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As for effective multimodal phototheranostic AIEgens, it is important to find strategies for manipulating photophysical dissipation to achieve optimized performance. Herein, a "all-in-one" phototheranostic AIEgen, (

Intrinsic tumor microenvironment (TME)-related therapeutic resistance and nontumor-specific imaging have limited the application of imaging-guided cancer therapy. Herein, a TME-responsive MnO2-based nanoplatform coupled with turn-on and always-on fluorescence probes was designed through a facile biomineralization method for imaging-guided photodynamic/chemodynamic/photothermal therapy (PDT/CDT/PTT). After the tumor-targeting delivery of the AuNCs@MnO2-ICG@AS1411 (AMIT) nanoplatform via aptamer AS1411, the TME-responsive dissociation of MnO2 generated sufficient O2 and Mn2+ with the consumption of GSH for improving PDT efficacy and Fenton-like reaction-mediated CDT. Simultaneously, the released small-sized ICG and AuNCs facilitated PDT and PTT efficacy via the deep tumor penetration. Moreover, the turn-on fluorescence of AuNCs revealed the real-time TME-responsive MnO2 degradation process, and the always-on ICG fluorescence enabled the in situ monitoring of the payload distribution in vitro and in vivo. The AMIT NPs also provided magnetic resonance and thermal imaging guidance for the enhanced PDT, CDT, and PTT. Therefore, this all-in-one nanosystem provides a simple and versatile strategy for multiple imaging-guided theranostic applications.

Chromium oxide (Cr2O3) is a promising material used in the applications such as photoelectrochemical devices, photocatalysis, magnetic random access memory, and gas sensors. But, its nonlinear optical characteristics and applications in ultrafast optics have not been studied yet. This study prepares a microfiber decorated with a Cr2O3 film via magnetron sputtering deposition and examines its nonlinear optical characteristics. The modulation depth and saturation intensity of this device are determined as 12.52% and 0.0176 MW/cm2. Meanwhile, the Cr2O3-microfiber is applied as a saturable absorber in an Er-doped fiber laser, and stable Q-switching and mode-locking laser pulses are successfully generated. In the Q-switched working state, the highest output power and shortest pulse width are measured as 12.8 mW and 1.385 µs, respectively. The pulse duration of this mode-locked fiber laser is as short as 334 fs, and its signal-to-noise ratio is 65 dB. As far as we know, this is the first illustration of using Cr2O3 in ultrafast photonics. The results confirm that Cr2O3 is a promising saturable absorber material and significantly extend the scope of saturable absorber materials for innovative fiber laser technologies.

Niobium diselenide (NbSe2), an emerging group VB transition metal dichalcogenide, has been widely used in materials science, chemistry, and physics, while the applications of NbSe2 in ultrafast photonics are still rare. In this study, a NbSe2-based saturable absorber (NbSe2-SA) is proposed by depositing NbSe2 nanosheets on the surface of a microfiber, whose modulation depth is up to 8.8%. Based on the NbSe2-SA, conventional solitons with an ultrashort pulse duration of 697 fs are achieved, which are proved to be polarization-locked vector solitons by further study. The results show that group VB transition metal dichalcogenides, including NbSe2, could be developed as effective SAs for generating ultrafast pulses, especially vector pulses.

Broad applications of electropolymerized conducting polymers (CPs) often prefer thinner soft electrodes to comply with downscaling of the fabrication resolution. However, high conductivity of existing CP films vanishes as thickness decreases to the nanoscale (i.e., below 100 nm), with an unclear mechanism so far. In this study, with an unprecedented family of polypyrrole (PPy) nanofilms that can be easily transferred in a fast and contamination-free manner, we are able to trace the initial development of electrical conductance along with chains' arrangement starting from the very early electrochemical deposition. Our results evidence that the classical nodular polymeric aggregation fundamentally accounts for the persistent losses of interchain connectivity and macroscopic conductivity at a limited thickness. Surprisingly, this seemingly disadvantageous structure can be altered into a large conjugated network to robustly restore the conductivity back to over 80 S cm-1 even below 100 nm, while the controllable formation, growth, and collapse of such networks radically vary the conductivity over a range of 3 orders of magnitude (0.8-129 S cm-1). These observations depict the first physical picture detailing how the long-range conductivity builds up in a growing conjugated network, which opens a route to fast synthesis and diverse applications of such highly conductive CP nanofilms.

