两种细菌的存活率为7.5%与9.0%,优于DCDPP-2TPA(10%与14%)。同时该复合材料可以方便地实现磁性分离,在光照下产生ROS后循环杀菌。

基于蒽醌的红色延迟荧光材料的设计合成及光电性质

由于受到能隙定律的严重约束,激发态的有机红光材料的非辐射衰减较大,从而导致其荧光量子产率普遍较低。该文利用电子给/受体(donor-acceptor,D-A)之间不同的连接方式,在有无苯环作为π桥的情况下合成了AQ-2DPAC和AQ-2PDPAC两种红光蒽醌材料。并系统地研究了上述两种材料的电子结构、热性能、光物理性能和电致发光性能,以评估苯环作为π桥对材料发光性能的影响。两种蒽醌材料采取高度扭曲构造,均具有优良的聚集诱导发光和延迟荧光特性。该研究表明,就两种电荷转移发光材料而言,苯环作为π桥的引入使D-A得到了更有效的分离,并减小了最低单重态和三重态激发态之间的能级差,提高了辐射复合速率,从而提高荧光量子产率。因此,荧光量子产率从D-A型分子AQ-2DPAC的19%显著提升至D-π-A型分子AQ-2PDPAC的52%。采用AQ-2PDPAC发光材料的有机发光二极管器件性能更为优异,最大外量子效率为13.7%,最大亮度为12260 cd·m^(-2)。

Effects of nonaromatic through-bond conjugation and through-space conjugation on the photoluminescence of nontraditional luminogens

Photoluminescence(PL)mechanisms of nontraditional luminogens(NTLs)have attracted great interest,and they are generally explained with intra/intermolecular through-space conjugation(TSC)of nonconventional chromophores.Here a new concept of nonaromatic through-bond conjugation(TBC)is proposed and it is proved that it plays an important role in the PL of NTLs.The PL behaviors of the three respective isomers of cyclohexanedione and gemdimethyl-1,3-cyclohexanedione were studied and correlated with their chemical and aggregate structures.These compounds show differentfluorescence emissions as well as dif-ferent concentration,excitation and solvent-dependent emissions.The compounds which undergo keto-enol tautomerism and hence with a conjugated ketone-enol structure(i.e.,nonaromatic TBC)show more red-shifted emissions.TBC effect reduces the energy gaps and facilitates the formation of stronger TSC in the aggre-gate state.The compounds in the ketone-enol form are also prone to occur excited state intra/intermolecular proton transfer(ESIPT).The cooperative effect of nonaro-matic TBC and TSC determines the PL behaviors of NTLs.This work provides a novel understanding of the PL mechanisms of NTLs and is of great importance for directing the design and synthesis of novel NTLs.

Triphenylamine-AIEgens photoactive materials for cancer theranostics

Triphenylamine(TPA)-based aggregation-induced emission luminogens(TPA-AIEgens),a type of photoactive material utilizing the typical TPA moiety,has recently attracted increasing attention for the diagnostics and treatment of tumors due to their remarkable chemo-physical performance in optoelectronic research.TPA-AIEgens are distinguished from other photoactive agents by their strong fluorescence,good sensitivity,high signal-to-noise ratio,resistance to photobleaching,and lack of high concentration or aggregation-caused fluoresce quenching effects.In this review,we summarize the current advancements and the biomedical progress of TPA-AIEgens in tumor theranostics.First,the design principles of TPAAIEgens photoactive agents as well as the advanced targeting strategies for nuclei,cell membranes,cell organelle and tumors were introduced,respectively.Next,the applications of TPA-AIEgens in tumor diagnosis and therapeutic techniques were reviewed.Last,the challenges and prospects of TPA-AIEgens for cancer therapy were performed.The given landscape of the TPA-AIEgens hereby is meaningful for the further design and utilization of the novel photoactive material,which could be beneficial for the development of clinic applications.

Molecular docking-aided AIEgen design: concept, synthesis and applications

Aggregate-induced emission luminogens(AIEgens) have been widely used in biological imaging, chemical sensing, and disease treatments. The rational design and construction of AIEgens have received considerable research interests during the last few years. Herein, molecular docking-aided AIEgen design has been reasonably proposed and AIEgen TBQZY with excellent ~1O_(2) generation ability has been synthesized. The newly developed TBQZY could efficiently kill S. epidermidis and methicillinresistant S. epidermidis(MRSE) by tightly binding to bacteria and triggering the accumulation of ~1O_(2) in bacteria. TBQZY specifically regulated the immune system and polarized macrophages from M1 to M2 to accelerate the elimination of biofilm in vivo. In addition, healing acceleration was observed in chronic wounds treated with TBQZY, and side effects were negligible.Meanwhile, TBQZY had extraordinary potential for combating drug-resistant bacteria in the clinical setting. This research not only provided new concepts for the design of AIEgens, but also shed some lights on the discovery of drugs against drug-resistant bacteria.

