The design and fabrication of advanced soft actuators with programmable actuation are highly desirable in constructing intelligent soft robots. In this work, a programmable light-driven liquid crystalline network (LCN)-based soft actuator was judiciously designed and prepared by constructing structural anisotropy across the thickness of the film. A three-dimensional (3D) deformable LCN actuator was realized by polymerization-induced phase separation of small-molarweight monomers and polymer networks. The resultant anisotropic LCN displays anisotropic microscale nanoporous architecture across the thickness in addition to uniform alignment at the molecular scale. The actuation behaviors of LCN film are tunable by adjusting the size and distribution of nanopores in LCN bulk via changing polymerization conditions and monomer components. More importantly, the nanoporous LCN film can be harnessed as a promising template to achieve diverse light responsiveness by changing the photothermal dyes via a feasible washing and refilling process, demonstrating a reprogrammable light-driven soft actuator.

Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super-resolution is highly demanded yet quite challenging. Herein, a ratiometric HClO probe AHOH is designed and synthesized which is capable of simultaneously staining lysosomes and mitochondria with red and green colour, respectively. AHOH could be selectivity oxidized by HClO, leading to a large emission blue shift (90 nm) and an over 1300-fold enhancement of the emission ratio of Fl_547nm/Fl_637nm. We apply AHOH in super-resolution microscopy and clearly visualize the dynamics of mitochondria–lysosomes interactions and the oxidative stress states upon different stimuli. Mitochondria dysfunction triggered by different drugs and genetic defect lead to elevated oxidative stress and higher levels of mitophagy. Moreover, AHOH could serve as a reliable tool for evaluating the efficacy of drugs regulating mitochondria dysfunction. This work provides a powerful dual-colour super-resolution imaging agent for real-time monitoring the dynamics of organelle interactions and oxidative stress.

Fluorescence signal “turn-on” lateral flow immunoassay (FONLFA) through nanomaterial labeled quenching fluorescent nanomaterial has shown significant potential for the detection of small molecules. However, the fluorescent nanomaterial immobilization on nitrocellulose (NC) membrane commonly requires tedious chemical modification and only a few combinations of fluorescence donor and quencher have been applied in FONLFA. In this work, bright fluorescent metal nanoclusters (Prot-AuNCs) were prepared and self-assembled into Prot-AuNCs/antigen aggregates with three typical small molecule antigens, respectively. The aggregates can be readily immobilized on the surface of the NC membrane, indicating that this strip fabrication strategy has good versatility. Moreover, we evaluated the performances of this FONLFA platform by using carbendazim as a model target and investigated four typical nanomaterials as colorimetric nanoprobes and fluorescence quenchers. We found that all the nanoprobes demonstrated significantly improved naked eye detection sensitivity (vLOD) and limits of detection (LODs) in quantitative analysis. Among them, combing the Fe-polydopamine nanoparticles as quencher with the above aggregates, the FONLFA in signal “turn-on” mode achieved 200-fold improved vLOD (0.05 ng mL^–1) compared with conventional colorimetric AuNPsbased lateral flow immunoassay (AuNPs-LFA) (10 ng mL^–1). In addition, the LOD in quantitative analysis also was improved by 22-fold and the whole test process was completed within 10 min. With the advantages of efficient fabrication, extraordinary sensitization, and good biocompatibility, our FONLFA platform is expected to have great potential in the rapid detection of various small molecules.

Accumulating evidence indicates that G-quadruplexes (G4s) are involved in transcriptional regulation. Previous studies have demonstrated that DHX36 preferentially resolves G4s, suggesting its potential impact on gene transcription mediated by these structures. However, systematic validation is required to establish a link between DHX36 activity and its roles in transcriptional regulation. In this study, we investigate the role of DHX36 in transcription. First, we employ the cleavage under targets and tagmentation (CUT&Tag), an efficient method for mapping protein– DNA interactions, to identify the binding sites in the chromatin of MCF-7 cells. Subsequently, we use the auxin-inducible degron (AID) protein degradation system and improved nascent RNA sequencing method acrylonitrile-mediated uridine-tocytidine conversion sequencing (AMUC-seq) to pinpoint genes directly regulated by DHX36. Our results reveal a significant enrichment of G4 structures at DHX36 target sites, predominantly located in active genomic regions. In vitro assays further demonstrate DHX36’s interaction with G4 sequences from three specific oncogenes. These findings underscore the potential role of DHX36 in modulating gene transcription through G4 structures.