As a focus issue, the study of lysosomal pH has attracted much attention as it is closely associated with the state of lysosome, which plays a vital role in endocytosis and autophagy. In order to investigate the lysosomal pH, fluorescence bioimaging is one of the most widely-explored approaches. Unfortunately, the probes are insufficient to absorb or emit in the near-infrared (NIR) region, which could minimize photodamage to organisms and maximize tissue penetration in living systems. As a novel family of NIR dyes, hemicyanine has been selected for NIR bioimaging and biosensing owing to its excellent optical properties, easy preparation and good biocompatibility. Employing a classic rhodamine–hemicyanine hybrid, we first designed and synthesized a NIR boron complex (HCy-BIZ-BF2) with lysosome-targeting and pH-sensing properties. It is worth mentioning that after HCy-BIZ was coordinated with boron fluoride, HCy-BIZ-BF2 exhibited an improved photostability as well as an enlarged Stokes shift, and was subsequently applied to monitor the lysosomal pH in cells stimulated with chloroquine. Further investigation of pH changes in mice illustrated that HCy-BIZ-BF2 performed well in detecting the pH in living organisms. Therefore, this concept of boron complex derived from hemicyanine is not only applicable in pH detection, but also conducive for preparing promising novel NIR bioprobes and obtaining precise measurements of physiological parameters in specific physiological processes.

Background Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration. However, the expression and function of Mc4r in the mouse limb and digit has not been fully investigated. Our previous work showed that Mc4r−/− mice fail to regenerate the digit, but whether activation of MC4R signaling could rescue digit regeneration, or stimulate proximal digit regeneration is not clear. Results We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice. We found that Mc4r-GFP is mainly expressed in the limb nerves, and in the limb muscles that are undergoing secondary myogenesis. Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix. We also examined the effect of α-MSH on mouse digit regeneration. We found that administration of α-MSH in the Mc4r+/− mice rescue the delayed regeneration of distal digit tip. α-MSH could rescue distal digit regeneration in denervated hindlimbs. In addition, α-MSH could stimulate regeneration of the proximally amputated digit, which is non-regenerative. Conclusions Mc4r expression in the mouse limb and digit is closely related to nerve tissues, and α-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.

DNAzyme-based chemiluminescence assay exhibits excellent performance in bioanalysis but their operation in acid conditions remains challengeable. Herein, we constructed an acid-improved DNAzyme-based isothermal enzyme-free concatenated DNA circuit with significantly reduced background and simultaneously improved signal-to-noise ratio for miRNA detection. The chemiluminescence miRNA assay is composed of catalyzed hairpin assembly (CHA), hybridization chain reaction (HCR), and hemin/G-quadruplex DNAzyme units. The analyte initiates the self-assembly of CHA hairpins into numerous dsDNA, which triggers the subsequent autonomous cross-opening of HCR hairpins to generate long nanowires consisting of the hemin/G-quadruplex DNAzyme. The DNAzyme catalyzes the oxidation of luminol by hydrogen peroxide for the cascaded amplified chemiluminescence signal. The acid-improved property was demonstrated to be closely associated with the low catalytic activity of aggregated hemin under acidic conditions and the remained multiple amplified signal through concatenated DNA circuit. The general DNA circuit exhibited high sensitivity for miRNA-21 detection and chemiluminescence imaging under acidic conditions with a recognition hairpin. The acid-improved DNAzyme-based concatenated DNA circuit is promising to expand the application of chemiluminescence assay and provide a valuable strategy for early diagnosis and prognosis of cancer.

A water-soluble phosphorescent bioprobe was successfully developed by introducing an iridium(III) complex as a phosphorescent signaling unit with poly(N-isopropylacrylamide) (PNIPAM) as the stimuli-responsive backbone. The probe was used for the effective detection of cysteine (Cys)/homocysteine (Hcy) and temperature based on changes in the phosphorescence signal. The design principle was based on the fact that the aldehyde groups in the cyclometalated ligands of the iridium(III) complex moiety can react with the β- or γ-aminothiol group to form thiazolidine or thiazinane, respectively, resulting in a phosphorescence change in the iridium(III) complex, thereby facilitating the detection of Cys and Hcy. Moreover, a phosphorescent hydrogel based on this probe was formed upon cross-linking and was then used as a quasi-solid sensing system for detecting Cys and Hcy. Furthermore, by using a time-resolved photoluminescence technique, the probe can detect Hcy in the presence of intense background fluorescence. In addition, phase changes in temperature-responsive PNIPAM can result in a switch of microenvironment between hydrophilicity and hydrophobicity, to which the phosphorescent emission of the iridium(III) complex is very sensitive. This bioprobe integrates water solubility, biocompatibility, and sensing capability into one system, which is advantageous for biological applications. Further investigation of the application of the bioprobe for living-cell imaging confirmed that the probe is membrane permeable and is capable of detecting Cys in living cells with notable phosphorescence enhancement. Fluorescence lifetime imaging microscopy is successfully applied for sensing and bioimaging of intracellular Cys in the presence of short-lived background fluorescence.