Photodynamic and photothermal therapies for bacterial infection treatment

Bacteria can cause numerous infectious diseases and has been a major threat to human humans.Although antibiotics have partially succeeded in treating bacteria,owing to antibiotic abuse,the emergence of multidrug-resistant(MDR)bacteria has drastically diminished their potency.Since the invention of laser,the combination of light and photosensitizers,photodynamic therapy(PDT),has become an effective noninvasive treatment along with photothermal therapy(PTT),in which heat is generated by nonradiative relaxation.Antimicrobial PDT and PTT are emerging as effective treatments for bacterial infection,particularly against MDR bacteria.This mini review covers the recent progresses in PDT and PTT for bacterial treatment.

Crystallization-induced phosphorescence of pure organic luminogens

This review summarizes the recent progress of efficient room temperature phosphorescence（RTP） from pure organic luminogens achieved by crystallization-induced phosphorescence（CIP）,with focus on the advances in our group.Besides homocrystals,mixed crystals and cocrystals are also discussed.Meanwhile,intriguing RTP emission from the luminogens without conventional chromophores is demonstrated.

A highly sensitive DNA-AIEgen-based ＂turn-on＂ fluorescence chemosensor for amplification analysis of Hg^2+ ions in real samples and living cells

Functional nucleic acids(FNAs)-based biosensors have shown great potential in heavy metal ions detection due to their low-cost and easy to operate merits. However, in most FNAs based fluorescence probes, the ingenious designs of double-labeled(fluorophore and quencher group) DNA sequence, not only bring the annoyance of organic synthesis, but also restrict its use as a robust biosensor in practical duties. In this paper, we design a simple AIEgens functional nucleic acids(AFNAs) probe which consists of only fluorogen but no quencher group. With the help of duplex-specific nuclease(DSN) enzyme based target recycling, high fluorescence signal and superior sensitivity towards Hg^(2+) are achieved. This robust assay allows for sensitive and selective detection of Hg^(2+) in real water samples and mapping of intracellular Hg^(2+), without double-labeling of oligonucleotide with a dye-quencher pair, nor the multiple assay steps.

A gelable pure organic luminogen with fluorescence-phosphorescence dual emission

Pure organic luminogens with room temperature phosphorescence(RTP) have drawn much attention due to their fundamental importance and promising applications in optoelectronic devices, bioimaging, sensing, etc. Fluorescence-phosphorescence dual emission at room temperature, however, is rarely observed in pure organic materials. Herein, we reported a metal-and heavy-atom free pure organic luminogen with tert-butyl groups, DtBuCZBP, which is ready to form organogels in dimethylsulfoxide(DMSO).It emits prompt and delayed fluorescence, as well as RTP, namely dual emission in as-prepared solid, gels and polymeric films.To the best of our knowledge, it is the first example of metal-and heavy-atom free pure organic gelator with RTP emission. Such unique RTP and moreover dual emission properties in different states make DtBuCZBP a potential material for diverse applications.

Stimulus-responsive room temperature phosphorescence in purely organic luminogens

Luminogens that exhibit stimulus-responsive room temperature phosphorescence(RTP)have attracted significant attention for their applications in a wide range of fields such as data storage,sensors,and bio-imaging.However,very few such materials are known,partly because of the unclear internal mechanism.In this review,we summarize recent advances in the field of stimulusresponsive RTP in purely organic luminogens,focusing on their unique emission behaviors and internal mechanisms governing the phenomena.We also attempt to identify the relationship between the mechanism,luminogens,and possible applications.

How do molecular interactions affect fluorescence behavior of AIEgens in solution and aggregate states?

Molecular interactions are crucial in diverse fields of protein folding,material science,nanotechnology,and life origins.Although mounting experimental research controls luminescent behavior by adjusting molecular interactions in light-emitting materials,it remains elusive to correlate microscopic molecular interactions with macroscopic luminescent behavior directly.Here,we synthesized three red luminogens with subtle structural variation and investigated the influence of molecular interactions on their luminescent behavior in solution and aggregate states.Our results indicate that strongπ-πand D-A interactions in both dilute solution(between luminogen and solvent molecules)and aggregate(between luminogens)states cause the redshift in emission,while weak interactions(e.g.,Van der Waals,C–H…π,and C–H…F interactions)enhance the quantum yield.This work provides a thoughtful investigation into the complicated influence of various molecular interactions on luminescent behavior.

Aggregation-induced emission luminogens for highly effective microwave dynamic therapy

Aggregation-induced emission luminogens(AIEgens)exhibit efficient cytotoxic reactive oxygen species(ROS)generation capability and unique light-up features in the aggregated state,which have been well explored in image-guided photodynamic therapy(PDT).However,the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications.Coincidentally,microwaves(MWs)show a distinct advantage for deeper penetration depth in tissues than light.Herein,for the first time,we report AIEgen-mediated microwave dynamic therapy(MWDT)for cancer treatment.We found that two AIEgens(TPEPy-I and TPEPy-PF6)served as a new type of microwave(MW)sensitizers to produce ROS,including singlet oxygen(1O2),resulting in efficient destructions of cancer cells.The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22μM,respectively.Overall,the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT,but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome,thus reducing the occurrence of side-effects of MW radiation.