Numerous reports have demonstrated the construction of supramolecular nanodrugs (SNDs) via the π–π stacking of drug molecules for antitumor applications because most drugs possess aromatic rings or other planar conjugate units. However, the destruction of π–π stacking and the subsequent disassembly of SNDs under tumor microenvironment (TME), which is the precondition for drug release, have not been clearly described. In this work, based on a disassembly model of π–π stacked naphthoquinone SNDs, the influence of co-assembled drugs on disassembly is delineated. Both the experimental observation and computational simulation indicate that the disassembly of SNDs under simulated TME highly depends on the disassembly activation energy (ΔE_dis) of neighboring π–π stacked molecules. Owing to the high ΔE_dis, the disassembly of self-assembled naphthoquinone SNDs is greatly restricted. Meaningfully, the ΔE_dis is the sum of a series of activation energy according to the specific stimuli of TME. Thus, a concept of stimuli-responsive drug-mates is proposed for boosting the disassembly of π–π stacked SNDs, namely the foremost co-assembly of π-conjugated drugs with additional drug molecules that possess relatively weak π–π interaction but high TME responsiveness. Further computational simulation reveals that the introduction of stimuli-responsive drug-mates significantly lowers the ΔE_dis, thus accelerating the disassembly of SNDs and the release of drug payloads. Holding the advantages of π-conjugated drug library, the concept of stimuli-responsive drug-mates gives an extensive design of π–π stacked SNDs toward heterogeneous nidus microenvironment responsiveness, which highlights the superiority of widely used drug co-assembly strategy in constructing multifunctional SNDs.

Recent experiments have shown that hole traps could be suppressed in polymer light-emitting diodes under current stress by diluting the light-emitting conjugated polymers within an “inert” large-bandgap host material. However, it is unclear why there is an enhanced dilution effect in partially miscible blends rather than fully miscible blends, as intuition would suggest that better miscibility leads to better dilution. In this work, we propose a cascade analysis by combining multiple fluorescence microscopic techniques and all-atom molecular dynamics simulations to study the solid-to-solid dilution of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) inMEH-PPV/polystyrene (PS) blends and MEH-PPV/poly(vinylcarbazole) (PVK) blends. By varying the molecular weights of PS and PVK, we can regulate their miscibility with MEH-PPV. The results corroborate that the dilution effect is enhanced in partially miscible blends rather than fully miscible ones. This is because, in partially miscible blends undergoing phase separation, the concentration of MEH-PPV is notably decreased in the phase occupying the majority of the volume, leading to an overall greater dilution effect than in fully miscible blends. Moreover, MEH-PPV could adopt the more extended conformation in the fully miscible blend, causing a shorter intermolecular distance to further undermine the dilution effect. These findings explain the seemingly counterintuitive more effective dilution effect observed in the recently reported partially miscible blends and provide guidance for further enhancing the performance of future generations of polymer light-emitting diodes.

Poly-substituted olefins, one of the most important aggregation-induced emission luminogens (AIEgens), have garnered significant attention due to their various applications in chemical- and bio-sensing, bio-imaging, and opto-electronics. However, the synthetic methods for these olefins remain limited, impeding the progress of AIEgens. This study introduces an unprecedented cross-coupling reaction between aryl sulfonium triflates and tosylhydrazones from naturally abundant thioethers and ketones. The generality of this method is exemplified by the facile synthesis of over forty poly-substituted olefins. Importantly, the luminescent properties of these AIEgens (e.g., quantum yield and emission color) can be easily tuned by adjusting the substituents of the electrophile and nucleophile substrates, exhibiting excellent performance in bio-imaging. Notably, the mechanistic studies reveal the critical role of β-H elimination in the formation of the double bond. This contribution provides an efficient method to synthesize poly-substituted olefins, pushing forward the development of AIEgens.