A scalable and low-cost strategy is developed to fabricate a novel CuS/SiO2-based nanotherapeutic agent for dual-model imaging-guided photothermal/photodynamic combined therapy. In this design, mesoporous silica nanoparticles (MSNs) with CuS bundled in the channel are obtained in aqueous solution via in situ growth route for the first time. Furthermore, to achieve a more efficient therapy, photosensitizer (complex Ir-2) and bovine serum albumin are sequentially assembled via layer-by-layer method. The as-prepared complex Ir-2 presents a remarkably high 1O2 generation (ΦΔ = 1.3) under light illumination to offer effective photodynamic cell killing, and MSN/CuS exhibits high photothermal conversion efficiency (η = 31.7%) under illumination by 808 nm light to offer hyperthermia tumor ablation. In vitro and in vivo analyses show that the as-obtained nanotherapeutic agents exhibit excellent performance in tumor therapy even under irradiation with low power because of the high yield of 1O2 combined with the hig...

Engineered functional neural interfaces (fNIs) serve as essential abiotic–biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms. fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.

We design an organic photosensitizer with a donor-π-acceptor configuration. The photosensitizer exhibits aggregation-induced emission characteristics and efficient singlet oxygen production in the aggregated state. It is then enveloped into the water-soluble micelle to afford a nanoprobe. The water-soluble nanoprobe keeps the photosensitizer in the aggregation state and is used for imaging-guided photodynamic ablation of cancer cells.

Tungsten disulfide (WS2), which possesses broadband nonlinear saturable absorption property, displays promising applications in passively mode-locked lasers. Recent research works have demonstrated that WS2 shows much higher thermal conductivity than other transition metal dichalcogenides, which can withstand higher optical intensity and exhibit a higher damage threshold. However, the WS2-based high-energy fiber lasers have not been extensively studied. Here, a WS2-clad microfiber (WCM) saturable absorber (SA) is exploited by an effective transferring approach, which is precisely accomplished under optical microscope. The evanescent field interaction scheme has ability to further raise the optical damage threshold, as well as take full advantage of the nonlinear effect of WS2. Based on the WCM SA, high-energy rectangular pulses are achieved in an Er-doped fiber laser whose pulse duration and energy almost increase linearly with the enhancement of pump power. The maximum energy of single pulse in the cavity can reach 810 nJ under pump power of 800 mW. The experimental results open up venues to create new high-energy laser systems with rich functionalities and novel physical effects.

Photothermal therapy (PTT) as a kind of noninvasive tumor treatment has attracted increasing research interest. However, the efficiency of existing PTT agents in the near-infrared (NIR) region is the major problem that has hindered further development of PTT. Herein, we present an effective strategy to construct the efficient photothermal agent by utilizing an intramolecular photoinduced electron transfer (PeT) mechanism, which is able to dramatically improve photothermal conversion efficiency in the NIR region. Specifically, an NIR dye (A1) constructed with dimethylamine moiety as the electron donor and the aza-BODIPY core as the electron acceptor is designed and synthesized, which can be used as a class of imaging-guided PTT agents via intramolecular PeT. After encapsulation with biodegradable polymer DSPE-mPEG5000, nanophotothermal agents with a small size exhibit excellent water solubility, photostability, and long-time retention in tumor. Importantly, such nanoparticles exhibit excellent photothermal conversion efficiency of ∼35.0%, and the PTT effect in vivo still remains very well even with a low dosage of 0.05 mg kg-1 upon 808 nm NIR laser irradiation (0.5 W cm-2). Therefore, this reasonable design via intramolecular PeT offers guidance to construct excellent photothermal agents and subsequently may provide a novel opportunity for future clinical cancer treatment.