Peptide-Based AIEgens:From Molecular Design,Stimuli Responsiveness to Biomedical Application

Luminogens with aggregation-induced emission(AIEgens)have a wide range of biomedical applications in bioimaging,photodynamic anticancer,antibacterial therapy,and other fields,owing to their unique photophysical properties.The precise structural design and modification of AIE molecules have aroused great interest in the past years.As peptides-AIE hybrid materials,peptide-based AIEgens generally have better solubility,biocompatibility,and lower systemic toxicity.The functional diversity,modularity,and portability of peptides provide more possibilities for the intelligent structure and functional design of AIEgens.This review summarizes the recent research progress of peptide-based AIEgens nanomaterials,from molecular design,stimuli responsiveness to biomedical application,focusing on the advantages of peptides and AIE molecules as conjugates.Finally,a summary of the challenges and opportunities of peptide-based AIEgens nanomaterials for future clinical biomedical applications is presented.

An AIEgens and exonuclease Ⅲ aided quadratic amplification assay for detecting and cellular imaging of telomerase activity

Monitoring telomerase activity with high sensitive and reliable is of great importance to cancer analysis. In this paper, we report a sensitive and facile method to detect telomerase activity using AIEgens mod- ified probe （TPE-Py-DNA） as a fluorescence reporter and exonuclease llI （Exo lIl） as a signal amplifier. With the aid of telomerase, repeat units （TrAGGG）n are extended from the end of template substrate oligonucleotides （TS primer） that form duplex DNAs with TPE-Py-DNA. Then, Exo llI catalyzes the diges- tion of duplex DNAs, liberating elongation product and releasing hydrophobic TPE-Py. The released hydrophobic TPE-Py aggregate together and produce a telomerase-activity-related fluorescence signal. The liberated product hybridizes with another TPE-Py-DNA probe, starting the second cycle. Finally, we obtain the target-to-signal amplification ratio of 1 ：N2. This strategy exhibits good performance for detecting clinical urine samples （distinguishing 15 cancer patients＇ samples from 8 healthy ones） and checking intracellular telomerase activity （differentiating cell lines including HeLa, MDA-MB-231, MCF-7, A375, HLF and MRC-5 from the cells pretreated with telomerase-related drug）, which shows its potential in clinical diagnosis as well as therapeutic monitoring of cancer.

Recent Development of DNA-modified AIEgen Probes for Biomedical Application

A variety of DNA-based probes are utilized for the detections of multiple analytes and DNA nanotechnology has been thriving for recent decades and achieving numerous nanostructures,mainly focusing on DNA morphology modulation and multifunctional systems engineered into to the complicated works.Among the numerous detections,fluorescence method is a non-invasive,highly selective and sensitive means for varieties of applications,but their emissions are often compromised by the aggregation-caused quenching(ACQ)effect,which weakens their applications.The aggregation induced emission luminogens(AIEgens)are created with non emissive or weakly emissive in a low concentration but emit strong fluorescence in a high concentration with aggregated states.Herein,numerous functionalized AIEgens have been emerged and used for detection and imaging and DNA-modified AIEgen probes are introduced.In this vein,here we report the progress on DNA-modified AIEgen probes in recent years and highlight their conjugation strategies including covalent bonding,electrostatic interaction and their applications of biosensing.Moreover,multiple DNA strands are needed to introduce into the DNA-modified AIEgen probes for more purposes.At the end,some challenges are mentioned to discuss the new trend of DNA-modified AIEgen probes.

Exceptionally efficient deep blue anthracene-based luminogens:design,synthesis,photophysical,and electroluminescent mechanisms

Achieving high-efficiency deep blue emitter with CIE_(y)<0.06(CIE,Commission Internationale de L’Eclairage)and external quantum efficiency(EQE)>10%has been a long-standing challenge for traditional fluorescent materials in organic light-emitting diodes(OLEDs).Here,we report the rational design and synthesis of two new deep blue luminogens:4-(10-(4’-(9 H-carbazol-9-yl)-2,5-dimethyl-[1,1’-biphe nyl]-4-yl)anthracen-9-yl)benzonitrile(2 M-ph-pCzAnBzt)and 4-(10-(4-(9 H-carbazol-9-yl)-2,5-dimethyl phenyl)anthracen-9-yl)benzonitrile(2 M-pCzAnBzt).In particular,2 M-ph-pCzAnBzt produces saturated deep blue emissions in a non-doped electroluminescent device with an exceptionally high EQE of 10.44% and CIE_(x,y)(0.151,0.057).The unprecedented electroluminescent efficiency is attributed to the combined effects of higher-order reversed intersystem crossing and triplet-triplet up-conversion,which are supported by analysis of theoretical calculation,triplet sensitization experiments,as well as nanosecond transient absorption spectroscopy.This research offers a new approach to resolve the shortage of high efficiency deep blue fluorescent emitters.