The elucidation of hierarchical assembly structure of metal nanoclusters is of fundamental importance in the context of bottom-up fabrication and functionalization. While recent studies have provided valuable insights into the multiscale assembly patterns of gold or silver-based nanoclusters, the success in achieving similar results for copper analogues has been notably limited. Herein, by virtue of a slow-ligand-release strategy, a copper nanocluster denoted as [Cu₆₆Cl₈(PPh₃)₈(SC₂H₅)₃₂H₂₄](SbF₆)₂ was synthesized, resulting in the formation of fresh hierarchical assembly structures in one-pot. The arrangement of the metal atoms within the cluster reveals an orderly of 16 Cu₄ squares, representing a rare copper nanocluster comprising square motifs. Additionally, the ligands (phosphine, thiolate, and halide) coordinate to the surface of the cluster in a regiospecific manner, displaying square patterns as well. The self-assembly facilitated by the C-H···F interaction between the cluster moieties and SbF₆^– anions further induces the formation of three-dimensional cubes and eventually large nanocrystals. Density functional theoretical (DFT) calculations reveal that hydride atoms with low chemical shifts typically exhibit short Cu-H distances. The cluster demonstrates moderate stability and high catalytic activity in the chemoselective hydrogenation of cyclohexanone under mild conditions.

Current radiotherapy (RT) lacks the ability to accurately discriminate between tumor and healthy tissues, resulting in significant radiation-induced damage for patients. Therefore, there is an urgent need for precise RT techniques that can optimize tumor control while minimizing adverse effects on surrounding healthy tissues. In this study, we developed a nanodrug (AuNR@Peptide) composed of furin-responsive RVRR peptide-conjugated AuNRs, which integrates an activatable probe and a radiosensitizer into a single system for accurate tumor localization, enabling imageguided precision RT. Upon reaching the tumor site after intravenous administration, proteolytic cleavage of RVRR substrates on AuNR@Peptide by biomarker triggers aggregation of gold nanorods (AuNRs) into larger aggregates, leading to activation of near-infrared (NIR)-II photoacoustic (PA) signals to precisely localize the tumor and enhance tumor retention by preventing migration and backflow of AuNRs. This significantly amplifies radiosensitivity efficiency. The peak time point at which the NIR-II PA signal was observed at the tumor site after injection serves as a reference for initiating RT, demonstrating substantial improvement in tumor RT through investigations related to radiosensitization mechanisms. The integration of imaging and therapy in this study offers a promising image-guided therapeutic modality for tumors.

Osteosarcoma (OS) is characterized by an unfavorable prognosis and high mortality rates, with the local recurrence attributed to residual lesions post-surgery being a major reason for treatment failure. Precise and tumor-specific resection guidance to minimize recurrence remains a significant challenge. In the present study, a nanosystem based on aggregation-induced emission (AIE) molecules with emission in the second near-infrared window is proposed for the synergistic fluorescence (FL) and chemiluminescence (CL) imaging-guided surgical resection for the elimination of tumor foci. The designed AIE molecule, BBTD14, exhibits stable FL with a high quantum yield of up to 3.95%, which effectively matches the energy levels of CL high-energy states, generating the longest emission wavelength of CL reported to date. Targeted tumor imaging-guided surgery (IGS) is facilitated by FL and CL nanoprobes (FLNP and CLNP) constructed based on BBTD14. During OS surgery, the FLNP, with the stability of FL and a high targeting capability, was first intravenously used to guide the surgical removal of the main tumor. Subsequently, CLNP was locally incubated to facilitate rapid and accurate evaluation of residual tumors at the operative border. High signal-to-noise ratio CL imaging was achieved after spraying with hydrogen peroxide, thereby overcoming the limitations of intraoperative frozen sections. The proposed technique also significantly reduced the recurrence rates in OS mouse models and exhibited high marker specificity in ex vivo OS patient pathology samples, confirming its potential in clinical applications and providing a unique perspective for developing IGS.