Transition metal dichalcogenides (TMDs) have attracted considerable attention in electronics and photonics. Tantalum diselenides (TaSe2) as a member of TMDs has been employed for field effect transistors and all-optical switching, and its nonlinear optical response has also been investigated. However, the applications of TaSe2 in ultrafast fiber lasers have not been exploited. Here, TaSe2 deposited on D-shaped fiber is used as saturable absorber (SA) in Er-doped fiber laser, and four switchable operating states (bright solitons, dark solitons, bright-dark soliton pairs and their HML counterparts, as well as bright-dark-bright soliton pairs) are realized successfully. To the best of our knowledge, this is the first presentation of a mode-locked fiber laser with the TaSe2-based SA, and also the first study of bright and dark soliton properties of a TaSe2-based fiber laser. It is foreseeable that TaSe2 will become an appealing candidate for bright and dark soliton fiber lasers.

Most recently, stimuli-responsive luminescent materials have attracted increasing interest because they can exhibit tunable emissive properties which are sensitive to external physical stimuli, such as light, temperature, force, and electric field. Among these stimuli, electric field is an important external stimulus. However, examples of electrochromic luminescent materials that exhibit emission color change induced by an electric field are limited. Herein, we have proposed a new strategy to develop electrochromic luminescent materials based on luminescent ion pairs. Six tunable emissive ion pairs (IP1–IP6) based on iridium(III) complexes have been designed and synthesized. The emission spectra of ion pairs (IPs) show concentration dependence and the energy transfer process is very efficient between positive and negative ions. Interestingly, IP6 displayed white emission at a certain concentration in solution or solid state. Thus, in this contribution, UV-chip (365 nm) excited light-emitting diodes showing orange, light yellow and white emission colors were successfully fabricated. Furthermore, IPs displayed tunable and reversible electrochromic luminescence. For example, upon applying a voltage of 3 V onto the electrodes, the emission color of the solution of IP1 near the anode or cathode changed from yellow to red or green, respectively. Color tunable electrochromic luminescence has also been realized by using other IPs. Finally, a solid-film electrochromic switch device with a sandwiched structure using IP1 has been fabricated successfully, which exhibited fast and reversible emission color change.

Delayed fluorescence (DF) materials have shown great potential in time‐resolved luminescence imaging (TRLI), due to the relatively elongated emission lifetimes. However, the sensitivity of DF to environmental quenching leads to a challenge to realize TRLI directly using pure thermally‐activated DF (TADF) molecules. Herein, two TADF molecules, namely CzPOTCF and tBCzPOTCF, are designed and synthesized, featuring a diphenylphosphine oxide (DPPO) group substituted at the ortho‐position of the carbazole group. Compared with DPPO‐free CzTCF, the steric hindrance of DPPO groups enlarges dihedral angles between TCF and the carbazole groups in CzPOTCF and tBCzPOTCF; meanwhile, PO provides other channels for forming intermolecular hydrogen bonds. The optimized intermolecular interactions facilitate the dimer formation of CzPOTCF and tBCzPOTCF, which simultaneously enhance aggregation‐induced DF and mitigate disordered packing‐induced quenching. As a consequence, CzPOTCF and tBCzPOTCF show the enhanced aggregation‐induced DF with largely increased lifetimes. Without any additional assistance, the long‐lived fluorescence of CzPOTCF and tBCzPOTCF is successfully observed for cell TRLI, with 1–1.7 μs elongated average lifetimes of 6.69 and 7.41 μs, respectively.

Precisely engineered neuronal circuits are promising for both fundamental research and clinical applications. However, randomly plating thousands of cells during neural network fabrication remains a major technical obstacle, which often results in a loss of tracking in neurons' identities. In this work, we demonstrated an accurate and unique neural wiring technique, mimicking neurons' natural affinity to microfibers. SU-8 microridges, imitating lie-down microfibers, were photolithographically patterned and then selectively coated with poly-l-lysine. We accurately plated Aplysia californica neurons onto designated locations. Plated neurons were immobilized by circular microfences. Furthermore, neurites regrew effectively along the microridges in vitro and reached adjacent neurons without undesirable crosstalks. Functional chemical synapses also formed between accurately wired neurons, enabling two-way transmission of electrical signals. Finally, we fabricated microridges on a microelectrode array. Neuronal spikes, stimulation-evoked synaptic activity, and putative synaptic adaption between connected neurons were observed. This biomimetic platform is simple to fabricate and effective with neurite pathfinding. Therefore, it can serve as a powerful tool for fabricating neuronal circuits with rational design, organized cellular communications, and fast prototyping.

Organelle-targeted photosensitizers have been reported to be effective photodynamic therapy (PDT) agents. In this work, we designed and synthesized two iridium(III) complexes that specifically stain the mitochondria and lysosomes of living cells, respectively. Both complexes exhibited long-lived phosphorescence, which is sensitive to oxygen quenching. The photocytotoxicity of the complexes was evaluated under normoxic and hypoxic conditions. The results showed that HeLa cells treated with the mitochondria-targeted complex maintained a slower respiration rate, leading to a higher intracellular oxygen level under hypoxia. As a result, this complex exhibited an improved PDT effect compared to the lysosome-targeted complex, especially under hypoxia conditions, suggestive of a higher practicable potential of mitochondria-targeted PDT agents in cancer therapy.

Mercury is one of the most hazardous and ubiquitous heavy metals, which may accumulate in human body through the food chain. [ 1 ] It shows high permeability into skin, respiratory and gastrointestinal systems of the human body, and can cause serious damage to the central nervous system. [ 2 ] Therefore, it is very important to develop various methods to effi ciently detect mercury in vitro and in vivo. Luminescence bioimaging provides an important means of visualizing morphological details of tissues with subcellular resolution and has become a powerful tool for manipulation in the biological analysis and medical diagnosis and treatment. [ 3 ]

Hypoxia has been demonstrated to be associated with various diseases, such as cardiovascular diseases, stroke, and solid tumors. Hence, accurate determination of the oxygen content in biological systems is of great importance for disease diagnosis and therapy evaluation. Since the sensitivity of phosphorescent transition-metal complexes (PTMCs) to oxygen is dependent on their excited state properties. Hence, the rational tuning of the excited state of PTMCs is important to design excellent probes for oxygen. In this work, we designed and prepared four novel Ir(III) complexes (Ir1–Ir4) with two N^N ligands bearing carbazolyl and 1,2,3-trifluorobenzene. We confirmed that the complexes mainly originating from the 3ILCT excited state have a longer emission lifetime, resulting in a better oxygen sensitivity than those from the 3MLCT excited state. Additionally, Ir1 has been used for the detection of the intracellular oxygen distribution under complex conditions through time-resolved luminescence imaging (TRLI) techniques. Importantly, TRLI techniques can not only improve the accuracy of the intracellular O2 detection compared to intensity-based methods, but also minimize the short-lived fluorescence interference and improve the signal-to-noise ratio.

We demonstrate an effective approach to transferring micron-size CVD graphene layers onto freestanding microfibers. With micro-manipulation, the coating position and length of the graphene films can be precisely controlled. By coating micrometer-scale (e.g., 20 μm) graphene films onto microfibers with diameters down to 1 μm, we can achieve significantly enhanced light–graphene interaction (e.g., a low saturable-absorption threshold of 40 MW/cm2) and simultaneously maintain a high transmission (73% in maximum) as well. In addition, we use these microscale CVD graphene-coated microfibers (GCMs) as saturable absorbers for all-optical modulation at 1550-nm wavelength with a modulation depth of 12% and passively mode-locked fiber lasing with pulse duration down to 970 fs.

A phenazine derivative with a succinimide endcap (PHS) was designed and synthesized for cysteine (Cys) with near-infrared (NIR) emission. Upon the addition of Cys, the color of the solution changed clearly from greenish black to orange, which was attributed to the disappeared absorbance at 616 nm. An enhanced NIR emission band at 670 nm was found in the fluorescence spectra and a corresponding excitation peak at 466 nm arose in the excitation spectra. Verified by the dynamic reaction, the cyanoacetic acid moiety should be susceptible to be attacked by the –SH group in a fast rate through Michael addition reaction. Being highly reactive to the amino group (–NH2), the NHS-active carbonyl site could target the amino acid and accelerate the process of nucleophilic attack from the –SH group. This cycloaddition mechanism of the α,β-unsaturated carbonyl NHS-ester was proved by 1H NMR titration. In addition to its good biocompatibility, PHS was successfully applied to the detection of Cys in Hela cell lines with NIR fluorescence signals.