A family of responsive enaminitrile molecular switches showing tunable turn-on fluorescence upon switching and aggregation is reported. When activated by the addition of acid/base, isomerization around the C═C bond could be effectuated, resulting in complete and reversible switching to the E- or Z-isomers. Typical aggregation-induced emission (AIE) could be recorded for one specific state of the different switches. By subtle tailoring of the parent structure, a series of compounds with emissions covering almost the full visible color range were obtained. The switchable AIE features of the enaminitrile structures enabled their demonstration as solid-state chemosensors to detect acidic and basic vapors, where the emission displayed an “off-on-off” effect. Furthermore, switching to the Z-configuration could be driven out-of-equilibrium through transient changes in acidity while giving rise to fluorescence. Single-crystal X-ray diffraction measurements suggested a luminescence mechanism based on restriction of intramolecular rotation and an intramolecular charge transfer effect in the AIE luminogens.

Nematic liquid crystals (NLCs), that is, fluids with optical anisotropy as well as electric- and magnetic-field responsiveness, have been widely used in commercial liquid crystal displays. Recent advancements have extended the scope of NLC molecules to large calamitic π-conjugated systems, which heralds prospects for novel applications that exploit their superior electronic or optical functionalities in, for example, electric field controlled fluorescence switch devices. However, NLC phases of such extended π-systems usually flow only at high temperatures, which hampers device applications that operate around room temperature. Here, we show near-room-temperature NLCs of a π-conjugated fluorophore by introducing a flexible cyclic structure into the mesogenic core. 3,8-Bis(4-propylphenyl)-6,7-dihydro-5H-benzo[7]annulene (DPB[7]-C3) has a nematic phase in a significantly lower temperature range (52.6–160.4°C) than the DPB[7]-C3 analog without flexible alkylene bridges, (E)-4-propyl-4′-(4-propylstyryl)-1,1′-biphenyl (248–262°C). We attribute this large decrease in the phase transition temperature to large intramolecular conformational entropies that arise from the geometric change of the cyclic structure, which involves rotational motion of single biaryl-bonds and bending motions along the long molecular axis in the thermal equilibrium state. The practical utility of these NLC molecules is demonstrated by preparing an electric-fieldresponsive large-area fluorescent switch device with a sub-millisecond response time from a mixture of 3,8-bis(4-alkylphenyl)-6,7-dihydro-5H-benzo[7]annulenes (DPB[7]-Cns).

Solution coating of organic semiconductors offers great potential for achieving low-cost and high-throughput manufacturing of large-area and flexible electronics. However, the solution processability of semiconducting small molecules for fabricating uniform and reliable thin-film devices poses challenges due to the low viscosities of small-molecule solutions. Here, we report a universal approach employing a primer template (PT) to enhance the spreadability of small-molecule solutions on silicon wafers, enabling the spin-coating fabrication of uniform thin films composed of millimeter-scale grains with complete large-area coverage and well-ordered molecular packing. Using PT, we fabricated organic thin-film transistors (OTFTs) using solutions containing various small molecules such as rubrene and 2-decyl-7-phenyl-[1]benzothieno[3,2-b][1]benzothiophene. The device yield of all fabricated OTFTs is consistently 100% while achieving a high average mobility of 1.62 cm² V^–1 s^–1 with a device-to-device variation of 7.7% measured in ambient air condition. In addition, the utilization of PT resulted in a batch-to-batch variation of 12.5% in device performance over dozens of OTFT devices. The key industrial manufacturing metrics, such as device yield, reproducibility, and performance uniformity of the PT OTFTs, are among the best for devices fabricated using solution spin-coating techniques.

Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme-nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme-based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three-dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near-infrared light-mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug-resistant bacteria by the skeleton modification with genipin to produce genipin-conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO₄-crosslinked GLZF hydrogel is constructed to sensitize the cGAS-STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti-recurrence of diabetic wound infection via photo-enhanced bacterial killing and the cGAS-STING pathway. Thereby, it paves the way to employ the universal divalent anion-mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.

Colorectal cancer (CRC) is one of the most prevalent forms of cancer. CircRNAs have emerged as promising biomarkers for cancer diagnosis and prognosis evaluation. However, novel circRNAs as potential biomarkers for CRC still need further exploration and validation, and precise detection methods are yet to be developed. Herein, we report for the first time the use of droplets Cas13a to detect the circWDR37 as a biomarker of CRC. The arraystar circRNA microarray assays, functional experiments in vitro and in vivo, and qPCR were performed to discover and validate that circWDR37 is a biomarker for early screening and prognosis evaluation of CRC. A new technology named µDCR, which accurately detects circWDR37, has been developed by combining microfluidic droplets with CRISPR/Cas13a and recombinase polymerase amplification (RPA). Meanwhile, the role of crowding agent in improving the performance of Cas13a was uncovered. The 4% polyethylene glycol 8000 and 3% dextran-10 significantly improved the response speed and sensitivity of one-pot Cas13a-RPA reaction. The detection limit of circWDR37 by µDCR was found to be 10 copies/mL, which is higher than that of qPCR. The clinical sample findings demonstrated that circWDR37 detection can be utilized to effectively screen for CRC at an early stage and enable accurate assessment of prognosis. CircWDR37 is confirmed as a groundbreaking biomarker for both diagnosis and prognosis evaluation in CRC patients. Furthermore, our innovative µDCR method for detecting circWDR37 demonstrates impressive attributes such as streamlined operation, rapidity, and high-throughput, making it an optimal technology platform for the noninvasive screening of CRC.

Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment due to its non-invasive nature and high specificity toward malignant tissues. In recent years, a variety of protocols have been proposed to improve the PDT efficacy, of which organelle-targeted PDT strategy is supposed to be quite promising. Particularly, lipid droplets (LDs)-localized PDT attracts a lot of interest due to the inherent advantages such as abundant LDs in cancer cells and their close relation with ferroptosis. This review provides a comprehensive summary of the advancements of LDs-localized photosensitizers (PSs) according to their chemical structures and functions. Especially, these PSs are featured with fluorescence emission, thereby facilitating an imaging-guided phototherapy. The review highlights the cytocidal actions of these PSs, such as the cell death pathway and their cytotoxicity. Finally, some unresolved issues and challenges in this domain will be discussed.

Persistent biofilm infections pose a critical health threat with their relentless presence and amplified antibiotic resistance. Traditional antibacterial photodynamic therapy can inhibit bacteria extracellularly but struggles to control biofilm formation and virulence. Thus, there is an urgent need to develop photosensitizers, such as ultra-small gold nanoclusters (AuNCs), that can penetrate biofilms and internalize into bacteria. However, AuNCs still face the challenge of insufficient reactive oxygen species (ROS) production and limited near-infrared light absorption. This study develops a model of indocyanine green (ICG)-sensitized AuNCs with atomicprecision size effect. This approach achieved near-infrared light absorption while inhibiting radiation transitions, thereby regulating the generation of ROS. Notably, different-sized AuNCs (Au₁₀NCs, Au₁₅NCs, Au₂₅NCs) yielded varied ROS types, resulting from different energy level distributions and electron transfer rates. ICGAu15NCs achieved a treatment efficacy of 99.94% against Staphylococcus aureus infections in vitro and significantly accelerated wound healing in vivo. Moreover, this study highlights the unique role of ICG-AuNCs in suppressing quorum sensing, virulence, and ABC transporters compared to their larger counterparts. This strategy demonstrates that atomic-precision size effect of AuNCs paves the way for innovative approaches in antibacterial photodynamic therapy for infection control.

Circularly polarized luminescence (CPL) materials with delayed fluorescence have attracted much attention due to their ability to efficiently trap triplet state excitons, thereby improving the photoluminescence quantum yields of CPL materials. However, much effort has been normally focused on the utilization of T₁ excitons but seldom on the utilization of higher excited triplet state T_n (n > 1) excitons. Rational manipulation of higher excited triplet state T_n (n > 1) excitons and suppression of Kasha’s rule of CPL materials remains a major challenge. Herein, two gold complex enantiomers ((R/S)-BPAuBC) based on axially chiral binaphthyls and 3,6-Di-tert-butylcarbazole groups are synthesized and systematically investigated. These materials exhibit aggregation-induced circularly polarized delayed fluorescence. Circularly polarized delayed fluorescence was found to be enabled by activating high-level reverse intersystem crossing (hRISC). The anti-Kasha phosphorescence at 77 K proves that the exciton has a large population in the high-lying triplet state T₂, which allows the effective hRISC process to cross back to the singlet state S₁ and emit delayed fluorescence. In addition, CPL “on–off” switching is further achieved in nanoparticles by acid–base stimulus, showing its potential as an acid–base responsive material.

Donor‒acceptor covalent organic frameworks (D‒A COFs) have been regarded as promising materials for photocatalytic water splitting because of their tunable band gaps. However, their efficiency is hindered by fast charge recombination and low photostability. Herein, we proposed a donor structural engineering strategy for improving the photocatalytic activity of D‒A COFs to tackle these problems. Two benzothiadiazole-based D‒A COFs (DHU-COF-BB and DHU-COF-BP) with distinct donors were prepared for photocatalytic H2 evolution reaction (HER). As a comparison, DHU-COF-TB without benzothiadiazole moieties was also designed and synthesized. Impressively, the photocatalytic H₂ production rate of DHU-COFBB reaches 12.80 mmol g–1 h–1 under visible light irradiation (≥420 nm), which was nearly 2.0 and 3.1 times higher than that of DHU-COF-BP (6.47 mmol g^–1 h^–1) and DHU-COF-TB (4.06 mmol g^–1 h^–1), respectively. In addition, the apparent quantum efficiency (AQE) of DHU-COF-BB was up to 5.04% at 420 nm. Photocatalytic and electrochemical measurements indicate that the enhanced hydrogen evolution activity of DHU-COF-BB can be ascribed to the introduction of appropriate benzene moiety into the donors, which increases the charge separation efficiency and thereby suppresses the electron‒hole recombination. Density functional theory (DFT) calculations revealed that both triphenylamine and benzothiadiazole units are the main active sites for HER over the DHU-COF-BB. This work provides new insight into the photocatalytic hydrogen production activity of D‒A COFs by a donor structural engineering strategy.

Biomolecules with metals can form supramolecular nanomaterials through coordination assembly, opening new avenues for cancer theranostics and bringing unique insights into personalized nanomedicine. These biomaterials have been considered versatile and innovative nanoagents due to their structure‒function control, biological nature, and simple preparation methods. This review article summarized the recent developments in multicomponent nanomaterials formed from metal coordination interactions with amino acids, peptides, and proteins, together with anticancer drugs, for cancer theranostics. We discussed the role of functional groups anchored in building blocks for coordination interactions, and subsequently, the types of interactions were examined from a structure‒function perspective. Amino acids with different metals and anticancer drugs forming supramolecular nanomaterials and their anticancer mechanisms were highlighted. Peptides with different metals and anticancer drugs, proteins with metals and anticancer drugs used for material formations, and anticancer activity have been discussed. Ultimately, the conclusion and future outlook for multicomponent supramolecular nanomaterials offer fundamental insights into fabrication design and precision medicine.